HK1238233B - Fused pyrimidines as inhibitors of p97 complex - Google Patents

Description

Fused pyrimidines as inhibitors of the p97 complex

Background of the Invention

The AAA (ATPase associated with multiple activities) ATPase p97, descriptively named valosin-containing protein, is conserved in all eukaryotes and is essential for life in budding yeast (Giaever, G. et al. Nature (2002) 418, 387-391) and mice (Muller, J.M. et al. Biochem. Biophys. Res. Commun. (2007) 354, 459-465). Humans with reduced-function p97 alleles suffer from a syndrome that includes inclusion body myopathy and frontotemporal lobar degeneration (Weihl, C. et al. Hum. Mol. Genet. (2006) 15, 189-199). Loss-of-function studies in model organisms have shown that p97 plays a key role in a wide range of cellular processes including: Golgi membrane reassembly (Rabouille, C. et al. Cell (1995) 82, 905-914), membrane trafficking (Ye, Y. et al. Nature (2001) 414, 652-656; Ye, Y. et al. Nature (2004) 429, 841-847), degradation of misfolded membranes and secretory proteins via the ubiquitin proteasome system (UPS) (Golbik, R. et al. Biol. Chem. (1999) 380, 1049-1062; Richly, H. et al. Cell (2005) 120, 73-84), regulation of myofibril assembly (Janiesch, P.C. et al. Nat. Cell (2001) 43, 76-78), and regulation of mitochondrial membrane secretion (Janiesch, P.C. et al. Nat. Cell (2001) 44, 77-79). Biol. (2007) 9, 379-390), and cell division (Cao, K. et al. Cell (2003) 115, 355-367). The wide range of cellular functions of this protein is thought to derive from its ability to unfold proteins or dissociate protein complexes. The mechanochemical activity of p97 is associated with substrate proteins by binding to an array of at least 14 UBX domain binders of p97 as well as the non-UBX domain binders Ufd1 and Np14 (Meyer, H.H. et al. EMBO J. (2000) 19, 2181-2192).

The sequence of p97 shows three domains (N-domain, D1 ATPase domain, and D2 ATPase domain) connected by a linker region. X-ray crystallography of p97 shows that it forms a homohexamer of 97 kilodalton subunits that assemble to form two stacked rings. These two rings are formed by the ATPase domains (Huyton, T. et al., Struct. Biol. (2003) 144, 337-348; DeLaBarre, B. et al., Nat. Struct. Biol. (2003) 10, 856-863). The 'upper' ring is formed by a hexamer of D1 domains, while the 'lower' ring is formed by a hexamer of D2 domains. The N-domain extends outward from the D1 domain ring. Although it is clear that the D2 domain hydrolyzes ATP in vitro, the level of D1-specific ATPase activity reported by different researchers is variable. Nevertheless, genetic studies in yeast have shown that ATP hydrolysis by both the D1 and D2 domains is required for p97 function (Song, C. et al. J. Biol. Chem. (2003) 278, 3648-3655; Ye, Y. et al. J. Cell Biol. (2004) 162, 71-84). ATP binding to the D1 domain is also required for p97 assembly (Wang, Q. et al. Biochem. Biophys. Res. Commun. (2003) 300, 253-260). Although ATP hydrolysis by the D2 domain is not required for the assembly of the p97 hexamer, it is believed that ATP hydrolysis by the D2 domain is a substrate conversion that causes them to unfold or dissociate from their binding partners.

A prominent cellular function of p97 that has received considerable scrutiny is its role in the turnover of misfolded secretory proteins via the UPS (ubiquitin proteasome system). In this process, known as ERAD (for endoplasmic reticulum-associated degradation), proteins that fail to fold within the ER are translocated to the cytoplasm in a p97-dependent manner, where they are degraded by the UPS (Ye, Y. et al. Nature (2004) 429, 841-847). In this process, p97 is thought to mediate the extraction of substrates from the ER membrane. The p97 complex is also required for the turnover of cytoplasmic substrates of the UPS (Janiesch, P.C. et al. Nat. Cell Biol. (2007) 9, 379-390; Cao, K. et al. Cell (2003) 115, 355-367; Fu, X. et al. J. Cell Biol. (2003) 163, 21-26), although its role in the turnover of cytoplasmic proteins is poorly understood.

The valosin-containing protein p97 represents a suitable target for cancer therapeutics. The p97 complex and its functions are essential for sustained cell viability, and therefore drugs that inhibit it should be antiproliferative. In other words, inhibition of p97 will lead to undesirable protein aggregation within target cells. The resulting cellular response is often apoptosis or at least an improvement in cell growth and mitosis. Furthermore, p97 is known to be overproduced in many cancers (Yamamoto, S. et al. Ann. Surg. Oncol. (2005) 12, 925-934; Yamamoto, S. et al. Clin. Cancer Res. (2004) 10, 5558-5565; Yamamoto, S. et al. Ann. Surg. Oncol. (2004) 11, 697-704; Yamamoto, S. et al. Ann. Surg. Oncol. (2004) 11, 165-172), suggesting that its activity may be rate-limiting for the development of at least some cancers. p97 is known to be essential for ERAD (Carvalho, P. et al. Cell (2006) 126, 361-373), and recent studies have shown that cancer cells may be particularly dependent on ERAD (Boelens, J. et al. In Vivo (2007) 21, 215-226). Furthermore, p97 has been implicated in the turnover of IlcB and the subsequent activation of NF-κB (Dai, R.M. et al. J. Biol. Chem. (1998) 273, 3562-3573). NF-κB activity is important for the survival of some tumor cells, particularly in multiple myeloma (Keats, J.J. et al. Cancer Cell (2007) 12, 131-144; Annunziata, C.M. et al. Cancer Cell (2007) 12, 115-130). Bortezomib has been shown to be active in multiple myeloma due to its ability to block protein turnover via the ERAD pathway and its ability to block IkB turnover, thereby inhibiting NF-κB activity. Given that p97 is involved in ERAD and IlcB turnover, but also has a more restricted role in the UPS than the proteasome itself, drugs targeting p97 could retain much of the efficacy of bortezomib but with less toxicity. Additionally, compounds that interact with the p97 complex are disclosed in PCT/US2011/035654, filed May 6, 2011, and published as WO 2011/140527 on November 10, 2011.

Objectives of the invention

Therefore, there is a need to develop compounds useful for inhibiting p97 activity and methods of using such compounds to inhibit p97 activity. There is a need to develop such compounds for treating tumorous conditions.

Summary of the Invention

These and other needs are met by aspects of the present invention, one of which relates to a group of fused pyrimidine compounds having a cyclopentyl, cyclohexyl, or cycloheptyl ring as a fusion partner of the fused pyrimidine compound. The fusion partner optionally contains nitrogen, oxygen, or sulfur heteroatoms in its ring. The fused pyrimidine compounds have certain optionally substituted 5:6 heterocycles substituted at the 2-position of the pyrimidine ring and an optionally substituted benzylamine group substituted at the 4-position of the pyrimidine ring.

In another aspect of the present invention, the fused pyrimidines and pharmaceutical compositions thereof inhibit the valosin-containing protein p97 and improve, reduce, shrink, alleviate, and/or eliminate cells exhibiting tumorigenicity and/or abnormal function. In another aspect of the present invention, the compounds and compositions inhibit the ATPase activity of p97. Another aspect of the present invention relates to the treatment of adverse conditions and/or diseases, such as cancer, by using the compounds and compositions.

A first aspect of the present invention relates to fused pyrimidine compounds having a 5:6 heterocycle at the 2-position of the pyrimidine ring and an optionally substituted benzylamine group at the 4-position of the pyrimidine ring. Embodiments of the fused pyrimidine compounds of the present invention have a structure represented by Formula I, wherein Y is ^CR4 , NH, ^NR5 , O, or S, and C of ^CR4 is an ^sp3 carbon. The symbols m and n of Formula I are each independently an integer of 0, 1, 2, 3, or 4, and the sum of n and m is an integer of 2, 3, or 4. Ar is an optionally substituted aryl group, and the moiety at the 2-position of the pyrimidine ring is a 5:6 heterobicycle designated herein as HET.

The "backbone" of Formula I is a single fused pyrimidine ring and is represented by Formula II. Formula II presents an embodiment of a fused pyrimidine ring without -HET and -NHCH ₂ Ar moieties. The backbone (Formula II) is a fused pyrimidine wherein the saturated ring fused to the pyrimidine is a 5-, 6-, or 7-membered ring and the Y group or atom is at any position around the saturated ring, except for a position shared with the pyrimidine ring. Preferred saturated rings of the backbone are five- and six-membered saturated rings, wherein Y is located at any position around the saturated ring, except for the fused position. The preferred position of Y on the five- and six-membered saturated rings is a saturated ring position adjacent to the fused position. Other preferred backbones are five- and six-membered saturated rings, wherein Y is located at a saturated ring position other than adjacent to the fused position and Het is not an indole or benzimidazole moiety.

The HET moiety of Formula I is represented by the formula HET, wherein A, D, E, B, and Z have the following designations. The following designations of A, D, E, B, and Z also apply to the embodiment of the fused pyrimidine compound of the present invention represented by Formula I. The six-membered ring of Formula HET is aromatic, while the five-membered ring can be aromatic or partially saturated.

A, D, and E of formula HET (and thus formula I) are each independently C or N, wherein C is an ^sp2 carbon substituted with H or an alkyl group of one to four carbon atoms, unless one of the valences of C is otherwise specified. Z and B are each independently ^CR6 , N, ^NR7 , O, or S, wherein C as ^CR6 is an ^sp2 carbon. Certain restrictions apply to formula HET when used as part of formula I. These are:

1. At least one of D and E is C;

2. At least one of A, D, E, Z, and B is not C;

3. Z and B cannot be NR ⁷ , O or S at the same time;

4. When one of D and E is N and A is C, Z and B are each independently CR ⁶ , N or NR ⁷ ;

5. When D and E are both C and A is N, Z and B are each independently ^CR6 or N; and in this designation of D, E, A, Z, and B, when Y is carbon and ^R3 is hydrogen, or in this designation of D, E, A, Z, and B, when neither m nor n is 0 (zero integer), in any of these subdesignations, Z and B cannot both be ^CR6 and B cannot be N;

6. When D, E and A are all C, Z and B are each independently CR ⁶ , N, NR ⁷ , O or S;

7. When one of Z and B is O or S, the other is CR ⁶ or N, and A, D and E are all C;

8. When one of Z and B is NR ⁷ , the other is N or CR ⁶ , and A, D and E are all C.

With respect to constraint 5, there is one primary designation and two secondary designations. When D and E are both C and A is N, the primary designation is that Z and B are each independently CR ⁶ or N. Under this primary designation, two secondary designations apply. Under the primary designation of Z and B, when D and E are C and A is N, the first secondary designation is that when Y is carbon and the R ³ group attached to Y as C is hydrogen, Z and B cannot both be CR ⁶ and B cannot be N. And, under the primary designation of Z and B, when D and E are C and A is N, the second secondary designation is that when m and n are not 0 (i.e., m and n are independently integers of 1-4) and R ³ is hydrogen, Z and B cannot both be CR ⁶ and B cannot be N.

The substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ may each independently be selected from hydrogen, an optionally substituted aliphatic group, an optionally substituted aromatic group and/or an optionally substituted functional group.

These designations for substituent R groups are further described below in the definitions section.

Another aspect of the present invention relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I described above.

Another aspect of the present invention relates to a method for reducing the activity of valosin-containing protein (p97) or decreasing the degradation of substrates of the proteasome system, particularly ubiquitin substrates, by administering a therapeutically effective amount of one of the compounds of formula I to a patient in need thereof.

Yet another aspect of the present invention relates to treating tumor conditions, cancer and other adverse conditions associated with p97 by administering a compound of formula I or the above-described pharmaceutical composition to a patient in need thereof.

The fused pyrimidine compounds and pharmaceutical compositions of the present invention will inhibit or improve the activity of the biologically active enzyme p97, show a physiological profile and will preferably show a desired degree of inhibition or improvement, particularly with respect to the treatment of cancer and related adverse conditions.

Detailed Description of the Invention

definition

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

As used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

As used herein, the term "about" when used in reference to a numerical value or range allows for a degree of variability in the stated value or range, for example, within 10% or 5% of the stated value or limit of the stated range.

Unless otherwise indicated, all percentage compositions are given as weight percent.

Unless otherwise indicated, all average molecular weights for polymers are weight average molecular weights.

As used herein, "subject" (as in the subject of treatment) or "patient" refers to both mammals and non-mammals. Mammals include, for example, humans; non-human primates, such as apes and monkeys; and non-primates, such as dogs, cats, cows, horses, sheep, and goats. Non-mammals include, for example, fish and birds.

The term “may” in the context of this application means “allowing for” or “being able to” and is synonymous with the term “may.” The term “may” as used herein does not refer to possibility or probability.

The terms "disease" or "disorder" or "adverse condition" are used interchangeably and are used to refer to a disease or condition in which X plays a role in the biochemical mechanisms involved in the disease or adverse condition or its symptoms, such that a therapeutic benefit can be achieved by acting on X. "Acting on" X or "modulating" X can include binding to X and/or inhibiting the biological activity of X and/or allosterically modulating the biological activity of X in vivo.

The expression "effective amount" when used to describe a therapy for an individual suffering from a condition refers to the amount of a drug, agent, or compound of the present invention that will elicit the biological or medical response being sought by, for example, a researcher or clinician. Such responses include, but are not limited to, amelioration, inhibition, or other effects on a condition, adverse condition, disease, infection, or other problem in a tissue of an individual, wherein the condition, adverse condition, disease, etc. is active, wherein such inhibition or other effects occur to an extent sufficient to produce a beneficial therapeutic effect. Furthermore, the term "therapeutically effective amount" means any amount that results in an improved treatment, cure, prevention, or amelioration of a disease, condition, or side effect, or a slowing of the rate of progression of a disease or condition, as compared to a corresponding subject that has not received such amount. The term also includes within its scope amounts that are effective to enhance normal physiological function.

As used herein, the term "substantially" means completely or nearly completely; for example, a composition that is "substantially free" of a component does not contain that component or contains such trace amounts that any relevant functional properties of the composition are not affected by the presence of the trace amount, or a compound is "substantially pure" if only negligible trace amounts of impurities are present.

"Treating" or "treatment" within the meaning herein refers to alleviating the symptoms associated with a condition or disease, or inhibiting the further progression or worsening of those symptoms, or preventing or controlling a disease or condition, or curing a disease or condition. Similarly, as used herein, an "effective amount" or "therapeutically effective amount" of a compound of the invention refers to an amount of the compound that completely or partially alleviates the symptoms associated with a condition or disease, or stops or slows the further progression or worsening of those symptoms, or prevents or provides prophylaxis for the condition or disease. Specifically, a "therapeutically effective amount" refers to an amount that is effective at a dosage and continues for the period of time necessary to achieve the desired therapeutic result. A therapeutically effective amount is also an amount in which the therapeutically beneficial effects outweigh any toxic or deleterious effects of the compound of the invention.

In the context of synthetic methods, phrases such as "under conditions suitable to provide" or "under conditions sufficient to produce" and the like, as used herein, refer to reaction conditions such as time, temperature, solvent, concentration of reactants, etc., which are varied within the skill of the ordinary experimenter to provide an effective amount or yield of the reaction product. The desired reaction product need not be the only reaction product or the starting materials need not be completely consumed, provided that the desired reaction product can be isolated or otherwise used further.

"Chemically feasible" means bonding arrangements or compounds in which the generally understood rules of organic structure are not violated; for example, structures within the definition of a claim will be understood not to be within the claim, as will structures in some cases contain pentavalent carbon atoms that would not exist in nature. In all of its embodiments, the structures disclosed herein are intended to include only "chemically feasible" structures, and any such structures that are not chemically feasible (e.g., structures shown with variable atoms or groups) are not intended to be disclosed or claimed herein.

As used herein, the term "analog" of a chemical structure refers to a chemical structure that retains substantial similarity to a parent structure, but which is not readily synthetically derived from the parent structure. Related chemical structures that are readily synthetically derived from a parent chemical structure are referred to as "derivatives."

When a substituent is designated as an atom or atoms of a particular identity, "or a bond" (the configuration referred to when the substituent is a "bond") means that the groups immediately adjacent to the specified substituent are directly attached to each other in a chemically feasible bonding configuration.

Unless specifically indicated specific stereochemistry or isomeric formation, all chiral, diastereomeric, racemic forms of the structure are included. In some cases, although a single stereoisomer is described among the compounds specifically claimed, stereochemical designation does not mean that the alternative isomeric form is less preferred, undesirable or not claimed. The compounds used in the present invention may include optical isomers enriched or split at any or all asymmetric atoms, as is apparent from the description, at any enrichment level. Racemic and diastereomeric mixtures as well as single optical isomers can be separated or synthesized so as to be substantially free of their enantiomers or diastereomeric partners, and these are all within the scope of the present invention.

As used herein, the terms "stable compound" and "stable structure" are intended to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. Only stable compounds are contemplated herein.

The selected substituents within the compounds described herein are present to a recursive degree. In this context, a "recursive substituent" means another instance in which a substituent can list itself. Because of the reusable nature of such substituents, theoretically, a larger number can be present in any given claim. One of ordinary skill in the art of medicinal chemistry and organic chemistry understands that the total number of such substituents is appropriately limited by the desired properties of the intended compound. Such properties include, by way of example and not limitation, physical properties such as molecular weight, solubility, or log P, application properties such as activity against a predetermined target, and practical properties such as ease of synthesis. Reusable substituents are an anticipated aspect of the disclosed subject matter. One of ordinary skill in the art of medicinal and organic chemistry understands the versatility of such substituents. To the extent that reusable substituents are present in the claims of the disclosed subject matter, the total number should be determined as listed above.

When describing a group in which the group can exist in more than one orientation within the structure, thereby producing more than one molecular structure, for example, a carboxamide group C(=O)NR, unless the context clearly limits the orientation of the group within the molecular structure, it is understood that the group can exist in any possible orientation, for example, X-C(=O)N(R)-Y or X-N(R)C(=O)-Y.

When a group, such as an "alkyl" group, is referred to without any limitation on the number of atoms in the group, it is understood that the claim is well-defined and limited with respect to the size of the alkyl group by both: by definition, i.e., the size (number of carbon atoms) of a group such as an alkyl group is a finite number that is less than the total number of carbon atoms and is understood by one of ordinary skill in the art to be reasonable with respect to the size of the group for the molecular entity; and by functionality, i.e., the size of a group such as an alkyl group is defined by the functional property (e.g., solubility in aqueous or organic liquid media) that the group imparts to the molecule containing the group. Thus, a claim reciting an "alkyl" or other chemical group or moiety is well-defined because the number of atoms in the group cannot be infinite.

Generally speaking, "substituted" refers to an organic group as defined herein in which one or more bonds to a hydrogen atom contained therein are replaced by one or more bonds to a non-hydrogen atom. More specifically, the term "chemical substituent" refers to any and all aliphatic, aromatic, and functional groups listed in this section that can be attached to an organic molecule. Functional groups are inorganic moieties such as halogens, sulfates, nitro groups, amino groups, etc.; as well as non-carbon functional groups such as carboxyl groups, carbonyl groups, and formamide groups, which are common and typical optional substituents of organic molecules. In the context of the present invention, the description of this term without indicating a specific group constitutes the definition given above. The description of this term in conjunction with the Markush description of a specific group constitutes a subgenus of the understanding conveyed by the above definition. The term "substituent" generally means any appropriate group listed below, which ends with "radical," "y," or "and" to indicate that it is attached, connected, or covalently bonded to another moiety such as, but not limited to, an aromatic framework. Examples include, but are not limited to, halogens (i.e., F, Cl, Br, and I); oxygen atoms in groups such as hydroxy, alkoxy, aryloxy, aralkyloxy, oxo (carbonyl), carboxyl groups including carboxylic acids, carboxylates, and carboxyl esters; sulfur atoms in groups such as thiol, alkyl and arylsulfide groups, sulfoxide groups, sulfone groups, sulfonyl and sulfonamide groups; nitrogen atoms in groups such as amine, hydroxylamine, nitrile, nitro, N-oxide, hydrazide, azide, and enamine; and other heteroatoms in various other groups.

When a substituent is monovalent, such as, for example, F or Cl, it is single-bonded to the atom it replaces. When a substituent exceeds a monovalent valency, such as O, which is divalent, it may be bonded to the atom it replaces through more than one bond, i.e., the divalent substituent is double-bonded; for example, a C replaced by an O forms a carbonyl group, C=O, which may also be written as "CO," "C(O)," or "C(=O)," where the C and O are double-bonded. When a carbon atom is replaced by a double-bonded oxygen (=O) group, the oxygen substituent is referred to as an "oxo" group. When a divalent substituent such as NR is double-bonded to a carbon atom, the resulting C(=NR) group is referred to as an "imino" group. When a divalent substituent such as S is double-bonded to a carbon atom, the resulting C(=S) group is referred to as a "thiocarbonyl" or "thiocarbonyl" group.

Alternatively, a divalent substituent such as O or S can be attached to two different carbon atoms by two single bonds. For example, O, a divalent substituent, can be bonded to each of two adjacent carbon atoms to provide an epoxy group, or O can form a bridged ether group between adjacent or non-adjacent carbon atoms, known as an "oxy" group, for example, bridging the 1,4-carbon of a cyclohexyl group to form a [2.2.1]-oxabicyclic ring system. In addition, any substituent can be bonded to a carbon or other atom through a linker, such as (CH ₂ ) _n or (CR′ ₂ ) _n , where n is 1, 2, 3 or greater, and each R′ is independently selected.

For all substituents, the first atom of the molecular formula of the substituent is the atom that bonds the substituent to its corresponding moiety. For example, for the functional group N( ^Ra )C(O) ^Ra , the N is bonded to the corresponding moiety substituted by this group. If a substituent is described using words such as alkenylamine, then the phrase ending with "alkenyl" indicates the carbon atom at which the substituent is bonded to its corresponding moiety. For substituents that display single bond sites, such as carboxylic acid, sulfonic acid, fluoro, methyl, etc., the bonding arrangement is the expected arrangement.

"Aliphatic substituent, group, or component" refers to any organic group that is not aromatic. This includes acyclic and cyclic organic compounds composed of carbon, hydrogen, and optionally oxygen, nitrogen, sulfur, and other heteroatoms. This term encompasses all organic groups, excluding aromatic and heteroaromatic groups as defined below. Examples of such groups include, but are not limited to, alkyl, alkenyl, alkynyl, corresponding groups with heteroatoms, cyclic analogs, heterocyclic analogs, branched and straight-chain forms, and such groups optionally substituted with functional groups, as these groups and others that meet the definition of "aliphatic" are defined below.

"Aromatic substituent, group or component" refers to any and all aromatic groups, including but not limited to aryl, aralkyl, heteroalkylaryl, heteroalkylheteroaryl, and heteroaryl. The term "aromatic" is general in that it encompasses all compounds containing aryl groups optionally substituted with functional groups (all carbon aromatic groups) and all compounds containing heteroaryl groups optionally substituted with functional groups (carbon-heteroatom aromatic groups), as these groups and others that meet this definition of "aromatic" are defined below.

As used herein, the term "optionally" means that the corresponding substituent or thing may be present or absent. It includes both possibilities.

"Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, and having from one to ten carbon atoms (e.g., _C1 - _C10 alkyl). Whenever it appears herein, a numerical range such as "1 to 10" refers to each integer within the given range; for example, "1 to 10 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms, but this definition also includes occurrences of the term "alkyl" where no numerical range is specified. In some embodiments, it is _C1 - _C4 alkyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, and the like. The alkyl group is attached to the rest of the molecule by a single bond, for example, methyl (Me), ethyl (Et), n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (tert-butyl), 3-methylhexyl, 2-methylhexyl, and the like.

Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

"Alkylaryl" refers to an -(alkyl)aryl group where the aryl and alkyl groups are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for aryl and alkyl groups respectively.

"Alkylheteroaryl" refers to an -(alkyl)heteroaryl group where heteroaryl and alkyl are as disclosed herein and which is optionally substituted by one or more substituents described as suitable substituents for aryl and alkyl respectively.

"Alkylheterocycloalkyl" refers to an -(alkyl)heterocyclyl group where alkyl and heterocycloalkyl are as disclosed herein and which is optionally substituted by one or more substituents described as suitable substituents for heterocycloalkyl and alkyl respectively.

An "alkene" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon double bond, and an "alkyne" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon triple bond. Regardless of whether saturated or unsaturated, an alkyl moiety may be branched, straight chain, or cyclic.

"Alkenyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one double bond and having two to ten carbon atoms (i.e., _C2 - _C10 alkenyl). Whenever it appears herein, a numerical range such as "2 to 10" refers to each integer within the given range; for example, "2 to 10 carbon atoms" means that the alkenyl group can be composed of 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms. In certain embodiments, the alkenyl group comprises two to eight carbon atoms. In other embodiments, the alkenyl group comprises two to five carbon atoms (e.g., _C2 - _C5 alkenyl). The alkenyl group is connected to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, pent-1,4-dienyl, etc.

Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, fluoro, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, -N(Ra ⁾² , -C(O) ^Ra , -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^Ra , -N( ^Ra )C(O)N( ^{Ra )} ₂ , -N( ^{Ra )} C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Alkenyl-cycloalkyl" refers to an -(alkenyl)cycloalkyl group where alkenyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as substituents for alkenyl and cycloalkyl respectively.

"Alkynyl" refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one triple bond and having two to ten carbon atoms (i.e., C2-C10 alkynyl). Whenever it occurs in this article, a numerical range such as "2 to 10" refers to each integer within a given range; for example, "2 to 10 carbon atoms" means that the alkynyl group can be composed of 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms. In certain embodiments, the alkynyl group comprises two to eight carbon atoms. In other embodiments, the alkynyl group has two to five carbon atoms (e.g., C2-C5 alkynyl). The alkynyl group is connected to the remainder of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc.

Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, ^-ORa , -SRa, -OC(O)-Ra, ^-N (Ra), -C( ^O )Ra, -C(O) ^ORa , -C ⁽ O) ^N (Ra), -C(O)N( ^Ra ), -N( ^Ra )C(O) ^ORa , -N( ^Ra )C( ^O ) ^Ra , -N( ^Ra )C(O)N( ^Ra ), N( ^Ra )C( ^NRa )N( ^Ra ), -N( ^Ra )S(O ⁾ _tRa (where t is 1 or 2), -S(O ⁾ _tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra )2 (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

"Alkynyl-cycloalkyl" refers to an -(alkynyl)cycloalkyl group where alkynyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for alkynyl and cycloalkyl respectively.

"Formaldehyde" refers to a -(C=O)H group.

"Carboxy" refers to a -(C=O)OH group.

"Cyano" refers to a -CN group.

"Cycloalkyl" refers to a monocyclic or polycyclic group that contains only carbon and hydrogen and can be saturated or partially unsaturated. Cycloalkyl includes groups with 3 to 10 ring atoms (i.e., _C2 - _C10 cycloalkyl). Whenever it appears in this article, a numerical range such as "3 to 10" refers to each integer within the given range; for example, "3 to 10 carbon atoms" means that the cycloalkyl can be composed of 3 carbon atoms, etc., up to and including 10 carbon atoms. In some embodiments, it is _C3 - _C8 cycloalkyl. In some embodiments, it is _C3 - _C5 cycloalkyl. Illustrative examples of cycloalkyl include, but are not limited to, the following moieties: cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, norbornyl, etc.

Unless stated otherwise specifically in the specification, a cycloalkyl group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Cycloalkyl-alkenyl" refers to a -(cycloalkyl)alkenyl group where cycloalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heterocycloalkyl and cycloalkyl respectively.

"Cycloalkyl-heterocycloalkyl" refers to a -(cycloalkyl)heterocyclyl group where cycloalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heterocycloalkyl and cycloalkyl respectively.

"Cycloalkyl-heteroaryl" refers to a -(cycloalkyl)heteroaryl group where cycloalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heterocycloalkyl and cycloalkyl respectively.

