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MX2007016541A - Chemical compounds. - Google Patents

Chemical compounds.

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Publication number
MX2007016541A
MX2007016541A MX2007016541A MX2007016541A MX2007016541A MX 2007016541 A MX2007016541 A MX 2007016541A MX 2007016541 A MX2007016541 A MX 2007016541A MX 2007016541 A MX2007016541 A MX 2007016541A MX 2007016541 A MX2007016541 A MX 2007016541A
Authority
MX
Mexico
Prior art keywords
indole
carboxamide
piperidinyl
methyl
phenyl
Prior art date
Application number
MX2007016541A
Other languages
Spanish (es)
Inventor
Katherine L Widdowson
Hong Nie
Qi Jin
Xichen Lin
Jeffrey K Kerns
Christopher E Neipp
Sonia M Thomas
Michael Lindenmuth
Jianghe Deng
Guoliang Lin
Original Assignee
Smithkline Beecham Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp
Publication of MX2007016541A publication Critical patent/MX2007016541A/en

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Abstract

The invention is directed to novel indole carboxamide derivatives. Specifically, the invention is directed to compounds according to formula I: Formula (I) where R1 , R2, R3, U and V are defined below and to pharmaceutically acceptable salts thereof. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKK??) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Description

CHEMICAL COMPOUNDS FIELD OF THE INVENCIOM The invention relates to certain indolecarboxamide compounds, which are inhibitors of kinase activity. More specifically, the compounds are inhibitors of IKK2. These compounds are useful in the treatment of disorders associated with inadequate activity of IKK2 (also known as IKKß) and in particular in the treatment and prevention of disorders involving IKK2 mechanisms, including inflammatory and tissue repair disorders. These disorders include rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease (COPD).
ANTECEDENTS OF THE DNVEMCDON The enzyme family of protein kinases is a large and important family of enzymes. At present approximately 500 different protein kinases are known. However, since three to four percent of the human genome encodes the formation of protein-quinases, there could be many thousands of separate and separate kinases in the human body. Protein kinases serve to catalyze the phosphorylation of an amino acid side chain of various proteins, by transferring of the α-phosphate of the ATP-Mg2 + complex to said amino acid side chain. These enzymes control most of the signaling processes within the cells, thus governing cellular function, its growth, differentiation and destruction (apoptosis) through the reversible phosphorylation of the hydroxyl groups of the serine, threonine and tyrosine radicals of proteins. Several studies have shown that protein kinases are key regulators of many cellular functions, including signal transduction, transcriptional regulation, cell motility and cell division. It has also been shown that several oncogenes encode protein kinases, suggesting that kinases play a role in oncogenesis. These processes are highly regulated, often through complex interrelated pathways, where each kinase is in turn regulated by one or more kinases. Consequently, an aberrant or inappropriate protein kinase activity may contribute to the appearance of morbid states associated with such aberrant kinase activity. Due to their physiological importance, their variety and their ubiquity, protein kinases have become one of the most important and widely studied families of enzymes in biochemical and medical research. The enzyme family of protein kinases is typically classified into two major subfamilies: tyrosine protein kinases and serine / threonine protein kinases, depending on the amino acid radical they phosphorylate. Serine / threonine kinases (PSTK) include AMP-cyclic and GMP-dependent protein kinases cyclic, calcium- and phospholipid-dependent protein kinases, calcium-calmodulin-dependent protein kinases, casein kinases, cell division cycle protein kinases, and others. Usually, these kinases are cytoplasmic or are associated with cell fractions containing particles, possibly by means of protein anchoring. The aberrant activity of serine / threonine protein quinases has been implicated, or its implication has been suspected, in various pathologies such as rheumatoid arthritis, psoriasis, septic shock, osteopenia, many cancers, and other proliferative diseases. So. The serine / threonine kinases and signal transduction pathways of which they are a part are important objectives for drug design. Tyrosine kinases phosphorylate tyrosine residues. Thyrosine kinases play an equally important role in cell regulation. These kinases include several receptors for molecules such as growth factors and hormones, including the epidermal growth factor receptor., insulin receptor, platelet-derived growth factor receptor, and others. Several studies have indicated that many tyrosine kinases are transmembrane proteins that have their receptor domains located outside the cell, and their kinase domains inside. Much research work is also under way to identify tyrosine kinase modulators. The nuclear factor KB (English acronym NF-? B) belongs to a family of complexes of transcription factors dimers, closely related, composed of various combinations of the Rel / NF-? B polypeptide family. The family is composed in mammals by five individual gene products: RelA (p65), NF-B1 (p507 p105), NF-? B2 (p49 / p100), c-Rel, and RelB, and can form hetero- or homodimers all they. These proteins share a highly homologous 300 amino acid domain, the "Rei homology domain", which contains the dimerization and DNA binding domains. At the C-terminal end of the Rei homology domain is a nuclear translocation sequence important in the transport of NF-? B from the cytoplasm to the nucleus. In addition, p65 and cRel possess powerful transactivation domains at their C-terminal ends. The activity of NF-? B is regulated by its interaction with a member of the protein family of L? B inhibitors. This interaction effectively blocks the nuclear localization sequence of the NF-KB proteins, thus preventing migration of the dimer to the nucleus. A wide variety of stimuli activate NF-? B, through what are likely to be multiple signal transduction pathways. These include bacterial products (LPS), some viruses (HIV-1, HTLV-1), inflammatory cytokines (TNFa, IL-1), environmental and oxidative stress, and DNA-damaging agents. However, phosphorylation and subsequent degradation of lβB is apparently common to all these stimuli. The L? B is phosphorylated in two N-terminal serines by the newly identified L? B-kinases (I K-a and IKK-β). IKK-β is also known as IKK2. Studies of Locally directed mutagenesis indicates that these phosphorylations are critical for the subsequent activation of NF-? B, since once it has been phosphorylated. The protein is indicated for degradation through the ubiquitin-proteasome pathway. Free of L? B, the active NF-? B complexes are capable of being translocated to the nucleus, where they are selectively fixed to preferred gene-specific enhancer sequences. The genes regulated by NF-κB include various cytokines and chemokines, cell adhesion molecules, acute phase proteins, immunoregulatory proteins, eicosanoid metabolizing enzymes and anti-apoptotic genes. It is well known that NF-? B plays a key role in the regulated expression of a large number of pro-inflammatory mediators, including cytokines such as TNF, IL-1β, IL-6 and IL-8, adhesion molecules cells such as ICAM and VCAM, and inducible nitric oxide-synthase (iNOS). It is known that these mediators play a role in the recruitment of leukocytes at sites of inflammation, and in the case of NOS, they can lead to the destruction of the organ in some inflammatory and autoimmune diseases. The importance of NF-? B in inflammatory disorders is further highlighted by studies of airway inflammation, including asthma, in which it has been shown that NF-? B is activated. This activation may be the underlying cause of increased cytokine production and infiltration by leukocytes, which are characteristic of these disorders. In addition, it is known that inhaled steroids reduce airway hyperreactivity and suppress the inflammatory response in asthmatic airways. In light of recent findings about the inhibition of NF-? B by glucocorticoids, one might speculate that in these effects the inhibition of NF-? B intervenes. An additional test of the role of NF-? B in inflammatory disorders is provided by rheumatoid synovia studies. Although NF-? B is normally present in the form of an inactive cytoplasmic complex, recent immunohistochemical studies have indicated that NF-? B is present in the nuclei, and is therefore active, in the cells constituting the rheumatoid synovium. In addition, it has been shown that NF-? B is activated in human synovial cells in response to stimulation with TNF-α or IL-1β. Said distribution may constitute the mechanism responsible for the increased production of cytokines and eicosanoids characteristic of this tissue. See Roshak, A. K., et. al., J. Biol. Chem., 271, 31496-31501 (1996). The expression of IKK-β has been demonstrated in synoviocytes of patients with rheumatoid arthritis, and gene transfer studies have demonstrated the central role of IKK-β in the stimulated production of inflammatory mediator in these cells. See Aupperele et. al., J. Immunology 1999; 163: 427-433 and Aupperle et. al., J. Immunology 2001; 166: 2705-11, More recently, it has been shown that intra-articular administration of an adenoviral construct of wild-type IKK-β causes swelling of the legs in the rat, while intra-articular administration of IKKß dominant-negative inhibited adjuvant-induced arthritis in the rat. See Tak et. al., Arthritis and Rheumatism 2001, 44: 1897-1907. It is also likely that the NF-? B / Rel and l B proteins have a key role in the transformation and neoplastic metastases. The members of the family are associated with cell transformation in vitro and in vivo as a consequence of hyper-expression, gene multiplication, and gene translocations or translocations. In addition, in 20-25% of some human lymphoid tumors, transposition and / or multiplication of the genes encoding these proteins is observed. In addition, NF-? B is activated by oncogenic ras, the most common defect in human tumors, and blockade of NF-? B activation inhibits cellular transformation in which ras is involved. The role played by NF-? B in the regulation of apoptosis has also been reported, which reinforces the role of this transcription factor in the regulation of tumor cell proliferation. It has been shown that TNF, ionizing radiation, and DNA damaging agents activate NF-βB, which, in turn, leads to the expression, positively regulated, of various anti-apoptotic proteins. Conversely, it has been shown that inhibition of NF-? B enhances the apoptotic death caused by these agents in various types of tumor cells. By representing this fact as a major mechanism of resistance of tumor cells to chemotherapy, inhibitors of NF-β B activation can be useful chemotherapeutic agents, either as sole agents, or in the form of adjunctive therapy. Recent reports have implicated NF-? B as an inhibitor of skeletal cell differentiation, and as a regulator of cytokine-induced muscle wasting (Guttridge et al., Science; 2000; 289: 2363-2365) further confirming the potential of NF-? B inhibitors as new therapies against cancer. In C. Wahl, et al. J. Clin. Invest. 101 (5), 1163-1174 (1998), R.
W. Sullivan, et al. J. Med. Chem. 41, 413-419 (1998), J. W. Pierce, et al. J. Biol. Chem. 272, 21096-21103 (1997) several NF-DB inhibitors are described. It is known that the marine natural product hymenialdisin inhibits NF-? B (Roshak, A. et al., JPET, 283, 955-961 (1997), Breton, JJ and Chabot-Fletcher, M. C, JPET, 282, 459-466 (1997) In addition, patent applications have been submitted for inhibitor aminothiophenes of IKK2, see Callahan et al., WO 2002030353, Baxter et al., WO 2001058890, Faull et. Al., WO document. 2003010158; Griffiths et al., WO 2003010163; Fancelli, et al., WO 200198290; Granetto, et al., WO2003037886; Imidazoles IKK2 Inhibitors, see Callahan et al., WO 200230423; Anilinophenylpyrimidines; inhibitors of IK 2, see Kois et al., WO2002046171; ß-carbolines inhibitors of IKK2, see Ritzeler et al., WO 2001068648, Ritzeler et al., EP 1134221; Nielsch et. al., DE 19807993; Ritzeler et al., EP 1209158; Inhibitors of IKK2, see Ritzeler et al., WO 2001030774; imidazole inhibitors of IKK2, see Ritzeler et. al., DE 19928424; Ritzeler et. al., WO 2001000610; Ritzeler et. al., WO 2004022553; inhibitory aminopyridines of IKK2, see Lowinger et. al., WO2002024679; Murata et al, WO2002024693; Murata et al, WO2002044153; inhibitory aminopyrimidines of IKK2, see Bollbuck, et al., WO 2004089913; pyrazoles inhibitors of IKK2, see Bergmanis, et al., WO 2003024935;, Metz, et al., WO 2003024936; Geng et al., WO 2003027075; Stealey, et al., WO 2003035625; Xu, ef al., WO200307076; Lennon, et al., WO 2003095430; inhibitory pyrazinones of IKK2, see Boys, et al., WO 2005035527; IKK2-inhibiting pyrazolquinazolines, see Beaulieu et al, WO2002028860; Burke et al, WO2002060386; Burke, et al. US 20030022898; tricyclic thiophenes inhibitors of IKK2, see Belema, et al., WO 2003084959; IKK2-inhibiting pyrazolopurines, see Qiu, et al., WO 2004075846; oxazolo and thiazolo inhibiting pyridines of IKK2, see Pitts, et al., WO 2004106293; inhibitory quinolines of IKK2, Browner et. al., WO2002041843, Browner et. al., US 20020161004 and IKK2 inhibiting pyridylcyanguanidines, see Bjorkling et. al., WO 2002094813, Binderup et. al., WO 2002094322 and Madsen et. al., WO200294265; inhibitory thienopyridines of IKK2, see Cywin, et al., WO 2003103661; Liu, et al., WO2005035537; benzothiophenes inhibitors of IKK2, see Chen et al., WO 2005012283. It has been shown that the natural products staurosporine, quercetin, K252a and K252b are inhibitors of IKK2, see Peet, GW and Li, JJ Biol. Chem., 274, 32655-32661 (1999) and Wisniewski, D., ef al., Analytical Biochem. 21 A, 220-228 (1999). Synthetic inhibitors of IKK2 have also been described, see Burke, et al. J. Biol. Chem., 278, 1450-1456 (2003), Murata, et al., Bioorg. Med. Chem. Lett., 13, 913-198 (2003), Murata, et al., Bioorg. Med. Chem. Leti., 14, 4013-4017 (2004) and Murata, et al., Bioorg. Med. Chem. Lett., 14, 4019-4022 (2004) have described inhibitors of IKK2. Thus, attempts have been made to prepare compounds that inhibit the activity of IKK2, and several of these compounds have been disclosed in the art. However, in view of the number of pathological responses involving IKK2, there continues to be a continuing need for inhibitors of IKK2 that can be used in the treatment of various conditions. The present inventors have discovered new indole carboxamide compounds which are inhibitors of kinase activity, in particular the activity of inappropriate IKK2. Therefore, these indole carboxamide derivatives are useful in the treatment of disorders associated with inappropriate kinases, in particular with inappropriate IKK2 activity, in particular in the treatment and prevention of disease states mediated by IKK2 mechanisms including inflammatory disorders and tissue repair, particularly rheumatoid arthritis, inflammatory disease of the intestine, asthma and COPD (chronic obstructive pulmonary disease); osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and skin lesions induced by ultraviolet (UV) radiation, autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis , restenosis, diabetes, glomerulonephritis, cancer, including Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immunodeficiency syndrome (AIDS), respiratory distress syndrome in adults and ataxia telangiectasia .
BRIEF DESCRIPTION OF THE DNVE The invention relates to novel indole carboxamide derivatives. Specifically, the invention relates to compounds according to Formula (I): where R1, R2, R3, U and V are defined below and to pharmaceutically acceptable salts thereof.
The compounds of the invention are inhibitors of IKK2, and may be useful in the treatment of disorders associated with inadequate activity of IKK2 (also called IKKß), such as rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease (COPD, COPD). Accordingly, the invention further relates to pharmaceutical compositions comprising a compound of the invention.
The invention further relates to methods for inhibiting the activity of! KK2, and to the treatment of disorders associated therewith, employing a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
DETAILED DESCRIPTION OF THE INVENTION The invention relates to compounds according to the Formula X is phenyl, heteroaryl, 1, 2,3,4-tetrahydronaphthalenyl or 2,3-dihydro-1 H-indenyl, wherein said phenyl, heteroaryl, 1, 2,3,4-tetrahydronaphthalenyl and 2,3-groups Dihydro-1 H-indenyl are optionally substituted with one or two substituents each independently selected from the following: 1) halo, 2) nitro, 3) cyano, 4) -NR7R8, 5) C- | -C6 alkyl, 6) CHO, 7) CONH2 and 8) -OR4, where said alkyl C-C? is optionally substituted with a group - NR4R5; and is a C ^ -C Q bond or alkylene, where C-j-Cs alkylene is optionally substituted with one or two substituents each independently selected from the following: 1) C 1 -C 3 alkyl optionally substituted with an OR 4 group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) hydroxy and 5) heteroaryl; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or two substituents each independently selected from the group consisting of following: 1) C- | -C alkyl? optionally substituted with an OR4 group or a heterocycloalkyl group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) -CONH2 5) hydroxy, 6) heteroaryl, 7) CF3, 8) phenyl, 9) heterocycloalkyl and 10) N ( CH3) 2; R2 is selected from 1) H, 2) fluoro, and 3) chloro; R3 is selected from 1) H, 2) fluoro, and 3) chloro; R 4 is selected from 1) H and 2) C 1 -C 2 alkyl, wherein said C ^ -CQ alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C5-C6 heterocycloalkyl, 3) -C02Et, 4) C < \ -CQ, 5) cycloalkyl 03-07, 6) C ^ -CQ alkyl, 7) -SO2R10 and 8) -C (O) R10, where said C3-C7 cycloalkyl groups and C-j-C alkyl? are optionally substituted with one to three substituents selected from R6; each R6 is independently selected from 1) -NR7R8, 2) -S02R7, 3) -CONH2, 4) -CF3, 5) -CN, 6) -C02R7, 7) -OCH2CH2OR7, 8) -SRd, 9) C3 alkenyl -C4, 10) OH, 11) C 1 -C 5 alkoxy, 12) heteroaryl, 13) C 3 -C 7 cycloalkyl, 14) phenyl, 15) heterocycloalkyl and 16) halo, wherein said heteroaryl, cycloalkyl, phenyl and heterocycloalkyl groups are optionally substituted with each other two substituents selected from R9; R7 is selected from 1) H, 2) C1-C3 alkyl and 3) phenyl; R8 is selected from 1) H, 2) C1-C3 alkyl and 3) -C (0) R4; each R 9 is independently selected from 1) hydroxy, 2) -OMe, 3) nitro, 4) C 1 -Cg alkyl, 5) NH 2, 6) halo, 7) CF3, 8) alkoxy Ci-Cg and 9) CN; R 10 is selected from 1) H, 2) C 1 -C 4 alkyl, 3) phenyl, 4) C 3 -C 7 cycloalkyl, 5) heteroaryl, 6) C 1 -C 6 heteroaryl and 7) heterocycloalkyl, wherein said C 4 -C alkyl group ? is optionally substituted with one or two substituents each independently selected from C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a group -C (0) R7; and wherein said phenyl, heteroaryl and heteroaryl groups Ci-C? they are optionally substituted with one to two substituents selected from R11; each R 11 is independently selected from 1) H, 2) Ci-Cß alkyl and 3) halo; U is a bond, C ^ -Cg alkylene or C2-Cg alkenylene; V is phenyl, 5- or 6-membered heteroaryl, 5-7 membered heterocycloalkyl, C5-C7 cycloalkyl or C5-C7 cycloalkenyl, each of which is substituted with -N (R7) S (0) mR12, -S (0 ) mN (R7) R12, -S (0) mR12 or -C (0) R12; m is 1 or 2; and R12 is Ci-Cß alkyl, C3-C7 cycloalkyl, Ci-Cg alkyl C3-C7 cycloalkyl or C 1 -C β alkyl phenyl; or one of its pharmaceutically acceptable salts. One embodiment of the present invention is a compound according to formula (I): wherein R1 is the group -XYZ; X is phenyl or heteroaryl, wherein said phenyl and heteroaryl groups are optionally substituted with one or two substituents each independently selected from the following: 1) halo, 2) nitro, 3) cyano, 4) -NR7R8, 5) alkyl C ^ -Cg, 6) CHO, 7) CONH2 and 8) -OR4, where said alkyl group CjC? is optionally substituted with a group - NR4R5; Y is a bond or alkylene C-j-Cg, where the alkylene group C-J -CR. it is optionally substituted with one or two substituents each of them independently selected from the following: 1) C1-C3 alkyl optionally substituted with an OR4 group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) hydroxy and 5) heteroaryl; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two substituents each independently selected from the following: 1) C ^ - Q alkyl optionally substituted with an OR4 group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) hydroxy and 5) heteroaryl; R2 is selected from 1) H, 2) fluoro, and 3) chloro; R3 is selected from 1) H, 2) fluoro, and 3) chloro; R 4 is selected from 1) H and 2) alkyl C < Cg, where said alkyl group C < Cg is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) Cj-Cg alkoxy, 3) C3-C7 cycloalkyl, 4) C- | -Cg alkyl, 5) -SO2R10 and 6) -C (O) R10, wherein said C3 cycloalkyl groups -C7 and alkyl Cj-Cg are optionally substituted with one to three substituents selected from R6; each R6 is independently selected from 1) -NR7R8, 2) -S02R7, 3) OH, 4) meioxy, 5) heteroaryl, 6) C3-C7 cycloalkyl, 7) phenyl, 8) heterocycloalkyl and 9) halo, wherein said heleroaryl, cycloalkyl, phenyl and heterocycloalkyl groups are optionally substituted with one to two selected substitutents on R9; R7 is selected from 1) H and 2) C1-C3 alkyl; R8 is selected from 1) H and 2) C1-C3 alkyl; each R9 is independently selected from 1) hydroxy, 2) nilro, 3) C- | -Cg alkyl, 4) NH2, 5) halo, 6) CF3, 7) C-] -Cg alkoxy and 8) CN; R 10 is selected from 1) H, 2) C 1 -Cg alkyl, 3) phenyl, 4) C3-C7 cycloalkyl and 5) heleroaryl, wherein said C-Cg-Cg alkyl group is optionally substituted with one or two substituents each independently selected from C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a -C (0) R7 group; and wherein said phenyl and heteroaryl groups are optionally substituted with one to two substituents selected from R11; each R11 is independently selected from 1) H, 2) C < | -C and 3) halo; U is a bond, Ci-Cg alkylene or C2-C alkenylene; V is phenyl, 5- or 6-membered heteroaryl, 5-7 membered heterocycloalkyl, C5-C7 cycloalkyl or C5-C7 cycloalkenyl, each of which is substituted by -N (R7) S (0) mR12, -S (0 ) mN (R7) R12, -S (0) mR12, or -C (0) R12; m is 1 or 2; Y R12 is C- | -Cg alkyl, C3-C7 cycloalkyl, C3-Cg-Cg-C3-C7 cycloalkyl or C-j-Cg-phenyl alkyl; or one of its pharmaceutically acceptable salts. Another embodiment of the present invention is a compound according to formula (I): where R1 is the group -XYZ or; X is phenyl, heleroaryl, 1, 2,3,4-lelrahydronaphthalenyl or 2,3-dihydro-1H-indenyl; And it is a bond or alkylene C-j-Cg; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two substituents each independently selected from the following: 1) Cj-Cg alkyl optionally substituted with an OR4 group or a heterocycloalkyl group, 2) C3 cycloalkyl -C7, 3) methoxy, 4) -CONH2 5) hydroxy, 6) heteroaryl; 7) CF3, 8) phenyl, 9) heterocycloalkyl and 10) N (CH3) 2; R2 is H; R3 is H; R 4 is selected from 1) H and 2) Ci-Cg alkyl, wherein said C-j-Cg alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) Cs-Cg heterocyanoalkyl, 3) -C02Et, 4) C- | -Cg alkoxy, 5) C3-C7 cycloalkyl, 6) C- alkyl; -Cg, 7) -SO2R10 and 8) -C (O) R10, wherein said C3-C7 cycloalkyl groups and C-j-Cg alkyl are optionally substituted with one to substitute IEs selected from R6; each R6 is independently selected in 1) -NR7R8, 2) -S02R7, 4) -CF3, 5) -CN, 6) -C02R7, 7) -OCH2CH2OR7, 8) -SRd, 9) C3-C4 alkenyl, 10) OH, 11) Ci-Cg alkoxy, 12) heleroaryl, 13) C3-C7 cycloalkyl, 14) phenyl, 15) heterocycloalkyl and 16) halo, wherein said heteroaryl, cycloalkyl, phenyl and heterocycloalkyl groups are optionally substituted with one to two substituents selected from R9; R7 is selected from 1) H, 2) C1-C3 alkyl and 3) phenyl; R8 is selected from 1) H, 2) C1-C3 alkyl and 3) -C (0) R4; each R9 is independently selected from 1) hydroxy, 2) -OMe 3) nitro, 4) alkyl C-j-Cg, 5) NH2, 6) halo, 7) CF3, 8) C- alkoxy | -Cg and 9) CN; R10 is selected from 1) H, 2) C < Cg, 3) phenyl, 4) C3-C7 cycloalkyl, 5) heteroaryl, 6) heteroaryl C- | -Cg and 7) heterocycloalkyl, wherein said alkyl group C <; -Cg is optionally substituted with one or two substituents each independently selected from C3-C7 cycloalkyl and -SR7; wherein said heterocycloalkyl group is optionally substituted with a -C (0) R7 group; and wherein said phenyl, heteroaryl and C-Cg heteroaryl groups are optionally substituted with one to two substituents selected from R11; each R 11 is independently selected from 1) H, 2) C 1 -Cg alkyl and 3) halo; U is a link; V is a 5-7 membered heterocycloalkyl substituted with -S (0) mR12; m is 1 or 2; and R12 is C-j-Cg alkyl; or one of its salts pharmaceutically acceptable Another embodiment of the present invention is a compound according to formula (I): wherein R1 is the group -XYZ; X is phenyl or heteroaryl; Y is a bond or alkylene C-¡-Cg; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two substituents each independently selected from the following: 1) C-Cg alkyl optionally substituted with an OR4 group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) hydroxy and 5) heteroaryl; R2 is H; R3 is H; R4 is selected from 1) H and 2) C-j-Cg alkyl, wherein said C-Cg-alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C- | -Cg alkoxy, 3) C3-C7 cycloalkyl, 4) C- alkyl; -Cg, 5) -SO2R10 and 6) -C (O) R10, wherein said C3-C7 cycloalkyl groups and C- | -Cg alkyl are optionally substituted with one to three selected sulylyenics enire R6; each R6 is independently selected from 1) NR7R8, 2) S02R7, 3) OH, 4) methoxy, 5) heeroaryl, 6) C3-C7 cycloalkyl, 7) phenyl, 8) heterocycloalkyl and 9) halo, wherein said heteroaryl groups, cycloalkyl, phenyl and heterocycloalkyl are optionally substituted with one to two substituins selected from R9; R7 is selected from 1) H and 2) C1-C3 alkyl; R8 is selected from 1) H and 2) C1-C3 alkyl; each R9 is independently selected from 1) hydroxy, 2) nilro, 3) alkyl C-j-Cg, 4) NH 2, 5) halo, 6) CF 3, 7) alkoxy C-α-Cg and 8) CN; R10 is selected from 1) H, 2) Ci-Cg alkyl, 3) phenyl, 4) C3-C7 cycloalkyl and 5) heleroaryl, wherein said Cj-Cg alkyl group is optionally substituted with one or two substituents each selected independently between C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a group -C (0) R7; and wherein said phenyl and heteroaryl groups are optionally substituted with one to two substituents selected from R11; each R11 is independently selected from 1) H, 2) alkyl C-j-Cg and 3) halo; U is a link; V is a 5-7 membered heteroaryloalkyl substituted with -S (0) mR12; m is 1 or 2; and R12 is C- | -Cg alkyl; or one of its pharmaceutically acceptable salts. Another embodiment of the present invention is a compound of formula (I): wherein R1 is the group -XYZ; X is 2- or 3-iiophenyl; Y is a C1-C4 alkylene or bond; Z is -NR4R5 or heterocycloalkyl, 1) C-j-Cg alkyl optionally substituted with an OR4 group or a heyerocycloalkyl group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) -CONH2.5) hydroxy, 6) heteroaryl; 7) CF3, 8) phenyl, 9) heterocycloalkyl and 10) N (CH3) 2; R2 is H; R3 is H; R4 is selected from 1) H and 2) alkyl C-j-Cg, wherein said C - ^ - Cg alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) C3-C7 cycloalkyl, 2) C- alkyl; -Cg, wherein said C3-C7 cycloalkyl groups and C-Cg alkyl are optionally substituted with one to three substituents selected from R6; each R6 is independently selected from 1) -NR7R8, 2) -CONH2, 3) -CN, 4) -OCH2CH2OR7, 5) C3-C4 alkenyl, 6) OH, 7) C4-Cg alkoxy, 8) heteroaryl, C3-C7 cycloalkyl, 10) phenyl, 11) heteroarylcycloalkyl, and 12) halo, wherein said heyaroaryl, cycloalkyl, phenyl and heteroarylcycloalkyl groups are optionally susiluted with one to two selected hydrolenes on R9; R7 is selected enire 1) H, 2) C1-C3 alkyl and 3) phenyl; R8 is selected enlre 1) H, 2) C- alkyl; -C3 and 3) -C (0) R4; each R9 is independently selected from 1) alkyl C- | -Cg; U is a link; V is 4-piperidinyl substituted with -S (0) 2R12; and R12 is ethyl or Sopropyl; or one of its pharmaceutically acceptable salts. Another embodiment of the present invention is a compound of or II according to formula (I) in which the group U-V is and R12 is ethyl or isopropyl.
Another embodiment of the present invention is a compound of formula (II) (H) wherein R13 is -NR14R1 d or heterocycloalkyl wherein said heterocycloalkyl group is optionally substituted with one or two substituents selected from the following: 1) optionally substituted C-Cg alkyl optionally with a group OR14, 2) hydroxy, 3) meioxy and 4) heeroaryl; R14 is selected from 1) H and 2) C- alkyl; -Cg, wherein said C-Cg alkyl group is optionally substituted with a hydroxyl group or a meioxy group; R1d is selected to be 1) H, 2) meloxi, 3) C3-C7 cycloalkyl and 4) C-j-Cg alkyl, wherein said C3-C7 cycloalkyl group and C-i-Cg alkyl are optionally substituted with one to three selected substituents on R16; each R16 is independently selected from 1) -NR17R18, 2) -S02R17, 3) OH, 4) meloxy 5) heteroaryl, 6) C3-C7 cycloalkyl, 7) phenyl and 8) heterocycloalkyl, wherein said heteroaryl, cycloalkyl, phenyl groups and heterocycloalkyl are optionally substituted with one of the selected derivatives of R19; R17 is selected from 1) H and 2) C1-C3 alkyl; R18 is selected from 1) H and 2) C- alkyl; -C3; R19 is selected enire 1) hydroxy, 2) ni, 3) alkyl C-j-Cg, 4) NH 2, d) halo, 6) CF 3 and 7) alkoxy C- | -Cg; and n is 1 to 3; or one of its pharmaceutically acceptable salts. Specific examples of compounds of the present invention include the following: 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- (1-piperidinylmethyl) phenyl] -1- / - n-dol-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (1-piperazinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-pi? Eridinyl] -d- [3- ( {meiyl [2- (meilylsulfonyl) ethyl] amino} methyl) phenyl] -1 / - / - indole 7-carboxamide; 5- (3-. {[[[2- (dimethylamino) eyl] (meily) amino] methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - -indol-7 -carboxamide; 3- [1- (erylsulfonyl) -4-piperidinyl] -5-. { 3 - [(4- {2 - [(2-hydroxy-yl) oxy] ethyl} -1-piperazinyl) methyl] phenyl} -1 / - / - ndol-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3 { [3- (hydroxymethyl) -1-piperidinyl] methyl} phenyl) -1 / - / - indole-7 -carboxamida; 5- [3- (. {Bis [2- (meilyloxy) ethyl] amino] methyl] phenol] -3- [1- (ethylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; d-. { 3 - [(2,6-dimethyll-4-morpholinyl) meily] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- (3- {[[2- (1, 3-Jiazol-2-yl) -1-pyrrolidinyl] methyl} phenyl) -1 / - / -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- (3- {[2- (2-Kienyl) -1-pyrrolidinyl] -meiyl} phenyl) -1H-indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -d- (3. {[[(2-hydroxy-2-phenylethyl) (meityl) amino] methyl} phenyl) -1 / - / - indole -7-carboxamide; d- (3- { [elyl (melil) amino] methyl} phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1- f -indole-7-carboxamide; d- [3- (aminomethyl) phenyl] -3- [1- (ylsulfonyl) -4-pperidinyl] -1 / - / - indole-7-carboxamide; 5-. { 3 - [(Cyclopentylamino) meily] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5- [3- ( { [(3,4-Dihydroxyphenyl) methyl] amine} .methyl) phenyl] -3- [1- (et.sub.lsu] fonyl) -4-piperidinyl] -1- / -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-ynylmethyl) amino] -methyl} phenyl) -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- ( { [(2S) -2- (hydroxylmethyl) -3-methylobuyl] amino} methyl) phenyl] -1 / - -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-pyridinyl] -5- (3. {[[(2-hydro? -1-methylylyl) amino] methyl} phenyl) -1 / - -indol-7 -carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3. {[[(Fraps-4-hydroxycyclohexyl) amino] -methyl} phenyl) -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d-. { 3 - [( { [1- (1-piperidinyl) cyclohexyl] methyl.}. Amino) methyl] phenyl} -1 / - -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [3- ( { [(2S) -2-hydroxypropyl] amino} methyl) phenyl] -1 / - -indole-7-carboxamide; 5-. { 3 - [(eilamino) methyl] phenyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d-. { 3 - [(propylamino) meily] phenyl} -1 / - / - indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(1-methylethyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 5- (3-. {[[(1-elylpropyl) amino] -methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- [3- (1-piperidinylmethyl) phenyl] -1 H- n-dol-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [4- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(meilyamino) meily] phenyl} -1 - / - indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [4- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 5- [4- (aminomethyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; d-. { 3 - [(cyclopropylamino) meily] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -IH-indole-7-carboxamide; 5-. { 3 - [(cyclobuhlamino) methyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide; 3- (1- { [3- (dimethylamino) propyl] sulfonyl.} -4-piperidinyl) -5- [4- (1-piperidinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (erylsulfonyl) -4-piperidinyl] -d-. { 3 - [(2-meitylpropyl) amino] -2,3-dihydro-1 H -inden-5-yl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 8 - [(2-Meitylpropyl) amino] -5,6,7,8-tetrahydro-2-naphthalenyl} -1 H -indole-7-carboxamide; 5- (5- { [(2-cyanoethyl) amino] meiyl.} -2-fluorophenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- (2-fluoro-d-. {[[(2,2,2-lrifluoro-eyl) amino] -methyl] phenyl] -1 H- indole-7-carboxamide; 3- [1 - (ynylsulfonyl) -4-picperidinyl] -d- (1, 2,3,4-eeryhydro-7-isoquinolinyl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(2,2,2-trifluoroethyl) amino] methyl} phenyl) -1 H -indole-7- carboxamide; 5- (3- { [(2-amino-2-oxo-ethyl) (melil) amino] methyl} phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamida; 3- [1- (ethylsulphonyl) -4-piperidinyl] -d- (2- {[[(2,2,2-ylfluoroyl) amino] -methyl] -1,3-liazol-4-yl} ) -1 H -indole-7-carboxamide; d- (3-cyano-d-. {[[(2,2,2-ylfluoroyl) amino] -methyl] phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[Mei] l (1-methyl-4-piperidinyl) amino] meityl}. -3-thienyl) -1 H- indole-7-carboxamide; d- (d- { [(2-cyanoethyl) (meityl) amino] meityl} .3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; d- (d-. {[[(2-amino-2-oxo-ethyl) (meily) amino] -methyl] -3-ynyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- (. {Methyl} 2- (phenylsulfonyl) ell] amino} methyl) -3-ynyl] -1H-indole 7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-phenyl-1-pyrrolidinyl) methyl] -3-ynyl} -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-p -peridinyl] -5- (5- { [2- (1-piperidinylmethyl) -1-pyrrolidinyl] methyl.} -3- indium) -1 H -indole-7-carboxamide; 5- (5- { [(2R) -2- (aminocarbonyl) -1-pyrrolidinyl] -methyl] -3-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; d- (d- { [(2S) -2- (dimethylamino) -1-pyrrolidinyl] -methyl] -3-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (1 - { 2- [4- (dimethylamino) -1-piperidinyl] eyl.} -1 H -pyrazol-4-yl) -3- [1- (erylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 5- [3 - [(dimethylamino) methyl] -4,5-bis (mellyloxy) phenyl] -3- [1- (eylsu-fonyl) - 4-piperidinyl] -1 H -indole-7-carboxamide; d- [3,4-bis (methyloxy) -5- (4-morpholinylmethyl) phenyl] -3- [1- (eylsulfonyl) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-. { [(1-methyleryl) amino] methyl} -4,5-bis (methyloxy) phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3-. { [(1-Methyleryl) amino] methyl} -4,5-bis (methyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3-. { [(2,2-dimethypropyl) amino] meityl} -4,5-bis (methyloxy) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -d- [3-. { [(2-hydroxyielyl) (meityl) amino] meityl} -4,5-bis (methyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3,4-bis (meilyloxy) -5- (1-pyrrolidinylmethyl) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(dimethylamino) meily] -2,3-dihydro-1-benzofuran-6-yl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4- {[[(1-methyleryl) amino] -methyl} -2,3-dihydro-1-benzofuran-6-yl ) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- (4-morpholinylmethyl) -2,3-dihydro-1-benzofuran-6-yl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [5- ( { [1-methyl-2- (methyloxy) ellyl] amino} methyl) -2-ynyl] -1 H- indole-7-carboxamide; 5- (d- { [(2-Cyanoethyl) amino] methyl] -3-pyridinyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (5- {[[(2,2,2-ylfluoroyl) amino] methyl} - 3-pyridinyl) -1 H-indole-7 -carboxamide; 5-. { 3 - [(dimethylamino) meily] phenyl} -3- [1- (ynylsulfonyl) -4-pichandinyl] -1 H -indole-7-carboxamide; d- (d- { [elyl (methyl) amino] methyl] -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- (5-. {[[[2- (diethylamino) ethyl] (methyl) amino] methyl} -3-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 5- (5- { [Butyl (methyl) amino] -methyl] -3-thienyl) -3- [1- (ynylsulfonyl) -4-pperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5. {[[Meityl (propyl) amino] methyl} -3-ynyl) -1 H -indole-7-carboxamide; 5- (5- { [[2- (dimethylamino) yl]] (melil) amino] methyl} -3-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 5- (5-. {[[[3- (dimethylamino) propyl] (meityl) amino] meityl} -3-ynyl) -3- [1- (erylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; d- (d- { [cyclopenyl (methyl) amino] methyl] -3-lienyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[Methyl (penylyl) amino] -methyl] -3-ynyl) -1 H-indol-7- carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- (5- {[[meiyl (2-meitylpropyl) amino] -methyl] -3-ynyl) -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- {[mell (phenylmethyl) amino] meily}. 3-ynyl) -1 H-indol-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-hydroxyethyl) (methyl) amino] meityl}. -3-yenyl) -1 H -indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [d- ( {methyl [2- (2-pyridinyl) eyl] amino} methyl) -3-ynyl] -1 H-indole -7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-furanylmethyl) (methyl) amino] meilyl}. -3-lienyl) -1 H -indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- (5. {[[Meily (4-pyridinylmethyl) amino] methyl} -3-ynyl) -1 H -indole-7-carboxamide;; 3- [1- (allylsulfonyl) -4-piperidinyl] -5-. { 5 - [(meityl {[[1- (1-methylethyl) -3-pyrrolidinyl] methyl} amino) meityl] -3-ynyl} -1 H -indole-7-carboxamide;; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5. {[[Meily (2-lienylmethyl) amino] -methyl] -3-lienyl) -1H-indole-7-carboxam gives; 3- [1 - (elylsulfonyl) -4-piperidinyl] -d- [d- (. {Me.] -1- (2-ynyl) eyl] amino} methyl) -3-ynyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5. {[[Meily (3-ynylmethyl) amino] methyl} -3-ynyl) -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5. {[[Meityl (1-hydra-2H-pyran-4-ylmethylamino] -methyl] -3-ynyl) -1 H- indole-7-carboxamide; írífluoroacelaío 3- [1 - (eíilsulfonil) -4-piperidinyl] -d- (d- -3-lienil. {[meíil (3-piridinilmeíil) amino] meí¡l..}.) -1 H-indole-7 -carboxamide; írifluoroaceíaío 3- [1- (eíilsulfon¡l) -4-piperídin¡l] -d- (5- -3-íienil. {[meíil (4-pirimidinílmet¡l) am¡no] meíil..}.) - 1 H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- [d- ({methyl [2- (melyloxy) ethyl] amino} methyl) -3-lienyl] -1H-indol-7 -carboxamide; d-. { 3 - [(dimethylamino) meily] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- (d-. {[[Methyl (1-methylethyl) amino] rneyl} - 3-thienyl) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-propyl-1-pyrrolidinyl) methyl] -3-ynyl} -1 H-indol-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- { [2- (3-pyridinyl) -1-pyrrolidinyl] -methyl] -3-thienyl) -1H-indole 7-carboxamide; 5- (5- { [2- (1 J-dimethylethyl) -1-pyrrolidinyl] methyl} -3-ynyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H-indole -7-carboxamide; 5-. { d - [(2-eyl-1-pyrrolidinyl) meily] -3-lienyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- (d- { [2- (2-methylpropyl) -1-pyrrolidinyl] methyl} -3-lienl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-p -peridinyl] -d- (d- { [2- (1-methyleryl) -1-pyrrolidinyl] -methyl] -3-ynyl) -1 H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- [d- ( { (2S) -2 - [(mexyloxy) -methyl] -1-pyrrolidinyl} -methyl) -3 -lienyl] -1 H -indole-7-carboxamide; d- (d- { [cyclohexyl (meityl) amino] methyl} -3-ynyl) -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- (d- { [2- (2-methylpropyl) -1- pyrrolidinyl] methyl} -3-lienyl) -1 H -indole-7-carboxamide; 5- (5-. {[[Eyl (meily) amino] -methyl] -3-lienyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5. {[[Meily (propyl) amino] -methyl] -3-thienyl) -1 H -indole-7-carboxamide; 3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -5- (5-. {[[Methyl (propyl) amino] -methyl] -3-ynyl) -1 H -indole-7-carboxamide; 5- (5- { [Elyl (meily) amino] methyl.} -3Jienyl) -3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -d- [d- (. {Meylethyl [2- (mexyloxy) eyl] amino] -methyl) -3-thienyl] -1H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d-. { 5 - [(meitylamino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-meityl-1-pyrrolidinyl) meityl] -3-ynyl} -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- (d-. {[[(2-methylpropyl) amino] methyl] -3-ynyl) -1 H-indole-7 -carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5-. { 5 - [(propylamino) meily] -3-ienl} -1 H -indole-7-carboxamide; 5-. { 5 - [(Dienylamino) meily] -3-l-phenyl} -3- [1- (ynylsulfonyl) -4-pi? Eridinyl] -1 H -indole-7-carboxamide; 5- (d- { [(2R, 5R) -2,5-dimethyl-1-pyrrolidinyl] methyl} -3-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide; d-. { 5 - [(Cyclopropylamino) methyl] -3-ynyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(Cyclobutylamino) meityl] -3-ynyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(dimethylamino) meily] -3-ynyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5- (5-. {[[(Cyclopentelmethyl) amino] methyl} -3-lienyl) -3- [1- (ethyl sulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [5- ( { [(1 R) -1,2-dimethypropyl] amino] methyl) -3-t-phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(Cyclopenylamino) meily] -3-ynyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopropylmethyl) amino] methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- [5- ( { [(1S) -1,2-Dimethylpropyl] amino} .meiyl) -3-lienyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 5- (5- { [(2,2-dimethylpropyl) amino] methyl] -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- {[[(phenylmethyl) amino] methyl} -3-ynyl) -1 H -indole-7-carbo-amide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [5- ( { [(2SHelrahydro-2-furanylmethyl] amino} methyl) -3-lienyl] -1 H -indole-7- carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- ({[[(1-hydra-2H-pyran-4-) Lmeil) amino] meil} -3-yenyl) -1 H-indole-7-carboxamide; d-. { d - [(buleylamino) meyl] -3-l-phenyl} -3- [1- (ynylsulfonyl) -4-pichandinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- ( { [(2R) Jelrah ~ dro-2-furanylmethyl] amino} melyl) -3-lienyl] -1 H- indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [5- ( { (2S) -2 - [(mylyloxy) meily] -1-pyrrolidinyl} -methyl) -3-yenyl ] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [5- ( { (2R) -2 - [(methyloxy) meily] -1-pyrrolidinyl} .methyl) -3-lienyl] - 1 H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 4- [2- (meitylamino) eyl] phenl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d-. { 4- [2- (propylamino) elyl] phenyl} -1 H -indole-7-carboxamide; d-. { 4- [2- (the] amino) ethyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [( { [1- (1 J-dimethylylyl) -3-meityl-1 H -pyrazol-5-yl] carbonyl} amino) meilyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-. {[[(4-pyridinylcarbonyl) amino] methyl] phenyl) -1 H -indole-7-carboxam gives; 5- (4-. {[[(Cyclopenylcarbonyl) amino] meilyl} phenyl) -3- [1- (elysulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4- { [(2- furanylcarbonyl) amino] meityl} phenyl) -1 H -indole-7-carboxamide; d-. { 4- [2- (Acelylamino) elyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- (4-. {2 - [(methylsulfonyl) amino] eyl.} Phenyl) -1 H -indole-7-carboxamide; d- (4- {2 - [(cyclobuylcarbonyl) amino] eyl.} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- (4- {2 - [(cyclohexylcarbonyl) amino] eyl] phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- (3- {2- [(methylsulfonyl) amino] ethyl} phenyl) -1 H -indole-7-carboxamide; 5- (3- {2 - [(cyclohexylcarbonyl) amino] ethyl] phenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [6- (1-piperazinyl) -3-pyridinyl] -1 H -indole-7-carboxamide; Irifluoroacelalo; 5- [6- (4-elyl-1-piperazinyl) -3-pyridinyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (sulfonyl) -4-piperidinyl] -5- [3- (1-piperidinylmethyl) pheni-1 H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 4 - [(Mellylamino) meily] phenyl} -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-p -peridinyl] -5- (4- {[[(1-methylethylamino) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (erylsulfonyl) -4-piperidinyl] -d-. { 4 - [(propylamino) -methyl] phenyl} -1 H -indole-7-carboxamide; 5- (4-. {[[(1-eylpropyl) amino] meilyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(cyclopentylamino) meily] phenyl} -3- [1- (eylsulfonyl) -4-p-pentydinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(Cyclobutylamino) meily] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; d-. { 4 - [(elylamino) methyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d-. { 4 - [(dimethylammon) mey!] Phen} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d-. { 4 - [(diethylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- n-dol-7-carboxamide; 3- [1- (eylsulfonyl) -4-p-peridinyl] -5- [4- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- ( { [(1S) -2-hydroxy-1-mellylethyl] amino] methyl) phenyl] -1H-indole 7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -d- [4- ( { [(1 R) -2-hydroxy-1 - meilenyl] amino} meilyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- [4- ( { [(2R) -2-hydroxypropyl] amino}. Meilyl) phenyl] -1H-indole-7-carboxam gives; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [4- ( { [2-hydroxy-1- (hydroxymethyl) eyl] amino} meilyl) phenyl] -1H-indole -7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -d- (3. {[[(1-methyylbuyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -d- [3- ( { [(1 R) -1-metylpropyl] amino} meilyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -d- (3 { [(2-meitylpropyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-pyridinyl] -5- [3- ( { [(1S) -1-meitylpropyl] amino} methyl) phenyl] -1 H -indole-7 -carboxamide; 5-. { 4 - [(acetylamino) meily] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -d-. { 4 - [(Propanoylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 5- (4-. {[[(Cyclopropylcarbonyl) amino] methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (4- { [(Cyclo-butylcarbonyl) amino] -methyl} phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (4. {[[(2-ynedylacelyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; d- [4- ( { [(1S) -1,2-dimethypropyl] amino] .meiyl) phenyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide; 5-. { 4 - [(bulano -lamino) -methyl] -phenyl} -3- [1- (erylsulfonyl) -4-piperitinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (4-. {[[(2-methylpropanoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide 3- [1- (elylsulfonyl) -4-piperidinyl] -d- (4. {[[(3-methyl-butanoyl) amino] -methyl] -phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4- {[[(mlsylsulfonyl) amino] meily} phenyl) -1 H -indole-7-carboxamide; 5- [3- ( { [(1 R) -1,2-dimethypropyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H-indole -7-carboxamide; 5- (4- { [(Ethylsulfonyl) amino] meityl} phenyl) -3- [1- (ynylsulfonyl) -4-pipepdinyl] -1 H -indole-7-carboxamide; d- (4-. {[[(buylsulfonyl) amino] methyl} phenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- (. {[[(1-methyleryl) sulfonyl] amino} meleyl) phenyl] -1 H -indole-7-carboxamide; 5- (6-amino-2-pyridinyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -d- [3- (1 H -pyrazol-1-yl) phenyl] -1 H -indole-7-carboxamide; d- [4- (dimethylamino) phenyl] -3- [1- (ethylene sulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide; 5- (3-aminophenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 5 - [(2-meityl-1-pyrrolidinyl) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 5-. { d - [(ethylamino) meily] -2-lienyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d- (d-. {[[(1-methyleryl) amino] methyl} -2-lienyl) -1 H -indole-7-carboxamide; d-. { 5 - [(cyclopropylamino) meily] -2-lienyl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(2,2-dimethylaminopropyl) amino] methyl} -2-ynyl) -3- [1- (elylsulfonyl!) -4-piperidinyl] -1H-indole-7- carboxamide; d- (d- { [(cyclopropylmethyl) amino] -methyl} -2-thienyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopropylmethyl] amino] -methyl] -3-pyridinyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [d- ( { [2- (methyloxy) eyl] amino} -methyl) -3-pyridinyl] -1 H- indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- ( { [3- (meilyloxy) propyl] amino} melyl) -3-pyridinyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (4-morpholinylmethyl) -3-pyridinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(erylamino) meily] -3-pyridinyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d-. { d - [(d-dimethylamino) -methyl] -3-pyridinyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -d-. { d - [(2-methyl-1-pyrrolidinyl) methyl] -3-pyridinyl} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-meitylpropyl) amino] methyl} - 3-pyridinyl) -1 H -indole-7-carboxamide; d- (d- { [(2,2-Dimethylpropyl) amino] -methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-meitylbutyl) amino] methyl} -2-lienyl) -1 H -indole-7-carboxamide; 5- [5- ( { [(1 R) -1,2-dimethypropyl] amino.} .methyl) -2-ynyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide; 3- [1 - (ylsulfonyl) -4-piperidinyl] -5-. { d - [(pentylamino) meily] -2-thienyl} - 1 H-indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- [d- ( { [(2S) -2-methylbutyl] amino} methyl) -2-ynyl] -1 H-indole-7 -carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- {[[(1-meityyl-beyl) amino] -methyl} -2-thienyl) -1H-indole-7-carboxamide; 5-. { 5 - [(buílamino) meyil] -2-íienl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [d- ( { [2- (methyloxy) ethyl] amino.} Methyl) - 2-thienyl] -1 H -indole-7-carboxamide; d-. { d - [(cyclopentylamino) meily] -2-lienl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- { [(3-meityyl) -yl) amino] -methyl} -2-ynyl) -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1-methyleryl) amino] meilyl} - 3-pyridinyl) -1 H -indole-7-carboxamide; 5- (d- { [(2-elylisoyl) amino] meityl} -2-Kienyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- [d- ( { [3- (ethyloxy) propyl] amino.} methyl) -2-ynyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [d- ( { [3- (meyloxy) propyl] amino} meityl) -2-iienyl] -1 H -indole -7-carboxamide; d- (d- { [(cyclohexylmethyl) amino] methyl.} -2-yl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 5 - [( { 3 - [(1-Methylethyl) oxy] propyl] amino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; d- [d- ( { [2- (ethyloxy) ellyl] amino} .methyl) -2-thienyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [5- ( { [3- (propyloxy) propyl] amino} -methyl) -2-lienyl] -1H-indole-7- carboxamide; 5- (5- { [(3,3-dimethylbuyl) amino] me? Il.} -2-lienyl) -3- [1- (alkylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -d- [d- ( { [(1 S) -1,2,2-ylmethylpropyl] amino.} Methyl} -2-yenyl] -1 H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -d-. { d - [(hexylamino) meily] -2-iieni} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d-. { 4 - [(meilylsulfonyl) amino] phenyl} -1 H -indole-7-carboxamide; d- [2- (dimethylamino) -4-pyridinyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-pyrrolidinyl) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (4-morpholinyl) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2 - [(2-meitypropyl) amino] -4-pyridinyl} -1 H -indole-7-carboxamide; d-. { 2 - [(2,2-dimethylpropyl) amino] -4-pyridinyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [2- (propylamino) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 4 - [(methylamino) methyl] -2-thienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- (1-pyrrolidinylmethyl) -2-thyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-. {[[(2-methylpropyl) amino] methyl.} -2- thienyl) -1 H -indole-7-carboxamide; d-. { 4 - [(d.methylamino) met.l] -2-thienyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { d - [(1S) -1- (1-pyrrolidinyl) ethyl] -3-thienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 5 - [(1 R) -1- (1-pyrrolidinyl) etiI] -3-thienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- ( { [3- (methyloxy) propyl] amino} methyl) -2-thienyl] -1 H-indol-7- carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [4- ( { (2S) -2 - [(methyloxy) methyl3-1-pyrrolidinyl} methyl) -2-thienyl] -1 H-indol-7-carboxamide; d- (4-. {[[(2R, 5R) -2,5-dimethyl-1-pyrrolidinyl] methyl.} -2-Jannyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5- { [(2S) -2-methyl-1-pyrrolidinyl] methyl.}. -3-thienyl) -1H-indole 7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5- { [(2R) -2-methyl-1-pyrrolidinyl] methyl.}. -3-thienyl) -1H-indole 7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { d- [1 - (1-pyrrolidinyl) propyl] -3-thienyl} -1 H -indole-7-carboxamide; d-. { 5 - [(dimethylamino) methyl] -3-thienyl} -3-. { 1 - [(1-Methylethyl) sulfonyl-3-4-piperidinyl} -1 H -indole-7-carboxamide; 5- [d- (aminomethyl) -3-thienyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-p-peridinyl] -d- (d-. {2 - [(2-methylpropyl) amino] ethyl] -3-thienyl) -1H-indole-7 -carboxamide; d-. { d- [2- (dimethylamino) ethyl] -3-thienyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [6- (1-pyrrolidinyl) -3-pyridinyl] -1 H -indole-7-carboxamide; d-. { 6- [Ethyl (meth) amino] -3-pyridinyl} -3- [1- (ethylsulfonyl) -4-piperid: nil] -1 H -indole-7-carboxamide; 5- [6- (dimethylamino) -3-pyridinyl] -3- [1- (ethylsulfonyl) -4-piperidinyl!] - 1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [6- (propylamino) -3-pyridinyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 6 - [(1-methylethyl) amino] -3-pipdinyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [6- (4-morpholinyl) -3-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 5 - [(methylamino) methyl] -3-thienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5. {[[(1-methylethyl) amino] rpethyl] -3-thienyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [d- (1-pyrrolidinylmethyl) -3-thienyl] -1H-indole-7-carboxamide; 5-. { 5 - [(ethylamino) methyl] -3-thienyl} -3- [1- (ethylsulfonyl) -4-piperindin-1 H- indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [d- (. {[[(1 R) -2-hydroxy-1-methyl-ethyl] amino] methyl) -3-thienyl] -1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [d- (1-piperidinylmethyl) -3-thienyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [d- (4-morpholinylmethyl) -3-thienyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(methylamino) methyl] -3-furanyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { d- [1- (1-pyrrolidinyl) ethyl] -3-tiepyl} - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-pperidinyl] -d- [d- (1-pyrrolidinylmethyl) -2-thienyl] -1H-indole-7-carboxamide; d-. { 5 - [(dimethylamino) methyl] -2-thienyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(propylamino) methyl] -2-t: enyl} -1 H -indole-7-carboxamide; 5-. { d - [(diethylamino) methyl] -2-thienyl} -3- [1- (ethylsulfonyl) -4-piperidipyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[(2-methylpropyl) amino] methyl] -2-thienyl) -1 H -indole-7-carboxamide; d- (d- { [(2,2-dimethylpropyl) amino] methyl.}. -3-furanyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-methylpropyl) amino] me! Il.}. -3-furanyl) -1 H -indole-7-carboxamide; d- (d- { [(cyclopentylmethyl) amino] methyl.} - 3-furanyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [d- (1-pyrrolidinylmethyl) -3-furanyl] -1H-indol-7-carboxamide; 5-. { 5 - [(diethylamino) methyl] -3-furanyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [5- (1-pyrrolidinylmethyl) -1,3-thiazol-2-yl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5- [2-methyl-1- (1-pyrrolidinyl) propyl] -3-thienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- [4- (1-pyrrolidinylmethyl) -1,3-thiazol-2-yl] -1 H -indole-7-carboxamide; 5-. { 1 - [2- (Dimethylamino) ethyl] -1 H -pyrazol-4-yl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 1- [2- (1-pyrrolidinyl) ethyl] -1 H-pyrazol-4-yl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-p-pentyld] -d-. { 1 - [2- (4-morpholinyl) ethyl] -1 H -pyrazol-4-yl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (1- {2 - [(2-hydroxyethyl) amino] ethyl} -1-H-pyrazol-4-yl) -1 H- indole-7-carboxamide; d-. { 1 - [2- (Butylamino) ethyl] -1H-pyrazol-4-yl} -3- [1 - (ethylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; 5-. { 1 - [2- (Cyclobutylamino) ethyl] -1 H -pyrazol-4-yl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [1 - (2- { [2- (diethylamino) ethyl] amino.} Et.l) -1 H -pyrazol-4-yl] -3- [1 - (ethylsulfonyl) -4-piperidinyl ] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (1- {2 - [(1-methylethyl) amino] ethyl} -1 H -pyrazol-4-yl) -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (1- {2 - [(2-methylpropyl) amino] ethyl} -1 H -pyrazol-4-yl) -1 H- indole-7-carboxamide; d- (1- {2 - [(cyclopentylmethyl) amino] ethyl.} -1 H -pyrazol-4-yl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 3- [1- (ethylsulfonyl) -4-p-peridinyl] -d- [4- (methyloxy) -3- (1-pyrrolidinylmethyl) pheny] -1 H -indole-7-carboxamide; 5- [3 - [(dimethylamino) methyl] -4- (methyloxy) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- (methyloxy) -3- (4-moryolinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3-. { [(1-methylethyl) amino] methyl} -4- (methyloxy) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3 - [(methylamino) methy1] -4- (methyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3-. { [(2,2-dimethylpropyl) amino] methyl} -4- (methyloxy) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxyethyl) (methyl) amino] ethyl} -1 H -pyrazol-4-yl) - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 4-fluoro-3 - [(methylamino) methyl] phenyl} -1 H -indole-7-carboxamide; d-. { 3,5-bis [(methylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-pyridinyl] -1 H-indole-7-carboxamide; 5-. { 3 - [(ethylamino) methyl] -4-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4-fluoro-3- ( { [2-hydroxy-1- (hydroxymethyl) ethyl] amino} methyl) phenyl] -1 H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [4-fluoro-3- (. {[[(1 S) -2-hydroxy-1-methyl-ethyl] amino] methyl) phenyl] - 1 H-indole-7-carboxamide; 5-. { 3 - [(cyclopropylamino) methyl] -4-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3 - [(Cyclobutylamino) methyl] -4-fluorophenyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (1-pyrrolidinylmethyl) phenyl-1H-indole-7-carboxamide; d-. { 3, d-bis [(ethylamino) methyl] phenyl} -3- [1- (ethylene sulfonyl) -4-p-peridinyl] -1 H -indole-7-carboxamide; 5-. { 3,5-bis [(dimethylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (2-piperidinyl) phenyl] -1 H -indole-7- carboxamide; d-. { 3- [1 - (ethylamino) ethyl] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d-. { 3- [1 - (dimethylamino) ethyl] phenyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 3-fluoro-d - [(methylamino) methyl] phenyl} -1 H-Indole-7-carboxamide; d-. { 3 - [(ethylamino) methyl] -d-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d-. { 3-fluoro-5- [(propylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(1-methylethyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-methylpropyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 5-. { 3 - [(Cyclobutylamino) methyl] -d-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d-. { 3 - [(dimethylamino) methyl] -d-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (1-pyrrolidinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3-fluoro-5- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-pichandinyl] -5-. { 3- [1 - (methylamino) ethyl] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3- {1 - [(1-methylethyl) amino] ethyl} phenyl) -1H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3- {1 - [(2-methylpropyl) amino] ethyl} phenyl) -1 H -indole-7-carboxamide; d-. { 3- [1- (cyclobutylamino) ethyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 3- [1- (1-pyrrolidinyl) ethyl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- (3-thiomorpholinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [d- (2-piperazinyl) -2-thienyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [4- (2-piperazinyl) pheny] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- (2-piperazinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [6- (4-morpholinyl) -3-pyridazinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [6- (1-pyrrolidinyl) -3-pyridazinyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 2 - [(methylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3. {[[(2-thienylmethyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- (. {[[(5-methyl-2-furanyl) methyl] amino} methyl) phenyl] -1H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(2R) -tetrahydro-2-furanylmethyl] amino] methyl) phenyl] -1H-indole 7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- ( { [(2S) -tetrahydro-2-furanylmethyl] amino] methyl) phenyl] -1H-indol-7- carboxamide; 5- (3- { [(2,2-dimethylpropyl) amino] methyl.}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-methylbutyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- ( { [(2S) -2-methylbutyl] amino] methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(1 R) = 1, 2,2-trimethylpropyl] amino] methyl) phenyl] -1H-indole -7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2-furanylmethyl] amino] methyl) phenyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (. {[[(2R) -tetrahydro-2-furanylmethyl] amino] methyl) phenyl] -1 H-indole-7-carboxamide; 5- [3- ( { [(1 S) -1,2-dimethylpropyl] amino} methyl) -5-fluorophenyl] -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 5- [3- ( { [(1 R) -1,2-dimethylpropyl] amino.} Methyl) -5-fluorophenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(1-methylpropyl) amino] methyl] phenyl) -1H-indole 7-carboxamide; 3- [1 - (Ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(1 S) -1,2,2-trimethylpropyl] amino.} Methyl) phenyl] - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-d- ( { [(2S) -2-methylbutyl] amino] methyl) phenyl] -1H-indole 7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-methylbutyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (. {[[(1 R) -1,2,2-trimethylpropyl] amino] methyl) phenyl] - 1H-indole-7-carboxamide; 5- (3- { [(2,2-dimethylpropyl) amino] methyl.}. -d-fluorophenyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclopropylmethyl) amino] methyl]} - 5-fluorophenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclopentylmethyl) amino] methyl]} - 5-fluorophenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(Tetrahydro-2 H -pyran-4-ylmethyl) amino] methyl} phenyl) -1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3-fluoro-5-. {[[2- thienylmethyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3-fluoro-5- ( { [2- (methyloxy) ethyl] amine} methyl) phenyl] -1H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [3- (methyloxy) propyl] amino} methyl) phenyl] -1H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-furanylmethyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3-fluoro-d-. {[[(3-methylbutyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [3-fluoro-5- (. {[[(D-methyl-2-furanyl) methyl] amino.} Methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-methylpropyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (2-pyrrolidinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(propylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulphonyl) -4-pperidyl] -5- (2-fluoro-5-. {[[(2-methylpropyl) amino] methyl] phenyl) -1H-indole 7-carboxamide; 5- (d- { [(2,2-dimethylpropyl) amino] methyl.} -2-fluorophenyl) -3- [1- (ethylsulfonyl) -4-pperidyl] -1 H -indole-7-carboxamide; 5- [5- ( { [(1S) -1,2-dimethylpropyl] amino} methyl) -2-phlorophenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- [d- ( { [(1 R) -1,2-dimethylpropyl] amino.} methyl) -2-fluorophenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide; d- (d- { [(cyclopropylmethyl) amino] methyl.} -2-fluorophenyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [2-fluoro-d- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [2-fluoro-5- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2-fluoro-5- (. {[2- (methyloxy) ethyl] amino} methyl) phenyl] -1H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2-fluoro-5- ( { [3- (methyloxy) propyl] amino} methyl) phenyl] -1H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (1-methyl-2-pyrrolidinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {2 - [(2-methylpropyl) amino] ethyl} phenol) -1 H -indole-7-carboxamide; 5-. { 3- [2- (ethylamino) ethyl] phenyl} -3- [1- (ethylsulfonyl) -4-p-peridinyl-1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 3- [2- (propylamino) ethyl] phenyl} -1 H -indole-7-carboxamide; d-. { 3- [2- (dimethylamino) ethyl] phenyl} -3- [1- (Ethylsulfonyl) -4-piperidin [] - 1 H- indole-7-carboxamide; d-. { 3- [2- (Dipropylamino) ethyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidini!] - 1 H -indole-7-carboxamide; 5- [3- ( { [2- (3,5-Dimethyl-1 H -pyrazol-1-yl) ethyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [2- (4-morpholinylmethyl) -1,3-thiazol-4-yl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2- {[[(2-methylpropyl) amino] methyl} -1, 3-thiazol-4-yl) -1 H-indole -7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- [2- (1-pyrrolidinylmethyl) -1,3-thiazol-4-yl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-piperidinylmethyl) -1,44-azole-4-yl] -1 H -indole-7-carboxamide; 5-. { 2 - [(dimethylamino) methyl] -1,3-thiazol-4-yl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (2-. {[[Ethyl (methyl) amino] methyl]} -1, 3-Jiazol-4-yl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 5- (3-cyano-5- { [(2-methylpropyl) amino] methyl.}. Phen.l) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; d-. { 3-cyano-5 - [(dimethylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(methylsulfonyl) aminojfeni]} -1 H -indole-7-carboxamide; d- [4- (acetylamino) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- (acetylamino) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 5-. { 3 - [(acetylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-picperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(methylsulfonyl) amino] methyl} pheny] -1 H -indole-7-carboxamide; 5-. { 3 - [(butanoylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(4-fluorophenyl) carbonyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-methylpropanoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-furanylcarbonyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 5- (3- { [(Cyclopentylcarbonyl) amino] methyl.}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(pentanoylamino) methyljphenyl} -1 H -indole-7-carboxamide; d- (3-. {[[(2-ethylbutanoyl) amino] methyl.}. pheny] -3- [1- (ethylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(1-benzothien-2-ylcarbonyl) amino] methyl} phenyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(1-acetyl-4-piperidinyl) carbonyl] amino.} Methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indol-7 -carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(1-methyl-1 H -pyrrol-2-yl) carbonyl] amino} methyl) phenyl] -1H-Indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(3-methyl-2-butenoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(Heptanoylamino) methyl] phenyl} - 1 H-indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-pichandinyl] -5-. { 3 - [(octanoylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-methylpentanoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3. {[[(3-methylbutanoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-thienylacetyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(hexanoylamino) methyl] phenyl} - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-methyl-butanoyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclobutylcarbonyl) amino] methyl.}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclopropylcarbonyl) amino] methyl.}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 3 - [(Propanoylamino) methyl] phenyl} - 1 H-indole-7-carboxamide; 5- (3-. {[[(Cyclopentylacetyl) amino] methyl] phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (. {[[3- (methylthio) propanoyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (. {[[(1-methylethyl) sulfonyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; d- (3-. {[[(cyclopropylsulfonyl) amino] methyl.}. phen.l) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(2,5-Dichlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; d- [3- ( { [(4-Bromophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -> piperidinyl] -1 H -indole-7-carboxamide; d- [3- ( { [(4-chlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (. {[[(3-fluorophenyl) sulfonyl] amino] methyl) phenyl] -1H-indole-7-carboxamide; 5- [3- ( { [(2-chlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(2,5-dichloro-3-thienyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4-pperidinyl] -1 H -indole-7-carboxamide; d- [3- ( { [(2-Chloro-6-methylphenyl) sulfonyl] amino.} methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [3- (. {[[(5-fluoro-2-methylphenyl) sulfonyl] amino] methyl] phenyl] -1H-indole -7-carboxamide; 5- [3- ( { [(1,2-dimethyl-1 H-imidazol-4-yl) sulfonyl] amino} methyl) pheni] -3- [1 - (ethylsulfonyl) - 4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(Propylsulfonyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 5- (3- { [(Butylsulfonyl) amino] methyl.}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(phenylsulfonyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(4-fluorophenyl) sulfonyl] amino} methyl) phenyl] -1H-indole-7-carboxamide; d- [3- ( { [(4-Bromo-2-ethylfenyl) sulfonyl] amino.} methyl) phen.l] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 5- (3- { [(1-benzothien-3-ylsulfonyl) amino] methyl.}. Phenyl) -3- [1- (etüsu [fonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 5-. { 3 - [( { [4- (1 J-dimethylethyl) phenyl] sulfonyl.] Amino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(3,4-difluorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- (3-. {[[(ethylsulfonyl) amino] methyl] phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; d- (3-. {[[(2,1, 3-benzoxadiazol-4-ylsulfonyl) amino] methyl.}. pheny] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(Tetrahydro-3-furanylcarbonyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 5-. { 4 - [(Cyclopentylsulfonyl) amino] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indol-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [4- (4-methyl-2-oxo-1-piperazinyl) phenyl] -1H-indole-7-carboxamide; 5- [6- (4-acetyl-1-piperazinyl) -3-pyridinyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-. {[[(Methyloxy) amino] methyl} phenyl) -1H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3. {[[(Methyloxy) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5- { [4- (1-pyrrolidinyl) -1-piperidinyl] methyl.}. -3-thienyl) -1H-indole 7-carboxamide; 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- (d- { [(2S) -2- (trifluoromethyl) -1-pyrrolidinyl] methyl.} -3-thien l) -1 H -indole-7-carboxamide; d- (d- { [(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] methyl.} - 3-thienyl) -3-. { 1 - [(1- methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (d- { [(3S) -3-hydroxy-1-pyrrolidinyl] methyl.}. 3-thienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H-Indole-7-carboxamide; d- (5- { [cyclopentyl (methyl) amino] methyl.}. 3-thienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5- { [(2-hydroxyethyl) (methyl) amino] methyl.}. 3-thienyl) -3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5-. {[[(2-amino-2-oxoethyl) (methyl) amino] methyl} -3-thienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[Methyl (2-propen-1-yl) amino] methyl} -3-thienyl) -1H-indole 7-carboxamide; d- (d- { [[(3, d-dimethyl-1 H -pyrazol-4-yl) methyl] (methyl) amino] methyl.}. -3-thienyl) -3- [1- (ethylsulfonyl ) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5- { [(Cyanomethyl) (methyl) amino] methyl.}. -3-thienyl) -3- [1- (ethylsulfopyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (5-. {[[Methyl (1-methylpropyl) amino] methyl} -3-thienyl) -1 H -indole-7-carboxamide; 5- (d- { [[2- (ethyloxy) ethyl] (methyl) amino] methyl.}. -3-thienyl) -3- [1- (ethyl-sulphonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[Cyclobutyl (methyl) amino] methyl.} - 3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [d- (. {2 - [(methyloxy) methyl] -1-pyrrolidinyl}. Methyl) -3-Jienyl] -1H-indol-7 -carboxamide; 5- (d-. {[[(1,1-dimethylethyl) (methyl) amino] methyl] -3-t-ene] -3- [1- (ethyl-sulphonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d- { [3- (trifluoromethyl) -1-piperidinyl] methyl} -3-thienyl) -1 H -indole-7- carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[[(1 S) -2-hydroxy-1-methyl-ethyl] (methyl) amino] methyl.}. -3-thienyl ) -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopropylmethyl) (methyl) amino] methyl} -3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; d- (d- { [[2- (acetylamino) ethyl] (methyl) amino] methyl.}. -3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- (d-. {[[[(1 R, 2R) -2-hydroxycyclopentyl] (methyl) amino] methyl.}. -3-taryl) - 1 H-indole-7-carboxamide; 5- (5-. {[[(1,1-dimethylpropyl) (methyl) amino] methyl]} - 3-thienyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -d- (5-. {[[(2S) -2-hydroxypropyl] (methyl) amino] methyl.}. -3-thienyl) -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- ( { Methyl [(2R) -tetrahydro-2-furanylmethyl] amino]} methyl) -3-thienyl] -1 H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (d- { [ { 2 - [(2-hydroxyethyl) oxy] ethyl} (methyl) amino] methyl.} - 3-thienyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [5- (1-. {Meth] [2- (methyloxy) ethyl] amino} ethyl) -3-thienyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulphonyl) -4-pperidinyl] -5- (d-. {1- [methyl (propyl) amino] ethyl)} -3- thienyl) - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[[(1 S) -2-hydroxy-1-methylethyl] (methyl) amino] methyl} -3 -thienyl) -1 H -indole-7-carboxamide; and 5- (d-. {[[(1, 1-dioxidotetrahydro-3-thienyl) (methyl) amino] methyl} -3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; or one of its pharmaceutically acceptable salts.