"Alkoxy" refers to the radical -O-alkyl, which includes 1 to 8 carbon atoms in linear, branched, cyclic configurations, and combinations thereof, attached to the parent structure through an oxygen. Examples include methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy, and the like. "Lower alkoxy" refers to an alkoxy group containing from one to six carbon atoms. In some embodiments, _C1 - _C4 alkyl is an alkyl group including linear and branched alkyl groups of 1 to 4 carbon atoms.

"Substituted alkoxy" refers to an alkoxy group in which the alkyl component is substituted (ie, -O-(substituted alkyl)).

Unless stated otherwise specifically in the specification, the alkyl part of an alkoxy group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -C ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Alkoxycarbonyl" refers to a radical of the formula (alkoxy)(C=O)- attached through the carbonyl carbon, wherein the alkoxy group has the indicated number of carbon atoms. Thus, a _C1 - _C6 alkoxycarbonyl is an alkoxy group having from 1 to 6 carbon atoms attached through its oxygen to the carbonyl linker. "Lower alkoxycarbonyl" refers to an alkoxycarbonyl group in which the alkoxy group is a lower alkoxy group. In some embodiments, a _C1 - _C4 alkoxy group is an alkoxy group including straight and branched chain alkoxy groups of 1 to 4 carbon atoms.

"Substituted alkoxycarbonyl" refers to the group (substituted alkyl)-O-C(O)-, wherein the group is attached to the parent structure through the carbonyl functionality.

Unless stated otherwise specifically in the specification, the alkyl part of an alkoxycarbonyl group is optionally substituted with one or more substituents as defined above. The substituents further independently include: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C( ^O )Ra, -C(O) ^ORa , ^-OC (O) ^N (Ra) ₂ , -C(O)N( ^Ra ) ₂ , -( ^Ra )C( ^O ) ^ORa , -N( ^Ra )C(O) ^Ra , -N( ^Ra ₎ C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra ) ^S (O) _tRa (where t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ ⁽ wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , wherein each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

"Acyl" refers to the groups (alkyl)-C(O)-, (aryl)-C(O)-, (heteroaryl)-C(O)-, (heteroalkyl)-C(O)-, and (heterocycloalkyl)-C(O)-, wherein the group is attached to the parent structure through a carbonyl functional group. In some embodiments, it is a _C1 - _C10 acyl group, which refers to the total number of chain or ring atoms of the alkyl, aryl, heteroaryl, or heterocycloalkyl portion of the acyloxy group plus the carbonyl carbon of the acyl group, i.e., three other ring or chain atoms plus the carbonyl group. If the R group is heteroaryl or heterocycloalkyl, then the heterocyclic or chain atoms constitute the total number of chain or ring atoms.

Unless stated otherwise specifically in the specification, "R" of an acyloxy group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (where t is 1 or 2), -S(O) _tORa ⁽ where t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ (where t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl. "Acyloxy" refers to an R(C=O)O- group, where "R" is alkyl, aryl, heteroaryl, heteroalkyl, or heterocyclylalkyl, as described herein. In some embodiments, it is a _C1 - _C4 acyloxy group, which refers to the total number of chain or ring atoms of the alkyl, aryl, heteroaryl, or heterocyclylalkyl portion of the acyloxy group plus the carbonyl carbon of the acyl group, i.e., three other ring or chain atoms plus the carbonyl group. If the R group is heteroaryl or heterocyclylalkyl, the heterocycle or chain atoms make up the total number of chain or ring atoms.

Unless stated otherwise specifically in the specification, "R" of an acyloxy group is optionally substituted with one or more substituents as defined above. The substituents further independently include: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, ^-ORa , -SRa, -OC(O)-Ra, ^-N (Ra)2, -C( ^O )Ra, -C(O) ^ORa , ^-OC (O) ^N (Ra) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra ) ^S (O) _tRa (where t is 1 or 2) _tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ ⁽ wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , wherein each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

"Amino" or "amine" refers to an -N( ^Ra ) ₂ group, wherein, unless otherwise specifically indicated in the specification, each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl. When an -N( ^Ra ) ₂ group has two Ra that are not hydrogen, they may be combined with the nitrogen atom to form a 4-, 5-, 6-, or 7-membered ring. For example, -N( ^Ra ) ₂ is intended to include, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl.

Unless stated otherwise specifically in the specification, an amino group is optionally substituted with one or more substituents as defined above. The substituents further independently include: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, fluoro, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C( ^O )Ra, -C(O) ^ORa , ^OC (O)N(Ra) ₂ , -C(O) ^N ( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C( ^O ) ^Ra , -N( ^Ra )C(O)N( ^{Ra )} ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra ) ^S (O) _tRa (where t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ ⁽ wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl and each of these moieties can be optionally substituted as defined herein.

"Substituted amino" also refers to N-oxides of the groups ^-NHR and NR ^{R ,} each as described above. N-oxides can be prepared by treating the corresponding amino group with, for example, hydrogen peroxide or meta-chloroperbenzoic acid. Those skilled in the art are familiar with the reaction conditions for carrying out N-oxidations.

"Ammonium" ions include unsubstituted ammonium ions _NH4 ⁺ , but unless otherwise specified, also include any protonated or quaternized form of an amine. Thus, trimethylammonium hydrochloride and tetramethylammonium chloride are both ammonium ions and amines within the meaning herein.

"Amide" or "amido" refers to a chemical moiety having the formula -C(O)N(R) ₂ or -NHC(O)R, wherein R is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heteroalicyclic (bonded through a ring carbon), each of which moieties may itself be optionally substituted. In some embodiments, it is a C ₁ -C ₄ amide or amide group, which includes the amide carbonyl group in the total number of carbons in the group. The R ₂ of the -N(R) ₂ of the amide may optionally be combined with the nitrogen to which they are attached to form a 4-, 5-, 6-, or 7-membered ring. Unless otherwise specifically indicated in the specification, the amide group is optionally substituted independently with one or more substituents described herein for alkyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl. The amide may be an amino acid or peptide molecule attached to a compound of formula (I) to form a prodrug. Any amine, hydroxyl, or carboxyl side chain on the compounds described herein may be amidated. The procedures and specific groups for preparing such amides are known to those skilled in the art and can be readily found in references such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rd ed., John Wiley & Sons, New York, NY, 1999, which is incorporated herein by reference in its entirety.

"Aryl" refers to a conjugated π group with six or ten ring atoms, which has at least one ring with a conjugated π electron system that is carbocyclic (e.g., phenyl, fluorenyl, and naphthyl). Divalent groups formed from substituted benzene derivatives and having free valence bonds at ring atoms are referred to as substituted phenylene groups. Divalent groups derived from monovalent polycyclic hydrocarbon groups (whose names end in "-yl" by removing hydrogen atoms from carbon atoms with free valence bonds) are named by adding "-ylidene" to the name of the corresponding monovalent group, for example, naphthyl with two points of attachment is referred to as naphthylene. The term includes monocyclic or fused-ring polycyclic (i.e., rings sharing adjacent paired ring atoms) groups.

Unless stated otherwise specifically in the specification, aryl moieties are optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Aralkyl" or "arylalkyl" refers to an (aryl)alkyl- group in which aryl and alkyl are as disclosed herein and which is optionally substituted by one or more substituents described as suitable substituents for aryl and alkyl respectively.

"Ester" refers to a chemical group of the formula -COOR, where R is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heteroalicyclic (bonded through a ring carbon). Any amine, hydroxyl, or carboxyl side chain on the compounds described herein can be esterified. The procedures and specific groups for preparing such esters are known to those skilled in the art and can be readily found in references such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, New York, NY, 1999, which is incorporated herein by reference in its entirety.

Unless stated otherwise specifically in the specification, an ester group is optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra ⁾² , -C(O)Ra, -C(O) ^ORa , -OC ⁽ O) ^N ( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) _ORa , -N( ^Ra )C(O) ^{Ra ,} -N( ^{Ra )} C(O)N( ^Ra ) ₂ , N( ^Ra )C( ^NRa )N( ^Ra ) ₂ , -N( ^Ra )S(O ⁾ _tRa (wherein t is 1 or 2), -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), or _PO3 ( ^Ra ) ₂ , where each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Fluoroalkyl" refers to an alkyl group as defined above substituted with one or more fluoro groups as defined above, for example, trifluoromethyl, difluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. The alkyl portion of the fluoroalkyl group may be optionally substituted as defined above for an alkyl group.

"Functional substituent, group or component" refers to a substituent capable of exhibiting functional groups such as and including hydroxyl, ester, amide, amine, enamine, halogen, cyano, thiol, oxidized sulfur, nitrogen or phosphorus groups, alkoxy, olefinic, aldehyde, ketone, carboxylic acid, anhydride, polyurethane, urea, imine, amidine, hydroxyimine, hydroxylamine, nitrile, organometallic and any other group capable of exhibiting dipolar interactions and/or reactivity. See Basic Principles of Organic Chemistry, Roberts & Casario, W.A. Benjamin, Publishers New York, NY 1965, Chapter 10. Additional examples include hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilyl, ^-ORa , ^-SRa , -OC(O)-Ra, -N( ^Ra ) ₂ , -C(O) ^Ra , -C(O) ^ORa , ^C (O)N( ^Ra ) ₂ , -C(O)N( ^Ra ) ₂ , -N( ^Ra )C(O) ^ORa , -N(Ra)C(O) ^Ra , -N( ^Ra )C( ^O )N( ^Ra ) ₂ , N(Ra)C( ^NRa )N( ^{Ra )} ₂ , -N( ^Ra )S(O) _tRa (wherein t is 1 or 2 ⁾ , -S(O) _tORa (wherein t is 1 or 2), -S(O) ^tN ₍ ^Ra ) ₂ (wherein t is 1 or 2), ^-Ra -N( ^Ra ) ₂ or _PO3 ( ^Ra ) ₂ , wherein each ^Ra is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, or any combination thereof.

"Halo," "halide," or alternatively, "halogen" refers to fluorine, chlorine, bromine, or iodine. The terms "haloalkyl," "haloalkenyl," "haloalkynyl," and "haloalkoxy" include alkyl, alkenyl, alkynyl, and alkoxy structures substituted with one or more halo groups or combinations thereof. For example, the terms "fluoroalkyl" and "fluoroalkoxy" include haloalkyl and haloalkoxy, respectively, in which the halo group is fluorine.

"Heteroalkyl,""heteroalkenyl," and "heteroalkynyl" include optionally substituted alkyl, alkenyl, and alkynyl groups having one or more backbone chain atoms selected from atoms other than carbon (e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof). Numerical ranges may be given, for example, C ₁ -C ₄ heteroalkyl refers to the overall chain length, which in this embodiment is 4 atoms long. For example, a -CH ₂ OCH ₂ CH ₃ group is referred to as a "C ₄ " heteroalkyl group, which includes the heteroatom center in the atom chain length description. Attachment to the remainder of the molecule can be through a heteroatom or a carbon in the heteroalkyl chain.

The heteroalkyl group may be substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C(O)Ra, -C( ^O ) ^ORa , -C ⁽ O) ^N (Ra) ₂ , -N( ^Ra )C( ^O ) _ORa , ^-N (Ra)C( ^O ) ^Ra , -N( ^Ra )S(O) _tRa (wherein t is 1 or 2), -S(O) ^tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ (wherein t is 1 or 2) _, or _PO3 ( ^Ra ) ₂ , wherein each ^{R a} is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

"Heteroalkylaryl" refers to a -(heteroalkyl)aryl group where heteroalkyl and aryl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heteroalkyl and aryl respectively.

"Heteroalkylheteroaryl" refers to a -(heteroalkyl)heteroaryl group where heteroalkyl and heteroaryl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heteroalkyl and heteroaryl respectively.

"Heteroalkylheterocycloalkyl" refers to a -(heteroalkyl)heterocycloalkyl group where heteroalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heteroalkyl and heterocycloalkyl respectively.

"Heteroalkylcycloalkyl" refers to a -(heteroalkyl)cycloalkyl group where heteroalkyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more substituents described as suitable substituents for heteroalkyl and cycloalkyl respectively.

"Heteroaryl" refers to a 5-, 6-, or 10-membered aromatic radical (e.g., _C5 - _C13 heteroaryl) that includes one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur and that can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system. Whenever it appears herein, a numerical range refers to each integer within the given range. An N-containing "heteroaromatic" or "heteroaryl" moiety refers to an aromatic group in which at least one of the ring backbone atoms is a nitrogen atom. Polycyclic heteroaryls can be fused or non-fused. The heteroatoms in the heteroaryl group are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl group is attached to the rest of the molecule through any atom of the ring. Examples of heteroaryl groups include, but are not limited to, adeninyl, azabenzimidazolyl, azaindolyl, azapentyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzoxazolyl, benzopyranyl, benzopyrone, benzofuranyl, benzofuranone, benzofurazanyl, benzothiazolyl, benzothiophenyl, benzothieno[3,2-d] Pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclopenta[ 1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furazanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyridinyl, isothiazolyl, imidazolyl , imidazopyridinyl, isoxazolopyridinyl, indazolyl, indolyl, indazolyl, isoindolyl, dihydroindolinyl, isodihydroindolinyl, isoquinolinyl, indolizinyl, isoxazolyl, 5,8-methylene-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyldione, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7, 8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyridinyl pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d ]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, thianaphthyl, thiapyranyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl and phenylthio (i.e., thienyl), xanthinyl, guaninyl, quinoxalinyl and quinazolinyl.

Additional examples of aryl and heteroaryl groups include, but are not limited to, phenyl, biphenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl, N-hydroxyimidazolyl, anthracenyl (1-anthryl, 2-anthryl, 3-anthryl), thiophenyl (2-thienyl, 3-thienyl), furanyl (2-furyl, 3-furyl), indolyl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), thiazolyl, pyrrolyl (2-pyrrolyl), thiazolyl (3-pyrrolyl), thiazolyl (4 ... ), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl (4-Benzo[b]furanyl, 5-Benzo[b]furanyl, 2-Benzo[b]furanyl, 3-Benzo[b]furanyl, 4-Benzo[b]furanyl, 5-Benzo[b]furanyl, 6-Benzo[b]furanyl, 7-Benzo[b]furanyl, 8-Benzo[b]furanyl, 1-Benzo[b]furanyl, 3-Benzo[b]furanyl, 4-Benzo[b]furanyl, 5 ...2-Benzo[b]furanyl, 3-Benzo[b]furanyl, 4-Benzo[b]furanyl, 5-Benzo[b]furanyl, 8-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1-Benzo[b]furanyl, 2-Benzo[b]furanyl, 3-Benzo[b]furanyl, 4-Benzo[b]furanyl, 5-Benzo[b]furanyl, 8-Benzo[b]furanyl, 8-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1-Benzo[b]furanyl, 1 furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro-benzo[b]furanyl), 7-(2,3-dihydro-benzo[b]furanyl), benzo[b]phenylthio (2-benzo[b]phenylthio) phenylthio), (2-(2,3-dihydro-benzo[b]phenylthio), 3-(2,3-dihydro-benzo[b]phenylthio), 4-(2,3-dihydro-benzo[b]phenylthio), 5-(2,3-dihydro-benzo[b]phenylthio), 6-(2,3-dihydro-benzo[b]phenylthio), 7-(2,3-dihydro-benzo[b]phenylthio), (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl), benzoxazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 1-Benzothiazolyl, 2-Benzothiazolyl, 4-Benzothiazolyl, 5-Benzothiazolyl, 6-Benzothiazolyl, 7-Benzothiazolyl), Carbazolyl (1-Carbazolyl, 2-Carbazolyl, 3-Carbazolyl, 4-Carbazolyl), 5H-dibenzo[b,f]azepin-1-yl, 5H-dibenzo[b,f]azepin-2-yl, 5H-dibenzo[b,f]azepin-3-yl, 5H-dibenzo[b,f]azepin-4-yl, 5H-dibenzo[b,f]azepin-5-yl, 5H-dibenzo[b,f]azepin-6-yl, 5H-dibenzo[b,f]azepin-7-yl, 5H-dibenzo[b,f]azepin-8-yl, 5H-dibenzo[b,f]azepin-9-yl, 5H-dibenzo[b,f]azepin-10-yl, 5H-dibenzo[b,f]azepin-20-yl, 5H-dibenzo[b,f]azepin-30-yl, 5H-dibenzo[b,f]azepin-40 ... [b,f]azepin-5-yl), 10,11-dihydro-5H-dibenzo[b,f]azepin-1-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-2-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-4-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl), and the like.

Unless stated otherwise specifically in the specification, heteroaryl moieties are optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C(O)Ra, -C( ^O ) ^ORa , -C ⁽ O) ^N (Ra) ₂ , -N( ^Ra )C( ^O ) _ORa , ^-N (Ra)C( ^O ) ^Ra , -N( ^Ra )S(O) _tRa (wherein t is 1 or 2), -S(O) ^tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ (wherein t is 1 or 2) _, or _PO3 ( ^Ra ) ₂ , wherein each ^{R a} is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.

Substituted heteroaryl also includes ring systems substituted with one or more oxide (-O-) substituents, such as pyridyl N-oxide.

"Heterocyclyl" refers to any monocyclic or polycyclic moiety containing at least one heteroatom selected from nitrogen, oxygen and sulfur. As used herein, the heterocyclyl moiety can be aromatic or non-aromatic.

Unless otherwise indicated, heterocyclyl moieties are optionally substituted with one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C(O)Ra, -C( ^O ) ^ORa , -C ⁽ O) ^N (Ra) ₂ , -N( ^Ra )C( ^O ) _ORa , ^-N (Ra)C( ^O ) ^Ra , -N( ^Ra )S(O) _tRa (wherein t is 1 or 2), -S(O) ^tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ (wherein t is 1 or 2) _, or _PO3 ( ^Ra ) ₂ , wherein each ^{R a} is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

"Heteroarylalkyl" refers to a moiety having an aryl moiety as described herein attached to an alkylene moiety as described herein, wherein the bond to the remainder of the molecule is through the alkylene.

"Heterocycloalkyl" refers to a stable 5-, 6-, or 10-membered non-aromatic ring radical having one to six heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise specifically noted in the specification, a heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused or bridged ring systems. The heteroatoms in the heterocycloalkyl may optionally be oxidized. One or more nitrogen atoms, if present, may optionally be quaternized. The heterocycloalkyl is partially or fully saturated. The heterocycloalkyl may be attached to the remainder of the molecule via any atom of the ring. Examples of such heterocycloalkyl groups include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl.

Unless stated otherwise specifically in the specification, a heterocycloalkyl moiety is optionally substituted by one or more substituents as defined above. The substituents further independently include alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilyl, -ORa, -SRa, -OC(O)-Ra, ^-N (Ra) ² , -C(O)Ra, -C( ^O ) ^ORa , -C ⁽ O) ^N (Ra) ₂ , -N( ^Ra )C( ^O ) _ORa , ^-N (Ra)C( ^O ) ^Ra , -N( ^Ra )S(O) _tRa (wherein t is 1 or 2), -S(O) ^tORa (wherein t is 1 or 2), -S(O) _tN ( ^Ra ) ₂ (wherein t is 1 or 2) _, or _PO3 ( ^Ra ) ₂ , wherein each ^{R a} is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl.

“Heterocycloalkyl” also includes bicyclic ring systems in which one non-aromatic ring, typically having 3 to 7 ring atoms, contains at least 2 carbon atoms in addition to 1-3 heteroatoms independently selected from oxygen, sulfur and nitrogen, and combinations comprising at least one of the foregoing heteroatoms; and the other ring, typically having 3 to 7 ring atoms, optionally contains 1-3 heteroatoms independently selected from oxygen, sulfur and nitrogen and is not aromatic.

The term "(C _x -C _y )perfluoroalkyl" (wherein x<y) refers to an alkyl group having a minimum of x carbon atoms and a maximum of y carbon atoms, wherein all hydrogen atoms are replaced by fluorine atoms. Preferred is -(C ₁ -C ₆ )perfluoroalkyl, more preferred is -(C ₁ -C ₃ )perfluoroalkyl, and most preferred is -CF ₃ .

The term "(C _x -C _y )perfluoroalkylene" (wherein x<y) means an alkyl group having a minimum of x carbon atoms and a maximum of y carbon atoms, wherein all hydrogen atoms are replaced by fluorine atoms. Preferred is -(C ₁ -C ₆ )perfluoroalkylene, more preferred is -(C ₁ -C ₃ )perfluoroalkylene, and most preferred is -CF ₂ -.

"Sulfanyl" refers to the groups: -S-(optionally substituted alkyl), -S-(optionally substituted aryl), -S-(optionally substituted heteroaryl), and -S-(optionally substituted heterocycloalkyl).

"Sulfinyl" refers to the groups: -S(O)-H, -S(O)-(optionally substituted alkyl), -S(O)-(optionally substituted amino), -S(O)-(optionally substituted aryl), -S(O)-(optionally substituted heteroaryl), and -S(O)-(optionally substituted heterocycloalkyl).

"Sulfonyl" refers to the groups: -S( _O2 )-H, -S( _O2 )-(optionally substituted alkyl), -S( _O2 )-(optionally substituted amino), -S( _O2 )-(optionally substituted aryl), -S(O2)-(optionally _substituted heteroaryl), and -S( _O2 )-(optionally substituted heterocycloalkyl).

"Sulfonamidyl" or "sulfonamido" refers to a -S(=O) ₂ -NRR group, wherein each R is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heteroalicyclic (bonded through a ring carbon). The R groups in the -NRR of the -S(=O) ₂ -NRR group can be combined with the nitrogen to which they are attached to form a 4-, 5-, 6-, or 7-membered ring. In some embodiments, it is a _C1 - _C10 sulfonamido group, wherein each R in the sulfonamido group contains a total of 1 carbon, 2 carbons, 3 carbons, or 4 carbons. The sulfonamido group is optionally substituted with one or more substituents as described for alkyl, cycloalkyl, aryl, and heteroaryl, respectively.

"Sulfoxyl" refers to a -S(=O) _2OH group.

"Sulfonate" refers to a -S(=O) ₂ -OR group, where R is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heteroalicyclic (bonded through a ring carbon). The sulfonate group is optionally substituted on R with one or more substituents as described for alkyl, cycloalkyl, aryl, and heteroaryl, respectively.

"Azide" refers to an _N3 group. "Azide" can be an organic azide or can be a salt of an azide ( _N3- ⁾ anion. The term "nitro" refers to an _NO2 group bound to an organic moiety. The term "nitroso" refers to an NO group bound to an organic moiety. The term nitrate refers to an _ONO2 group bound to an organic moiety or a salt of a nitric acid ( _NO3- ⁾ anion.

"Polyurethane"("carbamoyl" or "carbamyl") includes N- and O-polyurethane groups, ie, -NRC(O)OR and -OC(O) _NR2 groups, respectively.

"Sulfonamide" (or "sulfonamido") includes S- and N-sulfonamide groups, i.e., _-SO2NR2 and _-NRSO2R groups, respectively. Thus, sulfonamide groups include, but are not limited to, sulfamoyl ( _-SO2NH2 ). An organosulfur structure represented by the formula -S(O)(NR)- is considered to refer to a sulfoxide amine in which both the _oxygen and _nitrogen atoms are bonded to a sulfur atom, which is also bonded to two carbon atoms.

"Amidine" or "amidino" includes groups of the formula -C(NR)NR _2. Typically, amidino is -C(NH)NH ₂ .

"Guandinium" or "guanidinium" includes groups of the formula -NRC(NR)NR _2. Typically, guanidinium is -NHC(NH)NH ₂ .

As is well known in the art, "salts" include organic compounds, such as carboxylic acids, sulfonic acids, or amines, in ionic form associated with a counterion. For example, acids in their anionic form can form salts with cations, such as metal cations, e.g., sodium, potassium, etc.; salts formed with ammonium, such as _NH4 ⁺ or cations of various amines, including tetraalkylammonium salts, such as tetramethylammonium; or other cations, such as trimethylsulfonium, etc. "Pharmaceutically acceptable" or "pharmacologically acceptable" salts are salts formed from ions that are approved for human consumption and are generally non-toxic, such as chloride or sodium salts. "Zwitterions" are internal salts, such as those that can form in a molecule, having at least two ionizable groups, one forming an anion and the other forming a cation, which serve to balance each other. For example, amino acids such as glycine can exist in zwitterionic form. "Zwitterions" are salts within the meaning of this document. The compounds of the present invention may be in the form of salts. The term "salt" includes addition salts of the free acids or free bases of the compounds of the present invention. Salts may be "pharmaceutically acceptable salts." The term "pharmaceutically acceptable salt" refers to salts having a toxicity profile within a range that provides utility in pharmaceutical applications. Salts that are not pharmaceutically acceptable may still possess properties, such as high crystallinity, that are useful in the practice of the present invention, such as, for example, in the synthesis, purification, or formulation of the compounds of the invention.

Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Examples of inorganic acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid and phosphoric acid. Suitable organic acids can be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic acid classes of organic acids, examples of which include formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, butanedioic, glutamic, benzoic, anthranilic, 4-hydroxybenzoic, phenylacetic, mandelic, pamoic, methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, trifluoromethanesulfonic, 2-hydroxyethanesulfonic, p-toluenesulfonic, sulfanilic, cyclohexylaminosulfonic, stearic, alginic, β-hydroxybutyric, salicylic, galactaric and galacturonic acid. Examples of pharmaceutically unacceptable acid addition salts include, for example, perchlorates and tetrafluoroborate. Representative salts include hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, toluenesulfonate, citrate, maleate, fumarate, succinate, tartrate, naphthoate, methanesulfonate, gluconate, lactobionate, laurylsulfonate, and amino acid salts, etc. (See, e.g., Berge et al. (1977) "Pharmaceutical Salts," J. Pharm. Sci. 66: 1-19.)

Suitable pharmaceutically acceptable base addition salts of the compounds of the present invention include, for example, metal salts, including alkali metal, alkaline earth metal and transition metal salts, such as calcium, magnesium, potassium, sodium and zinc salts. Pharmaceutically acceptable base addition salts also include organic salts made from basic amines, such as, for example, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. Examples of pharmaceutically unacceptable base addition salts include lithium salts and cyanates. Although pharmaceutically unacceptable salts are generally not suitable for use as medicaments, such salts may be suitable as, for example, intermediates in the synthesis of compounds of formula (I) (e.g., in their purification by recrystallization). All of these salts can be prepared from the corresponding compounds of formula (I) by conventional methods, such as reacting a suitable acid or base with a compound according to formula (I). The term "pharmaceutically acceptable salt" refers to non-toxic inorganic or organic acid and/or base addition salts, see, for example, Lit et al., Salt Selection for Basic Drugs (1986), Int J. Pharm., 33, 201-217, which is incorporated herein by reference.

A "hydrate" is a compound that exists in a composition with water molecules. The composition may include a stoichiometric amount of water, such as a monohydrate or dihydrate, or may include a random amount of water. As used herein, the term "hydrate" refers to a solid form, i.e., a compound in aqueous solution, which may be hydrated, but not a hydrate, as the term is used herein.

A "solvate" is a similar composition, except that the water is replaced with a non-aqueous solvent. For example, methanol or ethanol can form an "alcoholate," which can also be stoichiometric or non-stoichiometric. As used herein, the term "solvate" refers to a solid form, i.e., a compound in a dissolved state in a solvent, which may be solvated, not a solvate, as the term is used herein.

As is known in the art, "prodrugs" are substances that can be administered to a patient, wherein the substance is converted into an active pharmaceutical ingredient in the patient's body under the action of biochemical agents (such as enzymes). Examples of prodrugs include esters of carboxylic acid groups, which can be hydrolyzed by endogenous esterases such as those found in the bloodstream of humans and other mammals. Conventional procedures for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs", edited by H. Bundgaard, Elsevier, 1985.

In addition, when features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of that Markush group. For example, if X is described as being selected from the group consisting of bromine, chlorine, and iodine, then claims where X is bromine and claims where X is bromine and chlorine are fully described. In addition, when features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any combination of individual members or subgroups of members of that Markush group. Thus, for example, if X is described as being selected from the group consisting of bromine, chlorine, and iodine and Y is described as being selected from the group consisting of methyl, ethyl, and propyl, then claims where X is bromine and Y is methyl are fully described.

If the value of a variable that must be an integer (such as the number of carbon atoms in an alkyl group or the number of substituents on a ring) is described as a range, for example, 0-4, then this means that the value can be any integer between 0 and 4, inclusive, i.e., 0, 1, 2, 3, or 4.

In various embodiments, the compound or group of compounds as used in the methods of the present invention can be any of the combinations and/or subcombinations of the above-listed embodiments.

In various embodiments, compounds are provided as shown in any of the Examples or among the exemplary compounds. Limitations may be applied to any disclosed genus or embodiment, wherein any one or more other above-disclosed embodiments or substances may be excluded from such genus or embodiment.

As used herein, the term "amino protecting group" or "N-protected" refers to groups intended to protect an amino group from undesirable reactions during synthetic procedures and which can subsequently be removed to reveal the amine. Commonly used amino protecting groups are disclosed in Protective Groups in Organic Synthesis, Greene, T.W.; Wuts, P.G.M., John Wiley & Sons, New York, NY, (3rd ed., 1999). Amino-protecting groups include acyl groups such as formyl, acetyl, propionyl, pivaloyl, tert-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl, and the like; alkoxy- or aryloxy-carbonyl groups (which form polyurethanes with protected amines) such as benzyloxycarbonyl (Cbz), p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, and phenylthiocarbonyl; arylalkyl groups such as benzyl, trityl, benzyloxymethyl and phenylthiomethyl; and silyl groups such as trimethylsilyl. Amine protecting groups also include cyclic amino protecting groups such as phthaloyl and dithiosuccinimidyl, which incorporate the amino nitrogen into a heterocycle. Typically, amino protecting groups include formyl, acetyl, benzoyl, pivaloyl, tert-butylacetyl, benzenesulfonyl, Alloc, Teoc, benzyl, Fmoc, Boc, and Cbz. It is well within the skill of the artisan to select and use the appropriate amino protecting group for the synthetic task at hand.

As used herein, the term "hydroxy protecting group" or "O-protected" refers to groups that are intended to protect the OH group from undesirable reactions during synthetic procedures and that can subsequently be removed to reveal the amine. Commonly used hydroxy protecting groups are disclosed in Protective Groups in Organic Synthesis, Greene, T.W.; Wuts, P.G.M., John Wiley & Sons, New York, NY, (3rd ed., 1999). Hydroxyl protecting groups include acyl groups such as formyl, acetyl, propionyl, pivaloyl, tert-butylacetyl, 2-fluoroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, etc.; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl, etc.; acyloxy groups (which form polyurethanes with protected amines) such as benzyloxycarbonyl (Cbz), p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4, [00145] Examples of hydroxy protecting groups include 5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenyl)-1-methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, dibenzyloxycarbonyl, tert-butyloxycarbonyl (Boc), diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl (Alloc), 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethoxycarbonyl (Teoc), phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl (Fmoc), cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, and the like; aralkyl groups such as benzyl, trityl, benzyloxymethyl, and the like; and silyl groups such as trimethylsilyl, and the like. The selection and use of an appropriate hydroxy protecting group for the synthetic task at hand is well within the capabilities of the ordinary skilled artisan.

At various points in this specification, substituents of the compounds of the present invention are disclosed in groups or ranges. It is specifically noted that the present invention encompasses every individual subcombination of the members of such groups and ranges. For example, the term "C1-C6 alkyl" specifically refers to the individually disclosed methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and the like. For numbers defined by the term "about," variations of 2%, 5%, 10%, or even 20% are within the defined range.

Standard abbreviations for chemical groups as known in the art are used; for example, Me = methyl, Et = ethyl, i-Pr = isopropyl, Bu = butyl, t-Bu = tert-butyl, Ph = phenyl, Bn = benzyl, Ac = acetyl, Bz = benzoyl, etc.

Compound

The present invention relates to fused pyrimidine compounds that inhibit ATPases (AAA) associated with various activities, the ATPase having the descriptive name valosin-containing protein, also known as p97; and methods of treating or preventing diseases or conditions in subjects who would benefit from inhibiting p97. Compounds that embody the first aspect of the invention are cyclohexyl-pyrimidines, cyclopentyl-pyrimidines, and cycloheptyl-pyrimidines having an all-carbon, aza-, oxa-, or sulphur heterocycle as the cyclopentyl, cyclohexyl, or cycloheptyl fusion partner of the fused pyrimidine. The fused pyrimidine has a benzylamino or substituted benzylamino group at the 4-position of the fused pyrimidine or pyrimidine ring and a Het group at the 2-position. The Het group is as defined above. Formula I provides a schematic structural understanding of the above description of embodiments of the fused pyrimidine compounds of the present invention.

The substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ of formula I are each independently selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted aromatic and optionally substituted functional groups as described above in the definitions section.

Preferred designations for A, D, E, B, and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein A is N or A is C.

Preferred designations for A, D, E, B, and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein D and E are both C; and those wherein one of D and E is N.

Preferred designations for A, D, E, B, and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein A is N and D and E are both C.

Preferred designations for A, D, E, B, and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein A, D, and E are all C.

Preferred designations for A, D, E, B, and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein A and D are both C and B and E are both N.

Preferred designations for A, D, E, B and Z of the fused pyrimidine compounds of formula I are independently and individually those wherein A is C, one of D and E is N and the other is C, and Z and B are each independently N or CR ⁶ .

R ³ and any of the above preferred designations for A, B, D, E and Z of the fused pyrimidine compound of formula I are preferably designated as hydrogen or unsubstituted or substituted 1-4 carbon alkyl.

Y of the fused pyrimidine compound of formula I and any of the above preferred designations for A, B, D, E and Z are preferably designated as NR ⁵ and R ⁵ is hydrogen or unsubstituted or substituted 1-4 carbon alkyl.

The preferred designation for Y of the fused pyrimidine compound of formula I and any one of the above preferred designations for A, B, D, E and Z is O.

The preferred designation for Y of the fused pyrimidine compound of formula I and any one of the above preferred designations for A, B, D, E and Z is S.

Y of the fused pyrimidine compound of formula I and any one of the above preferred designations of A, B, D, E and Z is preferably designated as CR ⁴ .

Preferably, the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ of formula I are each independently selected from the group consisting of hydrogen, halogen, alkyl, CN, OR', CN, SR', SO ₂ R', NR'R", C(O)R', C(O)NR'R", C(O)OR', OC(O)R', OC(O)NR'R", N(R')C(O)OR', N(R')C(O)R", N(R')C(O)N(R"R), N(R')C(NR')N(RR ³ ), N(R')S(O) ₂ R", S(O) ₂ OR', S(O) ₂ N(R'R"), N(R ^d ) ₂ , (CR'R") ^t N(RR ³ ), (CR'R") ^t OR, PO ₃ (R'R"), _CF3 , wherein each R, ^R3 , R' and R" is independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, alkenyl, alkynyl or any combination thereof; and wherein each t is independently selected from the group consisting of an integer of 1 and 2.

More preferably, the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ of formula I are each independently selected from hydrogen, halogen, linear, branched or cyclic alkyl groups of 1 to 6 carbon atoms, carboxyl, carboxamide, substituted aminomethyl, sulfonyl, sulfonamide, amine, mono-, di- or trialkylamine of 1 to 6 carbon atoms, nitrile, halogen, N-alkylcarboxamide of 1 to 6 carbon atoms in the alkyl group, perfluoroalkyl groups of 1 to 3 carbon atoms, alkoxy groups of 1 to 6 carbon atoms.

It is particularly preferred for Formula I ^{that R1} is substituted at the 4-position of the Het group. It is also particularly preferred that the ^R2 group is hydrogen. It is also preferred that the fused pyrimidine compound of Formula I be substituted with ^R3 , ^which can be selected from an alkyl group having 1 to 3 carbon atoms, a perfluoroalkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, an alkylsulfone group having 1 to 3 carbon atoms, an _aminomethyl group ( _-NHCH3 ), a methylamine ( _-CH2NH2 ), a methanol ( _-CH2OH ), a nitrile, or a halogen. The substituents ^R1 , ^R2 , and ^R3 of the fused pyrimidine compound of Formula I may also preferably be hydrogen. Even more preferably, the substituents ^R1 , ^R2 , and ^R3 of Formula I are each independently hydrogen, methyl, trifluoromethyl, methoxy, or chlorine.

The radical R ¹ is a substituent of the benzo part of the HET radical, which may particularly preferably be:

1. Formic acid-CO ₂ H

2. Formamide-CONH ₂

3. _{Methylamine -CH2NH2}

4. Methanol - _CH2OH

5. _Acetic acid - _CH2CO2H

6. Acetamide -CH ₂ CONH ₂

7. Methylacetamide -CH ₂ NHCOCH ₃

8. Methylpropionamide -CH ₂ NHCOCH ₂ CH ₃

9. Methyl-2-methylpropionamide -CH ₂ NHCOCH(CH ₃ )CH ₃

10. Methylmethanesulfonamide -CH ₂ NHSO ₂ CH ₃

11. Methylethanesulfonamide -CH ₂ NHSO ₂ CH ₂ CH ₃

12. Methyl-2-methylethanesulfonamide -CH ₂ NHSO ₂ CH(CH ₃ )CH ₃

13. Methylpropanesulfonamide -CH ₂ NHSO ₂ CH ₂ CH ₂ CH ₃

14. Methyl-1-methylpropanesulfonamide -CH ₂ NHSO ₂ CH(CH ₃ )CH ₂ CH ₃

15. Methyl-2-methylpropanesulfonamide -CH ₂ NHSO ₂ CH ₂ CH(CH ₃ )CH ₃

The group ^R2 is an optional substituent of the benzo portion of the HET group and can be particularly preferably hydrogen, an alkyl group of 1 to 3 carbons, a nitrile, a perfluoroalkyl group of 1 to 3 carbons.

Embodiments of the backbone (Formula II) and the HET moiety (Formula HET) include the following structures. In each of these embodiments and preferred, more preferred, especially more preferred, and most preferred combinations, the substituent groups R ¹ , ^{R 2} , R 3, R ⁴ , R ⁵ , R ⁶ , and R ⁷ are included as provided by Formula I. For each of these embodiments and preferred, more preferred, especially more preferred, and most preferred combinations of Formula II and Formula HET that form Formula I, the preferred and more preferred designations given above for the substituent groups R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁷ , as well as the especially preferred designations for the substituent groups R ¹ , R ² , and R ³ , also apply to the preferences for these preferred combinations.

In the embodiment of Formula II, the backbone (denoted by S for the backbone) is:

When the HET embodiments described below include any structures other than H5 and H10, preferred backbone embodiments include S2, S3, S4, and S5. Particularly preferred backbone embodiments include S1, S3, S6, and S7 in combination with any of the HET embodiments described below.

Embodiments of the formula HET (labeled H for the heterocycle) in which N- represents the nitrogen of the following group NR ⁷ :

Particularly preferred combinations forming the backbone of preferred embodiments of Formula I and HET embodiments include each of S1, S2, S3, S4, S5, S6, and S7 in combination with any of H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H17, and H22. Subject to the limitations listed above for Formula I, H5 and H10 are not combined with S2, S4, and S5. As described above, the substituent groups ^R1 , ^R2 , ^R3 , ^R4 , ^R5 , ^R6 , and ^R7 are included as provided by Formula I. The preferred and more preferred designations given above for the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ and the especially preferred designations for the substituents R ¹ , R ² and R ³ are preferences for these substituents as applied to the above combinations of the skeleton of formula I and the HET embodiment.

Especially preferred combinations of the backbones and HET embodiments of Formula I include each of S1, S2, S3, S4, S5, S6, and S7 in combination with any of H4, H5, H6, H7, H9, H10, H13, and H17. Subject to the limitations listed above for Formula I, H5 and H10 are not combined with S2, S4, and S5. As described above, the substituent groups ^R1 , ^R2 , ^R3 , ^R4 , ^R5 , ^R6 , and ^R7 are included as provided by Formula I. The preferred and more preferred designations given above for the substituent groups ^R1 , ^R2 , ^R3 , ^R4 , ^R5 , ^R6 , and ^R7, as well as the especially preferred designations for the substituent groups ^R1 , ^R2 , and ^R3 , apply to the above combinations of the backbones and HET embodiments of Formula I for these substituent groups.

The most preferred combination of the backbone embodiment and the HET embodiment that forms the most preferred embodiment of Formula I is selected from the group consisting of S2, S4, S5, S9, S10, and the combination of S11 and H4. As described above, this combination includes the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁷ as disclosed in Formula I. The preferred and more preferred designations given above for the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁷ , as well as the especially preferred designations for the substituents R ¹ , R ² , and R ³ , are preferences for these substituents as applied to the above combinations of the backbone and HET embodiments of Formula I.

The most particularly preferred combination of the backbone embodiment and the HET embodiment is selected from the combination of S2, S4, S5, S9, S10 and S11 with H6, H7, H8, H9, H13, H17 and H22. As described above, this combination includes the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ as disclosed in Formula I. The preferred and more preferred designations given above for the substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ , as well as the particularly preferred designations for the substituents R ¹ , R ² and R ³ , are preferences for these substituents as applied to the above combinations of the backbone and HET embodiments of Formula I.

Mechanism of action and medical treatment

In certain embodiments, the present invention relates to methods of inhibiting p97. The fused pyrimidine compounds of the invention used in the methods disclosed herein bind, for example, non-covalently or covalently to the active site of p97. In certain such embodiments, the covalent bond can be reversible or irreversible.

The compounds of the present invention and their pharmaceutical compositions can act as "inhibitors" of p97, which means that they can block or reduce the activity of the enzyme, for example, inhibit various activities of p97. Inhibitors can act as competitive, non-competitive, or non-competitive inhibition. Inhibitors can bind reversibly or irreversibly, and thus the term includes compounds that suicide the enzyme, or that can cause a conformational change elsewhere on the enzyme.

The compounds of the present invention and their pharmaceutical compositions are used as therapeutic agents because they can prevent, improve, alleviate and/or affect a disease or condition, which refers to the following compounds: reducing the occurrence of a disease or condition in a treated sample relative to an untreated control sample in a statistical sample; or delaying the onset of one or more symptoms of the disease or condition or reducing its severity relative to an untreated control sample.

The ability to prevent, ameliorate, alleviate and/or affect related conditions such as local recurrence (e.g., pain), diseases such as cancer, complex syndromes such as heart failure, or any other medical condition is well known in the art and includes administering a composition that reduces the incidence of symptoms of the medical condition in a subject or delays its onset relative to a subject that does not receive the composition. Thus, prevention of cancer includes, for example, reducing the number of detectable cancerous growth clusters and/or delaying the appearance of detectable cancerous growths in a treated population, for example, by a statistically and/or clinically significant amount, as compared to an untreated control population.

Prevention of infection includes, for example, reducing the number of diagnoses of infection in a treated population compared to an untreated control population and/or delaying the onset of symptoms of infection in a treated population compared to an untreated control population. Prevention of pain includes, for example, reducing the intensity of pain sensations experienced by subjects in a treated population compared to an untreated control population or otherwise delaying the onset of pain sensations.

The compounds of the present invention and pharmaceutical compositions thereof can act prophylactically and/or therapeutically and comprise administering one or more compositions of the present invention to a host. If it is administered before the clinical manifestation of an undesirable condition (e.g., a disease or other undesirable condition of the host animal), then the treatment is prophylactic (i.e., it protects the host from the development of the undesirable condition), whereas if it is administered after the manifestation of the undesirable condition, then the treatment is therapeutic (i.e., it is intended to alleviate, ameliorate, or stabilize an existing undesirable condition or its side effects).

The compounds of the present invention and their pharmaceutical compositions can be used for preventive and/or therapeutic treatments. If the compound or pharmaceutical composition is administered before the clinical manifestation of an undesirable symptom (e.g., a disease or other undesirable condition of a host animal), the treatment is preventive (i.e., it protects the host from the occurrence of an undesirable symptom), and if it is administered after the manifestation of an undesirable symptom, the treatment is therapeutic (i.e., it is intended to alleviate, improve, or stabilize an existing undesirable symptom or its side effects). As used herein, the term "treating" or "treatment" includes reversing, alleviating, or inhibiting the symptoms, clinical signs, and underlying pathology of a symptom in a manner that improves or stabilizes the subject's symptom.

The compounds of the present invention and their pharmaceutical compositions can be administered in a "therapeutically effective amount" in connection with the treatment methods of the present invention. A therapeutically effective amount is an amount of one or more compounds in a pharmaceutical composition that, when administered as part of a desired dosing regimen (to a mammal, preferably a human), will alleviate symptoms, ameliorate symptoms, or slow the onset of a disease condition, according to clinically acceptable criteria for the disorder or condition to be treated or for cosmetic purposes, e.g., at a reasonable benefit/risk ratio applicable to any medical treatment.

Application

The compounds of the present invention and pharmaceutical compositions thereof, prepared as described herein, can be administered in a variety of forms, as is well known in the art, depending on the condition to be treated and the age, condition, and weight of the patient. Administration is ultimately provided under the guidance and prescription of the attending physician, whose wisdom, experience, and knowledge govern the patient's treatment, as consistent with, recommended by, or required by medical authorities and governmental registration bodies for drugs.

For example, when the compound is to be administered orally, it can be formulated into tablets, capsules, granules, powders or syrups; or for parenteral administration, it can be formulated into injections (intravenous, intramuscular or subcutaneous), drip preparations or suppositories. For administration via the ocular mucosal route or other similar transmucosal routes, it can be formulated into drops or ointments.

These preparations for oral administration or administration via the transmucosal route can be prepared by conventional methods, and if necessary, the active ingredient can be mixed with any of the following conventional additives or excipients, such as binders, disintegrants, lubricants, corrigents, solubilizers, suspension aids, emulsifiers, coating agents, cyclodextrins and/or buffers. Although the dosage will vary depending on the patient's symptoms, age and weight, the patient's sex, the nature and severity of the condition to be treated or prevented, the route of administration and the form of the drug, in general, 0.0001 to 2000 mg, preferably 0.001 to 1000 mg, more preferably 0.001 to 500 mg, even more preferably 0.001 to 250 mg, and most preferably 0.001 to 150 mg of the compound is recommended for adult patients, and this can be administered in a single dose or divided doses. Alternatively, the daily dose may be given based on body weight, such as 1 nanogram/kg (ng/kg) to 200 mg/kg, preferably 10 ng/kg to 100 mg/kg, more preferably 10 ng/kg to 10 mg/kg, and most preferably 10 ng/kg to 1 mg/kg. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound that produces a therapeutic effect.

The precise time of administration and/or amount of the composition that will produce the most effective results in terms of therapeutic efficacy in a given patient will depend on the activity, pharmacokinetics and bioavailability of the specific compound, the patient's physiological condition (including age, sex, disease type and stage, general physical condition, response to a given dose, and type of drug), the route of administration, etc. However, the above guidelines can be used as a basis for fine-tuning treatment, e.g., determining the optimal time and/or amount of administration, which will require only routine experimentation consisting of monitoring the subject and adjusting the dose and/or timing.

As used herein, the phrase "pharmaceutically acceptable" refers to those ligands, materials, compositions and/or dosage forms that are within the scope of sound medical judgment and can be used in contact with the tissues of humans and animals without excessive toxicity, irritation, allergic response, or other problems or complications, commensurate with a reasonable benefit/risk ratio.

Pharmaceutical compositions incorporating Formula I

The pharmaceutical compositions of the present invention incorporate an embodiment of the fused pyrimidine compound of Formula I of the present invention and a pharmaceutically acceptable carrier. The nature of the pharmaceutical carrier and the dosage of the fused pyrimidine compound of Formula I depend on the route of administration chosen, the effective dose for that route, and the wisdom and experience of the attending physician.

A "pharmaceutically acceptable carrier" is a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch, potato starch, and substituted or unsubstituted β-cyclodextrins; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, Olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer solution; and (21) other non-toxic compatible substances used in pharmaceutical preparations.

Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release agents, coating agents, sweeteners, flavoring agents, and fragrances, preservatives and antioxidants may also be present in the composition. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and (3) metal chelating agents, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

Formulations suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored base, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as a lozenge (using an inert base such as gelatin and glycerin, or sucrose and acacia), and/or as a mouthwash, etc., each containing a predetermined amount of a compound of the invention as the active ingredient. The composition may also be administered as a bolus, electuary, or paste.

In solid dosage forms for oral administration (capsules, tablets, pills, sugar-coated tablets, powders, granules, etc.), the compound of the present invention is mixed with one or more pharmaceutically acceptable carriers such as sodium citrate or dicalcium phosphate and/or any of the following:

(1) fillers or extenders, such as starch, cyclodextrin, lactose, sucrose, glucose, mannitol and/or silicic acid;

(2) binders, such as, for example, carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and/or gum arabic;

(3) Wetting agents, such as glycerin;

(4) disintegrants, such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate;

(5) Solution blockers, such as paraffin;

(6) Adsorption promoters, such as quaternary ammonium compounds;

(7) Wetting agents, such as acetyl alcohol and glyceryl monostearate; (8) Absorbents, such as kaolin and bentonite;

(9) Lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate, and mixtures thereof; and

(10) Coloring agents. In the case of capsules, tablets, and pills, the pharmaceutical composition may also contain a buffering agent. Similar solid compositions may also be used as fillers in soft and hard-filled gelatin capsules using excipients such as lactose or milk sugar and high molecular weight polyethylene glycols.

Tablets can be made by compression or molding, optionally with one or more auxiliary ingredients. Compressed tablets can be prepared using a binder (e.g., gelatin or hydroxypropyl methylcellulose), a lubricant, an inert diluent, a preservative, a disintegrant (e.g., sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), a surfactant, or a dispersant. Molded tablets can be made by molding a mixture of a powdered inhibitor moistened with an inert liquid diluent in a suitable machine.

Tablets and other solid dosage forms such as sugar-coated tablets, capsules, pills, and granules may optionally be impressed or prepared with coatings and shells, such as enteric coatings and other coatings known in the art of pharmaceutical formulation. They may also be formulated using, for example, hydroxypropylmethylcellulose (in varying proportions to provide the desired release profile), other polymer matrices, liposomes, and/or microspheres to provide slow or controlled release of the active ingredient therein. They may be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating a bactericide in the form of a sterile solid composition soluble in sterile water or some other sterile injection medium just before use. These compositions may also optionally contain opacifiers and may be compositions that release the active ingredient only or preferentially in certain parts of the gastrointestinal tract, optionally in a delayed manner.

Examples of embedding compositions that can be used include polymeric substances and waxes.The compounds of the invention can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage form may also contain an inert diluent commonly used in the art, such as, for example, water or other solvents, solubilizers, and emulsifiers such as ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (particularly cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofuranyl alcohol, polyethylene glycol, and sorbitan fatty acid esters and mixtures thereof.

Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.

Suspensions, in addition to one or more active inhibitor(s), may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

Formulations for rectal or vaginal administration may be presented as suppositories which may be prepared by mixing one or more inhibitors with one or more suitable non-irritating excipients or carriers including, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, which are solid at room temperature but liquid at body temperature and therefore will melt in the rectum or vaginal cavity and release the active agent.

Formulations for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are appropriate in the art.

Dosage forms for topical or transdermal administration of one or more inhibitors include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active ingredient may be mixed under sterile conditions with a pharmaceutically acceptable carrier and with any preservatives, buffers, or propellants that may be required.

Ointments, pastes, creams and gels may contain, in addition to a compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicone resins, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

Powders and sprays may contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. Sprays may additionally contain conventional propellants such as chlorofluorocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

The compounds of the present invention may alternatively be administered by aerosol. This is accomplished by preparing aqueous aerosols, liposomal formulations, or solid particles containing the composition. Non-aqueous (e.g., fluorocarbon propellants) suspensions may be used. Sonic nebulizers are preferred because they minimize exposure of the agent to shear that can lead to compound degradation.

Typically, aqueous aerosols are prepared by formulating an aqueous solution or suspension of the compound of the invention with conventional pharmaceutically acceptable carriers and stabilizers. Carriers and stabilizers vary depending on the requirements of the specific composition but typically include nonionic surfactants (Tweens, Pluronics, sorbitan esters, lecithin, Cremophors), pharmaceutically acceptable cosolvents such as polyethylene glycol, harmless proteins such as serum albumin, oleic acid, amino acids such as glycine, buffers, salts, sugars, or sugar alcohols. Aerosols are generally prepared from isotonic solutions.

Transdermal patches have the additional advantage of providing controlled release of the compounds of this invention to the body. This type of dosage form can be made by dissolving or being dispersed in a suitable medium. Absorption enhancers can also be used to increase the flux of one or more inhibitors through the skin. Rate-controlling membranes are provided or one or more inhibitors are dispersed in a polymer matrix or a gel, which can control the speed of this flux.

The pharmaceutical composition of the present invention that is suitable for parenteral administration comprises one or more compounds of this invention and one or more pharmaceutically acceptable sterile aqueous solutions or non-aqueous solutions, dispersions, suspensions or emulsions or can be reconstituted into sterile injectable solutions or dispersions of sterile powders or suspending agents or thickening agents before being isotonic with the blood of a predetermined receptor. Examples of suitable aqueous and non-aqueous carriers that can be used in the pharmaceutical composition of the present invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.) and suitable mixtures thereof, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate. Suitable mobility can be, for example, by utilizing coating materials such as lecithin, in the case of dispersions, by maintaining the desired particle size and by utilizing a surfactant to maintain.

These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers, and dispersants. Various antibacterial and antifungal agents may be included to ensure that the action of microorganisms is prevented: for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include tonicity modifiers such as sugars, sodium chloride, and the like in the composition. Additionally, prolonged absorption of injectable pharmaceutical forms may be achieved by including agents that delay absorption, such as aluminum monostearate and gelatin.

In some cases, in order to prolong the effect of a compound of the invention, it is desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. For example, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

Injectable depot forms are prepared by forming a microcapsule matrix of one or more inhibitors in a biodegradable polymer such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the properties of the specific polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by embedding the drug in liposomes or microemulsions that are compatible with body tissues.

The pharmaceutical compositions can be administered orally, parenterally, topically, or rectally. They are, of course, given in a form suitable for each route of administration. For example, they can be administered in tablet or capsule form, by injection, inhalation, eye lotion, ointment, suppository, infusion; topically via lotion or ointment; and rectally via suppository. Oral administration is preferred.

As used herein, the phrases "parenteral administration" and "administered parenterally" mean modes of administration other than enteral and topical administration, usually by injection, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection, and infusion.

The pharmaceutical compositions of the present invention may be "systemically administered," "administered systemically," "peripherally administered," and "peripherally administered," meaning administration where the ligand, drug, or other material does not enter the central nervous system directly, such that it enters the patient's system and thereby undergoes metabolism and other similar processes, e.g., subcutaneous administration.

The compounds of this invention may be administered to humans and other animals for therapeutic use by any suitable route of administration including orally, nasally, by, for example, spray, rectally, intravaginally, parenterally, intracisternal, and topically by powders, ointments or drops, including buccal and sublingual.

Regardless of the route of administration selected, the compounds of the present invention, which can be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art.

Actual dosage levels of the compounds of this invention in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

The concentration of the compound of the invention in the pharmaceutically acceptable mixture will vary depending on several factors, including the dose of the compound to be administered, the pharmacokinetic properties of the compound used, and the route of administration.

In general, the compositions of the present invention can be provided as aqueous solutions containing about 0.1-10% w/v of a compound disclosed herein, along with other substances for parenteral administration. Typical dosages range from about 0.001 to about 50 mg/kg body weight per day, administered in 1-4 divided doses. Each divided dose may contain the same or different compounds of the present invention. The dosage will be an effective amount, depending on several factors, including the patient's overall health, the formulation of the selected compound, and the route of administration.

Another aspect of the present invention provides a combination therapy in which one or more other therapeutic agents are administered with the compounds and compositions of the present invention. Such combination therapy will achieve the same or similar treatment, taking into account the additive effects of the combined therapeutic agents other than the compounds of the present invention.