Terms and definitions The term "alkyl" refers to a saturated hydrocarbon chain having the number of member atoms that is specified. For example, C 1 -C 6 alkyl refers to an alkyl group having from 1 to 6 member atoms. The alkyl groups may be optionally substituted with one or more substituents as defined herein. The alkyl groups can be linear or branched. Branched, representative alkyl groups have one, two or three branches. Alkyl includes methyl, ethyl, propyl (n-propyl and isopropyl), butyl (p-butyl, isobutyl and f-butyl), pentyl (n-pentyl, sopentyl and neopentyl) and hexyl. The term "alkylene" "when used alone or in the formation of other groups (such as the alkylene groups C- | -Cg-heteroaryl, C---Cg-heterocycloalkyl, Cj-Cg-C4-C7-cycloalkyl, and Cj alkylene -Cg -C5-C7 cycloalkenyl) refers to a saturated divalent hydrocarbon chain having the specified number of member atoms. For example, C1-C6 alkylene refers to an alkylene group having from 1 to 6 member atoms. The alkyl groups may be optionally substituted with one or more substituents as defined herein. The alkylene groups may be linear or branched. Branched, representative alkylene groups have one, two or three branches. Alkylene includes methylene, ethylene, propylene (n-propylene and isopropylene), butylene (n-butylene, isobutylene, and f-butylene), pentylene (p-pentylene, isopentylene, and neopentylene) and hexylene. The term "alkenyl" refers to an unsaturated hydrocarbon chain having the number of member atoms that is specified, and having one or more carbon-carbon double bonds within the chain. For example, C2-C6 alkenyl refers to an alkenyl group having from 2 to 6 member atoms. In some embodiments, the alkenyl groups have a carbon-carbon double bond within the chain. In other embodiments, the alkenyl groups have more than one carbon-carbon double bond within the chain. The alkenyl groups may be optionally substituted with one or more substituents as defined herein. The alkenyl groups may be linear or branched. Branched, representative alkenyl groups have one, two or three branches. Alkenyl includes ethylene, propenyl, butenyl, pentenyl, and hexenyl. The term "alkepolene" refers to an unsaturated divalent hydrocarbon chain having the number of member atoms that is specified, and having one or more carbon-carbon double bonds inside the chain. For example, C2-C6 alkenylene means an alkenylene group having 2 to 6 member atoms. In some embodiments, the alkenylene groups have a carbon-carbon double bond within the chain. In other embodiments, the alkenylene groups have more than one carbon-carbon double bond within the chain. The alkenylene groups may be optionally substituted with one or more substituents as defined herein. The alkenylene groups can be linear or branched. Branched, representative alkenylene groups have one, two or three branches. Alkenylene includes ethylene, propenylene, butenylene, pentenylene, and hexenylene. The term "alkylene" refers to an unsaturated divalent hydrocarbon chain having the number of member atoms that is specified, and having one or more triple carbon-carbon bonds within the chain. For example, C2-C6 alkynylene refers to an alkynylene group having 2 to 6 member atoms. In some embodiments, the alkynylene groups have a triple carbon-carbon bond within the chain. In other embodiments, the alkynylene groups have more than one carbon-carbon triple bond within the chain. For clarity, unsaturated divalent hydrocarbon chains having one or more triple carbon-carbon bonds within the chain and one or more carbon-carbon double bonds within the chain are alkynylene groups. The alkynylene groups may be optionally substituted with one or more substituents as defined herein. The alkynylene groups They can be linear or branched. Branched, representative alkynylene groups have one, two or three branches. Alkynylene includes ethynylene, propynylene, butynylene, pentynylene, and hexinylene. The term "arolo" refers to an aromatic hydrocarbon ring. The aryl groups are monocyclic ring systems or bicyclic ring systems. A monocyclic aryl ring refers to phenyl. Bicyclic aryl rings refer to naphthyl and rings in which phenyl is fused to a cycloalkyl or cycloalkenyl ring having d, 6, or 7 member atoms. The aryl groups may be optionally substituted with one or more substituents as defined herein. The term "cocloalkyl" refers to a saturated hydrocarbon ring having the number of member atoms that is specified. Cycloalkyl groups are monocyclic ring systems. For example, C3-C6 cycloalkyl refers to a cycloalkyl group having from 3 to 6 member atoms. Cycloalkyl groups may be optionally substituted with one or more substituents as defined herein. Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "cycloalkenyl" refers to an unsaturated hydrocarbon ring having the number of member atoms that is specified and having a carbon-carbon double bond within the ring. For example, C3-C6 cycloalkenyl refers to a cycloalkenyl group having from 3 to 6 member atoms. In some modalities, the groups Cycloalkenyl have a carbon-carbon double bond within the ring. In other embodiments, cycloalkenyl groups have more than one carbon-carbon double bond within the ring. However, the cycloalkenyl rings are not aromatic. Cycloalkenyl groups are monocyclic ring systems. Cycloalkenyl groups may be optionally substituted with one or more substituents as defined herein. Cycloalkenyl includes cyclopropenyl, cyclobutenyl, cyclopentenyl, and cyclohexenyl. The term "enantioméricatipieipite enriched" refers to products whose enantiomeric excess is greater than zero. For example, enantiomerically enriched refers to products whose enantiomeric excess (abbreviated ee) is greater than dO%, greater than 75% and greater than 90%. The term "enaniomeric excess" or "ee" is the excess of one enantiomer with respect to the other, expressed as a percentage. Accordingly, since the two enantiomers are present in equal amounts in a racemic mixture, the enantiomeric excess is zero (ee 0%).
However, if an enantiomer has been enriched so as to constitute 9d% of the product, the enantiomeric excess would be 90% (the amount of the enantiomer enriched, 9d%, minus the amount of the other enantiomer, 5%). The term "pure erartiomericanr.eir.te" refers to products whose enantiomeric excess is 99% or greater. The term "half-life" (or "half-lives") refers to! weather which is required so that half the amount of a substance is converted in vitro or in vivo into another chemically distinct species. The term "halo" refers to the halogen radical fluoro, chloro, bromo or iodo. The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom attached to a member atom within the alkyl group has been replaced by halo. Haloalkyl includes trifluoromethyl. The term "heteroaryl" refers to an aromatic ring containing 1 to 4 heteroatoms as ring member atoms. Heteroaryl groups containing more than one heteroatom may contain different heteroatoms. Heteroaryl groups may be optionally substituted with one or more substituents as defined herein. Heteroaryl groups are monocyclic ring systems, or are fused, spirobicyclic or linked bicyclic ring systems. The monocyclic heteroaryl rings have d or 6 member atoms. The bicyclic heteroaryl rings have 7 to 11 member atoms. Bicyclic heteroaryl rings include those rings in which a phenyl ring and a monocyclic heterocycloalkyl ring are attached, forming a fused, spirobicyclic or linked bicyclic ring system, and those rings in which a monocyclic heteroaryl ring and a cycloalkyl ring are attached , cycloalkenyl, heterocycloalkyl, or heteroaryl, monocyclic, forming a fused, spirobicyclic or linked bicyclic ring system. Heteroaryl includes pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, furazanyl, thienyl, triazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, isorazinyl, isodolyl, isoindolyl, indolizinyl, indazolyl, purinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, pteridinyl, cinolinyl, benzimidazolyl, benzopyranyl , benzoxazolyl, benzofuranyl, isobenzofuranyl, benzothiazolyl, benzothienyl, furopyridinyl, and naphthyridinyl. The term "heteroatom" refers to a nitrogen, sulfur, or oxygen atom. The term "heteirocycloalkyl" refers to a saturated or unsaturated ring that contains 1 to 4 heteroatoms as ring members. However, the heterocycloalkyl rings are not aromatic. Hetero-cycloalkyl groups that contain more than one heterolarum can contain different types of heterogeneous. The heteroarylcycloalkyl groups may optionally be substituted with one or more substituents as defined in this document. Heterocycloalkyl groups are monocyclic ring systems having from 4 to 7 member atoms. In some embodiments, heterocycloalkyl is saturated. In other modalities, heterocyclecycloalkyl is unsaturated, but it is not aromatic. Heterocycloalkyl includes pyrrolidinyl, eryhydridethuranyl, dihydrofuranyl, pyranyl, eeryhydropyranyl, dihydropyranyl, hydroxynyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, thiamorpholinyl, 1,3-dioxolanyl, 1,3-dioxanyl, 1,4-dioxanyl. , 1,3-oxathiolanyl, 1,3-oxathianyl, 1,3-dithianyl and azetidinyl.
The term "member members" refers to the atom or atoms that form a chain or a ring. When in a chain, and within a ring, more than one member atom is present, each mimemb atom is covalently bound to an adjacent member atom within the chain or ring. The atoms that form a substituent group of a chain or ring are not members of the chain or ring. The expression "optionally substituted" indicates that a group, for example alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heteroaryl, may be unsubstituted or may be substituted with one or more substituents such as those defined herein. "Substituted", in relation to a group, indicates that a hydrogen atom joined to a member atom within a group has been replaced. It should be understood that the term "substituted" includes the implicit condition that said substitution be in accordance with the valence allowed for the substituted aldehyde and the substituent and that the suspension result in a stable compound (ie, one that does not spontaneously undergo transformation). , for example, they were replaced, cyclized or eliminated).
In some embodiments, a single moiety may be substituted with more than one substituent provided that such substitution is in accordance with the allowed valence of the atom. As used herein, suitable substituents are defined for each substituted or optionally substituted group. The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and dosage forms that they are, within the scope of the well-founded medical opinion, suitable to be used in contact with the tissues of humans and animals, without excessive toxicity, irritation, or other problem or complication and which had a reasonable benefit / risk ratio. As used in this document, the symbols and conventions used in these processes, schemes and examples are consistent with those used in contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Generally single-letter or three-letter abbreviations are used to designate amino acid residues, which are considered to be in the L-configuration unless otherwise indicated. Unless the schedule is indicated, all the starting materials were obtained from commercial suppliers and used without further purification. Specifically, in the Examples, and throughout the entire specification, the following abbreviations may be used: g (grams); mg (milligrams); L (liters); ml (milliliters); μL (microliters); psi (pounds per square inch); M (molar); mM (millimolar); i. v. (Nlvevenoso); Hz (Hertz); MHz (megahertz); mol (moles); mmol (millimoles); t.a. (ambient temperature); min (minutes); h (hours); p.f. (fusion puncture); TLC (thin layer chromatography); Tr (re-session time); RP (inverted phase); MeOH (meianol); / -PrOH (isopropanol); TEA (írielilamina); TFA (uro-fluoroacetic acid); TFAA (Irifluoroacetic anhydride); THF (leirahydrofuran); DMSO (dimethylsulfoxide); AcOEí (aceylic acid); DME (1, 2-dimethoxieiane) DCM (dichloromean); DCE (dichloroean); DMF (N, N-dimethylformamide); DMPU (N, A / '- dimethylpropyleneurea); CDl (1,1-carbonyldiimidazole); IBCF (Isobuylochloroformialo); HOAc (acíic acid); HOSu (N-hydroxysuccinimide); HOBT (1-hydroxybenzotriazole); mCPBA (meta-chloroperbenzoic acid); EDC (1 - [(3-dimethylamino) -propyl] -3-ethylcarbodiimide hydrochloride); BOC (f-bulyloxycarbonyl); FMOC (9-fluorenylmedeoxycarbonyl); DCC (dicyclohexylcarbodiimide); CBZ (benzyloxycarbonyl); Ac (acetyl); aím (aímósfera); TMSE (2- (n-dimethylsilyl) ethyl); TMS (trimethylsilyl); TIPS (iriisopropylsilyl); TBS (f-butyldimethylsilyl); DMAP (4-dimethylaminopyridine); BSA (bovine serum albumin); ATP (adenosine glyphosate); HRP (horseradish peroxidase); DMEM (Eagle's medium modified by Dulbecco); HPLC (liquid chromatography of alia pressure); BOP (bis (2-oxo-3-oxazolidinyl) phosphinic chloride); TBAF (tetra-n-butylammonium fluoride); HBTU (0-benzoyriazole-1-yl-N, N, N ', N'-letramelyluronium hexafluorophosphate); HEPES (4- (2-hydroxy-yl) -1-piperazine-ene-sulphonic acid); DPPA (diphenylphosphoryl azide); fHN03 (HN03 fumanle); EDTA (elilendiamine-acetic acid); TMEDA (N.N.N'.N'-totramelyl-l, 2-eiandiamine); NBS (N-bromosuccinimide); HATU (0- (7-azabenzobenzoyriazol-1-yl) -N.N.N'.N'-N-methyl-melonuronium hexafluorophosphate); DIPEA (diisopropylethylamine); Imes (1,3-bis (2,4,6-lime-phenyl) imidazolium chloride); dppf (1, 1'-bis (diphenylphosphino) ferrocene); MDAP (AutoPrep Directed to Masses); CH3CN (aceyoniyryl); EOAc (ethyl acelate); and NIS (N-iodosuccinimide). Each time "ether" is mentioned it means diethyl ether, and "brine" means a saturated aqueous solution of NaCl. Compounds according to formulas 1-11 may contain one or more asymmetric centers (also referred to as a chiral center) and therefore may exist in the form of individual enantiomers, diastereomers or other stereoisomeric forms, or as mixtures thereof. The chiral centers, for example chiral carbon atoms, can also be present in a substituent, for example in an alkyl group. When the stereochemistry of a chiral center present in formulas 1-11 is not specified, or in any chemical structure used in this document, the structure is intended to include any stereoisomer and all mixtures thereof. In this manner, the compounds according to the formulas I-1 which contain one or more chiral rings can be used in the form of racemic mixtures, enanonyromically enriched mixtures or in the form of purely enanonymically pure individual stereoisomers. The individual stereoisomers of a compound according to the formulas 1-11 which contain one or more asymmetric centers can be solved by methods known to those skilled in the art. For example, this resolution can be carried out (1) forming salts, complexes, or other derivatives, diastereomers; (2) by selective reaction with a specific reactant for a stereoisomer, for example by oxidation or enzymatic reduction; or (3) mediating gas-liquid chromatography or liquid chromatography in a chiral environment, for example, on a chiral support such as silica with a fixed chiral ligand, or in the presence of a chiral solvent. The person skilled in the art will appreciate that when the desired stereoisomer is converted to another chemical entity by one of the separation methods described above, an additional operation is required to release the desired shape. Alternatively, specific stereoisomers can be synthesized by asymmetric synthesis, using reagents, substrates, catalysts or optically active solvents, or by converting an enantiomer in the medium through asymmetric transformation. The compounds according to formulas 1-11 may also contain double bonds or other centers of geometric asymmetry. When the stereochemistry of a center of geometrical asymmetry present in formulas 1-11 is not specified, or in any chemical structure illustrated in this document, the structure is intended to include the geometrical isomer (E), the geometric isomer cis (Z) and all the mixtures thereof. Likewise, all tauimeric forms are also included in formulas 1-11 if said laulomers exist in equilibrium or primarily in one form. The specialization in the technique will appreciate that they can prepare pharmaceutically acceptable salts of the compounds according to formulas l-ll. In fact, in certain embodiments of the invention, pharmaceutically acceptable salts of the compounds according to formulas 1-11 may be preferred over the free base or the free specific acid because such salts impart greater stability or solubility to the molecule thereby facilitating the formulation in a dosage form. Accordingly, the invention further relates to pharmaceutically acceptable salts of the compounds according to formulas l-ll. As used in the present specification, the term "pharmaceutically acceptable salts" refers to salts which retain the desired biological activity of the subject compound and which exhibit minimal undesired toxicological effects. These pharmaceutically acceptable salts can be prepared in situ during the final isolation and purification of the compound, or they can be reacted separately, in their free acid or free base form, with a suitable base or acid, respectively. In certain embodiments, the compounds according to formulas 1-11 may contain an acid functional group. Suitable pharmaceutically acceptable salts include salts of these acid functional groups. Representative salts include pharmaceutically acceptable salts with meals, such as sodium, potassium, lithium, calcium, magnesium, aluminum, and zinc salts; carbonaios and bicarbonates of a pharmaceutically acceptable meiotic cayion such as sodium, poiasium, liium, calcium, magnesium, aluminum, and zinc; organic primary, secondary, and tertiary, pharmaceutically acceptable amines, including aliphatic amines, aromatic amines, aliphatic diamines, and hydroxy alkylamines such as melamine, elylamine, 2-hydroxymylamine, diethylamine, ethyldiamine, ethylenediamine, elanolamine, dielanolamine, and cyclohexylamine. In certain embodiments, the compounds according to formulas 1-11 may contain a basic functional group and are therefore capable of forming pharmaceutically acceptable acid addition salts by irradiation with a suitable acid. Suitable acids include pharmaceutically acceptable inorganic acids and pharmaceutically acceptable organic acids. Representative pharmaceutically acceptable acid addition salts include hydrochloride, hydrobromide, nitrate, methyl nitrate, sulfate, bisulfate, sulphamate, phosphate, acetylation, ureaifluoroacetal, hydroxyacetal, phenylacelle, propionalo, butadiene, isobuíirate, valerate, maleate, hydroxyaleate, acrylate, fumarate, nanolay, iron, salicylate, p-aminosalicylic acid, glycolylate , lacy, heptanoate, phthalate, oxalate, succinate, benzoate, o-acetoxybenzoane, chlorobenzoaio, melilbenzoaio, diniirobenzoalo, hydroxybenzoane, meioxybenzoalo, mandelaie, amana, formiolo, esiaaraio, ascorbaio, palmiiaio, oleato, pyruvaio, pamoaio, malonaio, lauralo, gluioralo , gluIAmalo, esiolalo, measosulfonaio (mesyllalo), elanosulfonalo (esilaío), 2-hidroxieíanosulfonaío, bencenosulfonaío (besilaío), p-aminobenzenesulfonalo, p-íoluenosulfonaío (tosilaío) and nafíaleno-2-sulfonaio.
As used in this document, the term "compounds of the invention" means compounds according to formula I as compounds according to formula II and pharmaceutically acceptable salts thereof. The compounds of the invention can exist in solid or liquid form. In the solid state, the compounds of the invention can exist in crystalline form or in non-crislaline form or as a mixture of both. As regards the compounds of the invention which are in crystalline form, the person skilled in the art will appreciate that pharmaceutically acceptable solvates can be formed in which solvent molecules are incorporated within the crystalline lattice, during the chilling. Solvaios may involve non-aqueous solvents such as eneol, sopropanol, DMSO, acetic acid, eianolamine, and acetyl alcohol, or they may involve water as a solvent that is incorporated into the crislaline network. Solvates in which the solvent that is incorporated into the crystalline network is water, are called "hydrates". Hydrates include stoichiometric hydrates and also compositions containing varying amounts of water. The invention includes all these solvates. The person skilled in the art will further appreciate that some compounds of the invention that exist in crystalline form, including the various solvates thereof, may exhibit polymorphism (ie, the ability to occur in different crystalline esirucíuras). These different crystalline forms are typically called polymorphs. " invention includes all these polymorphs. The polymorphs have the same chemical composition, but they differ in the packing, the geomelic disposition and you will hear descriptive properties of the solid crisial alley. By the way, polymorphs can have different physical properties, such as shape, density, hardness, deformability, stability and dissolution properties. The polymorphs showed different melting points, IR spectra, and different X-ray diffraction diagrams, which can be used to identify them. The person skilled in the art will appreciate that different polymorphs can be produced, for example, by changing or adjusting the reaction conditions or the reagents, used in the preparation of the compound. For example, changes in temperature, pressure, or solvent, can result in polymorphs. In addition, under certain conditions a polymorph can be converted spontaneously into another polymorph.
Preparation of the Compounds The compounds of this invention can be obtained by a variety of methods, including conventional chemistry. Any previously defined variable will continue to have the previously indicated meaning, unless otherwise indicated. The general illustrative synthetic methods are then synthesized and the specific compounds of the invention are then prepared in the examples section. Compounds of formulas I and II can be prepared, for example, according to Schemes 1, 2, and 3 that were represented below: SCHEME 1 Conditions: a) (BOC) 20, THF; b) s-BuLi, CIC02Me, TMEDA, Et20; c) N-bromosuccinimide, Meiylene chloride; d) TFA; e) Mn02, THF; f) LiOH, MeOH, water; g) R1 B (OR) 2, Imes-HCl, Pd (OAc) 2, Dioxane / water; h) HATU, NH3, DMF; i) RCHO (o) RC (0) R \ NaOMe, MeOH; j) Pd (OH) 2, H2, HOAc, EtOH; k) R4CI, TEA, Methylene Chloride (o) (R4) 20, DMAP, Meyylene Chloride Scheme 1 represents a general scheme for the preparation of compounds according to formulas I and II in which R2 and R3 are H , F or Cl, U is a bond or alkylene Cj-Cg or C2-Cg alkenylene and V is Cd-C7 cycloalkyl or Cd-C7 cycloalkenyl or heyerocycloaikyl or heyerocycloalkenyl. Scheme 1 also represents a general scheme for the preparation of compounds according to formulas I and II in the that U is C---Cg alkylene or C2-C alkenylene and V is aryl, or heeroaryl. In Scheme 1, R1 has been defined earlier unless otherwise indicated. The indoline 1 represented as starting material is available in the market. The reaction conditions are those that have been described in the Scheme; however, the skilled person will appreciate that certain modifications are possible in the reaction conditions and / or in the reagents employed. Treatment of indoline 1 with di-fer-butyl dicarbonate in a suitable solvent such as THF or methylene chloride yields the desired BOC-protected product. Oral transformation to the desired bromide 2 can be carried out by liration using sec-buillillil in the presence of TMEDA and inactivating with meioyl chloroformia followed by bromination with N-bromosuccinimide. The irradiation of bromide 2 with uro-trifluoroacetic acid followed by oxidation of indoline results in indole with manganese dioxide and the subsequent hydrolysis of the methylester in the acid yields the desired carboxylic acid 3. The unsaturation of the R 1 can be carried out by a reaction of coupling mediated by an ionization signal using an appropriate cailater and a coupling molecule. As an example of ransformation, for the case of Scheme 1 condition "g", a cross-coupling reaction of Suzuki can be completed using an ester or boric acid in the presence of Pd (OAc) 2, Imes-HCI and Cs2C03 in 1, 4 -dioxane and water. The preparation of the primary carboxamide 4 can be carried out by reaction of the carboxylic acid with ammonia in the presence of HATU. The conversion from 4 to 5 incorporating the U-V group is done mid-way the reaction with the appropriate aldehyde or ketone precursor to U-V. This transformation can be done under basic or acidic conditions. For the case in which the UV group is totally saturated, a subsequent reduction of the intermediate production will produce the desired product 5. As an example of the reduction, for the case of Scheme 1 condition "j", a hydrogenation reaction in the presence of Pd (OH) 2 completes the transformation to 5. In the case where UV and / or R1 contains a suitable protecting group, the protective group can be removed under appropriate conditions and further transformation into other products. The subsequent transformation of the amine function of the UV group into the sulfonamide or amide of R 4 can be carried out with the sulfonyl chloride or appropriate acid or acid anhydride of R 4. It will be appreciated from the specialization that after conversion to the sulfonamide or amide of R4 the resulting product may require processing in R4. This may include but is not limited to adequate protection and manipulations of the functional group and reactions with amines / alcohols Rd.
SCHEME 2 Conditions: a) R1B (OR) 2, Imes-HCl, Pd (OAc) 2, dioxane / water; b) HATU, NH3, DMF; c) N-Yodosuccinimide, Melylene Chloride; d) VUB (OR) 2, Pd (PPh3), Cs2C03, 1,4-dioxane, water; e) R2CI, TEA, Meleylene Chloride (o) (R2) 2 ?, DMAP, Meyylene Chloride Scheme 2 represents a general scheme for the preparation of compounds according to formulas I and II in which U is a bond and V is aryl or heteroaryl. In Scheme 2, R1 has been previously defined unless otherwise indicated. The indolecarboxylic acid 3 represented as starting material is obtained as described in Scheme 1. The reaction conditions are those described above in the scheme; however, the skilled person will appreciate that certain modifications are possible in the reaction conditions and / or in the reagents employed. The skilled person will appreciate that if a substituent described herein is not comparable to the synthetic methods described herein, the substituent can be protected with a suitable protecting group, which is scalable under the reaction conditions. The protecting group can be removed at a suitable point within the sequence of reactions, to provide an intermediate or target compound, wanted. Suitable protecting groups, and methods for protecting and deprotecting different substitutes by employing such suitable protecting groups, are well known to those skilled in the art, and examples of them can be found in T. Greene and P. Wuis, Proiecíing Groups in Chemical Syníhesis (3rd edition), John Wiley & Sons, NY (1999). In some cases a substituent can be specifically selected to be reactive under the reaction conditions employed. In these circumstances, the reaction conditions convert the selected substituent into another substituent which is either useful as an intermediate or is a desired constituent in an objective compound.
Use methods The compounds of the invention are inhibitors of IKK2, These compounds can be useful in the treatment of disorders in which the underlying pathology is (at least in part) attributable to inadequate activity of IKK2 (also called IKKß), such as rheumatoid arthritis, inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease (COPD). The inadequate activity of IKK2 refers to any activity of IKK2 that deviates from the normal activity of IKK2 expected in a particular patient. The inadequate activity of IKK2 may take the form of, for example, an abnormal increase in activity or an aberration in the time and / or conirol of the activity of IKK2. Such inadequate activity may be the result, example, of overexpression or mutation of the protein kinase, which leads to inadequate or inconclusive secretion. For the sake of comparison, in another aspect, the invention refers to methods to eradicate uranium. These disorders include inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease (COPD).; osteoarthritis, osteoporosis and fibrotic diseases; dermatoses, including psoriasis, atopic dermatitis and skin lesions induced by ultraviolet (UV) radiation; autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, rejection of tissues and organs, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, include the acquired immunodeficiency syndrome (AIDS), respiratory distress syndrome in adults and ataxia telangieclasia. The methods of treatment of the invention comprise administering a safe and effective amount of a compound according to the formulas 1-11 or a pharmaceutically acceptable salt thereof to a patient in need thereof. The individual embodiments of the invention include methods of irradiating any one of the above-mentioned phenomena by administering a safe and effective composition of a compound according to formulas 1-11 or a pharmaceutically acceptable salt. acceptable to a patient who needs it. As used herein, the term "to treat", referring to an ransom, means: (1) to alleviate or prevent the írasíomo, or one or more of the biological manífalaciones of the írasíorno, (2) to interfere with (a) one or more points in the biological cascade leading to, or responsible for, the írasíorno, or (b) one or more of the biological manifestations of the íraslomo, (3) alleviating one or more of the symptoms or effects associated with the írasíorno, or (4) reírasar the progression of the írasíorno or one or more of the biological manifestations of the trasíorno. As indicated above, the "irrationality" of an erosion includes the prevention of such a disorder. Those skilled in the art will appreciate that "prevention" is not an absolute term. In medicine, it is understood that "prevention" refers to the prophylactic administration of a drug to diminish the probability or severity of an uranium or one of its biological manifestations, or to discuss the beginning of said uranium or its biological manifestation. As used in the present specification, "safe and effective quality", referring to a quality of the compound of the invention or of another pharmaceutically active agent, means an amount of the compound that is sufficient to erase the condition of the patient, but sufficiently low. to avoid serious side effects (with a reasonable benefit / risk ratio) within the scope of the founded medical opinion. The safe and effective quality of a compound will vary with the particular compound chosen (eg, depending on the power, efficiency and average life of the compound); the path of chosen admi- nisiration; of the transient that is being treated; of the severity of the disorder being treated; the age, size, weight and physical condition of the patient being brought; the clinical history of the patient to be treated; the duration of the treatment; the nature of simultaneous therapy; the desired therapeutic effect; and similar factors, but, no matter, it can be determined in a rulinal way by the expert in the technique. When used in memory, "patient" refers to a lower human or animal. The compounds of the invention can be administered by any suitable route of administration, including both general administration and topical administration. General administration includes oral administration, parenteral administration, transdermal administration, partial administration and administration by inhalation. Parenteral administration refers to administration routes different from enral, transdermal or inhalation, and is typically performed by injection or infusion. Parenteral administration includes intravenous, intramuscular and subcutaneous injection or infusion. Inhalation refers to administration in the patient's lungs, either through the mouth or through the nostrils. Topical administration includes the application to the skin as well as the intraocular, otic, iniravaginal and iniraranasal administration. The compounds of the invention can be administered from once or according to a dosing regimen in which several doses are administered at variable time intervals during a given period of time. For example, doses may be administered one, two, three or four times a day. The doses may be administered until the desired lepraeuic effect is obtained or indefinitely to maintain the desired lepraeuic effect. Suitable dosage regimens for a compound of the invention depend on the pharmacokinetic properties of that compound, such as absorption, distribution and half-life, which can be determined by the skilled artisan. In addition, suitable dosage regimens, including the duration thereof, for a compound of the invention, depend on the disorder being treated., of the seriousness of the transient that is being irradiated, of the age and physical condition of the patient that is being irradiated, of the clinical history of the patient that is going to be brought, of the nature of the simultaneous therapy, of the desired therapeutic effect and of similar factors in the knowledge and expertise of the expert in the technique. In addition, those skilled in the art will understand that suitable dosing regimens may require adjustments depending on the individual response of the patient to the dosing regimen or with the passage of time when the individual patient needs a change. Typical daily doses may vary depending on the particular route of administration chosen. Daily oral doses for oral administration vary from 0.001 mg to 10 mg per kg of body weight tolal.
In addition, the compounds of the invention can be administered as prodrugs. As the term is used herein, a "prodrug" of a compound of the invention is a functional derivative of the compound that, when administered to a patient, even releases the compound of the invention in vivo. The administration of a compound of the invention in the form of a prodrug can allow one skilled in the art to do one or more of the following: (a) modify the beginning of the action of the compound in vivo; (b) modifying the duration of the action of the compound in vivo; (c) modify the transport or distribution of the compound in vivo; (d) modifying the solubility of the compound in vivo; and (e) overcoming a side effect or other difficulty encountered with the compound. Typical functional derivatives used to prepare prodrugs include modifications of the compound that are chemically or enzymatically cleaved in vivo. Such modifications, which include the preparation of phosphates, amides, esters, thioesters, carbonates, and carbamates, are well known to those skilled in the art. The invention also provides a compound of the invention for use in medical therapy, and in particular in the irradiation of Irastomos in which the activity of IKK2 is involved. In this manner, in a further aspect, the invention relates to the use of a composed according to the formulas 1-11 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the irradiation of a disorder characterized by an inappropriate activity of IKK2.
Particular Iraslorns characterized by inadequate activity of IKK2 include inflammatory conditions and the repair of the ileum, in particular rheumatoid arthritis, inflammatory bowel disease, asthma and chronic obstructive pulmonary disease (COPD); osleoartrilis, osteoporosis and fibrotic diseases; dermatoses, including psoriasis, atopic dermatilis and cutaneous lesions induced by uliovioviole radiation (UV); autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, rejection of tissues and organs, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immunodeficiency syndrome (AIDS), respiratory distress syndrome in adults, and aiaxiaelangieclasia, as a consequence of the inhibition of prokin kinase IKK2.
Compositions The compounds of the invention will usually, but not necessarily, be formulated in pharmaceutical compositions prior to administration to a patient. Accordingly, in another aspect the invention relates to pharmaceutical compositions comprising a compound of the invention and one or more pharmaceutically acceptable excipients. The pharmaceutical compositions of the invention can be prepared and packaged wholesale, for example as powders or syrups, of where a safe and effective amount of a compound of the invention can be taken and then administered to the patient. Alternatively, the pharmaceutical compositions of the invention can be prepared and packaged in a unilary dosage form, wherein each physically discrete unit contains a safe and effective amount of a compound of the invention. When prepared in unit dosage form, the pharmaceutical compositions of the invention may contain, for example, from O.d mg to 1 g or from 1 mg to 700 mg or from d mg to 100 mg of a compound of the invention. The pharmaceutical compositions of the invention comprise a compound of the invention limitatively. However, in certain embodiments, the pharmaceutical compositions of the invention contain more than one compound of the invention. For example, in certain embodiments, the pharmaceutical compositions of the invention contain two compounds of the invention. In addition, the pharmaceutical compositions of the invention may also optionally comprise one or more additional pharmaceutically active compounds. As used herein, the term "pharmaceutically acceptable excipient" means a pharmaceutically acceptable material, composition or vehicle, involved in giving shape or consistency to the pharmaceutical composition. Each of the excipients must be compatible with the other ingredients of the pharmaceutical composition when mixed with them, so as to avoid interactions that would substantially reduce the efficacy of the compound of the invention when administered to the patient, and interactions that would result in pharmaceutical compositions that were not pharmaceutically acceptable. Furthermore, of course, each of the excipients must have a sufficiently high purity that makes it pharmaceutically acceptable. The compound of the invention and the pharmaceutically acceptable excipient or excipients will typically be formulated in a dosage form adapted to be administered to the patient by the desired administration route. For example, the dosage forms include those intended for (1) oral administration, such as tablets, capsules, oblong tablets, pills, ices, powders, syrups, elixirs, suspensions, solutions, emulsions, sachets and seals; (2) parenteral administration such as solutions, suspensions and reconstituted sterilized powders; (3) transdermal administration such as transdermal patches; (4) administration rectally, such as suppositories; (d) inhalation, such as aerosols, solutions and dry powders; and (6) topical administration, such as creams, ointments, lotions, solutions, pastes, aerosols, foams and gels. Suitable pharmaceutically acceptable excipients will vary depending on the particular dosage form chosen in each case. In addition, suitable pharmaceutically acceptable excipients can be chosen for a particular function they can play in the composition. For example, certain excipients pharmaceutically acceptable can be chosen by virtue of their ability to facilitate the production of uniform dosage forms. Certain pharmaceutically acceptable excipients may be chosen by virtue of their ability to facilitate the production of stable dosage forms. Certain pharmaceutically acceptable excipients may be chosen in virtue of their ability to facilitate the support and transport of the compound or compounds of the invention, once administered to the patient, from an organ or portion of the body, to the organ or portion thereof. body. Certain pharmaceutical excipients can be chosen by virtue of their ability to improve the patient's commitment to the treatment. Suitable pharmaceutically acceptable excipients include the following excipient liposomes: diluents, fillers, binders, disintegrants, lubricants, glidants, granulating agents, coating agents, wetting agents, solvents, co-solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, flavor masking agents, coloring agents, anti-caking agents, humectants, chelating agents, plasticizers, viscosity-increasing agents, antioxidants, preservatives, stabilizers, surfactants, and pH regulating agents. Those skilled in the art will appreciate that certain pharmaceutically acceptable excipients can fulfill more than one function and can fulfill food functions depending on the amount of excipient that is present in the formulation and the other ingredients that are present in the formulation.
Those skilled in the art possess knowledge and experience in the art which allows them to select suitable pharmaceutically acceptable excipients, in amounts appropriate for use in the invention. In addition, there are several sources available to those skilled in the art which describe pharmaceutically acceptable excipients and which may be useful in choosing suitable pharmaceutically acceptable excipients. As examples, Remington's can be cited Pharmaceutical Sciences (Mack Publishing Company), The Handbook of Pharmaceutical Additives (Gower Publishing Limited) and The Handbook of Pharmaceutical Excipient (the American Pharmaceutical Association and íhe Pharmaceutical Press). The pharmaceutical compositions of the invention are prepared using techniques and methods that are known to those skilled in the art. Some of the methods commonly used in the art are described in Remington's Pharmaceutical Sciences (Mack Publishing Company). In one aspect, the invention relates to a solid oral dosage form, such as a tablet or capsule, comprising a safe and effective amount of a compound of the invention and a diluent or filler. Such diluels and fillers include lactose, sucrose, dexlose, mannitol, sorbitol, starch (eg, corn starch, potato starch, and pregelatinized starch), cellulose and its derivatives (eg, microcrystalline cellulose), calcium and dibasic calcium phosphate. The way of Oral solid dosage may further comprise a binder. Suitable binders include starch (e.g., corn starch, potato starch and pregelatinized starch), gelatin, gum arabic, sodium alginate, alginic acid, fragrant, guar gum, povidone, and cellulose and their derivatives (p. .ej, microcrystalline cellulose). The oral solid dosage form may further comprise a disintegrant. Suitable disintegrants include crospovidone, sodium salt of starch glycolate, croscarmellose, alginic acid and sodium carboxymethyl cellulose. The oral solid dosage form may further comprise a lubricant. Suitable lubricants include stearic acid, magnesium eslearalo, calcium eslearalo and lalco. When appropriate, unilaried dosage formulations can be microencapsulated for oral administration. The composition can also be prepared to prolong or sustain the release, for example by coating particulate material with polymers, waxes or the like, or by including it therein. The compounds of the invention can also be combined with soluble polymers, as drug-targeting vehicles. Such polymers may include polyvinylpyrrolidone, pyran copolymers, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamide-phenol, or poly (ethylene oxide) -polylysine substituted with palmitoyl radicals. In addition, the compounds of the invention can be combined with a class of biodegradable polymers useful for achieving a controlled release of a drug, for example poly (lactic acid), poly (epsilon-caprolactone), poly (acid) hydroxybutyric), polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross-linked or amphipathic block copolymers of hydrogels. In another aspect, the invention relates to a liquid oral dosage form. Oral liquids such as solutions, syrups and elixirs can be prepared in a unit dosage form, such that a given amount contains a predetermined amount of a compound of the invention. Syrups can be prepared by dissolving the compound of the invention in a suitably flavored aqueous solution, while the elixirs are prepared using a non-toxic alcoholic vehicle. Suspensions may be formulated by dispersing the compound of the invention in a non-toxic vehicle. Solubilizers and emulsifiers may also be added such as eloxylated isostearyl alcohols, and polyoxyethylene sorbitan alcohols, preservatives, flavoring additives such as peppermint oil or natural sweeteners or saccharin or other artificial sweeteners, and the like. In one aspect, the invention relates to a dosage form adapted to be administered to a patient by inhalation. For example, the compound of the invention can be inhaled into the lungs in the form of a dry powder, an aerosol, a suspension, or a solution. The dry powder compositions for administration to the lung by inhalation typically comprise a compound of the invention in the form of a finely divided powder, June with one or more pharmaceutically acceptable excipients, in the form of finely divided powders. Pharmaceutically acceptable excipients suitable in particular for use in dry powders are known to those skilled in the art, and include lactose, starch, mannitol, and mono-, di-, and polysaccharides. The dry powder can be administered to the patient by means of a dry powder inhaler with reservoir (RDPI, English acronym for reservoir dry powder inhaler), which has a suitable deposit to contain multiple doses (not measured) of medication in the form of dry powder. The RDPIs typically include means for customizing each dose of medication from the reservoir to a management position. The dosing means may comprise, for example, a metering cup, which can be moved from a first position in which the cup can be filled with the drug from the reservoir, to a second position in which the dosage of the dosed medicament is available for inhalation for the patient. Alternately, dry powder can be presented in capsules (for example gelatin or plastic), cartridges or vesicular containers for use in a multi-dose dry powder inhaler (MDPI). MDPIs are inhalers in which the medication is included in a multi-dose container that contains (or otherwise carries) multiple defined doses (or parts thereof) of medication. When the dry powder is presented as a vesicular container, it comprises multiple vesicles to contain the medicament in the form of a dry powder. The vesicles are disposed, typically, in a regular manner to facilitate the release of the drug from them. For example, the vesicles may be arranged in a generally circular fashion on a disk-shaped vesicular container, or the vesicles may have an elongated shape, for example forming a strip or tape. Each capsule, cartridge or vesicle may contain, for example, between 20 Dg and 10 mg of compound of the invention. Aerosols can be formed by suspending or dissolving a compound of the invention in a liquefied propellant. Suitable propellants include halocarbons, hydrocarbons, and other liquefied gases. Representative propellants include: trichlorofluoromethane (propellant 11), dichlorofluoromethane (propellant 12), dichlorotetrafluoroethane (propelenide 114), tetrafluoroethane (HFA-134a), 1,1-difluoroethane (HFA-1 d2a), difluoromethane (HFA- 32), pentafluoroethane (HFA-12), heptafluoropropane (HFA-227a), perfluoropropane, perfluorobutane, perfluoropentane, butane, isobuany, and pentane. Aerosols comprising a compound of the invention will typically be administered to a patient by means of a metered dose inhaler (MDI). Such devices are known to those skilled in the art. The aerosol may contain additional pharmaceutically acceptable excipients, which are typically employed with MDI, such as surfactants, lubricants, cosolvents and other excipients, to improve the Physical stability of the formulation, to improve the functioning of the valve, to improve the solubility, or to improve the taste. Suspensions and solutions comprising a compound of the invention can also be administered to a patient by means of a nebulizer. The solvent or suspending agent used for nebulization may be any pharmaceutically acceptable liquid such as water, aqueous saline solution, alcohols or glycols, eg, ethanol, isopropyl alcohol, glycerol, propylene glycol, polyethylene glycol, ele, or mixtures thereof. same. Saline solutions use salts that have little or no pharmacological activity after administration. For this purpose, inorganic salts, such as halogen salts with alkali metals or with ammonium, eg sodium chloride, potassium chloride, or organic salts, such as potassium, sodium and ammonium salts can be used for this purpose. organic acids, eg ascorbic acid, citric acid, acetic acid, iartaric acid, eic. Other pharmaceutically acceptable excipients may be added to the suspension or solution. The compound of the invention can be characterized by the addition of an inorganic acid, for example hydrochloric acid, nitric acid, sulfuric acid and / or phosphoric acid; an organic acid, e.g., ascorbic acid, citric acid, acetic acid, and iartaric acid, ele, a complexing agent such as EDTA or citric acid, and salts thereof; or an antioxidant such as vitamin E or ascorbic acid. These agents can be used alone or in combination, to stabilize the compound of the invention. Hela preservatives such as benzalkonium chloride or benzoic acid, and salts thereof may be added. Surfactants may be added, in particular to improve the physical stability of the suspensions. These include lecithin, disodium dioclyl sulfosuccinate, oleic acid, and sorbiyan esters. Pharmaceutical compositions adapted for transdermal administration may be presented as discrete patches deigned to remain in minute con? Um with the epidermis of the patient for a prolonged period of time. For example, the active ingredient can be delivered from the patch by iontophoresis, as generally described in Pharmaceutical Research, 3 (6), 318 (1986). The pharmaceutical compositions adapted for topical administration can be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils. For treatments of the eye or other external tissues, for example the mouth and the skin, the compositions may be applied in the form of an ointment or topical cream. When formulated as an ointment, the compound of the invention may be employed with a paraffinic ointment base, or with a water-miscible ointment base. Alternatively, the compound of the invention can be formulated in a cream with an oil-in-water cream base or with a water-in-oil base. Pharmaceutical compositions adapted for nasal administration in which the carrier is a solid include a coarse powder having a particle size, for example, in the interval of 20 to 600 micrometers, which is administered by rapid inhalation through the nostrils from a container containing the powder, held near the nose. Suitable compositions in which the carrier is a liquid, for administration as nasal sprays or nasal drops, include aqueous or oily solutions of the compound of the invention. Pharmaceutical compositions adapted for parenteral administration include sterile aqueous and non-aqueous injection solutions, which may contain anti-oxidants, pH regulators, bacteriostatic agents and solutes which render the formulation isotonic with the blood of the intended delirium; and sterile, aqueous and non-aqueous suspensions, which may include suspending agents and thickening agents. The compositions can be presented in unit dose containers or in multi-dose containers, for example closed ampoules and vials and can be stored in lyophilized state, which requires only the addition of sterile liquid vehicle, for example water for injection, immediately before use. . Solutions and suspensions for extemporaneous injection can be prepared from powders, granules and sterilized tablets.
EXAMPLES The following examples illustrate the invention. These examples are not intended to limit the scope of the invention, but rather to provide guidance for the person skilled in the art to prepare and use the compounds, compositions and methods of the present invention. Although particular embodiments of the present invention are described, those skilled in the art will appreciate that some changes and modifications can be made without departing from the spirit and scope of the invention. All references to ether are to diethyl ether; brine refers to a saturated aqueous solution of NaCl. Unless otherwise indicated, all temperaments are expressed in ° C (Celsius degrees). Unless stated otherwise, all reactions are carried out under an inert atmosphere at ambient temperature. The spectra of 1 H NMR were recorded in a Brucker DPX400, a Brucker DPX2dO, a Brucker AC400 or a Varian Inova 400. The chemical shifts are expressed in parts per million (ppm, D units). The patterns of unfolding describe apparent multiplicities and are designated as s (singlet), d (doublet), t (multiply), c (quadruplet), quintuple, m (multiplet), a (width). The low resolution mass spectra (MS) were recorded in a spectrometer JOEL JMS-AXdOdHA, JOEL SX-102 or a SCIEX-APliii; the LC-MS was registered in Waters ZQ or PE Sciex Single tunnellers Quadrupole LC / MS API-150. Preparative HPLC refers to methods in which the material was purified by high performance liquid chromatography on a column of HPLC ABZ + d μm (10 cm x 21.2 mm d.i.) with 0.1% formic acid in water and 0.06% formic acid in acetonitrile using an elution gradient at a flow rate of 8 ml / min and UV detection at 264 nM. Unless otherwise indicated, the term "silica gel column flash chromatography" refers to the purification of material using prepackaged silica gel columns Redisep ™, in an ISCO sq16x apparatus, with solvent systems that are indicate The reverse phase HPLC method A refers to methods in which the materials were purified by high performance liquid chromatography on a Sd μm HPLC column (7d x 30 mm di) using gradient elution with the established solvent systems and UV detection at 2d4 nm. The reverse phase HPLC method B refers to methods in which the materials were purified by high performance liquid chromatography on a Luna C18 (2) 100A HPLC column (dO x 21.2 mm di) using gradient elution with the solvent system established and UV deletion at 2d4 nm. Experimental Conditions of LC-MS for PE Scie? Single Quadrupole LC / MS API-150: Liquid chromatograph: System: Shimadzu LC system with SCL-10A controller and dual UV detector Autosampler: Leap CTC with a six-port Valco injector Column: Aquasil / Aquasil (C18 40x1 mm) Injection volume (μL): 2.0 Solvent A: H20, 0.02% TFA Solvent B: MeCN, 0.018% TFA Gradient: linear Channel A: UV 214 nm Channel B: ELS Stage Time (min) Duration. (min) Flow (μl / min) Disol.A Disol.B 0 0.00 0.00 300.00 9d.00 d.OO 1 0.00 0.01 300.00 9d.00 d.OO 2 0.01 3.20 300.00 10.00 90.00 3 3.21 1.00 300.00 10.00 90.00 4 4.21 EYE 300.00 9d.OO 5. 00 d 4.31 0.40 300.00 9d.00 d.OO Mass spectrometer: PE Sciex Single Quadrupole LC / MS API-150 Polarity: Positive Acquisition Mode: Profile Intermediates Intermediate 1 1,3-dihydro-1 H-indol-1-carboxylate 1,1-dimethylethyl Indoline (10 g, 84 mmol) was dissolved in tetrahydrofuran (100 mL) and di-tert-bulyl dicarbonate (22 g, 0 J mol) was added. The mixture was allowed to stir for 16 hours at room temperature in an atmosphere of inert nitrogen. The tetrahydrofuran was removed in vacuo and the slurry was purified by vacuum stripping to give the title compound (15J g) in the form of a clear pale pink aceil which crystallized after a standing period (temperature: 160-162 ° C. , pressure 1 - 0J mm Hg). 1 H NMR (400 MHz, DMSO-D6) D ppm 1.50 (s, 9 H) 3.04 (t, J = 8. 7 Hz, 2 H) 3.89 (t, J = 8.8 Hz, 2 H) 6.91 (td, J = 7.3, 0.8 Hz, 1 H) 7.13 (i, J = 7.5 Hz, 1 H) 7.18 (d, J = 7.3 Hz, 1 H) 7.5-7.8 (sa, 1 H) ta 3.44 min.
Intermediate 2: 7-methyl 2,3-dihydro-1H-indol-1, 7-dicarboxylic acid 1- (1-dimethylethyl) 1,3-Dihydro-1 H-indol-1-carboxylate 1,1-dimethylethyl ether (5 g, 22.8 mmol) and N,? /, N, N-tetramethyl-1,2-ethanediamine (4.6 ml, 30.5 mmol) in dry diallyl ether (300 ml) and cooled to -78 ° C in an acetone / dry ice bath. Secon-butyl lithium (1.4 M solution in cyclohexanes, 17.6 ml, 24.6 mmol) was added dropwise over 10 minutes and the reaction was allowed to stir for 90 minutes at this temperature. To the mixture was added methyl chloroformate (8.8 ml, 10.8 g, 0J mol) and the reaction was allowed to warm to room temperature for 1 hour. Water was carefully added to the mixture and the organic layer was separated and washed 3 times with more water. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound (4.91 g) as a gummy yellow solid. 1H RM? (400 MHz, DMSO-D6) D ppm 1.44 (s, 9 H) 3.06 (i, J = 8.2 Hz, 2 H) 3.69 (s, 3 H) 4.02 (t, J = 8.3 Hz, 2 H) 7.06 ( t, J = 7.5 Hz, 1 H) 7.3d (d, J = 7.5 Hz, 1 H) 7.39 (dd, J = 7.4, 1.1 Hz, 1 H) MS m / z 278 (M + 1) + i.a. 3.18 min.
Intermediate 3: 7-methyl d-bromo-2,3-dihydro-1 H-indo! -1,7-dicarboxylic acid 1- (1 J-dimethylethyl. 7-Methyl-2,3-dihydro-1 H-indol-1,7-dicarboxylic acid 1- (1,1-dimethylethyl) (3 J g, 11.2 mmol) and N-bromosuccinimide (2.0 g, 11.2 mmol) were dissolved. in dry dichloromethane (100 ml) and stirred in a nitrogen atmosphere at room temperature for 16 hours. The reaction was partitioned with a sodium hydroxide solution (2 M), separated and washed with more sodium hydroxide solution. The organic layer was dried over magnesium sulfate and concentrated in vacuo to give the title compound as a gummy red solid (3.dd g). 1 H NMR (400 MHz, DMSO-D6) D ppm 1.41 (s, 9 H) 3.09 (t, J = 8.3 Hz, 2 H) 3.70 (s, 3 H) 4.02 (t, J = 8.3 Hz, 2 H ) 7.46 (s, 1 H) 7.60 (s, 1 H) MS m / z 3d6 / 3d8 (ratio 1: 1) (M + 1) + ta 3.d2 min.
Intermediate 4: 5-bromo-2,3-dihydro-1 H-indol-7-carboxylamino of meyilo 7-Methyll-5-bromo-2,3-dihydro-1 H-indol-1,7-dicarboxylane from 1- (1,1-dimethylethyl) (9 g, 2d mmol) was dissolved in rhipfluoroacetic acid (6 ml) and it was agitated at room temperature for 16 hours. Dichloromelan and a sodium hydroxide solution (2M) were added and the organic layer was washed twice with a sodium hydroxide solution until the aqueous layer reached a pH value of > 7. Then, the organic layer was concentrated in vacuo to give the title compound as a brown solid (6.5 g). 1 H NMR (400 MHz, DMSO-D6) D ppm 2.99 (t, J = 8.5 Hz, 2 H) 3.61 (i, J = 8.4 Hz, 2 H) 3.78 (s, 3 H) 6.72 (s, 1 H 7.28 (d, J = 1 Hz, 1 H) 7.46 (d, J = 2 Hz, 1 H) MS m / z 256/268 (ratio 1: 1) (M + 1) + ta 3.32 min.
Intermediate 5: methyl d-bromo-1 H-indole-7-carboxylic acid Methyl d-bromo-2,3-dihydro-1 H-indole-7-carboxylate (6.5 g, 25 mmol) was dissolved in tetrahydrofuran (100 ml). Dioxide was added activated manganese (particle size 5 Dm, 22 g, 0.25 mol) and the mixture was stirred at room temperature for 16 hours. An additional 22 g of manganese dioxide was added and the reaction was stirred for 96 hours. Then, the reaction was filtered through celite and concentrated in vacuo to give the title compound (5J g) as a beige solid. 1 H NMR (400 MHz, DMSO-D6) D ppm 3.94 (s, 3 H) 6.d8 (d, J = 3 Hz, 1 H) 7.48 (d, J = 3 Hz, 1 H) 7.8 (d, J = 2 Hz, 1 H) 8.07 (d, J = 1.8 Hz, 1 H) 11.39 (sa, 1 H) MS m / z 2d2 / 2d4 (ratio 1: 1) (M-1) ta 3.41 min.
Intermediate 6: d-bromo-1 H-indole-7-carboxylic acid D-Bromo-1 H-indole-7-carboxylate (d g, 19.7 mmol) was dissolved in methanol (200 ml) and a solution of lithium hydroxide (0.99 g, 41 mmol) in water (10 ml) was added. The mixture was heated to reflux for 10 hours. The methanol was removed in vacuo and the residue was diluted with aqueous hydrochloric acid (2M). The resulting precipitate was removed by filtration and dried in a heated vacuum gun to give the title compound as a beige solid (4.7 g). 1 H NMR (400 MHz, DMSO-D6) D ppm 6.64 (dd, J = 2.0, 3.2 Hz, 1 H) 7.42 (t, J = 2.8 Hz, 1 H) 7.77 (d, J = 2 Hz, 1 H ) 8.03 (d, J = 1.8 Hz, 1 H) 11. 27 (s, 1 H) 13.1-13.7 (s a, 1 H) MS m / z 238/240 (ratio 1: 1) (M-1) t.a. 3.41 min.
Intermediate 7: 5-bromo-1H-indole-7-carboxamide To a solution of 5-bromo-1 / -indol-7-carboxylic acid (10.0 g, 42 mmol) in CH2Cl2 (100 ml) at room temperature was added EDC (9.66 g, d? 4 mmol), HOBt (6.81 g, d? 4 mmol) and NH3 (2.0 M in MeOH, 84 ml, 168 mmol). The reaction mixture was stirred at room temperature during 16 hours. The solvent was evaporated and the residue partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml x 2) and the combined organic phase was dried over MgSO 4 and concentrated to give the crude product (10 g, 98%). This crude product was used directly in the next step without further purification. LC / MS: m / z 240.0 (M + H), 1.95 min.
Intermediate 8: 4- [7- (aminocarbonyl) -5-bromo-1H-indol-3-yl-1, 3,6-dhydro-1 (2H-pyridinecarboxylate, 1-dimethyethyl) To a solution of 5-bromo-1 H-indole-7-carboxamide (10 g, 41.84 mmol) in meianol (5 ml) was added 4-oxo-1-piperidinecarboxylic acid 1,1-dithylethylethyl ester (684 mg, 3.42 g). mmol) and sodium methoxide (Od M in THF, 13.7 ml, 6.84 mmol). The reaction mixture was stirred at reflux temperature for 16 hours. All the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate (100 ml) and water (100 ml). The combined organic phase was dried over MgSO4, concentrated under reduced pressure and purified by flash column chromatography (ethyl acetate / hexanes, 1/1) to give the desired product (7.4 g, 43%). LC / MS: m / z 420.0 (M + H), 2.35 min.
Intermediate 9: 4- [7- (aminocarbonyl) -d-bromo-1 / - / - indol-3-ill-1-piperidine-carboxylate, 1-dimethylethyl To a solution of 1,1-dimethylethyl 4- (7- (aminocarbonyl) -d-bromo-1 H -indol-3-yl] - 3,6-dihydro-1 (2H) -pyridinecarboxylate (7.41 g , 17.64 mmol) in ethanol (600 ml) was added with platinum oxide (200 mg, d%). The reaction mixture was hydrogenated under a H 2 atmosphere for 16 hours. The resulting mixture was filtered through celite and the filtrate was concentrated. The resulting residue was purified by flash column chromatography (ethyl acetate / hexanes, from 1: 4 to 2: 1 v / v) to give the desired product (3.6 g, 48%). LC-MS: m / z 422.0 (M + H), 2.2d min.
Intermediate 10: d-bromo-3- (4-piperidinyl) -1H-indole-7-carboxamide To a solution of 1,1-dimethylethyl 4- (7- (aminocarbonyl) -d-bromo-1 H-indol-3-yl] -1-piperidinecarboxylate (1.d6 g, 3.7 mmol) in methanol (10 ml ) was added HCl in dioxane (4 M, 3d.d ml). The reaction mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure and the resulting residue was partitioned between ethyl acetate (50 ml) and aqueous NaOH at d% (dO ml). The aqueous layer was washed with ethyl acetate (2 x 60 ml) and the combined organic phases were dried with MgSO 4 and concentrated under reduced pressure to give the desired product (685 mg, 58%), which was used in the reaction mixture. next stage without further purification. LC-MS: m / z 322.0 (M + H), 1.45 min.
Intermediate 11: d-bromo-3- [1- (ethanesulfonyl) -4-piperidin-1H-indole-7-carboxamide Ethanesulfonyl chloride (4.5 ml, 47.4 mmol) was added dropwise to a solution of 5-bromo-3- (4-piperidinyl) -1H-indole-7-carboxamide hydrochloride (8.49 g, 23.7 mmol) and triamylamine ( 13.2 ml, 94.7 mmol) in DMF (80 ml) at 0 ° C (bath temperature). The reaction mixture was stirred at 0 ° C for 4 d min and then poured into a 2: 1 mixture of EtOAc / H20 (300 mL).
The resulting precipitate was removed by filtration, washed with EtOAc (2 x dO ml) and removed. The bilayer of EtOAc / H20 was separated and the aqueous layer was extracted with EtOAc (2 x 100 ml). The combined organic layers were washed with salified NaCl (1 x 100 mL), dried (MgSO), filtered and concentrated under reduced pressure. The crude product was combined with the above isolated precipitate and washed with MeOH (1 x 10 ml) to give 8J9 g of the title compound (83%). Alternatively, the title compound can be prepared as follows: A d-bromo-3- (4-piperidinyl) -1 H -indole-7-carboxamide (900 mg, 2.8 mmol) in CH2Cl2 (100 ml) at 0 ° C, was added ethanesulfonyl chloride (0.8 mg, 8.4 mmol) and triethylamine (1.6 ml, 11.2 mmol). The reaction mixture was stirred at 0 ° C for 30 min, after which time the mixture was partitioned between CH 2 Cl 2 and water. The aqueous phase was extracted with CH2Cl2 (dO ml x 2) and the combined organic phase was dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified by solid phase extraction on a dOO mg aminopropyl column (International Sorbent Technologies) eluting with chloroform (30 ml x 2) and ethyl acetate (dO ml) to give 800 mg of the title compound (69 %). LC / MS: m / z 414.0 (M + H), 2.2 min.
Intermediate 12: 3-ri- (ethylsulfonyl) -4-pi? Eridinyl-1-d-f3- (hydroxymethyl) phenylH-1H-indole-7-carboxamide In a solution of d-bromo-3- [1- (ethylsulfonyl) -4-piperidinium] -1 / - / - indole-7-carboxamide (20.0 mg, 0.048 mmol), K3P04 (21.0 mg, 0.096 mmol) and acid [3- (hydroxymethyl) phenyljboric acid (30.0 mg, 0J93 mmol) in dioxane / H20 (2 ml / 0.7 ml) was bubbled argon for d minutes before the addition of Pd (PPh3) 4 (d.O mg, 0.0048 mmol). The reaction mixture was heated in a microwave reactor (Smith synthesizer) for 20 minutes at 160 ° C. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine (10 ml), dried over MgSO, concentrated and purified by reverse phase HPLC method A (water / CH3CN, 0.1% 10-90% TFA) to give the compound of the title (9.7 mg, 46%). 1 H NMR (400 MHz, DMSO-D6) D ppm 1.25 (t, J = 7.2 Hz, 3H), 1.65 (m, 2H), 2.02 (m, 2H), 2.99 (m, 7H), 3.71 (m, 2H), 7.16 (s, 1 H), 7.42 (m, 3H), 7.77 (m, 2H), 8.02 (m, 2H), 8.22 (m, 1 H), 10.91 (s, 1 H). LC / MS: m / z 442.4 (M + H), t.a .: 1.73 min.
Intermediate 13: 3-1 - (Ethylsulfonyl-4-piperidinium-5- (3-formylphenol.-1 H -indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (hydroxymethyl) phenyl] -1H-indole-7-carboxamide (62.0 mg, 0J20 mmol) in THF (10 ml) Mn02 (360.0 mg, 3.6 mmol) was added at room temperature. The The resulting suspension was stirred overnight, filtered through celite and the solid was rinsed with THF (3 x 10 ml). The filtrate was concentrated to give the title compound (61.0 mg, 98%) which was used in the next step without purification. LC / MS: m / z 440.4 (M + H), t.a .: 1.97 min.
Intermediate 14: 3- [1- (ethylsulfonyl) -4-piperidinyl-d-4- (hydroxymethyl) phenifl-1 H-indole-7-carboxamide In a solution of d-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (20.0 mg, 0.048 mmol), K3P04 (21.0 mg, 0.096 mmol) and acid [4- (hydroxymethyl) phenyl] boronic acid (30.0 mg, 0J93 mmol) in dioxane / H20 (2 ml / 0.7 ml) was bubbled argon for d minutes before the addition of Pd (PPh3) 4 (dO mg, 0.0048 mmol) . The reaction mixture was heated in a microwave reactor (Smith synthesizer) for 20 minutes at 160 ° C. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine (10 ml), dried over MgSO, filtered, concentrated and purified by reverse phase HPLC method A (water / CH3CN, 0.1% TFA at 10-90%) to give the title compound (6.4 mg, 30%). LC / MS: m / z 442.4 (M + H), t.a .: 1.78 min.
Intermediate 1 d: 3-1 - (Ethylsulfonyl-4-p -peridinyl-d- (4-formylphenyl) -1 H -indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- [4- (hydroxymethyl) phenyl] -1 / - -indol-7-carboxamide (2d mg, 0.068 mmol) in THF ( d ml) was added Mn02 (160.0 mg, 1.73 mmol) at ambient temperature. The resulting suspension was stirred overnight, filtered through celite and the solid was rinsed with THF (3 x 10 ml). The filtrate was concentrated to give the title compound (15 mg, 58%) which was used in the next step without purification. LC / MS: m / z 440.4 (M + H), t.a .: 2.02 min.
Intermediate 16: 3- [1- (ethylsulfonyl) -4-piperidinin-d- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -1 / - / - indole-7 -carboxamide To a solution of 5-bromo-3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (1.0 g, 2.42 mmol), Bis (pinacolato) diborane (2.45 g, 9.66 mmol) ) and potassium carbonate (2J0 g, 21.8 mmol) in DME (15.0 ml) was added Pd2CI2 (dppf) after degassing for 5 min. Then, the mixture was heated in the microwave at 130 ° C for 11000 sec. Then, the reaction mixture was diluted with EtOAc (300 ml) and H20 (100 ml) and the solid was filtered. Then, the organic layer was washed with H20 (3 x 80 ml) and brine. The organic layer was dried over MgSO and concentrated. Then, DCM (40 ml) was added to remove any by-products to produce 2.4 g of the title compound. LC / MS: m / z 462.3 (M + H), t.a .: 2.03 min.
Intermediate 17: 3- [1- (ethylsulfonyl) -4-piperidinyl-1-d- (d-formyl-2-thyl) -1 H -indole-7-carboxamide To a solution of d-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (200 mg, 0.49 mmol) in dioxane (4.6 ml) and H20 (1.5 ml ) were added [5- (hydroxymethyl) -2-thienyl] boronic acid (232 mg, 1.47 mmol), potassium carbonate (406 mg, 2.94 mmol) and tetrakis (trifluorophosphine) palladium (0) (57 mg, 0.049). mmol). The reaction was carried out in the microwave at 1d0 ° C for 20 min. Aqueous work-up with EtOAc / H20 gave 447 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (hydroxymethyl) -2-thienyl] -1H-indole-7-carboxamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (hydroxymethyl) -2-thienyl] -1H-indole-7-carboxamide (200 mg, 0.46 mmol) in THF ( dO ml) was added Mn02 (1.21 g, 13.9 mmol). The mixture was stirred at room temperature for 3 h. Filtration of the reaction mixture through celite afforded 100 mg of the title compound (48.8%) LC / MS: m / z 446.2 (M + H), t.a .: 2.27 min.
Intermediate 18: 3-H - (ethylsulfonyl) -4-p -peridinyl-d- (4-formyl-2-thienyl) - 1 / - / - indole-7-carboxamide To a solution of 3-thiophenecarbaldehyde (3.0 g, 26.8 mmol) in DCM (64 mL) was added aluminum trichloride (8.37 g, 63 mmol) at 0 ° C. Then, the reaction was heated to reflux and bromine (1.6 ml, 30.28 mmol) was added dropwise. After the addition, the reaction mixture was stirred at reflux for 4 h. After cooling to room temperature, cold H20 (100 ml) was added and exfoliated with DCM (2 x 100 ml). The combined organic layer was washed with NaHCO 3 and dried. Purified by flash chromatography to give 3.62 g of d-bromo-3-thiophenecarbaldehyde (71%). To a solution of d-bromo-3-iiophenecarbaldehyde (260 mg, 1.29 mmol) in dioxane (4.6 ml) and H20 (1.5 ml) were added 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- ( 4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1 H -indole-7-carboxamide (200 mg, 0.43 mmol), potassium carbonate (250 mg, 2.68 mmol) and tetrakis (triphenylphosphine) palladium (0) (66 mg, 0.049 mmol). The reaction was carried out in the microwave at 1 dO ° C for 20 minutes. Then, it was dried with EtOAc and H20 to obtain the crude product. Then, this was treated with MeOH (10 ml) and the The solid was filtered and collected to give 310 mg of the desired thioule compound. LC / MS: m / z 446.4 (M + H), t.a .: 1.94 min.
Intermediate 19: 3-f 1 - (ethylsulfonyl) -4-piperidinip-d- (d-formyl-3-thienyl) -1 - / - indole-7-carboxamide To a solution of 4-bromo-2-thiophenecarbaldehyde (1.0 g, 4.48 mmol) in DME (16 ml) was added Bis (pinacol diborane (1.48 g, 5.82 mmol), KOAc (1 J4 g, 5.11 mmol) and Pd2Cl2 (dppf) (106 mg, 0.448 mmol). The reaction was carried out in the microwave at 150 ° C for 20 min. The solvent was concentrated and an aqueous treatment was carried out using EOAc and H20. The compost was purified by flash chromraphy using hexanes and EtOAc to give 1.8 g of 4- (4,4,5,5-teremethyl-1, 3,2-dioxaborolan-2-yl) -2-iiophenecarbaldehyde. To a solution of 5-bromo-3- [1- (ethylsulphonyl) -4-piperidinyl] -1H-indole-7-carboxamide (909 mg, 2.2 mmol) in dioxane (7.5 ml) and H20 (2.5 ml) were added. they added 4- (4,4, d, d-tetramethyl-1, 3,2-dioxaborolan-2-yl) -2-thiophenecarbaldehyde (1.67 g, 6.6 mmol), potassium carbonate (1.82 g, 13.2 mmol) and tetrakis (triphenylphosphine) palladium (0) (30 mg, 0.22 mmol). The reaction was heated in the microwave at 150 ° C for 20 min. Then, the mixture was concentrated to dryness. EtOAc (50 ml) was added to the residue and washed with brine. The precipitate formed between the water and the organic layer was filtered and collected as a brown solid to give 874 mg of the title compound (89%). LC / MS: m / z 446.4 (M + H), t.a .: 1.93 min.
Intermediate 20: 5-Bromoisoindoline Into a 50 ml, two-necked round bottom flask, dried and equipped with an addition funnel and a CaCI2 drying tube were placed 2. 0 g (13.6 mmol) of phthalimide. Then, the flask was cooled to 0 ° C in a salt and ice bath. 8 ml of an ice-cooled mixture of concentrated sulfuric acid and fuming nitric acid (1: 1 v / v) were added gradually with constant stirring. The mixture was then stirred for 30 min at 0 ° C and allowed to slowly warm to room temperature with stirring over a period of 1 h. Then, the reaction mixture was poured into ice. The resulting solid product was filtered and dried to give 1.6 g (61.3%) of 5-nitro-1 H-isoindol-1,3 (2H) -dione as a yellow solid. To a solution of 5-nylro-1H-isoindol-1,3 (2H) -dione (1.0 g, 6.2 mmol) in dry THF (16 mL) was added 10% Pd / C (0.2 g). The mixture hydrogenated at 206.84-275.790 kPa (30-40 psi) during 17 h. The cayalizer was filtered and the filtrate was evaporated in vacuo to give 0.5 g (59.3%) of 5-amino-1 H-isoindol-1,3 (2H) -dione as a yellow solid. To a stirred solution of 5-amino-1H-isoindole-1,3 (2 / - /) -dione (1.0 g, 6.2 mmol) dissolved in a solution of sulfuric acid (2 ml of concentrated H2SO4 in 7.5 ml of H20) ) at 0 ° C, an ice-cooled solution of sodium nitrite (0.8 g in 2 ml of H20) was added dropwise. After 45 min of stirring at 0 ° C, CuBr (3.4 g, 23.7 mmol) and HBr [48%] (13.6 ml, 4 vol. P.l. CuBr) were added at the same temperature. The resulting mixture was stirred at 80 ° C for 8 h and then poured into crushed ice. The solid was filtered, washed with ice-cold water and dried thoroughly to give 0.6 g (43.0%) of 5-bromo-1H-isoindol-1,3 (2H) -dione as a brown solid. A solution of BH3-THF (160 ml) with dry THF (50 ml) was placed in a 600 ml three-necked round bottom flask, dried and equipped with a reflux condenser and addition funnel. The mixture was cooled to 0 ° C. To this cooled solution was gradually added 5-bromo-1H-isoindole-1,3 (2 / -) -dione (8.0 g, 35.4 mmol) in dry THF (100 mL) and allowed to warm to room temperature. After 10 min at ambient temperature, the mixture was refluxed for 16 h. Then, the reaction mixture was cooled to 0 ° C and quenched with methanol. (Caution: vigorous foaming will occur). 20-30 ml of 2 N HCl was added and the mixture was heated to reflux for 1 h. The mixture was cooled, basified with a NaOH solution and extracted with ethyl acetate. The organic extracts The combined extracts were washed with water and saturated NaCl solution, dried over Na2SO and concentrated in vacuo. To the crude product in MeOH (150 ml) were added Et3N (12 ml) and di-tert-butyl dicarbonate (13.8 g)., 63.23 mmol) and stirred at room temperature for 16 h. Then, the reaction mixture was concentrated in vacuo. The crude product was diluted with CH2Cl2 (200 ml), washed with water and with a saturated NaCl solution and dried over Na2SO4. The crude product was purified by column chromatography using 20% ethyl acetate in hexanes as eluent to yield a colorless solid. To this was added dioxane-HCl at room temperature and stirred for 10 min, then, the solid obtained was filtered and dried to give 3.0 g (42.8%) of d-bromoisoindoline hydrochloride salt as a solid of color ash.
Intermediate 21: 5-bromo-3- (4-piperidinyl) -1 / - / - indole-7-carboxamide hydrochloride A 4M solution of HCl in dioxane (194 ml) was added to a solution of 4- [7- (aminocarbonyl) -d-bromo-1 H-indol-3-yl] -1-piperidinecarboxylate of, 1-di-ethylethyl (10 g, 23.7 mmol) in methanol (60 ml). The reaction mixture was stirred at room temperature for 4 hours and the solvent was evaporated under reduced pressure to give the title compound (9.6 g), which was used in the next step without further purification. LC-MS: m / z 322.4 (M + H), 1.40 min.
Intermediate 22: d-bromo-3-. { 1 - [(1-methylethyl) sulfonyl-1-4-piperidinyl) -1 H -indole-7-carboxamide Triethylamine (2.6 ml, 18.7 mmol) was added to a solution of d-bromo-3- (4-piperidinyl) -1H-indole-7-carboxamide hydrochloride in DMF (16 ml) at 0 ° C. The mixture was stirred at room temperature for 10 min and 2-propanesulfonyl chloride (1.04 mL, 9.32 mmol) was added. The agitation was continued for a further 30 min and the reaction mixture was diluted with 1: 1 EOAc / H20 (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2 x 60 ml). The combined organic layers were washed with saturated NaCl (1 x 100 mL), dried (MgSO) and concentrated under reduced pressure. The crude product was washed with MeOH (2 x 10 ml) to give the title compound (1.5 g, 75%). LC / MS: m / z 427.8 (M + H), 1.98 min.