In certain embodiments, the compounds of the present invention can be administered in combination with one or more proteasome inhibitors. In certain embodiments, the compounds of the present invention are administered in combination with chemotherapeutic agents. Suitable chemotherapeutic agents may include natural products such as vinca alkaloids (i.e., vinblastine, vincristine, and vinorelbine), paclitaxel, epidipodophyllotoxins (i.e., etoposide, teniposide), antibiotics (dactinomycin (actinomycin D), daunorubicin, doxorubicin, and idarubicin), anthracyclines, mitoxantrone, bleomycin, plicamycin (mithramycin), and mitomycin, enzymes (L-asparaginase, which metabolizes L-asparagine systemically and deprives cells that do not have the ability to synthesize their own asparagine); antiplatelet agents; antiproliferative/antimitotic alkylating agents such as nitrogen mustards (nitrogen mustards, cyclic phosphamides, and analogs, melphalan, chlorambucil). , aziridines and methylmelamines (altretamine and thiotepa), alkyl sulfonates (busulfan), nitrosoureas (carmustine (BCNU) and analogs, streptozotocin), daptomycin (DTIC); antiproliferative/antimitotic antimetabolites such as folic acid analogs (methotrexate), pyrimidine analogs (fluorouracil, floxuridine, and cytarabine), purine analogs and related inhibitors (mercaptopurine, thioguanine, pentostatin, and 2-chlorodeoxyadenosine); aromatase inhibitors (carboplatin), procarbazine, hydroxyurea, mitotane, aminoglutethimide; hormones (i.e., estrogens) and hormone agonists such as luteinizing hormone-releasing hormone (LHRH) agonists (goserelin, leuprorelin, and triptorelin). Other chemotherapeutic agents may include nitrogen mustards, camptothecins, ifosfamide, tamoxifen, raloxifene, gemcitabine, navelbine, or any analog or derivative variant thereof.

In certain embodiments, the compounds of the present invention are administered in combination with a steroid. Suitable steroids may include, but are not limited to, 21-acetoxypregnenolone, alclometasone, algestrel, amcinolone acetonide, beclomethasone, betamethasone, budesonide, cloprednisone, clobetasol, clocortolone, clopredniol, corticosterone, cortisone, cortivazole, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate butyl, glycyrrhetinic acid, fluoxetine, fluclofenac, diflumethasone, flunisolide, fluocinolone acetonide, fluocinolone acetonide, fluocinolone butyl, fluocinolone, flumethas ... Oxyprednisolone, fluperone acetate, fluprednidine acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocort, halcitonide, ubetasol propionate, halometasone, hydrocortisone, loteprednol etabonate, flumethasone, prednicarbate, prednisolone, prednisolone 25-diethylaminoacetate, prednisolone, sodium phosphate, prednisone, prednisolone valerate, prednididine, dimethoprim-2, tixocortol, flurandrenolide, triamcinolone acetonide, fluphenazine, and their salts and/or derivatives.

In certain embodiments, the compounds of the invention are administered in combination with an immunotherapeutic agent. Suitable immunotherapeutics may include, but are not limited to, cyclosporine, thalidomide, and monoclonal antibodies. Monoclonal antibodies may be naked or conjugated, such as rituximab, tositumomab, alemtuzumab, epratuzumab, ibritumomab tiuxetan, gemtuzumab ozogamicin, bevacizumab, cetuximab, erlotinib, and trastuzumab.

Cancer treatment

Exemplary forms of cancer that can be treated by the methods of the present invention using the fused pyrimidine compounds of the present invention and pharmaceutical compositions thereof include, but are not limited to, prostate cancer, bladder cancer, lung cancer (including small cell or non-small cell cancer), colon cancer, kidney cancer, liver cancer, breast cancer, cervical cancer, endometrial cancer or other uterine cancer, ovarian cancer, testicular cancer, penile cancer, vaginal cancer, urethral cancer, gallbladder cancer, esophageal cancer, or pancreatic cancer.

Additional exemplary forms of cancer treatable by the methods of the invention include, but are not limited to, skeletal or smooth muscle cancer, stomach cancer, small intestine cancer, salivary gland cancer, anal cancer, rectal cancer, thyroid cancer, parathyroid cancer, pituitary cancer, and nasopharyngeal cancer.

The compounds of the present invention, and their salts and solvates thereof, may be employed alone or in combination with other therapeutic agents for the treatment of diseases or conditions associated with inappropriate P97 activity.

Additional diseases that can be treated according to the methods of the present invention include, in addition to cancer, autoimmune disorders, metabolic diseases, infectious diseases, neurological diseases, graft-versus-host disease, and other genetic diseases listed herein, beta (abeta)-lipoprotein deficiency, plasma copper protein deficiency, alpha-1-antichymotrypsin (ACT) deficiency, aspartylglucosaminuria, autosomal dominant retinitis pigmentosa, Brugada syndrome, Charcot-Marie-Tooth syndrome, congenital adrenal hyperplasia, congenital chloride diarrhea, congenital hypothyroidism, congenital long QT syndrome, congenital renal syndrome, congenital sucrase-isomaltase deficiency, Crigler-Najjar type II, cystic fibrosis, diabetes mellitus, dysplasia, Duchenne syndrome, Fabri disease, familial chylomicronemia, familial glucocorticoid deficiency, familial hypercholesterolemia, Gaucher disease, dysplasia, sclerostin-induced leukemia, sclerostin-induced leukocytosis ... disease), heavy chain disease, hereditary emphysema, hereditary emphysema with liver damage, hereditary bronze diabetes mellitus, hereditary hypofibrinogenemia, hereditary myeloperoxidase, hereditary spherocytosis, Hirschprung disease, hypogonadotropic hypogonadism, infantile systemic hyaline degeneration, infantile neuronal ceroid lipofuscinosis, Laron syndrome, liver failure, Marfan syndrome, medullary cystic kidney disease, familial juvenile hyperuricemic nephropathy, Menkes disease, nephrotic diabetes mellitus, pituitary neuropathic diabetes insipidus, oculocutaneous albinism, osteogenesis imperfecta, Pelizaeus-Merzbacher disease, Pendred syndrome syndrome), persistent hyperinsulinemic hypoglycemia of infancy, primary hypothyroidism, protein C deficiency, amyotrophic lateral sclerosis with multiple epiphyseal dysplasia, severe congenital neutropenia, Stargardt-like macular degeneration, steroid-resistant nephrotic syndrome, Tay-Sachs disease, hereditary angioedema type I, tyroxine-binding globulin deficiency, von Willebrand disease type IIA, X-linked Charcot-Marie-Tooth disease, X-linked hypophosphatemia, Alzheimer's disease, autosomal recessive juvenile parkinsonism, combined factor V and VIII deficiency, cranio-lenticulo-sutural dysplasia, hypotonia and congenital malformations, inclusion body myopathy, Paget's disease of bone disease, frontotemporal dementia (IBMPFD), lipid malabsorption, Marinesco-Sjoegren syndrome, Parkinson's disease, polycystic liver disease, spondyloepiphyseal dysplasia, Walcott-Rallison syndrome, and Lou Gehrig's disease (ALS).

In various embodiments, the compounds of the invention are useful for treating tumor growth, angiogenesis, infection, inflammation, immune-related diseases, ischemia and reperfusion injury, multiple sclerosis, rheumatoid arthritis, neurodegenerative conditions, or psoriasis.

Tumor growth may comprise cancer. Suitably, the present invention relates to a method for treating or lessening the severity of a cancer selected from the group consisting of brain cancer (glioma), glioblastoma, breast cancer, Wilm's tumor, Ewing's sarcoma, sarcoma), rhabdomyosarcoma, ependymoma, medulloblastoma, colon cancer, head and neck cancer, kidney cancer, lung cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, osteosarcoma, giant cell tumor of bone, thyroid cancer, lymphoblastic T-cell leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, hairy cell leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic neutrophilic leukemia, acute lymphoblastic T-cell leukemia, plasmacytoma, immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryocytic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia, malignant lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, lymphoblastic T-cell lymphoma, Burkitt's lymphoma ovarian cancer, ovarian cancer, pancreatic cancer, pancreatic cancer, ovarian cancer, esophageal cancer, salivary gland cancer, hepatocellular carcinoma, gastric cancer, nasopharyngeal cancer, buccal cancer, oral cancer, GIST (gastrointestinal stromal tumor), and testicular cancer.

In various embodiments, the cancer is selected from brain cancer (glioma), glioblastoma, breast cancer, colon cancer, head and neck cancer, kidney cancer, lung cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and thyroid cancer.

In various embodiments, the cancer to be treated is associated with the proteasome. See Voorhees et al., The Proteasome as a Target for Cancer Therapy, Clinical Cancer Research, Vol. 9, 6316-6325, December 2003, which is incorporated by reference in its entirety. In various embodiments, the cancer is associated with a specific target such as NFkB, p44/42 MAPK, P-gp, TopI, or TopIIα.

In various embodiments, the cancer is a solid tumor. In various embodiments, the cancer is selected from multiple myeloma, metastatic breast cancer, non-small cell lung cancer, prostate cancer, advanced colorectal cancer, ovarian cancer or primary peritoneal cancer, hormone-refractory prostate cancer, squamous cell carcinoma of the head and neck, metastatic pancreatic cancer, gastroesophageal junction or stomach, or non-Hodgkin's lymphoma.

Methods of treating conditions characterized by inappropriate levels of proteasome activity or in which normal levels of proteasome activity are reduced using the compounds described herein produce clinical benefit. Such conditions may include cancer or immune disorders characterized by excessive cell proliferation or cell signaling. Among cancers, this includes human cancers that overexpress c-Myc or express oncogenic forms of K-Ras proteins.

Neurodegenerative diseases and conditions may include, but are not limited to, stroke, ischemic injury to the nervous system, neurotrauma (e.g., impact head injury, spinal cord injury, and traumatic injury to the nervous system), multiple sclerosis and other immune-mediated neuropathies (e.g., Guillain-Barre syndrome and its variants, acute motor axonal neuropathy, acute inflammatory demyelinating polyneuropathy, and Fisher syndrome), HIV/AIDS dementia syndrome, axonomy, diabetic neuropathy, Parkinson's disease, Huntington's disease, ALS, multiple sclerosis, bacterial, parasitic, fungal, and viral meningitis, encephalitis, vascular dementia, multi-infarct dementia, Lewy body dementia, frontal lobe dementia such as Pick's disease, and other neurodegenerative diseases. disease), subcortical dementia (such as Huntington's or progressive supranuclear palsy), focal cortical atrophy syndrome (such as primary aphasia), metabolic toxic dementia (such as chronic hypothyroidism or B12 deficiency), and dementia caused by infection (such as syphilis or chronic meningitis). The compounds of the present invention can be used to treat Alzheimer's disease, comprising administering to a subject an effective amount of an agent or composition (e.g., a pharmaceutical composition) disclosed herein.

The compounds of the present invention are useful in treating cachexia and muscle wasting diseases. The compounds of the present invention are useful in treating such conditions, wherein the conditions are associated with cancer, chronic infectious diseases, fever, muscle wasting (atrophy) and denervation, nerve damage, fasting, acidosis-related renal failure, diabetes, and liver failure.

The compounds of the present invention can be used to treat hyperproliferative conditions such as diabetic retinopathy, macular degeneration, diabetic nephropathy, glomerulosclerosis, IgA nephropathy, cirrhosis of the liver, biliary atresia, congestive heart failure, scleroderma, radiation-induced fibrosis, and pulmonary fibrosis (idiopathic pulmonary fibrosis, collagen vascular disease, sarcoidosis, interstitial lung disease, and extrinsic lung disease). The treatment of burn victims is often hampered by fibrosis, and therefore, another embodiment of the present application is the topical or systemic administration of inhibitors to treat burns. Wound healing after surgery is often associated with disfiguring scars, which can be prevented by inhibiting fibrosis. Therefore, in certain embodiments, the present application relates to a method for preventing or reducing scars.

The compounds of the present invention are useful in the treatment of ischemic conditions or reperfusion injury, such as acute coronary syndrome (vulnerable plaque), arterial occlusive disease (cardiac, brain, peripheral arterial and vascular occlusion), atherosclerosis (coronary arteriosclerosis, coronary artery disease), infarction, heart failure, pancreatitis, myocardial hypertrophy, stenosis and restenosis.

The compounds of the present invention can be used to inhibit TNFα to prevent and/or treat septic shock.

The compounds of the present invention can be used to inhibit antigen presentation in cells, including exposing cells to reagents described herein. The compounds of the present invention can be used to treat immune-related conditions, such as allergies, asthma, organ/tissue rejection (graft versus host disease) and autoimmune diseases, including but not limited to lupus, rheumatoid arthritis, psoriasis, multiple sclerosis and inflammatory bowel disease (such as ulcerative colitis and Crohn's disease). Therefore, another embodiment is a method for regulating a subject's immune system (e.g., suppressing transplant rejection, allergies, autoimmune diseases and asthma), comprising administering to the subject an effective amount of a compound of the present invention.

The compounds of the invention can be used in methods for altering the repertoire of antigenic peptides produced by the proteasome or other protein assemblies with multiple catalytic activities.

The compounds of the present invention can be used in a method of inhibiting IKB-α degradation, comprising contacting a cell with an agent identified herein. Another embodiment is a method of reducing the cellular content of NF-KB in a cell, muscle, organ or subject, comprising contacting the cell, muscle, organ or subject with a compound of the present invention.

The compounds of the present invention can be used in methods for affecting the cyclin-dependent eukaryotic cell cycle. The compounds of the present invention can be used in methods for treating a proliferative disease (e.g., cancer, psoriasis, or restenosis) in a subject. The compounds of the present invention can be used to treat cyclin-related inflammation in a subject.

One embodiment is a method for treating p53-related apoptosis comprising administering to a subject an effective amount of a compound of the present invention.

In another embodiment, the compounds of the present application are useful in treating parasitic infections, such as infections caused by protozoan parasites. In certain such embodiments, the agents are useful in treating parasitic infections in humans caused by protozoan parasites selected from the group consisting of Plasmodium, Trypanosoma, Leishmania, Pneumocystis, Toxoplasma, Entamoeba histolytica, Entamoeba invasives, and Giardia lamblia. In certain embodiments, the agents are useful in treating parasitic infections in animals and livestock caused by protozoan parasites selected from the group consisting of Plasmodium hermani, Cryptosporidium, Echinococcus granulosus, Eimeria tenella, Sarcocystis fasciatus, and Neurospora crassa. Other compounds useful as proteasome inhibitors in treating parasitic diseases are described in WO98/10779, which is incorporated herein in its entirety.

Specifically, the treatment methods include inhibiting, preventing, ameliorating, minimizing and/or eliminating adverse conditions associated with the inability of cells to metabolize, degrade or otherwise remove ubiquitin-tagged proteins and peptides because the tags have been cleaved, degraded, removed or otherwise rendered inoperative by the activity of the P97 metalloproteinase domain. The methods include methods wherein the human condition is characterized by abnormal degradation of regulatory peptides, leading to excessive cell proliferation or cell signaling. The methods involve administering an effective amount of a compound or pharmaceutical formulation disclosed above to improve, reduce or inhibit abnormal degradation of regulatory peptides. Specifically, the human condition includes cancer or an immune disorder, cancer caused by overexpression of c-Myc or expression of an oncogenic form of the K-Ras protein. The methods also include inhibiting or ameliorating P97 metalloproteinase domain activity in human patients with abnormal P97 metalloproteinase domain activity on ubiquitin-modified proteins. As described above, these methods involve administering an effective amount of a compound or pharmaceutical formulation disclosed above to a patient to improve, reduce or inhibit abnormal P97 metalloproteinase domain activity.

diagnosis

Various cellular proteins undergo proteolytic processing during maturation or activation. The compositions identified herein are also useful as diagnostic agents (e.g., in diagnostic kits or for use in clinical laboratories) for screening for proteins (e.g., enzymes, transcription factors) that are processed by hydrolases, including the proteasome. The reagents are also useful as research reagents that specifically bind to the X/MB 1 subunit or α-chain and inhibit the proteolytic activity associated therewith. For example, the activity of (specific inhibitors of) other subunits of the proteasome can be assayed.

The compounds of the invention identified herein can be used to determine whether a cell, developmental or physiological process or output is regulated by proteolytic activity. One such method comprises obtaining an organism, a whole cell preparation or a cell extract; exposing the organism, cell preparation or cell extract to an agent identified herein; exposing the organism, cell preparation or cell extract exposed to the agent to a signal; and monitoring the process or output. See, for example, U.S. Patent No. 7,741,432.

The compounds of the present invention can be used as part of a diagnostic assay. For example, cells from a patient can be obtained and assays can be performed to determine whether a compound of the present invention may be an effective therapeutic compound for that patient. The cells obtained from the patient can, for example, be cancer cells from a tumor. The cells can be cultured and a compound of the present invention can be administered to determine how the cancer cells respond.

The diagnostic aspects of the present invention also include assays for determining inhibition of P97 activity. The assay involves combining a P97 enzymatic material with a protein substrate and determining whether a potential inhibitory candidate will work in this assay to reduce enzyme activity. The P97 enzymatic material is either standard or derived from patient cells. Similarly, the protein substrate is either standard or derived from patient cells. Specifically, the protein substrate is selected from the group consisting of proteins modified with ubiquitin, proteins modified with ubiquitin-like modifiers, and proteins modified with ubiquitin chains that can be isolated from patient cells. The combination of the P97 enzymatic material and the protein substrate produces an enzymatic mediator. For this mediator, the protein substrate is modified with a label that can be detected by measuring molecular weight, spectroscopic interaction, or chromatographic _Rf determination.

Following separation and labeling, the enzymatic medium is manipulated to perform a first measurement of the enzymatic medium relative to the protein substrate alone, wherein the first measurement is accomplished by detecting the label.

Following the first measurement procedure, potential inhibitory candidates are combined with a labeled protein substrate and the P97 enzymatic material is added to produce a candidate mediator.

The candidate mediator is manipulated to perform a second measurement of the candidate mediator relative to the protein substrate alone, wherein the second measurement is accomplished by detecting the label.

Ultimately, the ability of an inhibitory candidate to effectively treat a patient in need thereof is evaluated by comparing the first and second measurements to identify candidates that exhibit at least about 50% inhibition at a concentration of no more than 500 micromolar in the candidate medium, the difference between the first and second measurements being at least about 50%, wherein the second measurement is greater than the first measurement.

Specific embodiments of the fused pyrimidine compounds of formula I

Embodiments of the fused pyrimidine compounds of Formula I include the specific compounds mentioned in the following table according to their IUPAC (International Union of Pure and Applied Chemistry) nomenclature. All compounds in these tables can be synthesized according to the synthetic schemes listed below and will exhibit appropriate biological activity in one or more of the biological assays described herein. Table 1 divides these embodiments into three groups: preferred, more preferred, and most preferred.

Table I

List of individual compounds

Preferred

1-(4-((3,5-difluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole 4-carboxamide

2-(4-(Aminomethyl)-2-methyl-1H-indol-1-yl)-N-benzyl-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine

2-(Aminomethyl)-1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indole-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

N-Benzyl-2-(2-methyl-1H-indol-3-yl)-5,6,7,8-tetrahydroquinazolin-4-amine

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6-dimethyl-pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-benzo[d][1,2,3]triazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)isobenzofuran-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2H-isoindole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylindolizine-5-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]thiophene-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)isobenzofuran-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4.3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-[1,2,3]triazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylbenzo[b]thiophene-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylindolizine-8-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]isothiazole-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[c]isoxazole-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[d]isothiazole-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)benzo[d]isoxazole-7-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

More preferably:

1-(4-((3,5-difluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

2-(4-(Aminomethyl)-2-methyl-1H-indol-1-yl)-N-benzyl-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine

2-(Aminomethyl)-1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indole-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

N-Benzyl-2-(2-methyl-1H-indol-3-yl)-5,6,7,8-tetrahydroquinazolin-4-amine

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6-dimethyl-pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidine-2y1)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-5-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydrooxazo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,6,7,9-tetrahydrooxazo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,8,9-tetrahydrooxazo[4,5-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7,8,9-tetrahydrooxazo[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydrooxazo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dihydrofuro[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7,8,9-tetrahydro-5H-pyrimido[5,4-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-6H-pyrano[3,2-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methylpyrazolo[1,5-a]pyridine-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-c]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylimidazo[1,2-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)imidazo[1,5-a]pyridine-8-carboxamide

3-(4-(Benzylamino)-9-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)-2-methyl-1H-indole-7-carboxamide

Most preferred:

1-(4-((3,5-difluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-Fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-((Thien-2-ylmethyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-5-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6,7-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-6-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7,8-dimethyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-7-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide

1-(4-(Benzylamino)-8-methyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide

2-(4-(Aminomethyl)-2-methyl-1H-indol-1-yl)-N-benzyl-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine

2-(Aminomethyl)-1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indole-4-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-Fluorobenzyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methylbenzofuran-7-carboxamide

3-(4-(Benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-5-methyl-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-7-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

3-(4-(Benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide

N-Benzyl-2-(2-methyl-1H-indol-3-yl)-5,6,7,8-tetrahydroquinazolin-4-amine

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-5,6-dimethyl-pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

(1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methanol

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxylic acid

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-(3-fluorobenzyl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine

2-(4-(Aminomethyl)-1H-indazol-1-yl)-N-benzyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-(Benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)-2-methyl-propionamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)acetamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)ethanesulfonamide

N-((1-(4-((3-fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)methanesulfonamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propanamide

N-((1-(4-((3-Fluorobenzyl)amino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazol-4-yl)methyl)propane-2-sulfonamide.

Synthesis method

The following sections describe the preparation of representative compounds of the present invention in more detail. The following examples are provided for illustrative purposes and are not intended to limit the present invention in any way. Those skilled in the art will readily recognize a variety of noncritical parameters that can be changed or modified to produce substantially the same result.

Those skilled in the art will recognize or be able to determine the synthesis of many compounds equivalent to those described herein and their methods of use using only routine experimentation. Although certain exemplary embodiments are depicted and described herein, it should be understood that the compounds of the present invention can be prepared according to methods generally available to those of ordinary skill in the art. All references and publications cited above are incorporated herein by reference.

Synthesis preparation

The novel compounds of the present invention can be prepared in a variety of ways known to those skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below and synthetic methods known in the art of synthetic organic chemistry or variations thereon as known to those skilled in the art.

The preparation of compound can relate to the protection and deprotection of various chemical groups.The needs of protection and deprotection and the selection of suitable protecting groups can be easily determined by those skilled in the art.The chemical characteristics of protecting groups can be found in, for example, the following documents: Greene and Wuts, Protective Groups in Organic Synthesis, the 44th edition, Wiley & Sons, 2006 and Jerry March, Advanced Organic Chemistry, the 4th edition, John Wiley & Sons, publisher, New York, 1992, which are incorporated herein by reference in their entirety.

Fused pyrimidine backbones can be prepared by literature methods cited hereinafter. The following schemes depict established, known syntheses of these backbones.

The Het portion of the fused pyrimidine backbone and the amine substituents can be synthesized and linked to these backbones by literature methods cited below. The following scheme depicts known techniques for accomplishing this linkage.

General synthetic scheme for fused pyrimidines

The compounds of the present invention can be synthesized using the following methods. General reaction conditions are given and the reaction products can be purified by generally known methods including crystallization, silica gel chromatography using various organic solvents such as hexane, cyclohexane, ethyl acetate, methanol, preparative high pressure liquid chromatography or preparative reverse phase high pressure liquid chromatography.

Scheme 01: General synthetic route for the preparation of 2-chloro-substituted fused cycloalkylpyrimidines (Y is an ^sp3 carbon)

Cyclic ketoesters of general structure A1 can be reacted with urea in the presence of an acid such as HCl in a solvent such as ethanol at reflux temperature for 2 to 24 hours to provide pyrimidinedione A2. Pyrimidinedione A2 can be reacted with excess _POCl3 at reflux, optionally in the presence of a tertiary amine such as triethylamine, for 3 to 12 hours to provide fused dichloropyrimidines of general structure A3. Other chlorinating agents such as thionyl chloride or _PCl5 can be used in place of _POCl3 . A3 can be reacted with excess amounts of various substituted amines in solvents such as acetonitrile or dimethylformamide at temperatures ranging from room temperature to reflux to provide 4-amino-2-chlorofused pyrimidines of general structure A.

Scheme 02: General synthetic route for preparing 2-chloro-substituted fused dihydrofuranopyrimidines or tetrahydropyranopyrimidines (Y is oxygen)

Similarly, 2-Cl-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine BA can be prepared from the corresponding ketoester BA2, which can be prepared by treating 2-hydroxyacetic acid esters with ethyl acrylate in the presence of a strong base such as sodium hydride.

2-(2,4,6-Trichloropyrimidin-5-yl)ethanol BB1 can be converted to the dichloride BB2 by intramolecular cyclization in the presence of a strong base such as sodium hydride at room temperature. Similarly, the latter can react with amines to produce 2-chloro-5,6-dihydrofuro[2,3-d]pyrimidin-4-amine BB.

Tetrahydropyran-4-one BC1 can be reacted with dimethyl carbonate in the presence of sodium hydride to give 4-oxotetrahydro-2H-pyran-3-carboxylate BC2, which can then be converted to the corresponding diol BC4 in a two-step process via the intermediate 4-ureido-5,6-dihydro-2H-pyran-3-carboxylate BC3. Similarly, the diol can be converted to 2-chloro-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine BC.

Dihydrofuran-2(3H)-one BD1 can be converted to 4-hydroxybutyrate BD3 by hydrolysis using a strong base such as potassium hydroxide followed by treatment with an alkyl bromide. This can be reacted with propionyldiazenecarboxaldehyde in the presence of _Rh2 (OAc) ₄ to produce 4-(2-ethoxy-2-oxoethoxy)butyrate BD4, which can be converted to 3-oxotetrahydro-2H-pyran-4-carboxylate BD5 by treatment with potassium tert-butoxide. A similar method as used in the preparation of BC can be used to transfer the ketoester to 2-chloro-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-4-amine BD.

Tetrahydro-2H-pyran-2-one BE1 can be converted to 2,4-bis(methylthio)-pyrimidine BE2 in a single step with thiocyanomethane in the presence of TFA, albeit in relatively low yield. The latter is then oxidized to the disulfone BE3 with m-CPBA. The sulfone can be hydrolyzed to the diol BE4 using aqueous sodium hydroxide. Similarly, it can then be converted to 2-chloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine BE.

Scheme 03: General synthetic route for preparing 2-chloro-substituted fused dihydropyrrolopyrimidines or tetrahydropyridopyrimidines (Y is nitrogen)

Commercially available Boc-protected 2,4-dichloro-5H-pyrrolo[3,4-d]pyrimidine CA1 can be converted to the corresponding 2-chloro-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-amine CA in a similar manner.

2-(2,4,6-Trichloropyrimidin-5-yl)acetaldehyde CB1 can be reacted with amines such as methylamine by reductive amination in the presence of NaBH3CN according to PCT International Application No. 2011152485 to produce 2,4-dichloride CB2, which can be easily converted to 2-chloro-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-amine CB by the above method.

Benzyl-protected 4-oxopiperidine-3-carboxylate CC1 can be converted to its diol CC2 by treatment with urea under basic conditions such as sodium methoxide. This is then transferred to the dichloride CC3, followed by a conversion of the protecting group from the benzyl group to a Boc group, given the challenge of selectively removing the benzyl group from the aromatic methylamino group at the 4-position of the pyrimidine. Similarly, the Boc-protected dichloride CC5 can be reacted with an amine to produce the Boc-protected 2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine CC.

Similarly, Boc-protected 2-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine CD can be prepared from 1-benzyl-3-oxopiperidine-4-carboxylate CD1.

The regioisomer CE, 2-chloro-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-amine, can be prepared by several different methods. 2-Aminonicotinic acid CE1 can be reacted with urea, followed by hydrolysis to produce pyrido[2,3-d]pyrimidine-2,4-diol CE2, which can be readily converted to the dichloride CE3. CE3 can be selectively reduced to 2,4-dichloro-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine CE4 under one atmosphere of hydrogen in the presence of _PtO2 , although the yield is generally relatively poor. The introduction of a Boc protecting group on the amino group and replacement of the 4-chloride with an amine can then produce CE. Alternatively, first treating CE3 with an amine followed by reduction with higher pressures of hydrogen can achieve better yields.

A similar approach can be used to prepare another group of regioisomers, 2-chloro-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-4-amine CF. 3-Aminopicolinic acid CF1 is the starting material. Due to the substitution at the 4-position of the pyrimidine, it is difficult to introduce a protecting group such as Boc to protect the amino group in reasonable yields, however, a small alkyl group such as methyl can be easily inserted.

5,6,7,8-tetrahydropyridopyrimidin-4-amines with alkyl groups on saturated ring carbons can also be prepared using the above methods, provided their corresponding ketoesters can be prepared. For example, 1-benzyl-5-methyl-4-oxopiperidine-3-carboxylate can be prepared from methyl methacrylate CG1 in a three-step process. 3-(Benzylamino)-2-methylpropanoate can be prepared by Michael addition between methacrylate CG1 and benzylamine. Similarly, another Michael addition with an acrylate yields 3-(Benzyl(3-methoxy-3-oxopropyl)amino)-2-methylpropanoate CG3. Intramolecular cyclization of CG3 in the presence of sodium hydride at reflux yields 1-benzyl-5-methyl-4-oxopiperidine-3-carboxylate CG4. 2-Chloro-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine CG can then be achieved by a similar route as described above. A similar strategy can be used to prepare tetrahydropyridopyrimidin-4-amines with alkyl groups substituted at other positions or chiral derivatives if chiral acrylates are used as starting materials.

2,4-Dioxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine CH1 can react selectively with amines to produce intermediate CH2, which can be Boc-protected by reaction with Boca hydride to produce CH.

Scheme 04: General synthetic route for the preparation of 2-(1H-benzo[d]imidazol-1-yl)-substituted saturated fused pyrimidines (DA)

The general synthetic method for attaching benzo[d]imidazole DAl via its 1-position to the 2-position of a fused pyrimidine to produce the desired molecule DA is a Pd-based coupling reaction. Typical conditions include Pd(dba) ₂ as a transition metal catalyst, X-phos as a ligand, cesium carbonate as a base, and dioxane as an organic solvent. The reaction temperature varies between room temperature and reflux. For example, if Y is a Boc-protected nitrogen, an additional deBoc step can be used. For example, if ^R1 is a nitrile (CN), it can be converted to an amide in the presence of urea hydrogen peroxide (UHP). Alternatively, in some cases where ^R4 is an alkoxy or amino group, the coupling reaction can be performed between 2-chloro-pyrimidine DAO and benzene-1,2-diamine DA2 using Pd(OAc) ₂ as a catalyst and _CsCO3 as a base, followed by cyclization in the presence of cyanogen iodide or tetramethoxymethane.

Scheme 05: General synthetic route for the preparation of 2-(1H-indol-1-yl or 1H-indazol-1-yl)-substituted saturated fused pyrimidines (DB)

A solution of a substituted pyrimidine DAO can be coupled with an indole or indazole DB1 to produce the desired molecule DB using a method similar to that described in Zhou, H.-J. et al. WO 2014015291. To a solution of a substituted pyrimidine such as compound DAO, an indole or substituted indole such as compound DB1 and a base such as sodium carbonate or cesium carbonate are added in the presence of a palladium catalyst such as Pd(OAc) ₂ and a ligand such as triphenylphosphine in a solvent such as dioxane, and the reaction can be optionally heated to reflux for up to 48 hours.

Scheme 06: General synthetic route for the preparation of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-substituted saturated fused pyrimidines (DC)

Compounds containing the structure 1-pyrimidin-2-yl-1,2,3-benzotriazole DC can be produced using methods similar to those described in Zhou, H.-J. et al. WO 2014015291 and Ohlmeyer, Michael J. et al. WO 2008060301 and by using substituted 1,2,3-benzotriazole DC1 as described above.

Scheme 07: General synthetic route for the preparation of 2-(1H-indol-3-yl or benzofuran-3-yl or benzo[b]thiophen-3-yl)-substituted saturated fused pyrimidines (DD)

Under various conditions, such as NBS in DMF, 3-unsubstituted intermediates DD1 (X = O, S, substituted or appropriately protected nitrogen) undergo regioselective bromination at their 3-position to produce 3-Br-substituted intermediates DD2. This can then be converted to the boronate ester DD4 by treatment with the boronate ester DD3 under various conditions. Subsequently, a Pd-based coupling reaction between intermediate DD4 and DAO, similar to that described in Zhou, H.-J. et al. WO 2014015291, provides the desired molecule. For example, if Y or A is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 08: General synthetic route for the preparation of 2-(Benzo[d]isoxazol-3-yl or benzo[d]isothiazol-3-yl, 1H-indazol-3-yl)-substituted saturated fused pyrimidines (DE)

The key intermediate DE1, tributyl-2-pyrimidinyltin, can be prepared from intermediate DA0 using a similar procedure as described in the reference (Castanedo, Georgette et al., PCT International Application 2010138589). Bromination can occur selectively at the 3-position of these 5,6-bicyclic aromatic rings. Subsequently, a Pd-based coupling reaction between intermediates DE1 and DE2, similar to that described in Zhou, H.-J. et al., WO2014015291, provides the desired molecule DE. For example, if Y or A is a protected nitrogen, an additional deprotection step can be achieved using the reported conditions.

Scheme 09: General synthetic route for the preparation of 2-(imidazo[1,5-a]pyridin-1-yl)-substituted saturated fused pyrimidines (DF)

Aubration can occur selectively at the 3-position of imidazo[1,5-a]pyridine DF1. A Pd-based coupling reaction similar to that described above between intermediate DE1 and DF2 then provides the desired molecule DF. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Alternatively, the diatom DF2 can be converted to the boronate ester DF3 by treatment with the boronate ester DD3 under different conditions. A Pd-based coupling reaction similar to that described above between the intermediate DF3 and DAO provides the desired molecule. For example, if Y or A is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 10: General synthetic route for the preparation of 2-(imidazo[1,5-a]pyridin-1-yl)-substituted saturated fused pyrimidines (DG)

Imidazolo[1,5-a]pyridin-3(2H)-one DG1 can be converted to its triflate DG2. A Pd-based coupling reaction similar to that described above between intermediate DE1 and DG2 provides the desired molecule DG. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Alternatively, substituted imidazo[1,5-a]pyridine-3-carboxylates DG3 can be prepared by various methods including those described in Chen, Shaoqing et al. WO 2013030138, Bilodeau and Mark T. et al. WO 2008085302. Imidazolo[1,5-a]pyridine-3-carboxylates DG3 can be converted to the corresponding amidines DG4 using aminochloromethylaluminum in an organic solvent such as toluene at temperatures between ambient and 100° C. as described in Brockunier L. et al. WO 2010065275 and Gargiapati R.S. Tetrahedron Letters 1990, 31, 1969. The resulting imidazo[1,5-a]pyridine-3-carboximidamide DG4 can be reacted with the above-described ketoester DG5 in the presence of a catalytic amount of a base such as sodium ethoxide in ethanol at reflux to provide pyrimidin-4-ols DG6. The latter can be converted into the desired molecule DG using the methods described above.

Scheme 11: General synthetic route for the preparation of 2-(imidazo[1,2-a]pyridin-3-yl)- or 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-substituted saturated fused pyrimidines (DH)

Imidazolo[1,2-a]pyridine DH3 can be prepared by treating 2-aminopyridine DH1 with an aldehyde or ketone DH2 by methods similar to those described in the references of Ebetino, Frank Hallock et al. PCT International Application 2010033978. Iodination with NIS can produce 3-1-imidazo[1,2-a]pyridine DH4 by methods similar to those described in the references of Bifulco, Neil, Jr. et al. PCT International Application 2014011900. [[1,2,4]triazolo[4,3-a]pyridine-8-carbonitrile DH7 can be prepared in a two-step process by reaction of a substituted pyridine DH5 with hydrazine followed by treatment with triethoxymethane by methods analogous to those described in references such as Allen, Shelley et al., PCT International Application 2010022076; Potts, K.T. and Burton, H.R., Journal of Organic Chemistry, 31(1), 251-60; 1966. Subsequent bromination with NBS can produce the intermediate DH8. DH4 or DH8 can then be converted to the boronate ester DH9 by treatment with the boronate ester DD3 under different conditions. A Pd-based coupling reaction between the intermediate DH9 and DAO, analogous to that described above, provides the desired molecule DH. Alternatively, a Pd-based coupling reaction between the intermediate DE1 and DH4 or DH8, analogous to that described above, also provides the desired molecule DH. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 12: General synthetic route for the preparation of 2-(pyrazolo[1,5-a]pyridin-3-yl)- or 2-(11,2,3]triazolo[1,5-a]pyridin-3-yl)-substituted saturated fused pyrimidines (DI)

Various methods can be used to prepare substituted 3-pyrimidin-2-ylpyrazolo[1,5-a]pyridines DI1 (Z═CR 4 ) as described in Tsuchiya et al. Chemical & Pharmaceutical Bulletin 1983, 31, ⁴⁵⁶⁸ ; Hajos, G. and Riedl, Z. Science of Synthesis, 2002, 12, 613 and Aboul-Fadl, T. et al. Synthesis, 2000, 12, 1727-1732. Various methods can be used to prepare substituted [1,2,3]triazolo[1,5-a]pyridines DI1 (Z=N) as described in Latham, Elliot J. and Stanforth, Stephen P. Journal of Heterocyclic Chemistry, 32(3), 787-9; 199; Sheng et al., Organic Letters, 14(14), 3744-3747; 2012 and Prakash, Om et al., Synthetic Communications, 30(3), 417-425; 2000. Iodination with NIS can produce 3-iodo-pyrazolo[1,5-a]pyridines DI2 by methods similar to those described in Bifulco, Neil, Jr. et al., PCT International Application No. 2014011900; Wan, Huixin et al., PCT International Application No. 2013170774, November 21, 2013. DI2 can then be converted to the boronate ester DI3 by treatment with the boronate ester DD3 under various conditions. A Pd-based coupling reaction similar to that described above between intermediate DI3 and DAO provides the desired molecule DI. Alternatively, a Pd-based coupling reaction similar to that described above between intermediate DE1 and DI2 also provides the desired molecule DI. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 13: General synthetic route for the preparation of 2-(2-methylindolizin-1-yl)-substituted saturated fused pyrimidines (DJ)

1-Bromo-indolizine DJ2 can be prepared from substituted pyridines using methods described in Iizuka, Masato and Shimizu, Kazuo, PCT International Application No. 2012043638. DJ2 can then be converted to the boronate ester DI3 by treatment with the boronate ester DD3 under various conditions. A Pd-based coupling reaction between intermediate DJ3 and DAO, similar to that described above, then provides the desired molecule DJ. Alternatively, a Pd-based coupling reaction between intermediate DE1 and DJ2, similar to that described above, also provides the desired molecule DI. For example, if Y is a protected nitrogen, an additional deprotection step can be achieved using the reported conditions.

Scheme 14: General synthetic route for the preparation of 2-(indolizin-3-yl)-substituted saturated fused pyrimidines (DK)

A Pd-based coupling reaction between DJ1 and DAO using methods similar to those described above provides the desired molecule DK. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 15: General synthetic route for the preparation of 2-(2H-isoindol-1-yl)-substituted saturated fused pyrimidines (DL)

The boronate ester of 2H-isoindole DL3 can be prepared from substituted 1,2-dimethylbenzene DL1 according to the procedure described in the reference (Ohmura, Toshimichi et al. Journal of the American Chemical Society, 131(17), 6070-6071; 2009). A similar Pd-based coupling reaction between the intermediate DL3 and DAO as described above then provides the desired molecule DL. For example, if Y is a protected nitrogen, an additional deprotection step can be achieved using the reported conditions.

Scheme 16: General synthetic route for the preparation of 2-(Benzo[c]thiophen-1-yl)-substituted saturated fused pyrimidines (DM)

The key intermediate DM3, benzo[c]thiophen-1-yltrimethylstannane, can be prepared from intermediate DL2 according to a similar procedure in the reference (Kawabata, Kohsuke, and Goto, Hiromasa, Journal of Materials Chemistry, 22(44), 23514-23524; 2012). A Pd-based coupling reaction similar to that described above between intermediate DM3 and DAO then provides the desired molecule DM. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 17: General synthetic route for the preparation of 2-(isobenzofuran-1-yl)-substituted saturated fused pyrimidines (DN)

The key intermediate DN3, tributyl(isobenzofuran-1-yl)stannane, can be prepared from intermediate DN2, which can be prepared from lactone DN1. A Pd-based coupling reaction similar to that described above between intermediate DN3 and DAO then provides the desired molecule DN. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 18: General synthetic route for the preparation of 2-(Benzo[c]isoxazol-3-yl) or 2-(Benzo[c]isothiazol-3-yl)-substituted saturated fused pyrimidines DO

Substituted 3-methoxybenzo[c]isoxazoles DO2 can be prepared from 2-aminobenzoate DO1 by analogous procedures to those described in references such as Chauhan, Mohinder S., and McKinnon, David M., Canadian Journal of Chemistry, 53(9), 1336-42; Smalley, R.K., Science of Synthesis, 11, 337-382; 2002. Demethylation and conversion of the hydroxyl group to a triflate group can then produce the intermediate DO3. Substituted benzo[c]isoxazoles DO6 can be prepared from substituted o-toluidines DO4 by analogous procedures to those described in references such as Puetz, Claudia et al., European Patent Application 1352910. A Br group can then be selectively converted to its position DO7 by bromination with BNS. Subsequently, a Pd-based coupling reaction between the intermediates DO3 or DO7 and DAO, similar to that described above, provides the desired molecule DO. For example, if Y is a protected nitrogen, an additional step of deprotection can be achieved using the reported conditions.

Scheme 19: Conversion of nitrile to amide DP2

In some cases, the desired compound DP1 prepared in Schemes 5-18 above may have a nitrile substitution at the position shown in Scheme 19. This substituent can be converted to the corresponding carboxamide. The nitrile DP1 is dissolved in a 1/10 ratio of water/DMSO and treated with urea-hydrogen peroxide (UHP) and a base such as potassium carbonate. The reaction mixture is stirred at room temperature for up to 18 hours, then poured into ice water and stirred for two hours. The resulting solid is filtered, dried and, if necessary, purified by column chromatography to obtain the desired amide DP2.

Scheme 20: Conversion of nitrile to aminomethylamine DP3

In some cases, the desired compound DP1 prepared in Schemes 1-18 above may have a nitrile substitution at the position shown in Scheme 20. This substituent can be converted to the corresponding methylamine DP3. A solution of nitrile DP1 in an aprotic organic solvent such as THF is treated with LAH and the resulting mixture is stirred for up to 18 hours. The reaction mixture is treated with 15% aqueous NaOH and stirred for 1 hour, then filtered. The THF is removed under reduced pressure to yield the product DP3, which can be further purified by column chromatography.

Scheme 21: Conversion of ester to acid DP4 or amide DP5

In some cases, the desired compound DP1 prepared in Schemes 5-18 above may possess a carboxylate at the position shown in Scheme 21. This functionality can be readily converted to the corresponding acid DP4 or substituted amide DP5 using standard methods.

Scheme 22: Conversion of aldehyde DP6 to amine DP7 or methanol or ether DP8

In some cases, the desired compound DP1 prepared in Schemes 5-18 above may have a nitrile at the position shown in Scheme 22. This functionality can be readily converted to the corresponding amine DP7 or alcohol or ether DP8 via the intermediate aldehyde DP6 using standard methods.

Scheme 23: Conversion of aldehyde DP9 to methanol, ether DP10, or amine DP11

In some cases, the desired compound DP9 prepared in Schemes 5-18 above may have an aldehyde at the position shown in Scheme 23. This functional group can be readily converted to the corresponding alcohol or ether DP10 or amine DP11 using standard methods.

Bioassay

The biological activity of the fused pyrimidine compounds of the present invention can be determined by in vitro testing and cell-based assays using well-established protocols to identify and select compounds that exhibit anticancer activity. The present invention focuses on the ability of the fused pyrimidine compounds to interact with the p97 proteasome complex. As described in the Background, the function of the p97 complex is essential for sustained cell viability. Inhibition of the complex's activity leads to accumulation of the protein in the cell and subsequent apoptosis. Bioassays allow for the evaluation of the biological activity of the fused pyrimidine compounds of the present invention.

The primary biological assays are in vitro and cell-based assays for determining the inhibitory ability of the fused pyrimidine compounds of the invention against valosin-containing proteins (ie, p97). The assays also provide a primary indication of the bioavailability of the fused pyrimidine compounds of the invention.

The ability to inhibit the p97 complex was investigated using a p97 in vitro assay using a labeled p97 substrate, following the method described by Christianson in Nat Cell Biol. (2011) 14:93 for a p97 cell-based assay. A cell-based assay was used to test the antitumor effects of the inhibitors on cultured cancer cells. This antitumor assay is based on cultured cancer cells using a commercially available cell titer glo assay provided by Promega. Additional assays can assess bioavailability using art-recognized model studies designed to demonstrate the ability of the compounds of the invention to reach target cells in vivo. While all compounds tested exhibited antitumor activity, the assay also allowed the identification of fused pyrimidine compounds as candidates for further investigation in vivo antitumor testing in mouse, guinea pig, and dog models. Selected candidates were shown to have highly desirable pharmacokinetic properties in these in vitro assays.

P97 ATPase biochemical assay

ATPase assays were performed according to the following protocol: purified enzyme (20 nM p97), substrate (20 μM ATP), and dose titrations of compound were mixed in buffer (50 mM TRIS pH 7.5, 20 mM MgCl ₂ , 0.02% TX-100, 1 mM DTT, 0.2% (v/v) glycerol) and incubated at 37° C. for 15 minutes. The reaction was terminated and the level of generated product was measured using the ADP Glo assay kit (Promega, Madison, WI). The generated product was plotted against compound concentration and an IC50 value was generated for each compound using a four-parameter fitting model.

P97 cell-based assay

The on-target cell-based effects of the compounds of the present invention were monitored using the reporter cell line HEK-293TCRα-GFP as described in Christianson et al. Nat. Cell Biol. (2011) 14: 93. Inhibition of the turnover of the TCRα-GFP reporter gene is a hallmark of p97 inhibition. The protocol for monitoring reporter gene turnover by TCRα-GFP is as follows: reporter cells were inoculated and incubated with the proteasome inhibitor MG132 to accumulate TCRα-GFP. Subsequently, the medium containing MG132 was removed and the dose of the compound was titrated with cycloheximide and incubated with the cells. At the end of the incubation, the compound and medium were removed, the cells were fixed and GFP fluorescence was measured by standard external fluorescence microscopy techniques. Fluorescence was plotted against compound concentration and the IC50 value for each compound was generated using a four-parameter fitting model.

Image analysis is used to generate quantitative data from these assays, which can be fitted to a four-parameter sigmoidal curve to obtain IC50 values. Substrates of the ubiquitin-proteasome system, such as p53, are monitored after the tumor cell lines are incubated with the compounds for several hours. Accumulation of these proteins indicates inhibition of proteasome-mediated degradation. Accumulation of lysine-48 chains of polyubiquitin is also monitored by immunofluorescence as an indicator of ubiquitin-proteasome system inhibition. Both LC3 and SQSTM1 are mediators of autophagy. The localization and amount of these proteins are monitored by immunofluorescence and reports on the activity and inhibition of autophagy in response to p97 inhibition.

Cultured cancer cells

Antitumor effects were monitored in cultured cancer cells several days after compound treatment. The cell titer glo assay (Promega) measures the amount of ATP, which is a proxy for cell viability. Cell counting was performed using high-content microscopy followed by image analysis. A hanging drop 3D culture system (3D Biomatrix) was used followed by cell titer glo to measure growth in a tumor-like environment.

Absorption assay

The ability of a compound to be absorbed by the gastrointestinal lumen after oral administration is evaluated by measuring its permeability across a Caco-2 cell monolayer. Sun D, et al., Curr. Opin. Drug Discov. Develop [(2004) 75. The in vitro permeability of the compound (2 μM, in Kreb's buffer or HBSS buffer, n=2) was determined using a 21-day-old Caco-2 cell monolayer. The permeability coefficients from the apical side to the basolateral side (A to B) and from the basolateral side to the apical side (B to A) were determined after 120 min at 37°C. The efflux ratio was calculated based on the ratio of the permeability coefficients of B to A versus A to B to determine the possibility that the compound acts as a substrate for an efflux pump (e.g., Pgp). The protocol for this Caco-2 assay and the corresponding detailed description are provided in the following experimental section.

Metabolic stability assay

The metabolic stability of a compound can be evaluated by measuring its half-life in a liver microsomal preparation. Roserts, Sa, et al., Xenobiotica (2001) 37:557. Compounds are administered to a mouse liver microsomal preparation in the presence of NADPH and their half-life is determined by measuring the rate of disappearance of the compound from the preparation using LCMS/MS at 0, 15, 30, and 60 minutes. The protocol for determining metabolic stability in the mouse liver assay and the corresponding detailed description are provided in the experimental section below.

Nonspecific binding assay

Many compounds are known to bind nonspecifically to proteins that occur in high abundance in plasma. A fraction of the unbound drug (the free fraction) can be obtained to interact with targets found in tissues. Banker, M.J. et al., Curr. Drug Metab. (2008) 9:854. The ability of a compound to leave a chamber containing plasma and enter a chamber containing only buffer can be assessed by measuring the concentration that appears in the buffer chamber and the concentration that remains in the plasma chamber. These measurements can be used to determine the fraction of the compound that is bound to plasma proteins and its free fraction (100% bound to plasma proteins). The protocol and corresponding detailed instructions for determining nonspecific protein binding in a plasma protein binding assay are provided in the following experimental section.

The results of the primary assays performed with selected fused pyrimidine compounds of the present invention showed that the fused pyrimidine compounds of the present invention exhibited significant inhibitory activity ( _IC50 ) against the enzymatic action of p97 on its natural substrate. Some of these compounds also had greater potency in cell-based assays and had in vitro pharmacokinetic properties consistent with good oral bioavailability. These results are provided in Table II below.

Example

The preparation of representative compounds of the present invention is described in more detail below. The following examples are provided for illustrative purposes and are not intended to limit the present invention in any way. Those skilled in the art will readily recognize a variety of non-critical parameters that can be changed or modified to produce substantially the same results.

Those skilled in the art will recognize or be able to determine the synthesis of many compounds equivalent to those described herein and their methods of use using only routine experimentation. Although certain exemplary embodiments are depicted and described herein, it should be understood that the compounds of the present invention can be prepared according to methods generally available to those of ordinary skill in the art. All references and publications cited above are hereby incorporated by reference.

Unless otherwise stated, all solvents, chemicals and reagents are commercially available and used without purification. 1H NMR spectra are obtained under the following conditions: in CDCl 3 , d 6 -DMSO, CD 3 OD or d 6 -acetone, at 25 ° C, at 300 MHz, on an OXFORD (Varian) spectrometer, where chemical shifts (δ, ppm) are reported relative to TMS as an internal standard. HPLC-MS chromatograms and mass spectra are obtained with a Shimadzu LC-MS-2020 system. The preparative HPLC instrument used to purify some compounds is a Gilson GX-281 (Gilson) or P230 preparative gradient system (Elite). Preparative chira HPLC separations are carried out using an Elite P230 preparative gradient system, Thar Prep-80 or Thar SFC X-5. The reaction using microwave irradiation is carried out on a CEM Discover SP instrument.

Synthesis of 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide FF03:

To a solution of methyl 1H-indazole-4-carboxylate 2 (2.6 g, 14.7 mmol) and N-benzyl-2-chloro-5,6,7,8-tetrahydroquinazolin-4-amine 1 (4 g, 14.7 mmol) in dioxane (150 mL) were added Pd ₂ (dba) ₃ (2.7 g, 2.94 mmol), X-Phos (2.8 g, 5.88 mmol), and CS ₂ CO ₃ (9.6 g, 29.4 mmol). The mixture was degassed three times and then stirred at 100° C. for 12 hours. The resulting mixture was concentrated in vacuo and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 3:1) to give methyl 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylate 3 (2.74 g, 45%). LRMS (M+H+) m/z: Calculated: 414.47; Found: 414.

To a solution of methyl 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylate 3 (2.74 g, 6.63 mmol) in THF (12 mL), MeOH (4 mL), and _H₂O (4 mL) was added LiOH (836 mg, 19.9 mmol). The mixture was then stirred at room temperature for 3 h. The solvent was removed and the solid was dissolved in water, neutralized with HCl (1 M) to pH = 2-3, filtered, and dried to give 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylate 4 (2.3 g, 87%), which was used in the next step without further purification. LRMS (M+ ^H⁺ ) m/z: Calcd: 400.45; Found: 400.

To a solution of 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxylic acid 4 (2.3 g, 5.76 mmol) in DMF (60 mL) were added _NH₄Cl (930 mg, 17.3 mmol), HATU (3.3 g, 8.64 mmol), and _Et₃N (2.4 mL, 17.3 mmol). The reaction solution was then stirred at room temperature overnight. Water was added to the resulting solution, and the solid was filtered, dried, and purified by combiflash (dichloromethane/methanol = 20:1) to give 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide FF03 (1.6 g, 70%). LRMS (M+ ^H⁺ ) m/z: Calcd: 399.46; Found: 399. HPLC purity (214nm): 100%. ¹ HNMR (300MHz, DMSO): δ8.61 (s, 1H), 8.38 (d, J=8.4Hz, 1H), 8.09 (s, 1H), 7.70-7.68 (m, 2H), 7.54 (s, 1H), 7.42-7 .32 (m, 5H), 7.24-7.23 (m, 1H), 4.74 (d, J=5.6Hz, 2H), 2.70-2.68 (m, 2H), 2.50-2.48 (m, 2H), 1.83-1.82 (m, 2H).

Synthesis of 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide compound FF04:

A similar procedure was used to obtain the desired molecule FF04, 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide (60 mg, 52%) as a white solid. LRMS (M+H ⁺ ) m/z: Calcd: 400.16; Found: 401. HPLC purity (214 nm): 98%. ¹ HNMR (400MHz, DMSO): δ8.63 (s, 1H), 8.39 (d, J=5.4Hz, 1H), 8.11 (br, 1H), 7.69 (d, J=4.5Hz, 2H), 7.56 (b r, 1H), 7.41-7.20 (m, 5H), 4.73 (d, J=5.4Hz, 2H), 4.58 (s, 2H), 4.00-3.96 (m, 2H), 2.77 (t, .7=0.3Hz, 2H)

Synthesis of 3-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide FF05:

To a solution of 1H-indole-7-carbonitrile 1 (1.0 g, 7.04 mmol) in THF (30 mL) was added NaH (0.36 g, 9.15 mmol, 60%) at 0°C, and the reaction mixture was stirred at 20° _C for 30 min. Benzenesulfonyl chloride (1.49 g, 8.44 mmol) was then added. The mixture was stirred at room temperature for 2 h. The solution was quenched by adding aqueous _NH4Cl and extracted with EtOAc (300 mL x 2), dried over _Na2SO4 , and concentrated in vacuo. The residue was purified by flash chromatography (PE:EA = 3:1) to give 1-(phenylsulfonyl)-1H-indole-7-carbonitrile 2 (1.83 g, 92%). LRMS (M+H ⁺ ) m/z: Calcd: 282.32; Found: 282.

To a solution of 1-(phenylsulfonyl)-1H-indole-7-carbonitrile 2 (1.83 g, 6.49 mmol) in THF (30 mL) was added n-BuLi (3 mL, 7.14 mmol, 2.4 N) at -80°C, and the reaction mixture was stirred at -60°C for 1 h. Methyl iodide (1.38 g, 9.73 mmol) was then added. The reaction mixture was stirred at ambient for 1 h. The reaction was quenched with aqueous _NH₄Cl and extracted with EA (200 mL x 2), dried _{over Na₂SO₄} , and concentrated in vacuo. The residue was purified by flash chromatography (PE:EA = 3:1) to give 2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 3 (1.83 g, 95%). LRMS (M+ ^H⁺ ) m/z: Calcd: 296.34; Found: 296.