Intermediate 23: 5- (d-formyl-3-thienyl) -3- (1-r (1-methylethyl) sulfonyl-1-piperidinyl) -1 / - / - indole-7-carboxamide The ester boronate used to obtain the title compound was prepared in 6 equal batches separated according to the following procedure: To a solution of 4-bromo-2-thiophenecarbaldehyde (1.0 g, 4.48 mmol) in DME (20 ml) was prepared. they added bis (pinacolato) diborane (1.48 g, d.82 mmol), KOAc (1.14 g, d.11 mmol) and Pd2CI2 (dppf) (106 mg, 0.448 mmol). The reactions were carried out in a Smith microwave at 150 ° C for 20 min. The 6 reactions were combined and concentrated under reduced pressure. The residue was taken up in EtOAc (200 ml) and H20 (50 ml). The layers were separated, the organic layer was washed with saturated NaCl (1 x 50 ml), dried (Na 2 SO 4) and concentrated under reduced pressure. The crude product was purified by flash chromatography eluting with hexanes / EtOAc to give 4- (4,4,5, d-teremethyl-1, 3,2-dioxaborolan-2-yl) -2-thiophenecarbaldehyde (dg, 78%) . A solution of 5-bromo-3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} - 1 H-indole-7-carboxamide (428 mg, 1 mmol), 4- (4,4, d, d-tetrameryl-1, 3,2-dioxaborolan-2-yl) -2-thiophenecarbaldehyde (960 mg, 4 mmol), Cs2CO3 (800 mg, 2.46 mmol) and Pd (PPh3) 4 (100 mg, 0.0865 mmol) was heated in a Smith microwave at 160 ° C for 20 min. The reaction mixture was filtered and concentrated under reduced pressure. The crude product was washed with MeOH (1 x 5 ml) to give the title compound (395 mg, 86%). LC / MS: m / z 460.4 (M + H), 1.98 min.
EXAMPLES EXAMPLE 1 3 ^ 1"(ethyl sulfonyl) -4" piperidine81 ° 5 3"(1-pipe ^ ^ carfeoxaoroda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (15.0 mg, 0.034 mmol) in DCM (2 ml) was added piperidine (4.0 μl, 0.04 mmol). The reaction solution was stirred at ambient temperature for 1 h before the addition of NaBH (OAc) 3 (23.0 mg, 0.109 mmol). The resulting mixture was stirred overnight at room temperature environment, time after which the solvent was removed under reduced pressure. The resulting residue was dissolved in 1.2 ml of DMSO and all the undissolved solid was removed by filtration. This solution in DMSO of the crude product was purified by reverse phase HPLC (H20 / CH3CN, 0.1% 10-90% TFA) to give the title compound (8.8 mg, 50. d%). LC / MS: m / z 509.4 (M + H), t.a .: 1.87 min.
EXAMPLE 2 3 1 ° (ethyl sulphide IIH ° Pip®? Ridñnñl1 ° 5 ° P ° (1 ° pipe? Raz5oiBpp? Et.nl | f @ [p? IB1 ° 1W carboxamide Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (1 dO mg, 0.034 mmol) were reacted, piperazine (3.6 mg, 0.04 mmol) and NaBH (OAc) 3 (23.0 mg, 0.102 mmol) to give the title compound (3.4 mg, 19.7%). LC / MS: m / z 610.2 (M + H), t.a .: 1.43 min.
EXAMPLE 3 3-p- (Ethylsulfonyl) "4-piperid.n.l1-5-f3 ° (^^ carboxanamide Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (15.0 mg, 0.034 mmol), morpholine, was reacted (3.5 μl, 0.04 mmol) and NaBH (OAc) 3 (23.0 mg, 0.102 mmol) to give the title compound (7.5 mg, 43%). LC / MS: m / z 511.2 (M + H), t.a .: 1.58 min. Alternatively, example 3 can be prepared as follows: To a solution of 3- [1- (ethylsulfonyl) -4-piperidinylj-5- (3-formylphenyl) -1 H -indole-7-carboxamide (20 mg , 0.046 mmol) in dichloromethane (1.5 ml) and methanol (1.5 ml) were added morpholine (0.070 ml, 0.276 mmol) and 1 drop of acélic acid. This mixture was stirred for 2 h at ambient lemperauria and then sodium borohydride (11 mg, 0.276 mmol) was added. After 30 min, the mixture was poured into an SCX cartridge (5.0 g) and EtOAc (10.0) was used. ml) and MeOH (10.0 ml) to thoroughly wash the cartridge. A 2 M solution of NH3 / MeOH (10.0 mL) was used to elute the product and then concentrated. The residue was dissolved in dimethyl sulfoxide (1.0 ml) and purified by Gilson's preparative HPLC to give the title compound (17.6 mg, 75%).
EXAMPLE 4 3-ri- (ethylsulphonyl) -4-piperidinniin-5-r3- (f? Pr.st.iill'2 ° (methyBsyBonyl) ethyl ammonium.) Methy8) pheniB1 ° 11W ° i? R.dol ° 7 ° carboxa? Pp? Ida Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (42.0 mg, 0.096 mmol), N were reacted -methyl-2- (methylsulfonyl) ethanamine (12.0 mg, 0.087 mmol) and? aBH (OAc) 3 (68.0 mg, 0.261 mmol) to give the title compound (15.1 mg, 28.0%). LC / MS: m / z 561.2 (M + H), t.a .: 1.58 min.
EXAMPLE 5 5 ° (3- { Fr2- (d.meltílam.no) etip (methyl) amino1m pperiodid.il1 ° 1H ° indoB ° 7 ° caboxbox5da To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (45.0 mg, 0.101 mmol) in DCM (2 ml ) was added A /, N, N-ylmethyl-1,2-ethanediamine (116 μl, 0.90 mmol). The reaction solution was stirred at room temperature for 1 h before the addition of? ABH (OAc) 3 (69 mg, 0.326 mmol). The resulting mixture was stirred overnight at ambient temperature and more αBH (OAc) 3 (128 mg, 0.606 mmol) was added. The reaction was stirred for a further 2 h, after which time the solvent was removed under reduced pressure. The crude product was purified by reverse phase HPLC (water / CH 3 C ?, 0.1% 10-90% TFA) to give the title compound (16.0 mg, 29.6%). LC / MS: m / z 626.8 (M + H), t.a .: 1.28 min.
EXAMPLE d pipera2Ír.il) metinffenil) -1H-indoD = 7 = carboxa? pr.dda Following the general procedure of example ü, 3- [1- (erylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (50.0 mg, 0.112 mmol) was reacted , 2-. { [2- (1-piperazinyl) ethyl] oxy} Ethanol (150 mg, 0.87 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the title compound (16.7 mg, 26%). LC / MS: m / z 598.4 (M + H), t.a .: 1.48 min.
EXAMPLE 7 3-f1l ° (e < iisylfooi8) ° 4 ° piperidinil1 ° 5 ° (3 °. {F3 ° (lhi8d? Rox5ctf.e £ iB) ° 1l- piperidiniB1met58.}. FTPÍl) ° 1H "indoB ° 7-carboxamide Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (60.0 mg, 0.112 mmol) was reacted, -piperidinylmelanol (98.9 mg, 0.86 mmol) and NaBH (OAc) 3 (68.0 mg, 0.303 mmol) to give the compound of the product (10.2 mg, 17%). LC / MS: m / z 639.4 (M + H), t.a .: 1.62 min.
EXAMPLE 8 5 ° f3- (. {Bisí2 metiBoxi) etil1amino} metiS) faith? ¡gl | ° 3 1 ®tilsyBfor.5B) ° 4 ° piperi (- l? c 1.
Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (60.0 mg, 0.112 mmol) were reacted, 2- (Melyloxy) -? / - [2- (meyloxy) and amineamine (114.3 mg, 0.86 mmol) and NaBH (OAc) 3 (68.0 mg, 0.303 mmol) to give the title compound (10.6 mg, 16%). LC / MS: m / z 567.6 (M + H), t.a .: 1.62 min.
EXAMPLE 9 5- (3-f (2,6-dimethyl-4-morpholinyl) metinf nl> -3-rn-letillsu 5B) = 4 < 1 Following the general procedure of Example 1, 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (50.0 mg, 0.112 mmol) was reacted, , 6-dimethylmorpholine (98.9 mg, 0.86 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the title compound (19.6 mg, 32%). LC / MS: m / z 539.2 (M + H), t.a .: 1.75 min.
EXAMPLE 10 3-ri- (ethyl-sulphonyl-4-p-peridin-p-5- (3-phenyl- (1,3-phthiazole-2-ylH-1-yl. -.ndol ° 7 ° Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (50.0 mg, 0.112 mmol) was reacted. - (2-pyrrolidinyl) -1,3-iazole (132.4 mg, 0.86 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the title compound (20.0 mg, 30.4%). LC / MS: m / z 578.6 (M + H), t.a .: 1.57 min.
EXAMPLE 11 -H- (ethylsulfonip-4-pperidyl) 5- (3- (f2- (2-thienip-1-pyrro..dónM1met.B> ffB.) 7 = ca Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (50.0 mg, 0.112 mmol) was reacted. - (2-lienyl) pyrrolidine (132.4 mg, 0.86 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the compound of the extract (20.0 mg, 30.4%). LC / MS: m / z 577.4 (M + H), t.a .: 1.78 min.
EXAMPLE 12 3 1 ° (etillsulffonil) - 4-piperid.n¡p-5- (3-fr (2- id? Roxli-2-fe? R? Llet? L) ° A i -7- Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (50.0 mg, 0.112 mmol) was reacted. - (Melylamino) -1-phenylelanol (129.9 mg, 0.86 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the title compound (22.1 mg, 36.6%). LC / MS: m / z 575.4 (M + H), t.a .: 1.66 min.
EXAMPLE 13 5- (3- { { Ethyl (methy.) Amioo1met ...}. Phenol) ° 3-P 7 = carboxa? PpiDda Following the general procedure of Example 1, 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (60.0 mg, 0.112 mmol), N were reacted methyleneamine (50.7 mg, 0.86 mmol) and NaBH (OAc) 3 (58.0 mg, 0.303 mmol) to give the title compound (11.5 mg, 21%). LC / MS: m / z 483.4 (M + H), t.a .: 1.57 min.
EXAMPLE 14 5 3- (amipomethyl) pheniB1 ° 3 1 ® StilsylfoniB) ° 4 ° pipeodiniB1 ° 1W ° i doB ° 7 ° carboxamide In a solution of 5-bromo-3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (30.0 mg, 0.072 mmol), Cs2CO3 (96 mg, 0.290 mmol) and 1 - [3- (4,4,5, d-telramelyl-1, 3,2-dioxaborolan-2-yl) phenyl] melanamin (82 mg, 0.350 mmol) in dioxane / H20 (2 ml / 0.7 ml) was bubbled argon duranie 5 minutes before the addition of Pd (PPh3) 4 (7.6 mg, 0.0072 mmol). The reaction mixture was heated in a microwave reactor (Smith synthesizer) for 20 minutes at 160 ° C. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine (10 ml), dried over MgSO4, filtered, concentrated and purified by reverse phase HPLC method A (water / CH3CN, 0.1% 10-90% TFA) to give the title compound (2.7 mg, 8.6%). LC / MS: m / z 441.4 (M + H), t.a .: 1.64 min.
EXAMPLE 15 5-. { 3 ° f (cicBopenti] amino) methy1phenyl} ° 3 1 efilsylffo ilH ° P ° ig) ®r ^^^ indole-7 = carboxanp? Ida Following the general procedure of Example 5, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (45 mg, 0.101 mmol), cyclopentylamine were reacted (90 μl, 0.090 mmol) and NaBH (OAc) 3 (197 mg, 0.93 mmol) to give the title compound (33.0 mg, 64%). LC / MS: m / z 509.4 (M + H), t.a .: 1.64 min.
EXAMPLE 16 543 ° ((f (3,4 ° dihSdroxifT? IB ^ metiB1amino) meti8) fe? Nini ° 341 el.iBsunfopiiH ° To a solution of 3- [1- (alkylsulfonyl) -4-piperidinyl] -d- (3-formylphenyl) -1H-indole-7-carboxamide (60 mg, 0.114 mmol) in dichloroean (2 ml) was added 4- (aminomethyl) -1,2-benzenediol (12.1 mg, 0.087 mmol). The reaction solution was stirred at ambient temperature for 10 min before the addition of NaBH (OAc) 3 (68 mg, 0.261 mmol). The resulting mixture was stirred overnight at ambient temperature, after which the solvent was relieved under reduced pressure. The crude product was purified by reverse phase HPLC (water / CH 3 CN, 0.1% 10-90% TFA) to give the title compound (7.4 mg, 12%). LC / MS: m / z 563.2 (M + H), t.a .: 1.67 min.
EXAMPLE 17 - (eti8su8foni¡8) -4-pipe? Rid5niB1-5 ° (3- (f (3 ° tiieit? IlmetBl) amópolm®t¡iWen5l]) °: [ Following the general procedure of Example 16, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (60 mg, 0.114 mmol) was reacted. - (3-lienyl) melanamine (9.83 mg, 0.087 mmol) and NaBH (OAc) 3 (68 mg, 0.261 mmol) to give the compound of the extract (4.7 mg, 7.8%). LC / MS: m / z 537.2 (M + H), t.a .: 1.62 min.
EXAMPLE 18 341 -ethylHsulfonyl-4-piperidine-5-r3 - ((r (1 -fl-1 - (h -d? Roxi? Pp? ßt.l 2 ° m.l.lpropylamino.). met.il) fen8l1 ° 1HHir.dol ° 7 ° caboxbox? pp? ida Following the general procedure of Example 16, 3- [1- (ethylsulfonyl) -4-picperidinyl] -d- (3-formylphenyl) -1 H -indole-7-carboxamide (60 mg, 0.114 mmol) was reacted, ( 2) -2-amino-3-meityl-1-bulanol (10.2 mg, 0.087 mmol) and NaBH (OAc) 3 (68 mg, 0.261 mmol) to give the title compound (14.9 mg, 25%). LC / MS: m / z 527.6 (M + H), t.a .: 1.48 min.
EXAMPLE 19 341 ° (e < .s8syforf) ° 4 ° Piperidic? Ini-5 ° (3 ° (f (2 ° fí? DroxB ° 1 ° pr.eti8eti8) am¡? No] met¡ l.}. feniB) ° 1W ° ñrt) doB ° 7 ° caboxboxipiBda Following the general procedure of Example 16, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (60 mg, 0.114 mmol), 2 were reacted. -amino-1-propanol (6.5 mg, 0.087 mmol) and NaBH (OAc) 3 (58 mg, 0.261 mmol) to give the compound (3.4 mg, 6.0%). LC / MS: m / z 499.6 (M + H), l.a .: 1.46 min. 3-p- (ethyl-8-sulfyl) -4-pip? Ridini? -5- < 3-fr (trafi-s-4- h! Dr @ xiciclo exi8) anà ino] methyl > fe ?? i8! -1H = sridol = 7 = carb © K (aerated Following the general procedure of Example 18, 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 / - / - indo [-7-carboxamide (60 mg, 0J 14 mmol), frans-4-aminocyclohexanol (10 mg, 0.087 mmol) and NaBH (OAc) 3 (68 mg, 0.261 mmol) to give the compound of the product (6.0 mg, 9.8%). LC / MS: m / z 539.2 (M + H), t.a .: 1.54 min.
EXAMPLE 21 3 1- "etiisy8ffoni.H-pi? Eridirt) ip ° § 3 piperidin58 cic8ohexipmetil > ami o) methyphenyl} ° W ° 5r8? J? ° © aírb? Xa? Js- Following the general procedure of Example 1i, 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 were reacted. / - / - indole-7-carboxamide (50 mg, 0.114 mmol), 1- [1- (1-piperidinyl) cyclohexyl] meaminamine (17 mg, 0.087 mmol) and NaBH (OAc) 3 (58 mg, 0.261 mmol) to give the title compound (18.7 mg, 27%). LC / MS: m / z 620.6 (M + H), t.a .: 1.6 min.
EXAMPLE 22 3-ri-le ilsulffonl) - -p -peridn-5-P- (irf2S] > -2- hydroxyprdpiBlamino > m? Ethyl) feni81 ° W-indQB-7- (sarb? xamidii Following the general procedure of Example 18, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (dO mg, 0.114 mmol) was reacted, ( 2S) -1-amino-2-propanol (6.5 mg, 0.087 mmol) and NaBH (OAc) 3 (58 mg, 0.261 mmol) to give the title compound (13.1 mg, 23%). LC / MS: m / z 499.6 (M + H), t.a .: 1.46 min.
EXAMPLE 23 5 3-r (etiBamapoDmet »IWenil > ° 3 1 ° Ipsypsulfonyl ° P8Peridinium 1H-carboxasin To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (20 mg, 0.046 mmol) in dichloromethane (0.5 ml) and methanol ( 0.5 ml) was added eylamine (130 μl, 0.27 mmol). The mixture was stirred for 1 h at room temperature and then sodium borohydride (10 mg, 0.27 mmol) was added. The reaction was stirred at room temperature overnight and the solvent was removed under reduced pressure. The witch production was purified by reverse phase HPLC (water / CH 3 CN, 0.1% 10-90% TFA) to give the title compound (13.2 mg, 63%). LC / MS: m / z 469.4 (M + H), t.a .: 1.54 min.
EXAMPLE 24 3-ri "(ethylsulfooyl) ^ - piperidSnip ° g-f3-f (propyl-8-methyl-pyrrolidone.) (.H- = To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (20 mg, 0.046 mmol) in dichloromethane (0.7 ml) and methanol ( 0.7 ml) was added propylamine (22 μl, 0.27 mmol) and 1 drop of acetic acid. The mixture was stirred for 1 h at ambient temperature and then sodium borohydride (10 mg, 0.27 mmol) was added. The reaction was stirred for one night at room temperature and the solvent was reduced under reduced pressure. The crude product was purified by reverse phase HPLC (water / CH 3 CN, 0.1% 10-90% TFA) to give the title compound (22.1 mg, 99%). LC / MS: m / z 483.2 (M + H), t.a .: 1.58 min.
EXAMPLE 25 3 1- (Ethylsulfonyl) piperid.nip-5- (3-fr (1-methyletti.) Amnno1meft.l> fen.l) ° W ° i? Pdo8 = 7-ca? rboxamide Following the general procedure of Example 24, 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboxamide (20 mg, 0.046 mmol), isopropylamine was reacted (23 μl, 0.27 mmol) and NaBH 4 (10 mg, 0.27 mmol) to give the title compound (11.5 mg, 53%). LC / MS: m / z 483.2 (M + H), t.a .: 1.52 min.
EXAMPLE 28 5-Í3- f (1-ethylpr? PS) ami? No1methyl > feni8) -3 1 eti8su8f © niB ° P periodirii ^ H- ñndon-T-earboxamiel-a Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (20 mg, 0.046 mmol) was reacted , 3-penlanamine (32 μl, 0.27 mmol) and NaBH 4 (10 mg, 0.27 mmol) to give the title compound (18.6 mg, 80%). LC / MS: m / z 511.4 (M + H), t.a .: 1.66 min.
EXAMPLE © 27 341 - (etilsuifonSI) -4-pipe.ridinill-g-í4- (1 ¡perid¡ni.mat.l) fep? IllTl-1l H-inri® .-? - earboxaroida Following the general procedure of Example H, 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 - / - indole-7-carboxamide (40 mg, 0.09 mmol) were reacted, piperidine (0.009 ml, 0.09 mmol) and NaBH (OAc) 3 (58 mg, 0.27 mmol) to give the title compound (8 mg, 17.5%). LC / MS: m / z 509.4 (M + H), t.a .: 1.71 min.
EXAMPLE 3-M-Ethyl-8-phenyl-1-pperidin-3-r (metham-8-ene) -methiphenyl-8H-1-yr-dl < 5) n-7- car oxamide Following the general procedure of Example 24, 3- [1- (alkylsulfonyl) -4-piperidinyl] -d- (3-formylphenyl) -1 / - / - indole-7-carboxamide (20 mg, 0.046 mmol) were reacted , meilylamine (130 μl, 0.27 mmol) and NaBH (10 mg, 0.27 mmol) to give the title compound (17.0 mg, 83%). LC / MS: m / z 466.2 (M + H), t.a .: 1.48 min.
EXAMPLE © 28 3-p-ethylBuilil ° pipergdin¡81 ° S-r4- (4 ° orfo8iniBnn®tB Following the general procedure of Example 1, 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1H-indole-7-carboxamide (50 mg, 0.114 mmol), morpholine ( 18 μl, 0.206 mmol) and NaBH (OAc) 3 (290 mg, 1.37 mmol) to give the title compound (2.1 mg, 13%). LC / MS: m / z 511.4 (M + H), t.a .: 1.63 min.
EXAMPLE 30 S 4-faminomethyl) phenyl1 ° 341- (ethylphosphine H ° P1peridinyl1 ° W ° §nd ° n °? ° earboxamide In a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (30.0 mg, 0.072 mmol), Cs2CO3 (96 mg, 0.290 mmol) and acid [4- (aminomethyl) phenylboronic acid (56 mg, 0.290 mmol) in dioxane / H20 (1.5 ml / 0.5 ml) was bubbled argon duranie d min. before the addition of Pd (PPh3) (7.6 mg, 0.0072 mmol). The reaction mixture was heated in a microwave reamer (Smiíh sym erizer) for 20 minutes at 160 ° C. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine (10 ml), dried over MgSO, filtered, concentrated and purified by reverse phase HPLC (water / CH 3 CN, 0.1% 10-90% TFA) to give the title compound. tíulo (9.8 mg, 31%). LC / MS: m / z 424.4 (M-NH2), 1.a .: 1.48 min.
EXAMPLE 31 S 3 (cBcBopropyaminamin) methyl1feniB > -3 1 ° (etilsu8ff? B-.5BM-p80®rBdinoCμW ° ° 7 < -carb? Xart? Id @ To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 / - / - indole-7-carboxamide (50 mg, 0.113 mmol) in DCM (2 ml ) was added cyclopropanamine (19.3 mg, 0.339 mmol). The reaction solution was stirred at room temperature for 30 min after the addition of HOAc (1 gola) and NaBH (OAc) 3 (75 mg, 0.546 mmol). The resulting mixture was stirred overnight at room temperature, after which time the solvent was relieved under reduced pressure. The crude product was purified by reverse phase HPLC (water / CH3CN, 0.1% 10-90% TFA) to give the title compound (18.2 mg, 34%). LC / MS: m / z 481.2 (M + H), t.a .: 1.52 min.
EXAMPLE 32 5 3-r (cycloBuyBiBiPlC >? T.etiB1fenclV341- (etiisulforiiBH-piperidDnii-7-carboxas Following the general procedure of Example 31, 3- [1- (alkylsulfonyl) -4-piperidinyl] -d- (3-formylphenyl) -1H-indole-7-carboxamide (60 mg, 0.113 mmol), cyclobutenamine were reacted (24.1 mg, 0.339 mmoi) and NaBH (OAc) 3 (76 mg, 0.646 mmol) to give the compound of the extract (19.3 mg, 35%). LC / MS: m / z 495.6 (M + H), t.a .: 1.55 min.
EXAMPLE 33 methylpropBB) arpinol-2,3 = dihydro-1W-indeft? = 5 '• Bl} -1 H-.?mdol-7-ca?rlboxa?pr.Ddla To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (4,4, d, d-lettermethyl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7 carboamide (200 mg, 0.434 mmol) in dioxane (3.0 ml) and H20 (1.0 ml) were added 6-bromo-2,3-dih: dro-1 H-inden-1-one (274 mg, 1.30 mg). mmol) and polybasic carbonate (360 mg, 2.60 mmol) in a microwave tube. The reaction mixture was degassed for 5 min. From the addition of tetrakis (triphenylphosphine) palladium (0) (50 mg, 0.043 mmol). Then, the reaction was heated in the microwave for 30 min at 160 ° C. Then, the reaction was filtered and the solid was dissolved in EOAc and H20. The organic layer was separated and concentrated. The crude residue was purified by Gilson Preparative HPLC to produce 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (3-oxo-2,3-dihydro-1 H-inden-d-yl) -1 H -indole-7-carboxamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-oxo-2,3-dihydro-1 H -inden-5-yl) -1H-indole-7-carboxamide ( 45 mg, 0.097 mmol) in EOH (2 ml) and acetic acid (200 μl) were added 2-methyl-1-propanamine (170 μl, 1.93 mmol) and sodium cyanoborohydride (20 mg, 0.291 mmol). The resulting mixture was reacted in a CEM microwave tube at 150 ° C for 40 min. Then, it was purified by Gilson Preparative HPLC to give 4.5 mg of the title compound (8.9%). LC / MS = m / z 523.4 [M + H]. Time of ret .: 1.72 EXAMPLE 34 MetBBPBBBMB8nol-§.S "8th Bdro-2 ° naftaienBiμw ° ñndQn ° 7 ° earb @? §? g r.D the To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-erylamethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole -7-carboxamide (200 mg, 0.434 mmol) in dioxane (3.0 ml) and H20 (1.0 ml) were added 7-bromo-3,4-dihydro-1 (2H) -naphthalenone (292 mg, 1.30 mmol) and Potassium carbonate (360 mg, 2.60 mmol) in a microwave tube. The reaction mixture was degassed for 5 min before the addition of iron (l-phenylphenylphosphine) palladium (0) (60 mg, 0.043 mmol). Then, the reaction was heated in the microwave for 30 min at 160 ° C. Then, the reaction was filtered and the solid was dissolved in EOAc and H20. The organic layer was separated and concentrated. The crude residue was purified by Gilson's Preparaliva HPLC to produce 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (8-oxo-5,6,7,8-lerahydro-2-naphthalenyl) -1 H-Indole-7-carboxamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (8-oxo-5,6,7,8-letrahydro-2-naphthalenyl) -1 / - / - indole-7-carboxamide (40 mg, 0.08 mmol) in EOH (2 ml) and acetic acid (0.2 ml) were added 2-methyl-1-propanamine (140 μl, 1.6 mmol) and sodium cyanoborohydride (15 mg, 0.24 mmol). The resulting mixture was reacted in a CEM microwave tube at 150 ° C for 40 min. Then, it was purified by preparative HPLC Gilson to give 3.2 mg of the title compound (7.6%). LC / MS = m / z 637.4 [M + H]. Time of ret .: 1.71 EXAMPLE 3S S - ([Sf r (2-cyano-phenyl) -annoln-methyl} -2-fluo? RofBnIli-3 1l • ([atil8u8for.iil) ^ - piperidiniil ° 1H indoBV ° (SarboxaruBial? ? To a solution of 3- [1- (erylsulfonyl) -4-piperidinyl] -d- (4,4,5,5-yl-methyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole -7-carboamide (200 mg, 0.434 mmol) in dioxane (3.0 ml) and H20 (1.0 ml) were added 3-bromo-4-fluorobenzaldehyde (264 mg, 1.30 mmol) and K2C03 (360 mg, 2.60 mmol ) in a microwave oven. The reaction mixture was degassed for 5 min after the addition of letterche (triphenylphosphine) palladium (0) (48 mg, 0.043 mmol). The reaction was heated in a microwave for 30 min at 160 ° C. The organic layer was separated and concentrated. The residue was dissolved in MeOH until a solid precipitated to yield 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2-fluoro-5-formylphenyl) -1 / - / - indole-7-carboxamide. To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- (2-fluoro-5-formylphenyl) -1 / - / - indole-7-carboxamide (40 mg, 0.087 mmol) in dichloromethane ( 2 ml) and melanol (I ml) were added 3-aminopropanonilril (53 μl, 0.524 mmol) and 1 was acetic acid. The reaction mixture was stirred at ambient temperature for 48 h. Then, sodium borohydride (20 mg, 0.524 mmol) was added and reacted for 30 minutes at ambient temperature. It was purified by Gilson Preparative HPLC to give 14.4 mg of the title compound (32.4%). LC / MS = m / z 512.2 [M + H]. Time of ret .: 1.45 EXAMPLE 36 Trifluoroacetate of 341 - (Ethylsulfonyl-p -peridinyl-5H2-ffluoro-5Hprt2.2.2- trBfBuoroethyl) amino-1-methyl> phenyl | ° 1H ° indoi ° 7 ° -. arboxam5d-a To a solution of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (2-fluoro-5-formylphenyl) -1 / - -indole-7-carboxamide (20 mg, 0.04 mmol) in dichloromethane (4 ml) and melanol (2 ml) were added 2 goats of acetic acid and 2,2,2-urea-fluoride (23 μl, 0.26 mmol). The resulting mixture was stirred overnight. All the solvent was evaporated and dissolved in dimethyl sulfoxide (1 ml).
Purified by Gilson Preparative HPLC to give 5.2 mg of the title compound (24.0%). LC / MS = m / z 541.4 [M + H]. Ret time 1.67 EXEMPL trifluoroacetat © of nlsuBfonil -pípeiridi. j - ** »'" ».soqu. oB.nii) ° 1H-ind © 8-7-sarbQxa¡pp.da To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7- carboxamide (60 mg, 0J 3 mmol) in dioxane (2 ml) and water (1 ml) were added 7-bromo-1, 2,3,4-tetrahydroisoquinoline (97 mg, 0.39 mmol) and potassium carbonate (108 mg 0.78 mmol). This mixture was degassed for 5 min before the addition of tetrakis (lypiphenophosphine) palladium (0) (15 mg, 0.013 mmol). The resulting mixture was reacted in a CEM microwave tube at 160 ° C for 30 min. The organic layers were separated and concentrated. The resulting residue was dissolved in dimethisulfoxide (1 ml) and purified by Gilson Preparative HPLC to give 3.5 mg of the title compound (5.7%).
LC / MS = m / z 467.2 [M + H]. Time of laugh. 1.48 EXAMPLE © 38 rifiu © roaeetat? of 341-.et¡BsulfoniBH ° piper.d.n¡BW3. '(í2 trBfau0roetiB) arr.Bnolmetil > feniB]) ° H ° .nde8 ° 7 ° -. airb? x ?? ¡t.gd To a solution of 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (200 mg, 0.483 mmol) in dioxane (3.0 ml) and H20 (1.0 ml) were they added (3-formylphenyl) boric acid (317 mg, 1.93 mmol) and Cs2CO3 (316 mg, 0.97 mmol) in a microwave tube. The reaction mixture was degassed for a few days after the addition of letterche (triphenylphosphine) palladium (0) (48 mg, 0.043 mmol). The reaction was heated in a microwave for 30 min at 160 ° C. The organic layer was separated and concentrated. The residue was dissolved in MeOH had a solid precipitated to produce 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3-formylphenyl) -1H-indole-7-carboxamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (3-formy! Phenyl) - 1 / - / - ndol-7-carboxamide (40 mg, 0.09 mmol) and 2,2,2-uro-fluoroethylamine (78 μl, 0.55 mmol) in dichloromethane (2 ml) and melanol (1 ml) were added 2 drops of acetic acid. Then, the mixture was stirred overnight. Then, sodium borohydride (20.8 mg, 0.55 mmol) was added and the mixture was stirred for 30 min. The resulting mixture was concentrated and dissolved in dimethisulfoxide followed by purification by Gilson Preparative HPLC to give 29.4 mg of the title compound (62.5%). LC / MS = m / z 523.2 [M + H]. Ret time 1.66 EXAMPLE (39 frifluoroacetate) of S43 (2-amin? -2-oxoeti8) (methyl) ami? 3 @ litr? EtinMe¡racn!) ° 3 1 - ([etiBsulfon¡8!) - 4 ° Piper »dinip ° 1H°indoB°7-g@rboxaBf.Bda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (44 mg, 0.1 mmol) and N 2 -methylglycinamide (76 mg, 0.6 mmol) in dichloromethane (3 ml) and methanol (1.5 ml) were added 3 drops of acetic acid. The mixture was agitated overnight. After, it was added Sodium Iodocetoxyborohydride (134 mg, 0.6 mmol) and stirred overnight. The resulting reaction was quenched with sodium bicarbonate (2 m!) And brine (2 ml). Then, the organic layer was collected and concentrated. Then, the resulting residue was purified by Gilson Preparative HPLC to give 13 mg of the title compound (25.4%). LC / MS = m / z 512.6 [M + H]. Time to laugh .. 1.20 EXAMPL © 4 © tpfluoroaeetato of 341-ethylsulfonyl-M-piperad-n-p-5-42-ffl2.2.2 ° -trifluoroethyl) amino] methyl > -1,3-thiazole ^ -il]) - 1H-ord.d? B-7-earl Qxam5 l§? To a solution of 4-bromo-1, 3-yiazole-2-carbaldehyde (192 mg, 1.0 mmol) in DCM (4.0 mL) were added acetic acid (3 goies) and 2,2,2-urea fluoride (120 μL). , 1.5 mmol). The reaction was stirred overnight. Then, sodium triacetoxyborohydride (335 mg, 1.5 mmol) was added and the reaction was stirred for 6 h. Then, it was quenched with sodium bicarbonate to produce 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4,4, d, 5-tetramethyl-1, 3,2- dioxaborolan-2-yl) -1H-indole-7-carboxamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-lelramethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole -7-carboxamide (46 mg, OJ mmol) in dioe (2 ml) and water (0.7 ml) were added N - [(4-bromo-1,3-thiazol-2-yl) methyl] -2 , 2,2-trifluoroethanamine (30 mg, 0.11 mmol) and potassium carbonate (83 mg, 0.6 mmol). The resulting mixture was degassed for 5 min after the addition of terachis (lyphenephosphine) palladium (0) (11 mg, 0.01 mmol). The mixture was reacted in a CEM microwave tube at 160 ° C for 20 min. The organic layers were separated and concentrated. The residue was purified by Gilson's Preparative HPLC to give 25 mg of the compound of the extract (47.2%). LC / MS = m / z 530.2 [M + H]. Time of laugh. 1.94 trifluoroaeetat? d® S - ([3-CBanQ-5- r (2.2a2-trifluor? etf8! lanr? 8r.? 1metli> f6 [H -ethyl-sulfonyl-4-piperidinyl-1 H-? ndoB-7 ° earboxamide To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- (4,4,5,5- tetramethyl-1,2,3-dioxaborolan-2-yl) -1 H -indole-7-carboxamide (46 mg, OJ mmol) in dioxane (2.0 ml, 0.7 ml) was added 3-bromo-d- formilbenzonitrile (68 mg, 0.3 mmol) and K2C03 (83 mg, 0.6 mmol) in a microwave tube. The reaction mixture was degassed for 5 min before the addition of telraquis (triphenylphosphine) palladium (0) (11 mg, 0.01 mmol). The reaction was heated in a microwave for 20 min at 160 ° C. Then, it was purified by Gilson's Preparative HPLC to give 5- (3-cyano-5-formylphenyl) -3- [1- (ylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide. To a solution of d- (3-cyano-d-formylphenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 - / - indole-7-carboxamide (62 mg, 0J 1 mmol) in dichloromethane ( 3 ml) and melanol (1 ml) were added 20 golas of acetic acid and 2,2,2-urea-fluoride (63 μl, 0.66 mmol). The mixture was stirred for 48 h followed by addition of sodium triacetoxyborohydride (140 mg, 0.66 mmol). Then, the mixture was stirred for 48 h. The resulting reaction was quenched with sodium bicarbonate and brine was added. The organic layer was separated and purified by Gilson Preparative HPLC to give 3.6 mg of the title compound (6.0%). LC / MS = m / z 648.2 [M + H]. Time of laugh. 1.88 EXAMPLE 42 Trifluoroahetate 34 eti8sy8foniB) Piperid6iBll ° S iimetB 1-m (i; ftg ° 4 piperidinyl) amino] methyB] f-3-tninB) -1 -? NdoB ° 7- € arbo? apr.ida To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (d-formyl-3-thienyl) -1H-indole-7-carboxamide (50 mg, 0J 1 mmol) in dimethyl sulfoxide (2 ml N, 1-dimethyl-4-piperidinamine (128.22 mg, 1.0 mmol) and 2 drops of acetic acid were added and reacted overnight. Then, sodium idioceroxyborohydride (212 mg, 1 mmol) was added and reacted overnight at room temperature. Then, it was purified by Gilson Preparative HPLC to give 8 mg of the title compound (13.0%). LC / MS = m / z 558.4 [M + H]. Time of ret .: 1.32 min EXEMPL © 43 trifluoroaeetate of S S fff2? EBaoethyl) (metinamS? N © 1metiBμ3 ie9 i íetiHsu> ffonil] | -4-pipe? Rid5nip - '. H-5ndo.-7 ° carboxanrDBd§ The title compound was prepared according to the general procedure for irifluoroacelaio of 3- [1- (allylsulfonyl) -4-piperidini [] - 5- (5- ({[[meily (1-methyl-4-piperidinyl) amino] ] -3-ynyl) -1 / - -indole-7-carboxamide, substituting N, 1-dimethyl-4-piperidinamine for 3- (meitylamino) propanoniyryl (84.12 mg, 1.0 mmol) to yield 24 mg of the compound of the item (42.5%). LC / MS = m / z 514.4 [M + H]. Time of laugh .: 1.56 min EXAMPLE 44 S- (S-ir (2-amino-2-oxoetype (methyl) aminol? Go ill> -3-tt3®? P: 341 - (ethyl-unsol. piperidinii1 ° 1 H-máoti-7- <swbox®m & amp; The title compound was prepared according to the general procedure for trifluoroacety of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- {[meityl (1-meityl-4-p-peridinyl) amino] methyl] .3. -3-lienyl) -1 / - / - indole-7-carboxamide, suspending NJ-dimethyl-4-piperidineamine by N2-methylyglycinamide (88.11 mg, 1.0 mmol) to yield 19 mg of the compound of the title (33.3%). LC / MS = m / z 518.2 [M + H]. Retreat time: 1.43 min EXAMPLE 45 trifluoroacetate of 341 ° (etiBsulfonil) -4 ° Pipe? Rdio? P ° §4§ í? Pp? Et5BÍ2 ° (phenylsulfooyl) etillant? Ir.o} methyl) ° 3 ie [piB | ° 1M4ndoB ° 7 ° cairboxa? pr.ida The title compound was prepared according to the general procedure for 3- [1- (ethylsulfonyl) -4-pperidinyl] -d- (5- {[melyl (1-methyl-4-trifluoroacetyl]] piperidinyl) amino] -methyl] -3-lienyl) -1H-indole-7-carboxamide, suspending? / J-dimethyl-4-piperidinamines by N -methyl-2- (phenylsulfonyl) eanamine (199.27 mg, 1.0 mmol) to produce 30 mg of the compound of the product (47.3%). LC / MS = m / z 629.4 [M + H]. Time of laugh .: 1.57 min EXAMPLE 46 341 ° (e ^ SsulfonB]) ° 4 ° pBperidini8 | ° 5 °. { 5 ° f (2 eniB ° 1 ° pirroB5d8rBB • 3 5®? Pg [.}. ° To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 / -and-indole-7-carboxamide (60 mg, 0.11 mmol) in DMSO (2.0 ml) was added 2-phenylpyrrolidine (147 mg, 1.0 mmol). Then, the reaction mixture was reacted in a microwave at 120 ° C for 10 min. Then, sodium iryacetoxyborohydride (220 mg, 1.0 mmol) was added and the reaction was reacted at ambient temperature for one night. Then, it was purified by Gilson Preparative HPLC to give 14.0 mg of the title compound (22%). LC / MS = m / z 677.2 [M + H]. Retreat time: 1.65 min.
EXAMPLE 47 341 Hethylsulfonyl-piperiidinin-S- (5-ir2 - ('il -piperldin? Lmotyl) -'. • pyrrolidinipmetiB-34ieni8i-'i] H -? Ndol ° 7 ° earb © xa8n5 la The title compound was prepared according to the general procedure for 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { d - [(2-phenyl-1-pyrrolidinyl) methyl] -3-thienyl} -1 / -. -indole-7 -carboxamide, suspending 2-phenylpyrrolidine for 1- (2-pyrrolidinylmethyl) piperidine (168.3 mg, 1.0 mmo!) To yield 21 mg of the title compound (32%). LC / MS = m / z 598.4 [M + H]. Time of ret .: 1.34 EXAMPL © 48 454f (2ffl ° 2- (amsnoearbopi8]) ° 1-pyrroiidini8] metBBμ34ae [f ([@ tilsy8for? I8 | - ° piperpdinin ° 1H4ndoB ° 7 ° @ arb @ xarraD ( The title compound was prepared according to the general procedure for 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 5 - [(2-phenyl-1-pyrrolidinyl) methyl] -3-thienyl} -1H-indole-7-carboxamide, substituting 2-phenylpyrrolidine for D-prolinamide (114 mg, 1.0 mmol) to yield 14 mg of the title compound (23%). LC / MS = m / z 644.2 [M + H]. Time of ret .: 1.39 EXAMPLE 4 (4954) 3 -3-dimethylamine) -1-pyrrolidinylmethyl} -34B®rii íulltf®. 4-piperidinyl-1W-indoB-7-carboxanfiiidé Quiral The title compound was prepared according to the general procedure for 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { 5 - [(2-phenyl-1-pyrrolidinyl) methyl] -3-thienyl} -1H-indole-7-carboxamide, substituting 2-phenylpyrrolidine for (2f.) -? /, N-dimethyl-2-pyrrolidinamine (114 mg, 1.0 mmol) to yield 11 mg of the title compound (18%). LC / MS = m / z 644.2 [M + H]. Time of ret .: 1.36 EXAMPLE 50 Toifluoroacetate of 541 2444 dimethylamin.o) ° 1 ° p5pe? Rñdi?,. SBletol} ° 1l! Hl ° p ?? razg 4 ° iB) -3414et ° isu ^ oniQ ° 4-P ° Per'din581 ° 18-. ° iriido8 ° 7 ° carbo? A? Pr.5da To a solution of 3- [1- (ethylsulfonyl) -4-capperdinyl] -5- (4,4,5,5-teremethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole-7-carboxamide (40 mg, 0.090 mmol) in dioxane (750 μl) and H20 (250 μl) were added with sodium carbonate (53 mg, O.dO mmol) and 4-bromo-1- (2 -chloroetyl) -1 / - / - pyrazole (26 mg, 0.126 mmol). The reaction mixture was flushed in an Argon atmosphere for 10 min before the addition of iron (phenylphosphine) palladium (0) (5 mg, 0.004 mmol). The reaction was heated in a microwave at 120 ° C for 20 min. Then, it was diluted with ElOAc (10 ml) and filtered through celite, followed by an aqueous treatment. The compound was purified by Gilson Preparative HPLC to give 10 mg of 5- [1- (2-chloro-eyl) -1 H -pyrazol-4-yl] -3- [1- (allylsulfonyl) -4-picperidinyl] -1 H -indole-7-carboxamide (24%). To a solution of 5- [1- (2-chloroethyl) -1 H -pyrazol-4-yl] -3- [1- (allylsulfonyl) -4-picperidinyl] -1 / - / - indole-7-carboxamide ( 33 mg, 0.071 mmol) in α-hydrofuran (500 μl) were added A /, N-dimethyI-4-piperidinamine (100 μL, 0.71 mmol) and Sodium iodide (5 mg, 0.018 mmol). The resulting mixture was reacted in a microwave oven at 130 ° C for 2 hours. An aqueous wash was performed with EtOAc and water, the organic layers were isolated and all the solvent was removed. Then, it was purified by Gilson Preparative HPLC to give 7.0 mg of the title compound (14.7%). LC / MS = m / z 556 [M + H]. Retreat time: 1.23 min.
JE §434 (dimeti8anr.ino pnetii1-4.S-bisírnetiioxi) f? dl P8peridini81 ° 1H-indoB ° 7 ° carb @ xarBi? ida To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-telramethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / -indole-7-carboamide (600 mg, 1.09 mmol) in dioxane (9.0 ml) and H20 (3.0 ml) were added sodium carbonate (690 mg, 6.61 mmol) and 5-bromo-2,3-bis ( methyloxy) benzaldehyde (7.95 mg, 3.25 mmol). The reaction mixture was flushed abundantly in an Argon atmosphere for 10 min before the addition of terachis (pyridylphosphine) palladium (0) (63 mg, 0.064 mmol). Then, the reaction was heated in a microwave at 120 ° C for 30 min. Then, the solvent was concentrated and an aqueous wash was carried out with ElOAc and H20. Then, the desired compound was precipitated and filtered to give 322 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-formyl-4,5-bis (methyloxy) phenyl] -1H-indole 7-carboxamide (69%). To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-formyl-4, d-bis (methyloxy) phenyl] -1 / - / - indole-7-carboxamide (30 mg, 0.06 mmol) in methanol (2 ml), zinc chloride (5 mg, 0.03 mmol), sodium cyanoborohydride (d mg, 0.06 mmol) and dimethylamine (100 μl, 0.30 mmol) were added. The mixture was stirred at room temperature for 2 h and then reacted in the microwave at 100 ° C for 30 min. The resulting mixture was purified by Gilson Preparative HPLC to give 11 mg of the title compound (34.7%). LC / MS = m / z 529 [M + H]. Retreat time: 1.67 min.
EXAMPLE © 32,44-bis (methyBox? -§44-mo? O 8 ethyl ethyl) fe8i.B1 ° 34 4et.8g PBpec°Bdir.Bp°1H-§ndoB°7°earb@xa8iriiida The title compound was prepared according to the general procedure of d- [3 - [(dimethylamino) methyl] -4, d-bis (methyloxy) phenyl] -3- [1- (eylsulfonyl) -4-piperidinyl ] -1 H-indole-7-carboxamide, substituting dimetuamine for morpholine (20 μl, 0.30 mmol) to yield 8.0 mg of the compound of the íílulo (23.4%). LC / MS = m / z 571 [M + H]. Retreat time: 1.59 min.
EXAMPLC 3414-ethyl-sulphonyl) -4-p8peridium-1-S434r1-methyBetiB!) Arid? mefiBMa bi8Ímeti8oxB) fenil1-1H-.ndoB-7-earb@xam¡dci The title compound was prepared according to the general procedure of d- [3 - [(dimethylamino) methyl] -4, d-bis (methyloxy) pheny] -3- [1- (ethylsulfonyl) -4-piperidinyl ] -1 H-indole-7-carboxamide, substituting dimethylamine for 2-propanamine (20 μl, 0.30 mmol) to yield 15 mg of the title compound (46.1%). LC / MS = m / z 543 [M + H]. Retreat time: 1.59 min.
EXAMPL © 3- s) is | [ifnetyloxy) phenyl - '. H-indo8 ° 7 ° carboxamid? The title compound was prepared according to the general procedure of 5- [3 - [(dimethylamino) methyl] -4, d-bis (methyloxy) phenyl!] - 3- [1- (ethylsulfonyl) -4-piperidinyl ] -1 H-Indole-7-carboxamide, substituting dimethylamine for 40% by weight meyilamine (60 μl, 0.30 mmol) to yield 6 mg of the iodine compound (19.4%). LC / MS = m / z 515 [M + H]. Time of laugh .: 1.46 min.
EXAMPLC 434 R2"2-d8rt.etiiprPPBB aminolmetgi) - ai-bis etB¡oxilf®oiB¡1 ° Iethylsulfon§l) -4-piper5dinip-1H-indole ° 7 ° cairb? Xa? ]to The title compound was prepared according to the general procedure of d- [3 - [(dimethylamino) methyl] -4, d-bis (methyloxy) pheny]] - 3- [1- (ethylsulfonyl) -4-piperidinyl ] -1H-indole-7-carboxamide, substituting dimethylamino for (2,2-dimethylpropyl) amine (20 μl, 0.30 mmol) to yield 10 mg of the compound of the extract (29.2%). LC / MS = m / z 571 [M + H]. Time of laugh .: 1.76 min.
EXEMPL © SS 3414etilsulf @ nBBM-pipergdinill-S43 rí2-ll? Drox¡eti8) ímeti8 amaBio1metñB. fois (meti.oxi) fen.l1-1H4ndoB-7 ^ arboxam8da The title compound was prepared according to the general procedure of d- [3 - [(dimethylamino) methyl] -4, d-bis (methyloxy) phenyl] -3- [1- (eylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide, substituting dimethylamine for 2- (meitylamino) elanol (20 μl, 0.30 mmol) to yield 10 mg of the title compound (29.8%). LC / MS = m / z 659 [M + H]. Retreat time: 1.54 min.
EXAMPLE §43,4-bis (n-nyloxyl ° i41-Ptrro88din8methyl in LBTl ° 34 etB88y¡f? P§8]) V ° p5perBdinil1"1H4ndoB" 7 ° earboxa? T.Sda The title compound was prepared according to the general procedure of 5- [3 - [(dimethylamino) methyl] -4, d-bis (methyl]!) Phenyl] -3- [1- (ethylsulfonyl) -4 -piperidinyl] -1H-indole-7-carboxamide, substituting dimethylamine for pyrrolidine (50 μl, 0.30 mmol) to yield 13 mg of the compound of the lipoid (39.1%). LC / MS = m / z 566 [M + H]. Time of laugh .: 1.61 min.
EXAMPLE 58444 (dimethylamino ^ metiB1 ° 2.3-d8hydro-1-benzofurari ° S4Bμ 4 ° p8per8dinii1 ° 1H-indo8-7 ° carboxar¡r.§ To a solution of d-bromo-3- [1- (ethylsulfonyl) -4-piperidine: l] -1 / -. Indole-7-carboxamide (113 mg, 0.274 mmol) in dioxane (9.0 ml) and H20 ( 3.0 ml) was added sodium carbonate (174 mg, 1.64 mmol) and 6- (4,4,5, d-terylammell-1, 3,2-dioxaborolan-2-yl) -2,3-dihydro-1- benzofuran-4-carbaldehyde (150 mg, 0.647 mmol). The reaction mixture was flushed in an Argon atmosphere for 10 min. After addition of leirac (triphenylphosphine) palladium (0) (16 mg, 0.014 mmol). The reaction was heated in a microwave at 120 ° C for 30 min. Then, the solvent was concentrated and purified by flash chromatography using DCM and MeOH to give 120 mg of 3- [1- (ethylsulfonyl) -4-pperidinyl] -d- (4-formyl-2,3-d. Hydro-1-benzofuran-6-yl) -1 / - / - indole-7-carboxamide (91%). To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formi [-2,3-dihydro-1-benzofuran-6-N) -1H-indole-7-carbo-amide (20 mg, 0.042 mmoi) in Melanol (2 ml) was added dimellylamine (3 μl, 0.050 mmol), zinc chloride (3 mg, 0.021 mmol) and sodium cyanoborohydride (4 mg, 0.062 mmol). This mixture was reacted in the microwave at 100 ° C for 1 h and then all the solvent was removed. The residue was washed with EtOAc and water. All the solvent was removed and purified by Gilson Preparative HPLC to give 6.0 mg of the title compound (19.6%). LC / MS = m / z 525 [M + H]. Retreat time: 1.56 min.
EXAMPLE 58 3414-ethylsulfon II) - -piperidini81-5- (44r (1-methyl-ethyl-Biary? Lno-1-y) to B 2, 2- 1 -benzofuran-6-yl]) - 1 H -i? P? D © -7-carb © xamidg? The title compound was prepared according to the general procedure of 5-. { 4 - [(dimethylamino) methyl] -2,3-dihydro-1-benzofuran-6-yl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, suspending the dimethylamine by 2-propanamine (3 mg, 0.050 mmol) to yield 9.0 mg of the compound of the íílulo (28.6%).
LC / MS = m / z 511 [M + H]. Retreat time: 1.58 min.
EXEMPL © ßC 414etiBsuif? NB8]) ^ pgperidini81-54444-rr? Orfol¡n§8rinet8Bμ2 ° dihgdro- i-C The title compound was prepared according to the general procedure of 5-. { 4 - [(dimethylamino) meily] -2,3-dihydro-1-benzofuran-6-yl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, suspending dimethylamine by 2,2-dimethyl-1-propanamine (4 mg, 0.050 mmol) to produce 8. 0 mg of the compound of the product (24.1%). LC / MS = m / z 664 [M + H]. Time of laugh: 1.71 min.
EXAMPLE 3 1 ^ ethylsulfonyl) ^ pipeoidin ~ p ^ -r54fp-methyl-2 ^ methylox8) et8IT] aminoto® < anti-? iBl-1 W-indole-7-earboxast.i lg? [5- ( { [1-Methyl-2- (methyloxy) ethyl] amino} methyl) -2-lienyl] boronic acid (60 mg, 0.262 mmol) was transferred to a CEM microwave lubricant with mei nol. The methanol was evaporated in an atmosphere of N2. To this was added 5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (80 mg, 0.19 mmol), potassium carbonate (160 mg, 1.16 mmol) , teirakis (triphenylphosphine) palladium (0) (5 mg, 0.004 mmol), dioxane (1.5 ml) and water (0.5 ml). The vial was capped and reacted in a CEM microwave at 150 ° C for 30 min. This solution was loaded onto a 2 g SCX SPE cartridge primed with 3 ml of methanol. Then, the cartridge was sequentially eluted with water (3 ml), methanol (9 ml) and 2 M NH 3 in MeOH (6 ml). The NH3 fractions in MeOH were dried under an N2 atmosphere at 40 ° C. The crude product was taken up in dimethyl sulfoxide (1 ml) and purified on an Agilent MDAP with UV detection (230 nm) and MS. The desired fractions are they were passed through two sequential Pharmasil CHQAX 500 mg cartridges primed with 1 ml of melanol and 1 ml of water. The solvents were evaporated in an N2 atmosphere at 60 ° C to give 34.7 mg of the title compound (34%). LC / MS = m / z 430 [M + H]. Retreat time: 1.32 min.
EXAMPLE 82 545 f (2-cñanoeti8) anriir. @ Lmet8iμ3 °? IridBni¡) -3414etiBsu 1 H-iifido8-7-caB'boxamide To 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 / - / - indol-7-carboxamide (30 mg, 0.072 mmol) was added 3- ( { [5- (4 , 4,5,5-letter-methyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] -methyl.} Amino) propane-trichloride (24.8 mg, 0.086 mmol). To this mixture was added dioxane (0.75 ml) followed by a solution of potassium carbonate (60 mg, 0.434 mmol) in water (0.25 ml) and SK-CC02-A (4.4 mg, 0.007 mmol). The vials were lapaned and reacted in a CEM microwave at 150 ° C for 30 minutes. The reaction was loaded onto a 2 g SCX SPE cartridge primed with 3 ml of methanol. Afterwards, the cartridge was eluted sequentially with water (3 ml), melanol (9 ml) and 2 M NH3 in MeOH (6 ml). The NH3 fractions in MeOH were dried under an N2 atmosphere at 40 ° C. The crude product was purified on the Agilent MDAP with UV detection (230 nm) and MS. The desired fractions were passed through a 5 g CHQAX cartridge primed with 4 ml of methanol and 4 ml of water. The solvents were evaporated under an N2 atmosphere at 65 ° C to give 6.2 mg of the title compound (17.4%). LC / MS = m / z 495 [M + H]. Retreat time: 1.29 min.
EXEMPL © S3 3414eti8su8fon¡IM ° Píperídinil1-54S4r ([2,2,24pflyoroe < t¡B) amg [no1 ???? PBrid5nBB) -1H-indo8-7-earboxaot.ida The title compound was prepared according to the general procedure of 5- (5- { [(2-Cyanoethyl) amino] methyl.} - 3-pyridinyl) -3- [1- (ethylsulfonyl) -4- piperidinyl] -1 / - / - indole-7-carboxamide, suspending 3- ( { [5- (4,4, d, 5-tetramethyl-1, 3,2-d¡oxaborolan-2-yl) - 3-pyridinyl] methyl.} Amino) propanoniyryl by 2,2,2 Crifluoro-N-. { [d- (4,4, d, d-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] methyl} elanamine (24.3 mg, 0.077 mmol) to yield 8.3 mg of the title compound (22.0%). LC / MS = m / z 524 [M + H]. Retreat time: 1.55 min.
EXAMPLE © 84 S 34 (dimetiBan.ino ^ mietipfeniB> 3414eti8sulfoni8) -4°pap@r? Dio-.5B To a solution of 3- [1- (ethylsulphonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (46 mg, EIGHT mmol) in DMSO (2 ml) was added dimethylamine. 2 M in THF (600 μl, 1.0 mmol). The reaction mixture was stirred at room temperature for d h before the addition of sodium triacedoxyborohydride (220 mg, 1.04 mmol). Then, the reaction was stirred overnight. The compound was purified by Gilson Preparative HPLC to give 9.0 mg of the title compound (19.2%). LC / MS = m / z 469 [M + H]. Retreat time: 1.55 min EXAMPLE © SS ftrifluoroahetate of 54§ retB8 (methyl.am.no1metiB.}. 34i®rpB8]) ° 34t inii To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (d-formyl-3-ynyl) -1 / - / - indole-7-carboxamide (50 mg, 0.11 mmol) in dimethyl sulfoxide ( 2 ml) was added N-methylethanamine (59.1 mg, 1.0 mmol) and 2 drops of acetic acid and reacted overnight. Then, sodium triacetoxyborohydride (212 mg, 1 mmol) was added and reacted overnight at room temperature. Then, it was purified by Gilson Preparative HPLC to give 20.0 mg of the title compound (33.2%). LC / MS = m / z 489 [M + H]. Time of ret .: 1.50 min EXAMPLE 86 5- (5-Crr2- (d-ethylamino) -βtin (nr? Et ') amnol? PrBethyl -3-341- (ethylsulfonBBl-4-piperidiniBl- H ° 8ndo8"7 ° © arbexapr! Trifluoroacetate. Bd§? The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5-. {[[Ethyl (methyl) amino] methyl] -3-ynyl) -3- [1- (ethylsulfonyl) -4] -piperidinyl] -1H-indole-7-carboxamide, substituting N,? / -diethyl-N-methyl-1,2-ethanediamine | 130 mg, 1.0 mmol) to yield 30.0 mg of the title compound ( 44.6%). LC / MS = m / z 560 [M + H]. Retreat time: 1.41 min.
EXAMPLE 4 § trifluoroahetate of 454fbuti8 (met8l) anri8n @ 1metgB} ° 34Deo o8 34 '(íetiisulfon8l) ° 4 ° Píper? Dipi8l ° 1W4ndoB ° 7 ° earí 0xaBtri¡da The title compound was prepared according to the general procedure of d- (5-. {[[Ethyl (methyl) amino] methyl] -3-thienyl) -3- [1- (ethylsulfonyl) -4 trifluoroacetate. -piperidinyl] -1 / - / - indole-7-carboxamide, substituting N-meliletanamine for buyl (methyl) amine (87 mg, 1.0 mmol) to yield 10 mg of the title compound (16.8%). LC / MS = m / z 617 [M + H]. Time of laugh .: 1.61 min.
EXAMPLE 68 rifjuoroacetat? of 3414 ethyl SulfonB) -4-pBperidinium (rmetiB (prop88) amBpo1met8l) -348er.i »l ° 1H4nd © B ° 7- (Ea The title compound was prepared according to the general procedure of 5- (d-. {[[(Methyl (amino) amino] -methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-trifluoroacetyl. -piperidinyl] -1 / - / - indole-7-carboamide, substituting N-methylenyamine for methyl (propyl) amine (73 mg, 1.0 mmol) to yield 20.0 mg of the compound of the lipoid (32.4%). LC / MS = m / z 503 [M + H]. Time of laugh: 1.54 min.
EXAMPLES © 8. trifluoroacetate 5- (S tl [2- (d¡mßtilam¡no) ßtill (methyl) am¡r.olm til ° @ ° tieniB?.) ° 3414et8lsu8f N88 |? -4-piperidinil1-1 -8rid © 8 ° 7- £ arboxamid? A The title compound was prepared according to the general procedure of trifluoroacetyl of 5- (6- ({[[eyl (meily) amino] me! I). -3-ynyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, N-melileíanamina susíiíuyendo by [2- (dimeíilamino) EIIL] methylamine (102 mg, 1.0 mmol) to yield 26.0 mg of the title (40.3%) compound. LC / MS = m / z 532 [M + H]. Retreat time: 1.48 min.
EXAMPLES © rifluoroacetato of 54§-IE [34diineti8am8no) prop¡¡Mrriet6itorfiiñriio1ryBetó [l} 3- ° t8enil) ° 3414etBlsulforiBB]) - 4-Piperid¡n88l ° 1M-BBidoB ° 7th CARBOXYLIC t? §gives The title compound was prepared according to the general procedure of d- (d-. {[[Ethyl (methyl) amino] methyl] -3-lienyl) -3- [1- (ethylsulfonyl) -4 trifluoroacetate. piperidinyl] -1 H-indole-7-carboxamide, N-melileíanamina by susíiíuyendo [3- (dimeíilamino) propyl] meíilamina (116 mg, 1.0 mmol) to yield 21.0 mg of the title compueslo (31.8%). LC / MS = m / z 546 [M + H]. Retreat time: 1.49 min.
EXAMPLES © trifluoroacetate 54§4.eiel@p ntil (methyl) aroBro1m @ ^ 34g t¡a NIBD Vfl-3 - (®til8ulfonil -piperidinill-1H-Indoi ° 7 ° cag, boxam5da The title compound was prepared according to the general procedure of trifluoroacetate of 5- (d-. {[[Ethyl (methyl) amino] -methyl] -3-thienyl) -3- [1- (ethylsulfonyl) -4 -piperidinyl] -1 / - / - indole-7-carboxamide, substituting N-methylethanamine for cyclopentyl (methyl) amine (99 mg, 1.0 mmol) to yield 5.0 mg of the title compound (7.78%). LC / MS = m / z 529 [M + H]. Retreat time: 1.65 min.
EXAMPLES © 72 trófluoroacetato of 341- (eti8su8fon§B) -4 ° p¡p® ridír.¡B1 ° G4i ° (rmetil (pentyl) aminolmet58 >? -34ienB -1H-ind @ 8-7- € arb © xa ? tiiid].
The title compound was prepared according to the general procedure of trifluoroacetamide of 5- (5-. {[[Ethyl (methyl) amino] methyl] -3-yl) -3- [1- ( elylsulfonyl) -4-p-peridinyl] -1H-indole-7-carboamide, substituting N-methylethanamine for methyl (pentyl) amine (101 mg, 1.0 mmol) to yield 19.0 mg of the title compound (29.5%). LC / MS = m / z 531 [M + H]. Retreat time: 161 min.
EJEMPLC trifluoroacetate 341 et.lsulfoniiH-piperidiniB1l-§ § met8¡propil? Amino? Methyl} ° 34ieni8HW ° indole ° 7 ° carbQ The title compound was prepared according to the general procedure of trifluoroacetate of 5- (d-. {[[Elly (methyl) amino] -methyl] -3-thienyl) -3- [1- (ethylsulfonyl) -4 -piperidinyl] -1 / -and-indole-7-carboxamide, substituting N-methyleneamine for methyl (2-methylpropyl) amine (87 mg, 1.0 mmol) to yield 3.0 mg of the title compound (4.8%). LC / MS = m / z 617 [M + H]. Retreat time: 1.61 min.
EXAMPLE 34-4-ethyl-sulphon-8-triluoroacetate) -4 ° piperidin-B-1 (methylmethyl-8-methyl-1> amir-methyl-34iNi-8iWpd <n ° 7 ° carl The title compound was prepared according to the general procedure of Irifluoroacelalo of d- -3- [1 (-3-d- íienil. {[Elil (meíil) amino] meíil..}.) - (eíilsulfonil) -4 -piperidinyl] -1H-indole-7-carboamide, substituting N-methylethylamine for methyl (phenylmethyl) amine (121 mg, 1.0 mmol) to yield 15 mg of the title compound (22.6%). LC / MS = m / z 551 [M + H]. Retreat time: 1.67 min.
EXAMPLE trifluoroacetate d © 3- [1- (ethylsulfoni8) - -piperdibi? IBl ° 54 h8drox8etiMmeti8! | ABtpi8po3meti8 -34ien¡8 ^ 1W4g? Doi ° 7 ° earb © xanr.Bda The title compound was prepared according to the general procedure of d- (d-. {[[Ethyl (methyl) amino] methyl] -3-ynyl) -3- [1- (ethylsulfonyl) -4-trifluoroacetyl. -piperidinyl] -1H-indole-7-carboamide, suspending N-meliletanamine by 2- (melilamino) elanol (76 mg, 1.0 mmol) to yield 27.0 mg of the title compound (43.6%). LC / MS = m / z 506 [M + H]. Retreat time: 1.46 min.
EXAMPLE © trifluoroacetate of 341-.ethyl8u8foni8 -P8peridBnñB1-g4§ ° piridini8) etillami? R. @ > metiB) ° 34ieni8] ° W4ndoi - 7 ° carbopamBd? The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5. {[[Ethyl (meth) amino] -methyl] -3-ynyl) -3- [1- (erylsulfonyl) -4 -piperidinyl] -1H-indole-7-carboxamide, suspending N-methylethylamine per meity [2- (2-pyridinyl) ethyl] amine (75 mg, 1.0 mmol) to yield 5.0 mg of the title compound (7.36%). LC / MS = m / z 566 [M + H]. Retreat time: 1.59 min.
EXAMPLE 77 nlB1 = 5 § fyranil eti8Mmetil) a ?? t 8no3metil -34ier? Il ^ 1. 4rid? I-7 ° € arbexarnB (-íl- ?? The title compound was prepared according to the general procedure of 5- (5. {[[Ethyl (methyle) amino] -methyl] -3-yl] -3- [1- (allylsulfonyl) trifluoroacetate. -4-piperidinyl] -1 / - / - indole-7-carboxamide, suspending N-methyleneamine by 1- (2-furanyl) -? / - meitylmethanamine (111 mg, 1.0 mmol) to yield 19.0 mg of the compound of the compound ( 29.0%). LC / MS = m / z 541 [M + H]. Time of laugh: 1.59 min.
Trifluoroacetate of 34-4-sulfonyl8]) - -piperSdÍB, iSp ° §4S- pyridinylmethy8) amBBio1nnet¡B-34ienyl) ° 1H ° ÍBidQ8 ° 7 ° < £ arboxa? T.idg? The title compound was prepared according to the general procedure of trifluoroacelate of 5- (5. {[[Elyl (melyl) amino] methyl] -3-amino) -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 / - -indol-7-carboamide, suspending N-methylenatamine by methyl (4-pyridinylmethyl) amine (122 mg, 1.0 mmol) to yield 31.0 mg of the composed of the title (46.6%). LC / MS = m / z 552 [M + H]. Time of laugh .: 1.37 min.
EXAMPLE: Trifluoroacetate of 34-ethylsulfonyl-Pyridinium-5-S4 ([6-methylethyl) -3-pyrroBid-8-methyl-amino) methyl-4-H4rBdo8 ° 7 ° arb8s} 07.i (- 1§ The title compound was prepared according to the general 5- (5. {[[Eyl (methyle) amino] methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-trifluoroacetyl process. -piperidinyl] -1 / - / - indole-7-carboxamide, suspending N-methylenediamine per methyl. { [1- (1-Methyleryl) -3-pyrrolidinyl] meityl} amine (156 mg, 1.0 mmol) to yield 21.0 mg of the compound of the extract (30.0%). LC / MS = m / z 586 [M + H]. Time of laugh .: 1.43 min.
EXAMPLE 8 (34H-.ethylsulfonyl trifluoroacetate) -4-pipe? RtdS thieniimethyl) aminolmethyl ^ -34ien8MlH4ndofl-7 ° @ a? Rb @ xa? Praide The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5-. {[[Ethyl (me) yl) amino] -meiyl] -3-ynyl) -3- [1- (allylsulfonyl) -4 -piperidinyl] -1 / - / - indole-7-carboxamide, suspending N-melilelanamine per meityl (2-ynylmethyl) amine (127 mg, 1.0 mmol) to yield 26.0 mg of the title compound (38.8%). LC / MS = m / z 557 [M + H]. Retreat time: 1.72 min.
EXAMPLE 81 81 ethyl 3uBfl32l-4 pgperidgnaBl-S454 ^ phenylethyl) ethylammonium trifluoroacetate of 34 ethyl ether 1u-indone 7 ° © arboxap 8da The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5. {[[Ethyl (methyle) amino] methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, suspending methyl [1- (2-lienyl) -yryl] amine N-methylethanamine (141 mg, 1.0 mmol) to yield 6.0 mg of the compound of the icle (8.76% ). LC / MS = m / z 571 [M + H]. Time of laugh .: 1.78 min.
EXAMPL © 82 trifluoroacetate of 34 etg8su8foniBM-PiperidBipg »1 ° 454 ry? ®tgB (3 thienymethyl) amino] metH] h34ien? 1HM4ndoB ° 7 ^ arboxamide The title compound was prepared according to the general procedure of 5- (5. {[[Ethyl (methyl) amino] methyl] -3-thienyl) -3- [1- (ethylsulfonyl) -4 trifluoroacetate. -piperidinyl] -1H-indole-7-carboxamide, substituting N-methylethanamine for methyl (3-ynylmethyl) amine (127 mg, 1.0 mmol) to yield 7.0 mg of the compound of the same (10.4%). LC / MS = m / z 557 [M + H]. Time of laugh .: 1.78 min.
EXAMPLE Trifluoroacetate of 341 et? Isu? Fonilí- < -piperidir.ii1-5 S rm®tiiítetraBt_] 7® = 2H-pyran-44¡meti8]) aminolmetBl} -34yenii.-1H- indoB = 7 = earboxaranida The title compound was prepared according to the general procedure of 5- (d-. {[[Ethyl (methyl) amino] -methyl] -3-ynyl) -3- [1- (ethylsulfonyl) -4-trifluoroacetate. -pperidinyl] -1 / - / - indole-7-carboamide, suspending N -methyleniaamine by methyl (leihydro-2 / - / - pyran-4-ylmethylamino) amine (129 mg, 1.0 mmol) to yield 11.0 mg of the compound of the product (16.4%). LC / MS = m / z 559 [M + H]. Time of laugh .: 1.63 min.
EXAMPLE 4 84 trifluoroacetic acid of 34 et) isu8fon88) -4-piper8dirag81-§45 ili3-pyridinylmethyl) amino] methyl > -34ienall ° 1i -inde) B ° 7 ° (£ arbe)? Amid The title compound was prepared according to the general procedure of 5- (5-. {[[Ethyl (methyl) amino] methyl] methyl] -3-ynyl) -3- [1- (allylsulfonyl) trifluoroacetate. -4-piperidinyl] -1 / - / - indole-7-carboamide, suspending N-methylenatamine by methyl (3-pyridinylmethyl) amine (122 mg, 1.0 mmol) to yield 9.5 mg of the title compound (14.3%) . LC / MS = m / z 552 [M + H]. Retreat time: 1.56 min. rifluoroaeetato d 341 etalsylfoniB) ^ -piperidiiigi §4g ífmet¡B ^ pirimidinilmeti8) amino1meti8} -34¡enJ8 ° 1H4r.d©fl°7°carb@xaiit?gd?i The title compound was prepared according to the general procedure of 5- (5. {[[Ethyl (methyl) amino] methyl] methyl] -3-ynyl) -3- [1- (eylsulfonyl) trifluoroacetate. -4-piperidinyl] -1 / - / - indole-7-carboamide, suspending N-methyleneamine per me (4-pyrimidinylmethyl) amine (123 mg, 1.0 mmol) to yield 4.0 mg of the title compound (6.0%) . LC / MS = m / z 665 [M + H]. Retreat time: 1.65 min.
EXAMPLE © 88 ethylene sulfonyl) -4-p8peridg8 ° §45 ° WmetiB [f-ímeti8o? G! Letil1am? S? O > rr? et8) -34ienil1 ° 1Wndo¡ ° 7 ° earboxarrii? d§? To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-phenyl) -1 / - / - indole-7-carboamide (884 mg, 1.98 mmol) in dimethyl sulphide (5 ml) was added methyl [2- (methyl? i) elly] amine (1.86 g, 21 mmol) and HOAc (2 ml, 36 mmol). The reaction was stirred overnight at ambient temperature and sodium iaoxyloxyborohydride (212 mg, 1 mmol) was added. Stirring was continued for 1 h and CHCl3 (50 mL) was added. The mixture was filtered, CHCl3 was concentrated under reduced pressure and the crude / dmso production solution was purified by Gilson Preparative HPLC to give the title compound (590 mg, 47%). LC / MS = m / z 519 [M + H]. Time of laugh: 1.50 min.
EXAMPLE © trifluoroacetat © d® 5H, 34 (dimethylamine) methyllpH ^ 3 1- (efti: piperidinyl-1H-indole-7-carboxamide To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 - / - indole-7-carboxamide (45 mg, 0.1 mmol) in DMSO (2 mL) was added 2 M methylamine in THF (500 μL, 1.0 mmol) and stirred at ambient temperature for 5 h. Then, sodium iaoxyloxyborohydride (220 mg, 1.0 mmol) was added to the mixture and it was stirred for one night. Then, it was purified by Gilson Preparative HPLC to give 9.0 mg of the title compound (15.4%). LC / MS = m / z 469 [M + H]. Retreat time: 1.56 min.