To a solution of 2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 3 (1.6 g, 5.67 mmol) in DCM (15 mL) was added _Br₂ (1.81 g, 11.34 mmol), and the reaction mixture was stirred at ambient temperature for 2 h. The reaction was quenched by the addition of aqueous _NaHCO₃ and extracted with EA (60 mL x 2), dried _{over Na₂SO₄} , and concentrated in vacuo. The residue was purified by flash chromatography (PE:EA = 3:1) to give 3-aus-2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 4 (1.8 g, 85%). LRMS (M+ ^H⁺ ) m/z: Calcd: 375.24; Found: 375. ¹ HNMR (300MHz, CD ₃ OD): δ7.66-7.84 (m, 5H), 7.46-7.58 (m, 3H), 2.66 (s, 3H).

To a solution of 3-ausino-2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 4 (900 mg, 2.4 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 5 (450 mg, 2.4 mmol) in THF (15 mL) was added n-BuLi (1 mL, 2.4 mmol, 2.4 N) at -78°C, and the reaction mixture was stirred at -78°C for 1 h. The solution was then warmed to room temperature and stirred for 1 h. The reaction was quenched by aqueous _NH4Cl solution and extracted with EA (50 mL x 2), _dried over _Na2SO4 , and concentrated in vacuo. The residue was purified by flash chromatography (PE:EA=2:1) to give 2-methyl-1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carbonitrile 6 (760 mg, 75%). LRMS (M+H ⁺ ) m/z: Calcd: 422.31; Found: 422. ¹ HNMR (300MHz, CDCl ₃ ): δ8.28 (d, J=3.6Hz, 1H), 7.97 (t, .7=4.8Hz, 2H), 7.60-7.63 (m, 2H), 7.54 (t, J=5.4Hz, 2H), 7.30 (t, J=7.8Hz, 1H), 2.89 (s, 3H), 1.37 (s, 12H). A mixture of 2-methyl-1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carbonitrile 6 (360 mg, 0.85 mmol), N-benzyl-2-chloro-5,6,7,8-tetrahydroquinazolin-4-amine 7 (232 mg, 0.85 mmol), Pd( _PPh3 ) ₄ (196 mg, 0.17 _mmol ) and _Na2CO3 (176 mg, 1.7 mmol) in dioxane (10 mL) and _H2O (3 mL) was heated at 100°C under nitrogen for 16 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was purified by flash chromatography (PE:EA=1:1) to give 3-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 8 (217 mg, 48%). LRMS (M+H ⁺ ) m/z: Calcd: 533.64; Found: 533.

To a solution of 3-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1-(phenylsulfonyl)-1H-indole-7-carbonitrile 8 (120 mg, 0.22 mmol) in DMSO (5 mL) was added UHP (165 mg, 1.76 mmol), _K2CO3 (15 mg, 0.11 mmol) and water (0.3 mL) at 0°C, and the reaction mixture was stirred overnight at 60 _° C. Water (100 mL) was added to the mixture and dissolved the solid, which was filtered to give the crude product, which was purified by flash chromatography (DCM:MeOH=20:1) to give 3-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-7-carboxamide 65 mg (72%) FF05. LRMS (M+H ⁺ ) m/z: Calculated: 411.5; Found: 411. HPLC purity (214 nm): 97.6%. ¹ HNMR (400MHz, DMSO): δ10.97 (s, 1H), 8.52 (d, J=4.0Hz, 1H), 8.00 (s, 1H), 7.57 (d, J=4.0Hz, 1H), 7.27-7.35 (m, 5H), 7.18 (t, J=7.2H z, 1H), 7.12 (t, J=6.0Hz, 1H), 6.97 (t, J=8.0Hz, 1H), 4.73 (d, J=2.8Hz, 2H), 2.70 (s, 3H), 2.66 (bs, 2H), 2.44 (bs, 2H), 1.81 (bs, 4H).

Synthesis of 1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF06:

At -78 ° C, under a nitrogen atmosphere, to a mixture of tetrahydropyran-2-one 1 (1.0 g, 10 mmol) and thiocyanamide (2.93 g, 40 mmol) in DCM (25 mL) was added dropwise Tf ₂ O (4.23 g, 15 mmol) in DCM (25 mL). After addition, the resulting mixture was stirred at 0 ° C for 3 h, then stirred at room temperature overnight. The volatile phase was removed under reduced pressure. The residue was dissolved in DCM (40 mL), washed with sodium bicarbonate and brine, and dried over sodium sulfate. The organic layer was concentrated under reduced pressure. The residue was applied to a silica gel column eluted with DCM. Thus, 2,4-bis (methylthio) -6,7-dihydro -5H- pyrano [2,3-d] pyrimidine 2 (0.4 g, 17.5%) was obtained as a white solid. LRMS (M+H ⁺ ) m/z: Calculated: 229.0; Found: 229.

To a mixture of 2,4-bis(methylthio)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 2 (0.4 g, 1.75 mmol) in DCM (20 mL) was added m-CPBA (2.47 g, 12 mmol) in batches. The resulting mixture was stirred at room temperature for 5 h. It was quenched with Na ₂ S ₂ O ₃ (5%, 20 mL), and then saturated NaHCO ₃ (20 mL) was carefully added. The mixture was stirred for 30 min. The organic layer was separated. The aqueous layer was extracted with DCM (20 mL × 2). The organic layers were combined, washed with brine, dried over Na ₂ SO ₄ , filtered and concentrated. Thus 0.42 g (82%) of 2,4-bis(methylsulfonyl)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 3 was obtained as a white solid. LRMS (M+H ⁺ ) m/z: Calculated: 293.0; Found: 293.

A mixture of 2,4-bis(methylsulfonyl)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 3 (1.5 g, 5.1 mmol) in 10% NaOH (30 mL) was refluxed for 2 h, then the reaction mixture was acidified with HCl (10%) until pH = 2 and the solid was collected by filtration and washed with H ₂ O. Recrystallization from H ₂ O gave 0.82 g (95.7%) of 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-2,4-diol 4 as a white solid. LRMS (M+H ⁺ ) m/z: calcd: 169.0; found: 169.

A mixture of 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-2,4-diol 4 (0.4 g, 2.4 mmol) in _POCl₃ (10 mL) was stirred at 100°C for 4 h. The volatile phase was removed under reduced pressure. The residue was dissolved in DCM (50 mL), then ice/water was added, washed with _NaHCO₃ and brine, dried over sodium sulfate, filtered, and concentrated. The residue was applied to a silica gel column eluted with PE/EA = 4/1. This gave 0.25 g (50%) of 2,4-dichloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 5 as a white solid. LRMS (M+ ^H⁺ ) m/z: Calcd: 205.0; Found: 205.

A mixture of 2,4-dichloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 5 (0.16 g, 0.8 mmol) and _Et₃N (0.24 g, 2.4 mmol) in DMF (15 mL) was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (50 mL), washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The residue was applied to a silica gel column eluted with PE/EA = 2/1. This afforded 0.16 g (74.5%) of N-benzyl-2-chloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine 6 as a white solid. LRMS (M+ ^H⁺ ) m/z: Calcd: 276.1; Found: 276.

A mixture of N-benzyl-2-chloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine 6 (82 mg, 0.3 mmol), 2-methyl-1H-indole-4-carbonitrile 7 (48 mg, 0.3 mmol), Pd ₂ (dba) ₃ (55 mg, 0.06 mmol), X-Phos (57 mg, 0.12 mmol), and Cs ₂ CO ₃ (196 mg, 0.6 mmol) in dioxane (8 mL) was stirred at 100° C. overnight. The volatile phase was removed under reduced pressure. The residue was applied to a silica gel column eluted with PE/EA=2/1. This gave 80 mg (68%) of 1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 8 as a yellow solid. LRMS (M+H ⁺ ) m/z: calcd: 396.2; found: 396.

A mixture of 1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 8 (72 mg, 0.182 mmol), 1-urea peroxide (112 mg, 1.45 mmol) and K ₂ CO ₃ (13 mg, 0.09 mmol) in DMSO/H 2 O (10 mL/1 mL) was stirred at room temperature for 3 h. The mixture was diluted with 50 mL of water and extracted with ethyl acetate (20 mL×3).

The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was applied to a silica gel column eluted with PE/EA=2/1. 50 mg (66%) of 1-(4-(benzylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF06 were obtained as a yellow solid. LRMS (M+H ⁺ ) m/z: calculated: 414.2; found: 414. HPLC purity (214 nm): 97%. ¹ HNMR (400MHz, DMSO): δ7.88 (d, J=8.0Hz, 1H), 7.75-7.71 (m, 1H), 7.69-7.7.65 (m, 1H), 7.45 (d, J=8.0Hz, 1H), 7.40-7.30 (m, 4H), 7.28 -7.20 (m, 2H), 6.94 (t, J=8.0Hz, 1H), 4.69 (d, J=8.0Hz, 2H), 4.31 (t, J=4.0Hz, 2H), 2.52-2.50 (m, 2H), 2.48 (s, 3H), 2.06-2.02 (m, 3H).

Synthesis of 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF07:

To a solution of pyrido[2,3-d]pyrimidine-2,4-diol 1 (0.80 g, 4.9 mmol) in AcOH/H ₂ O (12 mL/8 mL) was added Pd(OH) ₂ (0.08 g, 0.57 mmol). The mixture was heated at 70° C. overnight under a hydrogen atmosphere. The mixture was filtered to give 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2,4-diol 2 (0.5 g, 61%). LRMS (M+H ⁺ ) m/z: Calcd: 168.07; Found: 168.

A mixture of 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2,4-diol 2 (500 mg, 2.99 mmol) and PCl ₅ (300 mg, 1.5 mmol) in POCl ₃ (10 mL) was heated at 130° C. overnight. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was dissolved in DCM (20 mL) and poured into ice water (20 mL). The oil layer was concentrated in vacuo and the residue was purified by flash chromatography (petroleum: ethyl acetate = 5:1) to give 2,4-dichloro-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine 3 (150 mg, 25%). LCMS (M+H ⁺ ) m/z: Calculated: 204.00; Found: 203.9.

A mixture of 2,4-dichloro-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine 3 (150 mg, 0.74 mmol), DMAP (91 mg, 0.74 mmol) and Boc ₂ O (241 mg, 1.1 mmol) in CH ₃ CN (10 mL) was stirred at room temperature for 0.5 h. The reaction mixture was concentrated in vacuo, and the residue was purified by flash chromatography (petroleum:ethyl acetate=10:1) to give tert-butyl 2,4-dichloro-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 4 (100 mg, 45%). LRMS (M+H) m/z: Calcd: 248.05; Found: 247.9.

To a solution of tert-butyl 2,4-dichloro-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 4 (100 mg, 0.33 mmol) and TEA (100 mg, 0.99 mmol) in CH ₃ CN (10 mL) was added phenylmethylamine (43 mg, 0.39 mmol) stirred overnight at 70° C. The reaction mixture was cooled to room temperature and concentrated in vacuo, and the residue was purified by flash chromatography (petroleum/ethyl acetate) to give tert-butyl 4-(benzylamino)-2-chloro-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 5 (100 mg, 81%). LRMS (M+H+) m/z: Calcd: 375.15; Found: 375.1.

A mixture of tert-butyl 4-(benzylamino)-2-chloro-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 5 (100 mg, 0.27 mmol), 2-methyl-1H-indole-4-carbonitrile 6 (41 mg, 0.32 mmol), tris(dibenzylideneacetone)dipalladium (98 mg, 0.11 mmol), X-phos (26 mg, 0.05 mmol) and _Cs2CO3 (174 mg, 0.54 mmol) in _dioxane (10 mL) was heated at 100°C for 3 hours under nitrogen atmosphere.

The reaction mixture was cooled to room temperature and concentrated in vacuo, and the residue was purified by flash chromatography (petroleum/ethyl acetate) to give tert-butyl 4-(benzylamino)-2-(4-cyano-2-methyl-1H-indol-1-yl)-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 7 (80 mg, 61%). LCMS (M+H ⁺ ) m/z: Calcd: 495.24; Found: 495.2.

To a solution of tert-butyl 4-(benzylamino)-2-(4-cyano-2-methyl-1H-indol-1-yl)-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 7 (80 mg, 0.16 mmol) in DMSO (8 mL) was added UHP (123 mg, 1.29 mmol) and _K2CO3 (12 mg, 0.081 mmol), water (0.5 mL) was added and the reaction was stirred at room temperature for 2 hours _. Water (100 mL) was added to the mixture and the solid formed was filtered to give tert-butyl 4-(benzylamino)-2-(4-carbamoyl-2-methyl-1H-indol-1-yl)-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 8 (60 mg, 70%). LCMS (M+H ⁺ ) m/z: calcd: 513.25; found: 513.

To a solution of tert-butyl 4-(benzylamino)-2-(4-carbamoyl-2-methyl-1H-indol-1-yl)-6,7-dihydropyrido[2,3-d]pyrimidine-8(5H)-carboxylate 8 (60 mg, 0.12 mmol) in EtOAc (2 mL) was added HCl/EA (5 mL, 2N) and stirred at room temperature for 1 hour. The resulting solid was filtered to give 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF07 (20 mg, 40%) as a white solid. LCMS (M+H ⁺ ) m/z: Calcd: 413.2; Found: 413.1. HPLC purity (214 nm): 100%. ¹ HNMR (400MHz, DMSO): δ7.79-7.65(m, 2H), 7.50-7.41(m, 2H), 7.38-7.19(m, 7H), 6.97-6.89(m, 1H), 6.88 -6.79 (m, 1H), 4.62-4.59 (m, 2H), 3.33-3.26 (m, 2H), 2.54-2.52 (m, 2H), 2.45 (s, 3H), 1.94-1.86 (m, 2H).

Synthesis of 1-[4-(benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl]-2-methyl-indole-4-carboxamide FF08:

To a solution of EtOH (400 mL) was added Na (2.66 g, 0.12 mol) in batches. After all sodium was dissolved, ethane-1,1,2-tricarboxylic acid triethyl ester (19 g, 77.16 mmol) and urea (5.1 g, 84.87 mmol) were added sequentially to the reactant. The white suspension was refluxed for 16 h. A large amount of white solid was formed. TLC showed that the reaction was complete. The reaction mixture was filtered and the filter cake was washed with EtOH (200 mL). The filtrate was concentrated in vacuo to obtain the desired 2- (2,4,6- trioxohexahydropyrimidin-5-yl) ethyl acetate (15 g, 81.7%) as a white solid, which was confirmed in the next step. LCMS (MH ⁺ ) m/z: calculated value: 213.05; found value: 213.3.

A white suspension of ethyl 2-(2,4,6-trioxohexahydropyrimidin-5-yl)acetate (19 g, 88.71 mmol) in _POCl₃ (100 mL) was refluxed for 16 h. The reaction mixture turned brown. TLC indicated the reaction was complete. The reaction mixture was concentrated in vacuo. The brown residue was purified by chromatography on a silica gel column (PE:EA = 20:1 to 5:1) to afford the desired ethyl 2-(2,4,6-trichloropyrimidin-5-yl)acetate (1.8 g, 6.8%) as a brown oil. LCMS (M+ ^H⁺ ) m/z: Calcd: 268.97; Found: 269.0.

To a solution of ethyl 2-(2,4,6-trichloropyrimidin-5-yl)acetate (500 mg, 1.86 mmol) in THF (20 mL) was added DIBAL-H (1 M in toluene, 7.42 mL) dropwise at 0°C. The pale yellow solution was stirred at 15°C for 12 h. TLC showed that the reaction was complete. The reaction was quenched with 1N HCl (20 mL). The resulting mixture was extracted with EA (20 mL*3). The combined organic layers were dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE:EA=10:1 to 1:1) to give the desired 2-(2,4,6-trichloropyrimidin-5-yl)ethanol (0.2 g, 42.7%) as a brown solid. LCMS (M+H ⁺ ) m/z: calculated: 226.95; found: 227.0

To a colorless solution of 2-(2,4,6-trichloropyrimidin-5-yl)ethanol (500 mg, 2.2 mmol) in anhydrous THF (50 mL) was added NaH (131.87 mg, 3.3 mmol, 60% in mineral oil) at room temperature. The reaction mixture was stirred at room temperature overnight. TLC showed that the reaction was complete. The reaction was quenched by adding saturated NH ₄ Cl (20 mL) and then extracted with EA (20 mL*3). The combined organic layers were dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by preparative TLC to give the desired 2,4-dichloro-5,6-dihydrofuro[2,3-d]pyrimidine (0.1 g, 21.4%) as a white solid. LCMS (M+H ⁺ ) m/z: calculated value: 190.97; found value: 191.1

A colorless solution of 2,4-dichloro-5,6-dihydrofuro[2,3-d]pyrimidine (90 mg, 0.47 mmol), phenylmethylamine (55.54 mg, 0.52 mmol) and TEA (57.21 mg, 0.57 mmol) in MeCN (25 mL) was refluxed for 16 h. LCMS showed the reaction was complete. The reaction mixture was concentrated in vacuo and purified by preparative TLC (PE:EA=1:1) to give the desired N-benzyl-2-chloro-5,6-dihydrofuro[2,3-d]pyrimidin-4-amine (50 mg, 36.5%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.30 (m, 5H, Ph ), 5.50 (s, 1H, NH ), 4.63 (m, 4H, NH CH ₂ , O CH ₂ ), 3.18 (m, 2H, Ph CH ₂ ). LRMS (M+H ⁺ ) m/z: calcd: 262.07; found: 262.1.

A _red suspension of N-benzyl-2-chloro-5,6-dihydrofuro[2,3-d]pyrimidin-4-amine (45 mg, 0.17 mmol), 2-methyl-1H-indole-4-carbonitrile (32.23 mg, 0.21 mmol), _Pd (dba) ₍ 31.49 mg, 0.03 mmol), _{KCO (} 47.53 mg, 0.34 mmol) and X-Phos (16.39 mg, 0.03 mmol) in dioxane (5 mL) was refluxed for 2 h under N. LCMS showed the reaction was complete. The reaction was filtered and the filtrate was concentrated in vacuo. The crude product was purified by preparative TLC (PE:EA=5:1) to give the desired 1-[4-(benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl]-2-methyl-indole-4-carbonitrile (50 mg, 68.6%) as a light yellow solid. LRMS (M+H ⁺ ) m/z: Calcd: 382.16; Found: 382.2

A pale yellow solution of 1-[4-(benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl]-2-methyl-indole-4-carbonitrile (45 mg, 0.12 mmol), UHP (55.49 mg, 0.59 mmol) and K ₂ CO ₃ (16.31 mg, 0.12 mmol) in DMSO (20 mL) and H ₂ O (1 mL) was stirred at 15° C. for 2 h. TLC showed the reaction was complete. EA (20 mL) and brine (20 mL) were added to the reaction. The organic layer was separated and washed with brine (20 mL*3), dried over Na ₂ SO ₄ and concentrated in vacuo. The yellow residue was purified by preparative TLC to give the desired 1-[4-(benzylamino)-5,6-dihydrofuro[2,3-d]pyrimidin-2-yl]-2-methyl-indole-4-carboxamide FF08 as a white solid (30 mg, 63.7%). ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.28 (d, 1H, Ph ), 7.49 (d, 1H, Ph ), 7.43-7.30 (m, 5H, CH ₂ Ph ), 7.10 (m, 1H, Ph ), 6.83 (s, 1H, 3- H indole ), 6.15 (s, 2H, NH ₂ ), 4.98 (s, 1H, NH ), 4.81-4.61 (m, 4H, OCH ₂ +NHCH ₂ ), 3.08 (m, 2H, CH ₂ ). 2.74-2.57 (s, 3H, CH ₃ ). LRMS (M+H ⁺ ) m/z: calcd: 400.18; found: 400.2.

Synthesis of 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF09:

To a mixture of 2,4-dichloro-6,7-dihydro-5H-pyrans and [2,3-d] pyrimidine (250 mg, 1 mmol) in ACN (20 mL) was added DIPEA (464 mg, 4 mmol) and compound 2 (604 mg, 5 mmol). The reaction mixture was refluxed for 16 h. TLC (PE: EA = 2: 1) showed that the reaction was complete. The mixture was then concentrated and purified by silica gel (PE: EA = 6: 1 to 3: 1) to obtain the desired 2-chloro-N-(3-fluorobenzyl)-6,7-dihydro-5H-pyrans and [2,3-d] pyrimidine-4-amine (240 mg, 67.67%) as a white solid. LCMS (M+H ⁺ ) m/z: calculated: 294.07; found: 294.1.

To a solution of 2-chloro-N-(3-fluorobenzyl)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine (820 mg, 3 mmol) in dioxane (150 mL) were added 2-methyl-1H-indole-4-carbonitrile (654 mg, 4 mmol), _Cs2CO3 (1.819 g, 6 mmol), X-Phos (532 mg, 1 mmol), and _Pd2 (dba) ₃ (767 mg, 0.838 mmol). _The resulting mixture was stirred at 100°C under _N2 for 12 h. TLC (PE:EA=1:1) indicated the reaction was complete. The mixture was then filtered, and the filtrate was concentrated and purified on silica gel (PE:EA=10:1) to give the desired 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile (600 mg, 52%). LCMS (M+H ⁺ ) m/z: calculated: 414.17; found: 414.2.

To a mixture of 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile (0.6 g, 1 mmol) in DMSO (50 mL) was added UHP (0.697 g, 7 mmol) and K ₂ CO ₃ (0.1 g, 0.726 mmol). The reaction mixture was stirred for 10 min. H ₂ O (5 mL) was then added and stirred at 25° C. for 12 h. TLC (PE:EA=1:2) indicated the reaction was complete. H ₂ O (500 mL) was then added, followed by extraction with EA (200 mL*3). The combined organic phases were concentrated and purified on silica gel (PE:EA=5:1 to 1:1) to give a crude product, which was washed with ACN (10 mL), filtered, and concentrated to give the desired 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF09 (0.2 g, 31.3%). LCMS (M+H ⁺ ) m/z: Calcd: 432.18; Found: 432.2. ¹ H NMR (400 MHz, CD ₃ OD): δ 7.73 (d, J = 8.4 Hz, 1H, Ph ), 7.47 (d, J = 7.2 Hz, 1H, Ph ), 7.34 (m, 1H, Ph ), 7.16-7.14 (d, J = 7.2 Hz, 1H, Ph ), 7.04 (m, 1H, Ph ), 7.00-6.97 (m, 2H, Ph ), 6.77 (s, 1H, 3- H of indole), 4.73 (s, 2H, PhC H ₂ NH), 4.40-4.38 (m, 2H, OCH ₂ CH ₂ CH ₂ ), 2.61-2.58 (m, 2H, OCH ₂ CH ₂ CH ₂ ), 2.46 (s, 3H, NCC H ₃ ), 2.17-2.14(m, 2H, OCH ₂ CH ₂ CH ₂ ).

Synthesis of 3-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl-2-methyl-1H-indole-7-carboxamide FF10:

To a solution of 2,4-dichloro-7,8-dihydro-5H-pyrano[4,3-d]pyrimidine (1 g, 4.877 mmol) in ACN (50 ml) was added BnNH ₂ (0.78 g, 7.316 mmol). The mixture was stirred at 25 ° C for 12 h under N _2. TLC showed that the reaction was complete. The reaction was concentrated in vacuo and purified by column chromatography (PE/EA=10/1 to 5/1) to give the desired N-benzyl-2-chloro-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine (0.85 g, 60.5% yield) as a white solid.

To a solution of N-benzyl-2-chloro-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine (300 mg, 1.09 mmol) and 1-(phenylsulfonyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-7-carbonitrile (551 mg, 1.31 mmol) in dioxane (10 mL) and H ₂ O (2 mL) was added K ₂ CO ₃ (300 mg, 2.17 mmol) and Pd(PPh ₃ ) ₄ (126 mg, 0.11 mmol). Under N ₂ , the mixture was stirred at 100 ° C for 3 h. TLC showed that the reaction was complete. The mixture was diluted with EA (20 mL) and H ₂ O (5 mL). The organic phase was separated, dried _{over Na2SO4} , concentrated and purified by column chromatography (PE:EA=10:1 to pure EA) to give the desired 1-(phenylsulfonyl)-3-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-indole-7-carbonitrile (300 mg, 50.5%) as a white solid. LCMS (M+H ⁺ ) m/z: Calcd: 536.17; Found: 536.2.

To a solution of 1-(phenylsulfonyl)-3-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-indole-7-carbonitrile (150 mg, 280 mmol) in DMSO (10 mL) and _H₂O (0.2 mL) was added UHP (130 mg, 1.4 mmol) and _K₂CO₃ (19 _mg , 140 mmol). The mixture was stirred at 60°C for 12 h. TLC showed 10% of 1-(phenylsulfonyl)-3-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-indole-7-carbonitrile remaining. The mixture was poured into _H₂O (100 mL) and extracted with EA (50 mL*2).

The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , concentrated to dryness in vacuo and purified by column chromatography (PE:EA=5:1 to 100% EA) to give the desired 3-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl-2-methyl-1H-indole-7-carboxamide FF10 (60 mg, 50.3%). LCMS (M+H ⁺ ) m/z: Calcd: 414.19; Found: 414.3. ¹ HNMR (400MHz, CDCl ₃ ): δ11.05 (s, 1H, CON H ₂ ), 8.53 (d, J=8.0Hz, 1H, C ₆ H ₃ ), 8.02 (s, 1H, CON H ₂ ), 7.57-7.59 (m, 1H, C ₆ H ₃ ), 7.31-7.35 (m, 5H, C ₆ H ₅ ), 7.20-7.21 (m, 1H, C ₆ H ₃ ), 7.14-7.15 (m, 1H, N H ), 6.99-7.02 (m, 1H, N H ), 4.72-4.73 (d, J=7.2Hz, 2H, CH ₂ ), 4.55 (s, 2H, CH ₂ ), 3.96 (t, J=5.6Hz, CH ₃ ), 2.72-2.73 (m, 5H, CH ₂ , CH ₃ )

Synthesis of 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide FF11:

The mixture of 3-aminopicolinic acid (5.00 g, 36.2 mmol) and urea (10.9 g, 181 mmol) in a 100 mL flask was stirred at 170 ° C for 6 h. The reaction mixture was changed from a clear solution to a suspension. The reaction mixture was then cooled to 25 ° C and filtered. The filter cake was washed with water (50 mL) and dried to obtain the desired pyrido [3,2-d] pyrimidine -2,4- diol (3.2 g, 74.5%) as a white solid. ¹ HNMR (400MHz, CDCl ₃ ): δ 11.66 (s, 1H, O H ), 11.16 (s, 1H, O H ), 8.59 (d, J = 2.4Hz, 1H, C ₆ H ₃ ), 8.25 (d, J = 8.4Hz, 1H, C ₆ H ₃ ), 7.24 (t, J = 2.4Hz, 1H, C ₆ H ₃ ).

A mixture of pyrido[3,2-d]pyrimidine-2,4-diol (5.0 g, 0.031 mol), _POCl₃ (150 mL) and _PCl₅ (25.5 g, 0.128 mol) was stirred at 130° C. for 3 h. TLC showed the reaction was complete. It was concentrated in vacuo, and the residue was dissolved in DCM (1000 mL) and then poured into _H₂O (400 _mL ). The organic layer was separated, washed with saturated _Na₂CO₃ (400 mL), _dried over _Na₂SO₄ , filtered, concentrated in vacuo and purified by column chromatography (PE:EA=10:1 to PE:EA=3:1) to give pure desired 2,4-dichloropyrido[3,2-d]pyrimidine (3.5 g, 57.4%) as a yellow solid. ¹ HNMR (400MHz, CDCl ₃ ): 9.33 (t, J=2.4Hz, 1H, C ₆ H ₃ ), 8.64 (d, J=7.6Hz, 1H, C ₆ H ₃ ), 7.71-7.75 (m, 1H, C ₆ H ₃ ).

To the yellow solution of 2,4-dichloropyrido [3,2-d] pyrimidine (500mg, 2.5mmol) in anhydrous THF (30ml), (3-fluorophenyl) methylamine (344mg, 2.75mmol) and TEA (379mg, 3.75mmol) were added. Then under N ₂ , the mixture was stirred at 60 ° C for 1h. TLC showed that the reaction was complete. The reaction mixture was concentrated in vacuo to dryness to obtain crude 2-chloro-N-[(3-fluorophenyl) methyl] pyrido [3,2-d] pyrimidine-4-amine (0.72g, 84.8%) as a yellow solid.

To a yellow suspension of 2-chloro-N-[(3-fluorophenyl)methyl]pyrido[3,2-d]pyrimidin-4-amine (0.72 g, 2.5 mmol) in EtOH (50 ml) was added PtO ₂ (110 mg). The mixture was then stirred at 60° C. under H ₂ (15 psi) for 6 h. TLC showed a 1:1 ratio of product:2-chloro-N-[(3-fluorophenyl)methyl]pyrido[3,2-d]pyrimidin-4-amine. The catalyst was removed by filtration. The filtrate was concentrated to dryness in vacuo and purified by column chromatography (PE:EA=5:1 to 1:1) to give the desired 2-chloro-N-[(3-fluorophenyl)methyl]-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-4-amine (300 mg, 37%) as a white solid.

To a white suspension of 2-chloro-N-[(3-fluorophenyl)methyl]-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-4-amine (250 mg, 0.854 mmol) in anhydrous THF (10 mL) was added paraformaldehyde (153.85 mg, 1.708 mmol) and one drop of AcOH. The white suspension was then stirred at 20° C. for 3 h. NaBH(OAc) ₃ (362 mg, 1.708 mmol) was added to the above mixture. The mixture was then stirred at 80° C. for 9 h. LCMS and TLC showed that 2-chloro-N-[(3-fluorophenyl)methyl]-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-4-amine:product=1:2. The white suspension was filtered through celite and the filtrate was concentrated to dryness in vacuo and purified by column chromatography (PE:EA=10:1 to 1:1) to give the desired 2-chloro-N-[(3-fluorophenyl)methyl]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-4-amine (200 mg, 57%) as a colorless oil. LCMS (M+H ⁺ ) m/z: calcd: 307.11; found: 307.10. ¹ HNMR (400MHz, CDCl ₃ ): δ7.32 (t, J=6.0Hz, 1H, C ₆ H ₄ ), 7.13 (d, J=7.6Hz, 1H, C ₆ H ₄ ), 7.06-7.00 (m, 2H, C ₆ H ₄ ), 5.67 (s, 1H, N H ), 4.69 (d, J=7.2Hz, 2H, CH ₂ Ph), 2.96-3.02 (m, 2H, CH ₂ ), 2.71-2.74 (m, 2H, CH ₂ ), 2.58 (s, 3H, CH ₃ ), 1.95-1.99 (m, 2H, CH ₂ ).

To a solution of 2-chloro-N-[(3-fluorophenyl)methyl]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-4-amine (50 mg, 0.16 mmol) and 1H-indazole-4-carbonitrile (25.66 mg, 0.18 mmol) in anhydrous dioxane (10 mL) were added X-Phos (15.52 mg, 0.033 mmol), Pd ₂ dba ₃ (29.83 mg, 0.033 mmol) and Cs ₂ CO ₃ (106.92 mg, 0.326 mmol). The mixture was then stirred at 100° C. under N ₂ for 12 hours. TLC showed the product: 2-chloro-N-[(3-fluorophenyl)methyl]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-4-amine = 1:1. The mixture was filtered through celite, concentrated to dryness in vacuo and purified by column chromatography (PE:EA=10:1 to 1:1) to give the desired 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]indazole-4-carbonitrile (20 mg, 23.7%) as a yellow oil. LCMS (M+H ⁺ ) m/z: calcd: 414.18; found: 414.2.

To a yellow solution of 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]indazole-4-carbonitrile (20 mg, 0.05 mmol) in DMSO (3 mL) and H ₂ O (0.3 mL) was added UHP (22.74 mg, 0.242 mmol) and K ₂ CO ₃ (3.338 mg, 0.024 mmol). The mixture was then stirred at 20° C. for 2 h. TLC showed the reaction was complete. H ₂ O (30 ml) and EA (20 mL) were added to the above mixture. The organic phase was separated and the aqueous layer was extracted with EA (10 mL*2). The combined organic layers were washed with brine (15 mL*5), dried over _Na2SO4 , concentrated to dryness in _vacuo , and purified by preparative TLC (EA:MeOH=3:1) to give the desired 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]indazole-4-carboxamide FF11 (6 mg, 26.4%) as a white solid. LCMS (M+H ⁺ ) m/z: calcd: 432.19; found: 432.3. ¹ HNMR (400MHz, CDCl ₃ ): δ8.73 (s, 1H, CH ), 8.55 (d, J=8.0Hz, 1H, C ₆ H ₄ ), 7.34-7.54 (m, 3H, C ₆ H ₄ ) , 7.01-7.22 (m, 3H, C ₆ H ₃ ), 6.12 (s, 2H, CON H ₂ ), 5.86 (s, 1H, N H ), 3.10 (m, CH ₂ ), 2.93 (m, CH ₂ ), 2.69 (s, CH ₃ ), 1.62 (s, CH ₂ ).

Synthesis of 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF12:

To a solution of 2-chloro-N-[(3-fluorophenyl)methyl]-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-4-amine (500 mg, 1.71 mmol) in anhydrous THF (50 mL) was added (HCHO) _m (923 mg, 10.27 mmol) and AcOH (5 drops). The mixture was then stirred at 25° C. with a drying tube for 8 h. NaBH ₃ CN (644 mg, 10.27 mmol) was then added. The mixture was stirred at 80° C. for another 48 h. The mixture was quenched with H ₂ O (20 mL) and extracted with EA (50 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , concentrated to dryness in vacuo and purified by column chromatography (PE:EA=10:1 to 5:1) to give the desired 2-chloro-N-[(3-fluorophenyl)methyl]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-4-amine (340 mg, 60.3%) as a red oil. LCMS (M+H ⁺ ) m/z: calcd: 307.11; found: 307.10. ¹ HNMR (400MHz, CDCl ₃ ): δ7.32 (t, J=6.0Hz, 1H, C ₆ H ₄ ), 7.13 (d, J=7.6Hz, 1H, C ₆ H ₄ ), 7.06-7.00 (m, 2H, C ₆ H ₄ ), 5.62 (s, 1H, N H ), 4.69 (d, J=7.2Hz, 2H, CH ₂ Ph), 2.96-3.02 (m, 2H, CH ₂ ), 2.71-2.74 (m, 2H, CH ₂ ), 2.58 (s, 3H, CH ₃ ), 1.93-1.99 (m, 2H, CH 2 ).

To a suspension of 2-chloro-N-[(3-fluorophenyl)methyl]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-4-amine (100 mg, 0.326 mmol) and 2-methyl-1H-indole-4-carbonitrile (61 mg, 0.392 mmol) in dioxane (10 mL) were added _Pd2 (dba) ₃ (60 mg, 0.065 mmol), X-Phos (31 mg, 0.065 mmol), and _Cs2CO3 (214 _mg , 0.978 mmol). The mixture was then stirred at 100°C under _N2 for 12 h. LCMS showed a product:byproduct (298) ratio of 4:1. The mixture was diluted with _H2O (10 mL) and extracted with EA (10 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , concentrated to dryness in vacuo and purified by preparative HPLC (TFA) to give the desired 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]-2-methyl-indole-4-carbonitrile (100 mg, 68.3%) as a white solid. LCMS (M+H ⁺ ) m/z: calcd: 427.20; found: 427.1.

To a solution of 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]-2-methyl-indole-4-carbonitrile (90 mg, 0.211 mmol) in DMSO (10 mL) and H ₂ O (1 mL) was added UHP (99 mg, 1.055 mmol) and K ₂ CO ₃ (15 mg, 0.105 mmol). The mixture was stirred at 20° C. for 4 h. TLC showed the reaction was complete. The mixture was quenched with H ₂ O (20 mL) and extracted with EA (10 mL*3). The combined organic layers were washed with brine (10 mL*5), dried over _Na2SO4 , concentrated to dryness in vacuo and purified by preparative TLC (PE _: EA=1:3) to give the desired 1-[4-[(3-fluorophenyl)methylamino]-5-methyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-2-yl]-2-methyl-indole-4-carboxamide FF12 (30 mg, 33.8%) as a white solid. LCMS (M+H ⁺ ) m/z: calcd: 445.22; found: 445.3. ¹ HNMR (400MHz, CDCl ₃ ): δ8.06 (d, J=8.0Hz, 1H, C ₆ H ₃ ), 7.51 (d, J=7.2Hz, 1H, C ₆ H ₃ ), 7.28-7.33 (m, 1H, C ₆ H ₃ ), 7.00-7.14 (m, 4H, C ₆ H ₄ ), 6.80 (s, 1H, CH ), 6.08 (s, 2H, CON H ₂ ), 5.77 (s, 1H, N H ), 4.74 (d, J=6.0Hz, 2H, PhC H ₂ ), 3.08-3.12 (m, 2H, CH ₂ ), 2.81-2.86 (m, CH ₂ ), 2.71(s, 3H, C H ₃ ), 2.59 (s, 3H, CH ₃ ), 2.04-2.06 (m, 2H, CH ₂ ).

Synthesis of 1-(4-(benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF13:

Under _N₂ , a solution of _BnNH₂ (50.0 g, 0.47 mol) and methyl methacrylate (56.04 g, 0.560 mol) in MeOH (1000 mL) was stirred at 25° C. for 5 h. TLC indicated 70% SM remained. The solution was then heated to reflux and stirred overnight. TLC indicated the reaction was complete. The solution was then concentrated in vacuo to afford methyl 3-(benzylamino)-2-methylpropanoate 2 (60 g, 62%) as a pink oil.

A solution of compound 2 (60.0 g, 0.29 mol) and methyl acrylate (30.0 g, 0.35 mol) in MeOH (800 mL) was heated to reflux and stirred overnight. TLC showed that the reaction was complete. The solution was then concentrated in vacuo to obtain the crude product 3-(benzyl(3-methoxy-3-oxopropyl)amino)-2-methylpropanoic acid methyl ester 3 (70 g, purity approximately 80%) as a pink oil.

To a solution of compound 3 (20 g, 68.18 mol) in toluene (300 ml) was slowly added NaH (3.272 g, 81.81 mmol). Under N ₂ , the mixture was stirred at 90 ° C for 12 h. TLC showed that the reaction was complete. After cooling, the reaction solution was quenched with 100 mL of water and then extracted with EA (200 mL * 2). The combined organic phases were concentrated in vacuo and purified by silica gel column chromatography (PE: EA = 50: 1 to 25: 1) to obtain 1-benzyl-5-methyl-4-oxopiperidine-3-carboxylic acid methyl ester 4 (13.6 g, 76.4%) as a colorless oil. LCMS (M+H ⁺ ) m / z: calculated value: 262.14; found value: 262.2.

To a solution of compound 4 (15 g, 0.06 mol) in MeOH (200 mL) was slowly added urea (6.89 g, 0.11 mol) and NaOMe (15.51 g, 0.29 mol). Under N ₂ , the mixture was stirred at 70 ° C for 16 h. TLC showed that the reaction was complete. The mixture was then cooled to room temperature and then filtered. The filter cake was washed with EtOH (100 mL * 2) and dried in vacuo to obtain the product 6-benzyl-8-methyl-5,6,7,8-tetrahydropyrido [4,3-d] pyrimidine-2,4 (1H, 3H) dione 5 (6.3 g, 40%) as a white solid. LCMS (M+H ⁺ ) m / z: calculated value: 272.14; found value: 272.10.

A solution of compound 5 (3.0 g, 0.011 mol) in _POCl₃ (100 mL) was stirred at 120° C. for ₄ h. LCMS showed the reaction was complete; the mixture was concentrated in vacuo to give a residue. It was diluted with EA (200 mL) and poured into _H₂O (50 mL). The organic layer was separated, dried over _Na₂SO₄ , filtered, and concentrated to give crude compound 6, which was suspended in MTBE (50 mL) and filtered to give pure 6-benzyl-2,4-dichloro-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine 6 (2.0 g, 54.58%) as a yellow solid. LCMS (M+ ^H⁺ ) m/z: Calcd: 308.06; Found: 308.1.

To a solution of compound 6 (4.1 g, 0.013 mol) in DCE (150 mL) was added 1-chloroethyl chloroformate (38.04 g, 0.266 mol) under N at ₂₅ ° C. The mixture was refluxed for 48 h. LCMS showed that the reaction was complete; it was concentrated to dryness and dissolved in anhydrous MeOH (150 mL) and stirred at 25 ° C for 12 h. LCMS showed that the reaction was complete; it was concentrated to dryness in vacuo to give a crude product. It was suspended in EA (5 mL) and filtered to give pure 2,4-dichloro-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine 7 (2.0 g, 68%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calculated: 218.02; found: 218.1.

A mixture of compound 7 (2.0 g, 9.171 mmol), Boc ₂ O (2.999 g, 13.76 mmol), and Et ₃ N (1.853 g, 18.34 mmol) in DCM (120 mL) was stirred at 25° C. for 3 h. TLC and LCMS showed the reaction was complete. The reaction mixture was concentrated to give a residue, which was suspended in MTBE (20 mL) and filtered to give pure tert-butyl 2,4-dichloro-8-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 8 (2.1 g, 72%) as a yellow solid. LCMS (M+H ⁺ ) m/z: Calcd: 318.02; Found: 318.1.

To a solution of compound 8 (1.9 g, 5.971 mmol) and TEA (1.206 g, 11.94 mmol) in ACN (50 mL) was added BnNH ₂ (0.768 g, 7.165 mmol). The mixture was stirred at 85 ° C for 3.5 h. TLC and LCMS showed that the reaction was complete, and it was concentrated in vacuo to give a residue, which was purified by column chromatography (PE/EA=10/1 to 5/1) to give tert-butyl 4-(benzylamino)-2-chloro-8-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 9 (1.9 g, 82%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calculated value: 389.17; found value: 389.2.

A mixture of compound 9 (389 mg, 1 mmol), 2-methyl-4-nitrile-indole (0.203 g, 1.3 mmol), Pd ₂ (dba) ₃ (0.275 g, 0.3 mmol), X-Phos (0.187 g, 0.4 mmol) and Cs ₂ CO ₃ (0.652 g, 2 mmol) in dioxane (50 mL) was stirred at 100° C. for 2 h under N _2. TLC showed that the reaction was complete. It was concentrated to give a residue, which was purified by column chromatography (PE/EA=5/1) to give tert-butyl 4-(benzylamino)-2-(4-cyano-2-methyl-1H-indol-1-yl)-8-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 10 (0.34 g, 67%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calcd: 509.27; found: 509.3.

A solution of compound 10 (0.28 g, 0.551 mmol) in TFA (20 mL, 20% in DCM) was stirred at 25° C. for 12 h. LCMS showed the reaction was complete, and the mixture was poured into saturated NaHCO ₃ (250 mL) and extracted with EA (100 mL*2). The combined organic phases were dried over Na ₂ SO ₄ , filtered, and concentrated to afford 1-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 12 (0.13 g, 60%) as a yellow solid. LCMS (M+H ⁺ ) m/z: Calcd: 409.21; Found: 409.3.

A mixture of compound 12 (110 mg, 0.269 mmol), (CH ₂ O) n (72.71 mg, 0.808 mmol) and three drops of AcOH in THF (40 mL) was stirred at 25° C. for 3 h, and then NaBH ₃ (AcO) ₃ (171.26 mg, 0.808 mmol) was added to the mixture. The reaction was stirred at 90° C. for 12 h. LCMS showed that the reaction was complete, and it was concentrated in vacuo to give a residue, which was purified by preparative TLC to give 1-(4-(benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 13 (0.095 g, 83.5%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calcd: 423.23; found: 423.3.

A mixture of compound 13 (95 mg, 0.098 _{mmol), UHP (0.106 g, 0.001 mol), and K₂CO₃ (0.031 g, 0.225 mmol) in DMSO/H₂O ( 6.0} mL, V/V, 10/1) was stirred at 25° C. for 12 h. LCMS showed the reaction was complete. It was poured into _H₂O (15 mL) and extracted with EA (25 mL*2). The combined organic phases were dried _{over Na₂SO₄} , filtered, and concentrated to give a residue. It was purified by preparative TLC to give 1-(4-(benzylamino)-6,8-dimethyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide FF13 (35 mg, 35.3%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calcd: 441.2; found: 441.3. ¹ HNMR (400MHz, DMSO-d ₆ ): δ7.81 (t, J=8.4Hz, 1H, Ph), 7.68-7.60 (m, 2H, CON H ₂ ), 7.44-7.73 (m, 1H, Ph), 7.34-7.24 (m, 5H, Ph), 6.91-6.84 (m, 2H, Ph), 4.64 (d, J=6.4Hz, 2H, CH ₂ Ph), 3.45-3.31 (m, 4H, CH ₂ NC H ₂ ), 2.87-2.83(m, 2H, CH CH ₃ +N H ), 2.54 (s, 3H, N CH ₃ ), 2.37 (s, 3H, CH ₃ ), 1.30 (d, J=2.8Hz, 3H, CH ₃ CH).

Synthesis of 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide FF14:

Under N ₂ , urea (9.17 g, 152.76 mmol) was added to a solution of 2-oxocyclohexane-ethyl formate (20.00 g, 117.50 mmol) in EtOH (250.00 mL) at room temperature. The solution was stirred at room temperature for 5 min. Then, MeONa (12.70 g, 235.01 mmol) in MeOH (200 mL) was added at one time. The white suspension was heated to 80 ° C and stirred for 16 h. A white solid precipitated during stirring. TLC showed that the reaction was complete. The suspension was then filtered. The filter cake was washed with MTBE (50 mL * 2) and then dried in vacuo to obtain the desired 5,6,7,8-tetrahydroquinazoline-2,4 (1H, 3H) -dione as a white powder: (14.00 g, 65% yield, 90% ¹ HNMR purity). ¹ HNMR (400 MHz, CD ₃ OD): δ (br s, 2H, CON H ), 2.38 (m, 2H, CH ₂ CH ₂ CCONH), 2.30 (m, 2H, CH ₂ CH ₂ CNHCO), 1.71 (m, 4H, CH ₂ CH ₂ CH ₂ CH ₂ ).

A suspension of 5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)dione (25.0 g, 0.151 mol) in POCl ₃ (100 mL) was heated to 120° C. and stirred for 2 h. TLC showed that the reaction was complete. The mixture was then concentrated in vacuo. The residue was dissolved in EtOAC (200 mL) at 0° C. and slowly poured into saturated NaHCO ₃ (500 mL). The organic phase was then separated and the aqueous phase was extracted with EtOAc (200 mL*2). The combined organic phases were dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by silica gel column (PE/EtOAc=20/1 to 10/1) to obtain 2,4-dichloro-5,6,7,8-tetrahydroquinazoline (10.3 g, 99.9% HPLC purity) as a white powder. ¹ HNMR (300MHz, CDCl ₃ ): δ 2.89 (m, 2H, CH ₂ CH ₂ CCONH), 2.73 (m, 2H, CH ₂ CH ₂ CNHCO), 1.88 (m, 4H, CH ₂ CH _{2 CH 2} CH2).

A mixture of 2,4-dichloro-5,6,7,8-tetrahydroquinazoline (1.0 g, 4.9 mmol), (3-fluorophenyl)methanamine (796 mg, 6.37 mmol) and TEA (1.48 g, 14.7 mmol) in MeCN (50 ml) was refluxed under _N for 4 h. TLC showed that the reaction was almost complete. The reaction was concentrated in vacuo and purified by column chromatography (PE/EA=10/1 to 5/1) to give the desired 2-chloro-N-(3-fluorobenzyl)-5,6,7,8-tetrahydroquinazoline-4-amine (800 mg, 56% yield) as a white solid. LCMS (M+H ⁺ ) m/z: calculated: 292.10; found: 292.1.

A mixture of 2-chloro-N-[(3-fluorophenyl)methyl]-5,6,7,8-tetrahydroquinazolin-4-amine (20 mg, 68.5 umol), 1H-indazole-4-carbonitrile (12 mg, 82.3 umol) _{, Pd2} ( _dba ) ₃ (13 mg, 13.7 umol), _Cs2CO3 (67 mg, 206 umol) and X-Phos (7 mg, 13.7 umol) in dioxane (5 ml) was stirred at 100°C for 4 h under N2. TLC showed SM:TM=2:1. The reaction mixture was concentrated in vacuo and purified by column chromatography (PE/EA = 10/1 to 5/1) to give 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carbonitrile (20 mg, 73%) as a pale yellow solid. LCMS (M+H+) m/z: calcd: 399.17; found: 399.2. _A mixture of 1-[4-[(3-fluorophenyl)methylamino]-5,6,7,8-tetrahydroquinazolin-2-yl]indazole-4-carbonitrile (90 mg, 0.23 mmol), UHP (21.25 mg, 0.23 mmol ₎ and _K2CO3 (31.22 mg, 0.23 mmol) in DMSO (10 ml) and _H2O (1 mL) was stirred at 20°C for 16 h under N2. TLC showed the reaction was almost complete. The reaction was concentrated in vacuo and purified by preparative HPLC ( _H2O , MeCN, HCl) to give the desired 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-1H-indazole-4-carboxamide FF14 (20 mg, 21.3%) as a white solid. LCMS (M+H ⁺ ) m/z: Calcd: 417.18; Found: 417.2. ¹ HNMR (400MHz, DMSO-d ₆ ): δ9.11 (s, 1H, CON H ₂ ), 8.91 (s, 1H, 3- H of pyrazole), 8.30-8.26 (m, 2H, Ph), 7.87-7.85 (m, 1H, Ph), 7.71 (s, 1H, CON H ₂ ), 7.56-7.54 (m, 1H, Ph), 7.43-7.42 (m, 2H, Ph), 7.09 (m, 1H, CH ₂ N H ), 4.88-4.87 (m, 2H, CH ₂ NH), 2.82 (s, 2H, NCC H ₂ ), 1.84 (s, 4H, CH ₂ CH H ₂ CH ₂ CH ₂ ).

Synthesis of 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide FF15:

To the mixture of compound 1 (13g, 0.057mol) in DCM (650mL) was added m-CPBA (73.69g, 0.342mol) in batches. The obtained mixture was stirred at room temperature overnight. _LCMS showed that the reaction was complete. It was filtered and the filtrate was quenched with 5% _Na2S2O3 ( _500mL ), and then saturated _NaHCO3 (500mL) was carefully added. The organic phase was separated, washed with brine (300mL), _dried over _Na2SO4 , filtered and concentrated to obtain crude compound 2. It was slurried with EA (100mL) and filtered to obtain pure 2,4-bis (methylsulfonyl) -6,7- dihydro -5H- pyrans also [2,3-d] pyrimidine 2 (15g, 72%) as a white solid. LCMS (M+H ⁺ ) m/z: calculated value: 293.03; found value: 293.0.

A mixture of compound 2 (10.0 g, 0.034 mol) in 10% NaOH (200 mL) was refluxed for 3 h. TLC indicated the reaction was complete, and the mixture was acidified with HCl (10%) until pH 2 and the solid was collected by filtration to afford 6,7-dihydro-1H-pyrano[2,3-d]pyrimidine-2,4(3H,5H)dione 3 (3.5 g, 60.8%) as a white solid. LCMS (M+H ⁺ ) m/z: Calcd: 169.06; Found: 169.10.

A mixture of compound 3 (3.5 g, 0.021 mol) in POCl ₃ (80 mL) was stirred at 100 ° C for 12 h. TLC showed that the reaction was complete, and the mixture was concentrated in vacuo to give a residue, which was diluted with DCM (500 mL) and poured into ice/water (200 mL). The organic layer was separated and washed with saturated NaHCO ₃ (150 mL), brine (150 mL), dried over Na ₂ SO ₄ , filtered and concentrated to give a residue. It was purified by column chromatography (PE/EA=10/1) to give 2,4-dichloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine 4 (2.2 g, 51.5%) as a white solid. LCMS (M+H ⁺ ) m/z: calculated value: 204.99; found value: 205.1.

A mixture of intermediate 4 (1.0 g, 0.005 mol), amine 5 (0.671 g, 0.005 mol), and TEA (0.985 g, 0.010 mol) in ACN (50 mL) was stirred at 90° C. for 12 h. LCMS showed 60% product formation. The mixture was concentrated to a residue, which was stirred in EA (10 mL) and filtered to give pure 2-chloro-N-(3-fluorobenzyl)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-4-amine 6 (0.4 g, 28%) as a white solid. LCMS (M+H ⁺ ) m/z: Calcd: 294.08; Found: 294.1. A mixture of intermediate 6 (100 mg, 0.340 mmol), compound 7 (70.75 mg, 0.409 mmol), Pd ₂ (dba) ₃ (93.53 mg, 0.102 mmol), X-Phos (63.70 mg, 0.136 mmol) and K ₂ CO ₃ (0.094 g, 0.68 mmol) in dioxane (30 mL) was stirred at 100 ° _C for 2 h under N 2. TLC showed that the reaction was complete. It was concentrated to give a residue, which was purified by column chromatography (PE/EA=5/1) to give 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carbonitrile 8 (0.11 g, 75.1%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calcd: 431.16; found: 431.2.

A mixture of compound 7 (90 mg, 0.209 mmol), acetaldehyde oxime (24.67 mg, 0.418 mmol), PPh ₃ -resin (17 mg, 0.042 mmol), and Pd(OAc) ₂ (9 mg) in EtOH/H ₂ O (5 mL, V/V = 10/1) was stirred at 80° C. for 4 h. LCMS showed the reaction was complete. The reaction mixture was concentrated in vacuo to give a residue, which was purified by preparative TLC to give 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazole-4-carboxamide FF15 (0.044 g, 47%) as a white solid. LRMS (M+H ⁺ ) m/z: Calcd: 449.17; Found: 449.30. ¹ HNMR (400MHz, DMSO-d ₆ ): δ8.76 (s, 1H, CONH ₂ ), 7.82-7.76 (m, 3H, Ph), 7.42-7.40 (m, 2H, Ph, CONH ₂ ), 7.18-7.13 (m, 3H, Ph, NH), 7.04-7.02 (m, 1H, Ph), 4.61 (d, J=6.4Hz, 2H, CH ₂ Ph), 4.32-4.30 (m, 2H, OC H ₂ CH ₂ ), 4.15 (s, 3H, OC H ₃ ), 2.02-1.98 (m, 2H, OCH ₂ CH ₂ CH ₂ ).

Synthesis of 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide FF16:

A mixture of compound 1 (50 mg, 0.170 mmol), compound 2 (29.24 mg, 204 mmol), Pd ₂ (dba) ₃ (46.67 mg, 0.051 mmol), X-Phos (31.85 g, 0.068 mmol) and Cs ₂ CO ₃ (0.111 g, 0.34 mmol) in dioxane (10 mL) was stirred at 110° C. for 24 h. Four identical reactions were performed in parallel. LCMS showed the reaction was complete; the four reactions were combined and concentrated to give a residue, which was purified by column chromatography (PE/EA=1/1) to give 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carbonitrile: 3 (163 mg, 43%) as a white solid. LCMS (M+H ⁺ ) m/z: calcd: 401.15; found: 401.20.