EXAMPLE 4 88 trifluoroacetate of 34 4et.lsulfoniB -Piperidipi81-545 mymethylethylmethylmethylbenzenethylbenzoate 7 ° earboxa ™ To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-ynyl) -1 / - / - indole-7-carboamide (46.0 mg, 0.1 mmol) in DMSO (2.0 ml) was added N-meityl-2-propanamine (73.1 mg, 1.0 mmol). Then, the reaction mixture was reacted in a microwave at 160 ° C for 10 min. Then, sodium triacetoxyborohydride (220 mg, 1.0 mrnoi) was added and the reaction was reacted at room temperature overnight. Then, it was purified by Gilson Preparative HPLC to give 24.0 mg of the title compound (44.2%). LC / MS = m / z 543 [M + H]. Retreat time: 1.70 min.
EXAMPLE (81) 3414-ethyl-sulphonyl)) - 4-P-pergdinyl-1-S454-2-propgB-1-pyrr © B8dir! 8) nr. @ TiBl ° 3 1 H-indoB-T-carboxamide To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0.11 mmol) in DMSO (2.0 ml) was added 2-propylpyrrolidine (113 mg, 1.0 mmol). Then, the reaction mixture was reacted in a microwave at 120 ° C for 10 min. Then, Iriaceous? -hydrochloride sodium (220 mg, 1.0 mmol) was added and the reaction was reacted at room temperature overnight. Then, it was purified by Gilson Preparative HPLC to give 21.0 mg of the thioule compound (38.7%). LC / MS = m / z 543 [M + H]. Time of laugh: 1.70 min. 3414etilsu8foni8]) - 4-PBper8dgpi81-g454r243 ° piridgngB] > -1 ° pgrro8Bd5niB1me • 1 H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { d - [(2-propyl-1-pyrrolidinyl) meily] -3-thienyl} -1 / - / - indole-7-carboamide, suspending 2-propylpyrrolidine for 3- (2-pyrrolidinyl) pyridine (148 mg, 1.0 mmol) to yield 13.0 mg of the title compound (22.5%). LC / MS = m / z 578 [M + H]. Time of day: 1.52 min.
EXAMPLE © trifluoroacetate of §454í2 1.1"dimethylethyl-pgrroJDgnS81me 114eti¡suBfoniBl) -4-piperidinylM H-indoll-7-carboxa ?.
The title compound was prepared according to the general procedure of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5-. { d - [(2-propyl-1-pyrrolidinyl) methyl] -3-thienyl} -1H-indole-7-carboamide, substituting 2-propylpyrrolidine for 2- (1,1-dimethylethyl) pyrrolidine (127 mg, 1.0 mmol) to yield 11.0 mg of the title compound (16.4%). LC / MS = m / z 567 [M + H]. Retreat time: 1.65 min.
EXAMPLE 92 S 54f2-ethyl-1 ° pyrrolidi il1metBl1 ° 34ieni8 3414ethyl8u8f © ngB ° PBperiding Vearboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-propyl-1-pyrrolidinyl) methyl] -3-thienl} -1 / - .indol-7-carboamide, substituting 2-propylpyrrolidine for 2-ethylpyrrolidine (99.0 mg, 1.0 mmol) to yield 15.0 mg of the title compound (28.4%). LC / MS = m / z 529 [M + H]. Retreat time: 1.66 min.
EXAMPLE © 9 trifluoroacetate of 34 etiisulfonBl -piperidniii 5454r242 ° metiBpr @ íDD "1 ° pirrolidin5.1metii) -34ienill, -1 H-lndoB-7-cairbQxa.t.o the The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-propyl-1-pyrrolidinyl) methyl] -3-thienyl} -1 / - / - indole-7-carboamide, substituting 2-propylpyrrolidine for 2- (2-methylpropyl) pyrrolidine (127 mg, 1.0 mmol) to yield 7.0 mg of the title compound (10.4%). LC / MS = m / z 557 [M + H]. Retreat time: 1.74 min.
EXAMPLE © 94 341 etilsu8foniB -PiperidBnil1-54g4r241 ° met8etiBμ e 'tieni8) -1 H-indol ^ -carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { d - [(2-propyl-1-pyrrolidinyl) methyl] -3-thienyl} -1 / - / - indole-7-carboxamide, suspending 2-propylpyrrolidine by 2- (1-methylethyl) pyrrolidine (113 mg, 1.0 mmol) to yield 16.0 mg of the title compound (29.5%). LC / MS = m / z 543 [M + H]. Time of laugh .: 1.61 min.
EXEMPL © M - (et8lsu8fon8B | -4 ° piperidinin-5454 (í2S) ° 24írr.etiB © xnlmetB8 ^ .inil.}. Meti8μ34ienil? ° 1H4ndo »-7 ° earb @ xam» dg? The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { d - [(2-propyl-1-pyrrolidinyl) methyl] -3-lienyl} -1 H -indole-7-carboamide, susliluyendo 2-propilpirrolidina by (2S) -2 - [(melilo? I) meíil] pirrolidina (115 mg, 1.0 mmol) to produce 22.0 mg of the title compound (40.4% ). LC / MS = m / z 544 [M + H]. Retreat time: 1.44 min.
EXAMPLE © 98 §454reSc8ohexil (m til, ami? P) oT] metiBμ34ier.8B paperBdi l1-1H-gndoB ° 7 ° earboxapt) gd.a The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { d - [(2-propyl-1-pyrrolidinyl) methyl] -3-thienyl} -1 / - / - indole-7-carboxamide, suspending 2-propylpyrrolidine per cyclohexyl (methyl) amine (113 mg, 1.0 mmol) to yield 15.0 mg of the title compound (27.6%). LC / MS = m / z 543 [M + H]. Retreat time: 1.64 min.
EXAMPLE 97 3414-ethylsulfoni-MB-piperidipyl-1 ^ 454r242-ethylprop8B!) ° 1-pyrr © Bgdg9t? IilBr? ®inμ 4 H4ndol-7- < sarboxa? The compound of the illole was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d-. { d - [(2-propyl-1-pyrrolidinyl) meily] -3-thienyl} -1H-indole-7-carboxamide, substituting 2-propylpyrrolidine for 2- (2-methylpropyl) pyrrolidine (127 mg, 1.0 mmol) to yield 12.0 mg of the title compound (21.6%). LC / MS = m / z 557 [M + H]. Time of laugh: 1.74 min.
EXAMPLE 98 5454fethyl (methyl) amino1? Pr.ethyl 348enyl) ° 3 r 4ethylSyB1fon?] ° p? P®? R5d? Nñni ° 1j iodoB = 7-carboxappiDda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-lienyl) -1 / - -indole-7-carboxamide (50 mg, 0.11 mmol) in DMSO (2.0 ml) was added 2 drops of acetic acid and ethyl (methyl) amine (59 mg, 1.0 mmol) and stirred at room temperature for 5 h. Then, sodium Iriacetoxyborohydride (212 mg, 1.0 mmol) was added thereto and reacted overnight. Then, it was purified by Gilson Preparative HPLC to give 30.0 mg of the title compound (61.4%). LC / MS = m / z 489 [M + H]. Retreat time: 1.50 min.
EXAMPLE 91 3-R4-4-ethyl-sulphon-8-piperidinyl-454-methyl (propi8 mgn ©] rnet-n3-tBeraDB]) ° 1W ° 5-di-7-earboxamgda The title compound was prepared according to the general procedure of 5- (5-. {[[Ethyl (meily) amino] -methyl] -3-thienyl) -3- [1- (eylsulfonyl) -4-piper. Din1] -1H-indole-7-carboxamide, substituting 2-propylpyrrolidine for methyl (propyl) amine (73 mg, 1.0 mmol) to yield 32.0 mg of the title compound (63.7%). LC / MS = m / z 503 [M + H]. Retreat time: 1.54 min. -5- methyl (propi.) aminolmeto * i1 trifluoroacetate 348en.lHH4ndoB-7? sarboxamide To a solution of 5- (5-formyl-3-lienyl) -3-. { 1 - [(1-methyleryl) sulfonyl] -4-piperidinyl} -1 / - / - indole-7-carboamide (46 mg, EIGHT mmol) in DMSO (2.0 ml) was added 2 drops of acetic acid and methyl (propyl) amine (73 mg, 1.0 mmol) and stirred at room temperature for 5 h. Then, iazoate, sodium hydrogen carbonate (212 mg, 1.0 mmol) was added thereto and reacted overnight. Then, it was purified by Gilson Preparative HPLC to give 26.0 mg of the title compound (39.6%). LC / MS = m / z 517 [M + H]. Retreat time: 1.61 min. 5454fetil (m.tininamino1metlll > -3-thienyl) -3-f1-lí < 1l-metiietill) 8Mhlonini-4- piper5dinil > ° 1W-indoB ° 7-carboxanpiBda The compound of the illole was prepared according to the general procedure of trifluoroacetate of 3-. { 1 - [(1-methyleryl) sulfonyl] -4-piperidinyl} -5- (d-. {[[(Propyl) amino] -methyl] -3-thienyl) -1H-indole-7-carboamide, substituting methyl (propyl) amine for ethyl (amyl) amine (59). mg, 1.0 mmol) to produce 8.0 mg of the compound of the extract (15.9%). LC / MS = m / z 503 [M + H]. Time of laugh: 1.59 min.
EXAMPLE 102 rt.etiletg8) 8ulfog? Ii1-4-piperidir.iBμ5454f6n®t§BÍ2 ° amino} metiH-34ien5p-1lH4ndoB ° 7-earboxanr.id? The compilation of the product was prepared in accordance with the general procedure of fluoridaceae of 3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -5- (d- { [Meityl (propyl) amino] methyl.}. -3-lienyl) -1H-indole-7-carbo-amide, suspending meityl (propyl) amine per meiyl [2- (methyloxy) elil] amine (89 mg, 1.0 mmol) to yield 37.0 mg of the tíulo compound (69.4%). LC / MS = m / z 633 [M + H]. Time of laugh: 1.68 min.
EXAMPLC ri4eti8sulffon8¡ -PÍperidinip-5454 (methyiamgn?]) Metg8μ24ii) g.iB} ° 1 ^ 7-carb xamide To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-formyl-2-ynyl) -1 / -and-indole-7-carboamide (35 mg, 0.078 mmol) in DMSO (1.0 ml) was added acetic acid (3 goies) and 2 M methylamine in THF (0.24 ml, 0.471 mmol) and reacted for 3 h. Then, sodium idioceroxyborohydride (100 mg, 0.471 mmol) was added and the reaction was stirred for one night. All the solvent was removed in vacuo and purified by Gilson Preparative HPLC. The desired impure fraction was concentrated under reduced pressure and loaded onto a 500 mg SCX SPE cartridge primed with 10 ml of melanol. Then, the cariucho was eluted sequentially with 2 M NH 3 in MeOH (10 ml x 2). The NH3 fractions in MeOH were concentrated to give 7.3 mg of the title compound (20%). LC / MS = m / z 459.6 [M + H]. Retreat time: 1.25 min.
EXAMPLE © trifluoroacetate of 3414etiisu8fonia]) - 4-pSperidingB1 ° 54§4í2 ° ?? tlB ^ - pirrolid5niü) methyl1-34ienlHH4ndol-7-earboxamBdlg? To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -d- (5-formyl-2-ynyl) -1 / - / - indole-7-carboxamide (60 mg, 0.112 mmol) in DMSO ( 3.0 ml) were added acrylic acid (3 golas) and 2-methylpyrrolidine (0.12 ml, 1.12 mmol) and reacted for 4 hours. Then, sodium triacetoxyborohydride (238 mg, 1.12 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 17 mg of the title compound (30%). LCMS: 615.4 (M + H), Rt 1.60 min EXAMPLE © 10. 341- (eti8su8foniB]) - 4-Pipegdinin-S454C2 ° methylpropg8) amBn @ 1rra 4? ©? P? B)) ° '-iip? DoB-7-earboxamide trifluoroacetat © To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 / - / - indole-7-carboamide (50 mg, 0.112 mmol) in DMSO (2.0 ml) was added acetic acid (4 drops) and reacted (2-methylpropyl) amine (0.17 ml, 1.68 mmol) and sodium triacerate-iborohydride (356 mg, 1.68 mmol). The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 15 mg of the title compound (27%). LCMS: 503.4 (M + H), Rt 1.60 min EXAMPLE © 106 trifluoroacetate © of 3414eti88u8for.ii | - "PBperidángBl" i), 5- fpropropylamino) metH1-34ienil) -1lH4ndoB-7 ^ arb © xa ?? ¥ .ida To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (d-formyl-3-thienyl) -1 / - / - indole-7-carboxamide (60 mg, 0.112 mmol) in DMSO ( 2.0 ml) was added acetic acid (3 drops) and reacted (2-methylpropyl) amine (0.17 ml, 1.68 mmol) and sodium triacetoxyborohydride (356 mg, 1.68 mmol). The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 15 mg of the title compound (27%). LCMS: 489 (M + H), Rt 1.61 min EXAMPLE 107 trifluoroacetate or 54g4.diet.8amir.o $ meti.1-34gen50? H3 pgperidgnii1-1H4ndoB "7" Carboxa8? .Sdcf To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0.11 mmol) in DMSO (2.0 ml) were added acetic acid (3 drops) and diethylamine (0.12 ml, 1.12 mmol) and stirred for 4 h at room temperature. Then, sodium triacerate-iborohydride (238 mg, 1.12 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 7.0 mg of the title compound (13%). LCMS: 501.4 (M + H), Rt 1.51 min EXAMPLE trifluoroacetat® of 5454 r 2 5ffl ° 2,5-dimethyl ° ^ p8rrQBgdir? I81nriietl} ° 34o®o-.3 34 4-ethyl sulphide. -4-Piperidni? 1-1] H-gndoB ° 7- (garboxapngda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formi [-3-thienyl) -1H-indole-7-carboxamide (50 mg, 0J 12 mmol) in DMSO ( 2.0 ml) was added acetic acid (3 drops) and (2R, 5R) -2,5-dimethylpyrrolidine (151 mg, 1 J23 mmol) and reacted for 4 h. Then, sodium iaoxyloxyborohydride (238 mg, 1 J23 mmol) was added. The reaction mixture was purified by reverse phase Gilson Preparaliva HPLC to give 27 mg of the title compound (46%). LCMS: 529.4 (M + H), Rt 1.64 min EXAMPLE © 101 trifluoroacetate of §454 (cie8opropi8amir. @ Lm®t¡.Í ° 34g®piS8.}. ° 3 1 ° ([eti8sulfonB8]) - 4 ° piperidinip ° 1M4r.doi ° 7 ° carboxarp? Ida To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (60 mg, 0.11 mmol) in DMSO ( 2.0 ml) were added acrylic acid (d drops) and cyclopropylamine (0.12 ml, 1.68 mmol) and reacted for 6 h. Then, sodium triacetoxyborohydride (366 mg, 1.68 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 8.0 mg of the title compound (10%). LCMS: 487.2 (M + H), Rt 1.64 min and 1.68 min EXAMPLE trifluoroacetate of 5454 (c. Obutilamino) met? Fl "3 ° tieni í-pipe, To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -d- (d-formyl-3-thienyl) -1H-indol-7-carboamide (60 mg, 0J 1 mmol) in DMSO (2.0 ml), acetic acid (4 goies) and cyclobuylamine (0J5 ml, 1.68 mmol) was added and reacted for 4 h. Then, sodium triacedoxyborohydride (356 mg, 1.68 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (10%). LCMS: 501.4 (M + H), Rt 1.51 min EXAMPLE © 111 trifluoroacetate of 5454 (dithmethamino) methylene-3-tert-3-pgpepdipi1 1H "indoB" 7 ° carboxar? Fl) gd-a To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4-formyl-2-ynyl) -1 / - / - indole-7-carboamide (300 mg, 0.67 mmol) in DMSO (4 ml) was added a solution of 2 M dimethylamine in THF (3.36 ml, 6.7 mmol). The reaction was stirred at ambient temperature for 7 h and triacetyl-sodium hydrogen carbonate (1.42 g, 6.7 mmol) was added. The stirring was continued overnight at room temperature. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give the thioule compound (205 mg, 64%). LCMS: 475.2 (M + H), Rl 1.51 min EXAMPLE m: §- cgcBopenti8metgi trifluoroacetate) arrainolmetifl) ° 1 (jStilsulfog? 86 | ° 4-PiperBdinil1-1H-gndoB ° 7 ° (sarboxarriiñ la To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in DMSO ( 2.0 ml) were added acetic acid (3 drops) and (cyclopentylmethyl) amine (112 mg, 1123 mmol) and reacted for 4 h. Then, sodium idioceroxyborohydride (238 mg, 1123 mmol) was added and the reaction was stirred for one night. The reaction mixture was purified by reverse phase Gilson Preparaliva HPLC to give 8.0 mg of the title compound (14%). LCMS: 529.4 (M + H), Rt 1.61 min and 1.64 min 113 trifluoroacetat © of V? BJJJ] ffl-1.2 ^ imetllprop¡pamno) met.u -3-t¡? ([Ethosulfoni8) -4-PBperidinyl3-1M4ndo¡7-ea? rb @ xa [¡t.ñ] a? To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-ynyl) -1 H -indole-7-carboamide (50 mg, 0J 12 mmol) in DMSO (2.0 ml) were added acetic acid (3 drops) and (2R) -3-methyl-2-butanamine (98 mg, 1 J23 mmol) and reacted for 4 h. Then, sodium triacehoxyborohydride (238 mg, 1 J23 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (10%). LCMS: 517.2 (M + H), Rt 1.65 min EXEMPL © 114 trifluoroacetate of 5454 (heavenly.tilamip © lmetil) ° 34i (§ (n8i ([eti¡sulfonglD-4-piper¡dini81-1H4ndo8 ° 7 ° € arboxarw5da To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in DMSO ( 2.0 ml) were added acetic acid (3 drops) and cyclopentanamine (0.11 ml, 1123 mmol) and reacted for 4 h. Then, sodium triacerate-iborohydride (238 mg, 1123 mmol) was added and the reaction was reacted overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (6.0%). LCMS: 515.6 (M + H), Rt 1.38 min EXAMPLE 1 '5454J trifluoroacetate, fcBc8opropiimethyl) amgpo1me ([etiÍ8ulfoni8) -4-piperidini83-1H4ndo8 ° 7 earboxamB To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-lienyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in DMSO ( 2.0 ml) was added acrylic acid (3 drops), 1-cyclopropylmethanamine (OJO ml, 1 J23 mmol) and reacted for 6 h. Then, sodium triacehoxyborohydride (238 mg, 1 J 23 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (10%). LCMS: 501.4 (M + H), Rt 1.53 min EXAMPLE © 111 trifluoroacetate of 5454ffl1 S) -1, 2-dimetiipr? P881amg¡n ©) etgfl]) ° 34ieng0l1 ° 3- íetiÍ8ulfoniB -Pperidinill-1H4ndoB ^ arb @ xamiid] a To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-ynyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in DMSO (2.0 ml) were added acrylic acid (3 drops) and (2S) -3-methyl-2-butanamine (98 mg, 1123 mmol) and reacted for 6 h. Then, triacetyl-sodium hydrogen carbonate (238 mg, 1123 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 8.0 mg of the title compound (15%). LCMS: 517.2 (M + H), Rí 1.65 min EXAMPLE © 117 trifluoroahetate of 5454f "2 dimetiipropgg) arniBi © 1meW- ([eti8sulfonylM-pgperidiniB1-1W-Bndo8 ° 7 ° carb @ xa To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indol-7-carboamide (50 mg, 0.112 mmol) in DMSO ( 2.0 ml) was added acetic acid (3 drops) and (2,2-dimethylpropyl) amine (0.13 ml, 1123 mmol) and reacted for 6 h. Then, sodium triacedoxyborohydride (238 mg, 1123 mmol) was added and stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 4.0 mg of the title compound (7%). LCMS: 517.2 (M + H), Rt 1.68 min and 1.71 min EXAMPLE © 118 341-1 fiífiß amino -3- -ea To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboxamide (50 mg, 0.112 mmol) in DMSO (2.0 ml ) acetic acid (5 goies) and (phenylmethyl) amine (0.14 ml, 1123 mmol) were added and reacted for 6 hours. Then, sodium triacetoxyborohydride (238 mg, 1123 mmol) was added and it was stirred for one night. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (8%). LCMS: 537.2 (M + H), Rt 1.68 min EXAMPLE 4 -3-dimethylsulfonyl) -pyridinyl-5-trifluoroacetate (2St-tetra-1-furanylmethylmethyl) -methiai-3-thienyl81-1H-gndoB 7-carb? 3 ainñda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-ynyl) -1 H -indole-7-carboxamide (50 mg, 0.112 mmol) in dichloromethane (3.0 ml. ) and methanol (1.5 ml) were added acetic acid (5 drops) and 1 - [(2S) -tetrshydro-2-furanyl] melanamine (0.12 ml, 1123 mmol) and reacted for 6 h. Then, sodium triacetoxyborohydride (238 mg, 1123 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 23 mg of the title compound (8%). LCMS: 531.4 (M + H), Rt 1.58 min EXAMPLE 12 (4-trifluoroacetate of 4-ethylphosphine) -4-pyridine-545 f (tetrahydro-2-pyro-4-amino-8-amino-3-thienyl-1H4-B-7-carb-x-xa) Going To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-ynyl) -1 H -indole-7-carboxamide (50 mg, 0.112 mmol) in DMSO (2.0 ml ) were added acetic acid (5 drops) and (tetrahydro-2H-pyran-4-ylmethyl) amine (130 mg, 1123 mmol) and reacted for 6 h. Then, sodium iaoceloxyborohydride (238 mg, 1123 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 7.0 mg of the title compound (11%). LCMS: 545.4 (M + H), Rt 1.52 min EXAMPLE 5 121 5-f (butylamino) methyl-3- ienii trifluoroacetate-34'a eti.sulfo? P? Iill] H.- p5perddinip-1W4ndoB-7-carboxa? M? Ñda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 H -indole-7-carboxamide (50 mg, 0.112 mmol) in dichloromethane (3.0 ml. ) and methanol (1.5 ml) were added 5 drops of acetic acid and butylamine (0.11 ml, 1123 mmol) and reacted for 6 h. Then, sodium borohydride (43 mg, 1123 mmol) was added and stirred at room temperature for one night. All the solvent was removed in vacuo and dissolved in DMSO (1.0 ml). Then, it was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (10%). LCMS: 503.4 (M + H), Rt 1.63 min EXAMPLC 34 4'i'ti'su8f © niB) -4-PIPperidi fi cation 54S4 (r.2H)) 4etrahg-l. furan-8-methyl-1-methyl-1-methyl) ^ 4ien? .l ° 1H4ndoB-7? garb? xamSda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0J 12 mmol) in DMSO (2.0 ml) were added acetic acid (5 drops) and 1 - [(2 /?) - tetrahydro-2-furanyl] methanamine (130 mg, 1 J23 mmol) and the reaction mixture was reacted for 6 h. Then, sodium triaceioxyborohydride (238 mg, 1 J23 mmol) was added and the reaction was stirred overnight. After, more was added tetrahydro-2-furanyl] methanamine (130 mg, 1 J23 mmol) followed by sodium triacetoxyborohydride after 6 h. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (8.0%). LCMS: 531.4 (M + H), Rt 1.50 min EXAMPLE 123 Trifluoroa-ethate of 3,414-methanediol, H-pyridinyl-1-phenyl-2-yl-2-yl-2-r (methyloxy) metip-1-pyrrolidinyl > methyl) ^ - thienin-1IH4r.doB-7 ^ a? rboxan.5 lg? To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-lienyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in dichloromethane ( 3.0 ml) and methanol (1.5 ml) were added 5 drops of acetic acid and (2S) -2 - [(methyl? I) methyl] pyrrolidine (129 mg, 1123 mmol) and reacted at room temperature for 6 h . Then, sodium borohydride (43 mg, 1123 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mixture was purified by reverse phase Gilson Preparative HPLC to give 8.0 mg of the title compound (13%). LCMS: 545.2 (M + H), Rt 1.62 min and 1.66 min.
EXAMPLE 4124-3,4-phenylsulfonyl trifluoroacetate) -4-pyrimidinium-5454 ^ 2-phenyl-2-6, methyl-ethyl-1-pyrrolidinyl > pr? ethyl) -34iengn-1W4ndoB ° 7 ° ea? rboxarfB? ls? To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-lienyl) -1 H -indole-7-carboxamide (50 mg, 0.112 mmol) in dichloromethane (3.0 ml. ) and methanol (1.5 ml) were added acetic acid (5 drops) and (2R) -2 - [(methyl? i) methyl] pyrrolidine (129 mg, 1123 mmol) and stirred at room temperature for 6 h. Then, sodium borohydride (43 mg, 1123 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was purified by reverse phase Gilson Preparative HPLC to give 5.0 mg of the title compound (13%). LCMS: 545.2 (M + H), Rt 1.62 min and 1.66 min.
EXAMPLE 125 3414etilsu8fongB) -4 ° pgpergdin¡p-544424oneti8anpigno) etinferiinMH-carboxamide To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (200 mg, 0.48 mmol) in dioxide and H20 were added acid [4]. - (Cyanomethyl) phenyl] boric (232 mg, 0.144 mmol), potassium carbonate (400 mg, 2.88 mmol) and teirac (methylfenylphosphine) palladium (0) (30 mg, 0.048 mmol). The solution was stirred and dried in the microwave at 160 ° C for 40 min. The reaction was diluted with EtOAc and H20 and filtered to obtain a yellow crystal in the form of the desired product. The solution was washed with brine and H20 and then the EtOAc was concentrated. To the residue was added MEOH which precipitated the desired product and then washed again with MeOH to give 5- [4- (cyanomethy) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide. To 5- [4- (cyanomethyl) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - -indol-7-carboamide (78 mg, 0.173 mmol) in DCM was added a Solution 1.5 fv? of diisobutylaluminum hydride in toluene (240 ml, 0.346 mmol) at 0 ° C. The reaction was agitated at 0 ° C for 20 min. Then, the reaction was stopped with a saturated solution of KNa tartrate. The bi-layer was filtered and the solid was the desired production. In addition, the organic layer was concentrated to give the desired compound, 3- [1 - (ylsulfonyl) -4-piperidinyl] -5- [4- (2-oxo-yl) phenyl] -1H-indole-7-carboxamide, which it was collected without further purification. To a solution of 3- [1- (ynylsulfonyl) -4-p-peridinyl] -5- [4- (2-o? Oyl) phenyl] -1H-indole-7-carboamide (50 mg, 0J 1 mmol) in melanol (5 ml) and melylene chloride (5 ml) at room temperature was added 2 M methylamine in tetrahydrofuran (0.4 ml) followed by 1 drop of acetic acid. The reaction was stirred at room temperature for 2 h followed by an addition of sodium triacetoxyborohydride (200 mg, 0.94 mmol). That reaction lasted for one night. Then, it was purified by ultra-rapid chromatography to give 10 mg of the title compound (19.4%). LC / MS = m / z 469.4 [M + H]. Retreat time: 1.63 min.
EXAMPLE © 128 1 ethyl8-sulfonyl-Piperidin-1 ^ 4-r2? Ropyllam.r.o) etinf n.nMH-i ?. l (D [ The title compound was prepared according to the general procedure of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5-. { 4- [2- (meitylamino) eyl] phenyl} -1 H -indole-7-carboamide, substituting me ylamine for 2 M propylamine in leihydrofuran (0.4 ml) to yield 15 mg of the compound of the extract (27.5%). LC / MS = m / z 497.6 [M + H]. Retreat time: 1.63 min.
EXAMPLE © 1; 544424etiBamgno) etipfenil} -3414eti8su8fonilM ° P8P®ridingl1 ° 1HHnid®nV ° carboxamide To a solution of 3- [1- (elylsulfonyl) -4-pperidinyl] -5-. { 4- (2-o? Oyl) phenyl] -1 / - -indol-7-carbo-amide (50 mg, 0.11 mmol) in meianol (5 ml) and melylene chloride (5 ml) at ambient temperature was added 2 M ethylamine in tetrahydrofuran (0.4 ml), followed by 1 drop of acetic acid. The reaction was stirred at room temperature for 2 h followed by an addition of sodium triacetoxyborohydride (200 mg, 0.94 mmol). This reaction was stirred overnight. Then, it was purified by flash chromatography to give 15 mg of the title compound (28.3%). LC / MS = m / z 483.2 [M + H]. Retreat time: 1.57 min.
EXAMPLE 128 Trifluoroacetate of 5444ff1-f11-d1metHetH) -3-methyll-1IHI-pyrazoic-Bncarbonyl > ami8io) methy1feniB) -3414ethylsulfonii piperidge? gni ° 1H4n cairboxaimiDda To a solution of [4- (aminomethyl) phenyl] boronic acid (145 mg, 0.966 mmol) in DMF (2 mL) was added 1- (1,1-dimethylethyl) -3-methyl-1H-pyrazole- 5-carbonyl (290 mg, 1.45 mmol) and triethylamine (403 μl, 2.90 mmol). The reaction was stirred for 2 h. Then, it was stopped and partitioned between EtOAc and H20 and the organic layer was concentrated to give acid. { 4 - [( { [1- (1, 1-dimethylyleyl) -3-meityl-1 / - / - pyrazol-5-yl] carbonyl} amino) meilyl] phenyl} boric. To a solution of 5-bromo-3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (50 mg, 0.120 mmol) in dioxane (1 ml) and water ( 0.4 ml) was added polybasic carbon (74 mg, 0.484 mmol) and acid. { 4 - [( { [1- (1, 1-dimethylyl) -3-methyl-1 / - / - pyrazol-5-yl] carbonyl} amino) methyl] phenyl} boric acid (153 mg, 0.483 mmol). The reaction mixture was stirred and bubbled with argon for 5 min before the addition of chlorine (di-2-norbornylphosphino) (2- dimethylammonyltroferro-1-yl) palladium (II) (7 mg, 0.012 mmol). The reaction was stirred for 10 min and then chalked at 150 ° C. The reaction was evaporated and purified by Gilson Preparative HPLC to give 5 mg of the title compound (5.8%). LC / MS = m / z 605.4 [M + H]. Time of laugh: 2.14 min. 129 414eti8su8fong8H ° p¡peridini81 ° §- p¡rid8niBearbonii) aminol? Methyl) phenylMH- The title compound was prepared according to the general trifluoroacetate procedure of 5-. { 4 - [( { [1- (1, 1-dimethylethyl) -3-meityl-1 H -pyrazol-5-yl] carbonyl} amino) methyl] phenyl} -3- [1- (Erylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, suspending the acid. { 4 - [( { [1- (1, 1-dimethylethyl) -3-methy1-1 H -pyrazol-5-yl] carbonyl} amino) methyl] phenyl} boric acid (4-. {[[(4-pyridinylcarbonyl) amino] -methyl] phenyl) boronic acid (124 mg, 0.480 mmol) to yield 30 mg of the title compound (45.8%).
LC / MS = m / z 537 [M + H]. Time of laugh .: 2.04 min.
EXAMPLE, 11 • piperódi l1 ° 1H4ndoB-7"Carboxam.da The title compound was prepared according to the general procedure of trifluoroacelate of 5-. { 4 - [( { [1- (1, 1-dimethylethyl) -3-meityl-1 H -pyrazol-5-yl] carbonyl} amino) methyl] phenyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, susliuuyendo acid. { 4 - [( { [1- (1, 1-dimethylethyl) -3-meiiii-1 H -pyrazol-5-yl] carbonyl} amino) methyl] phenyl} boric acid (4- {[[(cyclopentylcarbonyl) amino] methyl} phenyl) boronic acid (119 mg, 0.480 mmol) to yield 30 mg of the title compound (47%). LC / MS = m / z 537 [M + H]. Retreat time: 2.04 min.
EXAMPL © 131 3414etilsu8f © niB]) - -PÍpergdipi8] -5444f.2 uraniáearb © 6iiBDamgy. @ 1nr? EtiB 1 M-Bndofi-7-carboxamidg? The title compound was prepared according to the general procedure of 5- fluorifaceae. { 4 - [( { [1- (1, 1-dimethylethyl) -3-meityl-1 H -pyrrazole-5-yl] carbonyl] amino) methyl] phenol} -3- [1 - (Erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboamide, suspending acid. { 4 - [( { [1 ~ (1, 1-d-methylethyl) -3-methyl-1H-pyrazol-5-yl] carbonyl}. Amino) meilyl] phenyl} acid (4- {[[(2-furanylcarbonyl) amino] methyl} phenyl) boric acid (118 mg, 0.480 mmol) to yield 16 mg of the title compound (25%). LC / MS = m / z 535.5 [M + H]. Retreat time: 1.99 min.
EXEMPLQ 132 S44424 (ciciobuti8carbopBB) to inoleti8 > fer.iBμ3414eti8su8forii¡D ^ piperfl or? r.in-- -7-carboxamid? The title compound was prepared according to the general procedure of 5-. { 4- [2- (acetylamino) ethyl] phenyl} -3- [1- (erylsulfoniyl) -4-piperidinyl] -1H-indole-7-carboxamide, susliíuyendo? / - [2- (4-bromophenyl) ethyl] acetamide by? / - [2- (4-bromophenyl) ethyl] cyclobutanecarboxamide (100 mg, 0.324 mmol). It was purified by flash chromatography to yield 28 mg of the title compound (48.3%). LC / MS = m / z 537.2 [M + H]. Time of laugh: 1.99 min.
EXAMPLE ©! 44424.C8 iohexi8earbonil, aminoleti8) feniBD-3414 @ tIBsul pipergdinill-IIH-gndoB-7- arboxa? Nriflda The compose of the title was prepared according to the general procedure of 5-. { 4- [2- (acetylamino) eyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, suspending A / - [2- (4-bromophenyl) elly] acetylamide by? / - [2- (4 -bromophenyl) ethyl] cyclohexanecarboxamide (100 mg, 0.324 mmol). Purified by flash chromatography to yield 32 mg of the title compound (52.5%). LC / MS = m / z 565.4 [M + H]. Time of laugh: 2.14 min.
EXEMPLC g43424icge8or? ExicarboniBDamino1eti8) feniiD-3414eti¡syi PFer5din8] -1H-Bndol-7 ° carboxaro.d§? The compound of the tíulo was prepared according to the general procedure of 5-. { 4- [2- (acetylamino) eyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, suspending? / - [2- (4-bromophenyl) eyl] acetylamide by N- [2- ( 3-bromophenyl) elyl] cyclohexanocarboamide (100 mg, 0.324 mmol). The concentrated reaction mixture was purified by Gilson Preparative HPLC followed by re-purification by flash chromatography to give the compound of the extract. LC / MS = m / z 565.2 [M + H]. Time of laugh .: 2J6 min.
EXAMPLE 13 Trifluoroacetate of one thousand thirds To a solution of 5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1 - / - idol-7-carboamide (100 mg, 0.241 mmol) in dioe (1.0 ml) and H20 (0.8 ml) was added with cesium carbonate (314 mg, 0.964 mmol) and [6- (4- {[[(1,1-dimethylylyl) or? I] carbonyl} -1-piperazinyl) acid. -3-pyridinyl] boric acid (297 mg, 0.964 mmol). The reaction mixture was stirred before the addition of palladium ()) (28 mg, 0.024 mmol). The reaction was heated in a microwave at 160 ° C for 20 minutes. The mixture was concentrated and taken up in ElOAc (10 ml) and H20 (5.0 ml). The compound was purified by Gilson Preparative HPLC to give 129 mg of 4- (5-. {7- (aminocarbonyl) -3- [1- (ethylsulfonyl) -4-picperidinyl] -1H-indol-5-yl} -2- pyridinyl) -1-piperazinecarboyl-1,1-dimethylethyl ether and 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [6- (1-piperazinyl) -3-pyro Dyl] -1 / - / - indole-7-carboamide (44%).
To a solution of 4- (5-. {7- (aminocarbonyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indol-5-yl.} -2-pyridinyl) -1 -1,1-dimethylethylpiperazinecarboxylate (130 mg, 0.218 mmol) in methanol (0.3 ml) was added 4M HCl in dioxane (0.3 ml). The reaction was heated to 50 ° C and stirred for 3 h. The reaction mixture was concentrated and neutralized on an SCX cartridge primed with CH2Cl2, followed by MeOH and collection with ammonia in MeOH. 20 mg of the desired fraction was concentrated and purified using MDAP HPLC to give 9.4 mg of the title compound (7%). LC / MS = m / z 497.2 [M + H]. Retreat time: 1.45 min EXAMPL © 138 ftrifluoroaeetat © de 54644-eti-1-piperazinyl) ^ - pyridin5? 1-341l ®t¡Bs ridiniH-l W¡ndo8 ° 7-carboxam5da To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [6- (1-piperazinyl) -3-pyridinyl] -1 / - / - indole-7-carboxamide (40 mg, 0.081 mmol ) in dichloromethane was added acetaldehyde (7 mg, 0.162 mmol) and sodium triacehoxyborohydride (100 mg, 0.472 mmol). The reaction was stirred during a night at ambient ambience. Then, the reaction mixture was concentrated and dissolved in EtOAc and H20. The salts were filtered and the organic layer was concentrated and purified by Gilson Preparative HPLC to give 39 mg of the title compound (92%). LC / MS = m / z 525.6 [M + H]. Time of laugh .: 1.44 min EXAMPLE © 137 frrifluoroaeetat © de 341- (®tiBsuif @ ng8H-PíperidgrfigD1 ° 5444 'ffenül-ll H4ndol-7-earboxart.ida To a solution of j - ?? - ^ et ?? su? Ton ??; - 4-p? Per? A? N? Jb- (4-formylphenyl) -1 H -indole-7-carbo? Amide ( 40 mg, 0.09 mmol) in dichloromean was added piperidine (9 μl, 0.09 mmol). The reaction was agitated for 1 h before the addition of sodium triacerate-iborohydride (58 mg, 0.27 mmol). The reaction mixture was stirred overnight at room temperature. Then, the mixture was concentrated and purified by Gilson Preparative HPLC to give 8.0 mg of the title compound (14%).
LC / MS = m / z 509.4 [M + H]. Retreat time: 1.71 min EXAMPLE © 138 piperidiniBmetil) fenill-1H-indoB "7-earb @ xam5da To a solution of 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- (3-formy3pheny1) -1H-indole-7-carboxamide (50 mg, 0.114 mmol) in dichloromethane (2 ml) and acetic acid (1 drop) was added piperidine (46 μL, 0.456 mmol). The reaction was stirred for 2 h at room temperature before the addition of sodium idioceroxyborohydride (75 mg, 0.342 mmol). Then, the reaction was stirred for a further 3 h. Then, the mixture was purified by Gilson Preparative HPLC to give 36 mg of the title compound (61%). LC / MS = m / z 509.4 [M + H]. Time of laugh .: 1.80 min EXAMPLE 3 tributyanoacetate 3-Ri4ethylsulfonyl) -pipe? Riidip? Ll1-g4 - | fCmethylamino) methyl] phenyl > -1H4ndol-7-carboxapr.i the To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-form [phenyl] -1H-indole-7-carboxamide (20 mg, 0.045 mmol) in dichloromelane (12 ml ), Vleianol (2 ml) and acetic acid was added meilamine in THF (20 μ !, 0.54 mmol). The reaction mixture was agitated at room temperature for 2 h after the addition of sodium idioleoxyborohydride (10.3 mg, 0.270 mmol). Then, the mixture was agitated for a further 3 h before the mixture was concentrated and purified by Gilson Preparative HPLC to give 6 mg of the title compound (10%). LC / MS = m / z 454.6 [M + H]. Retreat time: 1.23 min EXAMPL © 14 © 3414eti »sulfor.8l) -4-piperidgnii1-5444r (1 ° meti8etiB | arragno1meteB feriin]) ° ^ - -Vearboxamidsi To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-formy! Phenyl) -1 / - / - indole-7-carboamide (40 mg, 0.09 mmol) in DMSO (900 μl) and acetic acid (2 golas) was added 2-propanamine (93 μl, 1.08 mmol). After 2 h, sodium iazoate iborohydride (172 mg, 0.81 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 30 mg of the title compound (69%). LC / MS = m / z 483.2 [M + H]. Retreat time: 1.56 min EXAMPLE 3414-Sulfsulphonyl-pópe? R? Diniiri- lamino ^ metipphenyl- trifluoroacetate-1lM4ndol-7-carl oxame l To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboamide (20 mg, 0.045 mmol) in DMSO (900 μL) and acetic acid (2 drops) was added propylamine (45 μl, 1.08 mmol). After 2 h, sodium triaceroxyborohydride (172 mg, 0.81 mmol) was added. The reaction mixture was stirred for one night. The compound was purified by Gilson Preparative HPLC to produce 21? mg of the tíulo compound (74%). LC / MS = m / z 483.2 [M + H]. Retreat time: 1.54 min.
EXAMPL © 142 5444f (1 • propyl) aminomethyl) phenol) -3- | .1 ethylsulfor.g8]) - 4-pgperidgn8B1 ° c0 H- -earboxarnsda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 / - / - indole-7-carboxamide (40 mg, 0.09 mmol) in DMSO (900 μl) and acetic acid (2 drops) was added 3-pentanamine (108 μl, 1.08 mmol). After 2 h, sodium triacetoxyborohydride (172 mg, 0.81 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 34.5 mg of the title compound (74%). LC / MS = m / z 511.4 [M + H]. Retreat time: 1.69 min EXAMPLE 143 §444 trifluoroacetate (cyclo-pentylamino) methy81phen? UJllTOT.t piperid5nil1-1H-indol-7-earbQxarc.iid.
To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1H-indole-7-carboamide (40 mg, 0.09 mmol) in DMSO (900 μl) and acid acetic acid (2 goies) was added cyclopentylamine (108 μl, 1.08 mmol). After 2 h, sodium triacerate-iborohydride (172 mg, 0.81 mmol) was added. The reaction mixture was stirred for one night. The compound was purified by Gilson Preparative HPLC to yield 11.1 mg of the title compound (20%). LC / MS = m / z 509.4 [M + H]. Retreat time: 1.66 min.
EXAMPLE 5 4-r (cyclobutylamino) methyn n.i > ^ 1-ethylsulfon-8) ^ pperiodone-1W4? P? Gilon-7-ca? Rboxamgda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 / - / - indole-7-carboamide (40 mg, 0.091 mmol) in DMSO (900 μl ) and acetic acid (2 drops) was added cyclobutylamine (94 μl, 1.08 mmol). After 2 h, sodium triacete-iborohydride (120 mg, 1.10 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 26.3 mg of the title compound (59%). LC / MS = m / z 495.4 [M + H]. Retreat time: 1.37 min EXAMPLE © 145 5 44 (ethylamino) metinfenia) ^ 41 et? sulfonyl) ^ - p? pe? r.d?? p? ilTI-1lH-indoa-7- carboxarnide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboamide (20 mg, 0.046 mmol) in DMSO and acetic acid ethylamine (32 μL, 0.547 mmol) was added. After 2 h, sodium triacete-iborohydride (120 mg, 1.10 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 11.5 mg of the title compound (55%). LC / MS = m / z 469.4 [M + H]. Retreat time: 1.52 min.
EXAMPL © 146 5444 (dimet »Ba? Tign © lmetñnfeniB -3414et88sulfongB!) - 4 ° P8per carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboxamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acetic acid N-dimethylamine (170 μl, 0.342 mmol) was added. After 2 h, sodium triacetoxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 28.9 mg of the title compound (54%). LC / MS = m / z 469.4 [M + H]. Retreat time: 1.52 min.
EXAMPLE > 444 (diethylmgr.o) methyl1fengBμ3414etilsu8foniH- ° pgpe .7.
To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acetic acid, diethylamine (36 μl, 0.342 mmol) was added. After 2 h, sodium triacetoxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 37.6 mg of the title compound (67%). LC / MS = m / z 497.6 [M + H]. Retreat time: 1.52 min.
EXAMPLE 48 3414-ethyl-8-sulfonyl) ^ piperidin-p ^ 444-morphol-.i.mepl) n.ni-1lH-iffi? D®n-y- To a solution of 3- [1- (alkylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1H-indole-7-carboamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acid acetic acid morpholine (30 μl, 0.342 mmol) was added. After 2 h, sodium idioceroxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was agitated overnight. The compound was purified by Gilson Preparative HPLC to yield 40.3 mg of the title compound (70%). LC / MS = m / z 511.4 [M + H]. Retreat time: 1.53 min EXAMPLE 149 341-Sulfsulfonitrile trifluoroacetate) -4-piperidinemp 5-pyrrolidinylmethyl) fenip-1H4ndol ° 7 ° earb @ xamBda To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 / - / - indole-7-carboxamide (50 mg, 0.114 mmol) in DMSO (3 ml ) and acetic acid was added cyclopentylamine (28 μl, 0.342 mmol). After 2 h, sodium triacetoxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 20.1 mg of the title compound (36%). LC / MS = m / z 495.4 [M + H]. Ret time: 1.58 min EXAMPLE © 15C 34? Ethylsulfonyl) -4-piperidiniBTl-methylethylamino trifluoroacetate > metñl) fenBl] | ° 1W4ndoB ° 7 ° ca5, boxam? da To a solution of 3- [1- (alkylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboxamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acetic acid (2S) -2-amino-1-propanol (56 μL, 0.745 mmol) was added. After 2 h, sodium iaoxyloxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred for one night. The compound was purified by Gilson Preparative HPLC to yield 25.9 mg of the title compound (15%). LC / MS = m / z 499.6 [M + H]. Retreat time: 1.54 min EXAMPLE © 151 frrifluoroacetat © of 34 4 @ t¡BsuBf © n88H-P¡peridingB1 ° §444ffl1 ffl, -2- eti8etiS1am8p? ©} meti8) phenyl1-1M-BndoB-7 ^ a [rb @ xamodii.
To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboxamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acetic acid (2R) -2-amino-1-propanol (56 μL, 0.745 mmol) was added. After 2 h, sodium triacetoxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 29.6 mg of the idyl compound (53%). LC / MS = m / z 499.6 [M + H]. Time of ret .: 1.47 min EXAMPLE 152 trifluoroahetate of 34 etg8sy8fongB.-4-pgperidgir.gl] hydroxypropyl81a? Rtr.gn @) metiB) feniB11 ° W To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1 H -indole-7-carboamide (50 mg, 0.114 mmol) in DMSO (3 mL) and acetic acid was added (2f?) - 1-amino-2-propanol (56 μL, 0.745 mmol). After 2 h, sodium triacetoxyborohydride (290 mg, 1.36 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 14.7 mg of the title compound (26%). LC / MS = m / z 499.6 [M + H]. Retreat time: 1.46 min.
EXAMPLE 15- Trifluoroacetate of 3414e8lsuBfoniB], - 4 ° Pidperid.gl] íhidroxirpetiBletipam8no etipfenip ° 1H-gr8d © B ° 7 ° arb © arr.gda To a solution of 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1H-indole-7-carboamide (40 mg, 0.091 mmol) in DMSO was added. 2-amino-1,3-propanediol (50 mg, 0.55 mmol) and acidic acid (1 gola). After 2 h, sodium triacete-iborohydride (232 mg, 1.10 mmol) was added. The reaction mixture was stirred overnight. The compound was purified by Gilson Preparative HPLC to yield 15.9 mg of the title compound (28%). LC / MS = m / z 515.4 [M + H]. Time of laugh: 1.45 min.
EXAMPLC 341 EthylsulfongBH-piperddi? P) trifluoroacetate gB1i5.5ethylbutyl) amino] met88) phen8IHH4ndoB "7-earboxarp5dg.}.
To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 / - / - indole-7-carboxamide (50 mg, 0J 14 mmol) in DMSO (3.0 ml) 1-2-penlanamine (324 μl, 2.74 mmol) and acélic acid (1 goía) were added. After 2 h, sodium idioceroxyborohydride (290 mg, 1 J0 mmol) was added. The reaction mixture was stirred overnight. Afterwards, the compost was filtered and concentrated. Then, it was purified by Gilson Preparative HPLC to yield 9.5 mg of the title compound (13%). LC / MS = m / z 511.4 [M + H]. Retreat time: 1.66 min EXAMPLE © 15S Trifluoroacetic acid of 34 ethylene sulfonyl) -piperidyl-allyl 54. methylpropyl1Bn} methyl) fengp ° 1H4ndoB ° 7 ° carboxaota To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (50 mg, 0.114 mmol) in DMSO ( 2.0 ml) were added (2R) -2-buanamine (69 μl, 0.684 mmol) and acyl acid (1 drop). After 2 h, sodium triacete-iborohydride (0.435 mg, 2.05 mmol) was added. The reaction mixture was stirred overnight. Then, the compound was filtered and concentrated. Then, it was purified by Gilson Preparative HPLC to yield 18.6 mg of the title compound (33%). LC / MS = m / z 497.6 [M + H]. Retreat time: 1.70 min EXAMPLE © 158 3414eti8sulfong8D- -PiperBdin581-S434r.2 ° meti8propiBlam .roo. -7-earboxamSda To a solution of 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- (3-formylfenyl) -1 / - / - mdol-7-carboamide (50 mg, 0.1%) mmol) in DCM (1.5 ml), MeOH (1.5 ml) and acetic acid (4 drops) was added 2-methyl-1-propanamine (137 μl, 1.37 mmol) and stirred at ambient temperature. After 2 h, sodium borohydride (23 mg, 0.684 mmol) was added and the reaction mixture was purified with a cariucho SCX to give 47.8 mg of the title compound (85%). LC / MS = m / z 497.2 [M + H]. Retreat time: 1.69 min EXAMPLE © 151 acetate of 341 et8lsulfoniBS-4"Pgperidin8B1 ° §434fflH D ° 1 ° methylpropipagno) metii) phenyl1 ° H4ndoB" 7 ° © arb © x @ mgda The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-meitylpropyl) amino] methyl} phenyl) - 1 / - / - indole-7-carboxamide, suspending 2-methyl-1-propanamine by (2S) -2-bulanamine (138 μL, 1.37 mmol) to yield 43.2 mg of the title compound (76%). LC / MS = m / z 497.4 [M + H]. Time of day: 1.84 min EXAMPLE © HS8 5444r.cgc8opropi8carbonil) aminolmethyl feniBl ° 3414etiisyBf © nalH ° piper.dinil1 ° 1lH-inol "7 ° earboxam.da The compound of the tíulo was prepared according to the general procedure of 5-. { 4 - [(acetylamino) methyl] phenyl} -3- [1- (elylsulfor.il) -4-piperidinyl] -1 / - / - indole-7-carbo-amide substituting acetyl chloride for cyclopropanecarbonyl chloride (14 μl, 1.37 mmol). The compound was purified by Gilson Preparative HPLC to yield 19.1 mg of the title compound (28%). LC / MS = m / z 509.2 [M + H]. Retreat time: 1.86 min EXAMPLE © 1S9 5444rfciclobuti8earboniBlarfi8no1rnetil > phenyl-3414ethyl8ulfor! 8 ° pper (£ 3? -? 5 1 H = Bnd © 8 = 7 = earboxamide The title compound was prepared according to the general procedure of 5-. { 4 - [(acetylamino) meily] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide suspending acetyl chloride with cyclobutanolcarbonyl chloride (17 μl, 1.37 mmol). The compost was purified by Gilson Preparative HPLC to produce 20.2 mg of the compound of the extract (28%). LC / MS = m / z 523.2 [M + H]. Time of laugh .: 1.94 min EXAMPLE © 11 m 3414etiisulfon¡8) ^ - piperidgnil1 ° 5444r (2 ieni8aeeti¡) amir. @ 1rir.etia) fey.5n]) ° W ° 5 [r.dol = 7 = earb © xannidü The title compound was prepared according to the general procedure of 5-. { 4 - [(acetylamino) meily] phenyl} -3- [1- (ethylsulfortyl) -4-piperidinyl] -1 / - / - indole-7-carbo-amide substituting acetyl chloride for (3Z) -3- (methylthio) -3,5-hexadienoyl ( 18 μl, 1.37 mmol). The compost was purified by Gilson Preparative HPLC to yield 13.5 mg of the title compound (18%). LC / MS = m / z 565.2 [M + H]. Ret Time: 1.98 min EXAMPLE 1S 1 trifluoroacetate d 5 = S) -1 ^ methylpropylmethylmethylphenylTWI) (! Ethyl8u8foniGI-4-p8peridini81 ° 1H4ndoB-7 ° € aF'b © xapn§ a To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (40 mg, 0.091 mmol) in DCM (1.5 mL), MeOH (1.5 ml) and acetic acid was added (2S) -3-meityl-2-bulanamine (128 μl, 1.10 mmol) and stirred at room temperature for 2 h. Then, sodium borohydride (19 mg, 0.546 mmol) was added and stirred for 48 h. Then, the compound was purified by Gilson Preparative HPLC to give 5.8 mg of the title compound (12%). LC / MS = m / z 511.2 [M + H]. Ret Time: 1.76 min To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidini!] - 1 / - / - indole-7-carboxamide (50 mg, 0.121 mmol) in dioxide. anus (1 ml) and H20 (0.4 ml) were And added potassium carbonate (74 mg, 0.484 mmol) and acid (4 { [(Methylsulfonyl) amino] meityl} phenyl) boronic acid (110 mg, 0.50 mmol). The reaction mixture was stirred and bubbled with Argon for 5 min before the addition of chloro (di-2-norbornylphosphino) (2-dimethylaminomethyl] -ferrocen-1-yl) palladium (II) (7 mg, 0.012 mmol). Then, the reaction was stirred and heated for 10 min in a microwave at 160 ° C. The mixture was concentrated and purified by Gilson Preparative HPLC to yield 34.3 mg of the title compound (55%). LC / MS = m / z 519.4 [M + H]. Retreat time: 1.77 min EXAMPLE © 182 trifluoroacetate of 5434ffpffl ° 2 ° dimetilpropg81amino > m® gB) feniB íetiB3ulfom8 ° Piperidinii1-1H4ndoB "7 ° earboxamg (3, B To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-mdol-7-carboxamide (50 mg, 0.114 mmol) in DCM (1.5 mL), MeOH (1.5 ml) and acetic acid was added (2f?) - 3-meityl-2-butanamine (160 μl, 1.37 mmol) and was stirred at room temperature for 2 h. Then, sodium borohydride (19 mg, 0.546 mmol) was added and stirred for 48 h. Then, the compound was purified by Gilson Preparative HPLC to give 50 mg of the compound of Iílulo (86%). LC / MS = m / z 511.4 [M + H]. Time of laugh .: 1.65 min EXAMPLE © 183 trifluoroacetat © of §48 ° art.an © ° 2-pyridin5l) 3414etilsylfoii.il V-ppperfcV To a solution of 3- [1- (allylsulfonyl) -4-pperidinyl] -5- (4,4,5,5-eerylamino-1, 3,2-dio? Aborolan-2-yl) -1 / - / - indole-7-carboamide (83 mg, 0.18 mmol) in dioe (5 ml) was added 6-bromo-2-pyridinamine (93 mg, 0.54 nmol), potassium carbonate (149 mg, 1.08 mmol) in H20 (1.5 ml) and chloro (di-2-norbornylphosphino) (2-dimethylaminomethyl] -troferro-1-yl) palladium (II) (19 mg, 0.031 mmol). The reaction was heated in the microwave at 150 ° C for 20 min. Then, the reaction mixture was concentrated and an aqueous extraction was carried out. Then, the organic layer was concentrated and purified on an HPLC Auto Prep. Directed to Masses to give 22.3 mg of the tíulo compound (29%). LC / MS = m / z 428.6 [M + H]. Time of laugh .: 1.34 min SEMPL © H & 341 etilsuífoniBD-4 ° pgperSdingl1-54341l H ° piraz © ¡1 B) feniB -dnd © fl = 7- = carboxamide To 5-bromo-3- [1 - (ylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (20 mg, 0.048 mmol) was added [3- (1 H-pyrazole-1) phenyl] boronic acid (36 mg, 0J93 mmol), dioxane (2.8 ml) and a polybasic carbonate solution (20 mg) in water (1.2 ml). To this mixture was added chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbomethylphosphine) palladium (II) (3 mg, 0.005 mmol). The resulting mixture was reacted in a CEM microwave for 10 min at 160 ° C and then concentrated in a nihinogen (greenhouse) atmosphere at 80 ° C. The production was partitioned between water (2 ml) and CH2Cl2 (2 ml). The layers were separated with a hydrophobic glaze and the aqueous layer was extracted with CH 2 Cl 2 (2 x 2 ml). The organic layers were combined and concentrated in a nitrogen atmosphere at 80 ° C. To the residue was added dimethylsulphonate (0.8 ml), which was sonic for 10 seconds, filtered through a bed of cotton and it was then filtered through a 0.2 μm filter. The crude product was purified on an Agilent MDAP using a Zorbax Eclipse XDB 610 column of 21.2? 50 mm to yield 2.3 mg of the title compound (10%). LC / MS = m / z 478.2 [M + H]. Time of laugh: 2.05 min.
EXAMPLE © 18. g444dimeti »amgno engBl) ° 3414eti8syBfoni¡.-4" P »P @ ~ 7- To a CEM microwave lubricant was added 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carbo-amide (40 mg, 0.097 mmol), dioxane (2.8 ml) and a solution of potassium carbonate (40 mg, 0.289 mmol) in water (1.2 ml). To this mixture were added [4- (dimethylamino) phenyl] boronic acid (65 mg, 0.386 mmol) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbomylphosphine) palladium (II) (1 mg, 0.002 mg). mmol). The vial was capped and the reaction was reacted in a CEM microwave for 10 min at 160 ° C. The reaction was concentrated under a nitrogen atmosphere at 80 ° C. He The crude product was taken up in dimellysulphonate (1 ml) and purified through a 1 g SPE silica cartridge eluting with dimethylsulphonido (4 ml). The dimellysulphonate was concentrated in a Genevac at 65 ° C for 3 h and the residue was reconstructed in dimethylsulfohydrate (1 ml) and filtered through an acrodisc. Then, the crude product solution was purified on the Agilent MDAP (UV selection 214). The purified product was passed through a polymer-bound carbonate SPE cartridge to yield 2.7 mg of the title compound (6.2%). LC / MS = m / z 455.2 [M + H]. Retreat time: 1.71 min.
EXAMPL © 1166 543-aminofenS8μ3414etiisu8fong8) - -piperidini81 ° H ndoB ° 7 ° (garb © aprañ l-a To a CEM microwave tube was added 5-bromo-3- [1- (ynylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (40 mg, 0.0965 mmol), potassium carbonate ( 80 mg, 0.578 mmol) and (3-aminophenyl) boric acid sulfate (145 mg, 0.386 mmol). The mixture was collected in water (1.2 ml) and dioe (2.8 ml) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbomylphosphine) palladium (II) (1 mg, 0.002 mmol) were added. Then, the mixture was reacted in a CEM microwave for 10 min at 150 ° C. Cellulose was added (2 ml) and the layers were separated. The aqueous layer was washed with ethyl acetate (1-2 ml). The organic layers were combined, concentrated under a nitrogen atmosphere and taken up in dimethylsulfoxide (0.89 ml) and uro-fluoroacetic acid (0J 5 ml). This solution of the crude product was purified on an Agilent MDAP eluting with a linear gradient of 30% CH3CN / H2O (0.1% TFA) to 70% CH3CN / H2O (0.1% TFA) at 20 ml / min for 9 min. . To the HPLC fraction containing the product was added a solution of salted K2C03 (1 ml), a 1M solution of sodium hydroxide (1 ml) and ethyl acetyl (2 ml). The layers were separated and the aqueous layer was extracted with ethyl acetate (2 x 2 ml). The organic layers were combined, filtered through a pad of magnesium sulfate and concentrated under a nitrogen atmosphere to give 14.9 mg of the title compound (36%). LC / MS = m / z 427.2 [M + H]. Time of laugh .: 1.39 min.
EXAMPLE © 187 3414EETLSU8FONIO8 -4-PiperidiniB1 ° S 54 (2 ° MET 1 ° p Rr8Q8idingBtoeti31 ° 2 ° tB®p? D [μ 1! H.-indoil ° 7-carboxamids.
The acid { 5 - [(2-Melyl-1-pyrrolidinyl) methyl] -2-thienyl} boric acid used to prepare 3- [1- (erylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-methyl-1-pyrrolidinyl) mei] [] -2-thienyl} -1 H-Indole-7-carboamide was prepared in separate batches using the procedures shown below: Lot 1: NaBH (OAc) 3 (271 mg, 1.28 mmol), HOAc were added (0.07 ml) and 2-Methylpyrrolidine (0.043 ml, 0.42 mmol) were added to a solution of (5-formyl-2-thienyl) boric acid (100 mg, 0.64 mmol) in CH2Cl2 (4 ml) in a 2-dram vial. The vial was capped and the reaction was stirred at room temperature for 15 h. The reaction mixture was loaded directly onto a 2 g SCX cartridge (pre-equilibrated with MeOH), eluting in sequence with MeOH (12 ml) and a 2 M solution of NH 3 / MeOH (8 ml). The fractions containing the boric acid boric acid product were concentrated under an N2 atmosphere and dried under high vacuum to give 45 mg of the crude product. The brute production was collected in NaHC03 saturated (2 ml) and it was brought with EtOAc (3? 2 ml) to give 6.6 prtg of acid. { 5 - [(2-methyl-1-pyrrolidinyl) methyl] -2-thienyl} rough boric Lot 2: NaBH (OAc) 3 (271 mg, 1.28 mmol), HOAc (0.07 ml) and 2-methylpyrrolidine (0.043 ml, 0.42 mmol) were added to a solution of (5-formyl-2-lienyl) boric acid ( 100 mg, 0.64 mmol) in 1: 1 CH2Cl2 / MeOH (4 mL) in a 2-dram vial. The vial was capped and the reaction was stirred at room temperature for 15 h. The reaction mixture was loaded directly onto a 2 g SCX cartridge (pre-equilibrated with MeOH), eluting in sequence with MeOH (12 ml) and a 2 M solution of NH 3 / MeOH (8 ml). The fractions containing the boric acid crude product were concentrated under an N2 atmosphere and dried under high vacuum to give 45 mg of the crude product. The crude product was taken up in saturated NaHC03 (2 ml) and brought with EtOAc (3 x 2 ml) to give 5 mg of (5 - [(2-methyl-1-pyrrolidinyl) methyl] -2-thienyl acid. Lot. 3: 2-Methylpyrrolidine (0.033 ml, 0.32 mmol) was added to a solution of (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol) in MeOH (1 ml) in a 2-dram vial The vial was capped and the reaction was stirred at room temperature for 2 h NaCNBH3 (40 mg, 0.64 mol) was added and the stirring was quenched for 19 h.The reaction mixture was loaded directly onto a 2 g SCX cartridge (pre-equilibrated with MeOH), eluting in sequence with MeOH (12 ml) and a 2 M solution of NH 3 / MeOH (9 ml) The fractions containing the crude product boric acid were concentrated in an atmosphere of N2 and dried under high vacuum to give 45 mg of the crude product The crude product was taken up in salted NaHCO3 (2 ml) and extracted with EOAc (3 x 2 ml). to give 7.8 mg of acid. { 5 - [(2-Methyl-1-pyrrolidinyl) methyl] -2-thienyl} rough boric The crude boric acids from the above three reactions were combined and taken for the preparation of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-meyi [-1-pyrrolidinyl] methyl] -2-thienyl} -1H-indole-7-carboamide (the final weight after bringing together the three batches of. {5 - [(2-methyl-1-pyrrolidinyl) methyl] -2-thienyl.} Boric acid was 19 mg). A solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (36 mg, 0.0862 mmol), acid. { 5 - [(2-Methyl-1-pyrrolidinyl) methyl] -2-thienyl-boronic acid (19 mg, 0.0862 mmol) and polybasic carbonate (71 mg, 0.517 mmol) was combined in a CEM microwave tube. To this mixture was added water (0.25 ml), dioxide (0.75 ml) and letterche (triphenylphosphine) palladium (0) (10 mg, 0.009 mmol). The vial was capped and reacted in a CEM microwave for 20 min at 150 ° C. To this reaction tetrakis (triphenylphosphine) palladium (0) (10 mg, 0.009 mmol) was added and reacted in a microwave for 20 min at 150 ° C. Additional tetrakis (triphenylphosphine) palladium (0) (10 mg, 0.009 mmol) was added and the reaction was heated in the CEM microwave for a further 20 min at 150 ° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml H20), eluting sequentially with water (3 ml), MeOH (9 ml) and a 2 × vi solution of NH3 / MeOH (9 ml). The fraction containing the solution of the crude product was concentrated under a nitrogen atmosphere and the residue was taken up in DMSO (3 ml). This solution in DMSO of the crude product was purified in the form of three separate injections (1 ml each) on the Agilent MDAP (Zorba column? Eclipse XDB-C18: 21.2? 50 mm) eluting at 20 ml per min for 1 min with 10% CH3CN / H2O (0.1% TFA) and then with a linear gradient of 10% CH3CN / H2O ( 0.1% TFA) to 95% CH3CN / H20 (0.1% TFA) for 8 min and maintaining the final concentration for 30 sec. The two fractions containing the product were filtered through a Pharmasil CHQAX 500 mg column (polymer-bound ammonium hydroxide, United Chemical Technologies) to re-circulate the TFA (2 columns per fraction were used) and concentrated in one atmosphere of nitrogen at 40 ° C to give 13 mg of the title compound (29.3%). LC / MS = m / z 515.6 [M + H]. Retreat time: 1.62 min.
EXAMPLE 188 S4ß4 (ethylamino) metin ° 2 ° tgenill ° 3414etgl8u8foni8 -piperido arboxa Sda The acid { 5 - [(ethylamino) methyl] -2-thienyl} boric used to prepare 5-. { 5 - [(ethylamino) methyl] -2-thienyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboamide was prepared as follows: A 2M solution of ethylamine in THF (0J6 ml, 0.32 mmol) was added to a solution of (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol) in MeOH (1 ml) in a 2-dram vial. The vial was capped and the reaction was stirred at room temperature for 2 h. NaCNBH3 (40 mg, 0.64 mmol) was added and stirring was continued for 17 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (6 rnl) and a 2 M solution of NH 3 / MeOH (9 ml). The NH.sub.4 / eOH fraction was concentrated under a nitrogen atmosphere to give 47 mg of acid. { 5 - [(ethylamino) methyl] -2-thienyl} rough boric To a CEM microwave tube that contained acid. { 5 - [(ethylamino) methyl] -2-thienyl} boric acid (47 mg, 0.254 mmol) was added 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carbo-amide (80 mg, 0J93 mmol), potassium carbonate (160 mg). mg, 1 J6 mmol), dioxide (1.5 ml), H20 (0.5 ml) and iorachi (ρiphenylphosphine) palladium (0) (5 mg, 0.004 mmol). The reaction was dropped in a CEM microwave for 30 min at 150 ° C. (This modality was aborted within 30 min due to the excessive accumulation of pressure). The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with H20 (3 ml), MeOH (9 ml) and a 2 M solution of NH3 / MeOH (6 ml). The NH.sub.4 / MeOH fraction was dried under a nitrogen atmosphere at 40.degree. C., and the crude product was taken up in dimethylsulfohydrate (1 ml) and purified on an Agilent MDAP (Zorba column? Eclipse XDB-C18: 21.2? 50 mm) eluting at 20 ml per min for 1 min with 10% CH3CN / H2O (0.1% TFA) and then a linear gradient of 10% CH3CN / H2O (0.1% TFA) to 95% CH3CN / H2O (0.1% TFA) for 8 min and maintaining the concentration final for 30 sec. The fractions containing the product were filtered through a Pharmasil CHQAX 500 mg column (polymer bound ammonium hydroxide, United Chemical Technologies) to remove the TFA, 2 columns per fraction were used) and concentrated in a nihinogen atmosphere. at 60 ° C to give 8.8 mg of the title compound (10%). LC / MS = m / z 429.8 [M + H]. Retreat time: 1.25 min.
EXAMPLE © 1S9 3414etiísulfom. -Piperidiml1- € 4§4í (í1 -gnetiletill) am8? Pollnna lin ^ 2 ° t¡er.linD ° 1l O- Bipdo8 ° 7 ° carboxamgda Following the general procedure of 5-. { 5 - [(erylamino) meiyl] -2-ienyl} -3- [1 - (Erylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, were made react (5-formyl-2-yl) boric acid (50 mg, 0.32 mmol), isopropylamine (0.027 mL, 0.32 mmol) and NaCNBH 3 (40 mg, 0.64 mmol) to give 41 g of acid (5- { [(1-Methyleryl) amino] methyl} -2-lienyl) boricorium. Then, the crude (5- {[[(1-methyleryl) amino] methyl} -2-lienyl) boric acid was reacted with 5-brorno-3- [1- (ylsylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (80 mg, 0.193 mmol), potassium carbonate (160 mg, 1 J6 mmol) and irraki (lypiphenylphosphine) palladium (0) (5 mg, 0.004 mmol) to give 74 mg of the compound of the íííulo (37%). LC / MS = m / z 430.2 [M + H]. Time of laugh .: 1.29 min.
EXAMPLE S454icic8opropJ8amino]) metill-2 ° t8eniB} ° 3414et883y8f © nnBM ^ 5peridgB; .ñCT1 ° '. [Ha- -7 ° carboxamld§ Following the general procedure of b-. { b - [(ethylamino) meily] -2-thienyl} -3- [1- (Erylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, (5-formyl-2-ynyl) boronic acid (50 mg, 0.32 mmol), cyclopropylamine ( 0.022 ml, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) to give 63 mg of acid { 5 - [(cyclopropylamine) methyl] -2-ynyl} boric boric After, the acid. { 5 - [(cyclopropylamine) methyl] -2-ylene} The boric acid was reacted with 5-bromo-3- [1- (eylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (80 mg, 0J93 mmol), carbonaceous (160 mg, 1 J6 mmol) and irrake (methylfenylphosphine) palladium (0) (5 mg, 0.004 mmol) to give the compound of the impure ileum. The impure thioule compound was again purified with the Agilent MDAP and isolated in the form of the free base according to the procedure outlined in Example 5 to give 6.8 mg of the iole compound (7.2%). LC / MS = m / z 430.2 [M + H]. Retreat time: 1.62 min.
IJEMPLC 5454 r2,2 ° dimethylpropy8) aminolmetii 2-tierBiiμ3414etiGs piperidini8] ° H4ndo8 ° 7"Carb © xaB rii8 la Following the general procedure of 5-. { 5 - [(ethylamino) methyl] -2-thienyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), (2 ,2- dimethylpropyl) amine (0.037 ml, 0.32 mmol) and NaCNBH 3 (40 mg, 0.64 mmol) to give 73 mg of (5-. {[[(2,2-dimethylpropyl) amino] methyl] .- Crude 2-lienyl). Then the (5- ({[[(2,2-dimethylpropyl) amino] methyl} -2-ynyl) boric acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) - 4-piperidinyl] -1 / - / - indole-7-carboamide (80 mg, 0J93 mmol), potassium carbonate (160 mg, 1.16 mmol) and tetrakis (triphenylphosphine) palladium (0) (5 mg, 0.004 mmol) to give 21 mg of the title compound (21%). LC / MS = m / z 430.2 [M + H]. Retreat time: 1.45 min. 454cicropropimethanol ammonolmethyl} ° 2 thien B) -34 4eti8ul piperidinifl-1H-andoB-7 ° carboxar? Ri5da Following the general procedure of 5-. { 5 - [(erylamino) methyl] -2-thienyl} -3- [1- (Erylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), (cyclopropylmethyl) was reacted ) amine (0.027 ml, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) to give 73 mg of crude (5- ({[[(cyclopropylmethyl) amino] methyl] -2-thienyl) boric acid. Thereafter, the crude 5- ({[[(cyclopropylmethyl) amino] methyl} -2-yenyl) boric acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H -indole-7-carboamide (80 mg, 0J93 mmol), potassium carbonate (160 mg, 1 J6 rrtmol) and tetrakis (triphenylphosphine) palladium (0) (5 mg, 0.004 mmol) to give 19.1 mg of the title compound (twenty%). LC / MS = m / z 430.2 [M + H]. Time of day: 1.33 min.
EXEMPL © 173 S454 rccyclopropymethyl amipolymethi-3-pyridgthl] 3414 © toBsuBf © nor piperidinill-IIH-indoll-7-carboxaroiide The (cyclopropylmelyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} amine used to prepare 5- (5-. {[[(cyclopropylmethyl) amino] rneryl} - 3-pyridinyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carbo Amide was prepared as follows: (cyclopropylmethyl) amine (0.011 ml, 0. 129 mmol) to a solution of 5- (4,4,5,5-tetramethyl-1,2,2-dio? Aborolan-2-yl) -3- pyridinecarbaldehyde (30 mg, 0J29 mmol) in MeOH (1 ml) in a 2-dram vial. The vial was capped and the reaction was stirred at room temperature for 17 h. NaCNBH3 (16 mg, 0.258 mmol) was added and stirring was continued for 30 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (6 ml) and a 2 M solution of NH 3 / MeOH (9 ml). The fraction of NriVMeO? it was concentrated in a nihigogen atmosphere to give 21 mg of (cyclopropylmethyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} amine bruise. To a CEM microwave tube containing (cyclopropylmethyl). { [5- (4,4,5,5-tetramethyl, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} Amine (21 mg, 0.0725 mmol) was added 5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (30 mg, 0.0723 mmol), gave Anal. (0.75 ml), a solution of polyacryl carbonate (60 mg, 0.434 mmol) in H20 (0.25 ml) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg). , 0.00723 mmol). The reaction was heated in a CEM microwave for 30 min at 150 ° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with H20 (3 ml), SvleOH (6 ml) and a 2 M solution of NH3 / MeOH (9 ml). The NH3 / MeOH fraction was dried in a nigerian atmosphere at 40 ° C and purified on an Agilení MDAP (Zorba column? Eclipse XDB-C18: 21.2 x 50 mm) eluting at 20 ml per min. 10% CH3CN / H2O (0.1% TFA) and then with a linear gradient of 10% CH3CN / H2O (0.1% TFA) to CH3CN at 95% / H20 (0.1% TFA) lasted 8 min and maintained at the final concentration for 30 sec. The fractions containing the product were filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide, United Chemical Technologies) to reagent the TFA and concentrated under a nitrogen atmosphere at 65 ° C to give the compound of the impure ileum, which was purified on the Agilenl MDAP as shown above to give 25 mg of the title compound (70%). LC / MS = m / z 496.6 [M + H]. Time of laugh .: 1.35 min. 1EMPLC 3414eti¡su8fon3n]) - 4-P8Peridir-gl1 ° 5454ir24metgi ©? G etiila? T.g [iioto € j Bn ^ piridin¡HH4ndol-7-earboxamiid§.
Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl.}. -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide, 5- (4,4,5,5-telramethyl-1, 3,2-dio? aborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0J29 mmol), [2- (methyloxy) ethyl] amine (0.011 ml, 0J29 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 19 mg of [2- (methyloxy) ethyl]. { [5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} crude amine. Then, the [2- (meilyloxy) eyl]. { [5- (4,4,5,5-Teramelyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} amine bruise was reacted with 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 - / - indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 15 mg of the compound of the extract (46%). LC / MS = m / z 500.6 [M + H]. Time of day: 1.52 min.
EXEMPL © 17i 3414etilsu8fon¡I ° Píper8din¡l] -S4ß4 (4meti8o? G) propilla [ífii¡n? nr! ett -indoB-7-carboxamide Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl} - 3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carbo Amide, 5- (4,4,5,5-telramelyl-1, 3,2-dio? aborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0.129 mmol), [3- (Melyloxy) propyl] amine (0.013 ml, 0J29 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 22 mg of [S-Imelyl? propylJtfd- ^ AS.d -lelramethyl-I. S ^ -dio? aborolan-2-yl) -3-pyridinyl] methyl} crude amine. Then, [3- (meilyloxy) propyl]. { [5- (4,4,5,5-eetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} Brula amine was reacted with 5-bromo-3- [1- (ethylsulfoni [) - 4-piperidinyl] -1H-indole-7-carboamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomeleyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 31 mg of the illole compound (83%). LC / MS = m / z 514.4 [M + H]. Time of laugh .: 1.46 min.
EXAMPLE © 171 3414etilsu8foni¡ -pgperidinil1-i4i44-morfo8ing8rpetB8]) ° 3-pflrgdgng81 ° Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl.}. -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- carboamide, 5- (4,4,5,5-tetramethyl-1, 3,2-dio? aborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0.129 mmol), morpholine (0.011 ml) were reacted , 0.129 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 28 mg of the 4-. { [5- (4,4,5,5-lelramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} morpholine bruise. After, the 4-. { [5- (4,4,5,5-leiramethyl-1, 3,2-dioxaborolan-2-y!) - 3-pyridinyl] meityl} Brula morpholine was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol ) and chloro-2- (dimethylaminomeyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 15.8 g of the title compound (43%). LC / MS = m / z 512.2 [M + H]. Time of laugh .: 1.38 min.
EXAMPLE S454methylamino methyl ° 3 ° pgriding8 3414eti8su8foni8 ^ - -pjp®r¡dgrtga Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl.} - 3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboamide, 5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0J29 mmol) was reacted, a 2 M solution of Ethylamine in THF (0.065 ml, 0J29 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 19 mg of ethyl. { [5- (4,4,5,5-lettermethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] meityl} brula amine. After, the ethyl. { [5- (4,4,5,5-Teremethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] meiil} amine was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 12.3 mg of the title compound (36%). LC / MS = m / z 470.4 [M + H]. Time of laugh .: 1.44 min.
EXAMPLE 5454 (dimethylamine) methyl 3-pBridinyl ° 3414eti8sulf © rtiB-gperidinoB 1 ^] - ondo8 ° 7 ° carbQxamide Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboamide, 5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0.129 mmol), a 2-fold solution was reacted. Vl of dimethylamine in THF (0.065 ml, 0J29 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 23 mg of dimethyl. { [5- (4,4,5,5-ioramelyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] methyl} crude amine. Then, the dial. { [5- (4,4,5,5-telramel] -1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] methyl} crude amine was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (30 mg, 0.0723 mmol), polybasic carbonate (60 mg, 0.434 mmol ) and chloro-2- (dimethylaminomeyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 5.4 mg of the title compound (16%).
LC / MS = m / z 470.6 [M + H]. Retreat time: 1.35 min.
IEMPL © 171 3414etiBsu8for.8¡] j-4 = p8peridinill-S4S4 (2-metiB ° 1 pgrttoBgdg [iBBlmetiS1 °; piridinii H-indole ° 7 ° carboxanriBda Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] methyl.}. -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-pyridinyl] -1H-indole 7-carboxamide, 5- (4,4,5,5-terylammell-1, 3,2-dio? Aborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0J29 mmol), 2-methylpyrrolidine ( 0.013 ml, 0J29 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 25 mg of 3 - [(2-methyl-1-pyrrolidinyl) meityl] -5- (4,4,5,5-lei-methyl-1, 3,2-dio? Aborolan-2-yl) pyridine brula. Then, 3 - [(2-meityl-1-pyrrolidinyl) meityl] -5- (4,4,5,5-lettermethyl-1, 3,2-dio? Aborolan-2-yl) pyridine was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 6 mg of the title compound (16%). LC / MS = m / z 512.6 [M + H]. Retreat time: 1.67 min.
EXAMPLE 18 © 4eti8sulfonglD-4 ° P8peridingl1-S454rí2- etgipr © pgB) arg? GB QlmetJBμ ° pir.dinilHH-indol-7-earboxap? Ida Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] -methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- carboamide, 5- (4,4,5,5-ioramelii-1, 3,2-dioxaborolan-2-yl) -3-pyrridinecarbaldehyde (30 mg, 0.129 mmol), isobutylamine (0.013 ml, 0.129) were reacted mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 21 mg of (2-meitylpropyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] meityl} brula amine. Then, (2-methylpropyl). { [5- (4,4,5,5-teramylamino-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] methyl} crude amine was reacted with 5- bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomethyl) - ferrocen-1-yl- (dinorbornylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 12.5 mg of the title compound (35%). LC / MS = m / z 498.2 [M + H]. Retreat time: 1.38 min.
EXAMPLE © 181 g454r.2"2-dgmetilpr © piltemino1metill-3-piriding¡¡ etalsu pgper¡dgnil1-1H4ndo8 ° 7 ° carb? Xartr.gda Following the general procedure of 5- (5-. {[[(Cyclopropylmethyl) amino] -methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboamide, 5- (4,4,5,5-tetramethyl-1,2,3-dio? aborolan-2-yl) -3-pyridinecarbaldehyde (30 mg, 0.129 mmol) was reacted, (2, 2-dimethylpropyl) amine (0.015 ml, 0.129 mmol) and NaCNBH3 (16 mg, 0.258 mmol) to give 25 mg of (2,2-dimethylpropyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] meityl} amina bruía. Then, (2,2-dimethylpropyl). { [5- (4,4,5,5-iolameryl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} amina bruía was made react with 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (30 mg, 0.0723 mmol), polybasic carbonate (60 mg, 0.434 mmol) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinorbomylphosphine) palladium (II) (4.4 mg, 0.00723 mmol) to give 12.7 mg of the title compound (34%). LC / MS = m / z 512.4 [M + H]. Retreat time: 1.51 min.
EXAMPLE © 182 3414ETylsulfoni8D- ° PIPperidI8iip ° S454rC2 ° methylbutgBlarriBraQlmetaBμ2-tg® The acid { 5 - [(ethylamino) methyl] -2-thienyl} boric acid used to prepare 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-methylbutyl) amino] methyl.} -2-thienyl) -1H-indole-7- carboamide was prepared as follows: A solution of (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol) in MeOH (0.5 ml) and a solution of NaCNBH3 (40 mg, 0.64) were added. mmol) in MeOH (0.5 ml) to (2-methylbutyl) amine (28 mg, 0.32 mmol) in a 2-dram vial. The vial was covered and the The reaction was stirred at room temperature for 20 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (6 ml) and a 2 M solution of NH 3 / MeOH (9 ml). The NH3 / MeOH fraction was concentrated under a nitrogen atmosphere to give 43 mg of 5- ({[[(2-methylbuyl) amino] -methyl} -2-thienyl) boronic acid. To a CEM microwave tube containing 5-bromine (5- ({[[(2-meitylvolyl) amino] methyl} -2-thienyl) boric acid (43 mg, 0.88 mmol) was added. -3- [1 - (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (65 mg, 0J57 mmol), K2CO3 (130 mg, 0.942 mmol), dioxide (1.5 ml), H20 ( 0.5 ml) and tetrakis (triphenylphosphine) palladium (0) (4 mg, 0.003 mmol). The reaction was heated in a CEM microwave for 30 min at 150 ° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with H20 (3 ml), MeOH (9 ml) and a 2 M solution of NH3 / MeOH (6 ml). The NH3 / MeOH fraction was dried under a nitrogen atmosphere at 40 ° C and the crude product was taken up in dimethylsulfoxide (1 ml) and purified on an Agilení MDAP (Zorba column? Eclipse XDB-C18: 21.2? 50 mm) eluting at 20 ml per min duranie 1 min with 10% CH3CMi / H2O (0.1% TFA) and then with a linear gradient of 10% CH3CN / H2O (0.1% TFA) to 95% CH3CN / H20 (0.1% TFA) lasted 8 min and maintained at the final concentration for 30 sec. The fractions containing the product were fi ltered through a 2 g Pharmasil CHQAX column (ammonium hydroxide bound to polymer; Chemical Technologies) to remove the TFA and concentrated under a nitrogen atmosphere at 50 ° C to give 16.2 mg of the title compound (17%). LC / MS = m / z 430.4 [M + H]. Retreat time: 1.75 min.
EXAMPLE © 183 54S4 (r.1 Rl-1,2-d-methylpropinamino) metin 2-thien-1 341l 4et? 8suifoff.gflM-pgperidinil1-1H4ndoB ° 7 ° earboxamiBiral Following the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-meitylbutyl) amino] meityl} -2-ynyl) -1H-indole 7-carboamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), | (1 R) -1,2-dimetylpropyl] amine (28 mg, 0.32 mmol) and NaCNBH3 were reacted (40 mg, 0.64 mmol) to give 30 mg of [5- ( { [(1 R) -1,2-dimethypropyl] amino] methyl] -2-thienylBoric acid. Then, the crude [5- ( { [(1 R) -1,2-dimeiylpropyl] amino} -methyl) -2-thienyl] boronic acid was reacted with 5-bromo-3- [1- ( ethylene sulfonyl) -4-piperidinyl] -1 / - / - indole 7-carboamide (65 mg, 0J57 mmol), K2CO3 (130 mg, 0.942 mmol) and teirac (triphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 20.5 mg of the title compound (30%). LC / MS = m / z 430.4 [M + H]. Retreat time: 1.75 min.
EXEMPL © 184 3414etilsu8fongiM-piperidin¡n-5454 (pentiíamgrio)) nraeti81-2 ¡®ngi ^ W ^^ 7-earboxamide Following the general procedure of 3- [1- (ethylsulphonyl) -4-piperidinyl] -5- (5-. {[[(2-meityyl-butyl) amino] -methyl] -2-lienyl) -1H-indole 7-carboamide, (5-formyl-2-lienyl) boric acid (50 mg, 0.32 nr.rr.ol), penlylamine (29 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted give 45 mg of acid. { 5 - [(Pentylamino) methyl] -2-lienyl} rough boric After, the acid. { 5 - [(Pentylamino) methyl] -2-thienyl} The crude boron was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (65 mg, 0.157 mmol), K2C03 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 20.7 mg of the title compound (20%). LC / MS = m / z 430.6 [M + H]. Retreat time: 1.75 min.
EXAMPLE © W? 3414-ethylsulfonyl ° PiperidiniB1-5454ffl2Sl ° 2-8T.eti8byti8larri5no mel • 1 H-indoi-7-earboxa? Pr.iid? Following the general procedure of 3- [1- (ethylsulfopi!) - 4-piperidinyl] -5- (5-. {[[(2-meitylbutyl) amino] methyl.} -2-ynyl) -1H-indole -7-carboamide, (5-formyl-2-lienyl) boronic acid (50 mg, 0.32 mmol), [(2S) -2-methylbutyl] amine (28 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.32 mmol) were reacted. mg, 0.64 mmol) to give 43 mg of crude [5- ( { [(2S) -2-methylbutyl] amino] methyl] -2-thienyl] boronic acid. Thereafter, crude [5- ( { [(2S) -2-meityl)] amino] methyl] -2-thienyl] boronic acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol) and teirac (triphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 37.6 mg of the composed of the title (39%). LC / MS = m / z 430 [M + H]. Retreat time: 1.67 min.
EXEMPL © 188 34 4etiisulf © nil]) - ° p5per8din§p ° S4S4r (! 1-methylbuti8) am8no11f! Rieti8 ^ 1 H4md © S-7 = earboxamide Following the general procedure of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-methylbutyl) amino] methyl.} -2-thienyl) -1H-indole 7-carboxamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), (1-methylbuyl) amine (29 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 43 mg of (5- ({[[(1-meityl) -yl) amino] -methyl} -2-yenyl) boric acid. Thereafter, (5. Bromo-3- [1- (allylsulfonyl) -4-piperidinyl] (5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] acid was reacted with the acid. -1H-indole-7-carboamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol) and irraki (methylfenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 35.2 mg of the title compound (60%). LC / MS = m / z 430 [M + H]. Retreat time: 1.62 min. 181 54S4 (butgiamino) eti1 ° 2 ieng8μ3414eti8sulfor? IBM ° PBpe [rBdgg? GBl ° 1H4p (ol @ n ° Following the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-methylbutyl) amino] methyl.} -2-thienyl) -1H-indole 7-carboamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), buylamine (24 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 49 mg of acid { 5 - [(buylamino) meily] -2-ienyl} boric boric After, the acid. { 5 - [(bulylamino) meilyl] -2-lienyl} boric boron was reacted with 5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (65 mg, 0J57 mmol), K2CO3 (130 mg, 0.942 mmol) and leirachis (lypiphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 27.2 mg of the title compound (24%).
LC / MS = m / z 430 [M + H]. Retreat time: 1.56 min. 1EMPL © 188 3414etilsu8fonglM-Piperidinip ° 54S4 (r24 ethyl? G etgi1amir? @ ^ Meti M [@ ra5 1 H-.ndo? -7-earboxap.ida Following the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- { [(2-methylbutyl) amino] methyl.} -2-thienyl) -1H- Indole-7-carboamide, (5-formyl-2-ynyl) boronic acid (50 mg, 0.32 mmo]), [2- (methyl? i) ethyl] amine (24 mg, 0.32 mmol) were reacted and NaCNBH3 (40 mg, 0.64 mmol) to give 42 mg of [5- ( { [2- (methyloxy) ethyl] amino} methyl] -2-thienyl] boronic acid. Then, the [5- ( { [2- (meilyoyl) i) eyl] amino} -methyl) -2-ynyl] boronic acid was reacted with 5-bromo-3- [1- (eylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (65 mg, 0J57 mmol), K2C03 (130 mg, 0.942 mmoi) and telraquis (triphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give the compound of the impure title. The compound of the impure ileum was repurified using the Preparation of HPLC and saturated ammonium hydroxide in the preparation of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- {[[(2-meityl)) amino] methyl} -2 -lienyl) -1H-indole-7-carboamide to give 15 mg of the title compound (15%). LC / MS = m / z 430.2 [M + H]. Retreat time: 1.33 min.
EXAMPLE © 189 §4ß4fciciopeptilamin © ^ meti¡1--2 ienil ° 3414eti8su8ffoir? GB] > -4 - p8perBd¡¡i! D [i'ñ ° IHl- Vearboxa nida Following the general procedure of 3- [1- (ethylsulphonyl) -4-piperidinyl] -5- (5-. {[[(2-meityyl-butyl) amino] -methyl] -2-yenyl) -1H-indole 7-carbohydrate, (5-formyl-2-ynyl) boronic acid (50 mg, 0.32 mmol), cyclopentylamine (28 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 48 mg of acid { 5 - [(Cyclopentylamino) meityl] -2-ynyl} boric boric After, the acid. { 5 - [(cyclopentylamino) meily] -2-ynyl} Boric boron was reacted with 5- bromo-3- [1- (allylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (65 mg, 0.157 mmol), K2C03 (130 mg, 0.942 mmol) and lelrachis (lypiphenylphosphine) palladium (0) (4 mg, 0.003 mmol) to give 93.5 mg of the title compound (85%). LC / MS = m / z 430.4 [M + H]. Retreat time: 1.64 min.
EXAMPLE 190 3414-ethylsulfonyl-piperidinyl-1-5454- (3-methylbutyl) aminolmethyl) -2-thienyl) -1H-indole-7-carboxamide Following the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-methylbutyl) amino] methyl.} -2-thienyl) -1H-indole 7-carboxamide, (5-formyl-2-thienyl) boronic acid (50 mg, 0.32 mmol), (3-methylbutyl) amine (28 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 46 mg of crude (5- ({[[(3-methylbutyl) amino] methyl} -2-thienyl) boronic acid. Then, the crude (5- ({3-methylbuyl) amino} methyl} -2-ynyl) boronic acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4- piperidinyl] -1H-indole-7-carboxamide (65 mg, 0.157 mmol), K2C3 (130 mg, 0.942 mmol) and lelrachis (phenylphenphine) palladium (0) (4 mg, 0.003 mmol) to give 38.3 mg of the compound of the title (37%). LC / MS = m / z 430.4 [M + H]. Retreat time: 1.75 min.
EXAMPLE 191 3414-ethylsulfonyl) -4-piperidinin-5454r (1-methylethyl) amino-1-methyl) -3-pyridinyl) -1H-indol-7-carboxamide The (cyclopropylmethyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} amine used to prepare 3- [1- (ethylsulphonyl) -4-piperidinyl] -5- (5-. {[[(1-methylethyl) amino] methyl] -3-pyridinyl) -1H-indole -7-carboamide was prepared as follows: isopropylamine (0.011 ml, 0.129 mmol) was added to a solution of 5- (4,4,5,5-tetramethyl-1,2,2-dio? Aborolan) -2-yl) -3-pyridinecarbaldehyde (30 mg, 0.129 mmol) in MeOH (1 ml) in a 2-dram vial. Then, NaCNBH3 (16 mg, 0.258 mmol) was added, the vial was capped and the reaction was stirred at ambient lemperairy for 24 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (6 ml) and a 2 M solution of NHs / MeOH (9 ml). The NH.sub.4 / MeOH fraction was concentrated under a nitrogen atmosphere to give 22 mg of (1-methylethyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -3-pyridinyl] meth} crude amine.
To a CEM microwave tube containing (1-methylethyl). { [5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -3-pyridinyl] methyl} Amine (22 mg, 0.080 mmol) was added 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 - / - indole-7-carboxamide (50 mg, 0 J21 mmol), K2CO3 (100 mg) , 0.724 mmol), dioxane (1.5 ml), H20 (0.5 ml) and chloro-2- (dimethylaminomethyl) -ferrocen-1-yl- (dinoorbomylphosphine) palladium (II) (7.3 mg, 0.012 mmol). The reaction was heated in a CEM microwave for 30 min at 150 ° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with H20 (3 ml), MeOH (6 ml) and a 2 M solution of NH3 / MeOH (9 ml). The NH3 / MeOH fraction was dried in an atmosphere of nihologen at 50 ° C and purified on an Agilenl MDAP (Zorbax Eclipse XDB-C18 column: 21.2 x 100 mm) eluting at 20 ml per min for 1 min with CH3CN at 10 % / H2O (0.1% TFA) and then with a linear gradient of 10% CH3CN / H2O (0.1% TFA) to 95% CH3CN / H20 (0.1% TFA) for 8 min and maintaining the final concentration for 30 sec. The fractions containing the product were filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide, United Chemical Technologies) to remove the TFA and concentrated under a nitrogen atmosphere at 50 ° C to give 27.2 mg of the composed of the title (70%). LC / MS = m / z 484 [M + H]. Retreat time: 1.25 min.
EXAMPLE 192 5454r (2-ethylbutyl amino-1-methyl-2-thienyl) -34-dimethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide The acid { 5 - [(ethylamino) methyl] -2-lienyl} boric acid used to prepare 5- (5-. {[[(2-eylylbuyl) amino] -methyl} -2-eneyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide was prepared as follows: A solution of (5-formyl-2-lienyl) boric acid (50 mg, 0.32 mmol) in MeOH (0.5 ml) and a solution of NaCNBH3 (40 mg, 0.64 mmol) were added. ) in MeOH (0.5 ml) to (2-eylilbuyl) amine (32 mg, 0.32 mmol) in a 2-dram vial. The vial was capped and the reaction was stirred at ambient temperature for 20 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (6 ml) and a 2 M solution of NH 3 / MeOH (9 ml). The NH.sub.4 / MeOH fraction was concentrated under a nitrogen atmosphere to give 48 mg of crude (5- ({[[(2-ethylbutyl) amino] methyl} -2-thienyl) boronic acid. To a CEM microwave tube containing the acid (5- { [(2- ethylbutyl) amino] methyl} -2- thienyl) boron (48 mg, 0J99 mmol) was added a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-pperidinyl] -1H-indole-7-carboamide ( 65 mg, 0.75 mmol) in dioe (1.75 ml), a solution of K2CO3 (130 mg, 0.942 mmol) in H20 (0.25 ml) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The reaction was heated in a CEM microwave for 30 min at 150 ° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (3 ml) and a 2 M solution of NH 3 / MeOH (9 ml). The NH3 / MeOH fraction was dried in a nitrogen atmosphere at 50 ° C and the crude product was taken up in dimethyl sulphide (1.1 ml) and purified on an Agilent MDAP (Zorbax Eclipse XDB-C18 column: 21.2 x 100 mm ) eluting at 20 ml per min for 1 min with 10% CH3CN / H2O (0.1% TFA) and then with a linear gradient of 10% CH3CN / H2O (0.1% TFA) to 95% CH3CN / H2O ( 0.1% TFA) lasting 8 min and maintaining the final concentration for 30 sec. The fractions containing the product were filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide: Uniled Chemical Technologies) to remove the TFA and concentrated under a nitrogen atmosphere at 50 ° C to give the impure title. The impure title compound was repurified on an Agilent MDAP and converted to the free base with the ammonium hydroxide column as shown above to give 8.5 mg of the title compound (10%). LC / MS = m / z 430 [M + H]. Time of day: 1.72 min.
EXAMPLE 193 5-5 5 - ((r3- (ethyloxy) propylamino) methyl) -2-thienyl-3-n- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide Following the general procedure of 5- (5-. {[[(2-eylilbuyl) amino] -methyl] -2-lienyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide, (5-formyl-2-ynyl) boronic acid (50 mg, 0.32 mmol), [3- (eryloxy) propyl] amine (34 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of [5- ( { [3- (Elyloxyl) propyl] amino] methyl] -2-ynyl] boric acid. Then, the crude [5- ( { [3- (elyloxy) propyl] amino} methyl) -2-lienyl] boronic acid was reacted with 5-bromo-3- [1 - (ethylsulfonyl) -4 -piperidinyl] -1H-indole-7-carboamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol) to give 8.1 mg of the title compound (10%). LC / MS = m / z 430 [M + H]. Retreat time: 1.62 min.
EXAMPLE 194 3- [1- (Ethylsulfonyl) -4-piperidinin-545 - (([3- (methyloxy) propynamine > methyl) -2- thienyl-1 H -indole-7-carboxamide Following the general procedure of 5- (5-. {[[(2-eylylbuyl) amino] methyl} -2-ynyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide, (5-formyl-2-lienyl) boronic acid (50 mg, 0.32 mmol), [3- (mellyloxy) propyl] amine (29 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted. ) to give 30 mg of crude [5- ( { [3- (Melyloxy) propyl] amino} -methyl) -2-thienyl] boronic acid. Then, the [5- ( { [3- (methyloxy) propyl] amino} -methyl) -2-thienylchloric acid was reacted with 5-bromo-3- [1- (allylsulfonyl) -4-piperidinyl. ] -1 / - / - indole-7-carboamide (65 mg, 0.157 mmol), K2C? 3 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The crude product was purified once in an MDL Agile using the procedure shown in the preparation of 5- (5- { [(2-ethylbubil) amino] methyl.} -2-thienyl) -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide to give 7.6 mg of the title compound (9%). LC / MS = m / z 430 [M + H]. Retreat time: 1.50 min.
EXAMPLE 195 5454f (cyclohexylmethyl amino-1-methyl) -2-thienyl) -34-dimethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide Following the general procedure of 5- (5-. {[[(2-ethylbutyl) amino] methyl] -2-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboamide, (5-formyl-2-thienyl) boronic acid (50 mg, 0.32 mmol), (cycloheptyl) amine (37 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of crude (5- ({[[(cyclohexylmethyl) amino] methyl] -2-thienyl) boric acid. Then, the crude (5- ({[[cyclohexylmethyl) amino] methyl} -2-thienyl) boronic acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol) and telrachis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The gross product is purified once in an Agilent MDAP using the procedure shown in the preparation of 5- (5- { [(2-ethylbubil) amino] methyl.} -2-ynyl) -3- [1- (eylsulfonyl) - 4-piperidinyl] -1 H -indole-7-carbo-amide. The purified product was washed with a 20: 4: 1 mixture of hexanes / EOAc / MeOH (2.5 mL), taken up in EtOAc (2 mL) and washed with saturated K2CO3 (1 mL). The organic layer was concentrated to give 4.7 mg of the title compound (6%). LC / MS = m / z 430 [M + H]. Retreat time: 1.82 min.
EXAMPLE 196 341 Ethylsulfonyl-piperidinin-54S4f 34f 1 -methylethyl) oxppropyl > amino) metin-2-thienyl) -1H-indole-7-carboxamide Following the general procedure of 5- (5-. {[[(2-ethylbuyl) amine] meilyl} -2-thienyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol) was reacted. { 3 - [(1-methyleryl) or? I] propyl} amine (38 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) to give 30 mg of acid. { 5 - [( { 3 - [(1- meli-ethyl) oxy] propyl} amino) methyl] -2-thienyl} rough corner. After, the acid. { 5 - [( { 3 - [(1-Methylethyl) oxy] propyl.] Amino) methyl] -2-thienyl} The crude boron was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (65 mg, 0.57 mmol), K2CO3 (130 mg, 0.942 mmol). and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). After purification twice in an Agilent MDAP as shown in the preparation of 5- (5-. {[[(2-ethylbutyl) amino] methyl.} -2-thienyl) -3- [1- ( ethylsulphonyl) -4-piperidinyl] -1H-indole-7-carbo-amide, the impure title compound was washed with a 20: 4: 1 mixture of halos / ElOAc / MeOH (2.5 ml) to give 7.6 mg of the title compound (9%). LC / MS = m / z 430 [M + H]. Retreat time: 1.62 min.
EXAMPLE 197 545 - ((r24ethyloxy) ethylamino) methyl) -2-thienin-34-dsynesulfonyl) -4-piperidinin-1 H-indol-7-carboxamide Following the general procedure of 5- (5-. {[[(2-ethylbutyl) amino] methyl.} -2-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7- carboxamide, (5-formyl-2-lienyl) boronic acid (50 mg, 0.32 mmol), [2- (ethyloxy) ethyl] amine (30 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted give 30 mg of crude [5- ( { [2- (ethyloxy) ethyl] amino} methyl] -2-thienyl] boronic acid. Then, crude [5- (. {[2- (ethyl?)) Ethyl] amino} methyl] -2-thienyl] boronic acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - -indole-7-carboxamide (65 mg, 0J57 mmol), K2CO3 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The crude prodrug was purified once in an Agilenl MDAP using the procedure shown for the preparation of 5- (5-. {[[(2-ethylbutyl) amino] methyl.} -2-yenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide to give 6 mg of the title compound (7%). LC / MS = m / z 430 [M + H]. Retreat time: 1.66 min.
EXAMPLE 198 341- (Ethylsulfonyl) -4-piperidinin-545 - ((r3- (propyloxy) propynamine > metip-2-thienyl-1 H-indol-7-carboxamide Following the general procedure of 5- (5-. {[[(2-ethylbulin) amino] methyl] -2-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), [3- (propyloxy) propyl] amine (38 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) to give 30 mg of crude [5- ( { [3- (propyloxy) propyl] amino} methyl] -2-thienyl] boronic acid. Then, crude [5- ( { [3- (propyloxy) propyl] amino} methyl] -2-thienyl] boronic acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4 -piperidinyl] -1 / - / - indole-7-carboxamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The crude product was purified twice in an Agilení MDAP using the procedure shown in the preparation of 5- (5- {[[(2-elylbuyl) amino] meily} -2-thienyl) -3- [ 1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboamide. The produelo The purified product was washed with a 20: 4: 1 mixture of hexanes / EtOAc / MeOH (2.5 ml), taken up in EtOAc (2 ml) and washed with saturated K2CO3 (1 ml). The organic layer was concentrated to give to give 1.4 mg of the title compound (2%). LC / MS = m / z 430 [M + H]. Retreat time: 1.66 min.
EXAMPLE 199 5- (54 I (3,3-dimethylbutyl) aminolmethyl) -2-thienin-3-n- (ethylsulfonyl) -4- piperidinip-1H-indol-7-carboxamide Following the general procedure of 5- (5- { [(2-elilbubil) amino] meilyl} -2-lienl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide, (5-formyl-2-thienyl) boric acid (50 mg, 0.32 mmol), (3,3-dimethylamino) amine (32 mg, 0.32 mmol) and NaCNBH3 (40 mg) were reacted , 0.64 mmol) to give 30 mg of (5- ({[[(3,3-dylmethylbuyl) amino] methyl] -2- thienyl) boric acid ester. Then, the crude (5- {[[3,3-dimethylbutyl) amino] methyl} -2-thienyl) boric acid was reacted with 5-bromo-3- [1- (ethylsulfonyl) -4- piperidinyl] -1H-indole-7- carboxamide (65 mg, 0J57 mmol), K2CO3 (130 mg, 0.942 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0079 mmol) to give 4.5 mg of the title compound (5%). LC / MS = m / z 430 [M + H]. Retreat time: 1.79 min.
EXAMPLE 200 341 - (Ethylsulfonyl, -4-piperidinyl-1-545- (ff (1 S) -1,2,2-trimethylpropyl] amino> methyl) -2-thienin-1H -indol-7 -carboxamide Following the general procedure of 5- (5-. {[[(2-ethylbubyl) amino] methyl} -2-ynyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole 7-carboamide, (5-formyl-2-thienyl) boronic acid (50 mg, 0.32 mmol), [(1 S) -1, 2,24 -rimethylpropyl] amine (32 mg, 0.32 mmol) were reacted and NaCNBH3 (40 mg, 0.64 mmol) to give 30 mg of [5- ( { [(1S) -1, 2,2-yrimethylpropyl] amino] -methyl) -2-ynyl] boronic acid. Then, [5- ( { [(1 S) -1,2, 2-trimethylpropyl] amino} methyl) -2-thienyl] boric acid was reacted with 5-bromo-3 -[1- (ethylene sulfonyl) -4-pyridinyl] -1 / - / - indol-7-carboxamide (65 mg, 0.57 mmol), K2CO3 (130 mg, 0.942 mmol) and letraqu¡s (triphenylphosphine) palladium (0) (9 mg, 0. 0079 mmol) to give 10.3 mg of the title compound (12%). LC / MS = m / z 430 [M + H]. Retreat time: 1.62 min.
EXAMPLE 201 341 Ethylsulfonyl-piperidinyl-1-5454 (hexylamino) methyl-2-thienyl) -1H-indol-7-carboxamide Following the general procedure of 5- (5-. {[[(2-eylilbuyl) amino] -methyl] -2-ynyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide, (5-formyl-2-ynyl) boronic acid (50 mg, 0.32 mmol), hexylamine (33 mg, 0.32 mmol) and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of acid. { 5 - [(heylmethyl) meily] -2-lienyl} boric After, the acid. { 5 - [(Hexylamino) -methyl] -2-t-phenyl} boricor was then reacted with 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (65 mg, 0J 57 mmol), K2CO3 (130 mg, 0.942 mmol) and teirak (ylphenylphosphine) palladium (0) (9 mg, 0.0079 mmol). The granular product was purified once in an Agilent MDAP using the procedure shown in the preparation of 5- (5-. {[[(2-ethylbutyl) amino] methyl.} -2-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide to give 13 mg of the title compound (16%). LC / MS = m / z 430.6 [M + H]. Retreat time: 1.92 min.
EXAMPLE 202 542- (dimethylamino.-4-pyridinip-341-ethylsulfonyl-piperidinin-1H-indol-7-carboxamide trifluoroacetate.
To 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (2-fluoro-4-pyridinyl) -1 / -indol-7-carboamide (40 mg, 0.093 mmol) was added dimethylamine ( 1 ml, 0.015 mmol) and DMF (0.3 ml). The resulting mixture was reacted in a microwell for 1 h at 180 ° C. All the solvent was evaporated and then the mixture was purified by HPLC Preparaiva Gilson to give 18.2 mg of the composed of the title (34.4%). LC / MS = m / z 456.2 [M + H]. Retreat time: 1.54 min.
EXAMPLE 203 5464ethyl (methyl.amino-3-pyridinyl) -341-ethylsulfonyl) -4- piperidinin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 5- [2- (dimethylamino) -4-pyridinyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- Irifluoroacetate. carboamide, suspending dimellylamine by pyrrolidine (1 ml) to yield 48.9 mg of the title compound (27.1%). LC / MS = m / z 482.2 [M + H]. Time of laugh .: 1.62 min.
EXAMPLE 204 3-F-14-ethyl-sulfonyl) -4-piperidimyl-54244-morpholinyl) -4-pyridin-p-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelale of 5- [2- (dimethylamino) -4-pyridinyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7- carboamide, substituting dimethylamine for morpholine (1 ml) to yield 12 mg of the title compound (21.1%). LC / MS = m / z 498.6 [M + H]. Retreat time: 1.47 min.
EXAMPLE 205 341- (Ethylsulfonyl-4-piperidinip-5424 (2-methylpropyl) amino-4-pyridinyl) -1H-indol-7-carboxamide trifluoroacetate The thioule compound was prepared according to the general procedure of 5- [2- (dimethylamino) -4-pyridinyl] -3- [1- (ethylsulfonyl) -4-pperidinyl] -1 H- trifluoroacetate. indole-7-carboamide, substituting dimethylamine for 2-methyl-1-propanamine (1 ml) to yield 11.1 mg of the title compound (20%). LC / MS = m / z 484.2 [M + H]. Retreat time: 1.68 min.
EXAMPLE 206 5424 (2,2-Dimethylpropyl) amino-1-4-pyridinyl) -3-rl • (ethylsulphonyl) -4-piperidinyl-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5- [2- (dimethylamino) -4-pyrridinyl] -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- carboamide, substituting dimethylamine for 2, 2-dimetiM -propanamine (1 ml) to yield 9 mg of the title compound (15.8%). LC / MS = m / z 498.6 [M + H]. Retreat time: 1.75 min.
EXAMPLE 207 341 - (Ethylsulfonyl) -4-piperidinip-5- [2- (propylamino.-4-pyridinyl-1H-indole-7-carboxamide trifluoroacetate.
The title compound was prepared according to the general procedure of trifluoroacetate of 5- [2- (dimethylamino) -4-pyridinyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7- carboamide, substituting dimethylamine for propylamine (1 ml) to yield 18.2 mg of the title compound (33.5%). LC / MS = m / z 470.4 [M + H]. Retreat time: 1.57 min.
EXAMPLE 208 341-ethylsulfonyl) -4-piperidinyl-5-444 (methylamino) metip-2-thienyl) -1H-indole-7-carboxamide trifluoroacetate | -5- (4-formyl-2-thienyl) -1 / - / - indole-7-carboxamide (45 mg, 0.1 mmol) in methylene chloride (2 mL) and methanol (1 mL) was added methylamine 2 M (0.5 ml). The reaction mixture was stirred at ambient temperature for 5 h followed by an addition of sodium terahydride sodium (37.83 mg, 1 mmol). The resulting mixture was agitated at room temperature overnight. The solvent was concentrated and purified using Gilson's Preparaliva HPLC to give 16.8 mg of the title compound (29.2%). LC / MS = m / z 461.6 [M + H]. Retreat time: 1.40 min.
EXAMPLE 209 341 - (Ethylsulfonyl) -4-piperidinyl] -544- (1-pyrrolidinylmethyl) -2-thienyl-1-H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 4 - [(methylamino) methyl] -2-l-phenyl} -1H-indole-7-carboamide, substituting 2 M methylamin for pyrrolidine (0.083 ml) to yield 14.8 mg of the title compound (24.1%). LC / MS = m / z 470.4 [M + H]. Retreat time: 1.57 min.
EXAMPLE 210 341- (Ethylsulfonyl) -4-piperidinin-5- (44- (2-methylpropyl-amino-methyl) -2-thienyl) -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 4 - [(methylamino) methyl] -2-thienyl} -1H-indole-7-carboxamide, substituting 2 M methylamine for 2-methyl-1-propanamine (0.1 ml) to yield 15.4 mg of the title compound (25%). LC / MS = m / z 503.2 [M + H]. Retreat time: 1.42 min.
EXAMPLE 211 5444 (dimethylamino) methyl] -2-thienyl) -341- (ethylsulfonyl, 4-piperidinin-1H-indole-7-carboxamide trifluoroacetate] The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5--trifluoroacelate. { 4 - [(methylamino) methyl] -2-thienyl} -1H-indole-7-carboamide, substituting 2 M methylamine for dimethylamine (0.5 ml) to yield 9 mg of the title compound (15.3%). LC / MS = m / z 475.2 [M + H]. Time of day: 1.27 min.
EXAMPLE 212 341 ethylsulfonyl) -4-piperidinin-5454 (1S) -1 1-pyrrolidinyl) etn-3-thienyl-M-indole-7-carboxamide To 5- (5-acetyl-3-lienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (10 mg, 0.02 mmol) was added cyanoborohydride sodium (7.5 mg, 0.12 mmol) and pyrrolidine (0.03 ml, 0.30 mmol). The resulting mixture was reacted in a microwave for 40 min at 150 ° C. All the solvent was evaporated and the crude prodrug was partitioned between ethyl acetate (1.5 ml) and 1 M sodium hydroxide (0.2 ml). The reaction was purified by SFC to give the title compound in chirally pure 100% form. LC / MS = m / z 515.4 [M + H]. Retreat time: 1.54 min.
EXAMPLE 213 341 Ethylsulfonyl) -4-piperidinin-5454 (1R) -1 1-Pyrrolidininetin-3-thienyl > -1H- indole-7-carboxamide To 5- (5-acetyl-3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (10 mg, 0.02 mmol) was added cyanoborohydride sodium (7.5 mg, 0.12 mmol) and pyrrolidine (0.03 ml, 0.30 mmol). The resulting mixture was reacted in a microwave for 40 min at 150 ° C. All the solvent was evaporated and the crude product was partitioned between ethyl acetate (1.5 ml) and 1M sodium hydroxide (0.2 ml). The reaction was purified by SFC to give the title compound in chirally pure 100% form. LC / MS = m / z 515.4 [M + H]. Time of laugh: 1.54 min.
EXAMPLE 214 3-M- (Ethylsulfonyl) -4-piperidyl-p544 ((3'- (methyloxy) propylamino> methyl-2-thienip-1H-indol-7-carboxamide trifluoroacetate To a solution of 5 - [(1Z) -1- (ethenylthio) -4-oxo-1-buten-1-yl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 - / - indole-7-carboxamide (45 mg, 0.1 mmol) in methylene chloride (2 ml) and melanol (1 ml) were added 3 golas of acetic acid and 3- (methyloxy) -1-propanamine (89.14 mg, 1 mmol ). The resulting mixture was stirred for 6 h followed by an addition of sodium borohydride (37.83 mg, 1 mmol). The reaction was stirred at ambient temperature for one night. The solvent was evaporated and then the mixture was purified by Gilson Preparative HPLC to give 23.7 mg of the title compound (37.5%). LC / MS = m / z 519.4 [M + H]. Retreat time: 1.69 min.
EXAMPLE 215 341-ethylsulfonyl) -4-piperidinin-5444 (f 2S) -2-r (methyloxy) metip-1-pyrrolidinyl) methyl) -2-thienin-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- ( { [3- (methyloxy) propyl] amino}. methyl) -2-thienyl] -1H-indole-7-carboxamide, substituting 3- (methyloxy) -1 -propanamine for (2S) -2 - [(methyl? i) methyl] pyrrolidine (115.18 mg, 1 mmol) to yield 3 mg of the title compound (4.6%). LC / MS = m / z 545.2 [M + H]. Retreat time: 1.78 min.
EXAMPLE 216 5- (44 (2R.5R) -2,5-Dimethyl-1-pyrrolidinylmethyl) -2-thienyl) -3- (ethylsulfonyl) -4-piperidinip-1 H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelale of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- ( { [3- (Melyloxy) propyl] amino}. methylene) -2-lienyl] -1H-indole-7-carboxamide 3- (methyloxy) -1 -propanamine per (64.3 mg, 1 mmol) to yield 6.4 mg of the compound of the idyll (10%). LC / MS = m / z 529.4 [M + H]. Time of day: 1.69 min.
EXAMPLE 217 3-Ri- (Ethylsulfonin-4-piperidinin-5- (54 (2S) -2-methyl-1-pyrrolidinyl-1-methyl-3-thienyl) -1H-indole-7-carboxamide To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 - / - indole-7-carboamide (600 mg, 1348 mmol) in dimethylsulphonate (10 ml) was added 20 drops of acetic acid and (2S) -1,2-dimethylpyrrolidine (1.37 ml, 13.483 mmol). The resulting mixture was stirred at ambient temperature for 6 h followed by an addition of sodium triacerate-iborohydride (2858 g, 13.483 mmol). The reaction was stirred at room temperature overnight and then purified by SFC. This compound was separated by RTP CASS Group. The fraction of enantiomer N ° 1 is chirally pure at 99.7% to give 119.9 mg of the title compound (17.3%). LC / MS = m / z 515.4 [M + H]. Retreat time: 1.56 min.
EXAMPLE 218 3-Ri- (Ethylsulfonyl) -4-piperidinyl-5- (54r (2R) -2-methyl-1-pyrrolidinylmethyl> -3-thienyl) -1H-indol-7-carboxamide To a solution ae á - ?? - (et ?? su? Ton? I) -4-p? Per? A? N? J-5- (5-formyl-3-thienyl) -1 / - / - indole-7-carboxamide (600 mg, 1.35 mmol) in dimethylsulfoxide (10 ml) was added 20 drops of acetic acid and 2-methylpyrrolidine (1.37 ml, 13.5 mmol). The mixture was stirred at room temperature for 6 h followed by an addition of sodium idioceroxyborohydride (2.86 g, 13.5 mmol). The reaction was stirred at ambient temperature for one night and then purified by Gilson Preparative HPLC. Then, this compound was separated to give the title compound in chirally pure form at 98.6%. LC / MS = m / z 515.4 [M + H]. Retreat time: 1.56 min.
EXAMPLE 219 341- (Ethylsulfonyl-4-piperidinip-54541- (1-pyrrolidinyl) propyl-3-thienyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7- carboxamide (250 mg, 0.541 mmol) in dioxane (4.5 ml) and H2O (1.5 ml) were added 1- (4-bromo-2-thienyl) -1-propanone (356 mg, 1.62 mmol), potassium carbonate (447 mg). mg, 3.24 mmol) and telrachis (methylfenylphosphine) palladium (0) (64 mg, 0.055 mmol). The reaction was carried out in the microwave at 150 ° C for 20 minutes. An aqueous treatment was carried out using EtOAc and H2O followed by addition of MeOH (20 ml) to the crude prodrug. The desired product was precipitated and filtered to give 110 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-propanoyl-3-thienyl) -1 / - / - indole-7-carboamide (43%). To 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5-propanoyl-3-thienyl) -1 / - / - indole-7-carboamide (60 mg, 0.13 mmol) was added cyanoborohydride sodium (49.2 mg, 0.78 mmol), pyrrolidine (0.2 ml, 1.95 mmol), ethanol (3 ml) and acetic acid (0.4 ml). The resulting mixture was reacted in a microwave for 30 min at 150 ° C. All the solvent was evaporated and then the mixture was purified by Gilson Preparative HPLC to give 12 mg of the title compound (14.4%). LC / MS = m / z 529.4 [M + H]. Retreat time: 1.65 min.
EXAMPLE 220 5454 (dimethylamino) met.l-3-thienyl) -3414 (1-methylethyl) sulfonyl-piperidinyl) -1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ynylsulfonyl) -4-p-peridinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboxamide (50 mg, 0.11 mmol) in dimethylsulfoxide (2 ml) was added 3 golas of acetic acid and frimethylamine (0.55 ml, 1.1 mmol). The resulting mixture was stirred at room temperature for 6 h followed by an addition of sodium triacetoxyborohydride (233 mg, 1 mmol). Then, it was agitated at room temperature overnight and then purified by Gilson Preparative HPLC to give 29.4 mg of the title compound (44.3%). LC / MS = m / z 489.4 [M + H]. Retreat time: 1.32 min.
EXAMPLE 221 545- (aminomethyl) -3-thienip-341- (ethylsulfonyl) -4-piperidinyl] -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 / - / - indole-7-carboamide (50 mg, 0.11 mmol) in Methylene chloride (2 ml) and methanol (1 ml) were added ammonium acetate (84.7 mg, 1.1 mmol) and sodium cyanoborohydride (4.84 mg, 0.077 mmol). The resulting mixture was stirred at room temperature overnight. All the solvent was evaporated and then the mixture was purified by Gilson's Preparaliva HPLC to give 1.8 mg of the title compound (2.9%). LC / MS = m / z 447.2 [M + H]. Retreat time: 1.53 min.
EXAMPLE 222 341-.ethylsulfonyl-4-piperidinium-5- (5424 (2-methylpropyl) aminoethyl) -3-thienyl-1H-indole-7-carboxamide trifluoroacetate.
To a solution of [2- (4-bromo-2-thienyl) ethyl] amine (100 mg, 0.48 mmol) in DCM (2.0 mL) and MeOH (1.0 mL) were added acetic acid (3 drops) and 2- methylpropanal (105 mg, 1.44 mmol). The reaction was stirred overnight at room temperature before the addition of sodium borohydride (53.3 mg, 1.44 mmol). The reaction proceeded for 1 h and then was treated with EtOAc and brine. AfterThe organic layers were dried and concentrated to give 80 mg of [2- (4-bromo-2-thienyl) ethyl] (1-methylethyl) amine (64%). To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -1 / - / -indole-7-carboamide (139 mg, 0.3 mmol) in dioe (3 ml) and water (1 ml) were added [2- (4-bromo-2-thienyl) ethyl] (1-methylethyl) ) amine (50 mg, 0.2 mmol), potassium carbonate (82.8 mg, 0.6 mmol) and tetrakis (phenyl) -phenylamine (0) (22 mg, 0.019 mmol). The mixture turns out was reacted in a microwave for 20 min at 150 ° C. All of the solvent was evaporated and then the mixture was purified by Gilson Preparative HPLC to give 18 mg of the title compound (9.5%). LC / MS = m / z 517.2 [M + H]. Retreat time: 1.68 min.
EXAMPLE 223 54542- (dimethylamino) etip-3-thienyl) -341- (ethylsulfonyl-piperidin-p-1H-indole-7-carboxamide trifluoroacetate To a solution of [2- (4-bromo-2-ynyl) -yryl] amine (100 mg, 0.48 mmol) in DCM (2.0 mL) and MeOH (1.0 mL) were added acrylic acid (3 goles) and formaldehyde, to 37% in H20 (105 mg, 1.44 mmol). The reaction was agitated overnight at room temperature before the addition of sodium borohydride (53.3 mg, 1.44 mmol). The reaction proceeded for 1 h and then brought with EOAc and brine. Then, the organic layers were dried and concentrated to give 50 mg of 2- (4-bromo-2-lienyl) -N, N-dimethylamineamine (44%).
To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -1H-indole -7-carboamide (139 mg, 0.345 mmol) in dioe (3 ml) and water (1 ml) were added 2- (4-bromo-2-lienyl) -N, N-dimethylenamine (50 mg. , 0.23 mmol), potassium carbonate (82.8 mg, 0.69 mmol) and iron (lriphenophosphine) palladium (0) (22 mg, 0.019 mmol). The resulting mixture was reacted in a microwave for 20 min at 150 ° C. All of the solvent was evaporated and then the mixture was purified by Gilson Preparative HPLC to give 12 mg of the title compound (5.8%). LC / MS = m / z 489.2 [M + H]. Retreat time: 1.54 min.
EXAMPLE 224 341 - (Ethylsulfonyl) -4-piperidinyl-546- (1-pyrrolidinyl) -3-pyridinip-1H-indol-7-carboxamide trifluoroacetate To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (110 mg, 0.27 mmol) in dioe (2.0 ml) and H20 ( 0.7 ml) was added (6-fluoro-3-pyridinyl) boric acid (151 mg, 1.08 mmol), polasic carbonate (298 mg, 2J6 mmol) and iorachis (ureaphenylphosphine) palladium (0) (31 mg, 0.026 mmol). The reaction was carried out in the microwave for 20 min at 150 ° C. Then, the reaction was brought with EtOAc and brine and purified by ull-speed chromatography to give 50 mg of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 / - / -indole-7-carboxamide (43%). To 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 H -indole-7-carboxamide (25 mg, 0.058 mmol) was added pyrrolidine (3 ml) . The resulting mixture was reacted in a microwave for 30 min at 100 ° C. All of the exrol pyrrolidine was evaporated and then purified by Gilson's Preparative HPLC to give 25 mg of the title compound (72.4%). LC / MS = m / z 482.2 [M + H]. Retreat time: 1.67 min.
EXAMPLE 225 546- [ethyl (methyl) amino1-3-pyridinyl) -341- (ethylsulfonyl) -4-piperidinin-1H-indol-7-carboxamide trifluoroacetate To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (110 mg, 0.27 mmol) in dioxane (2.0 ml) and H20 (0.7 ml ) were added (6-fluoro-3-pyridinyl) boric acid (151 mg, 1.08 mmol), potassium carbonate (298 mg, 2.16 mmol) and tetrakis (triphenylphosphine) palladium (0) (31 mg, 0.026 mmol). The reaction was carried out in the microwave for 20 min at 150 ° C. Then, the reaction was treated with EtOAc and brine and purified by flash chromatography to give 50 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 H- indole-7-carboxamide (43%). To 3- [1 - (ethylsulfonyl) -4-p-peridinyl] -5- (6-fluoro-3-pyridinyl) -1H-indole-7-carboxamide (40 mg, 0.093 mmol) was added dimethylamine (1 ml) and DMF (0.3 ml). The resulting mixture was reacted in a microwave for 1 h at 200 ° C. The resulting mixture was washed with water. Ethyl acetate was added and the organic layer was evaporated and purified by Gilson Preparative HPLC to produce 34.4 mg of the title compound (63.4%). LC / MS = m / z 470 [M + H]. Retreat time: 1.50 min.
EXAMPLE 226 5- [6- (Dimethylamino) -3-pyridinyl-341 - (ethylsulfonyl-piperidin-1H-indole-7-carboxamide trifluoroacetate To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - -indole-7-carboxamide (110 mg, 0.27 mmol) in dioxane (2.0 ml) and H20 (0.7 ml) were added (6-fluoro-3-pyridinyl) boric acid (151 mg, 1.08 mmol), potassium carbonate (298 mg, 2.16 mmol) and letterche (lypiphenylphosphine) palladium (0) (31 mg, 0.026 mmol). ). The reaction was carried out in the microwave for 20 minutes at 150 ° C. Then, the reaction was treated with EtOAc and brine and purified by flash chromatography to give 50 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 / - / -indole-7-carboxamide (43%). To 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1H-indole-7-carboamide (50 mg, 0.116 mmol) was added dimethylamine (1 ml) and DMF (0.3 ml). The mixture was reacted in a microwell for 1 h at 200 ° C and purified by Gilson Preparative HPLC to yield 8.4 mg of the title compound (12.7%). LC / MS = m / z 456.2 [M + H]. Retreat time: 1.39 min.
EXAMPLE 227 341 - (Ethylsulfonyl) -4-piperidini.1-546- (propylamino) -3-pyridin-1H-indol-7-carboxamide trifluoroacetate To a solution of 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboxamide (110 mg, 0.27 mmol) in dioxane (2.0 ml) and H20 (0.7 ml ) were added (6-fluoro-3-pyridinyl) boric acid (151 mg, 1.08 mmol), polybasic carbonate (298 mg, 2.16 mmol) and irraki (phenylphenylphosphine) palladium (0) (31 mg, 0.026 mmol) . The reaction was carried out in the microwave for 20 minutes at 150 ° C. Then, the reaction was quenched with EtOAc and brine and purified by flash chromatography to give 50 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 / - / -indole-7-carboxamide (43%).
A 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (6-fluoro-3-pyridinyl) -1 / - / - indole-7-carboxamide (50 mg, 0.116 mmol) is added propylamine (1 ml) and DMF (0.3 ml). The resulting mixture was reacted in a microwave for 5 h at 200 ° C and purified by Gilson Preparative HPLC to yield 24.5 mg of the title compound (36.2%). LC / MS = m / z 470.2 [M + H]. Retreat time: 1.49 min.
EXAMPLE 228 Trifluoroacetate of 341 ethylsulfonH) -4-piperidinyl1-5464 (1-methylethiDaminol-3-pyridinyl) -1H-indole-7-carboxamide The title compound was prepared according to the general trifluoroacety procedure of 5-. { 6- [Ellyl (meily) amino] -3-pyridinyl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, susíítuyendo dimelilamina by 2-propanamina (64.3 mg, 1 mmol) to produce 9.8 mg of the title compound (14.5%). LC / MS = m / z 470.4 [M + H]. Retreat time: 1.52 min.
EXAMPLE 229 3414-ethylsulfonyl) -4-piperidinin-546-f4-morpholinyl) -3-pyridinin-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 5-. { 6- [ethyl (methyl) amino] -3-pyridinyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, substituting dimethylamine for morpholine (1 ml) to yield 40.1 mg of the title compound (69.5%). LC / MS = m / z 498.6 [M + H]. Retreat time: 1.44 min.
EXAMPLE 230 341 - (Ethylsulfonyl) -4-piperidinyl-5454 (methylamino) methi.1-3-thienyl) -1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 - / - indole-7-carboxamide (20 mg, 0.045 mmol) in methanol (1.5 ml) and methylene chloride (1.5 ml) was added methylamine (0.13 ml). The resulting mixture was stirred at room temperature for 2 h followed by the addition of sodium telrahydridoboralo (9.18 mg, 0.27 mmol). She stirred at room temperalure for 1 h. All the solvent was evaporated and then purified by Gilson Preparative HPLC to give 12.4 mg of the title compound (48%). LC / MS = m / z 461.4 [M + H]. Retreat time: 1.48 min.
EXAMPLE 231 341- (Ethylsulfonyl) -4-piperidinyl] -5- (54f (1-methylethyl) aminolmethyl} -3-thienyl-1H-indol-7-carboxamide trifluoroacetate.
To a solution of 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- (5-formyl-3-fienyl) -1H-indole-7-carboxamide (30 mg, 0.067 mmol) in melanol (0.5 ml) and methylene chloride (1 ml) was added 2-propanamine (23.8 mg, 0.402 mmol). The resulting mixture was stirred for 2.5 h followed by an addition of sodium telrahydrate borate (15.2 mg, 0.402 mmol). The reaction was stirred at room temperature for 1 h. All the solvent was evaporated and then purified by Gilson Preparative HPLC to give 19.5 mg of the title compound (48.3%). LC / MS = m / z 489.2 [M + H]. Retreat time: 1.54 min.
EXAMPLE 232 3- [1 - (Ethylsulfonyl) -4-piperidin-p-545- (1-pyrrolidinylmethyl) -3-thienin-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (30 mg, 0.067 mmol) in methanol (0.5 ml) and methylene chloride (1 ml) was added pyrrolidine (85 mg, 1195 mmol). The resulting mixture was stirred for 1.5 h followed by an addition of sodium triacerate-iborohydride (85 mg, 0.402 mmol). The reaction was stirred at room temperature for 2 h. All the solvent was evaporated and then purified by Gilson Preparative HPLC to give 22.5 mg of the title compound (54.6%). LC / MS = m / z 501.4 [M + H]. Retreat time: 1.52 min.
EXAMPLE 233 Trifluoroacetate of 5454 (ethylamino) metM1-3-thienyl) -3- [1 - (ethylsulfonyl) -4- p -peridinyl-1H-indol-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (30 mg, 0.067 mmol) in melanol (3 ml) and methylene chloride (3 ml) was added ethylamine (0.2 ml, 0.402 mmol). After 2 h, sodium tetrahydridoborate (27 mg, 0.402 mmol) was added and the mixture was allowed to stand for 1 h. All the solvent was evaporated and then purified by Gilson Preparative HPLC to give 15 mg of the title compound (38%). LC / MS = m / z 475.4 [M + H]. Retreat time: 1.52 min.
EXAMPLE 234 Trifluoroacetate (salt) of 341- (Ethylsulfonyl-piperidinyl-1-545 - ((r (1R.-2-hydroxy-1-methylethylamino) methyl) -3-thienyl-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacety of 5-. { 5 - [(ethylamino) methyl] -3-thienyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, substituting ethylamine for (2R) -2-amino-1-propanol (0.031 ml, 0.402 mmol) to yield 16.2 mg of the composed of the title (39.1%). LC / MS = m / z 505.4 [M + H]. Retreat time: 1.42 min.
EXAMPLE 235 Trifluoroacetate of 341 - (ethylsulfonyl) -4-piperidin-p-54541 -piperidinylmethyl-3-thienin-1H-indol-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1 / - / - indole-7-carboamide (30 mg, 0.067 mmol) in dimethyl sulfoxide (2 ml) was added piperidine (70 mg, 0.670 mmol). The resulting mixture was allowed to stand for 2 h and then sodium triacetoxyborohydride (142 mg, 0.670 mmol) was added. This mixture was stirred at room temperature overnight and then purified by Gilson Preparative HPLC to give 16.2 mg of the title compound (38.5%). LC / MS = m / z 514.8 [M + H]. Time of laugh .: 1.37 min.
EXAMPLE 236 341-Ethylsulfoni-4-piperidinyl-545- (4-morpholinylmethyl) -3-thienyl-1-H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (1-pyrrolidinylmethyl) -3-thienyl] -1H-indole trifluoroacetate. 7-carboamide, substituting piperidine for morpholine (70 mg, 0.670 mmol) to yield 6.3 mg of the title compound (14.9%). LC / MS = m / z 517 [M + H]. Retreat time: 1.54 min.
EXAMPLE 237 Trifluoroacetate of 341-f-ethylsulfonyl-M-piperidinip-5454.methylamino-methy-3-furanyl) -1H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-telramethyl-1, 3,2-dio? Aborolan-2-yl) -1H-indole- 7-carboamide (50 mg, 0.11 mmol) in dioxane (3.0 ml) and H20 (1.0 ml) were added 4-bromo-2-furancarbaldehyde (58 mg, 0.33 mmol), potassium carbonate (89.8 mg, 0.66 mmol). ) and tetrakis (triphenylphosphine) palladium (0) (14 mg, 0.012 mmol). The reaction was heated in the microwave for 20 min at 150 ° C to give 58 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-furanyl) -1 / - / - indol-7-carboamide. To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-furanyl) -1H-indole-7-carboxamide (20.6 mg, 0.05 mmol) in DMSO (0.5 ml) methylamine (0.24 ml, 0.5 mmol) in 2 M telrahydrofuran was added. The resulting mixture was reacted for 6 h, followed by an addition of sodium triacetoxyborohydride. Then, it was purified by Gilson Preparative HPLC to yield 5.5 mg of the title compound (32.8%).
LC / MS = m / z 459.4 [M + H]. Retreat time: 1.42 min.
EXAMPLE 238 3-H- (Ethylsulfonyl-4-piperidinopyr-5- (541- (1-pyrrolidinyl.etip-3-thienyl) -1H-indol-7-carboxamide trifluoroacetate.
To a solution of 3- [1- (ethylsulfonyl) -4-p-peridinyl] -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1 / - / -indole-7-carboxamide (300 mg, 0.65 mmol) in dioxane (9 ml) and H20 (3 ml) were added 1- (4-bromo-2-thienyl) ethanone (400 mg, 1.95 mmol), potassium carbonate (538 mg, 3.90 mmol) and tetrakis (triphenylphosphine) palladium (0) (70 mg, 0.060 mmol). The reaction was carried out in the microwave at 150 ° C for 20 min. Aqueous work-up was performed using EtOAc and H20 followed by addition to the crude product of MeOH (3 ml). The desired product was precipitated and filtered to give 230 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-propanoyl-3-thienyl) -1 / - / - indole-7-carboamide (77%). To a solution of 5- (5-acetyl-3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 / - / - indole-7-carboamide (50 mg, 0.11 mmol) in DMF (0.8 ml) and acetic acid (0.2 ml) were added pyrrolidine (30.92 mg, 0.44 mmol) and N, N- dimethylformamide (30 mg, 0.44 mmol). The reaction mixture was reacted in a microwave for 20 min at 150 ° C. Then, the results were purified twice by Gilson Preparative HPLC to give 3.7 mg of the title compound (5.3%). LC / MS = m / z 515.4 [M + H]. Retreat time: 1.62 min.
EXAMPLE 239 341 - (Ethylsulfonyl) -4-piperidinyl-545- (1-pyrrolidinylmethyl-2-thienHl-1 H -indole-7-carboxamide trifluoroacetate.
A 3- [1 - (Ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-2-thienyl) -1H-indole-7-carboxamide (40 mg, 0.09 mmol) in dimethyl sulfoxide (0.5 ml) is added 2 M pyrrolidine (0.074 ml, 0.90 mmol). The resulting mixture was allowed to stand for 6 h followed by an addition of sodium triacetoxyborohydride (233 mg, 9.90 mmol). Then, it was allowed to stand for 2 h and then purified by Gilson Preparative HPLC to give 6.5 mg of the title compound (11.7%).
LC / MS = m / z 515.4 [M + H]. Time of laugh .: 1.62 min.
EXAMPLE 240 5454 trifluoroacetate (dimethylamino.metip-2-thienyl.) - 341-.ethylsulfonyl) -4- piperidinyl-1H-indole-7-carboxamide A 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5-formyl-2-lienyl) -1 H -indole-7-carboamide (35 mg, 0.09 mmol) in dimethylsulfohydrate (0.5 ml) was added 2 M dimethylamine (0.4 ml, 0.90 mmol). The resulting mixture was allowed to stand for 6 h followed by an addition of sodium friacefo-iborohydride (233 mg, 9.90 mmol). Then, it was allowed to stand for 2 h and then purified by Gilson's Preparative HPLC to give 17.8 mg of the title compound (33.6%). LC / MS = m / z 475.2 [M + H]. Retreat time: 1.53 min.
EXAMPLE 241 3-RI-Ethylsulfonyl) -4-piperidinyl-1-545- [(propylamino.-methyl-2-thienyl) -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5-. { 5 - [(dimethylamino) meily] -2-ynyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, susilating 2M dimellylamine by propylamine (0.064 ml, 0.90 mmol) to yield 8.9 mg of the title compound (16.4%) . LC / MS = m / z 487.2 [M + H]. Retreat time: 1.80 min.
EXAMPLE 242 5454.dietylamino) metip-2-thienyl) -341- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5-. { 5 - [(dimethylamino) methyl] -2-thienyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, suspending 2 M dimethylamine per diethylamine (0.081 ml, 0.90 mmol) to yield 16.6 mg of the title compound (29.9%). LC / MS = m / z 502.0 [M + H]. Time of laugh: 1.71 min.
EXAMPLE 243 341-fetylsulfonyl) -4-piperidinin-5454r (2-methylpropyl) amino] methyl) -2-thienyl) -1H-indole-7-carboxamide trifluoroacetate A 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5-formyl-24-eneyl) -1 H -indole-7-carboamide (30 mg, 0.09 mmol) in dimethylsulfoxide (0.5 ml) was added 2-methyl-1-propanamine (0.068 ml, 0.90 mmol). The resulting mixture was allowed to stand for 6 hours followed by an addition of sodium triacerate-iborohydride (233 mg, 9.90 mmol). Then, it was allowed to stand for 2 h and then purified by Gilson Preparative HPLC to give 2.7 mg of the title compound (4.9%). LC / MS = m / z 501.4 [M + H]. Retreat time: 1.79 min.
EXAMPLE 244 5- (54f (2,2-Dimethylpropyl) amino-1-methyl) -3-furanyl) -341- (ethylsulfonyl) -4-piperidinyl-1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1 / - - indole-7-carboxamide (50 mg, 0.11 mmol) in dioxane (3.0 ml) and H2O (1.0 ml) were added 4-bromo-2-furancarbaldehyde (58 mg, 0.33 mmol), potassium carbonate (89.8 mg, 0.66 mmol) ) and tetrakis (triphenylphosphine) palladium (0) (14 mg, 0.012 mmol). The reaction was heated in the microwave for 20 min at 150 ° C to give 58 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-furanl) -1 / - / - indole-7-carboxamide. To 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-furanyl) -1 H -indole-7-carboxamide (60 mg, 0.14 mmol) was added 2, 2-dimethyl. -1-Propanamine (60 mg, 0.14 mmol) in dimethyl sulfoxide (0.5 mL) and 2,2-dimethyl-1-propanamine (122 mg, 1.40 mmol) was added. The resulting mixture was allowed to stand for 6 h followed by an addition of sodium triacedoxyborohydride (233 mg, 9. 90 mmol). Then, it was left to stand for 2 hours and then purified by Gilson's Preparative HPLC to give 23.8 mg of the title compound (27.7%). LC / MS = m / z 501.1 [M + H]. Retreat time: 1.67 min.
EXAMPLE 245 3-H- (Ethylsulfonyl) -4-piperidinip-5- (54r (2-methylpropyl) amino-methyl) -3-furanyl) -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 5- (5- {[[(2,2-dimethylpropyl) amino] -methyl} -3-furanyl) -3- [1- (eylsulfonyl) trifluoroacetate. ) -4-piperidinyl] -1H-indole-7-carboxamide, suspending 2,2-dimethy1-propanamine with 2-meityl-1-propanamine (102.4 mg, 1.4 mmol) to yield 31.7 mg of the title compound (37.7%). LC / MS = m / z 487.2 [M + H]. Retreat time: 1.44 min.
EXAMPLE 246 5- (54f (cyclopentylmethyl) aminomethyl) -3-furanyl) -341- (ethylsulphonyl-4-piperidinyl] -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5-. {[[(2,2-dimethylpropyl) amino] methyl] -3-furanl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, substituting 2,2-dimethyl-1-propanamine for 1-cyclopenylammelanamine (137 mg, 1.4 mmol) to yield 22 mg of the title compound (25.1 %). LC / MS = m / z 513.4 [M + H]. Retreat time: 1.59 min.
EXAMPLE 247 341 Ethylsulfonyl-piperidinyl] -545- (1-pyrrolidinylmethyl) -3-furani trifluoroacetate] - 1H-indol-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 5- (5-. {[[(2,2-dylmethylpropyl) amino] methyl] -3-furanyl) -3 - [1- (ethylsulfonyl) -4-pperidyl] -1 H -indole-7-carboamide, substituting 2,2-dimethyl-1-propanamine for pyrrolidine (99.6 mg, 1.4 mmol) to produce 6 mg of the title compound (7.2%). LC / MS = m / z 485.2 [M + H]. Retreat time: 1.50 min.
EXAMPLE 248 545 - [(diethylamino) methyl-3-furanyl) -341- (ethylsulfonyl-piperidinin-1H-indol-7-carboxamide trifluoroacetate] The title compound was prepared according to the general procedure of 5- (5- {[[(2,2-dimethylpropyl) amino] methyl} -3-furanl] -3- [1-] trifluoroacetate. (ethylsulfonyl) -4-pichandinyl] -1H-indole-7-carboamide, substituting 2,2-dimethyl-1-propanamine for 2 M diethylamine (102.4 mg, 1.4 mmol) to yield 10.1 mg of the title compound (12 %). LC / MS = m / z 487.4 [M + H]. Retreat time: 1.50 min.
EXAMPLE 249 341 - (Ethylsulfonyl-piperidinip-54541-pyrrolidinylmethyl) -1,3-thiazole-2-i.1-1 H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-telramethyl-1, 3,2-dio? Aborolan-2-yl) -1 / - / -indole-7-carboamide (500 mg, 1.1 mmol) in dioxane (12 ml) and H20 (4 ml) were added 2-bromo-1,3-thiazole-5-carbaldehyde (634 mg, 3.3 mmol ), potassium carbonate (898 mg, 8.8 mmol) and tetrakis (triphenylphosphine) palladium (0) (210 mg, 0.181 mmol). The reaction was carried out in the microwave at 150 ° C for 20 min. Aqueous treatment was carried out to give the crude product. Then, the reaction was repeated in the microwave at 150 ° C for 30 min to give 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyM, 3-lilyzol-2-yl) -1 H -indole-7-carboxamide. To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-formyl-1,3-thiazol-2-yl) -1 / - / - indole-7-carboamide (25 mg, 0.06 mmol) in dimethyl sulfoxide (1 ml) was added pyrrolidine (0.05 ml, 0.60 mmol). The resulting mixture was agitated at room temperature for 6 h followed by an addition of triacele? -hydrochloride sodium (160 mg, 0.60 mmol). The mixture was stirred for one night and then purified by Gilson's Preparative HPLC to give 6.3 mg of the title compound (17.1%). LC / MS = m / z 502.2 [M + H]. Retreat time: 1.35 min.
EXAMPLE 250 341- (Ethylsulfonyl) -4-piperidinyl-1-54542-methyl-1- (1-pyrrolidinyl-propyl-3-thienyl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / -indole-7-carboxamide (50 mg, 0.11 mmol) in dioxane (3 ml) and H20 (1 ml) were added potassium carbonate (89.8 mg, 0.66 mmol), 1- (4-bromo-2-thienyl) - 2-methyl-1-propanone (87 mg, 0.33 mmol) and tetrakis (triphenylphosphine) palladium (0) (14 mg, 0.012 mmol). The reaction was carried out in a microwave for 20 min at 150 ° C followed by an aqueous treatment with EtOAc and H20. The reaction was then concentrated, dried with 1 N NaOH and it was exfoliated with ElOAc. The compound was purified by flash chromatography using DCM and MeOH to give 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (2-meitylpropanoyl) -3-ynyl] -1 / - / - indole 7-carboxamide. To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [5- (2-methylpropanoyl) -3-thienyl] -1 / - / - indole-7-carboxamide (40 mg, 0.02 mmol in EOH (1.5 ml) and acetic acid (0.2 ml) were added sodium cyanoborohydride (7.5 mg, 0J2 mmol) and pyrrolidine (0.03 ml, 0.3 mmol). The resulting mixture was reacted in a microwave for 40 minutes at 150 ° C. Then, all the solvent was evaporated, basified in sodium hydroxide and extracted with ethyl acetate. Then, it was purified by Gílson Preparative HPLC to give 13 mg of the title compound. LC / MS = m / z 543.4 [M + H]. Retreat time: 1.71 min.
EXAMPLE 251 341 - (Ethylsulfonyl) -4-piperidinyl-544- (1-pyrrolidinylmethyl) -1,3-thiazol-2-Ml-1 H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (2-formyl-1,3-yiazol-4-yl) -1 / - / - indol-7-carboxamide (42 mg, 0.094 mmol) in DMSO (2 ml) was added pyrrolidine (0.08 ml, 0.940 mmol). The resulting mixture was stirred at room temperature for 6 h followed by an addition of sodium triacetoxyborohydride. This mixture was stirred at room temperature overnight and then purified by Gilson Preparative HPLC to give 15.1 mg of the compound of the extract (26.1%). LC / MS = m / z 502.4 [M + H]. Time of laugh: 1.54 min.
EXAMPLE 252 54142- (dimethylamino) etp-1 H -pyrazol-4-yl) -3- | i - (ethylsulfonyl-piperidinyl-1 H -indole-7-carboxamide A solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / -indole-7-carboxamide (40 mg, 0.084 mmol), [2- (4-bromo-1H-pyrazol-1-yl) elyl] dimethylamine (27 mg, 0.126 mmol) and sodium carbonate (53 mg, 0.5 mmol) it was suspended in dioxane (750 μl) and water (250 μl). She was flushed with argon for 10 min before the addition of tetrakis (triphenylphosphine) palladium (0) (5 mg, 0.004 mmol). The resulting mixture was reacted in a microwave for 20 min at 120 ° C and then diluted with EtOAc (10 mL). The mixture was filtered through Celite and an aqueous wash was carried out. Then, it was purified by Gilson Preparative HPLC to give 6 mg of the title compound (15%). LC / MS = m / z 473.4 [M + H]. Retreat time: 1.48 min.
EXAMPLE 253 341 - (Ethylsulfonyl) -4-piperidinyl-54142- (1-pyrrolidinyl) etM1-1 H-pyrazol-4-yl) -1 H -indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (erylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-teremethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole -7-carboamide (40 mg, 0.090 mmol) in dioxide (750 μl) and H20 (250 μl) were added sodium carbonate (53 mg, 0.50 mmol) and 4-bromo-1- (2-chloroel). L) -1 / - / - pyrazole (26 mg, 0.126 mmol). The reaction mixture was flushed in an Argon aminosphere for 10 min before the addition of tetrakis (triphenylphosphine) palladium (0) (5 mg, 0.004 mmol). The reaction was heated in a microwave at 120 ° C for 20 min. Then, it was diluted with EtOAc (10 ml) and filtered through celile, followed by an aqueous phase. The compound was purified by Gilson Preparative HPLC to give 10 mg of 5- [1- (2-chloro-eyl) -1 / - / - pyrazol-4-yl] -3- [1- (allylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboamide (24%). To a solution of 5- [1- (2-chloro-eyl) -1 / - / - pyrazol-4-yl] -3- [1- (ethylsulphonyl) -4-piperidinyl] -1H-indole-7-carboxamide (33 mg, 0.071 mmol), pyrrolidine (60 μl, 0.710 mmol) and sodium iodide (5 mg, 0.018 mmol) was added to it with hydro-hydrofuran (500 μl) . This mixture was reacted in a microwave for 2 h at 130 ° C and an aqueous wash was carried out with ElOAc and water. Then, the organic layer was isolated and the solvent was removed. Then, it was purified by Gilson Preparative HPLC to give 11 mg of the title compound (25%). LC / MS = m / z 499.6 [M + H]. Retreat time: 1.34 min.
EXAMPLE 254 341 - (Ethylsulfonyl) -4-piperidinyl-5414244-morpholinyl) etip-1 H-pyrazol-4-yl) -1 H -indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 1- [2- (1-pyrrolidinyl) etl] -1 H -pyrazol-4-yl} -1 H-Indole-7-carboxamide, substituting pyrrolidine for morpholine (70 μl, 0.71 mmol) to produce 15 mg of the compound of the titulus (34%). LC / MS = m / z 515.4 [M + H]. Time of laugh .: 1.46 min.
EXAMPLE 255 341 Ethylsulfonyl-piperidinin-541 24 (2-hydroxyethyl) aminoethyl) -1H-pyrazol-4-yl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-teremethyl-1, 3,2-dioxaborolan-2-yl) -1 / - / - indole -7-carboxamide (40 mg, 0.090 mmol) in dioxane (750 μl) and H20 (250 μl) were added sodium carbonate (53 mg, 0.50 mmol) and 4-bromo-1- (2-chloroethyl) -1 H -pirazole (26 mg, 0.126 mmol). The reaction mixture was flushed in an Argon's atmosphere for 10 min. After the addition of leirachis (l-phenylphenyl) palladium (0) (5 mg, 0.004 mmol). The reaction was heated in a microwave at 120 ° C for 20 min. Then, it was diluted with ElOAc (10 ml) and filtered through celite, followed by an aqueous treatment. The compound was purified by Gílson Preparative HPLC to give 10 mg of 5- [1- (2-chloroethyl) -1H-pyrazol-4-yl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide (24%). A solution of 5- [1- (2-chloro-eyl) -1 H -pyrazol-4-yl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide ( 20 mg, 0.043 mmol), 2-aminoethanol (26 mg, 0.43 mmol) and sodium iodide (5 mg, 0.022 mmol) in telrahydrofuran (1 ml) was reacted in a microwave for 2 h at 130 ° C. Then, the tetrahydrofuran was removed and the mixture was given an aqueous wash of EtOAc and water. Then, the organic layer was separated and all the solvent was removed. Then, the mixture was purified by Gilson Preparative HPLC to give 8 mg of the title compound (31%). LC / MS = m / z 489.2 [M + H]. Retreat time: 1.40 min.
EXAMPLE 256 Trifluoroacetate of 541-f2- (butylamino) etn-1H-pyrazol-4-? L) -341- (ethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxy-ethyl) amino] eyl}. -1 H-pyrazol-4-yl) -1 H -indole-7-carboxamide, substituting the 2-aminoenolol for 1-buanamine (31 mg, 0.43 mmol) to yield 7 mg of the title compound (26%). LC / MS = m / z 499.4 [M + H]. Retreat time: 1.39 min.
EXAMPLE 257 Trifluoroacetate of 541424cyclobutylamino) etip-1 H-pyrazol-4-yl > -341- (Ethylsulfonyl-4-piperidin-p-1H-indol-7-carboxamide) The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxyethyl) amino] ethyl trifluoroacetate. -1 H-pyrazol-4-yl) -1 H -indole-7-carboxamide, substituting 2-aminoelanol for cyclobutamine (31 mg, 0.43 mmol) to yield 10 mg of the title compound (38%). LC / MS = m / z 501.4 [M + H]. Retreat time: 1.48 min.
EXAMPLE 258 Trifluoroacetate of 541- (24-2- (diethylamino) etipamino) ethyl.-1 H-pyrazol-4-Ml-341 - (ethylsulfonyl) -4-piperidinin-1 H-indol-7-carboxamide The thioule compound was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (1 -. {2 - [(2-hydroethyl) amino] ethyl trifluoroacetate. .) -1 H-pyrazole-4-yl) -1 H -indole-7-carboamide, substituting 2-aminoethanol for N, N-diethyl-1,2-ethanediamine (50 mg, 0.43 mmol) for produce 12 mg of the title compound (42%). LC / MS = m / z 545.2 [M + H]. Retreat time: 1.25 min.
EXAMPLE 259 3- [1 - (Ethylsulfonyl) -4-piperidinin-5-f-1424 (1-methylethyl) amino] ethyl) -1 H -pyrazol-4-yl) -1 H -indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxyethyl) amino] ethyl trifluoroacetate .) -1 H-pyrazol-4-yl) -1H-indole-7-carboxamide, substituting 2-aminoethanol for 2-propanamine (25 mg, 0.43 mmol) to yield 9 mg of the title compound (35% ). LC / MS = m / z 487.2 [M + H]. Retreat time: 1.47 min.
EXAMPLE 260 341 - (Ethylsulfonyl-4-piperidinium-5- (1-2- (2-methylpropyl) aminoethyl) -1H-pyrazol-4-yl) -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxyethyl) amino] trifluoroacetyl. 1.) -1H-pyrazol-4-yl) -1 H -indole-7-carboxamide, suspending 2-aminoelanol for 2-methyl-1-propanamine (31 mg, 0.43 mmol) to yield 8 mg of the composed of the tíulo (30%). LC / MS = m / z 501.2 [M + H]. Time of laugh: 1.45 min.
EXAMPLE 261 5- (1 2-f (cyclopentylmethyl) aminoethyl) -1 H -pyrazol-4-yl) -3- f 1 - (ethylsulfonyl) -4-piperidinin-1 H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelaio of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydro? Yly) amino] elil .) -1 H -pyrazol-4-yl) -1 H -indole-7-carboamide, suspending 2-aminoelanol for cyclopentalamine (37 mg, 0.43 mmol) to yield 11 mg of the title compound (40% ). LC / MS = m / z 513.4 [M + H]. Retreat time: 1.47 min.
EXAMPLE 262 341 - (Ethylsulfonyl) -4-piperidinin-544- (methyloxy) -3- (1-pyrrolidinylmethyl) phen-1H-indole-7-carboxamide trifluoroacetate To a solution of 2- (meiílo? I) -5- (4,4,5,5-eetramethyl-1, 3,2-dioxaborolan-2-yl) benzaldehyde (610 mg, 2.33 mmol) in dioxane (19 ml ) and H 2 O (6.3 ml) were added 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide (963 mg, 2.33 mmol) and sodium carbonate (1.48 g, 13.9 mmol). After washing abundantly with Argon for 10 min, tetrakis (phenylphenylphosphine) palladium (0) (134 mg, 0.166 mmol) was added. The reaction was heated in the microwave at 120 ° C for 120 min. The compound was purified by flash chromatography using DCM and MeOH to give 632 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-formyl-4- (methyl] i) phenyl] -1H-indole -7-carboxamide (58%). A solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-formyl-4-] (methyl? i) phenyl] -1H-indole-7-carbo-amide (50 mg, 0J07 mmol), pyrrolidine (45 μl, 0.214 mmol), zinc chloride (10 mg, 0.054 mmol) and sodium cyanoborohydride (7 mg , 0J07 mmol) in methanol (5 ml) was stirred at room temperature for 2 h. To this mixture was added a normal 0J solution of sodium hydroxide in water (2 ml). Then, the methanol was evaporated. The aqueous phase was extracted three times with EtOAc (5 ml). Then, the organic phase was washed twice with brine (5 ml). Then, all the solvent was removed. The mixture was purified by Gilson Preparative HPLC to give 9 mg of the title compound (13%). LC / MS = m / z 525.6 [M + H]. Retreat time: 1.67 min.
EXAMPLE 263 5434 (dimethylamino) methyl-4- (methyloxy) phenyl] -341- (ethylsulfonyl) -4-piperidinyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 2- (methyloxy) -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) benzaldehyde (610 mg, 2.33 mmol) in dioxane (19 ml) and H20 (6.3 ml) was added 5-bromo-3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (963 mg, 2.33 mmol) and sodium carbonate (1.48 g, 13.9 mmol). After washing abundantly with Argon for 10 min, tetrakis (phenylphosphine) palladium (0) (134 mg, 0J66 mmol) was added. The reaction was heated in the microwave at 120 ° C for 120 minutes. The compound was purified by flash chromatography using DCM and MeOH to give 632 mg of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3-formyl-4- (melyloxy) phenyl] -1H-indole-7 -carboxamide (58%). A solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [3-formyl-4- (methyloxy) phenyl] -1H-indole-7-carboxamide (50 mg, 0.214 mmol), dimethylamine (107 μl, 0.214 mmol), zinc chloride (10 mg, 0.054 mmol) and sodium cyanoborohydride (7 mg, 0J07 mmol) in methanol (5 ml) was stirred at ambient temperature for 2 h. To this mixture was added a normal 0J solution of sodium hydroxide in water (2 ml). Afterwards, he evaporated. The aqueous phase was extracted three times with EtOAc (5 ml). Then, the organic phase was washed twice with brine (5 ml). Then, all the solvent was removed. The mixture was purified by Gilson Preparative HPLC to give 4 mg of the title compound (6.1%). LC / MS = m / z 499.4 [M + H]. Retreat time: 1.56 min.
EXAMPLE 264 341 - (Ethylsulfonyl-piperidinyl-544- (methyloxy) -3- (4-morpholinylmethyl) phenyl-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5- [3 - [(dimethylamino) methyl] -4- (methyloxy) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, susliluding dimellylamine by morpholine (20 μl, 0.214 mmol) to yield 12 mg of the title compound (17%). LC / MS = m / z 541.6 [M + H]. Retreat time: 1.69 min.
EXAMPLE 265 3- [1- (Ethylsulfonyl) -4-piperidinyl-5434r (1-methylethyl) amino] methyl) -4- (methyloxy) phenin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 5- [3 - [(dimethylamino) methyl] -4- (methyl? I) phenyl] -3- [1- (ethylene sulfonyl) -4- piperidinyl] -1H-indol-7-carboamide, substituting dimethylamine for 2-propanamine (15 μl, 0.214 mmol) to yield 16 mg of the title compound (24%). LC / MS = m / z 513.2 [M + H]. Retreat time: 1.62 min.
EXAMPLE 266 341 - (Ethylsulfonyl) -4-piperidinyl-1-5- [34 (methylamino) methi.1-4- (methyloxy) fenip-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 5- [3 - [(dimethylamino) meily] -4- (meloxy) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] trifluoroacetate] -1H-Indole-7-carboamide, suspending the dimethylamine by methylamine (50 μl, 0.214 mmol) to yield 10 mg of the compound of the amide (16%). LC / MS = m / z 485.2 [M + H]. Time of laugh .: 1.57 min.
EXAMPLE 267 5434r.2.2-dimethylpropyl) amino-1-methyl-(methyloxy) phenyl] -3- [1 - (ethylsulfonyl-piperidinip-1 H -indole-7-carboxamide trifluoroacetate] The title compound was prepared according to the general procedure of trifluoroacetate of 5- [3 - [(dimethylamino) meily] -4- (mellyloxy) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboamide, suspending the dimethylamine by 2, 2-dimethy1-1-propanamine (20 μl, 0.214 mmol) to yield 11 mg of the title compound (16%). LC / MS = m / z 541.2 [M + H]. Retreat time: 1.77 min.
EXAMPLE 268 3-ri- (Ethylsulfonyl) -4-piperidinin-5- (142-r (2-hydroxyethin (methyl) aminoethyl) -1H-pyrazol-4-yl.-1H-indol-7-carboxamide A solution of 5- [1- (2-chloroethyl) -1H-pyrazol-4-yl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (30 mg, 0.065 mmol), 2- (meilylamine) elanol (500 μl, 6.5 mmol) and sodium iodide (3 mg, 0.016 mmol) in tetrahydrofuran (1 ml) was reacted in a microwave for 2 h at 130 ° C. Aqueous evaporation was carried out on the resulting mixture. Then, this was purified by HPLC Preparafiva Gilson to give 9 mg of the thioule compound (17%). LC / MS = m / z 503.2 [M + H]. Time of laugh: 1.40 min.
EXAMPLE 269 3-f 1 - (Ethylsulfonyl) -4-piperidinyl-544-fluoro-3- [(methylamino-methylphenyl) -1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-fluoro-3-formylphenyl) -1H-indole-7-carboamide (16.0 mg, 0.035 mmol) in dichloromethane (1 ml) and meianol (1 ml) were added 2 M methylamine in THF (105 μl, 0.21 mmol) and 1 g of acélic acid. The mixture was stirred for 3 hours. Sodium tetrahydroate was added (8.4 mg, 0.21 mmol) and the mixture was stirred for 1 h. The mixture was concentrated and dissolved in dimellysulphonate (1.5 ml). Then, it was purified by Gilson Preparative HPLC to give 6.4 mg of the compound of the ileum (31.2%). LC / MS = m / z 473.4 [M + H]. Time of laugh: 1.50 min.
EXAMPLE 270 543,5-bisr (methylamino) methylphenyl) -341- (ethylsulfoni-4-piperidinyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 5- (3,5-diformylphenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (10 mg, 0.2 mmol) in dichloromethane (1 ml) and methanol (1 ml) were added methylamine (64 μl, 0.128 mmol) and 1 drop of acetic acid. The resulting mixture was stirred for 3 h at ambient temperature and then sodium tetrahydridoborate (5.1 mg, 0.128 mmol) was added. This was stirred for 1 h, then concentrated and purified by Gilson Preparative HPLC to give 3 mg of the title compound (23.4%). LC / MS = m / z 498.6 [M + H]. Retreat time: 1.17 min.
EXAMPLE 271 Trifluoroacetate of 543 - [(ethylamino) methyH-4-fluorophenyl) -3- | - (Ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-fluoro-3-formylfenyl) -1H-indole-7-carboamide (35 mg, 0.076 mmol) in dichloromelane (1 ml) and methanol (1 ml) were added 2 M ethylamine (230 μl, 0.46 mmol) and 1 drop of acetic acid. The mixture was stirred for 1 h at ambient temperature and then tetrahydrofuran (1 ml) was added. The mixture was stirred for 30 min followed by the addition of sodium tetrahydridoborate (17.5 mg, 0.46 mmol). The resulting mixture was stirred for a further 1 h, concentrated and purified by Gilson Preparative HPLC to give 20 mg of the triflate compound (43.8%). LC / MS = m / z 487.4 [M + H]. Time of laugh .: 1.46 min.
EXAMPLE 272 Trifluoroacetate (salt) of 341- (ethylsulfonyl) -4-piperidin-n-544-fluoro-3 - ((r2-hydroxy-1- (hydroxymethipetinamino) methyfenin-1 H -indole-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacelafo of 5-. { 3 - [(elylamino) methyl] -4-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide, suspending efilamine by 2-amino-1,3-propanediol (42 mg, 0.46 mmol) to yield 21 mg of the composed of the title (42.7%). LC / MS = m / z 533.2 [M + H]. Retreat time: 1.39 min.
EXAMPLE 273 Trifluoroacetate (salt) of 3-M4-ethyl-sulfonyl-4-piperidinip-544-fluoro-3- ((1 (1 S) -2-hydroxy-1-methyl-ethyl-amino) -methyl-phenyl-1-H-indol-7- carboxamide The title compound was prepared according to the general procedure of trifluoroacelale of 5-. { 3 - [(elylammon) methyl] -4-fluorophenyl} -3- [1- (alkylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, suspending eylamine by (2S) -2-amino-1-propanol (37 mg, 0.46 mmol) to yield 26 mg of the compound of the title (54.2%). LC / MS = m / z 517.2 [M + H]. Time of ret .: 1.44 EXAMPLE 274 5434 trifluoroacetate (cyclopropyllamine.metip-4-fluorophenyl) -341 • (ethylsulfonyl) -4-piperidinin-1H-indol-7-carboxamide The title compound was prepared according to the general Irifluoroacelalo procedure of 5-. { 3 - [(elylamino) meily] -4-fluorophenyl} -3- [1- (elylsulfonyl) -4-picperidinyl] -1H-indole-7-carboamide, substituting ethylamine for cyclopropylamine (32 mg, 0.46 mmol) to yield 23 mg of the compound of the amino acid (49.4%). LC / MS = m / z 499.6 [M + H]. Time of laugh: 1.75 min.
EXAMPLE 275 Trifluoroacetate of 5434 (cyclobutylamino) met.p-4-fluorophenyl) -341 - (ethylsulfonyl-piperidinyl-1H-indole-7-carboxamide The compound of the title was prepared according to the general procedure of ír if lu lu lu lu lu... { 3 - [(elylamino) methyl] -4-fluorophenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide, susilating elylamine by cyclobutamine (39 mg, 0.46 mmol) to yield 20 mg of the title compound (42%). LC / MS = m / z 513.2 [M + H]. Time of laugh: 1.58 min.
EXAMPLE 276 3-H-.ethylsulfonyl) -4-piperidinyl] -543- (1-pyrrolidinylmethyl) phenyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1 H -indole-7-carboamide (33 mg 0.74 mmol) in dichloromethane (0.5 mL) and methanol (0.5 ml) were added pyrrolidine (32 mg, 0.444 mmol) and 1 drop of acetic acid. The mixture was stirred for 2 min and then sodium hydrohydroboradic acid (17.8 mg, 0.444 mmol) was added. Then, it was stirred for one night, then it was concentrated and purified by Gilson Preparative HPLC to give 9.7 mg of the title compound (21.5%) LC / MS = m / z 495.4 [M + H]. Retreat time: 1.67 min.
EXAMPLE 277 543,5-bis [(ethylamino) metM1-phenyl) -341- (ethylsulfonyl) -4-pperidinyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 5- (3,5-diformyphenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (27 mg, 0.058 mmol) in dichloromethane (1.5 ml) and meianol (1.5 ml) were added ethylamine (31.4 mg, 0.696 mmol) and 1 drop of acetic acid. The resulting mixture was agitated for 2 h and then sodium tetrahydridoborate (13.2 mg, 0.348 mmol) was added. This was stirred for a further 50 min and then purified by Gilson Preparative HPLC to give 20 mg of the title compound (53.9%). LC / MS = m / z 526.6 [M + H]. Retreat time: 1.41 min.
EXAMPLE 278 543.5-bisf (dimethylamino) methenylphenyl trifluoroacetate > -341 - (Ethylsulfonyl) -4-piperidinyl-1H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formyl-5-mercaptophenyl) -1H-indole-7-carboxamide (34 mg, 0.058 mmol) in dichloromethane (1.5 ml) and melanol (1.5 ml) were added dimethylamine (31.4 mg, 0.696 mmol) and one drop of acetic acid. The resulting mixture was stirred for 2 h at room temperature and then sodium tetrahydridoboralo (13.2 mg, 0.348 mmol) was added. This was stirred for a further 30 min and then purified by Gilson Preparative HPLC to give 11 mg of the title compound (29.6%). LC / MS = m / z 526.6 [M + H]. Time of day: 1.27 min.
EXAMPLE 279 341 - (Ethylsulfonyl) -4-piperidinyl-1-543- (2-piperidinyl) phenyl-11-H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-pyridinyl] -5- (4,4,5,5-telramelyl-1, 3,2-dio? Aborolan-2-yl) -1H- indole-7-carboamide (46 mg, 0.1 mmol) in dioxane (2 ml) and H20 (0.7 ml) was added 2- (3-chlorophenyl) piperidine (46 mg, 0.2 mmol). Phasic carbonate (55 mg, 0.4 mmol) was added and, after degassing for 5 min, terachis (l-phenylphenyl) palladium (0) (5 mg, 0.5 mmol) was added. The resulting mixture was reacted in a 300W CEM microwave for 30 min at 160 ° C and then the solids were relieved by filtration. The solvent was evaporated and the solution was purified by Gilson Preparative HPLC to give 13.2 mg of the title compound (21.7%). LC / MS = m / z 495.4 [M + H]. Time of ret .: 1.76 EXAMPLE 280 54341- (Ethylamino) ethyl-1-phenyl) -341- (ethylsulfonyl) -4-piperidine-1H-indole-7-carboxamide trifluoroacetate A solution of 5- (3-acetylphenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (50 mg, 0.11 mmol), ethylamine (19.9 mg, 0.441 mmol) and sodium cyanoborohydride (30 mg, 0.441 mmol) in N, N-dimethylylformamide (0.8 ml) and acetic acid (0.2 ml) was reacted in a microwave for 20 min at 150 ° C. The reaction was purified by Gilson's Preparative HPLC to give 20.6 mg of the iodine compound (39%). LC / MS = m / z 483.2 [M + H]. Time of day: 1.67 EXAMPLE 281 Trifluoroacetate of 54341 - (dimethylamino) ethyHphenyl) -341 - (Ethylsulfonium-4-piperidinin-1H-indol-7-carboxamide 5- (3-Acetylphenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (50 mg, 0.11 mmol), dimethylamine (220 μL, 0.44 mmol) were dissolved and sodium cyanoborohydride (30 mg, 0.44 mmol) in N, N-dimethylformamide (400 μl) and acetic acid (100 μl). The resulting mixture was reacted in a 150 W Smith microwave for 20 min at 150 ° C. The reaction was purified by Gilson Preparative HPLC to give 14.6 mg of the title compound (22.2%). LC / MS = m / z 483.2 [M + H]. Ret Time: 1.63 EXAMPLE 282 341 - (Ethylsulfonyl-4-piperidiniH-543-fluoro-5- [(methylamino) methyphenyl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-picperidinyl] -5- (3-fluoro-5-formylphenyl) -1H-indole-7-carboamide (32 mg, 0.07 mmol) in dichloromethane (1.5 ml) and methanol (1.5 ml) were added 2 M methylamine in THF (210 μl, 0.42 mmol) and 1 drop of acetic acid. The mixture was stirred for 3 h at room temperature and then sodium tetrahydroborate (15 mg, 0.42 mmol) was added. This mixture was stirred for 1 hour, then concentrated and purified by Gilson Preparative HPLC to give 30 mg of the title compound (73.1%). LC / MS = m / z 473.6 [M + H]. Retreat time: 1.73 min.
EXAMPLE 283 Trifluoroacetate of 5434 (ethylamino) metill-5-fluorophenyl) -3- | - (Ethylsulfonyl) - 4-piperidin-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5--trifluoroacelate. { 3-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboamide, substituting methanamine for 2 M ethanamine in THF (210 μL, 0.42 mmol) to yield 6.5 mg of the title compound (15.5%). LC / MS = m / z 487.4 [M + H]. Retreat time: 1.64 min.
EXAMPLE 284 341 - (Ethylsulfonyl-4-piperidinip-543-fluoro-5- [(propylamino) methyphenyl) -1H-indol-7-carboxamide trifluoroacetate The compound of the invention was prepared according to the general procedure of trifluoroacelale of 3- [1- (allylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(melilamino) meily] phenyl} -1 H-Indole-7-carboxamide, suspending melanamine by propylamine (21 mg, 0.42 mmol) to produce 31 mg of the title compound (72%). LC / MS = m / z 501.4 [M + H]. Time of ret .: 1.54 EXAMPLE 285 341- (Ethylsulfonyl) -4-piperidiniri-5- (3-fluoro-54r (1-methylethyl) aminolmethyl) phenol, 1 H -indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-pperidinyl] -5--trifluoroacetyl. { 3-fluoro-5 - [(mellylamino) methyl] phenol} -1H-Indole-7-carboamide, suspending meaminamine with 2-propanamine (21 mg, 0.42 mmol) to yield 28.5 mg of the compound of the extract (66.2%). LC / MS = m / z 501.4 [M + H]. Time of laugh: 1.53 min.
EXAMPLE 286 341 - (Ethylsulfonyl) -4-piperidinyl-5- (3-fluoro-54f (2-methylpropyl) aminomethyl) phenyl) -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general trifluoroacety procedure of 3- [1- (ynylsulfonyl) -4-piperidin] -5-. { 3-fluoro-5 - [(melilamino) meily] phenyl} -1H-Indole-7-carboamide, suspending methanamine by 2-methyl-1-propanamine (21 mg, 0.42 mmol) to yield 10 mg of the title compound (22.7%). LC / MS = m / z 515.4 [M + H]. Retreat time: 1.72 min.
EXAMPLE 287 5434 (cyclobutylamino) methyl-1-5-fluorophenyl) -3- | i - (ethylsulphonyl) -4-piperidinyl-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(methylamino) methyl] phenyl} -1 H-indole-7-carboxamide, substituting methanamine for cyclobuylamin (21.5 mg, 0.42 mmol) to yield 33 mg of the title compound (75.2%). LC / MS = m / z 513.2 [M + H]. Retreat time: 1.50 min.
EXAMPLE 288 543 - [(dimethylamino) metin-5-fluorophenyl) -3-f1- (ethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide trifluoroacetate The compound of the compound was prepared according to the general procedure of trifluoroacelain of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(meitylamino) methyl] phenyl} -1H-Indole-7-carboxamide, suspending meaminamine by 2 M dimethylamine in THF (210 μL, 0.42 mmol) to yield 33.7 mg of the title compound (80.2%). LC / MS = m / z 487.2 [M + H]. Retreat time: 1.43 min.
EXAMPLE 289 341-Ethylsulfonyl, -4-pperidinyl] -543-fluoro-5- (1-pyrrolidinylmethyl) phenyl] -1H-indole-7-carboxamide trifluoroacetate The organo compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5--trifluoroacetyl. { 3-fluoro-5 - [(methylamino) meily] phenyl} -1 H-Indole-7-carboamide, suspending melanamine by pyrrolidine (20.4 mg, 0.42 mmol) to yield 18 mg of the title compound (41%). LC / MS = m / z 513.4 [M + H]. Retreat time: 1.63 min.
EXAMPLE 290 341-ethylsulfonyl) -4-piperidinip-543-fluoro-5- (4-morpholinylmethyl) phenol-1H-indole-7-carboxamide trifluoroacetate The compound of the title was prepared according to the general procedure of Irifluoroacelalo of 3- [1- (efylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(meitylamino) meilyl] phenyl} -1 H-Indole-7-carboxamide, suspending meaminamine by morpholine (22 mg, 0.42 mmol) to yield 22.9 mg of the compound of the amino acid (50.9%). LC / MS = m / z 529.4 [M + H]. Time of laugh: 1.47 min.
EXAMPLE 291 341 - (Ethylsulfonyl) -4-piperidinium-543-fluoro-541-piperidinylmethyl) phen.p-1H-indol-7-carboxamide trifluoroacetate The compound of the illole was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboxamide, substituting methanamine for piperidine (22 mg, 0.42 mmol) to yield 13.4 mg of the title compound (29.9%). LC / MS = m / z 527.6 [M + H]. Ret time: 1.62 EXAMPLE 292 Trifluoroacetate of 341- (et, ilsulfonyl) -4-pperidinium.1-54341- (methylamino) et.-phenyl) -1H-indol-7-carboxamide To a solution of 5- (3-acetylflienyl) -3- [1- (efylsulfonyl) -4-p, pperidyl] -1H-indole-7-carboxamide (20 mg, 0.044 mmol) in ethanol was they added salt methylamine hydrochloride and 1 g of concentrated hydrochloride. The mixture was reacted in a CEM microwave at 100 ° C for 10 min and then sodium tetrahydroborate added. The resulting mixture was reacted in a CEM microwave at 50 ° C for 5 min and then all the solvent was evaporated. It was redissolved in dimethyl sulfoxide and then purified by Gilson Preparative HPLC to yield 16.5 mg of the title compound (64.4%). LC / MS = m / z 469.4 [M + H]. Time of laugh: 1.45 min.
EXAMPLE 293 3-H- (Ethylsulfonyl-4-piperidinip-5- (3414 (1-methylethyl) aminoethyl) phenyl-1H-indol-7-carboxamide trifluoroacetate.
To a solution of 5- (3-acelylphenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indol-7-carboamide (20 mg, 0.044 mmol), in N, N-dimethylformamide ( 0.8 ml) and acetic acid (0.2 ml) were added 2-propanamine (75 μl, 0.88 mmol) and sodium cyanoborohydride (6 mg, 0.09 mmol). The mixture was reacted in a Smith microwave at 70 ° C for 1 h. The solid was relieved by filtration and then purified by Gilson Preparative HPLC to yield 9.4 mg of the compound of the extract (72.2%). LC / MS = m / z 497.4 [M + H]. Time of laugh .: 1.44 min.
EXAMPLE 294 341- (Ethylsulfonyl) -4-piperidinin-5- (3414 (2-methylpropyl) aminolethyl) phenyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 5- (3-acelylphenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (30 mg, 0.066 mmol), in elanol (1.2 ml) and acetic acid (0.3 ml) were added (2-methylpropyl) amine (101 mg, 1.98 mmol) and sodium cyanoborohydride (13.5 mg, 0.198 mmol). The mixture was reacted in a Smííh microwave at 70 ° C for 1 hour. All the solvent was evaporated and dimethyl sulfoxide was used to dissolve the solid. Then, it was purified by Gilson Preparative HPLC to yield 22.7 mg of the title compound (55.1%). LC / MS = m / z 511.2 [M + H]. Time of day: 1.52 min.
EXAMPLE 295 54341- (Cyclobutylamino) ethyl-1-phenyl) -341- (ethylsulfonyl) -4-piperidinyl] -1H-indol-7-carboxamide trifluoroacetate The compound of the compound was prepared according to the general procedure of 3- [1- (ethyl-sulphonyl) -4-piperidinyl] -5- (3- { 1 - [(2-meitylpropyl) amino] trifluoroacelale. ].) phenyl) -1H-indole-7-carboamide, susliluting (2-methylpropyl) amine by cyclobutylamine (101 mg, 1.98 mmol) to yield 29.1 mg of the compound of the amine (70.8%). LC / MS = m / z 509.4 [M + H]. Time of day: 1.52 min.
EXAMPLE 296 341- (ethylsulfonyl) -4-piperidinyl-54341- (1-pyrrolidinyl) etphenyl) -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelale of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (3- {1 - [(2-meitylpropyl) amino] eyl}. pheny1) -1H-indole-7-carboxamide, suspending (2-meitylpropyl) amine by pyrrolidine (101 mg, 1.98 mmol) to yield 29.2 mg of the illous compound (71%). LC / MS = m / z 509.4 [M + H]. Time of laugh .: 1.49 min.
EXAMPLE 297 341- (Ethylsulfoni-4-piperidinyl-543- (3-thiomorpholinyl) pheniH-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfoniyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dio? Aborolan-2-yl) -1H- Indole-7-carboamide (60 mg, 0.13 mmol) in dioe (1.5 ml) and water (0.5 ml) were added 3- (3-chlorophenyl) thiomorpholine (84 mg, 0.39 mmol) and potassium carbonate (107.6 mg, 0.78 mmol). This mixture was degassed for 5 min and then there was added terache (lypiphenylphosphine) palladium (0) (14.0 mg, 0.013 mmol). The resulting mixture was reacted in a microwave for 30 min at 160 ° C. The solid was filtered by filtration and all solvents were evaporated. The resulting solution was redissolved in dichloromethane and a separator was used to re-rinse the water. The mixture was concentrated to give the organic solvent and then purified by Gilson's Preparative HPLC to give 7.4 mg of the iodine compound (11%). LC / MS = m / z 513.4 [M + H]. Time of day: 1.54 EXAMPLE 298 341 - (Ethylsulfonyl-4-piperidine-p-54542-piperazine D-2-thienyl-1 H -indole-7-carboxamide trifluoroacetate.
To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7- carboxamide (60 mg, 0.13 mmol) in dioe (1.5 ml) and water (0.5 ml) were added 2- (5-bromo-2-lienyl) piperazine (102 mg, 0.39 mmol) and potassium carbonate (108 mg. 0.78 mmol). This mixture was degassed for 5 min and then tetrakis (triphenylphosphine) palladium (0) (15.0 mg, 0.013 mmol) was added. The resulting mixture was reacted in a microwave for 30 min at 160 ° C. The solid was removed by filtration and all solvents were evaporated. The resulting solution was redissolved in dichloromethane and a separator was used to remove the water. The mixture was concentrated to give the organic solvent and then purified by Gilson Preparative HPLC to give 29.1 mg of the title compound (36.4%). LC / MS = m / z 502.4 [M + H]. Time of ret .: 1.31 EXAMPLE 299 341 - (Ethylsulfonyl) -4-piperidinium-544- (2-piperazinyl) phenM1- 1 H -indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (2-piperazinyl) -2-thienyl] -1H-indol- 7-carboamide, substituting 2- (4-bromo-phenyl) piperazine (94 mg, 0.39 mmol) to yield 20.5 mg of the title compound (25.9%). LC / MS = m / z 496.4 [M + H]. Withdrawal time: 1.25 EXAMPLE 300 341 - (Ethylsulfonyl) -4-piperidinip-543- (2-piperazinyl) phen.p- 1 H -indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-indol- 7-carboxamide (60 mg, 0.13 mmol) in dioxane (1.5 ml) and water (0.5 ml) were added 2- (3-chlorophenyl) piperazine (63.7 mg, 0.325 mmol) and potassium carbonate (90 mg, 0.650 mmol) . This mixture was degassed for 5 min and then tetraqu (triphenylphosphine) palladium (0) (12 mg, 0.011 mmol) was added. The resulting mixture was reacted in a microwave for 30 min at 160 ° C. The solid was removed by filtration and all solvents were evaporated. The resulting solution was redissolved in dichloromethane and a separator was used to remove the water. The mixture was concentrated to give the organic solvent and then purified by Gilson Preparative HPLC to give 21.7 mg of the title compound (27.4%). LC / MS = m / z 496.4 [M + H]. Retreat time: 1.28 min.
EXAMPLE 301 341- (Ethylsulfonyl) -4-piperidinin-5- [6- (4-morpholinyl) -3-pyridazinin-1H-indole-7-carboxamide trifluoroacetate The compound of the compound was prepared according to the general procedure of trifluoroacety of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- (2-piperazinyl) phenyl] -1H-indole-7-carboxamide , suspending 2- (3-chlorophenyl) piperazine by 4- (6-chloro-3-pyridazinyl) morpholine (65 mg, 0.325 mmol) to yield 3.1 mg of the title compound (3.9%). LC / MS = m / z 499.6 [M + H]. Retreat time: 1.57 min.
EXAMPLE 302 341 - (Ethylsulfonyl) -4-piperidinyl-546- (1-pyrrolidinyl) -3-pyridazinyl-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (2-piperazinyl) phenyl] -1H-indole-7-carbo Amide, substituting 2- (3-chlorophenyl) piperazine for 3-chloro-6- (1-pyrrolidinyl) pyridazine (60 mg, 0.325 mmol) to yield 4.1 mg of the title compound (5.3%). LC / MS = m / z 483.2 [M + H]. Retreat time: 1.44 min.
EXAMPLE 303 341- (Ethylsulfonyl) -4-piperidinin-542- [(methylampty) methylphenyl) -1H-indol-7-carboxamide trifluoroacetate The compound of the thioule was prepared according to the general procedure of frifluoroacety of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3- (2-piperazinyl) phenyl] -1H-indole-7-carboxamide , susliluyendo 2- (3-chlorophenyl) piperazina by 1- (2-bromophenyl) -N-melilmeíanamina (65 mg, 0.325 mmol) to produce 14.6 mg of the title compound (19.8%). LC / MS = m / z 455.0 [M + H]. Retreat time: 1.57 min.
EXAMPLE 304 341- (Ethylsulfonyl) -4-piperidinin-5- (34r- (2-thienylmethyl) amino-1-methyl} -phenyl-1H-indol-7-carboxamide trifluoroacetate.
To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (44 mg, 0.1 mmol) in dichloromethane (2 ml) and methanol (2 ml) was added 1- (2-amino) melanamin (33.6 mg, 0.6 mmol) and 1 was acrylic acid. The mixture was stirred for 2 h and then sodium tetrahydridoboraio (22.8 mg, 0.6 mmol) was added. The resulting mixture was stirred for 1 h. It was then concentrated and redissolved in dimellysulfoxide (3 ml). Then, it was purified by Gilson Preparative HPLC to give 41.7 mg of the title compound (74.5%). LC / MS = m / z 537.2 [M + H]. Retreat time: 1.81 min.
EXAMPLE 305 3,414-ethylsulfonyl trifluoroacetate) -4-piperidinHl-543- (. {R (5-methyl-2-furanylmethamino) methyl) phenyl-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-ynylmethyl) amino] meily}. phenyl) -1H-indole-7-carboamide, suslfluating 1- (2-thienyl) methanamine by 1- (5-meityl-2-furanyl) meamyamine (32 mg, 0.6 mmol) to yield 29.3 mg of the compound of the title (54.7%). LC / MS = m / z 535.2 [M + H]. Retreat time: 1.74 min.
EXAMPLE 306 341 - (Ethylsulfonyl-piperidinyl-543- (fr (2R) -tetrahydro-2-furanylmethyl] amino) methyl) phenyl-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-lienylmethyl) amino] methyl]. pheny1) -1H-indole-7-carboxamide, substituting 1- (2-thienyl) methanamine for 1 - [(2R) -tetrahydro-2-furanyl] methanamine (31.5 mg, 0.6 mmol) to yield 36.9 mg of the title compound (70.3%). LC / MS = m / z 525.6 [M + H]. Retreat time: 1.63 min.
EXAMPLE 307 341 - (Ethylsulfonyl-4-piperidineHl-543 - ((r (2S-tetrahydro-2-furanmethylpamino) methylphenip-1H-indole-7-carboxamide trifluoroacetate.
The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-thienylmethyl) amino] methyl} phenyl. ) -1 H -indole-7-carboxamide, substituting 1 - (2-thienyl) meaminamine for 1 - [(2S) -etrahydro-2-furanyl] melanamine (31.5 mg, 0.6 mmol) to yield 39.2 mg of the compound of the compound (74.7%). LC / MS = m / z 525.6 [M + H]. Time of laugh .: 1.61 min.
EXAMPLE 308 5- (34r (2,2-Dimethylpropyl) aminolmethyl> phenyl) -341- (ethylsulphonyl) -4-piperidine-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-ynylmethyl) amino] -methyl] phenyl. ) -1 H -indole-7-carboamide, suspending 1 - (2-thienyl) methanamine for 2,2-dimethy1-propanamine (30.6 mg, 0.6 mmol) to yield 30.4 mg of the title compound (59.5%) ). LC / MS = m / z 511.4 [M + H]. Retreat time: 1.69 min.
EXAMPLE 309 341- (Ethylsulfonin-4-pyridinyl-5- (34r (2-methylbutyl) amino-1-methyl) -phenyl) -1H-indol-7-carboxamide To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboxamide (44 mg, 0.1 mmol) in dichloromethane (2 ml) and methanol (1 ml) were added 2-methyl-1-bulanamine (52 mg, 0.6 mmol) and 1 gola of acyl acid. This mixture was stirred for 2 h and then sodium tetrahydridoborate (22.8 mg, 0.6 mmol) was added. The resulting mixture was stirred for 1 h. Then, it was concentrated and redissolved in dimethyl sulfoxide (3 ml). Then, it was purified by Gilson Preparative HPLC to give 28.4 mg of the title compound (55.6%). LC / MS = m / z 511.4 [M + H]. Time of day: 1.71 EXAMPLE 310 3414-ethylsulfonyl) -4-piperidinin-543 - ((r (2S) -2-methylbutylamino) methyl) phenin-1 H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-meyylbuyl) amino] methyl} phenyl) - 1 H-indole-7-carboxamide, substituting 2-methyl-1-bilanamine for (2S) -2-methyl-1-bulanamine (52 mg, 0.6 mmol) to yield 30 mg of the title compound (58.7%). LC / MS = m / z 511.4 [M + H]. Ret Time: 1.68 EXAMPLE 311 341- (Ethylsulfonyl) -4-piperidinin-5434 (r (1R) -1.2.2- trmethylpropylamino) methyl.fenip-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-methylbutyl) amino] methyl} phenyl) - 1 H-indole-7-carboxamide, substituting 2-methyl-1-butanamine for (2R) -3,3-dimethyl-2-butanamine (60 mg, 0.6 mmol) to yield 24.5 mg of the compound of the extract (46.7 %). LC / MS = m / z 525.6 [M + H]. Time of day: 1.67 EXAMPLE 312 341 - (Ethylsulfonyl-4-piperidinyl-543-fluoro-5 - ((r (2S) -tetrahydro-2-furanylmethylamino) methyl) phenyl-1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-formylphenyl) -1H-indole-7-carboxamide (40 mg, 0.087 mmol) in dichloromethane (2 ml) and methane (1 ml) were added 1 - [(2S) -tetrahydro-2-furanyl] methanamine (53 mg, 0.525 mmol) and 2 drops of acetic acid. The resulting mixture was stirred for 2 h at room temperature followed by an addition of sodium tetrahydridoborate (20 mg, 0.525 mmol). This mixture was stirred for 30 min, then concentrated and purified by Gilson Preparative HPLC to give 26.6 mg of the title compound (46.6%). LC / MS = m / z 543.4 [M + H]. Time of laugh: 1.60 min.
EXAMPLE 313 341 - (Ethylsulfonyl) -4-piperidinin-543-fluoro-5 - ((r (2R) -tetrahydro-2-furanylmethylamino> methyl) phenan-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro) -2-furanylmeiyl] amino] .meiyl) phenyl] -1H-indole-7-carboamide, susliluting 1 - [(2S) -irahydro-2-furanyl] melanamine by 1 - [(2R) -elhydro- 2-furanyl] meaminamine (53 mg, 0.525 mmol) to yield 27.1 mg of the title compound (47.4%). LC / MS = m / z 543.4 [M + H]. Retreat time: 1.58 min.
EXAMPLE 314 543 - ((r (1S) -1,2-dimethylpropinamino) methyl) -5-fluorophenin-341- (ethylsulfonyl) -4-piperidin-1H-indol-7-carboxamide The aeuuium compound was prepared according to the general trifluoroacety procedure of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -leralhydro) -2-furanylmethyl] amino.methyl) phenyl] -1H-indole-7-carbo-amide, substituting 1 - [(2S) -teyrahydro-2-furanyl] melanamine for (2S) -3-methyl-2 -buíanamine (45 mg, 0.525 mmol) to produce 19.3 mg of the title compound (42%). LC / MS = m / z 529.6 [M + H]. Time of ret .: 1.65 EXAMPLE 315 Trifluoroacetate of 5-f3 - (([(1 R) -1,2-dimethylpropiHamino) methyl) -5-fluorophenin-341- (ethylsulfonyl) -4-piperidinyl] -1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -lehydro-2-trifluoroacetyl) -furanylmethyl] amino.} methyl) phenyl] -1H-indole-7-carboamide, susliluting 1 - [(2S) -lethhydro-2-furanyl] methanamine by (2R) -3-methyl-2-butanamine (45 mg, 0.525 mmol) to yield 19.5 mg of the title compound (34.9%). LC / MS = m / z 529.4 [M + H]. Retreat time: 1.82 min.
EXAMPLE 316 341 Ethylsulfonyl) -4-piperidinin-5- (3-fluoro-54 (1-methylpropyl) amino-1-methyl) -phenyl) -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino.} mell) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 2-butanamine (37 mg, 0.525 mmol ) to yield 27.7 mg of the title compound (50.6%). LC / MS = m / z 515.4 [M + H]. Retreat time: 1.63 min.
EXAMPLE 317 341 - (Ethylsulfonyl) -4-piperidinyl-1-543-fluoro-5 - ((r (1 S) -1,2.2-trimethyl-propylamino) methyl-phenyl-1 H -indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelale of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -elhydro-2 -furanylmethyl] amine.) melyl) phenyl] -1H-indole-7-carboamide, suspending 1 - [(2S) -yalhydro-2-furanyl] melanamine by (2S) -3,3-dimethy-2. -bumanamine (52 mg, 0.525 mmol) to produce 19.8 mg of the title compound (34.7%). LC / MS = m / z 543.4 [M + H]. Retreat time: 1.78 min.
EXAMPLE 318 3,414-ethylsulfonyl) -4-piperidinyl-trifluoroacetate 1-543-fluoro-5 - ((r (2S) -2-methylbutylamino) methylphenip-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino] methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for (2S) -2-methyl-1-bulanamine (45). mg, 0.525 mmol) to yield 23.3 mg of the compound of the extract (41.7%). LC / MS = m / z 529.4 [M + H]. Time of laugh .: 1.62 min.
EXAMPLE 319 341 - (Ethylsulfonyl) -4-piperidinyl-1-5- (3-fluoro-54f (2-methylbutyl) aminomethyl) phenyl) -1H-indole-7-carboxamide trifluoroacetate The compound of the title was prepared according to the general procedure of trifluoroacelaio of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -telrahydro-2 -furanylmethyl] amino.} .methyl) phenyl] -1H-indole-7-carboamide, suspending 1 - [(2S) -lethhydro-2-furanyl] methanamine by 2-methyl-1-butanamine (45 mg, 0.525 mmol) to yield 30.5 mg of the title compound (54.5%). LC / MS = m / z 529.4 [M + H]. Retreat time: 1.73 min.
EXAMPLE 320 341- (Ethylsulfonyl-piperidinyl-1-543-fluoro-5 - ((r (1 R) -1,2,2-trimethylpropyl] amino) methyl) phenyl-1 H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro) trifluoroacetate. -2-furanylmethyl] amino.} Methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for (2R) -3,3-dimethyl-2 -butamine (52 mg, 0.525 mmol) to produce 24.9 mg of the compound of the íílulo (43.6%). LC / MS = m / z 543.4 [M + H]. Time of laugh: 1.73 min.
EXAMPLE 321 5- (34f- (2,2-Dimethylpropyl) amino-methyl) -5-fluorophenyl) -3- l-4-ethyl-sulfonyl) -4-piperidinin-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino] methyl) phenyl] -1H-indole-7-carboamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 2,2-dimethyl-1-propanamine (45). mg, 0.525 mmol) to yield 14 mg of the title compound (25%). LC / MS = m / z 529.4 [M + H]. Retreat time: 1.79 min.
EXAMPLE 322 5- (34f (Cyclopropylmethyl) amino] methyl) -5-fluorophenyl) -3- [i- (ethylsulfonyl) -4-piperidinin-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amine.} methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 1-cyclopropylmethanamine (37 mg, 0.525 mmol) for produce 21.1 mg of the title compound (38.7%). LC / MS = m / z 513.4 [M + H]. Retreat time: 1.69 min.
EXAMPLE 323 5- (34r- (Cyclopentylmethyl-aminolmethyl) -5-fluorophenyl) -3-H- (ethylsulphonyl) -4-piperidinyl] -1H-indol-7-carboxamide trifluoroacetate The compound of the thioule was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -lethhydro} trifluoroacetyla. -2-furanylmethyl] amino.} .methyl) phenyl] -1H-indole-7-carboxamide, suspending 1 - [(2S) -yrahydro-2-furanyl] meamyamine by 1-cyclopenylmelanamine (52 mg, 0.525 mmol) to produce 21.6 mg of the title compound (37.9%). LC / MS = m / z 541.4 [M + H]. Retreat time: 1.82 min.
EXAMPLE 324 341 - Trifluoroacetate (ethylsulfoniumH-4-piperidinin-5- (3-fluoro-5- (f (tetrahydro-2 H -pyran-4-ylmethyl amino-1-methyl-> phenyl) -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-picperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino.} methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 1- (tetrahydro-2H-pyran-4-) il) methanamine (60 mg, 0.525 mmol) to yield 40.1 mg of the title compound (68.7%). LC / MS = m / z 557.4 [M + H]. Time of laugh: 1.54 min.
EXAMPLE 325 341 - (Ethylsulfonyl) -4-piperidiniH-5- (3-fluoro-54r (2-thienylmethyl) aminomethyl) phenyl-1H-indole-7-carboxamide trifluoroacetate The compound of the illole was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino.} methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 1- (2-thienyl) melanamine (59 mg, 0.525 mmol) to produce 24.4 mg of the compound of the extract (41.9%). LC / MS = m / z 555.4 [M + H]. Time of laugh: 1.67 min.
EXAMPLE 326 341 - (Ethylsulfonyl) -4-piperidinip-543-fluoro-5 (T2- (methyloxy.ethyl) amino) methyl) phenyl-1H-indol-7-carboxamide trifluoroacetate The thioule compound was prepared according to the general procedure of trifluoroacelaio of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -leralhydro-2) -furanylmethyl] amino] -methyl) phenyl] -1H-indole-7-carboxamide, suspending 1 - [(2S) -ethahydro-2-furanyl] methanamine by 2- (methyloxy) ethanamine (39 mg, 0.525 mmol) to produce 31 mg of the title compound (56.5%). LC / MS = m / z 517.2 [M + H]. Retreat time: 1.52 min.
EXAMPLE 327 341 - (Ethylsulfonyl-4-piperidinip-543-fluoro-54f3- (methyloxypropylmethyl) methylphenyl] -IH-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S)) trifluoroacetyl. -teirahydro-2-furanylmethyl] amino.} methyl) phenyl] -1H-indole-7-carboamide, suspending 1 - [(2S) -elhydro-2-furanyl] melanamine by 3- (melyl? i) -l-propanamine (46 mg, 0.525 mmol) to yield 27.3 mg of the title compound (48.7%). LC / MS = m / z 531.4 [M + H]. Retreat time: 1.54 min.
EXAMPLE 328 341 - (Ethylsulfonyl-4-piperidinip-5- (3-fluoro-54r (2-furanylmethyl) amino] methyl) phenyl-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2 -furanylmethyl] amino.} methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] methanamine for 1- (2-furanyl) methanamine (50 mg, 0.525 mmol) to yield 24.8 mg of the title compound (43.7%). LC / MS = m / z 539.4 [M + H]. Retreat time: 1.63 min.
EXAMPLE 329 341 - (Ethylsulfonyl-4-piperidinyl-5- (3-fluoro-54r (3-methylbutyl) amino] methyl) phenyl) -1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelain of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -elhydro-2-furanylmeiyl] amino.} .methyl) phenyl] -1H-indole-7-carboxamide, susliluting 1 - [(2S) -etrahydro-2-furanyl] meamyamine by 3-meityl-1-bulanamine (45 mg, 0.525 mmol) to yield 27.6 mg of the title compound (49.4%). LC / MS = m / z 529.4 [M + H]. Retreat time: 1.67 min.
EXAMPLE 330 341 - (Ethylsulfonyl) -4-piperidinyl-543-fluoro-5 - ((r (5-methyl-2-furanyl) methylamino} methyl) phenyl-1H-indole-7-carboxamide trifluoroacetate The compound of the illole was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(2S) -tetrahydro-2-trifluoroacetate. -furanylmethyl] amino] methyl) phenyl] -1H-indole-7-carboxamide, substituting 1 - [(2S) -tetrahydro-2-furanyl] meamyamine for 1- (5-methyl-2-furanyl) methanamine ( 58 mg, 0.525 mmol) to yield 28.3 mg of the title compound (48.8%). LC / MS = m / z 553.6 [M + H]. Retreat time: 1.78 min.
EXAMPLE 331 3- [1- (Ethylsulfonyl) -4-piperidinyl-5- (34r- (2-methylpropyl) amino-1-methyl-> phenyl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (allylsulfonyl) -4-p-peridinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (50 mg, 0.114 mmol) in dichloromethane (2 ml) and melanol (1 ml) were added 2-meityl-1-propanamine (70 μl, 0.683 mmol) and 2 drops of acetic acid. This mixture was stirred for 2 h at room temperature and then sodium tetrahydridoborate (26 mg, 0.683 mmol) was added. After 30 min, the mixture was concentrated, dissolved in dimethisulfoxide (2 ml) and purified by Gilson Preparative HPLC to give 19.8 mg of the title compound (61%). LC / MS = m / z 497.4 [M + H]. Time of ret .: 1.57 EXAMPLE 332 3414-ethyl-sulphonyl) -4-piperidin-iyr-543- (2-pyrrolidinyl) phenyl-1-H-indole-7-carboxamide trifluoroacetate A solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -1H-indole-7-carboxamide (70 mg, 0.151 mmol) and 2- (3-iodophenyl) pyrrolidine (70 mg, 0.456 mmol) in poisic carbonate (126 mg, 0.910 mmol) in dioxide (2 mL) and water (1 mL) was degassed during heating. 5 min. And telrachis (lypiphenylphosphine) palladium (0) (17 mg, 0.015 mmol) was added. The mixture was reacted in a CEM microwave for 20 min at 160 ° C. Then, the organic layers were separated and concentrated. Then, it was dissolved in dimethylsulphonate (1 ml) and purified by Gilson's Preparative HPLC to give 48 mg of the title compound (59.5%). LC / MS = m / z 481.0 [M + H]. Ret Time: 1.47 EXAMPLE 333 341 - (Ethylsulfonyl-piperidinyl-1-5-fluoro-5- (methylamino-methyl) phenyl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2-fluoro-5-formylphenyl) -1H-indole-7-carboxamide (40 mg, 0.087 mmol) in dichloromelane (2 ml) and melanol (1 ml) were added melanamin (262 μl, 0.524 mmol) and 1 drop of acetic acid. After stirring for 2 h at temperalura ambienle, sodium tetrahydridoborate (20 mg, 0.524 mmol) was added and left to stand for 30 min. Then, the mixture was purified by Gilson Preparative HPLC to give 12.3 mg of the title compound (58.6%). LC / MS = m / z 473.4 [M + H]. Ret time: 1.55.
EXAMPLE 334 3- [1-ethylsulfonyl) -4-piperidinin-542-fluoro-5- (propylamino) methyphenyl) -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1 H -indole-7-carboamide, substituting methanamine for propylamine (44 μl, 0.524 mmol) to yield 15.4 mg of the title compound (61.5%). LC / MS = m / z 501.4 [M + H]. Time of day: 1.55 EXAMPLE 335 341 - (Ethylsulfonyl) -4-piperidinyl-5- (2-fluoro-54f (2-methylpropyl.amino-1-methyl-phenyl) -1H-indole-7-carboxamide trifluoroacetate The compound of the extract was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5--trifluoroacetate. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboxamide, substituting methanamine for 2-methyl-1-propanamine (53 μL, 0.524 mmol) to yield 15 mg of the title compound (62.9%) LC / MS = m / z 515.4 [M + H]. Time of ret .: 1.55 EXAMPLE 336 5- (54r (2,2-dimethylpropyl) amino-1-methyl) -2-fluorophenyl) -3- p - (ethylsulfonyl-piperidinyl-1 H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(meitylamino) meily] phenyl} -1 H -indole-7-carboxamide, suspending meaminamine by 2,2-dimamethyl-1-propanamine (46 μl, 0.524 mmol) to yield 14.3 mg of the title compound (64.3%). LC / MS = m / z 530.2 [M + H]. Time of ret .: 1.59 EXAMPLE 337 545 - ((r (1S) -1,2-dimethylpropyl] amino) methyl) -2-fluorophenin-341- (ethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboamide, substituting methanamine for (2S) -3-methyl-2-butanamine (46 μl, 0.524 mmol) to yield 17.3 mg of the title compound (64.3%) LC / MS = m / z 529.4 [M + H]. Time of ret .: 1.69 EXAMPLE 338 545- ( { [(1R.-1,2-dimethylpropylamino) methyl) -2-fluorophenin-341- (ethylsulfonyl) -4-piperidinin-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboxamide, substituting methanamine for (2R) -3-methyl-2-butanamine (46 μl, 0.524 mmol) to yield 15 mg of the title compound (64.3%). LC / MS = m / z 529.4 [M + H]. Time of ret .: 1.70 EXAMPLE 339 5- (54f (cyclopropylmethyl) aminolmethyl) -2-fluorophenyl) -341- (ethylsulfonyl) -4-piperidini.1-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of Irifluoroacelalo of 3- [1- (ethylsulfonyl) -4-piperidinii] -5-. { 2-fluoro-5 - [(meitylamino) methyl] phenyl} -1H-Indole-7-carboamide, suspending melanamine with 2-methyl-1-butanamine (38 μL, 0.524 mmol) to yield 16.2 mg of the title compound (62.7%). LC / MS = m / z 513.4 [M + H]. Time of ret .: 1.57 EXAMPLE 340 341 - (Ethylsulfonyl-4-piperidinip-542-fluoro-5- (1-pyrrolidinylmethyl) phenin-1H-indol-7-carboxamide trifluoroacetate.
The title compound was prepared according to the general procedure of trifluoroacelale of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1H-Indole-7-carboamide, suspending melanamine by pyrrolidine (44 μl, 0.524 mmol) to yield 10 mg of the title compound (62.7%). LC / MS = m / z 513.4 [M + H]. Ret time: 1.62 EXAMPLE 341 3,414-ethyl-sulphonyl-4-piperidine-p-542-fluoro-5- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(methylamino) methyl] phenyl} -1H-indole-7-carboamide, substituting methanamine for morpholine (45 μL, 0.524 mmol) to yield 15 mg of the title compound (64.3%) LC / MS = m / z 529.4 [M + H]. Withdrawal time: 1.52 EXAMPLE 342 trifluoroacetate of 3-f 1 - (ethylsulfonyl) -4-piperidinium-5,5-fluoro-5 - ((r 2 - (methyloxy) ethylamino) methyl) phenyl-1H-indol-7-carboxamide To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (2-fluoro-5-formylphenyl) -1H-indole-7-carboamide (40 mg, 0.087 mmol) in dichloromean (2 ml) and melanol (1 ml) were added 2- (mellyloxy) ethanamine (54 μl, 0.524 mmol) and 1 drop of acetic acid. After stirring over the weekend at ambient temperature, sodium urea hydrazole (20 mg, 0.524 mmol) was added and allowed to stand for 30 minutes. Then, the mixture was purified by Gilson Preparative HPLC to yield 11.4 mg of the title compound (63%). LC / MS = m / z 517.2 [M + H]. Time of ret .: 1.57 EXAMPLE 343 341 - (Ethylsulfonyl) -4-piperidinyl-1-542-fluoro-54 (r3- (methyloxy) propylamino) methyl) phenan-1H-indol-7-carboxamide trifluoroacetate The compound of the thioule was prepared according to the general procedure of trifluoroacety of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [2-fluoro-5- ( { [2- (methyloxy) eyl] amino.} .methyl) phenyl] -1H-indole-7-carboxamide, susíiluyendo 2- (methyl? i) eíanamina by 3- (meíilo? i) -1 -propanamina (53 μl, 0.524 mmol) to produce 15 mg of the Compound of the element (64.5%) LC / MS = m / z 531.4 [M + H]. Time of day: 1.60 EXAMPLE 344 341-Ethylsulfonyl-4-piperidin-543- (1-methyl-2-pyrrolidinyl) phen-1H-indol-7-carboxamide trifluoroacetate To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3- (2-pyrrolidinyl) phenyl] -1H-indole-7-carboxamide (20 mg, 0.04 mmol), formaldehyde (9.5 ml. , 0.125 mmol) and sodium idiocelloxyborohydride in dichloromethane (2 ml) were added 2 drops of acetic acid. The resulting mixture was agitated for one night at room temperature. All the solvent was evaporated and the resulting product was redissolved in dimethyl sulfoxide (1 ml). Then, the mixture was separated twice by Gilson Preparative HPLC to yield 8.9 mg of the title compound (60.9%). LC / MS = m / z 495.4 [M + H]. Time of ret .: 1.54 EXAMPLE 345 341- (Ethylsulfonyl) -4-piperidinyl-5- (3424 (2-methylpropyl) amino] ethyl> phenyl) -1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylene sulfonyl) -4-pperidinyl] -5- (4,4,5,5-tetramethyl-1,2,2-dio? Aborolan-2) -yl) -1H-indole-7-carbo-amide (60 mg, 0.13 mmol), [2- (3-bromophenyl) ethyl] (2-meitylpropyl) amine (100 mg, 0.39 mmol) and potassium carbonate (108 mg , 0.780 mmol) in dioxide (2 ml) and water (0.7 ml). The resulting mixture was degassed for 5 min, and then terachis (triphenylphosphine) palladium (0) (14 mg, 0.013 mmol) was added. She was reacted in a MEC microwave 20 minutes at 160 ° C. Then, the reaction was purified using Gilson Preparative HPLC to yield 44 mg of the title compound (62.5%). LC / MS = m / z 511.2 [M + H]. Time of ret .: 1.79 EXAMPLE 346 54342- (Ethylamino) -etinophenyl) -3- [1- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide trifluoroacetate A solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -1H-indole-7-carboxamide (40.4 mg, 0.09 mmol), 2- (3-bromophenyl) -N-ethyleneamine (60 mg, 0.263 mmol) and poasic carbonate (72 mg, 0.526 mmol) in dioxane (2 mL) and water (0.7 mL) were degassed duranie 5 min To this was added tetrakis (triphenylphosphine) palladium (0) (11 mg, 0.009 mmol). The resulting mixture was reacted in a CEM microwave for 20 min at 160 ° C. Then, the reaction was purified using Gilson Preparative HPLC to yield 38.6 mg of the title compound (59.7%). LC / MS = m / z 482.8 [M + H]. Time of ret .: 1.54 EXAMPLE 347 trifluoroacetate of 3- | - (Ethylsulfonyl-4-piperidinip-54342- (propylamino) etinphenyl> -1H-indole-7-carboxamide A solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-teremethyl-1, 3,2-dio? Aborolan-2-yl) -1H-indole -7-carboamide (25 mg, 0.055 mmol), carbonic acid (46 mg, 0.33 mmol) and [2- (3-bromophenyl) ethyl] propylamine (40 mg, 0.165 mmol) in dioxide (2 ml) and water (0.7 ml) was degassed for 5 min and then tetrakis (triphenylphosphine) palladium (0) (7 mg, 0.006 mmol) was added. The resulting mixture was reacted in a CEM microwave for 20 min at 160 ° C. Then, the reaction was separated using Gilson Preparative HPLC to yield 17.6 mg of the title compound (61%). LC / MS = m / z 497.4 [M + H]. Time of ret .: 1.97 EXAMPLE 348 54342- (dimethylamino) ethylphenyl) -341-ethylsulfonyl) -4- piperidinyl] -1H-indole-7-carboxamide trifluoroacetate A solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-terylammethyl-1, 3,2-dio? Aborolan-2-yl) -1H-indole -7-carboamide (60 mg, 0.13 mmol), polycarboxylic acid (108 mg, 0.78 mmol) and 2- (3-bromophenyl) -N, N-dimethylethanamine (90 mg, 0.39 mmol) in dioxide (2 ml) and water (0.7 ml) was degassed for 5 min and then tetrakis (triphenylphosphine) palladium (0) (15 mg, 0.013 mmol) was added. The resulting mixture was reacted in a CEM microwave for 20 min at 160 ° C. Then, the reaction was separated using Gilson's Preparaliva HPLC to yield 30 mg of the title compound (59.7%). LC / MS = m / z 483.2 [M + H]. Time of ret .: 1.60 EXAMPLE 349 54342- (Dipropylamino) -ethyl-phenyl) -341- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide trifluoroacetate A solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -1H-indole-7 -carboxamide (66 mg, 0.14 mmol), potassium carbonate (120 mg, 0.86 mmol) and (2-phenylethyl) dipropylamine (120 mg, 0.43 mmol) in dioxane (2 mL) and water (0.7 mL) was degassed for 5 min. and then tetrakis (triphenylphosphine) palladium (0) (15 mg, 0.014 mmol) was added. The resulting mixture was reacted in a CEM microwave for 20 min at 160 ° C. Then, the reaction was separated using Gilson Preparative HPLC to yield 9 mg of the title compound (65.3%). LC / MS = m / z 455.0 [M + H]. Time of day: 1.55 EXAMPLE 350 Trifluoroacetate of 543-r2- (3,5-d-methyl-1 H-pyrazol-1-yl) ethyl-amino) > methyl) phenin-341- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (44 mg, OJ mmol), 2- (3, 5-dimethyl-1H-pyrazol-1-yl) ethanamine (105 mg, 0.6 mmol) in dichloromethane (3 ml) and methanol (1.5 ml) were added 3 drops of acetic acid. The resulting mixture was stirred overnight and then sodium triacetoxyborohydride (134 mg, 0.6 mmol) was added. This mixture was stirred overnight. The resulting mixture was quenched with sodium bicarbonate (2 ml) and brine (2 ml) and the organic layer was collected and concentrated. Then, the reaction was separated using Gilson Preparative HPLC to yield 26 mg of the title compound (67.7%) LC / MS = m / z 563.2 [M + H]. Time of ret .: 1.51 EXAMPLE 351 341 - (Ethylsulfonyl) -4-piperidinin-542- (4-morpholinylmethyl) -1,3-thiazol-4-in-1 H-indole-7-carboxamide trifluoroacetate To a solution of 4-bromo-1, 3-yiazole-2-carbaldehyde (192 mg, 1. 0 mmol) in DCM (4.0 ml) was added morpholine (130 μl, 1.5 mmol) and 3 drops of AcOH. The mixture was stirred for 12 h and then Na (OAc) 3BH (0.335 g, 1.5 mmol) was added. After 6 h, the mixture was quenched with NaHCO3 sai. (4.0 ml) and brine (3.0 ml). The organic layer was separated and concentrated to give 200 mg of 4 - [(4-bromo-1,3-liazol-2-yl) -methyl] morpholine (76%). A solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-lei-amylayl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7-carboxamide (46 mg, 0.1 mmol), 4 - [(4-bromo-1, 3-lyazol-2-yl) methyl] morpholine (79 mg, 0.3 mmol) and polycarboxylic carbonate (83 mg, 0.6 mmol) in dioxane (2 mg). ml) and water (0.7 ml) was degassed for 5 min and then triacexoxyborohydride (11 mg, 0.1 mmol) was added. This mixture was reacted in a CEM microwave for 20 min at 160 ° C. The organic layer was collected and concentrated. The residue was redissolved with dimellysulphonate (1 ml) and then purified using HPLC Gilson Preparaliva to yield 26.6 mg of the title compound (63.2%) LC / MS = m / z 518.2 [M + H]. Time of ret .: 1.49 EXAMPLE 352 341- (Ethylsulfonyl-4-piperidinyl-1-5- (24r- (2-methylpropyl) aminolmethyl) -1,3-thiazol-4-yl) -1H-indole-7-carboxamide trifluoroacetate To a solution of 4-bromo-1,3-thiazole-2-carbaldehyde (192 mg, 1.0 mmol) in DCM (4.0 mL) were added iso-propylamine (152 μL, 1.5 mmol) and 3 drops of AcOH. The mixture was stirred for 12 h and then Na (OAc) 3BH (0.335 g, 1.5 mmol) was added. After 6 h, the mixture was quenched with sat. NaHCO3. (4.0 ml) and brine (3.0 ml). The organic layer was separated and concentrated to give 145 mg of the title compound (58%). To a solution of 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-indole-7 -carbaldehyde (46 mg, 0.1 mmol), 2-meliM -propanamine (70 mg, 0.3 mmol) and p-phasic carbonation (83 mg, 0.6 mmol) in dioxane (2 mL) and water (0.7 mL) was added iriaoxyborohydride (11 mg, 0.01 mmol). This solution was degassed for 5 min and then reacted in a microwave CEM lasts 20 min at 160 ° C. The organic layer was separated and concentrated. Then, it was purified using Gilson Preparative HPLC to yield 24 mg of the title compound (61.8%) LC / MS = m / z 504.2 [M + H]. Time of day: 1.43 EXAMPLE 353 341 - (Ethylsulfonyl-piperidinin-54241-pyrrolidinylmethin-1,3-thiazol-4-ill-1 H -indole-7-carboxamide To a solution of 4-bromo-1, 3-yiazole-2-carbaldehyde (192 mg, 1. 0 mmol) in DCM (4.0 ml) was added pyrrolidine (124 μl, 1.5 mmol) and 3 drops of AcOH. The mixture was stirred for 12 h and then Na (OAc) 3BH (0.335 g, 1.5 mmol) was added. After 6 h, the mixture was quenched with sat. NaHCO3. (4.0 ml) and brine (3.0 ml). The organic layer was separated and concentrated to give 200 mg of the íllulo compound (82%). The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2- {[[(2-methylpropyl) amino] methyl] trifluoroacetate. 1,3-thiazol-4-yl) -1H-indole-7-carboamide, substituting 2-methyl-1-propanamine for pyrrolidine (74 mg, 0.3 mmol) to yield 6.3 mg of the title compound (50%) LC / MS = m / z 500.4 [M + H]. Time of ret .: 1.22 EXAMPLE 354 341 - (Ethylsulfonyl) -4-piperidine-p-542- (1-piperidinylmethyl) -3-thiazol-4-ill-1 H-indole-7-carboxamide To a solution of 4-bromo-1,3-yiazole-2-carbaldehyde (192 mg, 1.0 mmol) in DCM (4.0 mL) were added piperidine (150 μL, 1.5 mmol) and 3 golas of AcOH. The mixture was agitated for 12 h and then Na (OAc) 3BH (0.335 g, 1.5 mmol) was added. After 6 h, the mixture was quenched with sat. NaHCO 3. (4.0 ml) and brine (3.0 ml). The organic layer was separated and concentrated to give 166 mg of the title compound (64%). The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2- {[[2-methylpropyl] amino] met L.) -1, 3-thiazol-4-yl) -1 H -indole-7-carboxamide, substituting 2-methyl-1-propanamine for perpperidine (78 mg, 0.3 mmol) to yield 15.5 mg of the compound of the title (51.6%).
LC / MS = m / z 517.4 [M + H]. Time of day: 1.29 EXAMPLE 355 5424 (dimethylamino) methyp-1,3-thiazol-4-yl) -341- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide trifluoroacetate To a solution of 4-bromo-1, 3-yiazole-2-carbaldehyde (192 mg, 1.0 mmol) in DCM (4.0 mL) were added dimethylamine (2.0 M, 3.0 mL) and 3 golas of AcOH. The mixture was stirred for 48 h and then Na (OAc) 3BH (1.33 g, 6.0 mmol) was added. After 12 h, the mixture was quenched with NaHCO3 sai. (4.0 ml) and brine (3.0 ml) and a separator was used to remove the organic layer of DCM. The organic layer was concentrated to give 90 mg of the desired product (40%). To a solution of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-tetramethyl-1,2,2-dio? Aborolan-2-yl) -1H-indole- 7-carboamide (46 mg, 0.1 mmol), dimethylamine (69 mg, 0.3 mmol) and potassium carbonate (83 mg, 0.6 mmol) in dioe (2 ml) and water (0.7 ml) were added triacete? iborohydride (12 mg, 0.01 mmol). This mixture was degassed for 5 min. Then, the mixture was reacted in a microwave for 20 min at 160 ° C. The Organic layers were separated and concentrated. Then, it was purified using Gilson Preparative HPLC to yield 23 mg of the title compound (59%) LC / MS = m / z 474.4 [M + H]. Time of ret .: 1.20 EXAMPLE 356 5- (24-ethyl (methyl) amino-1-methyl) -1,3-thiazol-4-yl) -3- [1 • (ethylsulfonyl-4-piperidinyl] - 1 H -indole-7-carboxamide trifluoroacetate To a solution of 4-bromo-1,3-thiazole-2-carbaldehyde (192 mg, 1.0 mmol) in DCM (4.0 mL) were added N-Methylenamine (470 μL, 6.0 mmol) and 3 mg of AcOH. The mixture was stirred for 48 h and then αa (OAc) 3BH (1.33 g, 6.0 mmol) was added. After 12 h, the mixture was inactivated with? AHCO3 sai. (4.0 ml) and brine (3.0 ml) and a separator was used to remove the organic layer of DCM. The organic layer was concentrated to give 160 mg of the title compound (68%). The thioule compound was prepared according to the general trifluoroacelale process of 5-. { 2 - [(dimethylamino) -methyl] -1,3-liazol-4-yl} -3- [1- (alkylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboamide, suspending dimeylamine by elil (meityl) amine (73 mg, 0.3 mmol) to produce 25 mg of the compound of the ileum (60.4%). LC / MS = m / z 490.4 [M + H]. Time of day: 1.25 EXAMPLE 357 5- (3-Cyano-54r (2-methylpropyl) aminomethyl) phenyl) -341-trifluoroacetate (ethylsulfonyl-4-piperidinyl-1H-indole-7-carboxamide) To a solution of 3-formylbenzoniiril (1.0 g, 7.6 mmol) in TFA (4.0 ml) at 0 ° C in an argon atmosphere was added gola to concentrate H2SO4 gaseous (6.0 ml) followed by the addition in small portions of NBS . The mixture was slowly warmed to room temperature and then agitated for 12 hours in an argon atmosphere. When the reaction was completed, the mixture was poured into ice-H 2 O (80 ml), PdCl 2 (117 mg, 0.658 mmol) and the solid were collected and dried under vacuum overnight to give 1.50 g of 3-bromo-5 -formylbenzamide (86%). LC / MS = m / z 228.2 [M + H]. Ret Time: 1.37 To a solution of 3-bromo-5-formylbenzamide (1.5 g, 6.58 mmol) in H2O (50.0 ml) and MeCN (50.0 ml) was added PdCI2 (117 mg, 0.658 mmol). The mixture was stirred for 72 h at ambient temperature and another portion of H 2 O (100 ml) and MeCN (100 ml) was added followed by the addition of PdCl 2 (100 mg, 0.56 mol). The mixture was stirred for a further 12 h and concentrated. The residue was dissolved in ElOAc (200 ml), washed with brine (3 x 50.0 ml), dried over Na2SO4, concentrated and then purified by chromatography (10% EtOAc in hexanes) to give 550 mg of 3- Bromo-5-formylbenzonitrile (40%). To a solution of 3- [1- (ethylsulfonyl) -4-pperidinyl] -5- (4,4,5,5-iolamethyl-1, 3,2-dioxaborolan-2-yl) - 1H-indole-7-carboxamide (46 mg, 0J mmol) in dioxane (2.0 ml) and H2O (0.7 ml) were added with 3-bromo-5-formylbenzoniiril (68 mg, 0.3 mmol) and polycarboxylic acid (83 mg, 0.6 mmol). The mixture was degassed for 5 min before the addition of tetrakis (triphenylphosphine) palladium (0) (12 mg, 0.01 mmol). The mixture was reacted in the microwave at 160 ° C for 20 min. The compound was purified by Gilson Preparative HPLC to give 5- (3-cyano-5-formylphenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide. To a solution of 5- (3-cyano-5-formylphenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (47 mg, 0J mmol) in dichloromethane (3 ml) and methanol (1 ml) were added a few drops of acetic acid and methyl (2-methylpropyl) amine (64 μl, 0.6 mmol). The mixture was stirred for one night followed by an addition of 20 golas of acetic acid and triacetate-sodium hydrogen carbonate (0.6 mmol). The reaction was mixed for 4 h followed by an addition of methyl (2-methylpropyl) amine (64 μl, 0.6 mmol) and sodium triacetoxyborohydride (0.6 mmol). The mixture was stirred for one night and then inactivated with sodium biocarbonate and brine. The organic layer was separated with a SOX caustic and concentrated. Then, it was separated using Gilson Preparative HPLC to yield 10.3 mg of the title compound (63.6%). LC / MS = m / z 522.4 [M + H]. Time of ret .: 1.65 EXAMPLE 358 543-Cyano-5 - [(dimethylamino) methyrophenyl) -3- [1- (ethylsulfonyl) -4-piperidin-1H-indol-7-carboxamide trifluoroacetate The compound of the compound was prepared according to the general procedure of 5- (3-cyano-5. {[[(2-methylpropyl) amino] methyl] phenyl) -3- [1- (allylsulfonyl) -fluoroacetate. -4-piperidinyl] -1H-indole-7-carboamide, substituting methyl (2-meitylpropyl) amine for trimethylamine (300 μl, 0.3 mmol) to yield 10.5 mg of the title compound (61%). LC / MS = m / z 494.4 [M + H]. Withdrawal time: 1.48 EXAMPLE 359 3- [i- (Ethylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenin-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (80 mg, 0.181 mmol) in DCM was added morpholin (50 mg). μl, 0.545 mmol). The reaction was stirred at room temperature for 30 min. After the addition of idioel? -hydrochloride sodium (120 mg, 0.545 mmol). The reaction was carried out at ambient temperature for one night and then concentrated. The compound was purified by Gilson Preparative HPLC to yield 28.6 mg of the title compound (25%). LC / MS = m / z 511.4 [M + H]. Ret time: 1.48 min EXAMPLE 360 341- (Ethylsulfonyl) -4-piperidinyl-543- (fr (4-fluorophenyl) carbonyl-amino) -methylphenyl-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 5-. { 3 - [(acetylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide substituting N-. { [3- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} acetamide by 4-fluoro -? / -. { [3- (4,4,5,5-tetramethyl-1, 3,2-d-oxaborolan-2-yl) phenyl] methyl} benzamide (125 mg, 0.352 mmol). The compound was purified by Gilson Preparative HPLC to give 18.3 mg of the title compound (27%). LC / MS = m / z 563.1 [M + H]. Ret Time: 2.07 min EXAMPLE 361 341- (EthylsulfoniH-4-piperidiniri-5- (34 [(2-furanylcarbonyl-aminolmethyl) phenyl) -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 5-. { 3 - [(acetylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide substituting N-. { [3- (4,4,5,5-terylammethyl-1, 3,2-dio? Aborolan-2-yl) phenyl] meityl} aceiamide for? / -. { [3- (4,4,5,5-ylmethylayl-1, 3,2-dio? Abrolan-2-yl) phenyl] meilyl} -2-furancarboamide (115 mg, 0.352 mmol). The compost was purified by Gilson Preparative HPLC to give 8.1 mg of the title compound (12%). LC / MS = m / z 535 [M + H]. Retreat time: 1.89 min EXAMPLE 362 5- (34r (cyclopentylcarbonyl) aminolmethyl] phenyl) -341- (ethylsulphonyl) -4-piperidinyl] -1H-indole-7-carboxamide trifluoroacetate The compose of the title was prepared according to the general procedure of 5-. { 3 - [(acetylamino) -methyl] phenyl} -3- [1- (ethylene sulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide susíiuuyendo N-. { [3- (4,4,5,5-lelramelyl-1, 3,2-dioxaborolan-2-yl) phenyl] meityl} acelamide by N-. { [3- (4,4,5,5-leiramyl-1, 3,2-dio? Aborolan-2-yl) phenyl] meityl} cyclopenianecarboamide (116 mg, 0.352 mmol). The compound was purified by Gílson Preparative HPLC to give 9.2 mg of the compound of the extract (14%). LC / MS = m / z 535 [M + H]. Time of laugh: 1.89 min EXAMPLE 363 5- (34f (1-benzothien-2-ylcarbonyl) aminolmethyl phenyl) -341- (ethylsulfonyl) -4- piperidinyl-1H-indol-7-carboxamide The compound of the isolate was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(pentanoylamino) meily] phenyl} -1H-indole-7-carboxamide substituting N-. { [3- (4,4,5,5-leiramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] meityl} penanamide by N-. { [3- (4,4,5,5-lelramelyl-1, 3,2-dioxaborolan-2-yl) phenyl] meityl} -1-benzoyiophen-2-carboxamide (57 mg, 0.144 mmol). The compost was purified by Gilson Preparative HPLC to give the title compound. LC / MS = m / z 601.2 [M + H]. Time of ret .: 2.18 min EXAMPLE 364 543 - ((r (1-acetyl-4-piperidinyl) carboninamino> methyl) fenin-3414-ethylsulfonyl) -4-piperidinium-1-yl-indole-7-carboxamide The thioule compound was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5-. { 3- [(pentanoylamino) methyl] phenyl} -1H-indole-7-carboxamide substituting N-. { [3- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} pentanamide by 1-acetyl-N-. { [3- (4,4,5,5-Teiramelyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} -4-piperidinecarboxamide (56 mg, 0.144 mmol). The compound was purified by Gílson Preparaliva HPLC to give the title compound. LC / MS = m / z 594.4 [M + H]. Retreat time: 1.87 min EXAMPLE 365 341 - (Ethylsulfonyl-4-piperidinyl-5-y3 - ((r (1-methyl-1 H -pyrrol-2-yl) carbonyl] amino) methyl) phenin-1H-indol-7 - carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3- [(pennylamino) methyl] phenyl} -1 H -indole-7-carboxamide substituting N-. { [3- (4,4,5,5-iolameryl-1, 3,2-dioxaborolan-2-yl) phenyl] meityl} penanamide for 1-methyl-N-. { [3- (4,4,5,5-lelramelyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} -1H-pyrrole-2-carboxamide (49 mg, 0.144 mmol). The compound was purified by preparative Gilson HPLC to give the title compound. LC / MS = m / z 548.4 [M + H]. Time of ret .: 2.02 min EXAMPLE 366 3- [1- (Ethylsulfonyl) -4-piperidinyl] -5- (34 [(2-thienylacetyl) aminomethyl> phenyl) -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3- [(pennylamino) methyl] phenyl} -1 H -indole-7-carboxamide susliluyendo N-. { [3- (4,4,5,5-yl-methyl-1, 3,2-dioxaborolan-2-yl) phenyl] -methyl} penanamide by N-. { [3- (4,4,5,5-eerymethyl-1, 3,2-dio? Abrolan-2-yl) phenyl] meityl} -2- (2-ynyl) acetylamide (51 mg, 0.144 mmol). The compound was purified by HPLC Auto Prep. Directed to masses to give 10.3 mg of the compound of the product (18.2%). LC / MS = m / z 565.2 [M + H]. Time of laugh .: 1.95 min EXAMPLE 367 - (34r (cyclobutylcarbonyl) aminomethyl> phenyl) -341- (ethylsulfonyl) -4-piperidinin-1H-indol-7-carboxamide 1"! -" -. 'Or according to the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3- [(pentanoylamino) methyl] phenyl} -1 H-Indole-7-carboxamide susíiluyendo N-. { [3- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] meityl} penanamide by N-. { [3- (4,4,5,5-letramethyl-1, 3,2-dio? Aborolan-2-yl) phenyl] meily} cyclobialcarboxamide (45 mg, 0.144 mmol). The compound was purified by HPLC Auto Prep. Directed to masses to give 4.3 mg of the title compound (8%). LC / MS = m / z 523.4 [M + H]. Retreat time: 1.90 min EXAMPLE 368 5- (34f (cyclopropylcarbonyl) amino] methyl &phenyl) -341- (ethylsulfonyl) -4- piperidinium-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3- [(penlanoylamino) meily] phenyl} -1 H-indole-7-carboxamide susliíuyendo N-. { [3- (4,4,5,5-lettermethyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} pentanamide by N-. { [3- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] methyl} Cyclopropanecarboxamide (43 mg, 0.144 mmol). The compound was purified by AuCl Prep HPLC. Directed to Masses to give 5.5 mg of the title compound (11%). LC / MS = m / z 509.2 [M + H]. Retreat time: 1.85 min EXAMPLES 369 5- (34 I (cyclopropylsulfonyl) amino] methyl> phenyl) -341- (ethylsulfonyl) -4- piperidinin-1H-indol-7-carboxamide To a solution of 5- [3- (aminomethyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (35 mg, 0.079 mmol) in DMF (1.0 ml ) and DCM (1.0 ml) were added cyclopropanesulfonyl chloride (11 mg, 0.079 mmol) and DIEA (14 μl, 0.079 mmol). The reaction was stirred at room temperature for one night. The compost was purified by Gilson Preparative HPLC to give 7.2 mg of the title compound (17%). LC / MS = m / z 545.4 [M + H]. Retreat time: 1.94 min EXAMPLE 370 543-r (2,5-dichlorophenyl) sulfoninamino) methyl) phenyl-341- (ethylsulfonyl-4- piperidinyl-1,1-H-indol-7-carboxamide To a solution of 5- [3- (aminomethyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (40 mg, 0.096 mmol) in DMF (1.0 ml ) and DCM (1.0 ml) were added with 2,5-dichlorobenzenesulfonyl chloride (86 mg, 0.352 mmol) and DIEA (62 μl, 0.352 mmol). The reaction was stirred at room temperature for 6 h. Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 6.6 mg of the title compound (11%). LC / MS = m / z 649.2 [M + H]. Time of ret .: 2.25 min EXAMPLE 371 543 - ((r (4-bromophenyl) sulfoninamino> methyl) phenin-341- (ethylsulfonyl) -4- piperidinium-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 4-bromobenzenesulfonyl chloride (90 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson's Preparaliva HPLC to give 19.4 mg of the title compound (31%). LC / MS = m / z 659.4 [M + H]. Time of ret .: 2.20 min EXAMPLE 372 543 - ((r (4-chlorophenyl) sulfoninamino) methyl phenin-341- (ethylsulfonyl) -4- piperidinyl-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-Dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) ) -4-piperidinyl] -1H-indole-7-carboxamide substituting 2,5-dichlorobenzenesulfonyl chloride for (2F, 4E) -5-chloro-2,4,6-heptalrieno-2-sulfonyl chloride (80 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 7.5 mg of the title compound (13%). LC / MS = m / z 615.2 [M]. Time of ret .: 2.19 min EXAMPLE 373 341- (Ethylsulfonyl-piperidin-p-5434 (r (3-fluorophenyl) sulfoninamino) methyl) phen-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 3-fluorobenzenesulfonyl chloride (69 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 7.3 mg of the title compound (13%). LC / MS = m / z 599.2 [M + H]. Time of laugh .: 2.15 min EXAMPLE 374 5434 (r (2-chlorophenyl) sulfoninamino> methyl) phenin-341- (ethylsulfonyl) -4- piperidin-p-1H-indol-7-carboxamide The compound of the illole was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino} methyl) phenol] -3- [1- (ethylsulfonyl ) -4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 2-chlorobenzenesulfonyl chloride (74 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 17.3 mg of the title compound (29%). LC / MS = m / z 615.2 [M]. Retreat time: 2.15 min EXAMPLE 375 543-r (2,5-dichloro-3-thienin sulfoninamino> methyl) phenin-341- (ethylsulfonyl) -4- piperidinyl-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-Dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) ) -4-piperidinyl] -1H-indole-7-carbo-amide substituting 2,5-dichlorobenzenesulfonyl chloride for 2,5-dichloro-3-thiophenesulfonyl chloride (86 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 16.7 mg of the title compound (27%). LC / MS = m / z 655.2 [M]. Time of ret .: 2.24 min EXAMPLE 376 5-r3 - ((r (2-Chloro-6-methylphenyl) sulfonyl-amino) methylene) phenyl-341- (ethylene sulfonyl) -4-pyrimidin-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 2-chloro-6-methylbenzenesulfonyl chloride (86 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 17.9 mg of the title compound (30%). LC / MS = m / z 629.4 [M]. Time of ret .: 2.19 min EXAMPLE 377 3-, 1- (Ethylsulfonyl) -4-p -peridinyl-1-543 - ((r (5-fluoro-2-methylphenyl) sulfonyl-amino) methyl) phenyl-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- ( { [(2,5-Dichlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (sulphonyl) 4-pperidinyl] -1H-indol-7-carboamide by substituting 2,5-dichlorobenzenesulfonyl chloride for 5-fluoro-2-methylbenzenesulfonyl chloride (86 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give the title compound. LC / MS = m / z 613.2 [M + H]. Time of laugh .: 2.18 min EXAMPLE 378 543 - ((rd, 2-dimethyl-1 H-imidazol-4-yl) sulfonylamino) methyl) phenyl-341 • (ethylsulfonyl-4-piperidinium.) - 1 H -indole-7-carboxamide The compound of the title was prepared according to the general procedure of 5- [3- (. {[[(2,5-Dichlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (sulphonyl) ) -4-pyridinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 1,2-dimethyl-1H-imidazole-4-sulfonyl chloride (69 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson's Preparaliva HPLC to give 1.9 mg of the title compound (3.3%). LC / MS = m / z 599.2 [M + H]. Retreat time: 1.76 min EXAMPLE 379 341- (Ethylsulfonyl) -4-piperidinyl-5- (34 [(phenylsulfonyl) amino] methyl) phenyl) -1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for benzenesulfonyl chloride (62 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 13.4 mg of the title compound (24%). LC / MS = m / z 581.6 [M + H]. Time of laugh .: 2.10 min EXAMPLE 380 341- (Ethylsulfonyl) -4-piperidinin-543 - ((r (4-fluorophenyl) sulfonamino) methyl.fenip-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-Dichlorophenyl) sulfonyl] amino} -methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboxamide substituting 2,5-dichlorobenzenesulfonyl chloride for 4-fluorobenzenesulfonyl chloride (69 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson's Preparaliva HPLC to give 11.5 mg of the title compound (20%). LC / MS = m / z 599.2 [M + H]. Time of ret .: 2.10 min EXAMPLE 381 5-f3 - ((r (4-bromo-2-ethylphenylsulfoninamino> methyl) phenyl-341- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboxamide substituting 2,5-dichlorobenzenesulfonyl chloride for 4-bromo-2-ethylbenzenesulfonyl chloride (100 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 2.7 mg of the title compound (4%). LC / MS = m / z 687.6 [MJ. Time of ret .: 2.38 min EXAMPLE 382 5- (34 - [(1-benzothien-3-ylsulfonyl) amino-1-methyl-phenyl) -341- (ethylsulfonyl) -4-piperidinyl] -1- phiol-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- ( { [(2,5-Dichlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 1-benzoliofen-3-sulfonyl chloride (82 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson's Preparative HPLC to give 3.9 mg of the title compound (6%). LC / MS = m / z 637.4 [M + H]. Time of laugh .: 2.19 min EXAMPLE 383 5434 (fr4- (1,1-dimethylethyl) phenylsulfonyl > amino) methyphenyl) -341- (ethylsulfonyl) -4-piperidin-1H-indol-7-carboxamide The compound of the illole was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carboamide, substituting 2,5-dichlorobenzenesulfonyl chloride for 4- (1,1-dimethylethyl) benzenesulfonyl chloride (82 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give 15.6 mg of the title compound (26%). LC / MS = m / z 637.4 [M + H]. Ret time: 2.35 min EXAMPLE 384 543 - ((r (3,4-difluorophenyl) sulfoninamino> methyl) phen-341- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide The compound of the extract was prepared according to the general procedure of 5- [3- ( { [(2,5-dichlorophenyl) sulfonyl] amino} .methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indol-7-carboxamide substituting 2,5-dichlorobenzenesulfonyl chloride for 3,4-difluorobenzenesulfonyl chloride (75 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give the title compound. LC / MS = m / z 617.2 [M + H]. Time of ret .: 2.16 min EXAMPLE 385 5- (34f (2.1.3-benzoxadiazol-4-ylsulfonyl) amino-1-methyl) -phenyl) -341- (ethylsulfonyl) -4-piperidin-1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino] methyl) phenyl] -3- [1- (ethylsulfonyl) - 4-piperidinyl] -1H-indole-7-carbo-amide substituting 2,5-dichlorobenzenesulfonyl chloride for 2,1, 3-benzoxadiazole-4-sulfonyl chloride (77 mg, 0.352 mmol). Then, the reaction mixture was concentrated and purified by Gilson Preparative HPLC to give the title compound. LC / MS = m / z 623.4 [M + H]. Time of ret .: 2.10 min EXAMPLE 386 3414-ethylsulfonyl-piperidinyl-5- (34r (tetrahydro-3-furanylcarbonyl) amino-1-methyl) -phenyl) -1H-indole-7-carboxamide To a solution of telrahydro-3-furancarboxylic acid (17 mg, 0.144 mmol) in DCM (2.0 ml) were added pyridine (3 drops) and o? Allyl chloride (18 mg, 0.144 mmol). The reaction mixture was stirred overnight at room temperature. Then, 5- [3- (aminomethyl) phenyl] -3- [1- (ethylsulfonyl) -4-pperidinyl] -1H-indole-7-carboamide (40 mg, 0.096 mmol) in DMF (1.0 ml) and DIEA (33 μl, 0.192 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under a nitrogen atmosphere and purified by Gilson Preparative HPLC to give 5.3 mg of the title compound (10%). LC / MS = m / z 539.2 [M + H]. Retreat time: 1.80 min EXAMPLE 387 544 - [(Cyclopentylsulfonyl) amino1-phenyl) -3- [1 - (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide trifluoroacetate To 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (20 mg, 0.048 mmol) was added chlorine (di-2-norbornylphosphino) (2-dimethylaminomeleyl ferrocen- 1-yl) palladium (II) (10 mg, 0.016 mmol), potassium carbonate (13.4 mg, 0.097 mmol) and N- [4- (4,4,5,5-ylmethyl-1, 3,2-dioxaborolan- 2-yl) phenyl] cyclopentanesulfonamide (34 mg, 0.097 mmol) in dioxane (3 ml) and H2O (1 ml). The reaction mixture was heated in a microwave at 160 ° C for 10 minutes. The reaction mixture was concentrated under a nitrogen atmosphere and purified by Gilson Preparative HPLC to give 8.6 mg of the title compound (32%). LC / MS = m / z 559.2 [M + H]. Time of ret .: 2.00 min EXAMPLE 388 341- (Ethylsulfonyl) -4-piperidinin-544- (4-methyl-2-oxo-1-piperaziniphenin-1H-indole-7-carboxamide) To 5-bromo-3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (20 mg, 0.048 mmol) was added 4-methyl-1- [4- (4.4 , 5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] -2-piperazinone (31 mg, 0.097 mmol) in dioxane (3.0 ml) and H2O (1.0 ml), potassium carbonate (13 mg , 0.097 mmol) and chloro (di-2-norbomilfosfino) (2-dimethylaminomeyl-ferrocen-1-yl) palladium (II) (10 mg, 0.016 mmol). The reaction mixture was reacted in a microwave at 160 ° C for 10 minutes. The reaction mixture was heated in a microwave at 160 ° C for 10 min. The reaction mixture was concentrated under a Nitrogen atmosphere and purified by Gilson Preparative HPLC. The desired fraction in CH3CN and H2O was irradiated with potassium carbonate to neutralize the salts and then concentrated to give 1.9 mg of the compound of the illam (8%).
LC / MS = m / z 524.6 [M + H]. Retreat time: 1.49 min EXAMPLE 389 546- (4-acetyl-1-piperazinyl) -3-pyridinyl-3-i- (ethylsulfonyl-4-piperidinyl-1H-indole-7-carboxamide trifluoroacetate.
To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [6- (1-p-piperazinyl) -3-pyridinyl] -1H-indole-7-carboamide (40 mg, 0.080 mmol) in dichloromethane at 0 ° C was added acetyl chloride (7 μl, 0.096 mmol) and DIEA (11.6 μl, 0.12 mmol). The reaction mixture was reacted for 0.5 h at 0 ° C at room temperature and then quenched with H2O. The compound was purified by MDAP HPLC to give 7 mg of the title compound (40%). LC / MS = m / z 539.4 [M + H]. Retreat time: 1.27 min EXAMPLE 390 3-f1- (Ethylsulfonyl) -4-piperidinyl-5- (44f (methyloxy) aminomethyl) phenyl) -1H-indol-7-carboxamide To a solution of 3- [1- (alkylsulfonyl) -4-piperidinyl] -5- (4-formylphenyl) -1H-indole-7-carboamide (50 mg, 0.114 mmol) in DCM (1.5 mL) and MeOH (1.5 ml) was added O-methylhydro-ylamine (114 mg, 1.71 mmol). The reaction waned during one night. The solvent was then concentrated and purified by Gilson's Preparative HPLC to give 38 mg of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4. {[[(Meloxy) imino] methyl] phenyl. ) -1H-indole-7-carboxamide (76%). To a solution of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4- {[[(melyloxy) imino] methyl} phenyl) -1H-indole-7-carboxamide (21.5 mg, 0.046 mmol) in DCM (3.0 ml) and MeOH (3.0 ml) were added HCl in 1,4-dioxane to maintain the pH = 4 at 0 ° C. Then, sodium cyanoborohydride (29 mg, 0.46 mmol) was added and the mixture was stirred overnight at ambient temperature. More HCl in 1,4-dioxane was added to maintain pH = 4 in addition to sodium cyanoborohydride (45 mg, 0.72 mmol). Then, the reaction mixture was stirred for 48 h. More HCl in 1,4-dioxane was added to maintain the pH = 4 at 0 ° C and was stirred until the ambient temperature was reached. The mixture is quenched with H2O. Then, DCM was added for the aqueous treatment and the mixture was concentrated. Then, the residue was taken up in DCM and purified on the SCX SPE cartridge to yield 15.2 mg of the title compound (70%). LC / MS = m / z 471.6 [M + H]. Retreat time: 1.67 min EXAMPLE 391 341- (Ethylsulfonyl) -4-piperidinin-5- (34f (methyloxy) aminomethyl> phenyl) -1H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3-formylphenyl) -1H-indole-7-carboamide (50 mg, 0.114 mmol) in DMSO (3.0 mL) was added O-methylhydroxylamine (57 mg, 0.684 mmol). The reaction was agitated during one night. More O-methylhydroxylamine (0.342 mmol) was added to the reaction mixture and it was stirred for 48 h. The solvent was then concentrated and purified by Gilson Preparative HPLC to give 29.8 mg of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(Methyloxy) imino] methyl] phenyl. ) -1H-indole-7-carboxamide (56%). To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(Methyloxy) imino] methyl} phenyl) -1H-indole-7-carboxamide (58 mg, 0J23 mmol) in DCM (3.0 mL) and MeOH (3.0 mL) was added HCl in 1,4-dioxane to maintain the pH = 4 at 0 ° C. Then, sodium cyanoborohydride (176 mg, 3.69 mmol) was added and the solution was stirred for one night for 48 h. The compound was purified by Gilson Preparative HPLC to give 20.0 mg of the title compound (89%). LC / MS = m / z 471.6 [M + H]. Retreat time: 1.75 min EXAMPLE 392 Trifluoroacetate of 341- (ethylene sulfonyl) -4-piperidinyl-5- (54f4- (1-pyrrolidinyl) -1- piperidinophenyl) -3-thienyl-1H-indole-7- carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-dol-7-carboxamide (50 mg, 0.112 mmol) in DMSO (2.0 ml) 4- (1-pyrrolidinyl) piperidine (173 mg, 1.12 mmol) and acetic acid (5 drops) were added. After 6 h, sodium triacetoxyborohydride (238 mg, 1.12 mmol) was added and the reaction was stirred overnight. The reaction mixture was purified by Gilson Preparative HPLC to give 17.0 mg of the title compound (26%). LC / MS = m / z 584.4 [M + H]. Retreat time: 1.38 min EXAMPLE 393 341 - (Ethylsulfonyl) -4-piperidinin-5- (54r (2S) -2- (trifluoromethyl) -1-pyrrolidinylmethyl) -3-thienyl-1H-indole-7-carboxamide trifluoroacetate To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboamide (50 mg, 0.112 mmol) in DCM (3.0 ml) and MeOH (1.5 ml) were added (2S) -2- (trifluoromethyl) pyrrolidine (156 mg, 1.12 mmol) and acetic acid (5 drops). After 6 h of stirring at room temperature, sodium borohydride (43 mg, 1.12 mmol) was added and the reaction was stirred overnight at ambient temperature. The reaction mixture was purified by Gilson Preparative HPLC to give 5.0 mg of the title compound (8%). LC / MS = m / z 569.4 [M + H]. Time of ret .: 2.37 min EXAMPLE 394 5454r (2R) -2- (hydroxymethm-1-pyrrolidininmethyl) -3-thienyl) -3414 (1-methylethyl) sulfonin-4-piperidinyl > -1H-indol-7 -carboxamide To a solution of 5- (5-formyl-3-ynyl) -3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1H-indole-7-carboxamide (25 mg, 0.054 mmol) in DMSO (2 ml) was added (2R) -2-pyrrolidinylmeanol (101.15 mg, 1 mmol) and 2 gols of acyl acid. The mixture was stirred at room temperature for 4 h followed by an addition of sodium triacedoxyborohydride (212 mg, 0.54 mmol). The mixture was reacted overnight. Then, it was purified by Gilson Preparative HPLC to give 20.5 mg of the compound of the extract (69.7%). LC / MS = m / z 546 [M + H]. Time of laugh: 1.47 min.
EXAMPLE 395 5- (54r (3S) -3-hydroxy-1-pyrrolidininmethyl > -3-thienyl) -3414 (1-methylethyl) sulfonyl-4-piperidinyl) -1H-indol-7-carboxamide The compound of the illole was prepared according to the general procedure of 5- (5- { [(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] methyl.} - 3-thienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1H-indole-7-carboamide, substituting (2R) -2-pyrrolidinylmethanol for (3S) -3-pyrrolidinol (90.13 mg, 1.20 mmol) to yield 12.8 mg of the title compound (53.1%). LC / MS = m / z 532 [M + H]. Retreat time: 1.45 min.
EXAMPLE 396 5- (54 [cyclopentyl (methyl) amino-1-methyl) -3-thienyl) -341-f (1-methylethyl) sulfonin-4-piperidinyl) -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- (5- { [(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] methyl] -3-thienyl) - 3-. { 1 - [(1-Melleyl) sulfonyl] -4-piperidinyl} -1H-Indole-7-carboamide, susliluting (2R) -2-pyrrolidinylmelanol by N-methylcyclopentamine (90.13 mg, 1.20 mmol) to yield 10 mg of the compound of the citric acid (54.3%) LC / MS = m / z 544.2 [M + H]. Time of laugh .: 1.65 min.
EXAMPLE 397 545 - ([(2-hydroxyethyl) (methyl) amino-1-methy1-3-thienyl) -3414 (1-methylethyl) sulfonin-4-piperidinyl) -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- (5- { [(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] -methyl] -3-thienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1H-Indole-7-carboamide, substituting (2R) -2-pyrrolidinylmethanol for 2- (meitylamino) elanol (90.13 mg, 1.20 mmol) to yield 8 mg of the compound of the extract (51.9%), LC / MS = m / z 520 [M + H]. Time of laugh .: 1.44 min.
EXAMPLE 398 5- (54r (2-amino-2-oxoethyl) (methyl) amino-1-methyl-3-thienyl) -3414 (1-methylethyl) sulfonyl-4-pperidinyl) -1H-indole 7 -carboxamide The compound of the invention was prepared according to the general procedure of 5- (5- { [(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] -methyl] -3-thienyl) -3- . { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1H-Indole-7-carboxamide, suspending (2R) -2-pyrrolidinylmelanol by N2-meitylglycinamide (90.13 mg, 1200 mmol) to yield 15 mg of the title compound (53.2%). LC / MS = m / z 520 [M + H]. Retreat time: 1.44 min.
EXAMPLE 399 341- (Ethylsulfonyl) -4-pperidinyl-5- (54-methyl-2- (2-propen-1-yl) aminolmethyl) -3-thienyl-1H-indole-7-carboxamide Allylamine (0.034 ml, 0.449 mmol) and HOAc (0.026 ml, 0.449 mmol) were added to a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1. H-Indole-7-carboamide (20 mg, 0.0449 mmol) in DMSO (0.5 ml) in a 1-dram vial. Then, NaBH (OAc) 3 (95 mg, 0.449 mmol) was added, the vial was capped and the reaction was stirred at room temperature for 15 h. NaCNBH3 (28 mg, 0.449 mmol) and MeOH were added and the reaction was stirred for a further 4 h. An aqueous solution of formaldehyde at 37% by weight (0.069 ml, 0.898 mmol) was added and the reaction was stirred for a further 1 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 ml of MeOH), eluting in sequence with MeOH (3 ml) and a 2 M solution of NH 3 / MeOH (9 ml). The NH3 / MeOH fraction was concentrated under a nitrogen atmosphere at 50 ° C and the residue was dissolved in DMSO (1 ml) and purified on Gilson HPLC (Xbridge Prep C18 column: 19-100 mm) eluting at 20 ° C. ml per min with a linear gradient ranging from 10% CH3CN / H2O (0.1% NH OH) to 70% CH3CN / H2O (0.1% NH4OH) for 15 min. Fractions containing the title compound were concentrated in a nitrogen atom at 50 ° C to give 5.2 mg of the title compound (23%). LC / MS = m / z 501.4 [M + H]. Retreat time: 1.48 min.
EXAMPLE 400 5- (54rr (3,5-dimethyl-1H-pyrazol-4-yl) metin (methyl) amino-1-methyl) -3-thienin-3-ri- (ethylsulfonyl) -4-piperidinyl-1H-indol-7- carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboxamide (45 mg, 100 μmol) in dimethyl sulfoxide (1.0 ml) 1- (3,5-dimethyl-1 Hp -razol-4-yl) -N-methylmethanamine (320 μmol) and 2 to 3 drops of glacial acetic acid were added. The resulting mixture is stirred overnight. After 18 h, sodium triacetoxyborohydride (200 mg, 1000 μmol) is added. This mixture is stirred for 1.5 h followed by purification by HPLC Preparaliva Gilson to give 6.24 mg of the title compound (11.0%). LC / MS = m / z 569.3 [M + H]. Time of laugh: 1.42 min.
EXAMPLE 401 5- (54f (cyanomethyl) (methyl) amino-1-methyl) -3-thienyl) -3- [1- (ethylsulfonyl) -4- piperidinip-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 5- (5-. {[[[(3,5-dimethyl-1 H -pyrazol-4-yl) methyl] (methyle) amino] meilyl}. -3-lienyl) -3- [1- (erylsulfonyl) -4-p -peridinyl] -1H-indole-7-carboamide, substituting 1- (3,5-dimethyl-1H-pyrazole-4-) il) -N-meilymeanamine by (meitylamino) acetonitrile (320 μmol) to yield 6.36 mg of the title compound (12.7%). LC / MS = m / z 430 [M + H]. Time of laugh: 1.70 min.
EXAMPLE 402 341- (Ethylsulfonyl) -4-piperidinyl-5- (54-methyl (1-methylpropyl) aminolmethyl) -3-thienyl) -1H-indol-7-carboxamide To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carboxamide (45 mg, 0.1 mmol) in dimethylsulfoxide (1 ml) were added 2-bulanamine (1 mmol), 1 to 2 drops of acetic acid and triacehoxyborohydride sodium (211 mg, 1 mmol). The mixture was filtered and stirred for 18 h followed by addition of sodium cyanoborohydride (62 mg, 1 mmol) in methanol (0.5 ml). This was stirred for 3 h followed by an addition of formaldehyde, 37% in water, (1.5 ml). It was purified from an SCX cartridge (2 g) eluting with melanol followed by NH 3 in melanol. Additional purification was performed by Gilson Preparative HPLC. Column XBridge C18 (P / N 186002978) using a gradient of 10% acetonitrile to 70% acetonitrile in water with 0.1% NH4OH to give 14.4 mg of the title compound (27.9%). LC / MS = m / z 517.3 [M + H]. Retreat time: 1.58 min.
EXAMPLE 403 5- (54 i2- (Ethyloxy) ethyl (methyl) aminomethyl) -3-thienl) -341- (ethylsulfonyl) -4-piperidinin-1H-indole-7-carboxamide The compound of the isolate was prepared according to the general procedure of 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5. {[[Meily (1-methylpropyl) amino] methyl.} -3 -lienyl) -1 H-indole-7-carboxamide, suspending the 2-bulanamine added by 2- (elyloxy) elanamine (1 mmol) to yield 6.1 mg of the compound of the extract (11.5%). LC / MS = m / z 533.2 [M + H]. Time of laugh .: 1.57 min.
EXAMPLE 404 5- (54-Cyclobutyl (methyl) amino-1-methyl) -3-thienyl) -341- (ethylsulfonyl) -4-piperidine-1H-indole-7-carboxamide trifluoroacetate The compound of the title was prepared according to the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[Methyl (1-methylpropyl) amino] methyl.} -3 -thienyl) -1H-indole-7-carboxamide, substituting the 2-buanamine added by cyclobutylamine (1 mmol) to yield 3.7 mg of the compound of the phycium (5.9%). LC / MS = m / z 515.3 [M + H]. Time of laugh: 1.64 min.
EXAMPLE 405 341- (Ethylsulfonyl-4-piperidini.l-545 - ((2-r (methyloxy) methyl-1-pyrrolidinyl) methyl) -3-thienyl-1-H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- {[methyl (1-methylpropyl) amino] methyl. 3-Ethyl) -1H-indole-7-carboxamide, suspending 2-bulanamine added by 2 - [(methyloxy) meilyl] pyrrolidine (1 mmol) to yield 5 mg of the title compound (7.6%). LC / MS = m / z 545.3 [M + H]. Retreat time: 1.65 min.
EXAMPLE 406 5- (54r (1,1-dimethylethyl (methyl amino-methyl) -3-thienyl-341- (ethylsulphonyl) -4-piperidinyl-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[Methyl (1-methylpropyl) amino] methyl] -3 -thienyl) -1H-indole-7-carboxamide, substituting the 2-bulanamine added by 2-methyl-2-propanamine (1 mmol) to yield 10.9 mg of the title compound (17.3%). LC / MS = m / z 517.3 [M + H]. Retreat time: 1.61 min.
EXAMPLE 407 341 - (Ethylsulfonyl) -4-pperidinyl-5- (54r3- (trifluoromethyl) -1-piperidinylmethyl) -3-thienyl trifluoroacetate. -1 H -indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5. {[[Methyl] (1-methylpropyl) amino] methyl.}. -3-thienyl) -1H-indole-7-carbo-amide, substituting the added 2-buíanamine for 3- (trifluoromethyl) piperidine (1 mmol) to yield 5.4 mg of the title compound (7.8%). LC / MS = m / z 583.3 [M + H]. Retreat time: 1.73 min.
EXAMPLE 408 341 - (Ethylsulfonyl) -4-piperidinin-5- (54f fd S-2-hydroxy-1-methyl-ethyl (methyl) amino-1-methyl) -3-thienyl-1H-indole-7-carboxamide trifluoroacetate To a vial containing (2f?) - 2-amino-1-propanol (90.13 mg, 1.2 mmol) was added a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl) -34) -1H-indole-7-carboamide (30 mg, 0.067 mmol) in DMSO (300 μl) and acetic acid (50 μl). The mixture was stirred for 5 min followed by an addition of triacetyl-sodiumborohydride (250 mg, 1.20 mmol) in DMSO (800 μl). The mixture was stirred overnight. Then, sodium cyanoborohydride (79 mg, 1.20 mmol) in methanol (300 μl) was added and it was stirred for 48 h. This was followed by an addition of formaldehyde (100 μl). Then, the reaction was stirred for 1 h followed by separation with a 2 g SCX cartridge. The solids were then relieved by filtration, the solution was concentrated and the purification was repeated on the 5 g SCX cartridge eluting with ammonia in MeOH. Ammonia from the collection of MeOH fractions was concentrated and separated using Gilson Preparaliva HPLC for yield 18.6 mg of the title compound (43.9%). LC / MS = m / z 519.3 [M + H]. Retreat time: 1.49 min.
EXAMPLE 409 5- (54f (cyclopropylmethyl) (methylamino-methyl) -3-thienyl-3- (3-H- (ethylsulphonyl) -4-piperidin-1H-indol-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetyla (salt) of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydro < RTI ID = 0.0 > 1-methylethyl < / RTI > (methylene) amino] -methyl] -3-ynyl) -1H-indole-7-carboamide, substituting (2f?) - 2-amino-1-propanol for (cyclopropylmethyl) amine (1.20 mmol) to yield 6.2 mg of the title compound (14.7%). LC / MS = m / z 515.3 [M + H]. Retreat time: 1.61 min.
EXAMPLE 410 5- (54fr2- (Acetylamino) ethyl] (methyl) aminolmethyl> -3-thienyl) -3- [1 - (ethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate (salt) of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[[(1S) -2- diethyl-1-methyleryl] (methyl) amino] methyl] -3-ynyl) -1H-indole-7-carboxamide, substituting (2f?) - 2-amino-1-propanol for N - (2-Amino-eyl) -acetylamide (1.20 mmol) to yield 13.6 mg of the Iulus Compound (30.8%) LC / MS = m / z 546.2 [M + H]. Retreat time: 1.47 min.
EXAMPLE 411 trifluoroacetate of 341- (ethylsulfonyl) -4-piperidinyl-5- (54rr (1R.2R? -2- hydrodicyclopentyl (methyl) amino] methyl) -3-thienyl) -1H -indol-7 -carboxamide Quiral The compound of the thioule was prepared according to the general procedure of trifluoroacetate (salt) of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydroxy] -1-methylethyl] (melil) amino] -methyl] -3-ynyl) -1 H -indole-7-carbo-amide, susliluyendo (2f?) - 2-amino-1-propanol per (1 R, 2f ?) - 2-aminocyclopentanol (1.20 mmol) to yield 9.6 mg of the title compound (21.8%) LC / MS = m / z 545.3 [M + H]. Retreat time: 1.54 min.
EXAMPLE 412 5- (54 [(, 1-dimethylpropyl) (methyl) aminolmethyl) -3-thienyl-3-f 1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate (salt) of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1S) -2-hydro? i-1-methyleryl] (methylamino) -methyl] -3-ynyl) -1H-indole-7-carboamide, substituting (2f?) -2-amino-1-propanol for (1, 1- dimethypropyl) amine (1.20 mmol) to yield 13.1 mg of the title compound (30.3%) LC / MS = m / z 531.3 [M + H]. Retreat time: 1.65 min.
EXAMPLE 413 341 - (Ethylsulfonyl-4-piperidinyl-5- (54rr (2S) -2-hydroxypropyl] (methyl) amino] methyl) -3-thienyl) -1H-indol-7-carboxamide Chiral trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate (salt) of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydroxy] -1-methylethyl] (methyl) amino] methyl.}. -3-thienyl) -1H-indole-7-carboamide, substituting (2R) -2-amino-1-propanol for (2S) -1- amino-2-propanol (1.20 mmol) to yield 15.3 mg of the title compound (36.1%) LC / MS = m / z 519.3 [M + H]. Retreat time: 1.49 min.
EXAMPLE 414 341- (Ethylsulfonyl) -4-piperidini.l-545 - ((methyl (2R) -tetrahydro-2-furanylmethylamino) methyl) -3-thienin-1H-indole-7-carboxamide trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacelale (salt) of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydroxy] -1-methyl-ethyl] (methyl) amino] -methyl] -3-l-phenyl) -1H-indole-7-carboxamide, susliluyendo (2R) -2-amino-1-propanol by [(2R) -tetrahydro -2-furanylmethyl] amine (1.20 mmol) to yield 15.5 mg of the title compound (35.1%) LC / MS = m / z 545.3 [M + H]. Retreat time: 1.58 min.
EXAMPLE 415 341 - (ethylsulfonyl) -4-piperidinyl-5- (54r (24 (2-hydroxyethyl) oxyethyl) (methyl) amino-methyl) -3-thienyl) -1H-indole-7- trifluoroacetate carboxamide The title compound was prepared according to the general procedure of fluorifluoroacety (salt) of 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydroxy] -1-methylethyl] (methyl) amino] meityl} -3-ynyl) -1 H -indole-7-carboamide, suspending (2f?) - 2-amino-1-propanol for 2 - [(2 -aminoethyl) oxy] ethanol (1.20 mmol) to yield 17.2 mg of the title compound (38.7%). LC / MS = m / z 549.5 [M + H]. Retreat time: 1.48 min.
EXAMPLE 416 341 - (Ethylsulfonyl) -4-piperidinyl-545- (1-ethylf2- (methyloxy) etH-amino) ethyl-3-thienip-1H-indol-7-carboxamide trifluoroacetate To a solution of 5- (5-acetyl-3-thienyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (46 mg, 0.1 mmol) in EtOH (2.0 ml) and AcOH (0.2 ml) were added methyl [2- (methyloxy) ethyl] amine (200 μl, 2.0 mmol) and sodium cyanoborohydride (50 mg, 0.8 mmol). The mixture was reacted in the microwave at 120 ° C for 2 h. More methyl [2- (methyloxy) ethyl] amine (100 μl, 1.0 mmol) and sodium cyanoborohydride (25 mg, 0.4 mmol) were added and reacted for a further 3 h in the microwave at 120 ° C for 2 h. This was followed by another addition of methyl [2- (methyloxy) ethyl] amine (100 μl, 2.0 mmol) and sodium cyanoborohydride (25 mg, 0.4 mmol) and reacted for a further 3 h in the microwave at 120 °. C for 2 h. All solvent was concentrated and purified by Gilson Preparative HPLC to yield 20 mg of the title compound (38%). LC / MS = m / z 533.2 [M + H]. Time of laugh .: 1.46 min.
EXAMPLE 417 341- (Ethylsulfonyl) -4-piperidinyl-5- (541-fmethyl (propyl) aminoethyl) -3-thienyl) -1H-indol-7-carboxamide trifluoroacetate To a solution of 5- (5-acetyl-3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (46 mg, 0.1 mmol) in EtOH (2.0 ml) and AcOH (0.2 ml) were added N-methyl-1-propanamine (200 μl, 2.0 mmol) and sodium cyanoborohydride (50 mg, 0.8 mmol). The mixture was reacted in the microwave at 120 ° C for 120 min. Additional N-methyl-1-propanamine (100 μl, 1.0 mmol) and sodium cyanoborohydride (25 mg, 0.4 mmol) were added and reacted for a further 3 h in the microwave at 120 ° C for 120 min. All the solvent was concentrated, dissolved in DMSO and the solids were filled. Then, it was purified by Gilson Preparative HPLC to yield 18 mg of the title compound (35%). LC / MS = m / z 517.2 [M + H]. Retreat time: 1.52 min.
EXAMPLE 418 5- (2,3-Dihydro-1 H-isoindol-5-yl-341 - (ethylsulfonyl) -4-piperidinyl-1 H-indole-7-carboxamide To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4,4,5,5-terylammell-1, 3,2-dio? Aborolan-2-yl) -1H-indole- 7-carboamide (150 mg, 0.325 mmol) in dioe (0.75 ml) and water (0.25 ml) were added 5-bromo-2,3-dihydro-1 H-isoindole hydrochloride (130 mg, 0.651) mmol) and cesium carbonate (636 mg, 1952 mmol). The reaction mixture was maintained under an atmosphere of argon for 10 min before the addition of tetrakis (trphenylphosphine) palladium (0) (19 mg, 0.016 mmol). The resulting mixture was heated in a microwave for 20 min at 150 ° C. Then, the mixture was purified by HPLC to give 11 mg of the title compound. LC / MS = m / z 453 [M + H]. Time of day: 1.33 min.
EXAMPLE 419 5- (2-Ethyl-2,3-dihydro-1H-isoindol-5-yl) -341- (ethylsulfonyl) -4-piperidinyl-1H-indole-7-carboxamide To a solution of 5- (2,3-dihydro-1H-isoindole-5-yl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide (20 mg, 0.044 mmol) in MeOH (1 ml) was added acelaldehyde (6 mg, 0.133 mmol), sodium cyanoborohydride (6 mg, 0.088 mmol) and zinc chloride (6 mg, 0.044 mmol). The mixture was heated in a microwave for 30 min at 100 ° C. Then, the mixture was concentrated, filtered and purified by Gilson's Preparaliva HPLC to give 8.2 mg of the title compound. LC / MS = m / z 481 [M + H]. Retreat time: 1.40 min.
EXAMPLE 420 341 - (Ethylsulfonyl-piperidinyl-54241-methyl ethyl, -2,3-dihydro-1 H-isoindol-5-ill-1 H-indol-7-carboxamide To a solution of 5- (2,3-dihydro-1H-isoindol-5-yl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboamide (30 mg, 0.066 mmol) in MeOH (0.5 ml) was added 2-propanone (12 mg, 0.198 mmol), sodium cyanoborohydride (8 mg, 0.133 mmol) and zinc chloride (9 mg, 0.066 mmol). The resulting mixture was heated in a microwave for 30 min at 100 ° C. Then, the mixture was concentrated, filtered and purified by Gilson Preparative HPLC to give 0.8 mg of the title compound. LC / MS = m / z 495.5 [M + H]. Retreat time: 1.56 min.
EXAMPLE 421 54241, 2-dimethylpropyl) -2,3-dihydro-1 H-isoindol-5-ill-341 - (ethylsulfonyl-4-piperidineM1-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1H-isoindol-5 -yl] -1H-indole-7-carboamide, substituting 2-propanone for 3-methyl-2-butanone (17 mg, 0.198 mmol) to yield 14.6 mg of the title compound. LC / MS = m / z 523 [M + H]. Retreat time: 1.55 min.
EXAMPLE 422 341- (Ethylsulfonyl) -4-piperidinyl-1-542- (1-methylpropyl) -2t3-dihydro-1H-isoindol-5411-1 fí-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1H-isoindol-5- il] -1H-indole-7-carboamide, substituting 2-propanone for 2-butanone (14 mg, 0.198 mmol) to yield 14.6 mg of the title compound. LC / MS = m / z 509 [M + H]. Time of laugh: 1.48 min.
EXAMPLE 423 542-d-ethylpropyl, -2,3-dihydro-1 H-isoindol-5-n-341 - (ethylsulfonyl-4-piperidinyl] -1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-pperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1H-isoindole -5-yl] -1H-indole-7-carboxamide, substituting 2-propanone for 3-pentanone (17 mg, 0.198 mmol) to yield 13.8 mg of the title compound. LC / MS = m / z 523 [M + H]. Retreat time: 1.58 min.
EXAMPLE 424 5- (2-cyclopentyl-2,3-dihydro-1H-isoindol-5-yl) -341- (ethylsulfonyl) -4-piperidin-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1H-isoindol-5 -yl] -1H-indole-7-carboxamide, substituting 2-propanone for cyclopentanone (17 mg, 0.198 mmol) to yield 4.8 mg of the title compound. LC / MS = m / z 521 [M + H]. Retreat time: 1.54 min.
EXAMPLE 425 542- (cyclopropylmethyl) -2,3-dihydro-1HJsoindol-5-yl] -341- (ethylsulfonyl) -4- piperidin-1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-methyleryl) -2,3-dihydro-1 H-isoindol-5 -yl] -1H-indole-7-carboxamide, substituting 2-propanone for cyclopropanecarbaldehyde (14 mg, 0.198 mmol) to yield 10.8 mg of the title compound. LC / MS = m / z 507 [M + H]. Retreat time: 1.47 min.
EXAMPLE 426 542- (2,2-Dimethylpropyl) -2,3-dihydro-1-t-isoindol-5-in-341- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide The compound of the illole was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1 H-isoindol-5 -yl] -1H-indole-7-carboxamide, substituting 2-propanone for 2,2-dimethylpropanal (17 mg, 0.198 mmol) to yield 12.7 mg of the title compound. LC / MS = m / z 523 [M + H]. Retreat time: 1.60 min.
EXAMPLE 427 341 - (Ethylsulfonyl, -4-piperidinin-5- (2-methyl-2,3-dihydro-1 H-isoindol-5-yl) -1 H -indole-7 -carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-methylethyl) -2,3-dihydro-1H-isoindol-5 -yl] -1H-indole-7-carboxamide, substituting 2-propanone for formaldehyde (6 mg, 0.198 mmol) to yield 1.2 mg of the title compound. LC / MS = m / z 467 [M + H]. Retreat time: 1.37 min.
EXAMPLE 428 341- (Ethylsulfonyl) -4-piperidinyl] -5- (24f (phenylsulfonyl) aminolcarbonyl> -2.3- dihydro-1-f-isoindol-5-iO-l H-indol-7 -carboxamide To a solution of 5- (2,3-dihydro-1H-isoindol-5-yl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indol-7-carboxamide (30 mg, 0.066) mmol) in DMSO (1.0 ml) was added benzenesulfonyl isocyanate (15 mg, 0.079 mmol). The resulting mixture was stirred overnight at room temperature. The mixture was purified by Gilson Preparative HPLC to give 15.5 mg of the title compound. LC / MS = m / z 637 [M + H]. Retreat time: 1.94 min.
EXAMPLE 429 5- (54. (2ft) -2- (aminocarbonyl, -1-pyrrolidinylmethyl) -3-thienyl) -3414 (1-methylethyl) sulfonyl-1-4-piperidinyl > -1H-indol-7 -carboxamide To a solution of 5- (5-formyl-3-thienyl) -3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1H-indole-7-carboxamide (25 mg, 0.054 mmol) in DMSO (2 ml) was added D-prolinamide (114 mg, 1 mmol) and 2 drops of acetic acid. The resulting mixture was stirred at room temperature for 4 h followed by an addition of sodium triacetoxyborohydride (212 mg, 1.0 mmol). The mixture was reacted overnight. Then, it was purified by Gilson Preparative HPLC to give 20.4 mg of the title compound. LC / MS = m / z 557 [M + H]. Retreat time: 1.56 min.
EXAMPLE 430 341- (Ethylsulfonyl) -4-piperidinin-5- (54rr2- (ethylthio) etin (methyl) aminomethyl) -3-thieniD-1 H-indol-7-carboxamide To a solution of 5- (5-formyl-3-lienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboamide (40 mg, 0.09 mmol) in DMSO (2 ml) was added [2- (ethylthio) ethyl] amine (105 mg, 1 mmol), acetic acid (50 μl). ) and sodium triacexoxyborohydride (212 mg, 1.0 mmol). The mixture turned out to be stiff during the night. To the mixture was added sodium cyanoborohydride (80 mg, 1.2 mmol) and was agitated overnight followed by addition of formaldehyde (100 μl, 1.2 mmol). Then, the mixture was stirred for a further 3 h. Then, it was purified by Gilson Preparative HPLC to give 7.0 mg of the title compound. LC / MS = m / z 550 [M + H]. Retreat time: 1.68 min.
EXAMPLE 431 341- (Ethylsulfonyl) -4-piperidinin-5454r (24 (2-hydroxyethyl) thio] ethyl> (methyl) amino1methyl> -3-thienyl) -1H-indole-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- {[[2- (ethylthio) ethyl] (methyl) amino] meily .3. -3-lienyl) -1H-indole-7-carboxamide susíiuuyendo [2- (eíilíio) éil] amina by 2 - [(2-aminoeil) íio] elanol (121 mg, 1.0 mmol) to produce 16.0 mg of the title compound. LC / MS = m / z 566 [M + H]. Retreat time: 1.52 min.
EXAMPLE 432 341 - (Ethylsulfonyl) -4-piperidinyl-5- (54rr2-hydroxy-1- (hydroxymethyl) ethyl] (methyl) aminolmethyl) -3-thienyl) -1H-indol-7-carboxamide The title compound was prepared according to the general procedure of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- {[[2- (ethylthio) ethyl] (methyl) amino] methyl .3. -3-thienyl) -1H-indole-7-carboxamide substituting [2- (eylidene) eyl] amine for 2-amino-1,3-propanediol (91 mg, 1.0 mmol) to yield 15.0 mg of the compound of the íííulo. LC / MS = m / z 535 [M + H]. Time of laugh .: 1.44 min.
EXAMPLE 433 [(4- {74-aminocarbonyl-34-dimethylsulfonyl) -4-piperidinyl-1H-indol-5-yl} -2- Ethyl tieniPmetillmetilcarbamate To a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5-. { 5- [(meitylamino) meityl] -3-yenyl} -1 H -indole-7-carboxamide (50 mg, 0.11 mmol) in DMF (1.0 ml) at 0 ° C was added arylamine (0.06 ml, 0.44 mmol) and ethyl chloridocarbonal (0.021 ml, 0.22 mmol). The resulting mixture was reacted for 30 min followed by purification on Gílson Preparative HPLC to yield 31.4 mg of the title compound (53.5%). LC / MS = m / z 533.2 [M + H]. Time of laugh .: 2.06 min.
EXAMPLE 434 N4 (447- (aminocarbonyl) -341- (ethylsulfonyl) -4-piperidinin-1H-indol-5-yl> 2-thienyl) methyl] -N-methylglycinate ethyl To a solution of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-formyl-3-thienyl) -1H-indole-7-carbo-amide (45 mg, 100 μmol) in dimethylsulfohydrate (1.0 ml) were added N-methyl glycine (320 μmol) and 2 to 3 gols of glacial acélico acid. The resulting mixture is stirred overnight. After 18 h, sodium triacerate-iborohydride (200 mg, 1000 μmol) is added. This mixture is stirred for 1.5 h followed by purification by Gilson Preparative HPLC to give 16.5 mg of the title compound (30.0%). LC / MS = m / z 547.1 [M + H]. Retreat time: 1.55 min.
EXAMPLE 435 trifluoroacetate (salt) of 3-y1 - (ethylsulfonyl) -4-pi peridinyl-5- (54f1 (1S) -2- hydroxy-1-methylenetin (methyl) aminolmethyl> -3-thienyl ) -1 H -indole-7 -carboxamide To a vial containing (2S) -2-amino-1-propanol (91 mg, 1.2 mmol) was added a solution of 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5-formyl). 3-ynyl) -1H-indole-7-carboamide (30 mg, 0.067 mmol) in DMSO (300 μl) and acetic acid (50 μl). The resulting mixture was stirred for 5 min followed by an addition of triacetyl-sodium hydrogen carbonate (250 mg, 1.20 mmol) in DMSO (800 μl). The mixture was stirred overnight. Then, sodium cyanoborohydride (79 mg, 1.20 mmol) in methanol (300 μL) was added and it was stirred for 48 h. This was followed by an addition of formaldehyde (100 μl).
Then, the reaction was agitated for 1 h followed by separation with a 2 g SCX cartridge. Then, the solids were removed by filtration, the solution was concentrated and the purification was repeated on a 5 g SCX cartridge eluting with ammonia in MeOH. The ammonia from the MeOH fraction collection was concentrated and separated using Gilson Preparative HPLC to yield 18.7 mg of the title compound. LC / MS = m / z 519.3 [M + H]. Retreat time: 1.49 min.
EXAMPLE 436 5- (54 I- (1,1-dioxidotetrahydro-3-thienyl) (methyl) aminomethyl> -3-thienyl) -341- (ethylsulphonyl) -4-piperidin-1H-indole trifluoroacetate The title compound was prepared according to the general procedure of trifluoroacetate of 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1 S) -2-hydro? I- 1-methylethyl] (meityl) amino] methyl.} - 3-ynyl) -1H-indole-7-carboamide, suspending (2S) -2-amino-1-propanol for (1,1-dio? Idofeirahydro) -3-ynyl) amine (1.20 mmol) to yield 9.3 mg of the title compound. LC / MS = m / z 579 [M + H]. Time of laugh: 1.54 min.
Biological data Assay with IKK2 Recombinant human IKKβ (residues 1-737) in baculovirus was tested as a fusion protein with C-terminal GST signal, and its activity was evaluated using a fluorescence resonance energy transfer-resolution test in the lime (TR-FRET). In summary, IKK2 (0.5 nM - 5nM final) diluted in assay lamp was added (50 mM HEPES), 10 mM MgCl2, CHAPS pH 7.4 1 mM with 1 mM DTT and 0.01% BSA w / w) to wells containing various concentrations of DMSO compound or vehicle (1.7% final). The reaction was initiated by the addition of substrate GST-IB (25 nM final) / ATP (1 μM final), in a total volume of 6 μl. The reaction was incubated for 15 minutes at room temperature, then terminated by the addition of 3 μl of sample removal reagent containing 50 mM EDTA (100 mM HEPES pH 7.4, 150 mM NaCl, 50 mM EDTA and 0.01% BSA). p / v) containing monoclonal antibody 12C2 antiphosfoserin-IB-32/36 (Cell Signaling Technology, Beverly Massachusetts, USA) labeled with europium chelate W-1024 (Wallac OY, Turku, Finland) and an anti-GST antibody was added labeled with APC (Prozyme, San Leandro, California, USA), and the reaction was further incubated for 60 minutes at room temperature. The degree of phosphorylation of GST-IB was measured using a BMG Rubyslar plate lecíter (BMG Labtech, Ailesbury, UK) as a ratio between the specific 665 nm energy transfer signal and the europium reference signal of 620 nm.
Results The compounds of Examples 1-31, 33, 35-51, 53-58, 60-97, 100-116, 118-121, 123-137, 139-163, 165-172, 174-197, 199-220, 222-242, 244-276, 279-330, 332-358, 360-385, 387-402, 404-419, 421-426, and 428-436 were tested for activity against IKK2 and it was found that These Examples were inhibitors of IKK2. These compounds had a pIC50 value of 5.0 or greater. Examples 277 and 278 were also tested for activity against IKK2 and it was found that these two compounds had pIC50 values less than 5.0.
Monocyte Assay The effect of inhibition of IKK-D on the production of cyclokines stimulated by human monocytes was evaluated as follows: Monocytes were isolated from heparinized whole blood by Ficoll gradient, followed by purification of CD14 + cells using magnetic beads for MACS cell separation. Monocytes isolated 6 were then adhered to 96 well cylindrical plates at 1 x 10 cells / ml in RPMI 1640 and 10% FBS (JRH Biosciences, Lenexa KS) for 2 h. The test compounds were added to the wells 30 minutes before stimulation with a final vehicle concentration of 0.1% DMSO. Monocytes were activated by the addition of 200 ng / ml endotoxin (LPS, E. coli serotype 026: B6) (Sigma, Yes. Louis, MO.) And incubated for 24 h at 37 ° C. Supernatants without cells were analyzed by ELISA or Alphascreen for TNF-D. The ELISAs were performed using paired Ab Pharmingen and the Alphascreen was performed using Alphascreen acceptor beads and Perkin Elmer donor beads and human anti-TNF Ab and biotinylated human anti-TNF from R &D Systems. The viability of the cells was determined by exclusion of 10% ipipic blue.
Resulted Certain Examples of this invention were tested in the monocyte assay. It was found that Examples 1-3, 5-13, 16-23, 25-31, 33, 37, 42-44, 61, 65-69, 71-73, 75-78, 83, 86-89, 92 , 96, 100-117, 119-121, 123-127, 129-131, 139, 141, 144, 151, 154-157, 160-164, 166-167, 169-172, 182, 191, 208-214 , 216-220, 222, 223, 227, 230-248, 250, 251, 269, 271, 273-276, 279-83, 285-90, 292-296, 298, 304-327, 329, 332-337 , 342, 343, 346, 348, 353, 356-358, 361, 366-368, 370-373, 376, 380, 382, 391, 394-397, 399-404, 406, 408, 409, 412, 417 -419, 432, 434, and 435 had an IC50 of < 2 DM in this essay. Examples 4, 15, 24, 34-36, 50, 70, 118, 128, 132-134, 136, 137, 140, 143, 146-148, 153, 158, 159, 165, 168, 192-194, 196, 197, 200-207, 224, 249, 253-262, 270, 272, 299-303, 330, 338-341, 360, 362, 363, 365, 374, 375, 377-379, 381, 383, 385, 388-390, 392, and 393 did not inhibit on > 65% at 1 DM (highest dose tested). Examples 39, 40, 45-49, 58-60, 62, 63, 74, 79-81, 84, 85, 90, 91, 94, 95, 97, 173-181, 184-190, 195, 198, 328, 345, 347, 349-353, 345, 355, 429-431, 433 and 436 showed an inhibition < 60% at 300 nM. Variable results were obviated in the monocyclic assay for Examples 38, 64, 82, 215, 297, 344, 364 and 369.

Claims (11)

  1. NOVELTY OF THE INVENTION CLAIMS 1. - A compound according to formula (I): in which or X is phenyl, heteroaryl, 1, 2,3,4-tetrah.dronaphthalenyl or 2,3-dihydro-1H-indenyl, wherein said phenyl, heteroaryl, 1, 2,3,4-tetrahydronaphthalenyl and 2,3-dihydrogen groups -1H-indenyl are optionally susliluted with one or two subsitutes each of them independently selected from the following: 1) halo, 2) nitro, 3) cyano, 4) -NR7R8, 5) C- | -C6 alkyl, 6) CHO, 7) CONH2 and 8) -OR4, wherein said alkyl group C < C6 is optionally susliluted with a group -NR4R5; Y is a C1-C6 alkylene or bond, wherein C- | -C6 alkylene is optionally substituted with one or two substituents each independently selected from the following: 1) C1-C3 alkyl optionally substituted with a group OR4, 2) C3- cycloalkyl C-j, 3) meloxi, 4) hydroxy and 5) heteroaryl; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two suslidines each independently selected from the following: 1) optionally substituted C-C alkyl with an OR4 group or a heterocycloalkyl group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) -CONH2 5) hydroxy, 6) heteroaryl; 7) CF3, 8) phenyl, 9) heterocycloalkyl and 10) N (CH3) 2 R2 is selected from 1) H, 2) fluoro, and 3) chloro; R3 is selected from 1) H, 2) fluoro, and 3) chloro; R4 is selected from 1) H and 2) Cj-Ce alkyl, wherein said C- | -C6 alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C5-C6 heterocycloalkyl , 3) - CO2El, 4) C- | -C6 alkoxy, 5) C3-C7 cycloalkyl, 6) C- | -C6 alkyl, 7) -S? 2R10 and 8) -C (O) R10, wherein said C3-C7 cycloalkyl groups and Cj-Ce alkyl are optionally substituted with one selected substituent on R6, each R6 is independently selected in 1) -NR7R8, 2) -S? 2R7 , 3) -CONH2, 4) -CF3, 5) -CN, 6) -C02R7, 7) -OCH2CH2OR7, 8) -SR5, 9) C3-C4 alkenyl, 10) OH, 11) C- | -C6 alkoxy , 12) heleroaryl, 13) cycloalkyl C3-C7, 14) phenyl, 15) helerocycloalkyl and 16) halo, wherein said heteroaryl, cycloalkyl, phenyl and heterocycloalkyl groups are optionally substituted with one to two substituents selected from R9; R7 is selected from 1) H, 2) C 1 -C 3 alkyl and 3) phenyl; R8 is selected from 1) H, 2) C1-C3 alkyl and 3) -C (0) R4; each R9 is independently selected from 1) hydroxy, 2) OMe, 3) nitro, 4) C- | -Ce alkyl, 5) NH2, 6) halo, 7) CF3, 8) C- alkoxy | -C6 and 9) CN; R10 is selected from 1) alkyl C < \ -CQ, 2) phenyl, 3) C3-C7 cycloalkyl, 4) heteroaryl, 5) C- | -Ce heleroaryl and 6) helerocycloalkyl, where said C- | -C alkyl group is substituted with one to two substitute each of them independently selected from C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a group -C (0) R7; and wherein said phenyl, heteroaryl and C- | -C6 heteroaryl groups are optionally substituted with one to two substituents selected from R11; each R 11 is independently selected from 1) H, 2) C 1 -C 6 alkyl and 3) halo; U is a bond, alkylene C < | -C6 or C2-C6 alkenylene; V is phenyl, 5- or 6-membered heteroaryl, 5-7 membered heterocycloalkyl, C5-C7 cycloalkyl or C5-C7 cycloalkenyl, each of which is substituted with -N (R7) S (0) mR12, -S (0 ) mN (R7) R12, -S (0) mR12, or -C (0) R12; m is 1 or 2; and R 12 is alkyl C < | -C6, C3-C7 cycloalkyl, C3 | -C6 alkyl-C3-C7 cycloalkyl or C- | -C6 alkyl-phenyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 2. The compound according to claim 1, further characterized in that: R1 is the group -XYZ; X is phenyl or heeroaryl, wherein said phenyl and heteroaryl groups are optionally substituted with one or two substituents each independently selected from the following: 1) halo, 2) nitro, 3) cyano, 4) -NR7R8, 5) alkyl C- | -C6, 6) CHO, 7) CONH2 and 8) -OR4, wherein said C ^-C alquilo alkyl group is optionally suslíuuido with a -NR4R5 group; And it's a bond or alkylene C- | -C6, wherein the C1-C6 alkylene group is optionally substituted with one or two substituents each independently selected from the following: 1) C1-C3 alkyl optionally substituted with an OR4 group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) hydroxy and 5) heteroaryl; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two substituents each independently selected from the following: 1) C- | -C alkyl optionally substituted with a group OR4, 2) C3-C7 cycloalkyl , 3) methoxy, 4) hydroxy and 5) heteroaryl; R2 is selected from 1) H, 2) fluoro, and 3) chloro; R3 is selected from 1) H, 2) fluoro, and 3) chloro; R 4 is selected from 1) H and 2) alkyl C < | -C6, wherein said C- | -C6 alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C- | -C6 alkoxy, 3) C3-C7 cycloalkyl, 4) C- | -C6 alkyl, 5) -SO2RIO and 6) C (O) R10, wherein said cycloalkyl groups C3-C7 and C4-CQ alkyl are optionally substituted with one to three substituents selected from R6; each R6 is independently selected from 1) -NR7R8, 2) -SO2R7, 3) OH, 4) methoxy, 5) heeroaryl, 6) C3-C7 cycloalkyl, 7) phenyl, 8) heteroarylcycloalkyl and 9) halo, wherein said groups Iron, aryl, cycloalkyl, phenyl and heteroaryloalkyl are optionally susiluted with one to two substituents selected from R 9; R7 is selected from 1) H and 2) C1-C3 alkyl; R8 is selected from 3) H and 4) C 1 -C 3 alkyl; each R 9 is independently selected from 1) hydroxy, 2) ni, 3) C 1 -C 6 alkyl, 4) NH 2, 5) halo, 6) CF 3, 7) alkoxy C < | -C6 and 8) CN; R10 is selected from 1) Ci-Ce alkyl, 2) phenyl, 3) C3-C7 cycloalkyl and 4) heteroaryl, wherein said C- | -C alkyl group is substituted with one to two substituents each independently selected from cycloalkyl C3-C7 and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a group -C (0) R7; and wherein said phenyl and heteroaryl groups are optionally substituted with one to two selected substituents on R11; each R 11 is independently selected from 1) H, 2) alkyl C < | -C6 and 3) halo; U is a bond, alkylene C- | -C6 or C2-C alkenylene; V is phenyl, 5- or 6-membered heteroaryl, 5-7 membered heterocycloalkyl, C5-C7 cycloalkyl or C5-C7 cycloalkenyl, each of which is substituted with -N (R7) S (0) mR12, -S (0 ) mN (R7) R12, -S (0) mR12 or -C (0) R12; m is 1 or 2; and R 12 is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkyl-C 3 -C 7 cycloalkyl or C 1 -C 6 alkyl phenyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 3. The compound according to claim 1, further acterized in that: R1 is the group -XYZ or X is phenyl, heteroaryl, 1, 2,3,4-telrahydronaphthalenyl or 2,3-dihydro-1H-indenyl; Y is a C1-C6 alkylene or bond; Z is -NR4R5 or helerocycloalkyl, wherein said helerocycloalkyl group is optionally substituted with one or two Each of them is selected independently from the following: 1) alkyl C < [-CQ] optionally substituted with an OR4 group or a heterocycloalkyl group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) -CONH2 5) hydroxy, 6) heteroaryl, 7) CF3, 8) phenyl, 9) heterocycloalkyl and ) N (CH3) 2 R2 is H; R3 is H; R4 is selected from 1) H and 2) C- | -C alkyl, wherein said alkyl group C < C6 is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C5-C6 heterocycloalkyl, 3) -C02Et, 4) C 1 -C 6 alkoxy, 5) C 3 -C 7 cycloalkyl, 6) C 1 -C 6 alkyl, 7) SO 2 IO and 8) -C (O) R 10, wherein said C 3 -C 7 cycloalkyl groups and alkyl C- | -CQ are optionally substituted with one of the selected hydrophilic groups on R6; each R6 is independently selected from 1) -NR7R8, 2) -S02R7, 3) -CONH2, 4) -CF3, 5) -CN, 6) -C02R7, 7) -OCH2CH2OR7, 8) -SRd, 9) C3-C4 alkenyl, 10) OH, 11) C-C6 alkoxy, 12) heteroaryl, 13) C3-C7 cycloalkyl, 14) phenyl, 15) heterocycloalkyl and 16) halo, wherein said heteroaryl, cycloalkyl, phenyl and heterocycloalkyl groups are optionally substituted with one to two substituents selected from R9; R7 is selected from 1) H, 2) C1-C3 alkyl and 3) phenyl; R8 is selected in line 1) H, 2) C1-C3 alkyl and 3) -C (0) R4; each R 9 is independently selected from 1) hydroxy, 2) -Orne 3) ni, 4) C 1 -C 6 alkyl, 5) NH 2, 6) halo, 7) CF 3, 8) Ci-Ce alkoxy and 9) CN; R10 is selected from 1) alkyl C < | -C6, 2) C3-C7 cycloalkyl, 3) heteroaryl, 4) C- | -C6 heteroaryl and 5) helerocycloalkyl, 6) wherein said C-J-C6 alkyl group is substituted with one to two substituents each independently selected from C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally substituted with a group -C (0) R7; and wherein said phenyl, heteroaryl and C 1 -C 6 heteroaryl groups are optionally substituted with one to two subluclyles selected from R 11; each R11 is independently selected in 1) H, 2) C < \ -CQ and 3) halo; U is a link; V is a 5-7 membered helerocycloalkyl substituted with -S (0) mR12; m is 1 or 2; and R12 is C-i-Co alkyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 4. The compound according to claim 1, further characterized in that: R1 is the group -XYZ; X is phenyl or heteroaryl; Y is a C-i-Ce bond or alkylene; Z is -NR4R5 or heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted with one or two substituents each independently selected from the following: 1) C- | -C6 alkyl optionally substituted with a group OR4, 2) C3-C7 cycloalkyl , 3) methoxy, 4) hydroxy and 5) heteroaryl; R2 is H; R3 is H; R4 is selected from 1) H and 2) C1-C6 alkyl, wherein said C- | -C alkyl group is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) H, 2) C- | -C6 alkoxy, 3) C3-C7 cycloalkyl, 4) C- | -C alkyl, 5) -SO2RIO and 6) -C (O) R10, wherein said C3-C7 cycloalkyl groups and alkyl C ^ -CQ are optionally substituted with one to three substituents selected among R6; each R6 is independently selected from 1) -NR7R8, 2) S02R7, 3) OH, 4) methoxy, 5) heteroaryl, 6) C3-C7 cycloalkyl, 7) phenyl, 8) heyerocycloalkyl and 9) halo, wherein said heyaroaryl groups , cycloalkyl, phenyl and helerocycloalkyl are optionally substituted with one to two selected substituents on R.sup.9; R7 is selected from 1) H and 2) C1-C3 alkyl; R8 is selected from 1) H and 2) C1-C3 alkyl; each R9 is independently selected in 1) hydroxy, 2) ni, 3) C- | -C6 alkyl, 4) NH 2, 5) halo, 6) CF 3, 7) C 1 -C 6 alkoxy and 8) CN; R10 is selected from 1) C- | -C6 alkyl, 2) phenyl, 3) C3-C7 cycloalkyl and 4) heteroaryl, wherein said C- | -C6 alkyl group is substituted with one or two substituents each independently selected between C3-C7 cycloalkyl and -S-R7; wherein said heterocycloalkyl group is optionally susliluted with a -C (0) R7 group; and wherein said phenyl and heteroaryl groups are optionally substituted with one to two substituents selected from R11; each R11 is independently selected from 1) H, 2) C- \ -CQ alkyl and 3) halo; U is a link; V is a 5-7 membered heterocycloalkyl substituted with -S (0) mR12; m is 1 or 2; and R12 is C ^ -CQ alkyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 5. The compound according to claim 1, further characterized in that: R1 is the group -XYZ; X is 2- or 3- iiophenyl; Y is a C 1 -C 4 bond or alkylene; Z is -NR4R5 or helerocycloalkyl, 1) optionally substituted C- ^ - Ce alkyl with an OR4 group or a heterocycloalkyl group, 2) C3-C7 cycloalkyl, 3) methoxy, 4) -CONH2.5) hydroxy, 6) heteroaryl; 7) CF3, 8) phenyl, 9) heyerocycloalkyl and 10) N (CH 3) 2 R 2 is H; R3 is H; R 4 is selected from 1) H and 2) alkyl C < \ -CQ, where said alkyl group C < \ -CQ it is optionally substituted with a hydroxy group or a methoxy group; R5 is selected from 1) C3-C7 cycloalkyl, 2) C-j-Ce alkyl, wherein said C3-C7 cycloalkyl groups and C- | -C6 alkyl are optionally substituted with one to three substituents selected from R6; each R6 is independently selected from 1) -NR7R8, 2) -CONH2, 3) -CN, 4) -OCH2CH2OR7.5) C3-C4 alkenyl, 6) OH, 7) alkoxy C < \ -CQ, 8) heteroaryl, 9) C3-C7 cycloalkyl, 10) phenyl, 11) heterocycloalkyl and 12) halo, wherein said heleroaryl, cycloalkyl, phenyl and helerocycloalkyl groups are optionally substituted with one to two substituents selected from R9; R7 is selected from 1) H, 2) C1-C3 alkyl and 3) phenyl; R8 is selected from 1) H, 2) C1-C3 alkyl and 3) -C (0) R4; each R9 is independently selected from 1) C- | -Co alkyl; U is a link; V is 4-piperidinyl susiiluted with -S (0) 2R12; and R12 is ethyl or isopropyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 6. The compound according to claim 1, further characterized in that the group U-V is and R12 is ethyl or isopropyl; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 7. The compound according to claim 1, Also characterized because it is a compound of formula (II): (II) wherein R 13 is -NR 14 R 15 or heterocycloalkyl wherein said heterocycloalkyl group is optionally substituted with one or two substituents selected from the following: 1) C 1 -C 6 alkyl optionally substituted with a group OR 14, 2) hydroxy, 3) methoxy and 4) heteroaryl; R14 is selected from 1) H and 2) C- | -C alkyl, wherein said C- | -Cg alkyl group is optionally susiluted with a hydroxyl group or a meloxi group; R15 is selected from 1) H, 2) methoxy, 3) C3-C7 cycloalkyl and 4) C- \ -CQ alkyl, wherein said C3-C7 cycloalkyl groups and C < \ -CQ are optionally substituted with one to three substituents selected from R16; each R16 is independently selected from 1) -NR17R18, 2) -S02R17, 3) OH, 4) methoxy, 5) heteroaryl, 6) C3-C7 cycloalkyl, 7) phenyl and 8) heterocycloalkyl, wherein said heteroaryl, cycloalkyl, phenyl and heterocycloalkyl are optionally substituted with one to three substituents selected from R19; R17 is selected from 1) H and 2) C1-C3 alkyl; R18 is selected from 1) H and 2) C1-C3 alkyl; R19 is selected from 1) hydroxy, 2) ni, 3) C- | -C6 alkyl, 4) NH2, 5) halo, 6) CF3 and 7) alkoxy C < \ -CQ; and n is 1 to 3; or a pharmaceutically acceptable, solvated or polymorphic salt thereof. 8. The compound according to claim 1, further characterized because it is: 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- (1-piperidinylmethyl) phenyl] -1H- indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (1-piperazinylmethyl) phenyl] -1H-indol-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3- (methylene [2- (methylsulfonyl) ellyl] amino} methyl) phenyl] -1H-indole-7-carboxamide; 5- (3-. {[[2- (dimethylamino) eyl] (mell) amino] methyl} phenyl) -3- [1- (ethylsulfonyl) -4-picperidyl] -1 H- indol-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(4- { 2 - [(2-hydroxyethyl) oxy] ethyl] -1-piperazinyl) mell] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[3- (hydroxymethyl) -1-p-peridinyl] methyl} phenyl) -1 H- indole -7-carboxamide; 5- [3- (. {Bis [2- (meilyloxy) eyl] amino] -methyl) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 5-. { 3 - [(2,6-dimethyl-4-morpholinyl) meily] phenol} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pyridinyl] -5- (3- {[[2- (1, 3-yiazol-2-yl) -1-pyrrolidinyl] methyl} phenyl} - 1 H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3 { [2- (2-lyl) -1-pyrrolidinyl] -methyl} phenyl) -1H-indole -7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-hydroxy-2-phenylethyl) (melil) amino] methyl} phenyl) - 1 H-indole-7-carboxamide; 5- (3. {[[Eyl (meily) amino] -methyl} phenyl) -3- [1 - (ef-lysulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- (aminomethyl) phenyl] -3- [1- (elylsulfonyl) -4- pyperidinyl] -1H-indole-7-carboxamide; 5-. { 3 - [(cyclopenylamino) meily] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5- [3- ( { [(3,4-Dihydroxyphenyl) -methyl] -amino} -methyl) -phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(2-ynylmethyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-p-peridinyl] -5- [3- ( { [(2S) -2- (hydroxymethyl) -3-methyl-vayl] -amino} -methyl) -phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-hydroxy-1-methyleryl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(Ire7S-4-hydroxycyclohexyl) amino] methyl] phenyl) -1H-indole-7- carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [( { [1 - (1-piperidinyl) cyclohexyl] -methyl} -amino) -methyl] -phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-p-peridinyl] -5- [3- ( { [(2S) -2-hydroxypropyl] amino] -methyl) phenyl] -1H-indole -7-carboxamide; 5-. { 3 - [(erylamino) methyl] phenyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -5-. { 3 - [(propylamino) meily] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulphonyl) -4-piperidinyl] -5- (3- {[[(1-methylethyl) amino] -methyl} phenyl) -1 H -indole-7-carboxamide; 5- (3-. {[[(1-ethylpropyl) amino] methyl} phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [4- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5-. { 3 - [(meilylamine) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [4- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 5- [4- (aminomethyl) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 5-. { 3 - [(cyclopropylamino) methyl] phenol} -3- [1- (sulfonyl) -4-piperidinyl] -1H-indole-7-carboamide; 5-. { 3 - [(cycloborylamino) methyl] phenol} -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- (1- { [3- (dimethylamino) propyl] sulfonyl} -4-piperidinyl) -5- [4- (1-piperidinylmethyl) phen] -1 H- indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-p-peridinyl] -5-. { 3 - [(2-meitylpropyl) amino] -2,3-dihydro-1 H-inden-5-yl} -1H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 8 - [(2-meitylpropyl) amino] -5,6,7,8-eeryhydro-2-naphthalenyl} -1 H -indole-7-carboxamide; 5- (5- { [(2-Cyanoethyl) amino] methyl.} -2-fluorophenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-picperidinyl] -5- (2-fluoro-5-. {[[(2,2,2-if-fluoro-eyl) amino] -methyl] phenyl) -1H-indole 7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (1, 2,3,4-tetrahydro-7-isoquinolinyl) -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (3. {[[(2,2,2-ylfluoro-eyl) amino] methyl] phenyl) -1 H -indole-7 -carboxamide; 5- (3-. {[[(2-amino-2-oxo-yl) -methyl) amino] -methyl] -phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (2. {[[(2,2,2-ylfluoro-eyl) amino] -methyl] -1,3-yiazol-4-yl) - 1 H-indole-7-carboxamide; 5- (3-cyano-5-. {[[(2,2,2-lrifluoroethyl] amino] methyl] phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[Meth] l (1-meityl-4-pyridinyl) amino] meityl} -3-lienl) -1 H -indole-7-carboxamide; 5- (5-. {[[(2-Cyanoyl) (meityl) amino] meiyl] -3-ynyl) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 5- (5-. {[[(2-amino-2-oxoethyl) (meth1) amino] -methyl] -3-thienyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [5- (. {Mell] [2- (phenylsulfonyl) eyl] amino} meityl) -3-tethyl) -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidiny] -5-. { 5 - [(2-phenyl-1-pyrrolidinyl) mell] -3-lienyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- { [2- (1-piperidinylmethyl) -1-pyrrolidinyl] meilyl} -3-ynyl) -1 H- Ndol-7-carboxamide; 5- (5- { [(2R) -2- (aminocarbonyl) -l-pyrrolidinyl] methyl.} - 3-ynyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 5- (5- { [(2S) -2- (dimethylamino) -1-pyrrolidinyl] -methyl] -3-ynyl) -3- [1- (allylsulfonyl) -4-pperidinyl] -1 H -indole-7-carboxamide; 5- (1- { 2- [4- (dimethylamino) -1-piperidinyl] eyl.} -1 H -pyrazol-4-yl) -3- [1- (erylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 5- [3 - [(dimethylamino) methyl] -4,5-bis (methoxy) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5- [3,4-bis (mephiloxy) -5- (4-morpholinylmethyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3-. { [(1-methyl-amino) amino] me} -4,5-bis (methyloxy) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3-. { [(1-methylethyl) amino] -mellyl} -4,5-bis (mexyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3-. { [(2,2-dimethylpropyl) amino] meiil} -4,5-bis (mexylloxy) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3-. { [(2-hydroxyethyl) (meily) amino] methyl} -4,5-bis (methyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3,4-bis (methyloxy) -5- (1-pyrrolidinylmethyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(dimethylamino) -methyl] -2,3-dihydro-1-benzofuran-6-yl} -3- [1- (allylsulfonyl) -4-idinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4- {[[(1-meilylethyl) amino] -methyl] -2,3-dihydro-1-benzofuran-6-yl ) -1 H -indole-7-carboxamide; 3- [1- (sulfonyl) -4-piperidinyl] -5- [4- (4-morpholinylmethyl) -2,3-dihydro-1-benzofuran-6-yl] -1H-indole -7-carboxamide; 3- [1 - (erylsulfonyl) -4- piperidinyl] -5- [5- ( { [1-Melyl-2- (melloxy) etl] amino} methyl) -2-ynyl] -1 H -indole-7-carboxamide; 5- (5- { [(2-cyano-eyl) amino] -methyl] -3-pyridinyl) -3- [1- (allylsulfonyl) -4-pperidyl] -1H-indole-7 -carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5. {[[(2,2,2-ylfluoro-eyl) amino] -methyl] -3-pyrridinyl) -1 H -indole-7 -carboxamida; 5-. { 3 - [(dimethylamino) methyl] phenyl} -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[Eyl (meily) amino] methyl] -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 5- (5- { [[2- (Di-ylamino) -yl] (melil) amino] -methyl] -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 5- (5- { [Buyl (meily) amino] -methyl] -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[Methyl (propyl) amino] meilyl} - 3-lienyl) -1 H -indole-7-carboxamide; 5- (5-. {[[2- (dimethylamino) -yryl] (methyl) amino] -methyl] -3-yl) -3- [1- (ynylsulfonyl) -4-piperidine ] -1 H -indole-7-carboxamide; 5- (5- { [[3- (dimethylamino) propyl] (meityl) amino] meityl}. 3-ynyl) -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H-indole -7-carboxamide; 5- (5-. {[[Cyclopentyl (methyle) amino] -mellyl] -3-ylene] -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[Meily (penylyl) amino] -methyl] -3-thienyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[Mel] l (2-methylpropyl) amino] methyl} -3-ynyl) -1 H- indole-7-carboxamide; 3- [1 - (allylsulfonyl) -4-pperidinyl] -5- (5- {[melyl (phenylmethyl) amino] methyl} -3-phenyl} -1 H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-p-peridinyl] -5- (5- { [(2-hydroxy-yl) -methyl) amino] -methyl] -3-lienyl) -1H-indole 7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- ( { Mell] [2- (2-pyridinyl) eyl] amino} -methyl) -3-i Enyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-furanylmethyl) (meityl) amino] meityl} -3-ynyl) -1 H -indole-7 - carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- { [Meityl (4-pyridinylmethyl) amino] methyl.} - 3-ynyl) -1 H-indol-7- carboxamide; 3- [1- (ethylsulfonyl) -4-pperidyl] -5-. { 5 - [(methyl { [1- (1-Methylethyl) -3-pyrrolidinyl] methyl} amino) methyl] -3-lienyl} -1 H-indol-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5- { [Methyl (2-ynylmethyl) amino] methyl] -3-yl) -1 H-indole-7- carboxamide; 3- [1 - (elylsulfonyl) -4-pperidinyl] -5- [5- (. {Meityl [1- (2-thienyl) ellyl] amino} melyl) -3-thienyl] - 1 H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- { [Methyl (3-thienylmethyl) amino] meityl} - 3-lyl) -1 H -indole-7- carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5. {[[Meityl (teirahydro-2H-pyran-4-ylmeryl) amino] meityl} -3-yl) -1 H -indole-7-carboxamide; trifluoroacelaio 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[methyl (3-pyridinylmethyl) amino] methyl} -3-lienl) - 1 H-indole-7-carboxamide; trifluoroacelaio 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[methyl (4-pyrimidinylmethyl) amino] meityl} -3-ynyl) - 1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- ( {methyl [2- (melloxy) -yl] -amino} -methyl) -3-thienyl] -1H-indole -7-carboxamide; 5-. { 3 - [(dimethylamine) meily] phenyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- {[[meiyl (1-methylethyl) amino] methyl} -3-yl) -1 H-indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-propyl-1-pyrrolidinyl) -methyl] -3-ionyl} -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-p-peridinyl] -5- (5- { [2- (3-pyridinyl) -1-pyrrolidinyl] methyl} -3- indium) -1 H -indole-7-carboxamide; 5- (5- { [2- (1 J-dimethyl-ethyl) -1-pyrrolidinyl] -methyl] -3-l-phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(2-eyl-1-pyrrolidinyl) methyl] -3-l-phenyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5- { [2- (2- meilypropyl) -1-pyrrolidinyl] meilyl} -3-thienyl) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-p-peridinyl] -5- (5- { [2- (1-Methylyl) -1-pyrrolidinyl] methyl} -3-ynyl) -1 H- indole-7-carboamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [5- ( { (2S) -2- [(mellyloxy) meily] -1-pyrrolidinyl} -methyl) -3-lienyl ] -1 H-indol-7-carboxamide; 5- (5-. {[[Cyclohexyl (methyl) amino] -methyl] -3-thienl] -3- [1 - (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-p -peridinyl] -5- (5-. {[2- (2-meitypropyl) -1-pyrrolidinyl] -methyl] -3-ynyl) -1 H -indole-7-carboxamide; 5- (5-. {[[Ethyl (methyl) amino] -methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- { [Meityl (propyl) amino] methyl} -3-yl) -1 H-indole 7-carboxamide; 3-. { 1 - [(1-Methyleryl) sulfonyl] -4-piperidinyl} -5- (5- { [Methyl (propyl) amino] meilyl} - 3-lenyl) -1 H -indole-7-carboxamide; 5- (5-. {[[Ethyl (methylal) amino] methyl] -3-thienyl) -3-. { 1 - [(1-Methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -5- [5- (. {-methyl [2- (mellyloxy) eyl] amino} -methyl) -3-ynyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-pyridinyl] -5-. { 5 - [(methylamino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-meityl-1-pyrrolidinyl) methyl] -3-ynyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidinyl] -5- (5-. {[[(2-methylpropyl) amino] -methyl] -3-thienyl) -1H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-pperidyl] -5-. { 5- [(propylamino) methyl] -3-ynyl} -1 H-indol-7-carboxamide; 5-. { 5 - [(dimethylamino) methyl] -3-diallyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5- { [(2R, 5R) -2,5-dimethyl-1-pyrrolidinyl] methyl.}. -3-thienyl) -3- [1- (elylsulfonyl) -4-piperidyl nyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(Cyclopropylamino) methyl] -3-l-phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(Cyclobutylamino) methyl] -3-ynyl} -3- [1 - (ethylene sulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(dimethylamino) methyl] -3-thienyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopenylmethyl) amino] -methyl] -3-yl) -3- [1- (ynylsulphonyl) -4-pperidyl] -1H-indole-7 -carboxamide; 5- [5- ( { [(1 R) -1,2-dimethylpropyl] amino} -methyl) -3-ynyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5- [(cyclopenylamino) -methyl] -3-thienyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopropylmethyl) amino] methyl} -3-yl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [5- ( { [(1 S) -1,2-dimethypropyl] amino} -methyl) -3-lienyl] -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 5- (5- { [(2,2-dimethylpropyl) amino] meilyl} .3-lienyl) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[(Phenylmethyl) amino] meityl} - 3-lienyl) -1 H -indole-7-carbo-amide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [5- ( { [(2S) -triahydro-2-furanylmethyl] amino} methyl) -3-lienyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5. {[[(1-Hydro-2H-pyran-4-ylmelll) amino] methyl} -3-lienyl) - 1 H-indole-7-carboxamide; 5-. { 5 - [(buylamino) methyl] -3-lienyl} -3- [1- (ynylsulfonyl) -4-pichandinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- ( { [(2R) -teyrahydro-2-furanylmethyl] amino} meityl) -3-lienyl] -1 H- ndol-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- ( { (2S) -2 - [(melyloxy) mell] -1-pyrrolidinyl}. Methyl) -3-thienyl ] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [5- ( { (2R) -2 - [(methyloxy) methyl] -1-pyrrolidinyl} .methyl) -3-lienyl] - 1 H-indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -5-. { 4- [2- (Melylamino) yl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-p-peridinyl] -5-. { 4- [2- (propylamino) ethyl] phenyl} -1 H -indole-7-carboxamide; 5-. { 4- [2- (elylamino) eyl] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [( { [1- (1, 1-dimethylylyl) -3-methyl-1 H -pyrazol-5-yl] carbonyl}. Amino) meilyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (4. {[[(4-pyridinylcarbonyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 5- (4-. {[[(Cyclopentylcarbonyl) amino] meityl}. Phen.l) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (4-. {[[(2-furanylcarbonyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 5-. { 4- [2- (acetylamino) ethyl] phenyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-p -peridinyl] -5- (4-. {2 - [(meitylsulfonyl) amino] ellyl} phenyl) -1 H -indole-7-carboxamide; 5- (4- {2 - [(cyclobutylcarbonyl) amino] eyl] phenyl] -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (4-. {2- [(cyclohexylcarbonyl) amino] ellyl} phenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1 - (ef.-sulfonyl) -4-p.peridinyl] - 5- (3-. {2- 2- [(methylsulfonyl) amino] eyl.} Phen.l) -1 H- indole-7-carboxamide; 5- (3- {2 - [(cyclohexylcarbonyl) amino] ellyl] phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [6- (1-piperazinyl) -3-pyridinyl] -1 H -indole-7-carboxamide trifluoroacety; 5- [6- (4-eyl-1-p-piperazinyl) -3-pyridinyl] -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [4- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidinyl] -5- [3- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidinyl] -5-. { 4 - [(methylamino) meily] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- (4-. {[[(1-methyleryl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4- piperidinyl] -5-. { 4 - [(propylamino) meily] phenyl} -1 H -indole-7-carboxamide; 5- (4-. {[[(1-ethylpropyl) amino] methyl] phenyl) -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carbo? amide; 5-. { 4 - [(cyclopenylamino) methyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(Cyclobutylamino) meily] phenyl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(elylamino) -methyl] phenyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4- [(dimethylamino) meily] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(dielylamino) methyl] phenyl} -3- [1 - (the sulfonyl) -4-capperidinyl] -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-pperidinyl] -5- [4- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [4- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [4- ( { [(1 S) -2-hydroxy-1-methyl-yl] amino] -methyl) phenyl] -1H-indole -7-carboxamide; 3- [1- (ethylsulfonyl) -4-pperidinyl] -5- [4- ( { [(1 R) -2-hydroxy-1-methyl-amino] -methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [4- ( { [(2R) -2-Hydroxypropyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-pperidinyl] -5- [4- ( { [2-hydroxy-1- (hydroxymethyl) eyl] amino} methyl) phenol] - 1 H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-pperidinyl] -5- (3. {[[(1-meityl)) amino] methyl} phenyl) -1 H -indole-7-carboxam gives; 3- [1- (eylsulfonyl) -4-pperidinyl] -5- [3- (. {[[(1 R) -1-meitylpropyl] amino] methyl) phenyl] -1H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (3 { [(2-methylpropyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3- ( { [(1 S) -1-methylpropyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(Acelylamine) methyl] phenyl} -3- [1- (eylsulfoniI) -4-piperidiny] -1 H -indole-7- carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 4 - [(Propanoylamino) me!] Phenyl} -1 H -indole-7-carboxamide; 5- (4-. {[[(Cyclopropylcarbonyl) amino] methyl] phenyl) -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (4-. {[[(Cyclobuylcarbonyl) amino] methyl} phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (4-. {[[(2-thienylacetyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 5- [4- ( { [(1 S) -1,2-dimethypropyl] amino] methyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 4 - [(buanyoylamino) meily] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulphonyl) -4-piperidinyl] -5- (4-. {[[(2-meitylpropanoyl) amino] melyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (4-. {[[(3-methyl-lanoyl) amino] -methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (4-. {[[(Mlsylsulfonyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 5- [3- ( { [(1 R) -1,2-dimetylpropyl] amino} methyl) phenyl] -3- [1- (alkylsulfonyl) -4-piperidinyl] -1 H -indole- 7-carboxamide; 5- (4- { [(Elylsulfonyl) amino] methyl} phenyl) -3- [1 - (ethylsulfonyl) -4-picperidinyl] -1 H -indole-7-carboxamide; 5- (4-. {[[(Builsulfonyl) amino] meityl} phenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4- ( { [(1-methylelyl) sulfonyl] amino} methyl) phenyl] -1H-indole -7-carboxamide; 5- (6-amino-2-pyridinyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3- (1 H -pyrazol-1-yl) pheny] -1 H -indole-7-carboxamide; 5- [4- (dimethylamino) phenyl] -3- [1- (ynylsulfonyl) -4-pperidyl] -1 H -indole-7-carboxamide; 5- (3-aminophenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-methyl-1-pyrrolidinyl) methyl] -2-thienyl} -1 H-Indole-7- carboxamide; 5-. { 5 - [(elylamine) meily] -2-lienyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (5- {[[(1-methyleryl) amino] methyl} -2-ynyl) -1 H -indole-7-carboxamide; 5-. { 5- [(cyclopropylamino) meily] -2-ynyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5- { [(2,2-dimethylpropyl) amino] meilyl} -2-ynyl) -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carbo ?amide; 5- (5-. {[[(Cyclopropylmethyl) amino] methyl} -2-ynyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5-. {[[(Cyclopropylmethyl) amino] methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [5- ( { [2- (Melyloxy) elyl] amino} -methyl) -3-pyridinyl] -1H-indole-7- carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [5- ( { [3- (Melyloxy) propyl] amino} -methyl) -3-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pyridinyl] -5- [5- (4-morpholinylmethyl) -3-pyridinyl] -1H-indole-7-carboxamide; 5-. { 5 - [(eylamlan) melyl] -3-pyridinyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 5 - [(dimethylamino) meily] -3-pyridinyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(2-Melyl-1-pyrrolidinyl) methyl] -3-pyridinyl} -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-pperidinyl] -5- (5- { [(2-meitylpropyl) amino] methyl} - 3-pyridinyl) -1H-indole-7 -carboxamide; 5- (5-. {[[(2,2-d-methylpropyl) amino] -methyl] -3-pyridinyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[(2-methyl-valyl) amino] -methyl] -2-amino} -1H-indole-7 -carboxamide; 5- [5- ( { [(1 R) -1,2-dimethylpropyl] amino.} Methyl) -2-thienyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4 -peridinyl] -5-. { 5- [(penlylamino) meily] -2-lienyl} -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4- piper.din.l] -5- [5- ( { [(2S) -2-methyl-bilyl] amino} -methyl) -2-lienl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5- {[[(1-methylbuyl) amino] methyl} -2-phenyl) -1 H -indole-7-carboxamide; 5-. { 5 - [(butylamino) meily] -2-l-yenyl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [5- ( { [2- (methyloxy) eyl] amino} methyl) -2-l-phenyl] -1 H -indol-7-carbo? amída; 5-. { 5 - [(cyclopenylamino) methyl] -2-yl-phenyl} -3- [1- (ethylene sulfonyl) -4-pentyldinyl] -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (5- {[[(3-Mellyl) yl) amino} -methyl} -2-ynyl) -1 H-indol-7 -carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[(1-methylethyl) amino] methyl} - 3-pyridinyl) -1 H -indole-7 -carboxamide; 5- (5- { [(2-ethylbu lyl) amino] meilyl} -2-lienyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [5- ( { [3- (ethyloxy) propyl] amino} .methyl) -2-lienyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indol-7- carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [5- ( { [3- (methyloxy) propyl] amino} methyl) -2-yenyl] -1 H -indole -7-carboxamide; 5- (5-. {[[(Cyclohexylmethyl) amino] methyl] -2-lienyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [( { 3 - [(1-methylyl) oxy] propyl} amino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 5- [5- ( { [2- (ethyloxy) eyl] amino} .methyl) -2-thienl] -3- [1- (eylsulfonyl) -4-piperidine l] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- ( { [3- (propyloxy) propyl] amino} methyl) -2-lhenyl] -1 H- indol-7-carboxamide; 5- (5-. {[[(3,3-dimethylamino) amino] methylene] -2-yl] -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole -7-carboxamide; 3- [1 - (ethylsulphonyl) -4-piperidinyl] -5- [5- ( { [(1 S) -1,2,2-dimethylpropyl] amino} .methyl) -2-thienyl] -1 H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(hexylamino) meily] -2-lienyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 4 - [(methylsulfonyl) amino] fenif} -1 H -indole-7-carboxamide; 5- [2- (dimethylamino) -4-pyridinyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [2- (1-pyrrolidinyl) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [2- (4-morpholinyl) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (erylsulfonyl) -4-picperidinyl] -5-. { 2 - [(2-Mellylpropyl) amino] -4-pyridine} -1 H -indole-7-carboxamide; 5-. { 2 - [(2,2-dimethylpropyl) amino] -4-pyridinyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [2- (propylamine) -4-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidinyl] -5-. { 4 - [(meitylamino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [4- (1-pyrrolidinylmethyl) -2-ynyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (4- { [(2-methylpropyl) amino] meilyl} -2-thyl) -1 H-indole-7 -carboxamide; 5-. { 4 - [(d-diallylamino) methyl] -2-lienyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(1S) -1- (1-pyrrolidinyl) eyl] -3-lienyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(1 R) -1- (1-pyrrolidinyl) eyl] -3-ylene} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [4- ( { [3- (methyloxy) propyl] amino} methyl) -2-thienyl] -1 H -indole-7- carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [4- ( { (2S) -2 - [(Melyloxy) meily] -1-pyrrolidinyl] methyl) -2-thienyl] -1 H -indole-7-carboxamide; 5- (4- { [(2R, 5R) -2,5-dimethyl-1-pyrrolidinylmethyl] -2-lienyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H-indole-7-carboxamide; 3- [1 - (ethylsulphonyl) -4-p -peridinyl] -5- (5- { [(2S) -2-meylyl-1-pyrrolidinyl] methyl] -3-lien l) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5- { [(2R) -2-meityl-1-pyrrolidinyl] methyl} -3-t-phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4- piperidinyl] -5-. { 5- [1- (1-pyrrolidinyl) propyl] -3-ynyl} -1 H -indole-7-carboxamide; 5-. { 5 - [(dimethylamino) methyl] -3-lienyl} -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- [5- (aminomethyl) -3-lienyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- (5- {2 - [(2-meitylpropyl) amino] ethyl] -3-lienl) -1 H-indole -7-carboxamide; 5-. { 5- [2- (dimethyl amine) eyl] -3-lienyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- [6- (1-pyrrolidinyl) -3-pyridinyl] -1H-indole-7-carboxamide; 5-. { 6- [ethyl (methyl) amino] -3-pyridinyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [6- (dimethylamino) -3-pyrridinyl] -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [6- (propylamino) -3-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (erylsulfonyl) -4-piperidinyl] -5-. { 6 - [(1-Methylethyl) amino] -3-pyridinyl} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [6- (4-morpholinyl) -3-pyridinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 5 - [(meitylamino) meityl] -3-ynyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5- {[[(1-methylethyl) amino] methyl} -3-yl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [5- (1-pyrrolidinylmethyl) -3-thienyl] -1H-indole-7-carboxamide; 5-. { 5- [(elylamino) methyl] -3-thienl} -3- [1- (elylsulfonyl) -4-picperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- [5- ( { [(1 R) -2-hydroxy-1-methyl-amino] -amino} -methyl. ) -3-yenyl] -1 H -indole-7-carboxamide; 3- [1 - (ylsulfonyl) -4-piperidinyl] -5- [5- (1-piperidinylmethyl) -3-lienyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [5- (4-morpholinylmethyl) -3-ynyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 5 - [(meitylamino) methyl] -3-furanyl} - 1 H-indole-7-carboxamide; 3- [1- (sulfonyl) -4-piperidinyl] -5-. { 5- [1- (1-pyrrolidinyl) ethyl] -3-lienyl} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-pipe dinyl] -5- [5- (1-pyrrolidinylmethyl) -2-ynyl] -1 H -indole-7-carboxamide; 5-. { 5- [(dimethylamino) meily] -2-yenyl} -3- [1- (Elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5-. { 5 - [(propylamino) methyl] -2-ynyl} -1 H -indole-7-carboxamide; 5-. { 5 - [(dielylamino) meily] -2-ynyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5- { [(2-meitylpropyl) amino] meilyl} -2-l-phenyl) -1 H -indole-7-carbo-amide; 5- (5- { [(2,2-dimethylpropyl) amino] methyl] -3-furanyl) -3- [1- (eylsulfonyl) -4-picperidinyl] -1H-indole -7-carboxamide; 3- [1 - (elylsulfonyl) -4-p-peridinyl] -5- (5- { [(2-methylpropyl) amino] meilyl} - 3-furanyl) -1H-indole-7- carboxamide; 5- (5- { [(Cyclopeniylmethyl) amino] meityl}. 3-furanyl) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [5- (1-pyrrolidinylmet) -3-furanl] -1 H-indole-7 -carboxamide; 5-. { 5 - [(di-ylamino) meily] -3-furanyl} -3- [1- (elylsulfonyl) -4-pperidinyl] -1H-indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- [5- (1-pyrrolidinylmethyl) -1, 3-yiazol-2-yl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidyl] -5-. { 5- [2-Melyl-1 - (1-pyrrolidinyl) propyl] -3-yl-phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [4- (1-pyrrolidinylmethyl) -1,3-lyozol-2-yl] -1 H -indole-7-carboxamide; 5-. { 1- [2- (dimethylamino) e / 1] -1 H-pyrrazol-4-yl} -3- [1- (elylsulfonyl) -4-p-peridinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5-. { 1 - [2- (1-pyrrolidinyl) eyl] -1 H -pyrazol-4-yl} -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 1 - [2- (4-morpholinyl) elyl] -1 H -pyrazol-4-yl} -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxy-yl) yl] -yl] -yl} -1-H-pyrazol-4-yl) -1 H- Ndol-7- carboxamide; 5-. { 1 - [2- (Buzylamine) eyl] -1 H -pyrazol-4-yl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 1 - [2- (Cyclobuylamino) -yl] -1 H -pyrazol-4-yl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [1- (2- { [2- (diethylamino) eyl] amino} ethyl) -1 H -pyrrazole-4-yl] -3- [1- (elylsulfonyl) -4 -pepper Dyl] -1 H-indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- (1-. {2 - [(1-methylethyl) amino] elyl.} -1 H-pyrazole-4- il) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-meitylpropyl) amino] elyl} -1H-pyrazol-4-yl) -1 H- indol-7-carboxamide; 5- (1- {2 - [(cyclopenylmethyl) amino] eyl] -1 H-pyrazol-4-yl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H- indole-7-carboxamide; 3- [1 - (ylsulfonyl) -4-piperidinyl] -5- [4- (methyloxy) -3- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 5- [3 - [(dimethylamino) -methyl] -4- (meilyloxy) phenyl] -3- [1- (ynylsulfonyl) -4-p-perpentyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [4- (mellyloxy) -3- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylene sulfonyl) -4-piperidinyl] -5- [3-. { [(1-methyl-ethyl) amine] -methyl} -4- (methyloxy) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3 - [(meitylamino) meily] -4- (methyloxy) phenyl] -1 H -indole-7-carboxamide; 5- [3-. { [(2,2-dimethylpropyl) amino] meilyl} 4- (Melyloxy) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (1- {2 - [(2-hydroxyethyl) (methyl) amino] ethyl} -1 H -pyrazol-4-yl) - 1 H-indole-7-carboxamide; 3- [1 - (ef] lsulfonyl) -4-piperin dl] -5-. { 4-fluoro-3 - [(methylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 5-. { 3,5-bis [(methylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-pichandinyl] -1 H -indole-7-carboxamide; 5-. { 3 - [(ethylamino) methyl] -4-fluorophenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [4-fluoro- 3- ( { [2-hydroxy-1- (hydroxymethyl) ethyl] amino.}. Meityl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [4-fluoro-3- ( { [(1S) -2-hydro? I-1-methylethyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 5-. { 3- [(cyclopropylamino) mel] l-4-fluorophenyl} -3- [1- (allylsulfonyl) -4-pperidinyl] -1 H -indole-7-carboxamide; 5-. { 3 - [(Cyclobuylamino) -methyl] -4-fluorophenyl} -3- [1 - (Ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [3- (1-pyrrolidinylmethyl) phenyl] -1H-indole-7-carboxamide; 5-. { 3,5-bis [(eylamlan) methyl] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3,5-bis [(d-diallylamino) methyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- [3- (2-piperidinyl) phenyl] -1H-indole-7-carboxamide; 5-. { 3- [1 - (elylamino) elly] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3- [1 - (dimethylamino) yl] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidin] -5-. { 3-fluoro-5 - [(meitylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 5-. { 3 - [(elylamino) meily] -5-fluorophenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3-fluoro-5 - [(pro? Ylamino) mel] phenyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-p-perpentyl] -5- (3-fluoro-5-. {[[(1-methyleryl) amino] methyl} phenyl) -1H-indole 7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-meitylpropyl) am.no] methyl} phenyl) -1 H -indole-7 -carboxamide; 5-. { 3 - [(Cyclobuylamino) mell] -5-fluorophenyl} -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3 - [(dimethylamino) methyl] -5-fluorophenyl} -3- [1- (ethylsulfonyl) -4-pichandidinyl] -1 H -indole-7-carboamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboamide; 3- [1- (allylsulfonyl) -4 -peridinyl] -5-. { 3- [1- (meilylamine) elil] phenyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3 { 1 - [(1-methylelyl) amino] ell.] Phenyl) -1 H -indole-7- carboxamida; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {1 - [(2-methylpropyl) amino] ethyl} phenyl) -1H-indole-7- carboxamide; 5-. { 3- [1- (cyclobuylamino) eyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3- [1- (1-pyrrolidinyl) el] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (ynylsulfonyl) -4-piperidinyl] -5- [3- (3-thiomorpholinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- (2-piperazinyl) -2-ynyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [4- (2-piperazinyl) phenyl] -1H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3- (2-p-pentazinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [6- (4-morpholinyl) -3-pyridazinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [6- (1-pyrrolidinyl) -3-pyridazinyl] -1 H -indole-7-carboamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 2- [(meilyamino) meily] phenyl} -1 H -indole-7-carbo-amide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-lienylmethyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pyridinyl] -5- [3- (. {[[(5-meityl-2-furan] l) -methyl] -amino} -methyl) -phenyl] - 1 H-indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3- ( { [(2R) -yrahydro-2-furanylmethyl] amino} .methyl) phenyl] -1H-indole 7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- ( { [(2S) -tetrahydro-2-furanylmethyl] amino} meleyl) phenyl] -1 H -indole-7- carboxamide; 5- (3-. {[[(2,2-dimethylpropyl) amino] meityl}. Phen.l) -3- [1- (allylsulfonyl) -4- piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-methyl-butyl) amino] -methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ylsylsulfonyl) -4-p, pperidyl] -5- [3- ( { [(2S) -2-meilyl-butyl] amino} -methyl) phenyl] -1 H- indole-7-carboxamide; 3- [1 - (ethylene sulfonyl) -4-piperidinyl] -5- [3- ( { [(1 R) -1, 2,2-trylmethylpropyl] amino] melyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-pyridinyl] -5- [3-fluoro-5- ( { [(2S) -leralhydro-2-furanylmethyl] amino} methyl) phenyl] -1 H-indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- (. {[[(2R) -tetrahydro-2-furanylmethyl] amino} meilyl) phenyl] -1 H-indole-7-carboxamide; 5- [3- ( { [(1 S) -1,2-dimethylpropyl] amino.}. Mell] -5-fluorophenyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(1 R) -1,2-dimethylpropyl] amino} -methyl) -5-fluorophenyl] -3- [1- (elylsulfonyl) -4-piper dinyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-p-peridinyl] -5- (3-fluoro-5-. {[[(1-methylpropyl) amino] methyl} phenyl) -1H-indole-7- carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(1 S) -1,2,2-trimethylpropyl] amino.} Methyl) phen L] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-pperidinyl] -5- [3-fluoro-5- ( { [(2S) -2-methylbuyyl] amino} .methyl) phenol l] -1 H -indole-7-carboxamide; 3- [1- (efylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-methylbuyl) amino] methyl] phenyl) -1H-indole 7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [(1 R) -1,2,2-limethylpropyl] amino.} Methyl) phenol ] -1 H -indole-7-carboamide; 5- (3-. {[[(2,2-dimethylpropyl) amino] methyl] -5-fluorophenyl) -3- [1- (alkylsulfonyl) -4-pperidinyl] -1H-indol- 7-carboxamide; 5- (3-. {[[(Cyclopropylmethyl) amino] -methyl] -5-fluorophenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide; 5- (3- { [(Cyclopentylmethyl) amino] -methyl] -5-fluorophenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4- pperidyl] -5- (3-fluoro-5. {[[(1-hydra-2H-pyran-4-methylmethyl) amino] methyl] phenyl) -1H-indole-7- carboamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5. {[[(2-lienylmethyl) amino] meily} phenyl) -1H-indole 7-carboamide; 3- [1 - (elylsulfonyl) -4-p -peridinyl] -5- [3-fluoro-5- ( { [2- (meyloxy) elly] amino} .methyl) phenyl ] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3-fluoro-5- ( { [3- (methyloxy) propyl] amino} .methyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(2-furanylmethyl) amino] meily} phenyl) -1 H -indole-7-carbo ?amide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3-fluoro-5-. {[[(3-meitylbutyl) amino] methyl} phenyl) -1 H -indole-7- carboxamide; 3- [1 - (eylsulfonyl) -4-p-peridinyl] -5- [3-fluoro-5- (. {[[(5-meityl-2-furanyl) -methyl] -amino} -methyl) -phenyl] - 1 H-indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-meitylpropyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3- (2-pyrrolidinyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(meitylamino) mel] phenyl} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 2-fluoro-5 - [(propyllamine) methyl] phenol} -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (2-fluoro-5-. {[[(2-meitylpropyl) amino] meilyl} phenyl) -1 H -indole-7- carboxamide; 5- (5-. {[[(2,2-dimethylpropyl) amino] melyl] -2-fluorophenyl) -3- [1- (ynylsulfonyl) -4-pperidinyl] -1H -indol-7-carboamide; 5- [5- ( { [(1S) -1,2-dimethyl-propyl] amino} -methyl) -2-fluorophenyl] -3- [1- (ethylsulfonyl) -4-piperidine L] -1 H -indole-7-carboamide; 5- [5- ( { [(1 R) -1,2-dimethylpropyl] amino.} Mell) -2-fluorophenyl] -3- [1- (allylsulfonyl) -4-piper dinyl] -1 H -indole-7-carboamide; 5- (5- { [(Cyclopropylmethyl) amino] -methyl} -2-fluorophenyl) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indol-7-carboamide; 3- [1 - (erylsulfonyl) -4- piperidinyl] -5- [2-fluoro-5- (1-pyrrolidinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [2-fluoro-5- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pyridinyl] -5- [2-fluoro-5- ( { [2- (methyloxy) ethyl] amino} .methyl) phenyl] -1H-indole -7-carboxamide; 3- [1 - (allylsulfonyl) -4-piperidin] -5- [2-fluoro-5- ( { [3- (methyloxy) propyl] amino} .methyl) phenol ] -1 H-Indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3- (1-methyl-2-pyrrolidinyl) pheny] -1 H -indole-7-carboamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (3. {2 - [(2-meitylpropyl) amino] ethyl} phenyl) -1 H -indole-7-carboxamide; 5-. { 3- [2- (elylamino) elly] phenyl} -3- [1 - (the sulfonyl) -4-capperidinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-pperidinyl] -5-. { 3- [2- (propylamino) elyl] phenyl} -1 H -indole-7-carboxamide; 5-. { 3- [2- (dimethylamino) eyl] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3- [2- (dipropylamino) elly] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [2- (3,5-Dimethyl-1 H -pyrazol-1-yl) eyl] amino} .methyl) phenyl] -3- [1- (alkylsulfonyl) -4 -piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [2- (4-morpholinyl-methyl) -1,3-thiazol-4-yl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (2- {[[(2-meitylpropyl) amino] methyl} -1, 3-thiazol-4-yl) -1 H-indole -7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [2- (1-pyrrolidinylmethyl] -1,3-yiazol-4-yl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [2- (1-piperidinylmethyl) -1,3-liazol-4-yl] -1 H -indole-7-carboxamide; 5-. { 2 - [(dimethylamino) -mellyl] -1, 3-yiazol-4-yl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (2-. {[[Eyl (melil) amino] meilyl} -1, 3-yiazol-4-yl) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 5- (3-cyano-5- { [(2-methylpropyl) amino] me.]. Phen.l) -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H -indole -7- carboxamide; 5-. { 3-cyano-5 - [(dimethylamino) methyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 3- [(Melylsulfonyl) amino] phenyl} -1 H -indole-7-carboxamide; 5- [4- (acetylamino) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- (Acelylamino) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ynylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 5-. { 3- [(acetylamino) meily] phenyl} -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(Methylsulfonyl) amino] methyl} phenyl) -1 H -indole-7-carboxamide; 5-. { 3 - [(butanoylamino) methyl] phenyl} -3- [1 - (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4-piperidinyl] -5- [3- ( { [(4-fluorophenyl) carbonyl] amino} meleyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-me ylpropropanoyl) amino] methyl] phenyl] -1 H -indole-7- carboamide; 3- [1 - (ethylsulfonyl) -4-pperidyl] -5- (3- {[[(2-furanylcarbonyl) amino] methyl} phenol) -1 H -indole-7- carboxamide; 5- (3-. {[[(Cyclopenylcarbonyl) amino] meityl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 3- [(pentanoyllamine) meilyl] phenyl} -1 H -indole-7-carboxamide; 5- (3-. {[[(2-eylilbinoyl) amino] methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(1-benzolinien-2-ylcarbonyl) amino] meilyl}. Phen.l) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 5- [3- ( { [(1-Acetyl-4-piperidinyl) carbonyl] amino} .methyl) phen.l] -3- [1- (allylsulfonyl) -4-piperidinyl] - 1 H-indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [3- ( { [(1-methyl-1 H-pyrrole-2- il) carbonyl] amino} melyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(3-methyl-2-buidooyl) amino] methyl} phenyl) -1 H-indole 7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3 - [(hepyaoylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(oclanylamino) metl] phenol} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3 { [(2-meilylpenlanoyl) amino] methyl} phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(3-meityylbulanyl] amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- (3- {[[(2-ethynylacetyl) amino] -methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3 - [(Hexanoylamino) mell] phenyl} -1 H-indol-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (3-. {[[(2-methylbuanyoyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 5- (3- { [(Cyclobulylcarbonyl) amino] -methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3- { [[(Cyclopropylcarbonyl) amino] meilyl}. Phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carbo? Ami gives; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 3 - [(Propanoylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclopentyl-acetyl) amino] -methyl] -phenyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- ( { [3- (meityllio) propanoyl] amino} meleyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-pyridinyl] -5- [3- ( { [(1-Methylethyl) sulfonyl] amino} meilyl) phenyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(Cyclopropylsulfonyl) amino] methyl} phenyl) -3- [1 - (allylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- (. {[[(2,5-dichlorophenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H- ndol-7-carboxamide; 5- [3- ( { [(4-Bromophenyl) sulfonyl] amino} .methyl) phenyl] -3- [1 - (elyisulfonyl) - 4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(4-chlorophenol) sulfonyl] amino} .methyl) phenyl] -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [3- ( { [(3-fluorophenyl) sulfonyl] amino} methyl) phenyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(2-chlorophenyl) sulfonyl] amino} meilyl) phenyl] -3- [1 - (ethylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide; 5- [3- ( { [(2,5-dichloro-3-ynyl) sulfonyl] amino} methyl) phenyl] -3- [1- (eylsulfonyl) -4-p Peridinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(2-Chloro-6-meitylphenyl) sulfonyl] amino} .methyl) phenyl] -3- [1- (eylsulfonyl) -4-piperidinyl] -1H-indole-7 -carboxamide; 3- [1- (ethylene sulfonyl) -4-piperidinyl] -5- [3- (. {[[(5-fluoro-2-methylphenyl) sulfonyl] amino} methyl) phenol] - 1 H-indole-7-carboxamide; 5- [3- ( { [(1, 2-dimethyI-1H-imidazol-4-yl) sulfonyl] amino} methyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1 H-indol-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (3. {[[(Propylsulfonyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 5- (3-. {[[(Butylsulfonyl) amino] methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3- {[[(phenylsulfonyl) amino] meily} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- [3- ( { [(4-fluorophenyl) sulfonyl] amino} meleyl) phenyl] -1H-indole-7-carboxamide; 5- [3- ( { [(4-Bromo-2-eliphenyl) sulfonyl] amino} methyl) phenyl] -3- [1- (ethylene sulfonyl) -4-piperidine ] -1 H -indole-7-carboxamide; 5- (3- { [(1-benzolinien-3-ylsulfonyl) amino] meilyl}. Phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indol-7- carboxamide; 5-. { 3 - [( { [4- (1, 1-dimethyleryl) phenyl] sulfonyl.] Amino) meilyl] phenyl} -3- [1- (erylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- ( { [(3,4-difluorophenyl) sulfonyl] amino} .methyl) phenyl] -3- [1- (allylsulfonyl) -4-piperidinyl] -1H-indole-7- carboxamide; 5- (3- { [(Eylsulfonyl) amino] methyl} phenyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (3-. {[[(2,1, 3-benzoxadiazol-4-lsulfonyl) amino] meilyl}. Pheny] -3- [1- (allylsulfonyl) -4-piperidinyl] - 1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3. {[[(Iorahydro-3-furanylcarbonyl) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 5-. { 4- [(cyclopentylsulfonyl) amino] phenol} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- [4- (4-methyl-2-oxo-1-piperazinyl) phenyl] -1H-indole-7-carboxamide; 5- [6- (4-Acetyl-1-piperazinyl) -3-pyridinyl] -3- [1 - (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (4- { [(Melyloxy) amino] methyl} phenyl) -1 H -indole-7-carboamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3. {[[(Melilo? I) amino] meilyl} phenyl) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5- { [4- (1-pyrrolidinyl) -1-p-peridinyl] methyl} -3-lienyl) -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidin] -5- (5- { [(2S) -2- (trifluoromethyl) -1-pyrrolidinyl] methyl} -3-iien l) -1 H -indole-7-carboxamide; 5- (5-. {[[(2R) -2- (hydroxymethyl) -1-pyrrolidinyl] methyl] -3-lienl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5- { [(3S) -3-hydroxy-1-pyrrolidinyl] -methyl] -3-lienyl) -3-. { 1 - [(1-methylethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5- { [Cyclopenyl (methyl) amino] methyl} -3-ynyl) -3-. { 1 - [(1-methyleryl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5-. {[[(2-Hydroxyethyl) (meityl) amino] meityl} -3-ynyl) -3-. { 1 - [(1-Melleyleyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 5- (5-. {[[(2-amino-2-oxo-ethyl) (melíl) amino] mel] yl-3-ynyl) -3-. { 1 - [(1-methyl-ethyl) sulfonyl] -4-piperidinyl} -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- (5 { [Meityl (2-propen-1-yl) amino] meilyl} -3-yi enyl) -1 H- indole-7-carboxamide; 5- (5-. {[[(3,5-dimethyl-1 H -pyrazol-4-yl) -methyl] (mell) amino] methyl} -3-ylene] -3- [ 1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- (5- { [(Cyanomethyl) (melil) amino] methyl} -3-ynyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7- carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- (5- { [Methyl (1-methylpropyl) amino] methyl} -3-ynyl) -1 H -indole-7- carboxamide; 5- (5- { [[2- (elyloxy) ellyl] (methyl) amino] meityl} .3-l-phenyl) -3- [1- (ethylsulfonyl) -4-piperidine l] -1 H -indole-7-carboxamide; 5- (5-. {[Cyclobuyl (methyle) amino] methyl} - 3-l-phenyl) -3- [1- (sulphonyl) -4-piperidinyl] -1 H- indol-7-carboamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- (. {2 - [(methyloxy) methyl] -1-pyrrolidinyl} -methyl) -3-ynyl] - 1 H-indole-7-carboxamide; 5- (5-. {[[(1,1-dimethylethyl) (melil) amino] methyl] -3-l-phenyl) -3- [1- (alkylsulfonyl) -4-p-peridinyl] -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-p -peridinyl] -5- (5- {[[3- (ír-fluoro-maleyl) -1-piperidinyl] -methyl} -3-l-phenyl} -1 H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5. {[[[(1 S) -2-hydroxy-1-methylaryl] (meityl) amino] methyl} -3- tolyl) -1 H-indole-7-carboxamide; 5- (5- { [(Cyclopropylmethyl) (male) amino] methyl} -3-lienyl) -3- [1- (ethylsulfonyl) -4-pperidinyl] -1H-indole-7- carboxamide; 5- (5- { [[2- (Ailylammonyl) ethyl] (methylamino) amino] methyl] -3-ynyl) -3- [1- (eylsulfonyl) -4-piperidine ] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {[[[(1 R, 2R) -2-hydroxycyclopenyl] (meily) amino] methyl}. -3-lienyl) -1 H -indole-7-carboxamide; 5- (5-. {[[(1,1-dimethylpropyl) (methyl) amino] methyl] -3-ylene] -3- [1- (ynylsulfonyl) -4-piperidi nyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (5-. {[[[(2S) -2-hydroxypropyl] (methyl) amino] meityl}. -3-lienyl) -1 H-indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- [5- ( {methyl [(2R) -lehydrohydro-2-furanylmethyl] amino} .methyl) -3-thienyl] -1H- indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (5- { [ { 2 - [(2- hydroxyelyl) oxy] ell} (melil) amino] meily} -3-thienyl) -1 H-indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-piperidinyl] -5- [5- (1- (methylene] [2- (methyloxy) ethyl] amino.} Eyl) -3-t Enyl] -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (5-. {1 - [meityl (propyl) amino] ethyl] -3-lienyl) -1H-indole 7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (5-. {[[[(1 S) -2-hydroxy-1-methylyl] (melil) amino] methyl}. 3-lienl) -1 H-indole-7-carboxamide; or 5- (5-. {[[(1 J-dioxydolehydro-3-lienyl) (methyl) amino] methyl} .3-lienyl) -3- [1- (ynylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; or a pharmaceutically acceptable salt, solvate or polymorph thereof. 9. The compound according to claim 1, further characterized in that it is 3- [1- (ethylsulfonyl) -4-picperidinyl] -5- [3- (1-piperidinylmethyl) phenyl] -1H-indole -7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- (1-piperazinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- [3- (4-morpholinylmethyl) phenyl] -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-p-peridinyl] -5- [3- ( {methyl [2- (meilylsulfonyl) eyl] amino} methyl) phenyl] -1H-indol-7 -carboxamide; 5- (3-. {[[[2- (dimethylamino) eyl] (methyl) amino] methyl} phenyl) -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidiny] -5-. { 3 - [(4- {2 - [(2-hydroxy-l, yl) oxy] ethyl.} -1-piperazinyl) methyl] phenyl} -1H-indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3- {[[3- (hydroxymethyl) -1-piperidinyl] methyl} phenyl) -1H-indole-7-carboxamide; 5- [3- (. {Bis [2- (methyloxy) yl] amino] -methyl) phenyl] -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole 7-carboxamide; 5-. { 3 - [(2,6-dimethyl-4-morpholinyl) meily] phenyl} -3- [1- (sulfonyl) -4-p-peridinyl] -1 H -indole-7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5- (3- {[[2- (1, 3-yiazol-2-yl) -1-pyrrolidinyl] meilyl}. ) -1 H -indole-7-carboxamide; 3- [1 - (erylsulfonyl) -4- piperidinyl] -5- (3- {[2- (2-taryl) -1-pyrrolidinyl] methyl} phenyl) -1 H -indole-7-carboxamide; 3- [1- (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-hydroxy-2-phenyletyl) (methyl) amino] methyl} phenyl] -1 H-indole-7-carboxamide; 5- (3-. {[[(Methyl) amino] methyl} phenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5- [3- (aminomethyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 5-. { 3 - [(cyclopenylamino) meily] phenyl} -3- [1 - (eylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5- [3- ( { [(3,4-dihydroxyphenyl) methyl] amino.} Methyl) phenyl] -3- [1- (ethylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-lienylmethyl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 3- [1 - (ethylsulphonyl) -4-piperidinyl] -5- [3- ( { [(2S) -2- (hydroxyethyl) -3-meityl] yl] amino} mephyl) phenyl] -1 H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(2-hydroxy-1-methyleryl) amino] meityl} phenyl) -1 H -indole-7- carboamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(Ia'7 / 4-hydroxycyclohexyl) amino] methyl} phenyl) -1H-indol- 7-carboxamide; 3- [1- (elylsulfonyl) -4-piperidinyl] -5-. { 3 - [( { [1- (1-piper.din.l) cyclohexyl] meilyl}. Amino) mephyl] phenol} -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- ( { [(2S) -2-hydroxypropyl] amino} methyl) phenyl] -1H-indole-7-carboxamide; 5-. { 3 - [(elylamino) meily] phenyl} -3- [1 - (ethylsulfonyl) -4-piperidiryl] -1 H -indole-7-carboxamide; 3- [1 - (ethylsulfonyl) -4-piperidinyl] -5-. { 3- [(propylamino) methyl] phenyl} -1 H -indole-7-carboxamide; 3- [1 - (eylsulfonyl) -4-piperidinyl] -5- (3. {[[(1-methylaryl) amino] methyl] phenyl) -1 H -indole-7-carboxamide; 5- (3-. {[[(1-ethylpropyl) amino] meityl} phenyl) -3- [1- (eylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5- [3- (1-pperidinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (erylsulfonyl) -4-piperidinyl] -5- [4- (1- piperidinylmethyl) phenyl] -1H-indole-7-carboxamide; 3- [1- (eylsulfonyl) -4-piperidinyl] -5-. { 3 - [(methylamino) mell] phenyl} -1 H -indole-7-carboxamide; 3- [1- (allylsulfonyl) -4-piperidinyl] -5- [4- (4-morpholinylmethyl) phenyl] -1H-indole-7-carboxamide; 5- [4- (aminomethyl) phenyl] -3- [1- (elylsulfonyl) -4-piperidinyl] -1 H -indole-7-carboxamide; 3- [1 - (elylsulfonyl) -4-pperidinyl] -5- [3- (4-morpholinylmethyl) pheny] -1 H -indole-7-carboxamide; 5-. { 3 - [(cyclopropylamino) methyl] phenyl} -3- [1- (ethylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 5-. { 3 - [(cyclobuhlamino) methyl] phenyl} -3- [1- (elylsulfonyl) -4-piperidinyl] -1H-indole-7-carboxamide; 3- (1- { [3- (dimethylamino) propyl] sulfonyl.} -4-piperidinyl) -5- [4- (1-piperidinylmethyl) phenyl] -1 H -indole-7-carboxam gives; or 3- [1- (ethylsulfonyl) -4-piperidinyl] -5-. { 3 - [(2-meitylpropyl) amino] -2,3-dihydro-1 H-inden-5-yl} -1 H -indole-7-carboxamide; or a pharmaceutically acceptable, solvated or polymorphic salt thereof. 10. A pharmaceutical composition comprising a compound of claims 1 or 2 and one or more pharmaceutically acceptable excipients. 11. The use of a compound of claims 1 or 2, in the manufacture of a medicament useful for treating a disorder mediated by the inappropriate activity of IKK2 in a patient. 12. The use as claimed in claim 11, wherein the disease in which an inappropriate activity of IKK2 is involved is selected from the group consisting of: rheumatoid arthritis, inflammatory bowel disease, asthma, chronic obstructive pulmonary disease (COPD); osteoartrilis, osleoporosis, psoriasis, atopic dermaitis, cullet lesions induced by ullraviolet radiation (UV), systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue rejection, organ rejection, Alzheimer's disease, stroke, aerosol, reesinosis, diabetes, glomerulonephritis, Hodgkin, caque? Ia, inflammation associated with infection and certain viral infections, including acquired immunodeficiency syndrome (AIDS), respiratory distress syndrome in adults, and ataxia lelangieciasia. 13. The use as claimed in claim 11, where the irasor in which an inadequate activity of IKK2 arises is an inflammatory or tissue repair disorder. 14. The use as claimed in claim 11, wherein the disorder in which inadequate activity of IKK2 arises is rheumatoid arthritis, asthma or COPD. 15. The use as claimed in claim 11, wherein the uranium in which an inadequate activity of IKK2 is involved is rheumatoid arthritis. 16. The use as claimed in claim 11, wherein the transient in which an inappropriate activity of IKK2 is involved is asthma. 17. The use as claimed in claim 11, wherein the disorder in which an inappropriate activity of IKK2 is involved is COPD. 18. - The use as claimed in claim 11, wherein the uranium in which an inappropriate activity of IKK2 is involved is selected from the group consisting of: Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, osteoaririlis, osleoporosis, and aiaxia lelangieclasia. 19. The use as claimed in claim 11, wherein the Irasorubium in which an inadequate activity of IKK2 is involved is an auloimmune disease. 20. The use as claimed in claim 19, wherein the autoimmune disease is systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis or ankylosing spondylitis. 21. Use as claimed in claim 11, wherein the transient in which an inadequate activity of IKK2 arises is cancer or cachexia. 22. Use as claimed in claim 21, wherein the cancer is Hodgkin's disease.
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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0315950D0 (en) 2003-06-11 2003-08-13 Xention Discovery Ltd Compounds
PE20060748A1 (en) * 2004-09-21 2006-10-01 Smithkline Beecham Corp INDOLCARBOXAMIDE DERIVATIVES AS KINASE INHIBITORS IKK2
GB0525164D0 (en) * 2005-12-09 2006-01-18 Xention Discovery Ltd Compounds
WO2007076286A2 (en) * 2005-12-16 2007-07-05 Smithkline Beecham Corporation Chemical compounds
PE20081889A1 (en) 2007-03-23 2009-03-05 Smithkline Beecham Corp INDOL CARBOXAMIDES AS INHIBITORS OF IKK2
JP5557849B2 (en) * 2008-12-19 2014-07-23 ブリストル−マイヤーズ スクイブ カンパニー Carbazole and carboline kinase inhibitors
US8354539B2 (en) 2009-03-10 2013-01-15 Glaxo Group Limited Indole derivatives as IKK2 inhibitors
US9567339B2 (en) * 2013-06-26 2017-02-14 Abbvie Inc. Primary carboxamides as BTK inhibitors
LT3209656T (en) * 2014-10-24 2020-07-27 Bristol-Myers Squibb Company Indole carboxamides compounds useful as kinase inhibitors

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HRP20000065A2 (en) * 1997-08-06 2001-04-30 Lilly Co Eli 2-acylaminopropanamines as tachykinin receptor antagonists
DE19807993A1 (en) 1998-02-26 1999-09-02 Bayer Ag Treating tumor necrosis factor mediated inflammatory disease, e.g. arteriosclerosis, using new or known beta-carboline derivatives
DE50010931D1 (en) 1999-06-23 2005-09-15 Aventis Pharma Gmbh SUBSTITUTED BENZIMIDAZOLE
DE19928424A1 (en) 1999-06-23 2000-12-28 Aventis Pharma Gmbh New aminoacid residue substituted benzimidazole derivative I(kappa)B-kinase inhibitors, useful for treating NF(kappa)B-related disorders e.g. rheumatoid arthritis, asthma, Alzheimer's disease and cancer
DE19951360A1 (en) 1999-10-26 2001-05-03 Aventis Pharma Gmbh Substituted indoles
GB0003154D0 (en) 2000-02-12 2000-04-05 Astrazeneca Uk Ltd Novel compounds
EP1209158A1 (en) 2000-11-18 2002-05-29 Aventis Pharma Deutschland GmbH Substituted beta-carbolines
EP1268477B1 (en) 2000-03-15 2010-04-21 Sanofi-Aventis Deutschland GmbH Substituted beta-carbolines with ikb-kinase inhibiting activity
EP1134221A1 (en) 2000-03-15 2001-09-19 Aventis Pharma Deutschland GmbH Substituted beta-carbolines as lkB kinase inhibitors
JP2001278886A (en) * 2000-03-28 2001-10-10 Dai Ichi Seiyaku Co Ltd Benzoxazine derivative and medicament containing the same
US6414013B1 (en) 2000-06-19 2002-07-02 Pharmacia & Upjohn S.P.A. Thiophene compounds, process for preparing the same, and pharmaceutical compositions containing the same background of the invention
JP4272338B2 (en) 2000-09-22 2009-06-03 バイエル アクチェンゲゼルシャフト Pyridine derivatives
US6869956B2 (en) 2000-10-03 2005-03-22 Bristol-Myers Squibb Company Methods of treating inflammatory and immune diseases using inhibitors of IκB kinase (IKK)
ATE319713T1 (en) 2000-10-03 2006-03-15 Bristol Myers Squibb Co AMINO-SUBSTITUTED TETRACYCLIC COMPOUNDS USEFUL AS ANTI-INFLAMMATORY AGENTS AND DRUGS CONTAINING SAME.
AU2002211662A1 (en) 2000-10-12 2002-04-22 Smith Kline Beecham Corporation Nf-kappab inhibitors
JP2004523476A (en) 2000-10-12 2004-08-05 スミスクライン・ビーチャム・コーポレイション NF-κB inhibitor
MXPA03003599A (en) 2000-10-26 2003-08-01 Tularik Inc Antiinflammation agents.
JP2002193938A (en) 2000-12-01 2002-07-10 Bayer Ag 4-arylpyridine derivative
US7122544B2 (en) 2000-12-06 2006-10-17 Signal Pharmaceuticals, Llc Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto
WO2002060386A2 (en) 2001-02-01 2002-08-08 Bristol-Myers Squibb Company METHODS OF TREATING INFLAMMATORY AND IMMUNE DISEASES USING INHIBITORS OF IλB KINASE (IKK)
US20030045515A1 (en) 2001-05-24 2003-03-06 Lise Binderup Combination medicament for treatment of neoplastic diseases
WO2002094813A1 (en) 2001-05-24 2002-11-28 Leo Pharma A/S Novel pyridyl cyanoguanidine compounds
WO2002094265A1 (en) 2001-05-24 2002-11-28 Leo Pharma A/S A method of modulating nf-$g(k)b activity
US6638679B2 (en) 2001-07-12 2003-10-28 Kodak Polychrome Graphics, Llc Photosensitive compositions having mixtures of alkoxy and non-alkoxy diazonium salt containing compounds
SE0102617D0 (en) 2001-07-25 2001-07-25 Astrazeneca Ab Novel compounds
SE0102616D0 (en) 2001-07-25 2001-07-25 Astrazeneca Ab Novel compounds
WO2003024935A2 (en) 2001-09-19 2003-03-27 Pharmacia Corporation Substituted pyrazolyl compounds for the treatment of inflammation
BR0212661A (en) 2001-09-19 2004-08-24 Pharmacia Corp Substituted pyrazolyl benzenesulfamide compounds for the treatment of inflammation
US20030109550A1 (en) 2001-09-19 2003-06-12 Michael Clare Substituted indazole compounds for the treatment of inflammation
CA2460939C (en) 2001-09-19 2008-07-29 Pharmacia Corporation Substituted pyrazolyl compounds for the treatment of inflammation
BR0213734A (en) 2001-10-30 2004-10-19 Pharmacia Corp Heteroaromatic carboxamide derivatives for the treatment of inflammation
ATE370145T1 (en) 2002-04-03 2007-09-15 Bristol Myers Squibb Co TRICYCLIC THIOPHENE-BASED COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
CA2485298C (en) 2002-05-09 2008-03-11 Pharmacia Corporation Substituted pyrazolyl compounds for the treatment of inflammation
AU2003237330A1 (en) 2002-06-06 2003-12-22 Boehringer Ingelheim Pharmaceuticals, Inc. Substituted 3-amino-thieno[2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses
GB0217757D0 (en) * 2002-07-31 2002-09-11 Glaxo Group Ltd Novel compounds
AU2003261415C1 (en) * 2002-08-09 2010-01-14 Merck Sharp & Dohme Corp. Tyrosine kinase inhibitors
DE10237722A1 (en) 2002-08-17 2004-08-19 Aventis Pharma Deutschland Gmbh Indole or benzimidazole derivatives for the modulation of IKappaB kinase
US7329668B2 (en) 2003-02-25 2008-02-12 Bristol-Myers Squibb Company Pyrazolopurine-based tricyclic compounds and pharmaceutical compositions comprising same
GB0308466D0 (en) 2003-04-11 2003-05-21 Novartis Ag Organic compounds
US7176214B2 (en) 2003-05-21 2007-02-13 Bristol-Myers Squibb Company Imidazo-fused oxazolo[4,5-β]pyridine and imidazo-fused thiazolo[4,5-β]pyridine based tricyclic compounds and pharmaceutical compositions comprising same
WO2005012283A1 (en) 2003-07-31 2005-02-10 Boehringer Ingelheim Pharmaceuticals, Inc. Substituted benzothiophene compounds and uses thereof
US7265148B2 (en) * 2003-09-25 2007-09-04 Wyeth Substituted pyrrole-indoles
US7291733B2 (en) 2003-10-10 2007-11-06 Boehringer Ingelheim Pharmaceuticals, Inc. Substituted tricyclic heterocycles and their uses
US20070225291A1 (en) 2003-10-14 2007-09-27 Pfizer Inc. Substituted Pyrazinone Compounds for the Treatment of Inflammation
GB0400895D0 (en) * 2004-01-15 2004-02-18 Smithkline Beecham Corp Chemical compounds
TW200616967A (en) * 2004-06-24 2006-06-01 Smithkline Beecham Corp Novel indazole carboxamides and their use
CN101060842A (en) * 2004-09-21 2007-10-24 葛兰素集团有限公司 Chemical compounds
PE20060748A1 (en) * 2004-09-21 2006-10-01 Smithkline Beecham Corp INDOLCARBOXAMIDE DERIVATIVES AS KINASE INHIBITORS IKK2

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