A solution of compound 3 (123 mg, 0.307 mmol), UHP (0.144 g, 0.002 mol), and _{K2CO3 (} 0.042 g, 0.307 mmol) in DMSO/ _H2O (10/1, 7 mL) was stirred at 25°C for 2 h. TLC and LCMS showed the reaction was complete. The mixture was poured into _H2O (30 mL) and extracted with EA ( ₈₀ mL*2). The combined organic layers were dried over _Na2SO4 , filtered, and concentrated to give a residue, which was purified by preparative TLC to give the desired 1-(4-((3-fluorobenzyl)amino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-yl)-1H-indazole-4-carboxamide FF16 (53 mg, 41%) as a yellow solid. LCMS (M+H ⁺ ) m/z: calcd: 419.2; found: 419.16. ¹ HNMR (400MHz, DMSO-d ₆ ): δ 8.61 (s, 1H, Ph ), 8.40 (d, J=8.4Hz, 1H, Ph ), 8.15-8.10 (m, 1H, CON H ₂ ), 7.71-7.67 (m, 2H, Ph ), 7.53-7.52 (m, 1H, CON H ₂ ), 7.40-7.36 (m, 2H, Ph ), 7.36-7.25 (m, 2H, PhN H ), 7.15-7.05 (m, 1H, Ph ), 4.73 (d, J＝6.0Hz, 2H, PhCH ₂ ), 4.31 (t, J＝4.4Hz, 2H, OC H ₂ CH ₂ CH ₂ ), 2.02-1.98 (m, 2H, OCH ₂ CH ₂ CH ₂ ).

Biological solutions

The above outlines in vitro and in vivo bioassays to determine the anticancer properties of the fused pyrimidine compounds of the present invention. The details of these protocols show how the assays were performed.

P97 Biochemical Assay Protocol

The p97 assay is an initial screening assay for determining the inhibitory activity of the fused pyrimidine compounds of the present invention against the p97 complex. As discussed above, inhibition of the activity of the p97 proteasome complex can induce apoptosis and lead to the elimination of neoplastic (cancer) cells. This method is based on the method of Christianson, Nat. Cell Biol., (2011) 14:93.

Reagents used for the p97 assay include:

The assay buffer was a mixture of 50 mM TRIS pH 7.5, 20 mM MgCl ₂ , 0.02% TX-100, 1 mM DTT, and 0.2% (v/v) glycerol. The well plate format was Corning 3674, 384w. The identification kit was the ADP glo kit (Promega): stop buffer, detection reagent.

The assay protocol was performed as follows:

Compounds were serially diluted in DMSO using a 1:3.33 fold 10-point dilution series.

Add the following reagents to each well of a 384w plate:

0.5 μL of serially diluted compound in DMSO (final concentration 10%)

2 μL ATP (final concentration = 20 uM, diluted in assay buffer)

2.5 μL p97 (final concentration = 20 nM, diluted in assay buffer)

Incubate at 37°C for 15 min.

Add 5 μL of stop buffer and incubate at room temperature for 40 min.

Add 10 μL of detection reagent and incubate at room temperature for 30 min.

Luminescence was read on an Envision plate reader.

After obtaining data from the luminescence readout, the data can be analyzed as follows:

Luminescence data were normalized using no enzyme (complete inhibition) and compound (no inhibition) controls. Normalized luminescence data were plotted against log-transformed concentration values and fitted to a sigmoidal curve to determine IC50 values (completed in CollaborativeDrug Discovery software).

Caco-2 permeability assay

This assay is designed as a model to indicate the permeability of the fused pyrimidine compounds of the present invention across the gut-blood barrier. The results will indicate whether the fused pyrimidine compound can be effectively absorbed into the patient's bloodstream. Efficient and effective absorption of an orally administered drug determines, in part, its bioavailability. For the fused pyrimidine compounds of the present invention, this assay is a model for evaluating the bioavailability of the compound as a result of its ability to cross biological barriers and enter the patient's physiological system.

The experimental goal of the Caco-2 assay is to measure the directional Caco-2 permeability of test compounds in cultured Caco-2 monolayers.

The test compound is a fused pyrimidine compound of the present invention.

Configuration

instrument

Tissue culture _CO2 incubator with humidity control

Liquid Handler

Fixed orbit shaking table

EVOM epithelial volt-ohmmeter (World Precision Instruments, Sarasota, FL) with planar electrodes for transepithelial electrical resistance (TEER) measurements

Benchtop centrifuge with 96-well plate adapter

Caco-2 cells (human colorectal adenocarcinoma, ATCC #37-HTB, passaged 30-45 times)

Cells were seeded at a density of 23,000 cells/well on PET membranes (1 μm pore size, 0.31 ^cm2 surface area) using 24-well plates (Becton Dickinson plates, part number 351181, Fisher Scientific, Inc.) in a Falcon HTS multiwell insert system. Cells were grown for 20-23 days, with medium changes every 2-3 days.

Reagents

Ringer's buffer solution (pH 7.4, at 25°C)

Ringer's buffer with 1% methanol

Blk solution: Ringer's buffer: methanol = 2:1 (v/v); 100% methanol including internal standard (IS); 10 mM stock dosing solution in DMSO; 100 μM dosing solution in buffer.

Solution Overview

Caco-2 permeability: 20-23 days/30-45 passages

24-well transwell format: 0.31 cm2 surface area

Donor concentration: 100 μM, including 1% DMSO

A: 300 μL pH 7.4 / B: 1200 μL pH 7.4 Ringer's buffer

Directionality: A B and B A (N=4)

Donor side sampling: 20 μL at the beginning and end (90 min)

Receptor side sampling: 100 μL at 30, 50, 70 and 90 minutes

Incubate at 50 shakes/min, 37°C, 5% CO ₂ , 95% humidity

Analysis: LC-UV, LC-MS or LSC

Output: Peff (cm/sec) = (dX/dt)/(A*Co*60), dX/dt: transported amount (nanomoles) versus time (minutes) profile in the acceptor compartment; A: surface area (cm ² ); and Co: initial donor concentration (μM)

Positive controls: atenolol and propranolol

Membrane integrity: TEER＞ ^200Ocm2

Required amount: approximately 1 mg or 100 μL of 10 mM test compound in DMSO

Instrumentation: _CO2 incubator with humidity control, liquid handler, epithelial volt-ohmmeter for TEER, Caco-2 cells (ATCC #37-HTB), and 24-well insert plates (PET membrane, 1 μm pore size, 0.31 ^cm2 plate, part number 351181), Becton Dickinson

Production capacity: 6 compounds/2 Caco-2 plates/1 FTE/day

preparation

Table 24. Preparation of Ringer's solution with glucose (isotonic = 290 mOsm/kg), pH 7.4

Preparation of 4 L solution

1. Add calcium sulfate and magnesium sulfate to 3.5 L of distilled water. Note: Add calcium sulfate and magnesium sulfate first due to low solubility, and add the remaining ingredients in the order listed in Table 1.

2. Under continuous stirring, adjust the final volume of the solution to 4 L with distilled water.

3. Adjust the final solution to pH 7.4 using 1 N HCl or 1 N NaOH.

4. Prepare an isotonic buffer solution using NaCl. Use a tensiometer to measure the tension of the solution. If the isotonic solution is equal to 0.9% NaCl (290 mOsm/L),

Y - {(290 - x)/290} x 9 mg x 4000 mL, where y = mg of NaCl required to make the isotonic solution and x = the observed tonicity of the solution (reported in mOsm/L).

Preparation of dosing solution in 15mL PP tube

1. In RG: 140 μL 10 mM stock solution + (14 mL - 140 μL) 100 μM dosing solution in RG

Preparation of calibration solution in 96 shallow wells

1. Prepare 10 μM standard solution: 100 μL of 100 μM dosing solution + 0.9 mL of Ringer's solution with 1% methanol.

2. Prepare analytical standard solutions at 10, 5, 2, 1, 0.5, 0.2, 0.1, 0.05, 0.02, 0.01, and 0 μM. (See Table 26)

Table 25. Preparation of analytical calibrants in 96-well plates

Transport studies

Drug administration and sampling

1. Equilibrate both sides of the monolayer with pre-warmed (37°C) drug-free Ringer's buffer (300 μL apical, 1,200 μL basolateral) supplemented with glucose (25 mM) for 10 minutes.

2. TEER measurement in a 37°C water bath

NOTE: The TEER value serves as a quality control check for monolayer integrity. At 21 days post-seeding, each Caco-2 cell monolayer should have a TEER value greater than or equal to 2000 x ^cm2 , and those that do not meet this criterion are not suitable for permeability evaluation.

3. When studying A to B transport: Fill the basolateral side with 1,200 μL of Ringer's buffer. Start the transport experiment by transferring the test drug dosing solution (320 μL) to the apical side.

4. When studying B to A transport: Fill the apical side with 300 μL of Ringer's buffer. Initiate transport experiments by transferring the test drug dosing solution (1,220 μL) to the basolateral side. Transport studies were performed in quadruplicate for each test drug in each direction (A to B, B to A).

5. Start timing after dosing the last donor well.

6. Remove 20 μL aliquots from the donor wells at 0 minutes (D ₀ ) and transfer these aliquots to the donor site of a 96-well plate containing 180 μL of buffer with 1% methanol. This step effectively dilutes D ₀ tenfold.

7. Transport studies were initiated by placing the plates on an orbital shaker maintained in a pre-heated (37°C) and humidified (5% _CO2 ) incubator. Studies were performed under agitation conditions at 50 shakes/minute.

8. Remove 100 μL aliquots from the receiving side of the monolayer at 30, 50, 70, and 90 minutes post-dose and transfer these aliquots to the corresponding 96-well sample plates (see Table 26). Replace with an equal volume of pre-warmed buffer.

9. At 90 minutes post-dose ( _Df ), remove 20 μL aliquots from the donor side of the monolayer and transfer these aliquots to the donor site of a 96-well plate containing 180 μL Ringer's buffer with 1% methanol. This step effectively dilutes _Df ten-fold.

10. Replace both sides of the monolayer with fresh drug-free pre-warmed Ringer's buffer (300 μL apical, 1,200 μL basolateral) and equilibrate for 10 minutes.

11. Measure TEER in a 37°C water bath.

Sample processing

The following steps refer to a 96-well Caco-2 assay plate, Table 26.

1. Transfer 20 μL of diluted _D0 and _Df to the corresponding 96-well sample plate, where each well contains 80 μL of buffer with 1% methanol. This step effectively dilutes the sample fivefold further. Therefore, the donor sample is diluted 50-fold from its initial concentration.

2. Transfer 100 μL of assay calibrants (ranging from 0 to 10 μM) to row 1 of the sample plate.

3. Add 50 μL of methanol including IS to all sample wells and mix (standards, samples, and D ₀ and D _f ).

4. Transfer 150 μL of Blk solution to row 2 of the assay plate.

5. Seal the assay plate with adhesive sealing film and store the samples with labels at -80°C for LC-UV or LC-MS analysis.

6. Analyze 20 μL aliquots of the individual permeability samples and the standards using a suitable analytical instrument.

7. Peff = (dX/dt)/(A x _Co x 60), where _Peff is the effective permeability in cm/ ^sec , X = mass transported, A is the surface area available for transport (cm2), Co _is the initial donor drug concentration (μM), and dX/dt is the slope of the best-fit line through the plot of amount transported (nmol) versus time in the receiving chamber (min).

Table 26. Caco-2 assay plate (96-well plate)

Positive control data

The average data in Table 27 represent the mean from 12 separate day experiments.

Mouse liver microsome assay

The liver microsomal assay is a model for studying the metabolic stability of the fused pyrimidine compounds of the present invention. Metabolic stability is another aspect that determines bioavailability. The facility with which a compound is bioabsorbed into the bloodstream, as shown in the Caco-2 model, indicates the extent to which an oral dose of the compound will reach the bloodstream. The body metabolizes substances efficiently to excrete them from the body and/or utilize them as nutrients. This aspect of bioavailability can be determined by model studies such as liver microsomal metabolism. Whether by oxidation, conjugation, or any other biological pathway, the metabolism of a drug at least partially determines the lifespan of the drug in the body.

The mouse liver microsome assay is a model designed to determine the in vivo half-life of drugs. Liver enzymes are responsible for converting substances into materials that can be easily excreted by the body. Other pathways of this type of metabolism include renal metabolism and cellular metabolism.

In this protocol, the compound is combined with a liver microsome preparation (protein) and NADPH. The mixture is incubated and the rate at which the compound disappears from the test solution is measured. Measurements are made by screening compound concentrations at designated times using liquid chromatography combined with mass spectrometry.

Prepare the concentrations of reactants to prepare the test solutions:

Protein: 1.0 mg/ml

Compound: 1um

Organic solvent: 0.4% DMSO

Culture medium: 0.1 M potassium phosphate (KB)

1 mM NADPH (Sigma N1630, FW 833.3, freshly prepared)

The test article (TA, i.e., the compound of the present invention) was prepared by dissolving solid TA in DMSO to make a 0.25 mM solution.

Amounts of reactant solutions to be combined to form the test solution:

423ul KB (potassium phosphate)

+25ul MLM (20mg/ml) (mouse liver microsome preparation)

448ul

+2ul test compound (fused pyrimidine compound in 0.25mM DMSO)

+50ul NADPH stock solution (10mM, 10x)

500ul

Test protocol used to perform the assay

1. Add 423ul KB to 8-strip deep well tubes

2. Add 25ul MLM for condition 1

3. Place on ice and add 2ul of compound (250x stock solution in DMSO, stock solution at 0.25mM)

4. Pre-incubate the reaction mixture at 37°C for 3 to 5 minutes (shaking at 150 rpm)

5. For condition 1, start the reaction by adding 50ul NADPH

6. For condition 2, add 50ul KB

7. Aliquots of 100 μl of sample were collected at 0, 15, 30 and 60 min time points and 200 μl of acetonitrile mixture containing IS was added to quench the reaction.

8. Centrifuge at 4000 rpm for 10 minutes

9. Inject the supernatant for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis

Protein binding procedure using a 96-well equilibrium dialyzer

Non-specific protein binding is another aspect that affects the bioavailability and effectiveness of drugs. In order to measure the non-specific binding of a compound, the compound is merged with human plasma and dialyzed with a membrane constructed to prevent larger molecules such as human plasma proteins from passing through but allowing small molecules such as the compounds of this invention to pass through. Typically, this type of membrane allows the compound to pass through, whether it is its salt or neutral form. The dialysate (solution passing through the membrane) is checked by liquid chromatography-mass spectrometry to determine the identity and concentration of the compounds of this invention. Whether non-specific protein binding occurs is indicated by the comparison of the concentration of the compound in the dialysate with the concentration of the compound merged with the plasma.

Equipment and reagents:

96-well equilibrium dialyzer (manufactured by Harvard Apparatus)

Plate rotator with dialyzer plates fixed in clamping fixtures

Buffer: DPBS (gibco, IX)

Compound concentration: 1 μM (~0.5 μg/mL) in human plasma

Process:

1. Seal the empty sample side hole on the colored side with the cover strip.

2. Turn the plate over and carefully pipette a 200 μL volume (equal to the sample volume) of buffer into the wells on the buffer side (transparent box) while not touching the membrane by allowing the liquid to flow along the inside wall of each well.

3. Gently seal the buffer-filled well with the cover strip.

4. Turn the plate over and carefully remove the cover strip from the sample side wells. Pipette the desired sample without touching the membrane.

5. Reseal the sample well with the cover strip.

6. Slide the assembled dialyzer plate into the plate rotator and hand-tighten the knob. Turn on and allow to rotate until equilibrium has been reached (24 hours at 37°C), remove the dialyzer plate from the rotator.

7. After equilibrium has been reached, remove the dialyzer plate from the rotator.

8. Carefully remove the cover strip from the buffer side of the plate (clear box) and slowly pipette the assay samples from the wells, being careful not to touch or puncture the membrane.

Samples will include controls at 4°C and stability of samples at 37°C in PBS and plasma.

MS analysis:

Prepare standard ranges of 5, 10, 50, 100, 500, and 1000 ng/mL in plasma

10 μL of each standard and sample were pipetted into 40 μL of blank buffer/blank plasma (ratio: 1 plasma/4 DPBS), and they were mixed.

Add 200 μL of Is (internal standard) in ACN and mix well.

The samples were centrifuged and the supernatant solution was transferred for LC/MS analysis.

Cell assay protocol

The cell-based assay provides information about the anti-neoplastic activity of the compounds of the invention. Compounds are tested against cultured cancer cells to determine whether the compounds of the invention are able to cross-react with the cancer cells to reduce or eliminate such cells. The assay involves establishing colonies of such cells and then treating them with the test compound under specified conditions and assay protocols to determine the results.

Day 1. Cell plating to establish cancer cell colonies

Cell plating:

Cells were seeded approximately 16 hours prior to compound treatment.

25 μL of A549 cells were plated into each well of a 384-well plate using multi-point plating.

For IF there are two (2) black plates, 2500 cells/well

The plates were allowed to sit at room temperature for 10-15 minutes before being placed in the incubator to allow the cells to adhere to the middle of the plate.

For viability there is one (1) white plate, 500 cells/well

Day 2: Treat cultured cells with test compounds

Treat cells:

Serially dilute compounds in DMSO using a 10-point 2-fold serial dilution to make 250X stock compound solutions.

Dilute the compound 1:125 in cell culture medium to make a 2X solution

Add 25 μl of diluted compound to the cell plate in duplicate wells

Return cells to the incubator (6 hours incubation for black plates; 72 hours incubation for white plates).

Fixing/staining black plates:

Cells in black plates were incubated with compounds at 37°C for 6 hours.

Add 15 μL of 16% paraformaldehyde (PFA) directly to the culture medium in each well.

Incubate at room temperature for 5 min, flick the plate and wash in 50 μL PBS.

Block in 50 μL blocking buffer for 30 minutes (or up to several hours)

Blocking buffer: 1XPBS, 1% BSA, 0.3% Triton-X100, Hoechst (1:10,000)

Incubate with 25 μL of primary antibody in blocking buffer overnight at 4 °C

Primary Antibody:

Plate A K48-Ub 1:20,000 (Millipore 05-1307 Lot No. 2049282) Rabbit

CHOP/Gadd153 1∶2,000 (SC-7351) mice

Plate B P53 1∶2,000 (SC-6243) rabbit

p62/SQSTM1 1∶2,000 (SC-28359) mice

Overnight at 4°C

Secondary Antibody:

AlexaFluor488 goat anti-rabbit 1:2,000 (Life Tech A11008)

AlexaFluor555 goat anti-mouse 1:2,000 (Life Tech A21422)

Day 3/4

Black plate staining (counting):

Wash the black plate 3X in 50 μL PBS (about 5 min each time)

Incubate with 25 μl of secondary antibody (1:2,000) in blocking buffer for 1-2 hours at room temperature (AlexaFluor 488-anti-rabbit/AlexaFluor 555-anti-mouse)

Wash 4X in 50 μL PBS (about 5 min each time)

Leave the plate in PBS for imaging

Clean the bottom of the plate with 70% EtOH

Imaging:

Image the plate in a high content microscope with 405 nm, 488 nm and 555 nm filters

Data Analysis:

The nuclear count and cellular intensity of each marker were measured using Matlab software (Math Works) with an automated image analysis protocol using Hoechst as a nuclear marker.

Day 5

Viability assay:

Frozen aliquots of CellTiter glo (Promega G7572) were thawed at room temperature.

Add 45 mL of NaCl/PBS solution to 5 ml of cell titer glo (10X).

Remove the white plate from the incubator and leave at room temperature for 30 minutes.

Add 25 μl of diluted cell titer glo to each well.

Shake the plate for >1 minute.

The plates were incubated for >5 minutes to allow luminescence to stabilize.

The glow is stable for up to 3 hours.

Luminescence was read on a plate reader.

Table II

Biological Data of Representative Compounds of Formula I

Contents

The inventions, examples, biological assays, and results described and claimed herein may have attributes and embodiments including, but not limited to, those listed or described or referenced in this application.

All patents, publications, scientific papers, internet sites, and other documents and materials referenced or mentioned herein are indicative of the level of skill of those skilled in the art to which the invention pertains, and each such referenced document and material is hereby incorporated by reference to the same extent as if fully incorporated or recited in its entirety. The right to fully incorporate into this specification any and all materials and information from any such patents, publications, scientific papers, internet sites, electronically available information, textbooks, or other reference materials or documents is reserved.

The written description of this patent application includes all claims. All claims, including all original claims, are hereby incorporated by reference in their entirety into the written description section of this specification, and the right to fully incorporate any and all such claims into the written description or any other part of this application is reserved. Thus, for example, in no event can this patent be interpreted as claiming that a written description of the claims is not provided, asserting that the precise wording of the claims is not set forth in a specific written manner (inhaec verba) in the written description section of this patent.

Although the present invention has been described in conjunction with the detailed description of the invention, the above description is intended to illustrate and not to limit the scope of the invention, which is defined by the scope of the appended claims. Therefore, it should be understood from the foregoing description that although specific non-limiting embodiments of the present invention are described herein for illustrative purposes, various modifications may be made without departing from the spirit and scope of the invention. Other aspects, advantages, and modifications are within the scope of the following claims and the invention is not to be limited except by the appended claims.

The particular methods and compositions described herein are representatives of preferred non-limiting embodiments and are exemplary rather than intended to limit the scope of the invention. Other objectives, aspects, and embodiments will occur to those skilled in the art when considering this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. It will be apparent to those skilled in the art that various substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention.

The invention illustratively described herein may also be suitably practiced in the absence of any element or elements, or any limitation or limitations, not specifically disclosed herein as essential. Thus, for example, in each instance herein, in the non-limiting embodiments or examples of the invention, the terms "comprises/comprising," "includes," "contains," etc. are to be understood as being extensible and non-limiting. The methods and processes illustratively described herein may suitably be practiced in a different order of steps and are not necessarily limited to the order of steps indicated herein or in the claims.

The terms and expressions used are used as descriptive and not limiting terms, and there is no intention that the use of these terms and expressions exclude any equivalents of the features shown and described or portions thereof, but it is understood that various modifications may be made within the scope of the invention as claimed. It is therefore understood that although the present invention has been specifically disclosed by various non-limiting embodiments and/or preferred non-limiting embodiments and optional features, it is contemplated that any and all modifications and variations of the concepts disclosed herein that may be undertaken by one skilled in the art are within the scope of the invention as defined by the appended claims.

The present invention has been described broadly and generally herein. Each of the more detailed categories and subgroups falling within the generic disclosure also forms part of the present invention. This includes generic descriptions of the invention with qualifications or implicit limitations that remove any subject matter from that generic description, regardless of whether the deleted matter is specifically recited herein.

It is also to be understood that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise, e.g., the term "X and/or Y" means "X" or "Y" or both "X" and "Y" and that the letter "s" following a noun denotes both the plural and singular forms of that noun. Additionally, where features or aspects of the invention are described in terms of Markush groups, then those skilled in the art intend and recognize that the invention includes and is described in terms of any individual member or subgroup of members of the Markush group, and the right to amend the application or the claims to specifically refer to any individual member or subgroup of members of the Markush group is reserved.

Claims (32)

1. Fused pyrimidine compounds of formula I in: Skeleton selected And Y is NR ⁵ ; and The double-ring P2 part of formula I HET HET Selected from H5 and H10, in: ^R1 is selected from the group consisting of: carboxyl, formamide, sulfonamide, and nitrile; ^R2 is hydrogen; R ³ is hydrogen or an alkyl group with 1 to 4 carbons; R ⁵ is hydrogen or an alkyl group with 1 to 4 carbons; Each R ⁶ is independently selected from hydrogen, one to four carbon alkyl groups, or one to four carbon alkoxy groups; Ar is either phenyl or fluorophenyl; This allows the combination of the skeleton and the HET to provide S6-H5, S6-H10, S7-H5, and S7-H10. 2. The fused pyrimidine compound of claim 1, wherein ^R6 is hydrogen. 3. The fused pyrimidine compound of claim 1, wherein ^R6 is one to four carbon alkyl groups. 4. The fused pyrimidine compound of claim 3, wherein ^R6 is methyl. 5. The fused pyrimidine compound of claim 1, wherein ^R6 is one to four alkoxy groups. 6. The fused pyrimidine compound of claim 5, wherein ^R6 is a methoxy group. 7. The fused pyrimidine compound according to any one of claims 1-6, wherein ^R3 is hydrogen. 8. The fused pyrimidine compound according to any one of claims 1-6, wherein ^R5 is hydrogen. 9. The fused pyrimidine compound of claim 7, wherein ^R5 is hydrogen. 10. The fused pyrimidine compound according to any one of claims 1-6, wherein ^R1 is a formamide group. 11. The fused pyrimidine compound of claim 7, wherein ^R1 is a formamide group. 12. The fused pyrimidine compound of claim 8, wherein ^R1 is a formamide group. 13. The fused pyrimidine compound of claim 9, wherein ^R1 is a formamide group. 14. The fused pyrimidine compound of claim 1, having any one of the following specific names: 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-(hydroxymethyl)-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methoxy-1H-benzo[d]imidazol-4-carboxamide, 1-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-fluoro-2-methyl-1H-indole-4-carboxamide, 3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-((3-fluorobenzyl)amino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-((3-fluorobenzyl)amino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, 3-(4-(benzylamino)-8-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-7-carboxamide, or 1-(4-(benzylamino)-5-methyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)isobenzofuran-4-carboxamide. 15. The fused pyrimidine compound of claim 14, having the following name: 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-indole-4-carboxamide, 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, 1-(4-((3-fluorobenzyl)amino)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-indole-4-carboxamide, or 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyridino[3,2-d]pyrimidin-2-yl)-2-methoxy-1H-indole-4-carboxamide. 16. The fused pyrimidine compound of claim 15, having the name 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-1H-indole-4-carboxamide. 17. The fused pyrimidine compound of claim 15, having the name 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyridino[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide. 18. A pharmaceutical composition comprising the fused pyrimidine compound of any one of claims 1-17 and a pharmaceutical carrier. 19. The fused pyrimidine compound of any one of claims 1-17, used to reduce the activity of valine peptide (p97) in patients with such need. 20. The pharmaceutical composition of claim 18, used to reduce the activity of valine peptide (p97) in patients with this need. 21. The fused pyrimidine compound according to any one of claims 1-17, used for treating tumor tissue in human patients. 22. The fused pyrimidine compound used in claim 21, wherein the tumor tissue is cancerous tissue. 23. The pharmaceutical composition of claim 18, for treating tumor tissue in a human patient. 24. The pharmaceutical composition used according to claim 23, wherein the tumor tissue is cancerous tissue. 25. Use of the fused pyrimidine compound of any one of claims 1-17 or the pharmaceutical composition of claim 18 in the preparation of a medicament for reducing the activity of valine-containing protein (p97). 26. Use of the fused pyrimidine compound of any one of claims 1-17 or the pharmaceutical composition of claim 18 in the preparation of a medicament for treating tumor tissue. 27. The use according to claim 26, wherein the tumor tissue is cancerous tissue. 28. The use of claim 26, wherein the treatment of tumor tissue comprises treating cancers selected from the group consisting of: chronic myeloid leukemia, chronic lymphocytic leukemia, hairy cell leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic neutrophilic leukemia, acute lymphoblastic T-cell leukemia, plasmacytoma, immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryocytic leukemia, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia, malignant lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, lymphoblastic T-cell lymphoma, Burkitt's lymphoma, and follicular lymphoma. 29. The use of claim 26, wherein the treatment of tumor tissue comprises treating cancers selected from the group consisting of: chronic myeloid leukemia, chronic lymphocytic leukemia, hairy cell leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic neutrophilic leukemia, acute lymphoblastic T-cell leukemia, immunoblastic large cell leukemia, multiple myeloma, and non-Hodgkin's lymphoma. 30. The use according to claim 26, wherein the treatment of tumor tissue includes treating cancers selected from the group consisting of: bladder cancer, urethral cancer, lung cancer, vulvar cancer, cervical cancer, endometrial cancer, kidney cancer, esophageal cancer, gastric cancer, prostate cancer, primary peritoneal cancer, gastroesophageal junction cancer, brain cancer, breast cancer, colon cancer, head and neck cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, sarcoma, and thyroid cancer. 31. The use of claim 26, wherein the treatment of tumor tissue comprises treating cancers selected from the group consisting of metastatic breast cancer, non-small cell lung cancer, advanced colorectal cancer, and hormone-resistant prostate cancer. 32. The use of any one of claims 26-31, wherein the compound is 1-(4-((benzyl)amino)-5,6,7,8-tetrahydropyridino[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide.