MXPA00008095A - N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted-alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors - Google Patents

Abstract

Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated inthe pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr;converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr;from membrane bound TNF-&agr;precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr;converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having formula (I), wherein R2 and R3 form a heterocyclic ring and A is S, S(O), or S(O)2 and R1 and R4 are defined herein.

Description

N-HYDROXY-2- (RENT, ARIL, OR HETEROARIL SULFANIL, HIS FINIL OR SULFONIL) -3-RENT, ARIL OR HETEROARILAMIDES REPLACED AS INHIBITORS OF MATRIX METALOPROTEINASE BACKGROUND OF THE INVENTION Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basal membranes. Those zinc containing endopeptidases consist of several subsets of enzymes including collagenases, estro elisins. and gelatinases. Of those classes, gelatinases have been shown to be the MMPs most intimately involved in the growth and spread of tumors. It is known that the level of expression of gelatinase is high in malignant conditions, and that gelatinase can degenerate the basement membrane, which leads to tumor metastasis. Angiogenesis, required for the growth of solid tumors, has also recently been shown to have a gelatinase component in its pathology. In addition, there is evidence that gelatinase is involved in the rupture of the plaque associated with atherosclerosis. Other conditions mediated by MMP are restenosis, osteopenias mediated by MMP, inflammatory diseases of the central nervous system, aging of the skin, tumor growth, osteoarthritis, arthritis Ref.:122093 rheumatoid, arthritis septic, corneal ulceration, wound healing abnormal, bone diseases, proteinuria, aneurysmal aortic disease, degenerative cartilaginous loss after traumatic joint injury, demyelinating diseases of the nervous system, liver cirrhosis, glomerular disease of the kidney, premature rupture of the fetal membranes, inflammatory bowel disease, periodontal disease, degeneration age-related macular disease, diabetic retinopathy, proliferative vitreoretinopathy, premature retinopathy, ocular inflammation, keratoconus, Sjorgen syndrome, myopia, ocular tumors, ocular angiogenesis / neovascularization and corneal graft rejection. For recent reviews, see: (1) Recent Developments in the Metalloproteinase Inhibitor Investigation of the Matrix, R. P. Beckett, A. H. Davidson, A. H. Drummond, P.

Huxley and M. Whittaker, Research Focus, Vol. 1, 16-26, (1996), (2) Curr. Opin. Ther. Patents (1994) 4 (1): 7-16, (3) Curr.

Medicinal Chem. (1995) 2: 743-762, (4) Exp. Opin. Ther. Patents (1995) 5 (2): 1087-110, (5) Exp. Opin. Ther. Patents (1995) 5 (12): 1287-1196. The enzyme that converts TNF-a (TACE) catalyzes the formation of TNF-a from the precursor protein of membrane-bound TNF-a. TNF-a is a proinflammatory cytokine that is now thought to play a role in rheumatoid arthritis, septic shock, graft rejection, cachexia, anorexia, inflammation, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, resistance to insulin and HIV infection in addition to its well-documented antitumor properties. For example, research with anti-TNF-α antibodies and transgenic animals has shown that blocking the formation of TNF-α inhibits the progress of arthritis. This observation has recently spread to humans as well. It is expected that the small molecule inhibitors of MMP and TACE therefore have the potential to treat a variety of disease states. Although several inhibitors of MMP and TACE have been identified and described in the literature, the vast majority of these molecules are peptide and peptide-like compounds that would be expected to have problems of bioavailability and pharmacokinetics common to such compounds that would limit their clinical effectiveness. Highly potent, long-acting, orally bioavailable inhibitors of MMPs and / or TACEs are therefore highly desirable for the potential chronic treatment of the disease states mentioned above.

Recently, two references have appeared (U.S. 5,455,258 and European Patent Application 606,046) which describe hydroxyamic acids substituted with arylsulfonamido. These documents cover communication exemplified by GCS 27023A. These are the only non-peptide matrix metalloproteinase inhibitors described to date.

CGS 27023A Salah et al., Liebigs Ann. Chem. 195, (1973) describes some sulfonyl acetohydroxamic acid derivatives substituted with aryl and thio substituted with aryl of general formula 1. These compounds were prepared to study the Mannich reaction. Subsequently, they were tested for their fungicidal activity.

In the United States Patent 4,933,367 some sulfon carboxylic acids are described. Those compounds showed to exhibit hypoglycemic activity.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to non-peptidic, low molecular weight, novel inhibitors of matrix metalloproteinases (MMP) and the enzyme that converts TNF-a (TACE) for the treatment of arthritis, Tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone diseases, diabetes (insulin resistance) and HIV infection. In accordance with this invention a group of compounds of formula I is provided wherein: R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono or bicyclic heterocycle containing a heteroatom selected from 0, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6- where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from 0, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; cycloalkyl or bicycloalkyl of C to Cs optionally substituted with one or two groups independently selected from R5; saturated or unsaturated 5- to 10-membered mono or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cn aroyl, C2-C6 alkanoyl, Ci to Ci2 alkyl, C2 to C2 alkenyl, C2-C2 alkynyl, F, Cl, Br, I, CN, CHO, C.sub.1 -C.sub.6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-Ce alkynyloxy, Ci-C.sub.x alkyloxy, C.sub.6 -C. alkoxyheteroaryl, C? -C6 alkylamino- C? -C6 alkoxy, C 1 -C 2 -alkylene dioxy, C 1 -C 6 aryloxy-alkyl-amine, perfluoro-C 1 -C 12 -alkyl, S (0) n -C 1 -C 6 alkyl, S (0) n -aryl where n is 0,1 or 2; OCOO-C6-C6 alkyl, OCOOaryl, OCONR6, COOH, COO-C6-C6alkyl, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, NR6CONR6R6, NHS02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02-C-alkyl? -C6 CONHS02-aryl, S02NHCOaryl, CONHS02-C? -C6 alkyl, CONHS02-aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; or 5- to 10-membered saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, where C? -C6 alkyl is linear or branched, heteroaryl is a mono or bicyclic heteroaryl group of 10 members having 1 to 3 heteroatoms independently selected from 0, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C 1 -C 6 alkoxy, or hydroxy; R6 is H, Ci to Cie alkyl optionally substituted with OH; C3 to C6 alkenyl, C3 alkynyl to Ce, perfluoro to Ci to C6 alkyl, S (0) n to C? -C6 alkyl, S (0) n aryl where n is 0, 1 or 2, or COheteroaryl, wherein the heteroaryl is a 5-10 membered mono or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; and R7 is C7-Cn aroyl, C2-C2 alkanoyl, perfluoro C? -C? 2 alkyl, S (O) n C? -C6 alkyl, S (0) n-aryl where n is 0, 1 or 2; COO-C?-C6 alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHSO-C de-C6 alkyl, C0NHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 -groups independently selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from 0, S or N-C6-C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from O, S or N and is optionally substituted with one or two groups independently selected from R 5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups independently selected from R5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from O, S or N-C6-C6 alkyl, optionally substituted with one or two groups independently selected from R5; or C8-C6-C6-C6-C6-alkyl-R6R9N-alkoxyaryl wherein R8 and R9 are independently selected from Ci-Cß alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring which optionally it contains an oxygen atom, wherein the aryl group is phenyl or naphthyl; and the pharmaceutically acceptable salts thereof. A more preferred aspect of the present invention is the group of compounds of general formula (la): wherein R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6 ~ where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from O, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; cycloalkyl or bicycloalkyl of C3 to Ce optionally substituted with one or two groups independently selected from R5; R5 is H, F, Cl, Br, I, CN, CHO, C7-Cn aroyl, C2-C6 alkanoyl, Ci to Ci2 alkyl, C2 to C2 alkenyl, C2-C2 alkynyl, C.sub.1 -C.sub.6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, Cx-C6 alkoxyaryl, Ct.-C6 alkoxyheteroaryl, C? -C6 alkylamino-C? -C6 alkoxy, C 1 -C 2 -alkylene dioxy, C 1 -C 6 aryloxy-alkyl-amine, C 1 -C 12 -alkyl perflide, S (0) n-Ci-Cd alkyl, S (0) n-aryl where n is 0-1 or 2; OCOO-C6-C6 alkyl, OCOOaryl, OCONR6, COOH, COO-C6-C6alkyl, COOaryl, C0NR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, NR6CONR6R6, NHS02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02-C-alkyl? -C6, CONHS02-aryl, S02NHCOaryl, CONHS02-C6-C6 alkyl, CONHS02aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; or 5- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7; where the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen , cyano, amino, nitro, C? -C6 alkyl, Ct.-C6 alkoxy, or hydroxy; R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 to C6 alkenyl, C3 alkynyl to Ce, perfluoro C1 to C6 alkyl, S (0) nalkyl or aryl where n is 0, 1 or 2; or COheteroaryl; where the heteroaryl is a 5-10 membered mono or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from O, S or NR, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Ce alkyl, C? -C6 alkoxy, or hydroxy; and R7 is aroyl of C-Cn, C2-C6 alkanoyl, perfluoro Ci-C ^ alkyl, S (O) n-alkyl, S (0) n-aryl where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02alkyl, CONHS02aryl, aryl, or heteroaryl; where C? -C6 alkyl is linear or branched, the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or NR7 and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from 0, S or N and is optionally substituted with one or two groups independently selected from R5; biphenylalkyl of from 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R 5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl is optionally substituted with one or two groups independently selected from R5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from O, S or N-C6-C6 alkyl, optionally substituted with one or two groups independently selected from R5; R8R9N-d-C6-alkoxyaryl of C? -C6 alkyl wherein R8 and R9 are independently selected from C? -C6 alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; and the pharmaceutically acceptable salts thereof. The most preferred group of compounds are those of the following formula (Ib): wherein: R1 is phenyl, naphthyl, alkyl of 1-18 carbon atoms or heteroaryl such as pyridyl, thienyl, imidazolyl or furanyl, optionally substituted with C? -C6 alkyl, C? -C6 alkoxy, C6 aryloxy -C? 0, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, halogen; or S (0) n-C 1 -C 6 alkoxy C 1 -C 6 alkoxy, or C 6 -C 6 alkoxyheteroaryl; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; C3 to C8 cycloalkyl or bicycloalkyl optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cn aroyl, C2-C6 alkanoyl, Ci to Ci2 alkyl, C2 to Ci2 alkenyl, C2-C2 alkynyl, F, Cl, Br, I, CN, CHO, alkoxy, C? -C6, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, C? -C6 alkylamino C? -C6 alkoxy, C? -C2 alkylene dioxy, C aryloxy alkyl amine? -C6, perfluoro alkyl of C? -C? 2, S (0) n-C? -C6 alkyl, S (0) n-aryl where n is 0, 1 or 2; OCOO C? -C6 alkyl, OCOOaryl, OCONR6, COOH, COO CX-C6 alkyl, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, -NR6CONR6R6, NHS02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02-C? -C6 alkyl , CONHS02aryl, S02NHCOaryl, CONHS02-C? -C6 alkyl, CONHS02aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; saturated or unsaturated 5- to 10-membered mono or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, where Ci-Cß alkyl is linear or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cß alkyl, Ci alkoxy -Cß, or hydroxy; R6 is H, Ci to C18 alkyl optionally substituted with OH; C3 alkenyl to Ce, C3 to C alkynyl, perfluoro Ci to Ce, S (0) nalkyl or aryl alkyl wherein n is 0, 1 or 2, or COheteroaryl, wherein the heteroaryl is a mono or bicyclic heterocycle. -10 members having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl , C? -C6 alkoxy, or hydroxy; and R7 is aroyl of C-Cn, C2-C6 alkanoyl, perfluoro C-C12 alkyl, S (O) n-alkyl,, S (0) n-aryl where n is 0, 1 or 2; COO-alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano , amino, nitro, C? -C6 alkyl, C? -Cs alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or C? -C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from 0, S or N and is optionally substituted with one or two groups independently selected from R5; biphenylalkyl of 13 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from 0, S or N-C6-C6alkyl, optionally substituted with one or two groups independently selected from R5; R8R9N-C6-C6-alkoxyaryl-C6-C6alkyl wherein R8 and R9 are independently selected from Ci-C3 alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; and the pharmaceutically acceptable salts thereof. The compounds that inhibit the most preferred matrix metalloproteinase and TACE of this invention are: l-benzyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-methoxy) hydroxyamide -benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid, 1- (3,4-dichlorobenzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxamide, hydroxamide 4- (4-methoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1-naphthalene-2-yl-methy1piperidin hydroxamide -4-carboxylic acid, hydroxyamide of 1-biphenyl-4-ylmethyl-4- (-methoxy-benzenesulfonyl) piperidin-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1- (3-methyl) hydroxamide -but-2-enyl) piperidin-4-carboxylic acid, 1- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-) hydroxyamide methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine -carb oxoyl, l-tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidin-4-carboxylic acid hydroxyamide, hydroxyamide -isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid, hydroxyamide of 1-methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid, hydroxyamide of l-benzyl-4 - (4-Butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid, 1- (4-fluoro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, hydroxyamide of 1- ( 4-fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide , 4- (4-methoxy-benzene) hydroxyamide sulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidin-4-hydroxyamide carboxylic acid 4- (4-n-butoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide 4- (4-methoxy-benzenesulfonyl) -1- (3 -phenoxy-propyl) -piperidine-4-carboxylic acid, 4- (4-n-butoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-hydroxyamide) -methoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid, 4- (4-n-butoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidin-4-hydroxyamide -carboxylic acid 4- (4-methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide, l-benzyl-4-hydroxyamide - (4-benzyloxy-benzenesulfonyl) -piperidine-carboxylic acid, 4- (4-Butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-caylic acid hydroxyamide, 4- (4-butoxy-benzenesulfonyl) hydroxyamide ) -1- [3- (2-morpholinyl-l-yl-ethoxy) -benzyl] -piperidine-4-caylic acid, 1-Methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-caylic acid hydroxyamide , Hydroxyamide of l-ethyl-4- (4-butoxy-benzenesulfonyl) -pip-eridin-caylic acid, Hydroxyamide of l-butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-caylic acid, Hydroxyamide of 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -1-methyl-piperidine-4-caylic acid, 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -l-ethyl-piperidine- hydroxyamide 4-caylic acid, Hydroxyamide of l-butyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-caylic acid, Hydroxyamide of l-benzyl-4- [4- (4-chloro- phenoxy) -benzenesulfonyl] -piperidine-4-caylic acid, l-benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -pip hydroxyamide] eridin-4-caylic acid, l-Butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-caylic acid hydroxyamide, l-benzyl-4- [4- (2- ethyl-butoxy) -benzenesulfonyl] -piperidine-4-caylic acid, 4- (4-Butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-caylic acid hydroxyamide, 4- (4-hydroxyamide) -methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-caylic acid, 4- (4-methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl) -hydroxyamide benzyl) -piperidine-4-caylic acid, 1- (3,4-dichlorobenzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-caylic acid hydroxyamide, [4- (4-chloro-benzyloxy) acid hydroxyamide) -benzenesulfonyl] -1-methyl-piperidine-caylic acid, 4- (4-butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-caylic acid hydroxamide, [4- (4-chloro]] -hydroxamide -benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-caylic acid, 4- (4-butoxyl) hydroxyamide i-Benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-caylic acid, 4- (4-Butoxy-benzenesulfonyl) -1- (4-cyano-benzyl) -piperidine-4-caylic acid hydroxyamide, Hydroxyamide 4- (4-butoxy-benzenesulfonyl) -l-pyridin-4-ylmethyl-piperidine-4-caylic acid, and pharmaceutical salts thereof. It is understood that the definition of the compounds of the formulas I, la and Ib, wherein R1, R2, R3 and R4 contain asymmetric cas, embraces all stereoisomers and possible mixtures thereof which possess the activity discussed below. In particular, it encompasses racemic modifications and any optional isomers possessing the indicated activity. The optical isomers can be obtained in pure form by standard separation techniques. Where otherwise stated, the term "alkyl" refers to a linear or branched C? ~C 4 alkyl group and the aryl is phenyl or naphthyl. The pharmaceutically acceptable salts are those derived from pharmaceutically acceptable organic and inorganic acids such as lactic, citric, acetic, tartaric, succinic, maleic, malonic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic acids and also known acceptable acids. The present invention accordingly provides a pharmaceutical composition which comprises a compound of this invention in combination or association with a pharmaceutically acceptable carrier. In particular, the present invention provides a pharmaceutical composition which comprises an effective amount of the compound of this invention and a pharmaceutically acceptable carrier. The compositions are preferably adapted for oral administration. However, they can be adapted for other modes of administration, for example, parenteral administration for patients. To obtain administration consistency, it is preferred that a composition of the invention be in the form of a unit dose. Suitable unit dosage forms include tablets, capsules and powders in bags or jars. Such unit dosage forms may contain from 0.1 to 100 mg of a compound of the invention. The compounds of the present invention can be administered orally in a dose range of about 0.01 to 100 mg per kg. Such a composition can be administered from 1 to 6 times a day, more usually 1 to 4 times a day. The compositions of the invention can be formulated with conventional excipients, such as fillers, a disintegrating agent, a binder, a lubricant, a flavoring agent and the like. They are formulated in a conventional manner. Also according to the present invention, there are provided processes for producing the compounds of the present invention. PROCESS OF THE INVENTION The compounds of the present invention can be prepared according to one of the general processes discussed below. The appropriately substituted mercaptan derivative was alkylated using ester derivative of substituted a-bromoacetic acid (Scheme I) or unsubstituted (Scheme 2) at reflux with acetone using K2CO3 as the base. The sulfide derivative thus obtained was oxidized using m-chloroperbenzoic acid in CH2C12 or using Oxone in methanol / water. The sulfone obtained in the aforementioned process can be further alkylated using a variety of alkyl halides to obtain the disubstituted derivative or can be hydrolyzed using NaOH / MeOH at room temperature. However, instead of using the ethyl ester, if the tertiary butyl ester is present, the hydrolysis can be carried out with TFA / CH2C12 at room temperature. Subsequently, the obtained carboxylic acid was converted to the hydroxamic acid derivative by reaction with oxalyl chloride / DMX (catalytic) and hydroxylamine / triethyl amine.

SCHEME 1 SYNTHESIS: to. K2C03 / Acetone / Ref luxury; b. M-chloroperbenzoic acid c. K2C03 / 18-Corona-6 / R3Br / Acetone / Ref luch / NaOH / MeoH / THF / RT (COCÍ) 2 / CH2Cl2 / Et3N / NH20H • HCl REACTION SCHEME 2 SYNTHESIS: to. K2C03 / Acetone / Reflux; b. M-chloroperbenzoic acid c. K2C03 / 18-Corona-6 / R2Br / Acetone / Ref lu / d. R3Br / NaOH 10 N / BzN (Et) 3 / CH2Cl2 / RT e. NaOH / MeOH / THF / RT f. (COCÍ) 2 / CH2Cl2 / Et3N / NH20H • HCl. As set forth in Scheme 3, the sulfide derivative can be further alkylated using lithium bis (methyl silyl) amide in THF at 0 ° C. The alkylated or monosubstituted compound was hydrolyzed and converted to the hydroxamic acid derivative. The sulfinyl derivatives were prepared by oxidizing the hydroxamic sulphide acid derivatives with H202 in MeOH solution.

REACTION SCHEME - 3 SYNTHESIS: NHOH to . K2C03 / Acetone / Reflux; b. R3Br / HMDS / THF; c. NaOH / MeoH / THF / RT d. (COCÍ) 2 / CH2Cl2 / Et3N / NH2OH • HCl. e. MeOH / H202 / RT The corresponding l-substituted-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxamides were prepared starting from diethanolamine and appropriately substituted alkyl or aryl halides (Reaction Scheme 4). The substituted diethanolamine derivatives at the N atom were converted to dichloro compounds using thionyl chloride. The corresponding dichlorides were reacted with substituted sulfonyl acetic acid ethyl ester derivatives in the presence of K2C03 / 18-Corona-6 in boiling acetone. The 1-substituted-4- (4-methoxy-benzenesulfonyl) -piperidine-carboxylic acid ethyl esters thus obtained were converted to the hydroxy amide as set forth in Reaction Scheme 4. Alternatively those classes of compounds and other heterocycles they can be prepared as indicated in Reaction Schemes 5 and 6.

REACTION SCHEME 4 to. K2C03 / RBr / Acetone / Refinery b. SOCI2 / CH2CI2 c. R1S02CH2COOEt / K2C03 / 18-Corona-6 / Acetone / Reflux d. NaOH? THF / MeOH / RT e. (COCI) JNH, OH.HCI / Et, N REACTION SCHEME 5 to. RBr / R1SH / CHCl3 / Reflux; b. Oxona / MeoH; and. (COCl) 2 / NH2OH.HCl / Et3N REACTION SCHEME 6 to. LiN (TMS) 2 / THF / 0 ° C / CO2; b. (COCÍ) 2 / NH2OH. HCl / Et3N Alternatively, Reaction Schemes 7 to 11 show methods for the preparation of hydroxamic acid compounds using a solid phase (P) support.

Reaction Scheme 7 Reactions and conditions: a) 2-halo acid (3.0 eq.); hydrate, 1-hydroxybenzotriazole (HOBt, 6.0 eq.); 1,3-diisopropylcarbodiimide (DIC, 4.0 eq.); DMF, 25 ° C; 2-16 hours, b) - Tiol (5.0 eq.); sodium iodide (5.0 eq.); 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 3.0 eq.); THF; 25 ° C; 12-16 hours. c) 70% tert-butylhydroperoxide (40 eq.); Benzenesulfonic acid (2.0 eq.); DCM; 25 ° C; 12-24 hours, d) jnCPBA (5.0 eq.); DCM; 25 ° C; 12-24 hours, e) TFA: DCM (1: 1); 25 ° C; 1 hour. 4-O-methylhydroxylamino-phenoxymethyl-copol (styrene-1% -divinylbenzene) -resin (hydroxylamine resin) can be coupled with 2-halo acid to give the hydroxamate ester resin. The coupling reaction can be carried out in the presence of carbodiimide, such as DIC, in an inert solvent such as DMF at room temperature. The halogen group can be displaced with a thiol in the presence of a base, such as DBU, in an inert solvent such as THF at room temperature. The sulfide can be oxidized to the sulfoxide by reaction with an oxidizing agent such as tert-butylhidoperoxide in the presence of an acid catalyst such as benzenesulfonic acid, in an inert solvent such as DCM at room temperature. Alternatively, the sulfide can be oxidized to sulfone by reaction with an oxidizing agent such as netachloroperbenzoic acid, in an inert solvent such as DCM at room temperature. The sulfur, sulfoxide or sulfone can be treated with an acid, such as trifluoroacetic acid, in an inert solvent such as DCM to liberate the free hydroxamic acid. Reaction Scheme 8 shows a method for preparing hydroxamic acids having alkoxy groups attached to the aromatic ring.

Reaction Scheme 8 n = 0, 1, 2 Reactions and conditions: a) 2-halo acid (3.0 eq.); 1-hydroxybenzotriazole hydrate (HOBt, 6.0 eq.); 1,3-diisopropylcarbodiimide (DIC, 4.0 eq.); DMF, 25 ° C; 2-16 hours, b) 4-Fluorobenzothiol (5.0 eq.); sodium iodide (5.0 eq.); 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 3.0 eq.); THF; ° C; 12-16 hours, c) Alcohol (15.0 eq.); sodium hydride (15.0 schematic.); DMF; 80 ° C; 15 hours, d) 70% tert-butylhydroperoxide (40 eq.); Benzenesulfonic acid (2.0 eq.); DCM; 25 ° C; 12-24 hours, e) mCPBA (5.0 eq.); DCM; 25 ° C; 12-24 hours, f) TFA: DCM (1: 1); 25 ° C; 1 hour.

The hydroxylamine resin can be coupled with the 2-halo acid and the halo group can be displaced by fluorobenzothiol as described above. The fluorine group can then be displaced with an alcohol in the presence of a base such as sodium hydride, in an inert solvent such as DMF at about 80 ° C. The alkoxybenzenesulfanyl hydroxamate ester can then be oxidized to any of the corresponding sulfinyl or sulphonyl hydroxamate ester as described above. The free hydroxamic acids can be released as described above. Reaction Scheme 9 shows a method for preparing 2-bisarylsulfanyl, sulfinyl and sulfonylhydroxamic acids.

Reaction Scheme 9 Reactions and conditions: a) 2-halo acid (3.0 eq.); 1-hydroxybenzotriazole hydrate (HOBt, 6.0 eq.); 1,3-diisopropylcarbodiimide (DIC, 4.0 eq.); DMF, 25 ° C; 2-16 hours, b) 4-Bromobenthiol (5.0 eq.); sodium iodide (5.0 eq.); 1,8-diazabicyclo [5. .0] undec-7-ene (DBU, 3.0 eq.); THF; ° C; 12-16 hours, c) 70% tert-butylhydroperoxide (40 eq.); Benzenesulfonic acid (2.0 eq.); DCM; 25 ° C; 12-24 hours, d) ÍIJCPBA (5.0 eq.); DCM; 25 ° C; 12-24 hours, e) Arylboronic acid (2.0 eq.); tetracis (triphenyl-phosphin) palladium (o) (0.1 eq.); 10% aqueous sodium carbonate (10.0 schematic.); DME; 80 ° C; 8 hours. TFA: DCM (1: 1); 25 ° C; 1 hour .

The hydroxylamine resin can be coupled with the 2-halo acid and the halo group can be displaced by bromobenzothiol as described above. The bromobenzenesulfanyl hydroxamate ester group can then be oxidized to any of the corresponding sulfinyl or sulphonyl hydroxamate ester as described above. The bromine group can then be replaced with an aryl group by reaction with the arylboronic acid in the presence of a catalyst such as tetracis (triphenylphosphine) palladium (0), and a base such as sodium carbonate, in an inert solvent such as the DME at approximately 80 ° C. The free hydroxamic acids can be released as described above. Reaction Scheme 10 shows a method for preparing hydroxamic acids having amine groups attached to the aromatic ring Reaction Scheme Reactions and conditions: a) 2-halo acid (3.0 eq.); 1-hydroxybenzotriazole hydrate (HOBt, 6.0 eq.); 1,3-diisopropylcarbodiimide (DIC, 4.0 eq.); DMF, 25 ° C; 2-16 hours, b) 4-Bromobenthiol (5.0 eq.); sodium iodide (5.0 eq.); 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 3.0 eq.); THF; 25 ° C; 12-16 hours. c) Amine (20.0 eq.); tris (dibenzylidenaceton) -dipaladium (0) (0.2 eq.); (S) - (-) - 2,2'-bis (diphenyl-phosphino) -l, l-binaphthyl ((S) -BINAP, 0.8 eq.); sodium tert-butoxide (18.0 eq.); dioxane; 80 ° C; 8 hours. TFA: DCM (1: 1); 25 ° C; 1 hour. The hydroxylamine resin can be coupled with the 2-halo acid and the halo group can be displaced by bromine. The bromine group can then be displaced with an amine in the presence of a catalyst such as tris (dibenzylidenaceton) -dipaladium (0) and a ligand such as (S) -BINAP and a base such as sodium tert-butoxide, in an inert solvent such as dioxane at about 80 ° C. The free hydroxamic acids can be released as described above. Reaction Scheme 11 shows a method for preparing hydroxamic acids having sulfonate groups attached to the aromatic ring.

Reaction Scheme 11 X = C -C alkyl, aryl Reactions and conditions: a) 2-halo acid (3.0 eq.); 1-hydroxybenzotriazole hydrate (HOBt, 6.0 eq.); 1,3-diisopropylcarbodiimide (DIC, 4.0 eq.); DMF, 25 ° C; 2-16 hours, b) 4-Hydroxybenzothiol (5.0 eq.); sodium iodide (5.0 eq.); 1,8-diazabicyclo [5. .0] undec-7-ene (DBU, 3.0 eq.); THF; 25 ° C; 12-16 hours. c) Sulfonyl chloride (5.0 eq.); triethylamine (2.0 eq.); DCM; 25 ° C; 8 hours, d) 70% tert-butylhydroperoxide (40 eq.); Benzenesulfonic acid (2.0 eq.); DCM; 25 ° C; 12-24 hours, e) mCPBA (5.0 eq.); DCM; 25 ° C; 12-24 hours, f) TFA: DCM (1: 1); 25 ° C; 1 hour. The hydroxylamine resin can be coupled with the 2-halo acid and the halo group can be displaced by hydroxybenzothiol as described above. The hydroxybenzylsulfanyl hydroxamate ester can then be oxidized to any of the corresponding sulfinyl or sulphonyl hydroxamate ester as described above. The hydroxy group can then be sulfonylated by reaction with sulfonyl chloride in the presence of a base such as triethylamine, an inert solvent such as DCM at about room temperature. The free hydroxamic acids can be released as described above. The following examples are presented to illustrate rather than to limit the scope of the invention. The purity by CLAP of the compounds prepared by combined procedures is presented as a percentage of area at a prescribed wavelength (% @ nm).

Example 1 N-Hydroxy-2- (4-methoxy-phenylsulfanyl) -2-methyl-3-phenyl-propionamide To a stirred solution of 4-methoxybenthiol (2.8 gm, 20 mmol) and anhydrous K2CO3 (10 gm, excess ) in dry acetone (100 ml), ethyl 2-bromo-propionate (3.6 gm, 20 mmol) was added in a spherical bottom flask and the reaction mixture was refluxed for 8 hours with good agitation. At the end, the reaction was allowed to cool and the potassium salts were filtered and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20 and 0.5 N NaOH solution. The organic layer was further washed well with water, dried over MgSO4, filtered and concentrated to give ethyl ester of 2- (4-methoxy) acid. phenylsulfanyl) -propionic as a light yellow oil. Performance of 4.5 gms (94%); MS: 241 (M + H) +. To a stirred solution of 2- (4-methoxy-phenylsulfanyl) -propionic acid ethyl ester (2.44 g, 10 mmol), in THF (100 ml) at -4 ° C, bis (trimethylsilyl) amide was slowly added. lithium (1 M solution, 15 ml, 15 mmol). The orange reaction mixture was stirred at room temperature for 15 minutes and then cooled to 0 ° C, at which time it was stirred for an additional hour. The temperature of the mixture was again brought to -40 ° C and benzyl bromide (1.72 gm, 10 mmol) in THF was added dropwise. The reaction was warmed to room temperature and stirred overnight before it was cooled in ice water, extracted with chloroform and washed with water. The organic layer was dried over MgSO, filtered and concentrated and chromatographed on a silica gel column with 10% ethyl acetate: hexane to give the ethyl ester of 2- (4-methoxy-phenylsulfanyl) -2 acid. -methyl-3-phenyl-propionic as a colorless oil. Yield of 860 mg, (26%); EM; 331 (M + H) +. The ethyl ester of 2- (4-methoxy-phenylsulfanyl) -2-methyl-3-phenyl-propionic acid (4.12 g, 12 mmol) was dissolved in methanol (50 ml) and 10 N NaOH (20 ml) was added. . The reaction was allowed to stir overnight at room temperature. The reaction mixture was concentrated, diluted with hexane: diethyl ether 1: 1 and extracted with H20. The aqueous layer was cooled with ice and acidified to pH 3. The acid was extracted with chloroform and the organic layer was dried over MgSO4, filtered and concentrated to give 2- (4-methoxy-phenylsulfanyl) -2-methyl -3-phenyl-propionic acid as a low melting solid. Yield 580 mg, 16%; EM; 303.2 (M + H) +. To a stirred solution of 2- (4-methoxy-phenylsulfanyl) -2-methyl-3-phenyl-propionic acid (0.5 g, 1.65 mmol) and DMF (2 drops) in CH2C12 (100 ml) at 0 ° C, oxalyl chloride (1.0 gm, 8 mmol) was added dropwise. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) in THF: water (5: 1, 30 ml) was stirred at 0 ° C for 1 hour in a separate flask. . At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH2C12 and slowly added to the hydroxylamine at 0 ° C. The reaction mixture was stirred at room temperature for 24 hours and concentrated. The residue obtained was extracted with chloroform and washed well with water. The obtained product was purified by chromatography on a column of silica gel and eluted with ethyl acetate. The N-hydroxy-2- (4-methoxy-phenylsulfanyl) -2-methyl-3-phenyl-propionamide was isolated as a colorless solid, mp 88 ° C; Yield of 300 mg, 57%; MS: 318 (M + H) +; 1 H NMR (300 MHz, CDC13): d 1.32 (s, 3 H), 3.07 (d, J = 11 Hz, 1 H), 3.23 (d, J = 11 Hz, 1 H), 3.79 (s, 3 H), 6.83- 7.36 (m, 9H).

Example 2 N-Hydroxy-2- (4-methoxy-phenylsulfanyl) -2-phenyl-acetamide. 2- (4-Methoxy-phenylsulfanyl) -phenyl acetic acid ethyl ester was prepared according to the general method set forth in Example 1. Starting with ethyl a-bromophenylacetate (7.18 g, 31.4 mmol) and 4-methoxythiophenol (4.4 g, 31.4 mmol), 8.5 g of the product was isolated as a light yellow oil. Yield 90%; EM; 273 (M + H) +. 2- (4-Methoxy-phenylsulfanyl) (2-phenyl) acetic acid was prepared starting from the ethyl ester of 2- (4-methoxy-phenylsulfanyl) -phenyl acetic acid (3.0 g, 10 mmol) dissolved in methanol (50 ml) and 10 N NaOH (20 ml) The resulting reaction mixture was worked up as in Example 1. Yield 1.9 g, 70% Low melting solid EM: 273 (M + H) +. -methoxy-phenylsulfanyl) -phenyl acetic acid (1.05 g, 3.83 mmol) and following the procedure set forth in Example 1, 154 g of N-hydroxy-2- (4-methoxy-phenylsulfanyl) -2-phenyl-acetamide were isolated as a colorless solid, mp 155 ° C; Yield 14%; MS: 290 (M + H) +; X H NMR (300 MHz. DMSO-d 6): d 3.72 (s, 3 H), 4.68 (s, 1 H), 6.86-7.44 (m, 9 H).

EXAMPLE 3 2- (4-Methoxy-phenylsulfanyl) -2,5-dimethyl-hex-4-enoic acid hydroxyamide 2- (4-methoxy-phenylsulfanyl) -2,5-dimethyl-hex- 4-enoic following the procedure of Example 1, second paragraph. Starting from the ethyl ester of (4-methoxy-phenylsulfanyl) -propionic acid (3.5 g, 14.3 mmol), and isoprenyl bromide (2.25 g, 15 mmol), 2.2 g of the product was isolated as an oil. Yield 50%; MS: 310 (M + H) +. 2- (4-Methoxy-phenylsulfanyl) -2,5-dimethyl-hex-4-enoic acid was prepared starting from 2- (4-methoxy-phenylsulfanyl) -2,5-dimethyl-hex-4-ethyl ester NaOH (2.0 g, 6.4 mmol) dissolved in methanol (50 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as in Example 1. The yield is 1.9 g, 99% low melting solids. MS: 280 (M + H) +. Starting with 2- (4-methoxy-phenylsulfanyl) -2,5-dimethyl-hex-4-enoic acid (1.67 g, 5.8 mmol) and following the procedure set forth in Example 1, 1.5 g of acid hydroxyamide was isolated. 2- (4-methoxy-phenylsulfanyl) -2,5-dimethyl-hex-4-enoic as a colorless solid. mp 89 ° C; Yield 94%; MS: 296 (M + H) +; X H NMR (300 MHz, CDC13): d 1.34 (s, 3 H), 1.61 (s, 3 H), 1.74 (s, 3 H), 2.41-2.58 (m, 2 H), 3.80 (s, 3 H), 5.17 (t , J = 7.5 Hz, 1H), 6.86 (d, J = 12.4 Hz, 2H), 7.35 (d, J = 12.4 Hz, 2H).

Example 4 N-Hydroxy-2- (4-methoxy-phenylsulfanyl) -3-methyl-butyramide Ethyl 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid ester was prepared according to the general method of Example 1 Starting with ethyl 2-bromo-3-methyl-butanoate (20.9 g, 100 mmol), and 4-methoxybenthiol (14.0 g, 100 mmol), 30 g of the product were isolated. Performance 99%; Light yellow oil; MS: 271 (M + H) +. 2- (4-Methoxy-phenylsulfanyl) -3-methyl-butyric acid was prepared starting from 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid ethyl ester (5.8 g, 21.6 mmol) dissolved in methanol ( 50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as set forth in Example 1. Yield 5.0 g, 99%. Low melting solid. MS: 242 (M + H) +. Starting with 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid (4.39 g, 18.3 mmol) and following the procedure set forth in Example 1, 1.5 g of N-hydroxy-2- (4-methoxy) were isolated. phenylsulfanyl) -3-methyl-butyramide as a colorless solid, mp 119 ° C; Performance 33%; MS: 256 (M + H) +; X H NMR (300 MHz. DMSO-d 6): d 0.90-1.07 (m, 6H), 1.84-1.96 (m, 1H), 3.07 (d, J = 8.8 Hz, 1H), 3.75 (s, 3H), 6.88. (d, J = 15 Hz, 2H), 7.35 (d, J = 15 Hz, 2H).

Example 5 N-Hydroxy-2- (4-methoxy-phenylsulfinyl) -2-methyl-3-phenyl-propionamide N-hydroxy-2- (4-methoxy-phenylsulfanyl) -2-methyl-3-phenyl-propionamide was dissolved (400 mg, 1.26 mmol) (prepared in Example 1) in methanol (100 ml) and 30% H202 (10 ml) was added. The reaction mixture was stirred for 48 hours at room temperature, time at which it was cooled to 0 ° C and quenched with saturated Na 2 SO 3 solution (20 ml). The reaction mixture became turbid. It was stirred for 4 hours before being concentrated with a water bath at room temperature, diluted with water, extracted with CHC13 and washed with H20. The organic layer was dried over MgSO4, filtered and concentrated. The title compound was isolated by column chromatography on silica gel, eluting with 75% ethyl acetate: hexane. Solid of low fusion. Yield: 220 mg, (52%); MS: 334 (M + H) +; X H NMR (300 MHz, CDC13): d 1.11 (s, 2 H), 1.22 (s, 3 H), 3.84 (s, 3 H), 7.00-7.61 (m, 9 H). Example 6 2- (4-Me oxy-benzenesulfinyl) -2,5-dimethyl-hexenic acid hydroxyamide Starting from 2- (4-methoxy-benzenesulfonyl) -2,5-dimethyl t -hexyl hydroxyamide -4 -neoxy (900 mg, 3.0 mmol) (prepared in Example 3) and following the procedure set forth in Example 5, 2- (4-methoxy-benzenesulfinyl) -2,5-dimethyl- hydroxyamide was isolated. hex-4-enoic as a colorless solid Yield: 104 mg (10%); mp 108 ° C; MS: 312 (M + H); * H NMR (300 MHz, DMSO-d6): d 0.88 (s, 3H), 1.59 (s, 3h), 1.68 (s, 3H), 2.27-2.80 (m, 2H), 5.02 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 9 Hz, 2H), 7.39 (d, J = 9 Hz, 2H).

Example 7 N-Hydroxy-2- (4-methoxy-benzenesulfinyl) -3-methyl-butyramide Starting with N-hydroxy-2- (4-methoxy-phenylsulfanyl) -3-methyl-butyramide (1 g, 3.9 mmol) ) prepared in Example 4, and following the procedure of Example 5, N-hydroxy-2- (4-methoxy-benzenesulfinyl) -3-methyl-butyramide was isolated as a colorless solid. Yield: 420 mg (40%); mp 163 ° C; MS: 272 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.89-1.12 (m, 6H), 1.63-1.74 (m, 1H), 3.13 (d, J = 7 Hz, 1H), 3.83 (s, 3H), 6.94. -7.65 (M, 4H).

EXAMPLE 8 N-Hydroxy-2- (4-methoxy-benzenesulfinyl) -2-phenyl-acetamide Starting from N-hydroxy-2- (4-methoxy-phenylsulfanyl) -2-phenyl-acetamide (240 mg, 0.83 mmole) prepared in Example 2, and following the procedure set forth in Example 5, N-hydroxy-2- (4-methoxy-benzenesulfinyl) -2-phenyl-acetamide was isolated as a colorless solid. Yield: 100 mg (40%); mp 135 ° C; MS 304 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 3.75 (s, 3 H), 4.38 (s, 1 H), 6.92-7.69 (m, 9 H) Example 9 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionamide. A stirred solution of 4-methoxybenzothiol (2.8 mg, 20 mmol) and anhydrous K2C03 (10 mg, excess) in dry acetone (100 ml), a-bromo ethyl acetate (3.3 mg, 20 mmol) in a spherical bottom flask and the alloy mixture heated to reflux for 8 hours with good agitation. At the end, the reaction mixture was allowed to cool and the potassium salts came in and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20 and 0.5 N NaOH solution. The organic layer was further washed well with water, dried over MgSO4, filtered and concentrated. The (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester was isolated as a pale yellow oil. Yield: 4.4 g (100%); EM; 227 (M + H) +. A stirred solution of 60% 3-chloroperbenzoic acid (14.0 mg, 40 mmol) in methylene chloride (100 mL) at 0 ° C, (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester (4.4 g, 20 mmol) in CH2C12 (15 ml). The reaction mixture turned cloudy and stirred at room temperature for 6 hours. The reaction mixture was then diluted with hexanes (300 ml) and stirred for 15 minutes. The solids were filtered and Na2So3 solution was added to the organic layer which was stirred for at least 3 hours before the mixture was extracted with CHC13 and washed with H2O. The organic layer was dried over MgSO4, filtered and concentrated and the colorless (4-methoxy-phenylsulfonyl) -acetic acid ethyl ester was isolated as an oil. Performance: 100%; MS: 259.1 (M + H) *. To a stirred solution of the ethyl ester of (4-methoxy-benzenesulfonyl) -acetic acid (2.5 g, 10 mmol) benzyl bromide (1.8 mg, 10 mmol) and 18-Corona-6 (500 mg) in acetone (250 ml) K2C03 (10 mg, excess) was added and the mixture was refluxed for 24 hours. At the end, the reaction mixture was filtered and the acetone layer was filtered. The residue obtained was extracted with chloroform, washed well with water, washed over anhydrous MgSO4, filtered and concentrated. The product obtained was purified by column chromatography on silica gel, eluting with 30% ethyl acetate: hexane. The product, 2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid ethyl ester was isolated as a low melting solid. Yield: 3.0 mg 86%; low melting solid; MS: 349 (M + H) +. To a stirred solution of 2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid ethyl ester (348 mg, 1 mmol) in methanol (25 ml), 10 N NaOH (10 ml) was added. The reaction mixture was stirred at room temperature for 48 hours. At the end, the reaction mixture was concentrated and carefully neutralized with dilute HCl. The residue obtained was extracted with chloroform, washed well with water, dried and concentrated. The obtained product was purified by column chromatography on silica gel eluting with ethyl acetate: methanol (95: 5) to give 2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid as a colorless oil. Yield: 250 mg, 89%; MS: 321 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -3-phenyl-propidic acid (200 mg, 0.625 mmol) and following the procedure set forth in Example 1, 150 mg of N-hydroxy-2- (4- methoxy-benzenesulfonyl) -3-phenyl-propionamide as a brown solid. Yield: 71%; mp 180 ° C; MS: 336 (M + H) +; X H NMR (300 MHz, CDCl 3): d 3.2 (m, 1 H), 3.8 (s, 3 H), 4.0-4.2 (m, 2 H), 7.0-8.0 (m, 9 H).

Example 10 2- (4-Methoxy-benzenesulfonyl) -hexanoic acid hydroxyamide 2- (4-methoxy-phenylsulfanyl) -hexanoic acid 2-ethyl ester was prepared according to the general method set forth in Example 1. Starting from 2- ethyl bromide hexanoate (7 g, 32 mmol) and 4-methoxybenthiol (4.2 g, 30 mmol), 8.3 g of the product were isolated. 98% yield; Light yellow oil; MS: 283 (M + H) +. Starting with ethyl ester of 2- (4-methoxy-phenylsulfanyl) -hexanoic acid (2.8 g, 10 mmol) and following the procedure set forth in Example 9, 3 g of ethyl ester of 2- (4-methoxy) acid were isolated. benzenesulfonyl) -hexanoic acid as a colorless solid. Yield: 95%; mp 62 ° C; MS: 314 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -hexanoic acid ethyl ester (2 g, 6.3 mmol), 1.5 g (83%) of 2- (4-methoxy-benzenesulfonyl) -hexanoic acid was isolated as a colorless solid isolated following the procedure outlined in Example 9. pf 116 ° C; MS: 287 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -hexanoic acid (1.0 g, 3.1 mmol) and following the procedure set forth in Example 1, 700 mg of 2- (4-methoxy-benzenesulfonyl) hydroxyamide were isolated -hexanoic as a colorless solid. Yield: 60%; mp 130 ° C; MS: 302 (M + H) +; XH MRN (300 MHz, CDCl 3): d 0.786 (t, J = 7.2 Hz, 3H), 1.1-1.3 (m, 4H), 1.6- 1.8 (m, 2H), 3.7 (m, 1H), 3.9 (s, 3H), 7.2 (d, J = 11 Hz, 2H), 7.8 (d, J = 11 Hz, 2H), 9.3 (s, 1H), 10.9 (s, 1H).

EXAMPLE 11 2- (4-methoxy-benzenesulfonyl) -tetradecanoic acid hydroxyamide 2- (4-methoxy-phenylsulfanyl) -tetradecanoic acid ethyl ester was prepared according to the general method set forth in Example 1. Starting with 2-bromomyristate of ethyl-corresponding (5.0 g, 14.9 mmmoles) and 4-methoxy thiophenol (1.9 g, 13.4 mmol), 5.0 g of the product was isolated. 98% yield; Light yellow oil; MS: 393 (M + H) +. Starting from 2- (4-methoxy-phenylsulfanyl) -tetradecanoic acid ethyl ester (3.9 g, 10 mmol) and following the procedure set forth in Example 9, 3.2 g of 2- (4-methoxy) ethyl ester were isolated. benzenesulfonyl) -tetradecanoic acid as a colorless solid. Yield: 76%; Oil; MS: 425 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -tetradecanoic acid ethyl ester (2.5 g, 5.9 mmmoles), 2.0 g (85%) of 2- (4-methoxy-benzenesulfonyl) -tetradecanoic acid was isolated as a colorless solid following the procedure set forth in Example 9. Mp 82 ° C; MS: 397 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -tetradecanoic acid (1.14 g, 2.9 mmol) and following the procedure set forth in Example 1, 670 mg of 2- (4-methoxy-benzenesulfonyl) hydroxyamide were isolated tetradecanoic as a matt white solid. Yield: 57%; mp 114 ° C; MS: 414 (M + H) +; X H NMR (300 MHz, DMS0-d 6): d 0.85 (t, J = 7 Hz, 3 H), 1.16-1.27 (m, 20 H), 1.66 (m, 2 H), 3.62-3.70 (m, 1 H), 3.87 (s, 3H), 7.12 (d, J = 15 Hz, 2H), 7.73 (d, J = 15 Hz, 2H).

Example 12 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-phenyl-propionamide To a stirred solution of 2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid ethyl ester (1.0 mg, 3 mmol) (example 9), methyl iodide (1 ml, in excess) and 18-Corona-6 (500 mg) in acetone (250 ml), K2C03 (10 mg, in excess) and the mixture of reaction was refluxed for 24 hours. At the end, the reaction mixture was filtered and the acetone layer was concentrated. The residue obtained was extracted with chloroform, washed well with water, dried over anhydrous MgSO4, filtered and concentrated. The obtained product was purified by column chromatography on silica gel eluting with 30% ethyl acetate: hexanes to give 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-phenyl-propionic acid ethyl ester as a colorless oil. Yield 1.0 g, 98%; AND; : 349 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-phenyl-propionic acid ethyl ester (900 mg, 2.7 mmol), 850 mg (quantitatively) of 2- (4-methoxy-benzenesulfonyl) acid was isolated -2-methyl-3-phenyl-propionic following the procedure set forth in procedure 9. Colorless oil EM 335 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-phenyl-propionic acid (900 mg, 2.7 mmol), and following the procedure set forth in Example 1, 450 mg of N-hydroxy-2- (methoxy-benzenesulfonyl) -2-met il-3-phenyl-propionamide as a brown solid. Yield: 48%; pf 58 ° C; MS: 350 (M + H) +; X H NMR (300 MHz, CDCl 3): d 1.4 (s, 3 H), 3.1 (d, J = 9 Hz, 1 H), 3.6 (d, J = 9 Hz, 1 H), 3.9 (s, 3 H), 6.8 - 7.8 (m, 9H).

Example 13 2- (4-Methoxy-benzenesulfonyl) -2,5-dimethyl-hex-4-enoic acid hydroxyamide Starting from 2- (4-methoxy-phenylsulfanyl) -propionic acid ethyl ester (Example 1) (12 g 50 mmol) and following the procedure set forth in Example 9, 12 g of 2- (4-methoxy-phenylsulfonyl) -propionic acid ethyl ester was isolated as a semi-solid. Yield, 100%; MS: 256.1 (M + H) +. Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2,5-dimethyl-hex-4-enoic acid ethyl ester was prepared, starting from (1 g, 3.6 mmol) of ethyl ester of 2- (4-methoxy-benzenesulfonyl) -propionic acid and isoprenyl bromide (1.0 g, 6 mmol). Yield, 1.0 g, 81%; Colorless oil; MS: 341 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2,5-dimethyl-hex-4-enoic acid ethyl ester (900 mg, 2.6 mmol) 800 mg (96%) of 2- (4-methoxy-benzenesulfonyl) acid -2,5-Dimethyl-hex-4-enoic as a semi-solid following the procedure set forth in Example 9. MS: 313 (M + H) +.

Starting with 2- (4-methoxy-benzenesulfonyl) -2,5-dimethyl-hex-4-enoic acid (1.0 g, 3.2 mmol) and following the procedure set forth in Example 1, 700 mg of 2-hydroxyamide were isolated. - (4-methoxy-benzenesulfonyl) -2,5-dimethyl-hex-4-enoic as a low melting solid. Yield: 67%; MS: 328 (M + H) +; XH NMR (300 MHz, CDC13): d 1.3 (s, 3H), 1.5 (d, J = 6.2 Hz, 6H), 2.3-3.0 (m, 2H), 3.9 (s, 3H), 7.0 (d, J = 11 Hz, 2H), 7.8 (d, J = 11 Hz, 2H).

Example 14 3- (Biphenyl-4-yl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide Following the procedure set forth in Example 12, ethyl ester of 3- (biphenyl) acid was prepared -4-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl propionic, starting from (2.7 g, 10 mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- ( chloromethyl) biphenyl (2.5 g, 12 mmol). Yield, 4.0 g, 91%; Colorless oil; MS: 438 (M + H) +. Starting from the 3- (biphenyl-4-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl propionic acid ethyl ester (3 g, 6.8 mmol), 2.5 g (89%) of 3- (biphenyl-4-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl propionic acid as a colorless solid following the procedure set forth in Example 9. mp 161 ° C; MS: 411 (M + H) +. Starting with 3- (biphenyl-4-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (2.0 g, 4.8 mmol) and following the procedure set forth in Example 1, 1.2 g of 3- (biphenyl-4-yl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide as a colorless solid. Yield: 58%; mp 177 ° C; MS: 426 (M + H) +; XH NMR (300 MHz, CDC13): d 1.4 (s, 3H), 3.2 (d, J = 9 Hz, 1H), 3.7 (d, J = 9 Hz, 1H), 3.9 (s, 3H), 7.0 - 7.8 (m, 12H), 9.7 (broad s, 1H).

Example 15 2- (4-Methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid hydroxyamide Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid ethyl ester was prepared starting from (2.7 g, 10 mmol) of 2-ethyl ester (4-methoxy-benzenesulfonyl) -propionic and geranyl bromide (3.0 g, 13 mmol). Yield, 4.0 g, 98%; Colorless oil; MS: 409 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid (3 g, 7.4 mmol), 2.8 g (96%) of acid were isolated. - (4-methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid as a colorless solid following the procedure set forth in Example 9. MS: 379 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid (2.0 g, 5.2 mmol) and following the procedure set forth in Example 1, 1.8 g of 2- (4-methoxy-benzenesulfonyl) -2,5,9-trimethyl-deca-4,8-dienoic acid hydroxyamide as a colorless solid. Yield: 88%; MS: 396 (M + H) +; XH NMR (300 MHz, CDC13): d 1.4 (s, 3H), 1.6 (s, 3H), 1.65 (s, 3H), 1.7 (s, 3H), 2.0 - 3.1 (m, 6H), 3.9 (s) , 3H), 5.5 (m, 2H), 6.98 (d, J = 9 Hz, 2H), 7.7 (d, J = 9 Hz, 2H).

Example 16 3-Cyclohexyl-N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide Following the procedure set forth in Example 2, 3-cyclohexyl-2- (4-methoxy) ethyl ester was prepared -benzenesulfonyl) -2-methyl-propionic, starting from (2.7 g, 10 mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and bromo methylcyclohexane (1.8 g, 10 mmol). Yield 3.5 g, 95%; Yellow oil; MS: 369 (M + H) +. Starting from the ethyl ester of 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (3 g, 8.1 mmol), 2.5 g (90%) of 3-cyclohexyl-2- ( 4-methoxy-benzenesulfonyl) -2-methyl-propionic acid as a colorless solid following the procedure set forth in Example 9. mp 116 ° C; MS: 341 (M + H) +. Starting with 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (2.0 g, 5.8 mmol) and following the procedure set forth in Example 1, 1.1 g of 3-cyclohexyl-N- were isolated. hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide as a colorless solid. Yield: 55%; mp 58 ° C MS: 356 (M + H) +; XH NMR (300 MHz, CDC13): d 1.4 (s, 3H), 2.3-1.0 (m, 13H), 3.9 (s, 3H), 7.0 (d, 8.8 Hz, 2H), 7.69 (d, 9.0 Hz, 2H).

Example 17 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide Following the procedure set forth in Example 12, ethyl 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (2.7 g, 10 mmol ) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- (2-piperidin-1-yl-ethoxy) -benzyl chloride (2.9 g, 10 mmol). Yield 4.8 g, 98%; Brown oil; MS: 490 (M + H) +.

Starting with ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid ester (4.0 gm, 7.9 mmol), isolated 3.5 g (Yield: 94%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid as colorless crystals following the procedure set forth in Example 9. Mp 106 ° C; MS: 462.5 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (2.0 g, 4.2 mmol) and following the procedure set forth in Example 1, 1 g of N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide was isolated as a colorless solid. Yield: 1 g, 48%; mp 98 ° C MS: 477 (M + H) +; XH NMR (300 MHz, CDC13): d 1.2 (s, 3H), 3.5-1.5 (m, 16H), 3.9 (s, 3H), 4.4 (m, 1H), 6.5-7.8 (m, 8H), 10.8 (s broad, 1H).

Example 18 2- [4- (2-Acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -propionic acid hydroxyamide Following the procedure set forth in Example 12, ethyl ester was prepared 2- [4- (2-Acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -propionic acid, starting from (2.7 g, 10 mmol) of ethyl ester of 2- ( 4-methoxy-benzenesulfonyl) -propionic acid and 1- [2- (4-chloromethyl-phenoxy) ethyl] -acepan (3.03 g, 10 mmol). Yield 4.5 g, 90%; Brown oil; MS: 504 (M + H) +. Starting from the ethyl ester of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -propionic acid (4.0 gm, 7.9 mmol), 3.5 g (Yield: 94%) of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) - propionic as a semi-solid following the procedure set forth in Example 9. MS: 476 (M + H) +. Starting from 2- [4- (2-acepan-l-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -propionic acid (2.0 g, 4.2 mmol) and following the procedure set forth in Example 1 , 1 g of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -propionic acid hydroxyamide was isolated as a colorless solid. Yield: 1.8 g, 87%; mp 68 ° C MS: 491 (M + H) +; * H NMR (300 MHz, CDC13): d 1.23 (s, 3H), 3.5-1.7 (m, 18H), 3.8 (s, 3H), 4.2 (m, 1H), 6.4-7.89 (m, 8H), 10.9 (broad s, 1H).

EXAMPLE 19 2- [4- (2-Acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid hydroxyamide Ethyl 2- [4- (2- (2-ethyl) ester was prepared acepan-l-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid according to the general method set forth in Example 12. Starting from ethyl ester of 2- (4-methoxy-benzenesulfonyl) - pentanoic acid (3.5 g, 11.7 mmol) and 1- [2- (4-chloromethyl-phenoxy) -ethyl] -acepan (3.9 g, 12.8 mmol). Yield 2.58 g, (42%); brown oil; MS: 532.4 (M + H) +. 2- [4- (2-Acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid prepared from the ethyl ester of 2- [4- (2-acetic acid 1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid (2 g, 3.76 mmol) was dissolved in methanol (300 ml) and 10 N NaOH (15 ml). The resulting mixture was worked up as set forth in Example 1. Yield of 830 mg (44%); solid brown; mp 55 ° C; MS: 504.4 (M + H) +. Starting with 2- [4- (2-acepan-l-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid (690 mg, 1.37 mmol) and following the procedure set forth in Example 1 , 240 mg of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -pentanoic acid hydroxyamide was isolated as a yellow solid. Performance 34%; mp 85 ° C MS: 519.2 (M + H) +; X H NMR (300 MHz, DMS0-d 6): d 0.71 (t, J = 7.3 Hz, 3 H), 0.78-1.77 (m, 16 H), 3.04-3.46 (m, 4 H), 3.87 (s, 3 H), 4.26 (m, 2H), 6.87 (d, J = 8.7 Hz, 2H), 7.14 (m, 4H), 7.71 (d, J = 9 Hz, 2H), 9.07 (s, 1H), 10 (s, 1H) ).

Example 20 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diisopropyl aminoethoxy) -phenyl] propionamide Following the procedure set forth in Example 12, prepared 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diisopropyl-amino-ethoxy) -phenyl] -propionic acid ethyl ester, starting from (5.4 g, 20 mmol ) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- (2-N, N-diisopropyl amino-ethoxy) -benzyl chloride (6.1 g, 20 mmol). Yield 8.9 g, 88%; Yellow oil; MS: 506.5 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diisopropyl amino-ethoxy) -phenyl] -propionic acid (4.0 gm, 7.9 mmol), 3.5 g (Yield: 92%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diisopropyl amino-ethoxy) -phenyl] -propionic acid were isolated as crystals colorless following the procedure set forth in Example 9. Mp 68 ° C; MS: 478.6 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, -diisopropyl-amino-ethoxy) -phenyl] -propionic acid (2.0 g, 4.1 mmol) and following the procedure set forth in Example 1, 1 g of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diisopropyl amino-ethoxy) -phenyl] -propionamide was isolated as a colorless solid. Yield: 1 g, 49%; mp 98 ° C (HCl salt); MS: 493 (M + H) +; 1 H NMR (300 MHz, CDC13): d 1.2 (s, 3H), 1.3 (d, 6H), 1.4 (d, 6H), 3.5-1.5 (m, 6H), 3.9 (s, 3H), 4.4 (s) , 2H), 6.5-7.8 (m, 8H), 10.8 (broad s, 1H).

Example 21 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl] propionamide Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid ethyl ester was prepared starting from (5.4 g, mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- (2-N, N-diethyl amino-ethoxy) -benzyl chloride (5.5 g, 20 mmol). Yield 8.5 g, 89%; Yellow oil; MS: 478.6 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (3.5 gm, 7.7 mmol), 3.0 g (Yield: 85%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid were isolated as crystals colorless following the procedure set forth in Example 9. Mp 96-98 ° C; MS: 450.5 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (2.0 g, 4.4 mmol) and following the procedure Exposed in Example 1, 1 g of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl] -propionamide was isolated as a solid colorless. Yield: 1 g, 48%; mp 56-59 ° C (HCl salt); MS: 465.5 (M + H) +; H NMR (300 MHz, CDC13): d 1.1 (t, 6H), 1.3 (s, 3H), 3.2-3.9 (m, 8H), 3.9 (s, 3H), 4.3 (s, 2H), 6.5 - 7.8 (m, 8H), 10.8 (broad s, 1H).

Example 22 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide Following the procedure set forth in Example 12, Ethyl 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (5.2 g, 20 mmol ) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 3- (2-piperidin-1-yl-ethoxy) -benzyl chloride (6.0 g, 20 mmol). Yield 8.2 g, 83%; Brown oil; MS: 490 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (6.0 gm, 12.2 mmol), isolated 4.9 g (Yield: 79%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid as colorless crystals following the procedure set forth in Example 9. Mp 112 ° C; MS: 462.5 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (3.0 g, 6.5 mmol) and following the procedure set forth in the example 1, 1.8 g of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide was isolated as a colorless solid. Yield: 1.8 g, 58%; mp 74 ° C MS: 477 (M + H) +; H NMR (300 MHz, CDC13): d 1.25 (s, 3H), 1.6-1.8 (m, 6H), 2.5-3.7 (m, 8H), 3.9 (s, 3H), 4.4 (t, 2H), 6.7 - 7.8 (m, 8H), 10.8 (broad s, 1H).

Example 23 3- (4- { 3- [4- (3-Chloro-phenyl) -piperazin-1-yl) -propoxy} phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide Following the procedure set forth in Example 12, ethyl ester of 3- (-. {3- [4- (3-chloro-phenyl) -piperazin-1-yl) -propoxy} phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic, starting from (2.72 g, 10 mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 1- [2 - (4-chloromethyl-phenoxy) -ethyl] -4- (3-chloro-phenyl) -piperazine (4.2 g, 11 mmol). Yield 5.5 g, 89%; Brown oil; MS: 616 (M + H) +.

Starting from the ethyl ester of 3- (4- { 3- [4- (3-chloro-phenyl) -piperazin-1-yl) -propoxy acid} phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (4.0 gm, 6.5 mmol), mmol), 3.0 g (yield: 78%) of 3- (4- (3 - [4- (3-Chloro-phenyl) -piperazin-1-yl) -propoxy.] -phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid as colorless crystals following the procedure set forth in Example 9. Mp 196 ° C; MS: 588.1 (M + H) +. Starting with 3- (4- { 3- [4- (3-chloro-phenyl) -piperazin-1-yl) -propoxy acid} phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (3.0 g, 5.1 mmol) and following the procedure set forth in Example 1, 1.8 g of 3- ( 4- { 3- [4- (3-chloro-phenyl) -piperazin-1-yl) -propoxy} phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide as a pale yellow solid. Yield: 1.8 g, 55%; mp 122 ° C (HCl salt); MS: 640 (M + H) +; XH NMR (300 MHz, CDC13): d 1.2 (s, 3H), 3.4-1.5 (m, 14H), 3.9 (s, 3H), 4.5 (m, 2H), 6.5 -8.2 (m, 12H), 10.3 (s broad, 1H).

Example 24 2- (4-Methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -hex-4-enoic acid hydroxyamide To a stirred solution of ethyl ester of (4-methoxy-benzenesulfonyl) -acetic acid (5.16 g, 20 mmol), isoprenyl bromide (3.0 g, 20 mmol) and 18-crown-6 (500 mg) in acetone (250 ml) was added K2C03 (10 gms, in excess) and the mixture was refluxed for 24 hours. At the end, the reaction mixture was filtered and the acetone layer was concentrated. The residue obtained was extracted with chloroform, washed well with water, dried over anhydrous MgSO4, filtered and concentrated. The product obtained was purified by column chromatography on silica gel, eluting with 30% ethyl acetate: hexane. The product of 2- (4-methoxy-benzenesulfonyl) -5-methyl-hex-4-enoic acid ethyl ester was isolated as a colorless oil. Yield: 3.0 g, 93%. Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -hexyl ethyl ester was prepared -4-enoic, starting from (3.26 g, 10 mmol) of 2- (4-methoxy-benzenesulfonyl) -5-methyl-hex-4-enoic acid ethyl ester and 4- (2-morpholin-4-) chloride il-ethoxy) -benzyl (3.0 g, 11 mmol). Yield 4.5 g, 82%; Brown oil; MS: 546 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -hex-4-enoic acid ethyl ester (3.0 gm, 5.5 mmol), 2.1 g were isolated (Yield: 75%) of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -hex-4-enoic acid as a semi-solid following the procedure set forth in Example 9. MS: 518.6 (M + H) +.

Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -hex-4-enoic acid (1.0 g, 1.9 mmol) and Following the procedure set forth in Example 1, 450 mg of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl hydroxyamide were isolated] -hex-4-enoic as a pale yellow solid. Yield: 450 mg, 45%; mp 92 ° C (HCl salt); EM: 570 (M + H) +; 1ti NMR (300 MHz, CDC13): d 1.3 (d, 3H), 1.65 (d, 2H), 3.5-1.8 (m, 14H), 3.9 (s, 3H), 4.5 (m, 2H), 5.4 (m , 1H), 6.5-7.9 (m, 8H), 11.5 (broad s, 1H).

Example 25 N-Hydroxy-2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl aminoethoxy) -phenyl] -propionamide To a stirred solution of 4-hydroxy thiophenol (12.6 g, 100 mmol) and triethyl amine (15.0 g, 150 mmol) in chloroform (400 ml) were added dropwise to propionate of 2-bromo ethyl (18.2 g, 100 mmol). The reaction mixture was refluxed for 1 hour and cooled to room temperature. The reaction mixture was washed with water, dried and concentrated. 2- (4-Hydroxy-phenylsulfanyl) -propionic acid ethyl ester was isolated as a colorless oil. Yield: 22.0 g, 99%, MS: 227 (M + H).

To a stirred solution of 2- (4-hydroxy-phenylsulfanyl) -propionic acid ethyl ester (11.3 g, 50 mmol), and K2CO3 (50 g, in excess) in acetone (300 mL) was added ethyl iodide ( 20 ml, excess) and refluxed for 8 hours. At the end, the reaction mixture was filtered and concentrated. The residue obtained was extracted with chloroform and washed well with water. It dried and concentrated. The product, 2- (4-ethoxy-phenylsulfanyl) -propionic acid ethyl ester was isolated as a colorless oil. Yield: 12.0 g, 98%; MS: 255 (M + H). The ethyl ester of 2- (4-ethoxy-phenylsulfanyl) -propionic acid was converted to 2- (4-ethoxy-phenylsulfonyl) -propionic acid ethyl ester following the procedure described in Example 9, paragraph 2. Following the above procedure in the example 12, 2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (3.5 g , 12.2 mmol) of 2- (4-ethoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- (2-N, N-diethyl amino-ethoxy) -benzyl chloride (3.5 g, 12.2 mmol). Yield 4.8 g, 80%; Brown oil; MS: 492.6 (M + H) +. Starting from the ethyl ester of 2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (4.0 gm, 8.1 mmol), 3.2 g (Yield: 80%) of 2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, -diethyl-amino-ethoxy) -phenyl] -propionic acid were isolated as a semi-solid colorless following the procedure set forth in Example 9. MS: 464.5 (M + H) +. Starting from 2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (2.0 g, 4.3 mmol) and following the procedure exposed in Example 1, 1.2 g of 2- (4-ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl aminoethoxy) -phenyl] -propionamide was isolated as a low colorless fusion. Yield: 1.2 g, 57%: (HCl salt); MS: 478.5 (M + H) +; XH NMR (300 MHz, CDC13): d 0.9 (t, 3H), 1.1 (t, 6H), 1.3 (s, 3H), 3.2-3.9 (m, 8H), 3.9 (s, 3H), 4.3 (s) , 2H), 6.5-7.8 (m, 8H), 10.8 (broad s, 1H).

Example 26 (4E) -2- (4-Methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -deca-4,8-hydroxyamide - dienoic acid To a stirred solution of (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester (5.16 g, 20 mmol), geranyl bromide (4.2 g, 20 mmol) and 18-Corona-6 (500 mg) in acetone (250 ml) was added K2C03 (10 gms, excess) and the mixture was refluxed for 24 hours. At the end, the reaction mixture was filtered and the acetone layer was concentrated. The residue obtained was extracted with chloroform, washed well with water, dried over anhydrous MgSO4, filtered and concentrated. The product obtained was purified by column chromatography on silica gel, eluting with 30% ethyl acetate: hexane. The product of 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-deca-4,8-dienoic acid ethyl ester was isolated as a colorless oil. Yield: 7.0 g, 89%. Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] ethyl ester was prepared. -deca-4, 8-dienoic, starting from (1.0 g, 2.5 mmol) of 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-deca-4,8-dienoic acid ethyl ester and sodium chloride. - (2-morpholin-1-yl-ethoxy) -benzyl (800 mg, 2.5 mmol). Yield 1.2 g, 76%; Brown oil; MS: 614 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -deca-, 8-dienoic acid (2.0 gm, 3.2 mmol), 1.5 g (Yield: 80%) of 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholin-4-yl-ethoxy) were isolated. -benzyl] -deca-4, 8-dienoic acid as a semi-solid following the procedure set forth in Example 9. MS: 586.6 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -deca-4,8-dienoic acid (1.0 g, 1.7 mmol) and following the procedure set forth in Example 1, 550 mg of (4E) -2- (4-methoxy-benzenesulfonyl) -5,9-dimethyl-2- [4- (2-morpholine) hydroxyamide were isolated. -4-yl-ethoxy) -benzyl] -deca-4,8-dienoic acid as a pale yellow solid. Yield: 550 mg, 53%; mp 61 ° C (Salt of HCl); MS: 638 (M + H) +.

Example 27 2- [4- (2-Diethylamino-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid hydroxyamide Ethyl 2- [4- (2-diethylamino-ethoxy) acid ethyl ester was prepared -benzyl] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid according to the general method set forth in Example 12. Starting from 2- (4-methoxy-benzenesulfonyl) -hexanoic acid ethyl ester (4 g, 12.7 mmol) and [2- (4-chloromethyl-phenoxy) -ethyl] -diethylamine (3.38 g, 14 mmol). Yield 8.21 g, crude, (100%); brown oil; MS: 520.4 (M + H) +. 2- [4- (2-Diethylamino-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid prepared from the ethyl ester of 2- [4- (2-diethylamino-ethoxy) -benzyl acid ] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid (8 g, 15.4 mmol) was dissolved in methanol (200 mL) and 10 N NaOH (30 mL). The resulting mixture was worked up as set forth in Example 1. Yield of 3.88 g, crude, (51%); brown oil; MS: 492 (M + H) +.

Starting with 2- [4- (2-diethylamino-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid (3.88 g, 7.89 mmol) and following the procedure set forth in Example 1, 800 were isolated mg of 2- [4- (2-diethylamino-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -hexanoic acid hydroxyamide as a yellow powder. Yield 20%; mp 67 ° C MS: 507.4 (M + H) +; XH NMR (300 MHz, DMS0-d6): d 0.75 (t, J = 7.1 Hz, 3H), 1.05 (m, 2 H), 1.23 (t, J = 7.2 Hz, 6H), 1.37-1.91 (m, 2H), 3.13 (m, 4H), 3.38-3.51 (m, 4H), 3.87 (s, 3H), 4.3 (t, J = 4.8 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 7.15 (m, 4H), 7.7 (d, J = 9 Hz, 2H), 9.07 (s, 1H), 10.1 (s, 1H).

Example 28 N-Hydroxy-2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide Following the procedure set forth in Example 12, 2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (3.1 g, 10 mlnol) of 2- (4-n-butoxy-benzenesulfonyl) -propionic acid ethyl ester (Prepared from 2- (4-hydroxy-phenylsulfanyl) -propionic acid ethyl ester and n-butyl bromide following the procedure set forth in example 27) 4- (2-piperidin-1-yl-ethoxy) -benzyl chloride (3.0 g, 10.1 mmol). Yield 4.5 g, 84%; Brown oil; MS: 532.7 (M + H) +. Starting from the ethyl ester of 2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (5.0 gm, 9.4 mmol) , 4.2 g (Yield: 88%) of 2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid were isolated. as a colorless solid following the procedure set forth in Example 9. MS: 504.6 (M + H) +. Starting with 2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (3.0 g, 5.9 mmol) and following the The procedure set forth in Example 1, 1.3 g of 2- (4-n-butoxy-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionamide were isolated as a colorless solid. PF. 65 ° C, Yield: 1.3 g, 42%; (Salt of HCl); MS: 478.5 (M + H) +; X H NMR (300 MHz, CDC13): d 0.9 (t, 3 H), 1.2 (s, 3 H), 1.3 - 1.9 (m, 10 H), 2.8 - 4.5 (m, 12 H), 6.8 - 7.8 (m, 8 H) ), 10.8 (s broad, 1H).

Example 29 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-die-yl-amino-ethoxy) -phenyl] -propionamide Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (5.0 g, mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 3- (2-N, N-diethyl amino-ethoxy) -benzyl chloride (4.9 g, 18 mmol). Yield 8.1 g, 93%; Brown oil; MS: 478.1 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (8.1 gm, 16.9 mmol), 6.7 g (Yield: 88%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid were isolated as a colorless semi-solid following the procedure set forth in Example 9. PF: 78-81 ° C; MS: 450.1 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (6.7 g, 15 mmol) and following the procedure Exposed in Example 1, 1.5 g of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-N, N-diethyl amino-ethoxy) -phenyl] -propionamide was isolated as a solid of low melting, colorless. Yield: 1.5 g, 21%; (Salt of HCl); MS: 450.5 (M + H) +; X H NMR (300 MHz, DMSO-de): d 1.21 (t, 6H), 1.26 (s, 3H), 3.18-3.24 (m, 2H), 3.38 (m, 4H), 3.43-3.46 (m, 2H) , 3.80 (s, 3H), 4.30 (s, 2H), 6.76-6.78 (d, 2H), 6.84-7.2 (m, 6H), 10.3 (s broad, H).

Example 30 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionamide Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (5.2 g, 20 mmol ) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 3- (2-morpholin-1-yl-ethoxy) -benzyl chloride (6.0 g, 20 mmol). Yield 9.1 g, 93%; Brown oil; MS: 492 (M + H) +. Starting with ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionic acid ester (101 gm, 20.3 mmol), isolated 8.0 g (Yield: 86%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionic acid as colorless crystals following the procedure set forth in Example 9. MS: 464.5 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionic acid (4.55 g, 9.8 mmol) and following the procedure set forth in Example 1, 440 mg of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [3- (2-morpholin-1-yl-ethoxy) -phenyl] -propionamide was isolated as a colorless solid. Yield: 440 mg, 9%; mp 63 ° C; MS: 479.5 (M + H) +; : H NMR (300 MHz, DMSO-d6): d 1.26 (s, 3H), 3.18-3.8 (m, 12H), 3.9 (s, 3H), 4.4 (m, 2H), 6.7-8.8 (m, 8H ), 10.8 (s broad, 1H).

Example 31 6- (1, 3-Dioxo-1,3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-methylhexanoic acid hydroxyamide Following the procedure set forth in Example 9 , 6- (1, 3-dioxo-l, 3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-hexanoic acid ethyl ester was prepared, starting from (5.0 g , 20 mmol) of 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester and 4-phthalimido bromobutane (5.66 g, 20 mmol). Yield 8.4 g, 97%; Brown oil; MS: 474 (M + H) +. Starting from the ethyl ester of 6- (1, 3-dioxo-1,3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-hexanoic acid (8.4 m, 17.7 mmol) , 6.95 g (88%) of 6- (1, 3-dioxo-l, 3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-hexanoic acid were isolated as a colorless oil following the procedure set forth in Example 9. MS: 446 (M + H) +. Starting from 6- (1, 3-dioxo-l, 3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-hexanoic acid (4.9 g, 11 mmol) and following the The procedure set forth in Example 1 was isolated from 3.1 g of 6- (1,3-dioxo-1,3-dihydro-isoindol-2-yl) -2- (4-methoxy-benzenesulfonyl) -2-hydroxyamide. -methyl-hexanoic acid as a light brown solid. Yield: 46%; mp 146-148 ° C; MS: 461.2 (M + H) +; 2 H NMR (300 MHz, DMSO-de): d 1.55 (s, 3 H), 1.61-3.77 (m, 8 H), 3.82 (s, 3 H), 6.92-8.21 (m, 8 H), 10.70 (s broad, 1 H ), 11.20 (s broad, 1H).

Example 32 3- [4- (2-Diethylamino-ethoxy) -phenyl] -2- (4-furan-2-yl-benzenesulfonyl) -N-hydroxy-2-methyl-propionamide To a solution with stirring 4-bromo trihophenol (19.0 g, 100 mmol) and triethyl amine (15.0 g, 150 mmol) in chloroform (400 ml) were added dropwise to propionate of 2-bromo ethyl (18.2 g, 100 mmol). The reaction mixture was refluxed for 1 hour and cooled to room temperature. The reaction mixture was washed with water, dried and concentrated. 2- (4-Hydroxy-phenylsulfanyl) -propionic acid ethyl ester was isolated as a colorless oil. Yield: 28.0 g, 99%, MS: 290 (M + H). The ethyl ester of 2- (4-bromo-phenylsulfanyl) -propionic acid was converted to 2- (4-bromo-phenylsulfonyl) -propionic acid ethyl ester following the procedure described in Example 9, paragraph 2. A mixture of ethyl 2- (4-bromo-phenylsulfonyl) -propionic acid ester (6.4 g, 20 mmol), 2- (tributyl stanyl) furan (7.5 g, 21 mmol) and (Ph3P) 4Pd (500 mg) were refluxed in degassed toluene (250 ml) for 8 hours. At the end the reaction mixture was filtered through Celite and concentrated. The product was purified by column chromatography on silica gel eluting with 50% ethyl acetate: hexane. Colorless oil Yield: 5.9 g, 95%, MS: 309 (M + H). Following the procedure set forth in Example 12, 2- (4- (2-furanyl-benzenesulfonyl-2-methyl-3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl ester ethyl ester was prepared. ] -propionic, starting from (3.08 g, 10.0 mmol) of 2- (4- (2-furanyl-benzenesulfonyl) -propionic acid ethyl ester and 4- (2-N, N-diethyl amino-ethoxy) - benzyl (3.5 g, 12.2 mmol) Yield 5.0 g, 97%; Brown oil; MS: 514.6 (M + H) +. Starting from the ethyl ester of 2- (4- (2-furanyl-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl-amino-ethoxy) -phenyl] -propionic acid (5.1 gm, 10.0 mmol), 3.8 g (Yield: 78%) of 2- (4- (2-furanyl-benzenesulfonyl-2-methyl-3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl ester were isolated. ] -propionic as a colorless solid following the procedure set forth in Example 9. PF: 58 C, MS: 486.5 (M + H) +. Starting from 2- (4- (2-furanyl-benzenesulfonyl) -2-methy1 -3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl] -propionic acid (5.0 g, 10.3 mmol) and following the procedure set forth in Example 1, 1.2 g of 2- (4- ethoxy-benzenesulfonyl) -2-methyl-3- [4- (2-N, N-diethyl amino-ethoxy) -phenyl] -propionamide as a low, colorless melting solid Yield: 3.2 g, 62%: (Salt HCl); MS: 502 (M + H) +; 1 H NMR (300 MHz, CDC13): d 1.23 (t, 6H), 1.4 (s, 2H), 2.8 (c, 4H), 3.0 (t, 2H ), 4.1 (t, 2H), 6.5 - 8.0 (m, 7H).

Example 33 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyramide Ethyl 2- (4-methoxy) -ethyl ester was prepared phenylsulfanyl) -butyric acid according to the general method set forth in Example 9. Starting with ethyl 2-bromobutyrate (10.71 g, 55 mmol) and 4-methoxythiophenol (7 g, 50 mmol), 5.19 g (40%); clear oil; MS: 255.2 (M + H) +. 2- (4-Methoxy-phenylsulfonyl) -butyric acid ethyl ester was prepared according to the general method set forth in Example 9. Starting with 2- (4-methoxy-phenylsulfanyl) -butyric acid ethyl ester (5 g, mmol). Yield 5.74 g (100%); clear oil; MS: 287.1 (M + H) +. Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyric acid ethyl ester was prepared, starting from ( 3.5 g, 12.2 mmol) of 2- (4-methoxy-benzenesulfonyl) -butyric acid ethyl ester and 4- [2- (chloromethyl-phenoxy) -ethyl] -morpholine (2.34 g, 6.7 mmol). Yield 5.7 g, 100%; Brown oil; MS: 506.4 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyric acid ethyl ester (5.54 gm, 11 mmol), 2.9 g were isolated ( Yield: 55%) of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyric acid as a colorless semi-solid following the procedure set forth in Example 9 MS: 478.3 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyric acid (2.6 g, 5.4 mmol) and following the procedure set forth in Example 1 , 510 mg of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -butyramide was isolated as a brown solid. Yield 2%; mp 51 ° C; MS: 493.3 (M + H) +; XH NMR (300 MHz, DMSO-de): d 0.90 (t, J = 7.2 Hz, 3H), 1.69-1.96 (m, 4H), 2. 67 (t, 2H), 3.34 (m, 8H), 3.87 (s, 3H), 4.04 (m, 2H), 6.8 (d, J = 8.7 Hz, 2H), 7.14 (m, 4H), 7.73 (d, J = 4.7 Hz, 2H), 9.08 (s, 1H), 10.8 (s, 1H).

Example 34 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyramide Following the procedure set forth in Example 12, ethyl ester was prepared 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyric acid, starting from (1.0 g, 3.33 mmol) of 2-ethyl ester (4-methoxy-benzenesulfonyl) -butyric acid and l- [2- (4-chloromethyl-phenoxy) -ethyl] -piperidine (0.85 g, 3.36 mmol). Yield 1.07 g, 62%; Brown oil; MS: 504.4 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyric acid ethyl ester (3.7 gm, 7.3 mmol), 2.2 g were isolated ( Yield: 63%) of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyric acid as a colorless semi-solid following the procedure set forth in Example 9 MS: 476 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyric acid (2.2 g, 4.63 mmol) and following the procedure set forth in Example 1 , 360 mg of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -butyramide was isolated as a brown solid. Performance 16%; mp 75 ° C; MS: 491.3 (M + H) +; H NMR (300 MHz, DMSO-d6): d 0.90 (t, J = 7.1 Hz, 3H), 1.36-1.96 (m, 4H), 2.4-2.63 (m, 14H), 3.87 (s, 3H), 4.01 (t, J = 5.9 Hz, 2H), 6.8 (d, J = 8.5 Hz, 2H), 7.11 (m, 4H), 7.71 (d, J = 8.8 Hz, 2H), 9.09 (s, 1H), 10.8 (s, 1H).

Example 35 2- (4-Methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid hydroxylamine 2- (4-methoxy-phenylsulfanyl) ethyl ester was prepared ) - pentanoic according to the general method set forth in Example 9. Starting with ethyl 2-bromovalerate (8.23 g, 39.3 mmol) and 4-methoxythiophenol (5 g, 35.7 mmol), 10.46 g (100%); clear oil; MS: 269 (M + H) +. Ethyl 2- (4-methoxy-phenylsulfonyl) -pentanoic acid ester was prepared according to the general method set forth in Example 9. Starting with 2- (4-methoxy-phenylsulfanyl) -pentanoic acid ethyl ester (6.9 g, 27.4 mmol). Yield 7.07 g (86%); clear oil; MS: 300.9 (M + H) +. Following the procedure set forth in Example 12, 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid ethyl ester was prepared, starting from ( 3.0 g, 10.8 mmol) of 2- (4-methoxy-benzenesulfonyl) -pentanoic acid ethyl ester and 4- [2- (chloromethyl-phenoxy) -ethyl] -morpholine (3.45 g, 11.9 mmol). Yield 3.08 g, 62%; Brown oil; MS: 520.4 (M + H) +.

Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid (2.73 gm, 5.27 mmol), 1.45 g were isolated ( Yield: 56%) of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid as a colorless semi-solid following the procedure set forth in Example 9 MS: 492.3 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid (1.01 g, 2.05 mmol) and following the procedure set forth in Example 1 , 190 mg of 2- (4-methoxy-benzenesulfonyl) -2- [4- (2-morpholin-4-yl-ethoxy) -benzyl] -pentanoic acid hydroxylamide was isolated as a brown solid. Yield 18%; mp 101 ° C; MS: 507.4 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.71 (t, J = 7 Hz, 3 H), 1.58-1.82 (m, 4 H), 3.12-3.98 (m, 12 H), 3.87 (s, 3 H), 4.35 (t, 2H), 6.89 (d, J = 8.7 Hz, 2H), 7.15 (m, 4H), 7.74 (d, J = 8.9 Hz, 2H), 9.08 (s, 1H).

Example 36 2- [4- (2-Acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -octanoic acid hydroxylamine 2- (4-methoxy-phenylsulfanyl) ethyl ester was prepared ) -octanoic acid according to the general method set forth in Example 9. Starting with ethyl 2-bromooctanoate (11.8 g, 47.3 mmol) and 4-methoxythiophenol (6 g, 43 mmol). Yield: 7.24 g (57%); clear oil; MS: 311.2 (M + H) +. Ethyl 2- (4-methoxy-phenylsulfonyl) -octanoic acid ester was prepared according to the general method set forth in Example 9. Starting from ethyl ester of the acid 2- (4-methoxy-phenylsulfanyl) -octanoic acid (4.0 g, 13.6 mmol).

Yield 3.7 g (83%); clear oil; MS: 343.3 (M + H) +. Following the procedure set forth in Example 12, 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -octanoic acid ethyl ester was prepared, starting from ( 1.69 g, 5.18 mmol) of 2- (4-methoxy-benzenesulfonyl) -octanoic acid ethyl ester and 1- [2- (4-chloromethyl-phenoxy) -ethyl] -acepan (1.73 g, 6.0 mmol). Yield 4.86 g, 99%; Brown oil; MS: 574.5 (M + H) +. Starting from ethyl 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -octanoic acid ethyl ester (4.8 gm, 8.37 mmol), 1.55 g (Yield: 34%) of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) - octanoic as a colorless semi-solid following the procedure set forth in Example 9. MS: 551 (M + H) +. Starting with 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -octanoic acid (1.09 g, 2.0 mmol) and following the procedure set forth in Example 1 , 300 mg of 2- [4- (2-acepan-1-yl-ethoxy) -benzyl] -2- (4-methoxy-benzenesulfonyl) -octanoic acid hydroxylamide was isolated as a yellow solid. Yield 27%; mp 65 ° C; MS: 561.6 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.81 (t, J = 6.6 Hz, 3 H), 1.08-1.82 (m, 14 H), 3.13-3.51 (m, 12 H), 3.87 (s, 3 H), 4.33 (t, 2H), 6.88 (d, J = 8.7 Hz, 2H), 7.14 (m, 4H), 7.7 (d, J = 9 Hz, 2H), 9.06 (s, 1H), 10.28 (s, 1H) .

Example 37 2- (4-Methoxy-benzenesulfanyl) -octanoic acid hydroxylamine 2- (4-methoxy-phenylsulfanyl) -octanoic acid ethyl ester was prepared according to the general method set forth in Example 9. Starting with 2-bromooctanoate ethyl (11.8 g, 47.3 mmol) and 4-methoxythiophenol (6 g, 43 mmol). Yield: 7.24 g (57%); clear oil; MS: 311.2 (M + H) +. Starting from 2- (4-methoxy-benzenesulfanyl) -octanoic acid ethyl ester (3.1 gm, 10 mmol), 2.55 g (Yield: 90%) of 2- (4-methoxy-benzenesulfanyl) -octanoic acid was isolated as a colorless semi-solid following the procedure set forth in Example 9. MS: 283 (M + H) +. Starting from 2- (4-methoxy-benzenesulfanyl) -octanoic acid (4.25 g, 16 mmol) and following the procedure set forth in Example 1, 3.64 g of 2- (4-methoxy-benzenesulfanyl) -octanoic acid hydroxylamide were isolated. as a colorless solid. Yield 76%, PF 90 ° C; MS: 298.2 (M + H).

Example 38 2- (4-Fluoro-phenylsulfanyl) -octanoic acid hydroxylamine 2- (4-Fluoro-phenylsulfanyl) -octanoic acid ethyl ester was prepared according to the general method set forth in Example 9. Starting with 2-bromooctanoate ethyl (6.47 g, 24.7 mmol) and 4-fluorothiophenol (3 g, 23.4 mmol). Yield: 6.31 g (90%); clear oil; MS: 299 (M + H) +. Starting from the ethyl ester of 2- (4-fluoro-benzenesulfanyl) -octanoic acid (3.1 gm, 10 mmol), 2.89 g (Yield: 100%) of 2- (4-fluoro-benzenesulfanyl) -octanoic acid were isolated. as a colorless semi-solid following the procedure set forth in Example 9. MS: 268.9 (M + H) +. Starting from 2- (4-fluoro-benzenesulfanyl) -octanoic acid (2.49 g, 9.2 mmol) and following the procedure set forth in Example 1, 2.72 g of 2- (4-fluoro-benzenesulfanyl) -octanoic acid hydroxylamide were isolated. as a colorless solid. Yield 99%, PF 58 ° C; MS: 284 (M + H).

Example 39 2- (l-Methyl-lH-imidazol-2-ylsulfanyl) -octanoic acid hydroxylamine 2- (1-Methyl-lH-imidazol-2-ylsulfanyl) -octanoic acid ethyl ester was prepared according to the general method exposed in Example 9. Starting with ethyl 2-bromooctanoate (12.1 g, 48 mmol) and l-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oil; MS: 285 (M + H) +. Starting from the ethyl ester of 2- (1-methyl-lH-imidazol-2-ylsulfanyl) -octanoic acid (12 gm, 42.2 mmol), 10.2 g (Yield: 95%) of 2- (1-methyl) acid were isolated. 1H-imidazol-2-ylsulfanyl) -octanoic acid as a colorless solid following the procedure set forth in Example 9. MP: 95 C, MS: 257.1 (M + H) +. Starting from 2- (l-methyl-lH-imidazol-2-ylsulfanyl) -octanoic acid (7.84 g, 30.6 mmol) and following the procedure set forth in Example 1, 2.77 g of 2- (1-) -hydroxylamide were isolated. methyl-lH-imidazol-2-ylsulfanyl) -octanoic acid as a colorless solid. Yield 33%, PF 125 C; MS: 272.1 (M + H).

Example 40 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -3-naphthalen-2-yl-propionamide Following the procedure set forth in Example 9, ethyl ester of 2- (4-methoxy-benzenesulfonyl) - 3-naphthalen-2-yl-propionic acid, starting from (5.0 g, 20 mmol) of 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester and 2-bromomethyl-naphthalene (4.4 g, 20 mmol). Yield 7.2 g, 91%; Colorless oil; MS: 399 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -3-naphthalen-2-yl-propionic acid ethyl ester (3.7 m, 9 mmol), 3.3 g (96%) of 2- (4-methoxy) acid were isolated. -benzenesulfonyl) -3-naphthalen-2-yl-propionic acid as a colorless oil following the procedure set forth in Example 9. MS: 369.1 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -3-naphthalen-2-yl-propionic acid (2.2 g, 5.9 mmol) and following the procedure set forth in Example 1, 820 mg of N-hydroxy-2- were isolated (4-methoxy-benzenesulfonyl) -3-naphthalen-2-yl-propionamide as a light brown solid. Yield: 36%, mp 161-163 ° C; MS: 385.9 (M + H) +; XH NMR (300 MHz, CDC13): d 3.32 (d, J = 7.0 Hz, 1H), 3.69 (s, J = 7.0 Hz, 1H), 3.82 (s, 3H), 5.02 (s, 1H), 6.92- 7.89 (m, 11H).

Example 41 N-Hydroxy-2- (4-methoxy-phenylmethanesulfonyl) -2-methyl-3-phenyl propionic acid hydroxyamide A mixture of 4-methoxybenzyl mercaptan (7.0 g, 45 mmol), ethyl 2-bromopropionate (8.2 g , 46 mmoles) and oven-dried potassium carbonate, pulverized (10 g, 72 mmol) in 150 mL of acetone was heated to reflux for 18 hours. The mixture was cooled, filtered and the filtrate was concentrated. The residue was extracted into 150 mL of methylene chloride, washed with water (150 mL), dried over anhydrous sodium sulfate and evaporated to give 12 g (99%); colorless liquid; MS 255.1 (M + H). This product was used without further purification. To a solution cooled with ice (5 ° C) of ethyl ester of 2- (4-methoxy-phenylmethanesulfanyl) -propionic acid (5.7 g, 21 mmol) in 100 mL of CH2C12 were added portions (7.2 g, 40 mmol) of m-chloroperbenzoic acid and the mixture was stirred for 1 hour. The reaction was eluted with hexanes (500 mL) and stirred at 25 ° C for 30 minutes at room temperature. The mixture was filtered and the organic layer was treated with saturated aqueous sodium disulphide (200 mL). The hexanes solution containing the product was washed with water, dried (Na2SO, j) and concentrated. Yield 5.5g (91%); colorless oil; MS 287.1 (M + H) +. Following the procedure set forth in Example 9, 2- (4-methoxy-phenylmethane-sulfonyl) -2-methyl-3-phenyl-propionic acid ethyl ester was prepared, starting from ethyl ester of 2-4 (methoxy-phenylmethanesulfonyl) ) -propionic (2 g, 7 mmoles) and benzyl bromide (1.3 g, .7.7 mmoles). Yield 3.0 g, 100%; low melting solids; MS: 377 (M + H) +. 2- (4-Methoxy-phenylmethanesulfonyl) -2-methyl-3-phenyl-propionic acid was prepared starting from 2- (4-methoxy-phenylmethanesulfonyl) -2-methyl-3-phenyl-propionic acid ethyl ester. (3.5 g, 9.0 mmol) dissolved in methanol (50 ml) and 10 N NAOH (30 ml). The resulting reaction mixture was worked up as set forth in Example 9. Yield, 930 mg, 31%. Colorless solid, mp: 106-108 ° C; EM; 347 (M + H) +. Starting from 2- (4-methoxyphenylmetanesulfonyl) -2-methyl-3-phenyl-propionic acid (2.7 g, 7.0 mmol) and following the procedure set forth in Example 1, 266 mg of N-hydroxy-2- ( 4-methoxy-phenylmethanesulfonyl) -2-methyl-3-phenylpropionic acid as a light colorless solid; Performance: %; mp 58-59 ° C; MS: 364.2 (M + H) +; X H NMR (300 MHz, DMSO-d 6: d 1. 28 (s, 3H), 2.84-2.88 (d,, 1H), 3.75 (s, 3H), 3.81-3.86 (d, 1H), 4.59-4.63 (d, 1H), 4.69-4.74 (d, 1H), 6.94-6.98 (d, 2H), 7.19 (m, 2H), 7.29-7.33 (d, 4H), 9.24 (s, 1H), 10.88 (s, 1H).

Example 42 5-Methyl-2- (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic acid hydroxyamide 5-Methyl-2-ethyl ester was prepared (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic according to the general method set forth in Example 9. Starting from ethyl α- (p-toluenesulfonyl) acetate (2.9 g, 10.9 mmol), and 4-bromo-2-methyl butene (3.42 g, 23 mmol). Yield, 4.6 g; solid brown; MS 379.2 (M + H) +. 5-Methyl-2- (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic acid was prepared according to the general method set forth in Example 9. Starting from ethyl 5-methyl-2- (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic acid ester (4.5 g, 11 mmol), ethanol (15 mL) and sodium hydroxide 10 N. Starting from 5-methyl-2- (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic acid (4.1 g, 11 mmol) and Following the procedure set forth in Example 1, 1.07 g of 5-methyl-2- (3-methyl-but-2-enyl) -2- (toluene-4-sulfonyl) -hex-4-enoic acid hydroxyamide were isolated. as a colorless solid; Yield: 30%; mp 108-110 ° C; MS: 3.66.2 (M + H) +; XH NMR (300 MHz, DMSO-d6: d 1.49 (s, 6H), 2.41 (s, 3H), 2.53-2.63 (m, 4H), 5.00-5.05 (t, 2H), 7.40-7.43 (d, 2H) ), 7.59-7.62 (d, 2H), 9.04 (s, 1H), 10.80 (s, 1H).

Q-7 Example 43 2-Methyl-2- (2-methyl-furan-3-sulfonyl) -3-phenyl-propionic acid hydroxyamide 2-Methyl-2- (2-methyl-furan-3-sulfonyl) ethyl ester was prepared ) -3-phenyl-propionic acid (prepared from 3-mercapto-2-methylfuran) according to the general method set forth in example 9. Starting from the ethyl ester of 2-methyl-2- (2-methyl-furan- 3-ylfuran) -propionic (2.9 g, 11.9 mmol), benzyl bromide (2.22 g, 13 mmol) and potassium carbonate (10 g) in acetone (75 mL). Performance (99%); amber oil; MS 337.1 (M + H) +. 2-Methyl-2- (2-methyl-furan-3-sulfonyl) -3-phenyl-propionic acid was prepared according to the general method set forth in Example 9. Starting from 2-methyl-2-ethyl-ethyl ester ( 2-methyl-furan-3-ylfuran) -propionic (4.8 g, 14.3 mmol), dissolved in ethanol (25 mL and 10 N sodium hydroxide (10 mL) Yield 3.7 g (84%), white solid, MS 307.4 (MH) Starting from 2-methyl-2- (2-methyl-furan-3-sulfonyl) -3-phenyl-propionic acid (3.58 g, 12 mmoles) and following the procedure set forth in example 1, isolated 1,078 g of 2-methyl-2- (2-methyl-furan-3-sulfonyl) -3-phenyl-propionic acid hydroxyamide as an orange solid; Yield: 29%, mp 68-70 ° C; : 324 (M + H) +;? H NMR (300 MHz, DMSO-d6): d 1.27 (s, 3H), 2.81-2.86 (d, 1H), 3.33 (s, 3H), 3.61-3.66 (d , 1H), 6.66 (s, 1H), 7.19-7.25 (m, 5H), 7.76 (s, 1H), 9.09 (s, 1H), 10.81 (s, 1H) Example 44 2-Methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid hydroxyamide Acid ethyl ester was prepared 2-Methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid according to the general method set forth in example 9. Starting from 2- (2-methyl-furan-3-sulfonyl) -propionic acid ethyl ester (2.4 g, 9.8 mmol) and 1- [2- (4-chloromethyl-phenoxy) -ethyl] -piperidine (2.96 g, 10.7 mmol) ); Yield, 2.4 g (92%); amber oil; EM 464.2 (M + H) +. 2-Methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid was prepared according to the general method set forth in example 1. Starting from 2-methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid ethyl ester (2.01 g, 4.5 mmol), dissolved in ethanol (20 mL) and ION sodium hydroxide (10 mL) the resulting mixture was worked up as set forth in Example 9. Yield, 2.03 g; amber crystals, mp 66-68 ° C; MS 434 (M-H). Starting from 2-methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (2.03 g, 6.0 mmol) and Following the procedure set forth in Example 1, 1.36 g of 2-methyl-2- (2-methyl-furan-3-sulfonyl) -3- [4- (2-piperidin-1-yl-ethoxy) hydroxyamide were isolated. ) -phenyl] -propionic with a solid amber color; Performance: 32%; mp 115-117 ° C; MS: 451.1 (M + H); X H NMR (300 MHz, DMSO-d 6): d 1.15- 122 (m, 2H), (1.75 (s, 3H), 1.78 (s, 3H) 2.98-3.03 (m, 2H), 3.42-3.47 (m, 2H), 3.5 (s, 3H), 6.65 (s, 1H), 6.87-6.90 (d, 2H), 7.12-7.17 (d, 2H), 10.35 (s, 1H), 10.60 (s, 1H), 11.70 (s, 1H).

Example 45 2-Methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid hydroxyamide 2-methyl-3-ethyl ester was prepared - [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid according to the general method set forth in example 9. Starting from ethyl ester of 2- (thiophene) acid -2-sulfonyl) -propionic (prepared from 2-mercaptothiophene and 2-bromopropionic acid ethyl ester) (4.4 g, 17.7 mmol) and 1- [2-4-chloromethylphenoxy) -ethyl] -piperidine (5.3 g, 19.5 mmoles); Performance (96%); semisolid; EM 466. 2-Methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid was prepared according to the general method set forth in the example 9. Starting from ethyl ester of 2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid (9.8 g, 20 mmol), dissolved in ethanol (20 mL) and 10 N sodium hydroxide (20 mL). The resulting mixture was worked up as set forth in example 1.

Yield, 4.5 g (49%); solid white pf 170-172 ° C; MS 436.3 (M-H). Starting from 2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid (3.6 g, 8.0 'I mmoles) and following the procedure outlined in the example 1, 345 mg of 2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl-2- (thiophene-2-sulfonyl) -propionic acid hydroxyamide was isolated as a clear, colorless solid; Yield: 10%; mp 115-118 ° C; MS: 451.2 (M + H) +; NMR (300 MHz, DMS0-d6): d 1.29 (s, 3H), 1.66-1.78 (m, 6H), 2.81-2.86 (d, 1H), 2.96-3.99 (m, 4H), 3.39-3.47 (m , 2H), 3.51-3.59 (d, 1H), 4.32 (m, 2H), 6.72-6.74 (d, 1H), 6.87-6.96 (d, 2H), 7.01-7.20 (m, 3H), 7.31-7.33 (m, 1H), 7.69-7.72 (m, 1H), 7.83-7.84 (m, 1H), 8.07-8.08 (dd, 1H), 8.17 (dd, 1H), 9.0 (s, 1H) 10.0 (s, 1H), 10.78 (s, 1H).

EXAMPLE 46 2- (Octane-1-sulfonyl) -3- [4- (2-piperidin-yl-ethoxy) -phenyl] propionic acid hydroxyamide 2- (octane-1-sulfonyl) -3-ethyl ester - [4- (2-piperidin-yl-ethoxy) -phenyl] -propionic acid according to the general method set forth in example 9. Starting from the ethyl ester of 2- (octan-1-sulfonyl) -propionic acid (5.0g, 18 mmol) and 1- [2- (4-chloro-methylphenoxy) -ethyl] -piperidine (5.6 g, 19.7 mmol); Yield, 8.9g (96%); amber oil, MS 495. 2- (Octane-1-sulfonyl) -3- [4- (2-piperidin-yl-ethoxy) -phenyl] propionic acid was prepared according to the general method set forth in example 9. Starting from 2- (octane-1-sulfonyl) -3- [4- (2-piperidin-yl-ethoxy) -phenyl] propionic acid ethyl ester (8.9g, 18 mmol), ethanol (25 mL) and sodium hydroxide 10 N (25 mL.) Yield, 6.0g (72%). Starting with 2- (octane-1-sulfonyl) -3- [4- (2-piperidin-yl-ethoxy) -phenyl] propionic acid (3.6 g, 7.7 mmol) and following the procedure set forth in Example 1, 3.3 g of 2- (octan-l-sulfonyl) -3- [4- (2-piperidin-yl-ethoxy) -phenyl] propionic acid hydroxyamide as a brown solid; Performance: 89%; mp 69-70 ° C; MS: 483.2 (M + H) +; X H NMR (300 MHz, DMSO-dd): d.687 (t, 3H), 127-1.69 (m, 15H), 2.71-2.75 (d, 1H), 3.51 (s, 3H), 3.65-3.69 (d , 1H), 6.68-6.89 (d, 2H), 7.08-7.11 (d, 2H), 9.16 (s, 1H), 10.70 (s, 1H).

EXAMPLE 47 3-Biphenyl-4-yl-2-methyl-2- (1-methyl-1H-imidazole-2-sulfonyl) -propionic acid hydroxyamide 3-biphenyl-4-yl-2-ethyl ester was prepared methyl-2- (1-methyl-1H-imidazole-2-sulfonyl) -propionic acid according to the general method as set forth in Example 9. Starting from 2-methyl- (1-methyl-1H-imidazolesulfonyl) ethyl ester ) -propionic prepared from (1-methyl-2-mercapto imidazole and 2-bromoethyl propionate) (3.0 g, 12.2 mmol) and 4-chloromethyl biphenyl) (2.97 g, 15 mmol). Performance 5.0g (99%); low melting solid; MS 413 (M + H) +. 3-Biphenyl-4-yl-2-methyl-2- (1-methyl-1H-β-midazole-2-sulfonyl) -propionic acid was prepared according to the general method set forth in Example 9. Starting from ethyl ester of the acid 3-biphenyl-4-yl-2-methyl-2- (l-methyl-lH-imidazole-2-sulfonyl) -propionic acid (5.0g, 11.9 mmol), ethanol (15 mL) and sodium hydroxide ION (10 mL) ). Yield 2.8 g (61%); brown solid mp 119-122 ° C; MS 385.2 (M + H) +. Starting from 3-biphenyl-4-yl-2-methyl-2- (l-methyl-lH-imidazole-2-sulfonyl) -propionic acid ethyl ester (2.8g, 7.0 mmol) and following the procedure set forth in the example 1, 112 mg of hydroxyamide of 3-biphenyl-4-yl-2-methyl-2- (1-methy1-1H-imidazole-2-sulfonyl) -propionic acid was isolated as a solid colored, brown, - yield: 4%; mp 112 ° C; MS: 399.0 (M + H) +; X H NMR (300 MHz, DMSO-dd): d 0.911 (s, 3 H), 3.3 (s, 3 H), 3.5 (d, 1 H), 4.2 (d, 1 H), 6.8 (d, 1 H), 6.9 (d , 1H), 7.18-7.66 (m, 5H), 7.30-7.33 (d, 2H), 7.55-7.58 (d, 2H).

Example 48 2-Methyl-3-phenyl-2- (thiophene-2-sulfonyl) -propionic acid hydroxyamide 2-Methyl-3-phenyl-2- (thiophene-2-sulfonyl) -propionic acid ethyl ester was prepared from according to the general method set forth in Example 9. Starting with ethyl ester of 2- (thiophene-2-sulfonyl) -propionic acid (30. Og, 12 mmol), benzyl bromide (2.48 g, 15 mmol). Yield, 5.2g (%); brown oil; MS 339.1 (M + H) +. 2-Methyl-3-phenyl-2- (thiophene-2-sulfonyl) -propionic acid was prepared according to the general method set forth in Example 9. Starting from 2-methyl-3-phenyl-2- (2-methyl) ethyl ester thiophen-2-sulfonyl) -propionic acid (5.0 g, 15 mmol), ethanol (30 mL) and sodium hydroxide ION (10 mL). Yield, 5.6g MS 310.0 (M + H) +. Starting from 2-methyl-3-phenyl-2- (thiophene-2-sulfonyl) -proic acid (5.0 g, 16 mmol) and following the procedure set forth in Example 1, 1.8 g of 2-hydroxyamide were isolated. methyl-3-phenyl-2- (thiophene-2-sulfonyl) -propionic acid as a colorless solid; Yield: 40%; mp 116-117 ° C; MS: 325.9 (M + H) +; X H NMR (300 MHz, DMSO-dd): d.1.29 (s, 3 H), 3.33 (d, 1 H), 3.69 (d, 1 H), 7.18-7.30 (m, 5 H), 7.74 (m, 1 H), 8.22 (m, 1H), 9.13 (s, 1H), 10.80 (s, 1H).

Example 49 2- [8- (1-Carboxy-ethanesulfonyl) octane-1-sulfonyl) -propionic acid hydroxyamide 2- [8- (1-carboxy-ethanesulfonyl) octane-1-sulfonyl) ethyl ester was prepared propic * according to the general method set forth in Example 9. Starting with 2- [8- (1-ethoxycarbonyl-ethylsulfanyl) -octylsulfanyl] -propidnic acid ethyl ester (10.2g, 26 mmol) and sodium peroxymonoperoxide sulfate (64g) 104 mmol). Yield 9.87g (86%); colorless liquid; MS 442.9 (M + H) +. 2- [8- (1-Carboxy-ethanesulfonyl) octane-1-sulfonyl] -propionic acid was prepared according to the general method set forth in example 1. Starting with ethyl ester of 2- [8- (1-carboxylic acid ethansulfonyl) octane-1-sulfonyl] -propionic acid (3.0 g, 6.8 mmol), ethanol (15 mL) and ION sodium hydroxide (15 mL). Performance, 2.7g (98%); solid white mp 99-102 ° C; MS 387 (M + NH3) +. Starting from 2- [8- (1-carboxy-ethanesulfonyl) octane-1-sulfonyl) -propionic acid (2.5 g, 6.5 mmol) and following the procedure set forth in Example 1, 641 mg of 2-hydroxyamide were isolated [8- (1-carboxy-ethansulfonyl) -octane-1-sulfonyl] -propionic acid as an amber oil; Yield: 23%; MS: 434.0 (M + NH 4) +; H NMR (300 MHz, DMSO-dd): d 1.27-3.23 (m, 22H), 3.33 (m, 2H), 8.9 (s, 1H), 9.28 (s, 1H).

EXAMPLE 50 2- (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid hydroxyamide 2-ethyl-2-ester was prepared (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid according to the general method set forth in Example 9. Starting with ethyl acetate a - (4-bromophenyl-sulfonyl). (5.0g, 16 mmol) and l- [2- (4-chloromethylphenoxy) -ethyl] piperidine (4.97g, 16 mmol). Performance 6.1g (71%); brown oil; EM 541.1 (M + H) +. 2- (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid was prepared according to the general method set forth in Example 9 . Starting off of 2- (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propidnic acid ethyl ester (6.5 g, 20 mmol), ethanol ( 30 mL) and ION sodium hydroxide (15mL). Yield, 6.3 g (100%); solid yellow mp 125-127 ° C; MS 512.5 (M + H) +.

Starting from 2- (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid (6.1 g, 612 mmol) and following the procedure set forth in Example 1, 1.107g of 2- (4-Bromo-benzenesulfonyl) -2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) -phenyl] -propionic acid hydroxyamide was isolated as a light yellow solid; Yield: 17%; MS: 525.4 (M + H) +.

Example 51 3- (4-Bromo-phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide Ethyl ester of 3- (4-bromo-phenyl) -2- ( 4-methoxy-benzenesulfonyl) -2-methylpropionic following the procedure set forth in Example 9, starting with 2- (4-methoxy-benzenesulfonyl) -propidic acid ethyl ester (3.0 g, 11 mmol) and 4-bromo -benzyl bromide (3.0 g, 11 mmol). Yield 4.67 g, 96%; colorless oil; MS 441 (M + H) +. 3- (4-Bromo-phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid was prepared starting from ethyl ester of 3- (4-bromo-phenyl) -2- (4-methoxy) -benzenesulfonyl) -2-methyl-propionic acid (4.0 g, 9.0 mmol), disulfides in methanol (50 mL) and NaOH ION (30 mL). The resulting reaction mixture was worked up as set forth in Example 9. Yield, 3.0 g, 78%. Solid of low fusion. MS: 413 (M + H) +.

Starting with 3- (4-bromo-phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (2.7 g, 6.5 mmol) and following the procedure set forth in Example 1, 2.26 g of 3- (4-Bromo-phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide as a clear colorless solid; Yield: 81%; mp 86-88 ° C; MS: 429.8 (M + H) +; XH NMR (300 MHz, DMS0-CDC13): d 1.42 (s, 3H), 1.77 (broad s, 1H), 3.26 (d, J = 7.0 Hz, 1H), 3.68 (d, J = 7.0 Hz, 1H) , 3.85 (s, 3H), 7.01-7.76 (m, 8H), 9.71-9.88 (s broad, 1H).

Example 52 N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionamide Ethyl 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-ethyl ester was prepared -naphthalene-2-yl-propionic following the procedure set forth in Example 9, starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionic acid ethyl ester (5.4 g, 20 mmol) and 2-bromo-methyl naphthalene (4.4 g, 20 mmol). Yield 8.0 g, 97%; colorless crystals, mp 182-184 ° C; MS: 413 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionic acid ethyl ester (4.6 g, 11 mmol), 4.25 (98%) of the 2- (4-) acid was isolated. methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionic acid, as colorless crystals, following the procedure set forth in Example 9. Mp 144-146 ° C; MS: 384.9 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionic acid (2.4 g, 6.2 mmol), and following the procedure set forth in Example 1, 1.6 g of N was isolated. -hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-naphthalen-2-yl-propionamide as a clear colorless solid; Yield: 64%; mp 185-187 ° C; MS: 400.2 (M + H) +; XH NMR (300 MHz, CDC13): d 1.56 (s, 3H), 3.28 (d, J = 8.0 Hz, 1H), 3.81 (d, J = 8Hz, 1H), 3.93 (s, 3H), 4.88 (s) large, 1H), 7.02-7.92 (m, 11H).

Example 53 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -3-methyl-butyramide Ethyl 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid ethyl ester was prepared according to the general method set forth in Example 1. Starting with ethyl 2-bromo-3-methyl-butanoate (20.9 g, 100 mmol) and 4-methoxybenthiol (14.0 g, 100 mmol), 30 g of ethyl ester of 2- (4-Methoxy) acid were isolated. phenylsulfanyl) -3-methyl-butyric acid. Yield, 99%; light yellow oil; EM 269 (M + H) +. Starting from 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid ethyl ester (2.68 g, 10 mmol) and following the oxidation procedure set forth in Example 9, 3 g of 2-ethyl ester - (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid as a colorless solid, yield: 99%; mp 53 ° C; MS: 273 (M + H) +. Starting with ethyl ester of 2- (4-methoxy-benzenesulfonyl) -3-methyl-butyric acid (3 g, 10 mmol), they were isolated 2. 7 g (96%) of 2- (4-methoxy-benzenesulfonyl) -3-methyl-butyric acid as a colorless solid following the procedure set forth in Example 9. Mp 96 ° C; MS: 273 (M + H) +. Starting from 2- (4-methoxy-phenylsulfanyl) -3-methyl-butyric acid (2.0 g, 7.34 mmol) and following the procedure set forth in Example 9, 590 mg of N-hydroxy-2- (4-methoxy) were isolated. -benzenesulfonyl) -3-methyl-butyramide as a colorless solid. Mp 220 ° C; Performance 28%; MS: 288 (M + H) +, XH NMR (300 MHz, DMSO-d6): d 0.88 (d, J = 6.7 (Hz, 3H), 1.07 (d, J = 6.7 Hz, 3H), 2.09-2.20 (s broad, 1H), 3.53 (d, J = 9, 1H), 7.12-7.17 (m, 2H), 7.74-7.79 (m, 2H).

EXAMPLE 54 1- (4-Methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid hydroxyamide Following the procedure set forth in Example 9, l- (4-Methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid ethyl ester was prepared, starting from ethyl ester of 2 - (4-methoxy-benzenesulfonyl) -acetic acid (3.0 g, 11.6 mmol) and 1,4-dibromobutane (2.4 g, 7.6 mmol). Yield 2.4 g, 78%; colorless solid, mp 86-88 ° C; MS: 313 (M + H) +. It was prepared starting from l- (4-methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid 1- (4-methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid ethyl ester (2.2 g, 7.0 mmol), dissolved in methanol (50 mL) and 10% NaOH. N (30 mL). The resulting reaction mixture was worked up as set forth in Example 9. Yield 1.66 g, 83%. Colorless solid; mp 112-115 ° C; MS: 285 (M + H) +. Starting from l- (4-methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid (442 mg, 1.5 mmol) and following the procedure set forth in Example 1, 410 mg of 1- (4-methoxy-benzenesulfonyl) -cyclopentanecarboxylic acid hydroxyamide was isolated. as a colorless solid, mp 89-91 ° C; Yield 88%; MS: 300 (M + H) +, * H NMR (300 MHz, CDC13): d 1.65-1.82 (m, 4H), 2.17-2.42 (m, 4H), 3.87 (s, 3H), 7.0 (d, J = 8Hz, 2H), 7.7 (broad s, 1H), 7.72 (d, J = 8 Hz, 2H), 9.73 (broad s, 1H).

Example 55 3- (2-Bromo-f-enyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide Following the procedure set forth in Example 9, ethyl ester of 3-acid was prepared 2-Bromo-phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic, starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -propionic acid (2.0 g, 7.3 mmol and 2- (bromine) benzyl bromide (2.0 g, 8 mmol) Yield 3.1 g, 87%; Colorless oil; MS: 441 (M + H) +. Prepared starting from 3- (2-Bromo-f-enyl) 2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid ethyl ester of 3- (2-bromo-phenyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (3.0 g. mmol), dissolved in methanol (50 mL) and 10 N NaOH (30 mL). The resulting reaction mixture was worked up as set forth in Example 9. Yield 1.7 g, 63%. Waxy solid; MS: 414 (M + H) +. Starting with 3- (2-Bromo-f-enyl) -2- (4-methoxy-benzenesulfonyl) -2-methyl-propionic acid (470 mg, 1.1 mmol) and following the procedure set forth in Example 9, 380 were isolated 3- (2-Bromo-phenyl) -N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-propionamide mg as a colorless solid, mp 93-96 ° C; Yield 77%; MS: 429 (M + H) +, H NMR (300 MHz, CDC13): d 1.3 (s, 3H), 3.32 (d, J = 7.0 Hz, 1H), 3.69 (d, J = 7.0 Hz, 1H) , 3.82 (s, 3H), 6.92-7.89 (m, 8H).

Example 56 2- (4-Methoxy-benzenesulfonyl) -2-methyl-5-phenyl-pent-4-enoic acid hydroxyamide Following the procedure set forth in Example 9, ethyl ester of 2- (4-methoxy) acid was prepared benzenesulfonyl) -2-methyl-5-f-enyl-pent-4-enoic, starting from 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester (3.0 g, 11 mmol) and cinnamyl bromide (2.1 g, 11 mmol).

Yield 3.51 g, 82%; Colorless oil; MS: 389 (M + H) +. It was prepared from 2- (4-Methoxy-benzenesulfonyl) -2-methyl-5-phenyl-pent-4-enoic acid from 2- (4-Methoxy-benzenesulfonyl) -2-methyl-5- ethyl ester phenyl-pent-4-enoic (3.0 g, 11 mmol), dissolved in methanol (50 mL) and 10 N NaOH (30 mL). The resulting reaction mixture was worked up as set forth in, Example 9. Yield 1.9 g, 68%; Yellowish oil; MS: 361 (M + H) +. Starting from 2- (4-Methoxy-benzenesulfonyl) -2-methyl-5-phenyl-pent-4-enoic acid (440 mg, 1.2 mmol) and following the procedure set forth in Example 1, 420 mg of hydroxyamide was isolated from the 2- (4-Methoxy-benzenesulfonyl) -2-methyl-5-phenyl-4-enoic acid as a colorless solid, mp 162-164 ° C; performance 92%; MS: 376 (M + H) +, XH NMR (300 MHz, CDC13): d 1.41 (s, 3H), 3.0-3.16 (m, 1H), 3.30 (d, J = 11 Hz, 2H), 3.92 ( s, 3H), 5.9-6.1 (m, 1H), 6.53 (d, J = 11 Hz, 1H), 7.1-7.72 (m, 9H), 9.12 (broad s, 1H). Example 57 2- (4-Methoxy-benzenesulfonyl) -5-phenyl-2- (3-phenyl-propyl) -pentanoic acid hydroxyamide Following the procedure set forth in Example 9, ethyl ester of 2- (4-) acid was prepared methoxy-benzenesulfonyl) -5-2- (3-phenyl-propyl) -pentanoic acid, starting with 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester (4.0 g, 15.8 mmol) and 3-bromo-propyl benzene (6.4 g, 32 mmol). Yield 3.7 g, 47%; Colorless oil; MS: 495 (M + H) +. It was prepared from 2- (4-methoxy-benzenesulfonyl) -5-phenyl-2- (3-phenyl-propyl) -pentanoic acid from 2- (4-methoxy-benzenesulfonyl) -5-phenyl- ethyl ester. 2- (3-phenylpropyl) -pentanoic acid (2.0 g, 4 mmol), dissolved in methanol (50 mL) and 10 N NaOH (30 mL). The resulting reaction mixture was worked up as described in Example 9. Yield 1.18 g, 63%; Waxy solid; MS: 449.2 (M + H-H20) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5-phenyl-2- (3-phenyl-propyl) -pentanoic acid (600 mg, 1.2 mmol) and following the procedure set forth in Example 1, 420 mg of 2- (4-methoxy-benzenesulfonyl) -5-phenyl-2- (3-phenyl-propyl) -pentanoic acid hydroxyamide as a colorless solid. Mp 118-120 ° C; 68% yield; MS: 482 (M + H) +XH NMR (300 MHz, CDC13): d 1.52-1.68 (m, 2H), 1.74-1.92 (m, 2H), 1.98-2.20 (m, 4H), 2.58-2.72 (m, 4H), 3.86 (s) , 3H), 6.93 (d, J = 11 Hz, 2H), 7.02-7.63 (m, 10H), 7.81 (d, J = 11 Hz, 2H). Example 58 2-Allyl-2- (4-methoxy-benzenesulfonyl-pent-4-enoic acid hydroxyamide) Following the procedure set forth in Example 9, 2-allyl-2- (4-methoxybenzenesulfuric acid ethyl ester was prepared. onyl-pent-4-enoic, starting with 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester (3.0 g, 11.6 mmol) and allyl bromide (excess of 4 ml) Yield 3.6 g, 92%; Yellow oil; MS: 338 (M + H) +. It was prepared from 2-allyl-2- (4-methoxy-benzenesulfonyl-pent-4-enoic acid from 2-allyl-2- (4-methoxybenzenesulfonyl-pent-4-enoic acid ethyl ester (2.2. g, 6.5 mmol), dissolved in methanol (50 mL) and 10 N NaOH (30 mL) The resulting reaction mixture was worked up as described in Example 9. Yield 1.76 g, 87%, yellowish oil, MS: 311 (M + H) +. Starting from 2-allyl-2- (4-methoxy-benzenesulfonyl-pent-4-enoic acid (1.5 g, 4.8 mmol) and following the procedure set forth in Example 1, 1.5 g of 2-allyl-2- (4-methoxy-benzenesulfonyl-pent-4-enoic acid hydroxyamide as a colorless solid, mp 114-116 ° C; Performance 99%; MS: 326 (M + H) +, XH NMR (300 MHz, CDC13): d 1.62 (m, 1H), 2.70-2.80 (m, 4H), 3.9 (s, 3H), 5.16-5.27 (m, 4H ), 5.81-5.94 (m, 2H), 7.12 (d, J = 8 Hz, 2H).

Example 59 2- (4-Methoxy-benzenesulfonyl) -2-propylpentanoic acid hydroxyamide 2-Allyl-2- (4-methoxy-benzenesulfonyl) -pent-4-enoic acid hydroxyamide (326 mg, 1.0 mmol) was dissolved. ) (example 26) in methanol (50 mL) and hydrogenated over 10% Pd / C (100 mg) at room temperature, under a pressure of 49 psi (3.99 kgf / cm2) for 4 hours. At the end, the reaction mixture was filtered and the methanol was removed. The resulting solid was crystallized from methanol. Yield: (250 mg, 75%; MS: 330 (M + H) \ XH NMR (300 MHz, CDC13): d 0.92 (t, J = 4.0 Hz, 6H), 1.27-1.59 (m, 4H), 1.78-2.02 (m, 4H), 3.86 (s, 3H), 6.04 (s broad, 1H) , 6.97 (d, J = 9 Hz, 2H), 7.76 (d, J = 9 Hz, 2H).

Example 60 2-Benzyl-N-hydroxy-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionamide Following the procedure set forth in Example 9, 2-benzyl-2- (4-methoxy) ethyl ester was prepared -benzenesulfonyl) -3-phenyl-propionic acid, starting from 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester (1.0 g, 3.8 mmol) and benzyl bromide (excess of 4 ml). Yield 1.2 g, 72%; Yellow oil; MS: 439 (M + H) +. It was prepared from 2-benzyl-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid from 2-benzyl-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid ethyl ester ( 1.0 g, 2.2 mmol), dissolved in methanol (50 mL) and 10 N NaOH (30 mL). The resulting reaction mixture was worked up as described in Example 9. Yield 580 mg, 62%; Waxy solid; MS: 409 (M-H) +. Starting from 2-benzyl-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid (410 mg, 1 mmol) and following the procedure set forth in Example 1, 225 mg of 2-benzyl-N- were isolated. hydroxy-2- (4-methoxy-benzenesulfonyl) -3-phenyl-propionamide as a waxy solid.

Yield 52%; MS: 426 (M + H) +, XH NMR (300 MHz, CDC13): d 3.25 (d, J = 14 Hz, 2H), 3.52 (d, J = 14 Hz, 2H), 3.9 (s, 3H) , 6.93 (d, J = 8Hz, 2H), 7.02 -7.26 (m, 9H), 7.61 (d, J = 8Hz, 2H), 7.87 (d, J = 4 Hz, 1H), 9.58 (s broad, 1H ).

Example 61 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionamide To a stirred solution of 2- (4-methoxy-benzenesulfonyl) propionic acid ethyl ester ( 2.7 mg, 10 mmol), 3-picolyl chloride hydrochloride (3.2 g, 20 mmol) and triethyl benzyl ammonium hydrochloride (1 g) in methylene chloride (400 mL), 10 N NaOH (30 mL) was added. . The reaction was continued at room temperature for 48 hours. At the end, the organic layer was separated and washed well with water. The organic layer was dried, filtered and concentrated. The crude product was purified by silica gel chromatography. The column was eluted with 50% ethyl acetate: hexane. 2- (4-Methoxy-benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionic acid ethyl ester was isolated as a brown oil. Yield 3.0 g, 82%; Brown oil; MS: 364 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionic acid ethyl ester (2.5 mg, 6.8 mmol) was isolated 1.8 g (79%) of 2- (4-methoxy) -benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionic acid as a colorless solid following the procedure set forth in Example 9. Mp 58 ° C; MS: 336 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionic acid (410 mg, 1 mmol) and following the procedure set forth in Example 1, 225 mg of N- was isolated. hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-pyridin-3-yl-propionamide as a colorless solid. Yield 52%; mp 98 ° C, MS: 351 (M + H) +, XH NMR (300 MHz, CDC13): d 1.4 (s, 3H), 3.1 (d, J = 9.0 1H), 3.65 (d, J = 9.1, 1H), 3.9 (s, 3H), 7.-8.5 (m, 8H). Example 62 2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid hydroxyamide Starting from 2- (4-methoxy-benzenesulfonyl) acetic acid ethyl ester (7.5 g, 29 mmol) and 1-bromooctane (6.7 g, 35 mmol) was isolated 8 g of the monooctylated compound of 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid following the procedure set forth in Example 9. Performance : 8.0 g 74%; MS: 370 (M + H) +. Following the procedure set forth in Example 29, 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid ethyl ester was prepared, starting from ethyl ester of 2- (4-methoxy) acid. benzenesulfonyl) -2-decanoic acid (8.0 g, 21.6 mmol) and picolyl chloride hydrochloride (4.1 g, 25 mmol). Yield 6.5 g, 68%; Coffee oil; MS: 462 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid ethyl ester (5.0 g, 11 mmol), 4.5 g (91%) of 2- (4-methoxy) were isolated. -benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid as a colorless solid following the procedure set forth in Example 9. mp 159 ° C, MS: 434 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid (2.5 g, 5.7 mmol) and following the procedure set forth in Example 1, 1.4 g of 2-hydroxyamide were isolated. - (4-methoxy-benzenesulfonyl) -2-pyridin-3-yl-methyl-decanoic acid as a colorless solid. Yield: 50%, mp 62 ° C; MS: 448 (M + H) +, XH NMR (300 MHz, CDC13): d 0.86 (t, 6.9Hz, 3H), 1.25-2.17 (m, 14H), 3.3 (d, J = 14, 1H), 3.5 (d, J = 14, 1H), 3.9 (s, 3H), .8-8.6 (m, 8H).

Example 63 2- (4-Methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid hydroxyamide Following the procedure set forth in Example 9, ethyl ester of 2 - (4-methoxy-benzenesulfonyl) -5-methyl-hex-4-enoic, starting with 2- (4-methoxy-benzenesulfonyl) -5-methyl-hex-4-enoic acid ethyl ester (6.0 g, 23 mmol ) and isoprenyl bromide (3.0 g, 20 mmol). Yield 6.52 g, 86%; Colorless oil; MS: 327 (M + H) +. Following the procedure outlined in the example 29, 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid ethyl ester was prepared, starting from 2- (4-methoxy) ethyl ester -benzenesulfonyl) -5-methyl-hex-4-enoic (4.0 g, 12.2 mmol) and picolyl chloride hydrochloride (2.1 g, 13 mmol). Yield 4.14 g, 81%; Coffee oil; MS: 418 (M + H) +). Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid ethyl ester (4.0 g, 9.5 mmol), dissolved in methanol (50 mL) and NaOH ION (30 mL), 2- (4-Methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid was prepared. The resulting reaction mixture was worked up as set forth in Example 9. Yield 3.2 g, 87%; solid ivory color; mp 117-119 ° C; MS: 390 (M + H) +).

Starting with 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid (2.1 g, 5.4 mmol) and following the procedure set forth in Example 1, isolated 1.82 g of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-yl-methyl-hex-4-enoic acid hydroxyamide as a colorless solid. Yield: 82%, mp 89-92 ° C; MS: 405 (M + H) +, XH NMR (300 MHz, CDC13): d 1.63 (s, 3H), 1.76 (s, 3H), 2.62-2.78 (m, 2H), 3.3 (d, J = 4.0 Hz, 1H), 3.63 (d, J = 4.0 Hz, 1H), 3.82 (s, 3H), 5.26 (m, 1H), 7.12-7.88 (m, 6H), 8.27-8.33 (m, 2H).

Example 64 2-Benzyl-4-diisopyrilamino-N-hydroxy-2- (4-methoxy-benzenesulfonyl) -butyramide Following the procedure set forth in the example 29, 2-benzyl- (4-diisopropyl-amino-2- (4-methoxy-benzenesulfonyl) -butyric acid ethyl ester, starting from ethyl ester of (4-methoxy-benzenesulfonyl) -3-phenyl-propionic acid, was prepared. (3.0 g, 8.5 mmol) (Example 9) and 2-diisopyrilaminoethyl chloride hydrochloride (4.0 g, 20 mmol) Yield 3.2 g, 79%; solid ivory color; mp 89-91 ° C; MS: 476.4 (M + H) +. Starting from 2-benzyl-4-diisopropylamine- (4-methoxy-benzenesulfonyl) -butyric acid ethyl ester (3.53 mg, 7.5 mmol) were isolated (2.8 g (86%) of 2-benzyl-4-diisopropylamino-2 acid. - (4-methoxy-benzenesulfonyl) -butyric acid as colorless crystals by the procedure set forth in Example 9, Mp 136-138 ° C; MS: 448.5 (M + H) +). Starting from 2-benzyl- (4-methoxy-benzenesulfonyl) -butyric acid (1.85 g, 4.1 mmol) and following the procedure set forth in Example 1, 1.13 g of 2-benzyl-4-diisopropylamino-N-hydroxy acid were isolated. -2- (4-methoxy-benzenesulfonyl) -butyramide solid low-melting waxy; Yield: 68%; MS: 463.3 (M + H) +, XH NMR (300 MHz, CDC13): d 0.98 (d, J = 11 Hz, 6H), 1.16 (d, J = 11 Hz, 6H), 1.92 (m, 2H) , 2.46 (m, 2H), 2.71 (m, 2H), 3.18 (m, 1H), 3.48 (m, 1H), 3.86 (s, 3H), 6.98 (d, J = 8 Hz, 2H), 7.18- 7.22 (m, 5H), 7.92 (d, J = 8 Hz, 2H), 8.12 (s, 1H).

Example 65 3-Cyclohexyl-N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionamide Following the procedure set forth in Example 9, 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester was prepared, starting from (4.0 g, 15 mmol) of ethyl ester of 2- (4-) acid. methoxy-benzenesulfonyl) -acetic acid and 1-bromomethyl cyclohexane (2.7 g, 15 mmol). Yield 5.0 g, 94%; Colorless oil; MS: 355 (M + H) +.

Following the procedure set forth in Example 29, 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionic acid ethyl ester was prepared, starting from 3-cyclohexyl-2-ethyl ester - (4-methoxy-benzenesulfonyl) propionic acid (1.5 g, 4.2 mmol) and 3-picolyl chloride (1.0 g, 6 mmol). Yield 1.0 g, 38%; Colorless oil; MS: 446 (M + H) +. Starting from ethyl ester of 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionic acid (1.3 m, 2.9 mmol), 1.0 g (83%) of 3-cyclohexyl acid was isolated -2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionic acid as colorless crystals following the procedure set forth in Example 9. Mp 92 ° C; MS: 417.5 (M + H) +. Starting from 3-cyclohexyl-2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionic acid (1.0 g, 2.4 mmol) and following the procedure set forth in Example 1, 80 mg of 3- cyclohexyl-N-hydroxy-2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-propionamide as a colorless hydrochloride salt. Yield: 71%, mp 57-60 ° C; MS: 433 (M + H) +; H NMR (300 MHz, CDC13): d 0.8-2.08 (m, 13 H), 3.3 (d, J = 14 Hz, 1H), 3.7 (s, J = 14 Hz, 1H) ', 3.9 (s, 3H) ), 7.0 -8.5 (m, 8H).

Example 66 2- (4-Methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid hydroxyamide Following the procedure set forth in Example 9, 2- (4-methoxy) -ethyl-ethyl ester was prepared benzenesulfonyl) -4-methyl-pentanoic, starting from (5.0 g, 20 mmol) of 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester and l-bromo-2-methyl propane (2.6 g, 20 mmol) . Yield 6.0 g, 95%; Colorless oil; MS: 315 (M + H) +. Following the procedure set forth in the Example 29, 2- (4-methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid ethyl ester was prepared, starting from (3.1 g, 10 mmol) of ethyl ester of 2- ( 4-methoxy-benzenesulfonyl) -4-methyl-pentanoic acid and 3-picolyl chloride hydrochloride (1.8 g, 11 mmol). Performance 3.0 g, 75%; Colorless oil; MS: 406 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid ethyl ester (1.2 g, 2.9 mmol), 1.0 g (91%) of 2- ( 4-methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid as colorless crystals following the procedure set forth in Example 9. Mp 188-186 ° C; MS: 378 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid (800 mg, 2.1 mmol) and following the procedure set forth in Example 1, 180 mg of hydroxyamide was isolated from the 2- (4-methoxy-benzenesulfonyl) -4-methyl-2-pyridin-3-ylmethyl-pentanoic acid as a colorless solid. Yield: 11%, mp 78 ° C; MS: 393.4 (M + H) +; XH NMR (300 MHz, CDC13): d 0.65 (d, 6.3 Hz, 3H), 0.89 (d, J = 6.2 Hz, 3H), 1.7 (m, 1H), 2.06 (m, 2H), 3.85 (s, 3H), 6.8-8.5 (m, 10H).

Example 67 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionamide Following the procedure set forth in Example 29, 2- (4-methoxy) ethyl ester was prepared -benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionic acid, starting from (5.2 g, 20 mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 7-bromomethyl quinoline (4.4 g, 20 mmol). Yield 4.5 g, 54%; Pale yellow solid; mp 86 ° C; MS: 414 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionic acid ethyl ester (3.0 gm, 7.2 mmol), 2.5 g (90%) of 2- ( 4-methoxy-benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionic acid as colorless crystals following the procedure set forth in Example 9. mp 106-108 ° C; MS: 386.4 (M + H) +.

Starting from 2- (4-methoxy-benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionic acid (2.0 gm, 5.2 mmol) and following the procedure set forth in Example 1, 1.2 g of N- were isolated. hydroxy-2- (4-methoxy-benzenesulfonyl) -2-methyl-3-quinolin-6-yl-propionamide as a colorless solid. Yield: 57%, mp 206 ° C; MS: 401.4 (M + H) +; 1 NMR (300 MHz, CDC13): d 1.4 (s, 3H), 3.19 (m, 1H), 3.8-4.0 (m, 4H), 7.1-8.95 (m, 12H).

EXAMPLE 68 2- (4-Methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide Following the procedure set forth in Example 9, 2- (4-methoxy) -ethyl-ethyl ester was prepared benzenesulfonyl) -6-phenoxy-hexanoic acid, starting from (2.5 g, 10 mmol) of 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester and l-bromo-2-phenoxy-butane (2.2, 10 mmol). Yield 3.8 g, 93%; Colorless oil; MS: 407 (M + H) +. Following the procedure set forth in Example 9, 2- (4-methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid ethyl ester was prepared, starting from (3.1 g, 10 mmol) of ethyl 2- (4-methoxy-benzenesulfonyl) -6-phenoxy-hexanoic acid ester and 3-picolyl chloride (1.8 g, 11 mmol). Yield 3.5 g, 71%; Colorless oil; MS: 498 (M + H) +.

Starting from 2- (4-methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid ethyl ester (3.0 g, 6.0 mmol), 2.8 g (Yield: Quantitative) of 2- acid were isolated. (4-methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid as colorless crystals following the procedure set forth in Example 9. Mp 148-151 ° C; MS: 470.5 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid (2.0 g, 4.3 mmol) and following the procedure set forth in Example 1, 1.5 g of hydroxyamide was isolated from the 2- (4-methoxy-benzenesulfonyl) -6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid as a colorless solid. Yield: 72%, mp 68 ° C; MS: 485.5 (M + H) +; XH NMR (300 MHz, CDC13): d 1.5-2.5 (m, 8H), 3.4 (broad s, 2H), 3.8 (s, 3H), 6.8-8.7 (m, 13H).

Example 69 2- (4-Methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide Following the procedure set forth in Example 9, 2- (4-methoxy-benzenesulfonyl) -5-methyl-hexanoic acid ethyl ester was prepared, starting from (10.0 g, 39 mmol) of 2- (4-methoxy-benzenesulfonyl) -acetic acid ethyl ester and l-bromo-3-methyl butane (6.0 g, 40 mmol). Yield 8.5 g, 62%; Colorless oil; MS: 329 (M + H) +. Following the procedure set forth in Example 9, 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid ethyl ester was prepared, starting from (6.0 g, 18 mmol) of ethyl 2- (4-methoxy-benzenesulfonyl) -5-methyl-hexanoic acid ester and picolyl chloride hydrochloride (4.1 g, 25 mmol). Yield 4.5 g, 60%; Brown oil; MS: 420 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid ethyl ester (3.0 g, 7.1 mmol), 2.6 g (92%) of 2- ( 4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid as a colorless solid following the procedure set forth in Example 9. Mp 173 C; MS: 392 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid (1.0 g, 2.5 mmol) and following the procedure set forth in Example 1, 800 mg of hydroxyamide was isolated from the 2- (4-methoxy-benzenesulfonyl) -5-methyl-2-pyridin-3-ylmethyl-hexanoic acid as a colorless solid; The hydrochloride was prepared by passing gaseous hydrogen chloride through a methanol solution of hydroxyamide. Yield: 72%, mp 62 ° C (HCl salt); MS: 408 (M + H) +; XH NMR (300 MHz, CDC13): d 0.76 (m, 6H), 1.2-2.0 (m, 5H), 3.5 (broad c, 2H), 7.1-8.8 (m, 8H), 11.1 (broad s, 1H) .

EXAMPLE 70 2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide The (4-methoxy-phenylsulfanyl) -acetic acid tert-butyl ester was prepared according to the general method set forth in Example 1. Starting with the corresponding 1-bromo-tert-butyl acetate (5.3 g, 27 mmol) and 4-methoxybenzothiol (3.7 g, 27 mmol), 6.4 g of the product was isolated. Yield 98%; Light yellow oil; MS: 255 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -acetic acid tert-butyl ester was prepared according to the general method set forth in Example 9. Starting from 2- (4-methoxy-benzenesulfanyl) tert-butyl ester -acetic (5.0 g, 20 mmol) and 3-chloroperoxybenzoic acid (12.0 g, 40 mmol), 5.3 g of the product was isolated. Yield 92%; Waxy solid; MS: 287.1 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -pyridin-3-ylpropionic acid tert-butyl ester was prepared according to the procedure set forth in Example 9. Starting with 2- (4-methoxy-benzenesulfonyl) tert-butyl ester acetic acid (20.0 g, 70.0 mmol) and 3-picolyl chloride (7.28 g, 44.4 mmol), 10.5 g of the product were isolated by chromatography on silica gel (50% ethyl acetate: hexane). Performance 63%; white solid; mp 93-94 ° C; MS: 378.0 (M + H) +. The 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid tert-butyl ester was prepared according to the procedure set forth in Example 9. Starting from the 2- (4-tert-butyl ester) -methoxy-benzenesulfonyl) -pyridin-3-ylpropionic acid (2.0 g, 5.3 mmol) and n-butyl bromide (0.73 g, 5.3 mmol), 1.20 g of the product were isolated. Yield 52%; yellowish gum; MS: 434.3 (M + H) +. A mixture of 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid tert-butyl ester (1.1 g, 2.5 mmol) in methylene chloride / TFA (1: 1) was stirred at room temperature for about 2 hours. The solvents were evaporated and 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid was purified by chromatography on silica gel (methanol / 30% methylene chloride). Yield 0.90 g, 94%; white solid; mp 70 ° C; MS 376.1 (MH). "2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide was prepared according to the method set forth in Example 1. Starting with 2- (4-) methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-hexanoic acid (0.31 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.13 g of the product were isolated.

Yield 37%; pale yellowish solid; mp 65 ° C; MS: 392.9 (M + H) +. X H NMR (300 MHz, DMSO-d 6): d 0.80 (t, J = 7.2 Hz, 3H), 1.10-1.25 (m, 2H), 1.25-1.50 (m, 2H), 1.70-2.00 (m, 2H) , 3.53 (d, J = 14.4 Hz, 1H), 3.62 (d, J = 14.4 Hz, 1H), 3.88 (s, 3H), 7.15 (d, J = 8.9 Hz, 2H), 7.71 (d, J = 8.9 Hz, 2H), 7.90-8.00 (m, 1H), 8.40-8.45 (m, 1H), 8.70-8.85 (m, 2H), 11.0 (broad s, 1H); IR (KBr, cm "1): 3064m, 2958s, 2871m, 1671m.

EXAMPLE 71 2- (4-Methoxy-benzenesulfonyl) -2-oct-2-ynyl-dec-4-ynoic acid hydroxyamide The title compound was prepared according to the procedure set forth in Example 9. Starting from the tert-butyl ester of 2- (4-methoxy-benzenesulfonyl) -acetic acid (2.86 g, 10 mmol) and l-bromo-2-octine (3.80 g, 20 mmol), 4.4 g of the product were isolated. 100% performance; yellowish gum; MS: 446.9 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -2-oct-2-ynyl-dec-4-ynoic acid was prepared according to the procedure set forth in Example 70. Starting from the 2- (4-) tert-butyl ester methoxy-benzenesulfonyl) -2-oct-2-ynyl-dec-4-ynoic (4.40 g, . 0 mmol), 2.0 g of the product were isolated. Performance 49%; white solid; mp 61 ° C; MS: 345.1 (M-H). " The hydroxyamide of 2- (4-methoxy-benzenesulfonyl) -2-oct-2-ynyl-dec-4-ynoic acid was prepared according to the method set forth in Example 1. Starting from 2- (4-methoxy-benzenesulfonyl) ) -2-oct-2-inyl-dec-4-inoic (0.36 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.25 g of the product was isolated. Yield 62%; white solid; mp 83-84 ° C; 462.0 (M + H) +. X H NMR (300 MHz, DMSO-de): d 0.82-0.90 (m, 6H), 1.15-1.45 (m, 12H), 1.90-2.05 (m, 4H), 2.86 (broad d, J = 17.0 Hz, 2H ), 3.00 (broad d, J = 17.0 Hz, 2H), 3.87 (s, 3H), 7.15 (d, J = 10.0 Hz, 1H), 7.71 (d, J = 10.0 Hz, 1H), 9.20 (s broad) , 1H), 10.90 (broad s, 1H); IR (KBr, cm "1): 3344s, 3208m, 2930m, 2870m, 1677s, 1592s; Calculated Analysis for C25H35N05S: C, 65.05; H, 7.64; N, 3.03 Found: C, 65.26; H, 7.68; N, 2.90.

Example 72 2- (4-Methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid hydroxyamide The 2- (4-methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid tert-butyl ester was prepared according to the procedure set forth in Example 9. Starting from the tert-butyl ester of the acid 2- (4-methoxy-benzenesulfonyl) -acetic acid (2.86 g, 10 mmol) and l-bromo-2-butine (2.68 g, 20 mmol), 3.50 g of the product were isolated. Yield 90%; white solid; mp 85-87 ° C; MS: 391.0 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid was prepared according to the procedure set forth in Example 70. Starting from the 2- (4-) 4- tert-butyl ester methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-inoic (3.0 g, 7.7 mmol), 2.5 g of the product was isolated. Yield 97%; white solid; mp 141-143 ° C; MS: 333.1 (MH). "The hydroxyamide of 2- (4-methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid was prepared according to the method set forth in Example 1. Starting from the acid 2- (4-methoxy-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynyo (0.27 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.23 g of the product were isolated. 89%; white solid; mp 135-137 ° C; 349.9 (M + H) +. XH NMR (300 MHz, DMSO-de): d 1.67 (s, 6H), 2.70-3.10 (m, 4H), 3.88 (s, 3H), 7.15 (d, J = 10.0 Hz, 2H), 7.71 (d, J = 10.0 Hz, 2H), 9.20 (s broad, 1H), 10.90 (s broad, 1H), IR (KBr, cm-1): 3301s, 3161m, 2922m, 1640m, 1595s, 1500m.

Example 73 2- (4-Methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynoic acid hydroxyamide The 2- (4-methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynoic acid tert-butyl ester was prepared according to the procedure set forth in Example 9. Starting from the tert-butyl ester of the acid 2- (4-methoxy-benzenesulfonyl) -acetic acid (2.0 g, 7.0 mmol) and propargyl bromide (1.77 g, 15 mmol), 1.90 g of the product were isolated. Yield 75%; white solid; mp 113-115 ° C; MS: 362.1 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynoic acid was prepared according to the procedure set forth in Example 70. Starting from the 2- (4-) tert-butyl ester methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynyl (1.70 g, 4.7 mmol), 1.30 g of the product was isolated. Yield 90%; white solid; mp 156 ° C; MS: 305.1 (MH). "2- (4-Methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynoic acid hydroxyamide was prepared according to the method set forth in Example 1. Starting from the acid 2- (4-methoxy-benzenesulfonyl) -2-prop-2-ynyl-pent-4-ynoic (0.25 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, mmol), 0.22 g of the product was isolated. Yield 85%; white solid; mp 156 ° C; MS: 321.9 (M + H) +. 1ti NMR (300 MHz, DMSO-de): d 2.00--2.13 (m, 2H), 3.00-3.30 (m, 4H), 3.90 (s, 3H), 7.01 (d, J = 9.0 Hz, 2H), 7.82 (d, J = 9.0 Hz, 2H), 8.76 (broad s, 1H), 10.65 (broad s, 1H); IR (KBr, cm-1): 3392s, 3293s, 3271m, 2955m, 1650s, 1594s; Analysis Calculated for C15H15NO5S: C, 56.07; H, 4. 70; N, 4.36. Found: C, 55.65; H, 4.67; N, 4.10.

Example 74 2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid hydroxyamide The title compound was prepared according to the procedure set forth in Example 38. Starting with the tert-butyl ester of 2- (4-methoxy-benzenesulfonyl) -pyridin-3-ylpropionic acid (2.20 g, 5.8 mmol) and l-bromo-2-octine (1.14 g, 6 mmol), 2.69 gm of the product were isolated. Yield 92%; yellowish gum; MS: 486.0 (M + H) +. A mixture of 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid tert-butyl ester (2.60 g, 5.35 mmol), in methylene chloride / TFA (1: 1) ) was stirred at room temperature for about 2 hours. (Reference is made to example 70). The solvents were then evaporated and 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid was purified by chromatography on silica gel (methanol / methylene chloride ~ 30%). ). Yield 2.0 g, 87%; White solid; mp 146 ° C; EM 428.1 (MH). "2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid hydroxyamide was prepared according to the procedure set forth in Example 1. Starting from - (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid (0.71 g, 1.62 mmol) and hydroxylamine hydrochloride (1.39 g, 20 mmol), 0.48 g of the product were isolated. %; matt white solid; mp 65 ° C; 445.0 (M + H) +. XH NMR (300 MHz, DMS0-d6): d 0.84 (t, J = 6.8 Hz, 3H), 1.10-1.40 (m, 6H), 1.85-2.00 (m, 2H), 2.79 (d, J = 17.9 Hz , 1H), 2.90 (d, J = 17.9 Hz, 1H), 3.50 (d, J = 13.7 Hz, 1H), 3.74 (d, J = 13.7 Hz, 1H), 3.89 (s, 3H), 7.19 (d , H = 9.0 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.85-7.89 (m, 1H), 8.37-8.40 (m, 1H), 8.70-8.80 (m, 2H), 11.0 ( s broad, 1H); IR (KBr, cm-1): 3157m, 3095m, 2954s, 2932s, 2858m, 1671m, 1593s; Analysis Calculated for C23H28N205S -HC1 • 0.9H20: C, 55.56; H, 6.24; N, 5.63. Found: C, 55.84; H, 6.19; N, 5.59.

Example 75 2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-pent-4-ynoic acid hydroxyamide The 2- (4-methoxy-benzenesulfonyl) -2-pyridine tert-butyl ester was prepared -3-ylmethyl-pent-4-ynoic acid according to the procedure set forth in Example 38. Starting with 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylpropionic acid tert-butyl ester (3.77 g, mmol) and propargyl bromide (1.74 g, 13 mmol), 2.50 g of the product were isolated. Yield 60%; yellowish solid; mp 132-133 ° C; MS: 416.0 (M + H) +. 2- (4-Methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-pent-4-ynoic acid was prepared according to the procedure set forth in Example 70. Starting from 2- (4-) 4- tert-butyl ester methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-pent-4-ynyo (2.0 g, 4.8 mmol), 1.2 g of the product was isolated. Performance 69%; white solid; mp 119-121 ° C; MS: 358.1 (MH) The 2- (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-pent-4-ynoic acid hydroxyamide was prepared according to the method set forth in Example 1. Starting from - (4-methoxy-benzenesulfonyl) -2-pyridin-3-ylmethyl-pent-4-ynyo (0.29 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.065 g of the product were isolated. Yield 25%; matt white solid; mp 70 ° C; MS: 375.0 (M + H) +. XH NMR (300 MHz, DMSO-de) • d 1.19 (broad s, 1H), 2.90-3.00 (m, 2H), 3.55 (d, J = 13.8 Hz, 1H), 3.67 (d, J = 13.8 Hz, 1H), 3.89 (s, 3H), 7.18 (d, J = 9.0 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H), 7.80-7.89 (m, 1H), 8.35-8.40 (m, 1H) ), 8.70-8.80 (m, 2H), 11.1 (broad s, 1H); IR (KBr, cm-1): 3168m, 3095s, 1670m, 1593s.

Example 76 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-hex-4-ynoic acid hydroxyamide The 2- (4-fluoro-benzenesulfanyl) -acetic acid tert-butyl ester was prepared in accordance to the procedure set forth in Example 1. Starting with 4-fluorothiophenol (30.0 g, 230 mmol) and tert-butyl bromoacetate (45.67 g, 233 mmol), 53.4 g of the product were isolated. 100% performance; pale yellowish oil; MS: 243.1 (M + H) +. 2- (4-Fluoro-benzenesulfonyl) -acetic acid tert-butyl ester was prepared according to the general method set forth in Example 9. Starting with 2- (4-fluoro-benzenesulfanyl) -acetic acid tert-butyl ester (48.4 g, 200 mmol) and 3-chloroperoxybenzoic acid (121.3 g, (57%), 400 mmol), 48.0 g of the product were isolated. Yield 88%; pale yellowish oil; MS: 275.1 (M + H) +.

The title compound was prepared according to the procedure set forth in Example 70. Starting with 2- (4-fluoro-benzenesulfonyl) -2-pyridin-3-ylpropionic acid tert-butyl ester (1.83 g, 5.0 mmol) and -bromo-2-butine (0.67 g, 5.0 mmol), 2.18 g of the product were isolated. 100% performance; yellowish gum; MS: 419.2 (M + H) +. 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-hex-4-ynoic acid was prepared according to the method set forth in Example 38. Starting from the 2- (4-) tert-butyl ester fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-hex-4-inoic (2.1 g, 5.0 mmol), 1.20 g of the product was isolated. Performance 67%; matt white solid; mp 150 ° C; MS: 360.2 (MH). "The hydroxyamide of 2- (4-fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-hex-4-ynoic acid was prepared according to the method set forth in Example 1. Starting from the acid 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-hex-4-yno (0.29 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.15 g of the product was isolated. 45%; white solid; mp 190 ° C; MS: 377.2 (M + H) +. 1 H NMR (300 MHz, DMSO-d 6): d 1.60 (s, 3H), 2.70-3.00 (m, 2H), 3.53 (d, J = 13.8 Hz, 1H), 3.74 (d, J = 13.8 Hz, 1H), 7.50-7.58 (m, 2H), 7.80-7.95 (m, 3H), 8.35-8.40 (m, 1H), 8.74-8.79 (m, 2H), 11.1 (broad s, 1H); IR (KBr, cm-1): 3154m, 3105s, 3068s, 2875m, 1696s, 1630w, 1590s: Analysis Calculated for C? 8H? 7FN204S • HCl • 0. 5H20: C, 51 24; H, 4 54; N, 6. 64. Found: C, 51.21; H, 4.35; N, 6.46.

Example 77 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid hydroxyamide The title compound was prepared according to the procedure set forth in Example 9. Starting from the tert-butyl ester 2- (4-fluoro-benzenesulfonyl) -2-pyridin-3-ylpropionic acid (1.83 g, 5.0 mmol) and l-bromo-2-octine (0.95 g, 5.0 pmol) were isolated from 1.80 g of the product. Yield 56%; yellowish gum; MS: 474.3 (M + H) +. 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid was prepared according to the method set forth in Example 70. Starting from the 2- (4-) tert-butyl ester fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-inoic (1.80 g, 3.8 mmol), 1.40 g of the product was isolated. Yield 88%; matt white solid; mp 123-124 ° C; MS: 416.3 (MH). "2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4-ynoic acid hydroxyamide was prepared according to the method set forth in Example 1. Starting from the acid 2- (4-Fluoro-benzenesulfonyl) -2-pyridin-3-ylmethyl-dec-4- inoic (0.67 g, 1.62 mmol) and hydroxylamine hydrochloride (1.39 g, 20 mmol), 0.22 g of the product were isolated. 29%; white solid; mp 180-182 ° C; MS: 433.2 (M + H) +. 1 H NMR (300 MHz, DMS0-d6): d 0.84 (t, J = 6.8 Hz, 3H), 1.20-1.40 (m, 6H), 1.90-2.05 (m, 2H), 2.75 (d, J = 19.9 Hz, 1H), 2.94 (d, J = 19.9 Hz, 1H), 3.54 (d, J = 13.7 Hz, 1H) , 3.75 (d, J = 13.7 Hz, 1H), 7.40-7.60 (m, 2H), 7.70-8.00 (m, 3H), 8.30-8.40 (m, 1H), 8.70-8.80 (m, 2H), 11.1 (s broad, 1H); IR (KBr, cm-1): 3154m, 3105s, 3067m, 2957s, 2933s, 2873m, 1690s, 1631m Analysis Calculated for C22H25FN204S • HCl: C, 56.34; H, 5.59; N, 5.97 Found: C, 56.18; H, 5.54; N, 5.76.

Example 78 2- (4-Fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid hydroxyamide The 2- (4-fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid tert-butyl ester was prepared according to the procedure set forth in Example 9. Starting from the tert-butyl ester of the acid 2- (4-Fluoro-benzenesulfonyl) -acetic (4.87 g, 20 mmol) and l-bromo-2-butine (5.36 g, 40 mmol), 6.0 g of the product were isolated. Yield 77%; white solid; mp 85 ° C; MS: 379.1 (M + H) +. 2- (4-Fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid was prepared according to the procedure set forth in Example 70, starting from the 2- (4-) tert-butyl ester fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4 -inoic acid (3.50 g, 8.47 mmol), 2.35 g of the product were isolated. Performance 79%; white solid; mp 129-131 ° C; MS: 642.8 (MH). "The hydroxyamide of 2- (4-fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4-ynoic acid was prepared according to the method set forth in Example 1. Starting from the acid 2- (4-Fluoro-benzenesulfonyl) -2-but-2-ynyl-hex-4-yno (0.26 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.21 g of the product was isolated. 77%; white solid; mp 161-163 ° C; MS: 338.1 (M + H) +. XH NMR (300 MHz, DMSO-dg): d 1.67 (s, 6H), 2.80-3.10 (m, 4H) , 7.51 (dd, J = 9.0, 9.0 Hz, 2H), 7.87 (m, 2H), 9.26 (s broad, 1H), 10.95 (s broad, 1H), IR (KBr, cm-1): 3336s, 3245m , 1681s, 1589m, 1493m; Calculated Analysis for C? 6H? 6FN04S: C, 56.96; H, 4. 78; N, 4.15. Found: C, 56.59; H, 4.75; N, 4.04.

Example 79 2- (4-Methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid hydroxyamide Following the procedure set forth in Example 9, ethyl was prepared 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid ester, starting from (5.0 g, 20 mmol) of ethyl ester of 2- (4-methoxy-benzenesulfonyl) -acetic acid and isoprenyl bromide (6.0 g, 40 mmol). Yield 7.0 g, 88%; Colorless oil; MS: 395 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid (3.5 g, 9 mmol), 3.3 were isolated g (97%) of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid as a colorless oil following the procedure set forth in Example 9. MS: 365 (M + H) +. Starting from 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid (2.6 g, 7.0 mmol) and following the procedure set forth in Example 1, 1.36 g of 2- (4-methoxy-benzenesulfonyl) -5-methyl-2- (3-methyl-but-2-enyl) -hex-4-enoic acid hydroxyamide was isolated as a colorless solid. Yield: 67%, mp 93-96 ° C; MS: 383 (M + H) +; X H NMR (300 MHz, CDC13): d 1.68 (s, 6H), 1.73 (s, 6H), 2.72 (m, 4H), 3.82 (s, 3H), 5.12 (m, 2H), 6.92 (d, J = 8 Hz, 2H), 7.33 (broad s, 1H), 7.72 (d, J = 8 Hz, 2H), 9.71 (broad s, 1H).

Example 80 2- (4-Methoxy-phenylsulfanyl) -heptanoic acid hydroxyamide 2- (4-Methoxy-phenylsulfanyl) -heptanoic acid ethyl ester (13.8 g, 98%) was prepared according to the general method set forth in Example 1 , starting with ethyl 2-bromoheptanoate (11 g, 47 mmol) and 4-methoxythiophenol (6 g, 42.8 mmol), as a yellow oil; MS: 297.2 (M + H) +. 2- (4-Methoxy-phenylsulfanyl) -heptanoic acid was prepared starting from the ethyl ester of 2- (4-methoxy-phenylsulfanyl) -heptanoic acid (4 g, 13.5 mmol) dissolved in methanol (300 ml) and 10 N NaOH ( 25 ml). The resulting mixture was worked up as set forth in example 1. Yield 3 g (83%), yellow oil, MS: 267.1 (MH). "Starting from 2- (4-methoxy-phenylsulfanyl) -heptanoic acid (2.49 g, 9.32 mmol) and following the procedure set forth in example 1, 1.83 g of 2- (4-methoxy-phenylsulfanyl) -heptanoic acid hydroxyamide were isolated as a white, off-white solid, mp 90-95 ° C, yield: 70%, EM: 284.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.826 (t, J = 6.9 Hz, 3H), 1. 135-1.76 (m, 8H), 3.35 (m, 1H), 3.82 (s, 3H), 6.91-7.49 (m, 4H).

Example 81 (49A) 2R * - (4-methoxy-phenyl-S * -sulfinyl) -heptanoic acid hydroxyamide and (49B) 2S * - (4-methoxy-phenyl-R * -sulfinyl) -heptanoic acid hydroxyamide Starting of 2- (4-methoxy-phenylsulfanyl) -heptanoic acid hydroxyamide (1.69 g), 6 mmol) and following the procedure set forth in Example 5, the diastereomers of the hydroxyamide of 2- (4-methoxy-phenylsulfanyl) -heptanoic acid were separated on a column of silica gel using 75% ethyl acetate: hexane. . The less polar isomer, hydroxyamide of 2R * - (4-methoxy-phenyl-S * -sulfinyl) -heptanoic acid was isolated as a white powder. Yield: 390 mg (22%); mp 115 ° C; MS: 300.0 (M + H) +; H NMR (300 MHz, DMSO-de): 0.828 (t, J = 6.2 Hz, 3H), 1.18-1.23 (m, 6H), 1.73-1.99 (m, 2H), 3.11-3.15 (m, 1H), 3.82 (s, 3H), 7.09-7.61 (m, 4H). The more polar isomer, hydroxyamide of 2S * - (4-methoxy-phenyl-R * -sulfinyl) -heptanoic acid was isolated as a gray solid. Yield: 200 mg (11%); mp 112 ° C; MS: 300.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.754 (t, J = 6.9 Hz, 3H), 1014-1.121 (m, 6H), 1.58-1.89 (m, 2H), 3.10-3.15 (m, 1H) , 3.834 (s, 3H), 7.13-7.65 (m, 4H).

EXAMPLE 82 2- (4-Methoxybenzenesulfonyl) -2-methyl-3- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -propionic acid hydroxyamide hydrochloride Following the procedure set forth in the example 12, 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -propionic acid ethyl ester was prepared, starting from (4.0 g, 15 mmol) of 2- (4-methoxy-benzenesulfonyl) -propionic acid ethyl ester and 4- (morpholin-1-yl-ethoxy) -benzyl chloride hydrochloride (2.9 g, 10 mmol). Yield 4.8 g, 98%; Brown oil; MS: 492 (M + H) +. Starting from the ethyl ester of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -propionic acid (4.9 gm, 8.1 mmol), isolated 3.2 g (Yield: 84%) of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-morpholin-1-yl-ethoxy) -phenyl] -propionic acid as colorless crystals following the procedure set forth in Example 9. Mp 171 ° C; MS: 464 (M + H) +. Starting with 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -propionic acid (4.0 g, 8.6 mmol) and following the procedure set forth in Example 1, 2.5 g of 2- (4-methoxy-benzenesulfonyl) -2-methyl-3- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -propionic acid hydroxyamide was isolated as a colorless solid. The hydrochloride salt was prepared by reacting the free base with methanolic hydrogen chloride at 0 ° C. Yield: 2.5 g, 60%, mp 98 ° C; MS: 479 (M + H) +; XH NMR (300 MHz, CDC13): d 1.36 (s, 3H), 3.8-12.6 (m, 16H), 3.9 (s, 3H), 4.1-4.3 (m, 1H), 6.6 (d, J = 8 Hz , 2H), 6.96 (d, J = 9 Hz, 2H), 7.1 (d, 8 Hz, 2H), 7.84 (d, 9 Hz, 2H), 10.8 (broad s, 1H).

Example 83 l-Benzyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide To a stirred solution of 4-methoxybenthiol (2.8 gm, 20 mmol) and anhydrous K2CO3 (10 gm, excess) in dry acetone (100 ml), a-bromo ethyl acetate (3.3 gm, 20 mmol) was added in a round bottom flask and the reaction mixture was refluxed for 8 hours with good agitation. At the end, the reaction mixture was cooled and the potassium salts were filtered and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20 and 0.5 N NaOH solution. The organic layer was further well washed with water, dried over MgSO4, filtered and concentrated. The (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester was isolated as a pale yellow oil. Yield: 4.4 g (100%); MS: 227 (M + H) +.

To a stirred solution of 60% 3-chloroperoxybenzoic acid (14.0 gm, 40 mmol) in methylene chloride (100 ml) at 0 ° C, (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester was slowly added. (4.4 g, 20 mmol) in CH2C12 (15 mL). The reaction mixture turned cloudy and was stirred at room temperature for 6 hours. The reaction mixture was then diluted with hexane (300 ml) and stirred for 15 minutes. The solids were filtered and a Na2S03 solution was added to the organic layer which was stirred at least 3 hours before extracting the mixture with CHC13, and washed with H20. The organic layer was dried over MgSO, filtered and concentrated and the colorless (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester was isolated as an oil. Performance: 100%; MS: 259.1 (M + H) +. To a stirring solution of diethanolamine (10.5 gm, 100 mmol) and anhydrous K2CO3 (30 gm, excess) in dry acetone (250 ml), benzyl bromide (17.2 gm, 100 mmol) was added in a round-bottomed flask and the reaction mixture was heated to reflux for 8 hours with good agitation. At the end, the reaction mixture was cooled and the potassium salts were filtered and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20. The organic layer was further well washed with water, dried over MgSO4, filtered and concentrated. Colorless oil Yield: 19.0 g, 97%; MS: 196 (M + H) +.

The N-benzyldiethanolamine (9.75 g, 50 mmol) was dissolved in saturated methanolic hydrochloric acid and concentrated to dryness. The hydrochloride formed in this way was dissolved in methylene chloride (300 ml) and thionyl chloride (20 g, excess) was added and stirred at room temperature for 1 hour. At the end the reaction mixture was concentrated to dryness and the bis- (2-chloro-ethyl) -benzyl amine hydrochloride product was used for further transformation without any purification. Yield: 13.0 g, 97%; Mp: MS: 232 (M + H). To a stirred solution of bis- (2-chloro-ethyl) -benzyl amine hydrochloride (6.6 gm, 24.7 mmol), 18-Corona-6 (500 mg), and anhydrous K2C03 (30 gm, excess) in acetone dried (250 ml), (4-methoxy-phenylsulfonyl) -acetic acid ethyl ester (6.12 gm, 24 mmol) was added in a round bottom flask and the reaction mixture was heated to reflux for 16 hours with good agitation. At the end, the reaction mixture was cooled and the potassium salts were filtered and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20. The organic layer was further well washed with water, dried over MgSO4, filtered and concentrated. The dark brown reaction mixture was purified by column chromatography on silica gel eluting with 30% ethyl acetate: hexane and the product of 4- (4-methoxy-benzenesulfonyl) -1-benzyl acid ethyl ester was isolated. piperidin-4-carboxylic acid as a brown oil. Yield: 6.0 g, 60%; MS: 196 (M + H). The 4- (4-methoxy-benzenesulfonyl) -l-benzyl-piperidine-4-carboxylic acid ethyl ester (5.0 g, 11.9 mmol) was dissolved in MeOH / THF (1: 1, 200 mL) and stirred at room temperature. environment for 72 hours. At the end the reaction mixture was concentrated and the product was neutralized with HCl by dissolving in water (200 ml). After neutralization, the reaction mixture was concentrated to dryness. Ice water (100 ml) was added to the solid and filtered. The 4- (4-methoxy-benzenesulfonyl) -l-benzyl-piperidine-4-carboxylic acid product was dried at 50 C and taken to the next step without any purification. Colorless solid. Yield: 3.2 g, 69%; MS: 390 (M + H). To a stirred solution of 4- (4-methoxy-benzenesulfonyl) -l-benzyl-piperidine-4-carboxylic acid (2.0 g, 5.1 mmol) and DMF (2 drops) in CH2C12 (100 mL) at 0 ° C, oxalyl chloride (1.0 gm, 8 mmol) was added dropwise. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) in THF: water (5: 1, 30 ml) was stirred at 0 ° C for 1 hour in a separating flask. . At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH2C12 and slowly added to the hydroxylamine at 0 ° C. The reaction mixture was stirred at room temperature for 24 hours and concentrated. The residue obtained was extracted with chloroform and washed well with water. The obtained product was purified by chromatography on a silica gel column and eluted with chloroform, the hydroxyamine product of 4- (4-methoxy-benzenesulfonyl) -1-benzyl-piperidine-4-carboxylic acid was isolated as a solid colorless, mp 90-95 ° C; Yield of 1.2 g, 48%; MS: 405 (M + H) +; 1 H NMR (300 MHz, DMSO-de): d 2.29 (m, 3H), 2.76-2.79 (m, 2H), 3.43 (m, 4H), 4.30 (s, 2H), 7.14-7.17 (d, 2H) 7.50-7.73 (m, 5H), 9.37 (s, 1H), 10.53 (s, 1H), 11.18 (s, 1H).

Example 84 4- (4-Methoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (3-methoxy-benzyl)] -amino] -ethanol according to the general method set forth in Example 83. Based on diethanolamine (3.1 g, 29.5 mmol) and 3-methoxybenzyl chloride (5 g, 31.9 mmol). Yield 9.28 g, (99%); yellow oil; MS: 226 (M + H). 3-Methoxybenzyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting with 3-methoxy-benzyl diethanolamine (4.4 g, 20 mmol). Yield 4.5 g, (93%); yellow solid, mp 86-88 C; MS: 263 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from ethyl ester - (methoxy-benzenesulfonyl) -acetic (5.0 g, 22 mmol) and bis- (2-chloro ethyl) - (3-methoxy-benzyl) -amine (8.0 g, 23.5 mmol). Yield 2.4 g, (24%); low melting solid; MS: 447.9 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) 1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-methoxy) ethyl ester -benzyl) -piperidine-4-carboxylic acid (2.4 g, 5.36 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (10 mL), tetrahydrofuran (20 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 710 mg (32%), white solid, mp 199 ° C, MS: 419.9 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid (830 mg, 1.98 mmol) and following the procedure set forth in Example 83, 190 mg of 4- (4-methoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide as a white solid, mp 130 ° C; Yield 20.4%; MS: 435.0 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.24-2.32 (m, 2H), 2.51 (d, 2H), 2.73-2.83 (m, 2H), 3.37 (d, 2H), 3.76 (s, 3H) , 3.88 (s, 3H), 4.32 (s, 2H), 7.01-7.77 (m, 8H), 9.38 (s, 1H), 10.1 (s, 1H).

EXAMPLE 85 1- (3,4-Dichlorobenzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide. 2- [(2-hydroxy-ethyl) - (3,4-dichloro- benzyl) -amino] -ethanol according to the general method set forth in Example 83. Starting with diethanolamine (4.84 g, 46 mmol) and 3-dichlorobenzyl chloride (9.0 g, 46 mmol).

Yield 13.8 g, (99%); colorless oil; MS: 264.3 (M + H) +. 3,4-Dichlorobenzyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting with 3-dichlorobenzyl diethanolamine (10.7 g, 41 mmol). Performance 99%; yellow solid, mp 218-220 ° C; EM: 301. 8 (M + H) +. The ethyl ester of 1- (3,4-dichloro-benzyl) -4- (methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in Example 83. Starting from ethyl ester of 4 - (methoxy-benzenesulfonyl) -acetic acid (2.9 g, 11 mmol) and 3,4-dichlorobenzyl-bis- (2-chloroethyl) -amine (3.4 g, 11 mmol). Yield 5.9 g, (60%); solid brown; MS: 494.5 (M + H) +. 1- (3,4-Dichloro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from 1- (3,4-dichloro-benzyl) -4 ethyl ester - (methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (5.0 g, 10 mmol) dissolved in methanol (50 mL), 10 N sodium hydroxide (15 mL), tetrahydrofuran (75 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.94 g (62%), MS: 458.3 (M + H) +. Starting from 1- (3,4-dichlorobenzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.67g, 5.8 mmol) and following the procedure set forth in Example 83, 2 g of L- (3,4-dichloro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxamide as a white solid, mp 192-195 ° C; Yield 10%; MS: 472.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.20-2.28 (m, 2H), 2.76-2.79 (m, 2H), 3.43-3.44 (m, 4H), 4.30 (s, 2H), 7.14-7.17 ( d, J = .030, 2H), 7.50-7.73 (d, J = .027, 1H), 7.65-7.68 (d, J = .029, 2H), 7.72-7.75 (d, J = .027, 2H ), 7.87 (s, 1H), 9.37 (s, 1H), 10.53 (s, 1H), 11.18 (s, 1H).

Example 86 4- (4-Methoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxyamide. 2- [(2-Hydroxy-ethyl) - (4-methyl-benzyl) -amino was prepared. ] -ethanol according to the general method set forth in Example 83. Starting with diethanolamine (4.8 g, 46 mmol) and 4-methylbenzyl chloride (8.5 g, 46 mmol). Yield 9.8 g, (99%); MS: 209.9 (M + H) +. 4-Methylbenzyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting from 4-methyl-benzyl diethanolamine (6 g, 20 mmol).

Yield 5.2 g (84%); yellow solid, mp 145-147 ° C; EM: 245. 9 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -1- (4-methyl-benzyl) piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from ethyl 4-ethyl ester (methoxy-benzenesulfonyl) -acetic acid (7.0 g, 27 mmol) and 4-methyl-bis- (2-chloro-ethyl) -amine (5.0 g, 17 mmol). Yield 4.64 g, (63%); low melting solid; MS: 431.9 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) 1- (4-methyl-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester ( 4.3 g, 9.9 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (10 mL), tetrahydrofuran (20 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.6 g (40%), white solid, mp 207-208 ° C, MS: 404.3 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid (1.59 g, 3.9 mmol) and following the procedure set forth in Example 83, .505 g of hydroxamide was isolated. 4- (4-methoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid as a white solid, mp 176-177 ° C; Performance 32%; MS: 419.0 (M + H) +; 2 H NMR (300 MHz, DMSO-d 6): d 2.24-2.32 (m, 2H), 2.51 (t, 3H), 2.73-2.80 (m, 2H), 3.35-3.50 (m, 4H), 3.87 (s, 3H), 4.24 (s, 2H), 7.13-7.17 (d, J = .039, 2H), 7.23-7.60 (d, J = .036, 2H), 7.38-7.41 (d, J = .025, 2H ), 7.65-7.68 (d, J = .039, 2H).

Example 87 4- (4-Methoxy-benzenesulfonyl) -1- naphthalen-2-yl-methyl-piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (2-naphthyl-2- ylmethyl) -amino] -ethanol according to the general method set forth in Example 83. Starting with diethanolamine (6.18 g, 59 mmol) and 2- (bromomethyl) naphthalene (10 g, 45 mmol). Yield 12.7 g, (96%); yellow solid, mp 162-164 ° C; MS: 246.0 (M + H) +. 2-Naphthyl-2-ylmethyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from 2-naphthyl-ylmethyl-diethanol amine (10 g, 36 mmol) . Yield 9.1 g (79%); brown solid, mp 124-126 ° C; MS: 281.9 (M + H) +.

The 4- (4-methoxy-benzenesulfonyl) -naphthalen-ylmethyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from ethyl ester of 4- (methoxy) acid. benzenesulfonyl) -acetic (8.4 g, 32 mmol) and 1-naphthalene-ylmethyl-bis- (2-chloro-ethyl) -amine ((8.6 g, 27 mmol) Yield 6.5 g, (52%); low: MS: 440.9 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- naphthalene-ylmethyl-piperidine-4-carboxylic acid was prepared starting from ethyl ester of 4- (4-methoxy) acid. benzenesulfonyl) -naphthalene-ylmethyl-piperidine-4-carboxylic acid (6.3 g, 13 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (30 mL), tetrahydrofuran (30 mL) The resulting reaction mixture was worked up as shown in Example 83. Yield 2.3 g (36%), yellow solid, mp 226-228 ° C, MS: 440.0 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1 -naphthalen-2-yl-methylpiperidine-4-carboxylic acid (2.18 g, 5.0 mmol) and following the p When exposed to Example 83, 753 g of 4- (4-methoxy-benzenesulfonyl) -1-naphthalen-2-yl-methyl-piperidine-4-carboxylic acid hydroxamide were isolated as a white, off-white solid, mp 168- 170 ° C; Performance 31%; MS: 455.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.29-2.33 (m, 2H), 2.86-2.89 (m, 2H), 3.42-3.46 (m, 4H), 3.85 (s, 3H), 4.46 (s, 2H), 7.13-7.16 (d, J = .030, 2H), 7.56- 7.64 (m, 3H), 7.65-7.68 (d, J = .030, 2H), 7.98-8.00 (m, 3H), 8.21 (s, 1H), 10.7 (s, 1H), 11.20 (s, 1H).

EXAMPLE 88 l-Biphenyl-4-ylmethyl-4- (4-methoxy-benzenesulfonyl) iperidine-4-carboxylic acid hydroxyamide. 2- [(2-Hydroxy-ethyl) -l-biphenyl-4-ylmethyl)] - amino] -ethanol according to the general method set forth in example 83. Starting from diethanol amine (5.2 g, 49 mmol) and 4- (chloromethyl) biphenyl (10 g, 49 mmol). Yield 9.98 g, (66%); white solid, mp 160-162 ° C; MS: 271.9 (M + H) +. This was converted to the dichloride as set forth in Example 83. The ethyl ester of 1-biphenyl-4-ylmethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (2.85 g, 11 mmol) and l-biphenyl-4-ylmethyl-bis- (2-chloro-ethyl) -amine (3.4 g, mmol). Yield 2.1 g, (39%); khaki solid, mp 176-178 ° C, MS: 494.1 (M + H) +. L-biphenyl-4-ylmethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 1-biphenyl-4-methylmethyl- (4-methoxy-benzenesulfonyl) -piperidin-4 acid carboxylic acid (5.7 g, 12 mmol) dissolved in ethanol (20 mL), tetrahydrofuran (20 mL), 10 N sodium hydroxide (10 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.1 g (39%), MS: 465.8 (M + H) +. Starting from 1-biphenyl-4-ylmethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (1.0 g, 2.2 mmol) and following the procedure set forth in Example 83, .132 g of hydroxamide was isolated. of 1-biphenyl-4-ylmethi-4- (4-methoxy-benzenesulfonyl) piperidin-4-carboxylic acid as a brown solid, mp 168 ° C; Yield 20%; MS: 440.9 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.30-2.35 (m, 2H), 2.83-2.87 (m, 2H), 3.35-3.5 (m, 4H), 3.87 (s, 3H), 7.15-7.721 ( d, J = .0590 Hz, 2H), 7.49-7.65 (m, 5H), 7.68-7.74 (d, J = .06 Hz, 2H), 9.3 (s, 1H), 10.3 (s, 1H), 11.15 (s, 1H).

Example 89 4- (4-Methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) -1 was prepared - (3-methyl-but-2-enyl) -amino] -ethanol according to the general method set forth in example 83. Starting from diethanol amine (4.1 g, 39 mmol) and 2-Bromo-2-methyl-butene (6.0 g, 40 mmol). Performance (98%); brown oil, MS: 173.8 (M + H) +. 1- (3-Methyl-but-2-enyl) -bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from 2- [(2-hydroxy-ethyl)] -1- (3-Methyl-but-2-enyl) -amino] -ethanol (10.4 g, 50 mmol). Yield 10.5 g (99%); solid brown, MS: 210.3 (M + H). The 4- (4-methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in example 1. Starting from ethyl 4- (methoxy-benzenesulfonyl) -acetic acid ester (11.32 g, 44 mmol) and 3-methyl-but-2-enyl) -bis- (2-chloroethyl) -amine (10.4 g, 50 mmol). Yield 6.2 g, (36%); brown oil; MS: 395.6 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1 ethyl ester - (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid (6.2 g, 16 mmol) dissolved in ethanol (15 mL), 10 N sodium hydroxide (10 mL) and tetrahydrofuran (75 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.2 g (21%), brown solid, mp 196-197 ° C, MS: 367.9 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid (1.0 g, 3.0 mmol) and following the procedure set forth in Example 83, isolated .110 mg of 4- (4-methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) -piperidine-4-carboxylic acid hydroxamide as a yellow solid, mp 142-145 ° C; Yield 12%; MS: 382.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 1.67 (s, 3H), 1.79 (s, 3H), 2.18-2.23 (m, 2H), 2.66-2.73 (m, 2H), 3.37-3.46 (m, 2H), 3.67-3.69 (m, 2H), 5.19-5.24 (m, 1H), 7.15-7.18 (d, J = .03, 2H), 7.67-7.70 (d, J = .030, 2H), 9.34 (s, 1H), 9.88 (s, 1H), 11.15 (s, 1H).

Example 90 1- (4-Bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide. 2- [(4-Bromobenzyl) - (2-hydroxy-ethyl) -amino was prepared. ] -ethanol according to the general method set forth in example 83. Starting from diethanolamine (22.5 g, 150 mmol) and 4-bromobenzyl bromide (25 g, 100 mmol). Yield 33.66 g, (99%); yellow oil, MS: 273.8 (M + H) +. (4-Bromo-benzyl) -bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting with 2- [(4-bromobenzyl) - (2-hydroxy-ethyl) -amino] -ethanol (33.28 g, 122 mmol). Yield 47 g (99%); solid brown; mp 125 ° C; MS: 309.8 (M + H) +. The l- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83.

Starting with 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (8.6 g, 33.5 mmol) and (4-bromo-benzyl) -bis- (2-chloro-ethyl) -amine (13.3 g, 38.6 mmol). Yield 17 g, (44%); brown oil; MS: 497.8 (M + H) +. The 1- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 1- (4-bromo-benzyl) -4- (4- methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (16.5 g, 33.3 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (20 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 6.18 g (40%), brown solid, mp 215 ° C, MS: 469.7 (M + H) +. Starting from 1- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (1.95 g, 4.2 mmol) and following the procedure set forth in Example 83, 1.29 g of L- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide as a white, off-white solid. Yield 60%; mp 180 ° C; MS: 484.7 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.18-2.29 (m, 2H), 2.46 (d, 2H), 2.74-2.89 (m, 2H), 3.39 (d, 2H), 3.87 (s, 3H) , 4.28 (s, 2H), 7.18 (d, J = 17 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.65-7.68 (m, 4H), 9.37 (s, 1H), 10.5 ( s, 1H).

Example 91 4- (4-Methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (3-phenyl-propyl)] amino) -ethanol according to the general method set forth in example 83. Starting with diethanolamine (15.8 g, 151 mmol) and l-bromo-3-phenylpropane (20 g, 101 mmol). Yield 21.31 g, (95%); yellow oil, MS: 223.9 (M + H) +. Bis- (2-chloro-ethyl) - (3-phenyl-propyl) -amine was prepared according to the general method set forth in Example 83.

Starting with 2- [(2-hydroxy-ethyl) - (3-phenyl-propyl) -amino] -ethanol (20.32 g, 90.7 mmol). Yield 24.9 g (92%); brown oil; MS: 259.8 (M + H) +. The 4- (4-Methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting with ethyl ester - (methoxy-benzenesulfonyl) -acetic acid (12 g, 46.5 mmol) and bis- (2-chloro-ethyl) - (3-phenylpropyl) -amine (24.8 g, 93.8 mmol). Yield 11.24 g, (54%); brown oil; MS: 446 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine-4-carboxylic acid was prepared starting from ethyl 4- (4-methoxy-benzenesulfonyl) -1- (3- phenylpropyl) -piperidine-4-carboxylic acid (10.74 g, 24.13 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.67 g (47%), white matte powder, mp 203 ° C, MS: 418.2 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine-4-carboxylic acid (4.37 g, 10.4 mmol) and following the procedure set forth in Example 83, 1.64 g of 4- (4-methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) -piperidine-4-carboxylic acid hydroxyamide as a white, off-white solid. Yield 37%; mp 143 ° C; MS: 432.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 1.92-1.97 (m, 2H), 2.18-2.29 (m, 2H), 2.47 (d, 2H), 2.58 (t, H = 7.7 Hz, 2H), 2.6 -2.73 (m, 2H), 3.0-3.06 (m, 2H), 3.60 (d, J = 12.3 Hz, 2H), 3.87 (s, 2H), 7.15-7.30 (m, 7H), 7.68, (d, J = 9 Hz, 2H), 9.3 (s, 1H), 10.1 (s, 1H).

Example 92 l-Tert-Butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide Tert-butyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from 1-tert-butyl-diethanolamine (6 g, 37.2 mmol). Yield 11.15 g (99%); white solid; MS: 197.8 (M + H) +. The ethyl ester of l-tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in Example 83. Starting from ethyl ester of 4- (methoxy) acid. benzenesulfonyl) -acetic (10 g, 38.76 mmol) and tert-butyl-bis- (2-chloro-ethyl) -amine (5.25 g, 22.54 mmol). Yield 5.37 g, (62%); brown oil; MS: 384 (M + H) +. L-tert-Butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidin-4-ethyl ester. carboxylic acid (5.37 g, 14 mmol) dissolved in methanol (300 ml) and 10 N NaOH (23 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.52 g (30.6%), white powder, mp 203 ° C, MS: 356 (M + H) +. Starting from l-tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (320 mg, 0.9 mmol) and following the procedure set forth in Example 83, 190 mg of hydroxyamide of the acid was isolated. -tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a green solid. Yield 52%; mp 40 ° C; MS: 371.1 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 1.29 (s, 9 H), 1.54 (m, 2 H), 1.66 (m, 2 H), 2.39 (m, 2 H), 2.98 (m, 2 H), 3. ' 88 (s, 3H), 7.18 (d, 2H), 7.67 (d, 2H).

Example 93 l-Butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide Butyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting from N-butyldiethanolamine (6 g, 37.2 mmol).

Yield 11.3 g (99%); white powder; mp 165 ° C; MS: 197.9 (M + H) +. The ethyl ester of l-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in Example 83. Starting from ethyl ester of 4- (methoxy-benzenesulfonyl) acid -acetic (5 g, 19.38 mmol) and butyl-bis- (2-chloro-ethyl) -amine (4.52 g, 19.38 mmol). Yield 6.86 g, (93%); brown oil; MS: 384 (M + H) +. L-Butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (6.42). g, 16.8 mmol) dissolved in methanol (200 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.6 g (27%), white powder, mp 206 ° C, MS: 356.4 (M + H) +. Starting from l-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (1.51 g, 4.3 mmol) and following the procedure set forth in Example 83, 200 mg of l-butyl hydroxyamide were isolated. -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a white matte solid. Performance 9.3%; mp 75 ° C; MS: 371.1 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.87 (t, J = 7.2 Hz, 3 H), 1.27 (m, 2 H), 1.59 (m, 2 H), 2.27 (m, 2 H), 2.45 (m, 2 H) ), 2.50 (m, 2H), 2.65 (m, 2H), 2.97 (m, 2H), 3.88 (s, 3H), 7.18 (d, 2H), 7.69 (d, 2H).

Example 94 l-Cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide Cyclooctyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from N-cyclooctyldiethanolamine (6 g, 28 mmol). Yield 10 g (99%); white solid; mp 158 ° C; MS: 251.9 (M + H) +. The ethyl ester of l-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in Example 83. Starting from ethyl ester of 4- (methoxy-benzenesulfonyl) acid -acetic (5 g, 19.4 mmol) and cyclooctyl-bis- (2-chloro-ethyl) -amine (5.57 g, 19.4 mmol). Yield 8.2 g, (96%); brown oil; MS: 438 (M + H) +.

L-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (8) g, 18.3 mmol) dissolved in methanol (200 ml) and 10 N NaOH (25 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.36 g (32%), white powder, mp 180 ° C, MS: 410 (M + H) +. Starting from l-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.26 g, 5.53 mmol) and following the procedure set forth in Example 83, 570 mg of l-cyclooctyl hydroxyamide were isolated. -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a white powder. Performance 22%; pf > 200 ° C; MS: 425 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 1.42-1.66 (m, 14H), 1.83 (m, 2H), 2.33 (m, 2H), 2.67 (m, 2H), 3.30-3.51 (m, 3H) , 3.88 (s, 3H), 7.17 (d, 2H), 7.66 (d, 2H).

Example 95 l-Ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (3 g, 11.6 mmol) and ethyl-bis- (2-chloro-ethyl) -amine (2.39 g) , 11.6 mmol). Yield 3.09 g, (75%); solid brown low melting; MS: 356 (M + H) +. The l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.42 g, 6.8 mmol) dissolved in methanol (100 ml) and 10 N NaOH (15 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.29 g (58%), white solid, mp 209 ° C, MS: 328 (M + H) +. Starting from l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (1.23 g, 3.76 mmol) and following the procedure set forth in Example 83, 1.02 g of l-ethyl hydroxyamide were isolated. -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a white matte powder. Performance 80%; mp 85 ° C; MS: 343 (M + H) +; ? H NMR (300 MHz, DMSO-d6): d 0.926 (t, J = 7.1 Hz, 3H), 1.68-1.89 (m, 4H), 2.05-2.24 (m, 4H), 2.73 (c, 2H), 3.85 ( s, 3H), 7.07 (d, 2H), 7.64 (d, 2H).

EXAMPLE 96 L-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The l-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (5.7 g, 22.2 mmol) and isopropyl-bis- (2-chloro-ethyl) -amine (4.9 g 22.2 mmol). Yield 5.64 g, (75%); solid brown low melting; MS: 370 (M + H) +. The l-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (5.6 g, 15.2 mmol) dissolved in methanol (75 ml) and 10 N NaOH (25 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.18 g (42%), white powder, mp 204 ° C, MS: 341.9 (M + H) +. Starting from l-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.13 g, 6.25 mmol) and following the procedure set forth in Example 83, 590 mg of l-isopropyl hydroxyamide were isolated. -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a white powder. Performance 2.4%; mp 75 ° C; MS: 357 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 1.21 (d, J = 6.6 Hz, 6H), 2.33-3.53 (m, 9H), 3.88 (s, 3H), 7.16 (d, 2H), 7.66 (d , 2H).

Example 97 l-Methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in Example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (3 g, 11.6 mmol) and methyl-bis- (2-chloro-ethyl) -amine (2.2 g) , 11.6 mmol). Yield 3.09 g, (75%); solid brown low melting; MS: 342 (M + H) +. L-Methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (8.7 g, 25.6 mmol) dissolved in methanol (300 ml) and 10 N NaOH (35 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.23 g (41%), white solid, mp 204 ° C, MS: 313.9 (M + H) +. Starting from l-methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.0 g, 6.38 mmol) and following the procedure set forth in Example 83, 1.10 g of l-methyl hydroxyamide were isolated. -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a yellow powder. Yield 53%; mp 89 ° C; MS: 329 (M + H) +; X H NMR (300 MHz, DMSO-de): d 1.67-1.76 (m, 2H), 1.85-1.96 (m, 2H), 2.05 (s, 3H), 2.17 (d, J = 11.4 Hz, 2H), 2.57 (d, J = 10.4 Hz, 2H), 3.83 (s, 3H), 7.02 (d, 2H), 7.62 (d, 2H).

Example 98 l-Benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in example 83. Starting from 4- (butoxy-benzenesulfonyl) -acetic acid ethyl ester (6 g, 20 mmol) and bis- (2-chloro-ethyl) -benzylamine (10 g, mmol). Yield 5.15 g, (75%); yellow oil; MS: 460 (M + H) +. L-benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (5.1 g, 11.1 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (10 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.66 g (56%), white solid, mp 210 ° C, MS: 432 (M + H) +.

Starting from l-benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.61 g, 6.06 mmol) and following the procedure set forth in Example 83, 860 mg of l-benzyl hydroxyamide were isolated -4- (4-Butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a white matte powder. Performance 32%; mp 144 ° C; MS: 446.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.94 (t, J = 7.3 Hz, 3 H), 1.44 (c, J = 7.5 Hz, 2 H), 1.70 (c, 2 H), 2.28-2.32 (m, 2 H) ), 2.50 (d, 2H), 2.74-2.83 (m, 2H), 3.35 (d, 2H), 4.08 (t, J = 6.3 Hz, 2H), 4.34 (s, 2H), 7.13 (d, J = 8.7, 2H), 7.45 (s, 3H), 7.54 (s, 2H), 7.74 (d, J = 8.7, 2H), 9.35 (s, 1H), 10.7 (s, 1H).

Example 99 1- (4-Fluoro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The 1- (4-fluoro-benzyl) -4- ethyl ester ( 4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (18.8 g, 72.8 mmol) and (4-fluoro) -benzyl) -bis- (2-chloro-ethyl) -amine (20.8 g, 73 mmol). Yield 25 g, (79%); brown oil; MS: 436.9 (M + H) +. 1- (4-Fluoro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 1- (4-fluoro-benzyl) -4- (4- methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (17.4 g, 40 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 10.8 g (66%), colorless solid, mp 154 ° C, MS: 408 (M + H) +. Starting with 1- (4-fluoro-benzyl) -4- (4-ethoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (8.14 g, 20 mmol) and following the procedure set forth in Example 83, 4.3 g of L- (4-Fluoro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide as a white, off-white solid. Yield 51%; mp 176-178 ° C; MS: 484.7 (M + H) +; : H NMR (300 MHz, DMSO-de): d 2.12-2.20 (m, 2H), 2.64-2.79 (m, 2H), 3.32-3.45 (m, 4H), 3.87 (s, 3H), 4.31 (s) , 2H), 7.14-7.19 (d, J = 17 Hz, 2H), 7.27-7.33 (d, J = 8.1 Hz, 2H), 7.50-7.54 (d, 2H), 7.65-7.68 (d, 2H), 9.38 (s, 1H), 9.75 (s, 1H).

EXAMPLE 100 1- (4-Fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l- (4-fluoro-benzyl) -4- ( 4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid according to the general method set forth in Example 83.

Starting with 4- (butoxy-benzenesulfonyl) -acetic acid ethyl ester (6 g, 20 mmol) and (4-fluoro-benzyl) -bis- (2-chloro-ethyl) -amine (5.73 g, 20 mmol). Yield 8.2 g, (86%); yellow oil; MS: 478 (M + H) +. 1- (4-Fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 1- (4-fluoro-benzyl) -4- (4- butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (4.77 g, 10 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (10 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.5 g (79%), off white solid, mp 114 ° C, MS: 450 (M + H) +. Starting from 1- (4-fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (2.24 g, 5.0 mmol) and following the procedure set forth in Example 83, 200 mg of L- (4-Fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide as a white matte powder. Performance 9%; mp 112 ° C; MS: 465.9 (M + H) +; H NMR (300 MHz, DMSO-d6): d 0.94 (t, J = 7.3 Hz, 3H), 1.35-1.50 (m, 2H), 1.68-1.77 (m, 2H), 2.20-2.28 (m, 2H) , 2.66-2.77 (m, 2H), 3.77-3.78 (m, 4H), 4.06-4.10 (m, 2H), 4.19 (s, 2H), 7.14-7.19 (d, J = 8.7, 2H), 7.27- 7.33 (d, 2H), 7.50-7.54 (d, 2H), 7.65-7.68 (d, 2H), 9.34 (s, 1H), 10.55 (s, 1H).

Example 101 4- (4-Methoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (4-methoxy-benzyl)] amino) -ethanol according to the general method set forth in example 83. Starting from diethanolamine (12.0 g, 114 mmol) and 4-methoxybenzyl chloride (14.2 g, 100 mmol). performance 17. 5 g, (77%); yellow oil; MS: 226 (M + H). 4-Methoxybenzyl-bis- (2-chloro-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting from 4-methoxy-benzyl diethanolamine (10 g, 44 mmol). Yield 10 g, (75%); yellow solid, mp 55 C; EM: 263. 1 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from ethyl ester - (methoxy-benzenesulfonyl) -acetic (5.0 g, 20 mmol) and bis- (2-chloro ethyl) - (4-methoxy-benzyl) -amine (7.0 g, 22 mmol). Yield 5.0 g, (56%); low melting solid; MS: 448.5 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) 1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy) ethyl ester -benzyl) -piperidine-4-carboxylic acid (4.2 g, 10 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (10 mL), tetrahydrofuran (20 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.0 g (71%), white solid, mp 190 ° C, MS: 420.4 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid (2.0 g, 4.7 nmol) and following the procedure set forth in Example 83, 1.2 g of 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide as a white solid, mp 175 ° C (HCl); Yield 1.2 g, 59%; MS: 433.0 (M + H) +; 1 H NMR (300 MHz, DMSO-de): d (1.8 (m, 4H), 2.3 (m, 2H), 2.73 (m, 2H), 3.37 (d, 2H), 3.76 (s, 3H), 3.88 ( s, 3H), 6.87 (d, 2H), 7.11 (d, 2H), 7.21 (d, 2H), 7.65 (d, 2H), 9.2 (broad s, 1H), 10.9 (broad s, 1H).

Example 102 4- (4-Methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - [2- (4-methoxy-phenyl) -ethyl] -amino] -ethanol according to the general method set forth in Example 83. Starting with diethanolamine (10 g, in excess) and 1- (2-chloroethyl) -4-methoxybenzene (8.5 g, 50 mmol). Yield 11 g, (92%); yellow oil; MS: 240 (M + H) +.

The corresponding dichloride of bis- (2-chloro-ethyl) - (4-methoxyphenyl-2-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from 2-. { (2-hydroxy-ethyl) - [2- (4-methoxy-phenyl) -ethyl] -amino} Ethanol (10 g, 41.8 mmol). Yield 11 g, (95%); brown oil; EM: 277. 2 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from ethyl 4- (methoxy-benzenesulfonyl) -acetic acid ester (5.0 g, 20 nmol) and bis- (2-chloro ethyl) - (4-methoxyphenyl) -2-ethyl] -amine (6.4 g, 20 mmol). Yield 6.0 g, (65%); solid brown; MS: 462.5 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1 ethyl ester - [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid (5.0 g, 10.8 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.0 g (85%), white matte powder, mp 205 ° C, MS: 434.5 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid (1.5 g, 3. 46 mmol) and following the procedure set forth in Example 83, 900 mg of 4- (4-methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid hydroxamide was isolated. like a matt white solid. Yield 58%; mp 206 ° C (HCl); MS: 449.5 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.3 (m, 2 H), 2.5 (m, 3 H), 2.8 (m, 2 H), 2.95 (m, 2 H), 3.25 (m, 2 H), 3.4 (m , 4H), 3.60 (d, J = 12.3 Hz, 2H), 3.77 (s, 3H), 3.99 (s, 3H), 6.9 (d, 2H), 7.1 - 7.25, (c, 4H), 7.7 (d , 2H), 9.3 (s, 1H), 10.6 (s, 1H).

Example 103 4- (4-Methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidine-4-carboxylic acid hydroxyamide. 2- [(2-hydroxy-ethyl) - (2-phenyl-ethyl)] -amino] -ethanol according to the general method set forth in example 1. Starting with diethanolamine (6.0 g, 57) and 2-bromo-ethylbenzene (9.0 g, 48.3 mmol). Yield 9 g, (90%); yellow oil; MS: 210 (M + H) +. Bis- (2-chloro-ethyl) - (2-phenyl-ethyl) -amine was prepared according to the general method set forth in Example 83.

Starting from 2- [(2-hydroxy-ethyl) - (2-phenyl-ethyl) -amino] -ethanol (8.5 g, 40.6 mmol). Yield 11 g, (95%); brown oil; MS: 247.1 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83.

Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (5.0 g, 20 mmol) and bis- (2-chloro-ethyl) - (2-phenyl-ethyl) -amine (5.6 g, 20 mmol). Yield 5.5 g, (63%); brown oil; MS: 432.5 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (2- phenyl-ethyl) -piperidine-4-carboxylic acid (3.0 g, 6.9 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.0 g (72%), white matte powder, mp 208 ° C, MS: 404.5 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidine-4-carboxylic acid (1.5 g, 3.7 mmol) and following the procedure set forth in Example 83, 900 mg of 4- (4-methoxy-benzenesulfonyl) -1- (2-phenyl-ethyl) -piperidine-4-carboxylic acid hydroxyamide as a white matte solid. Yield 58%; mp 205 ° C (HCl); MS: 419.4 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.3 (m, 2 H), 2.5 (m, 3 H), 2.8 (m, 2 H), 2.95 (m, 2 H), 3.25 (, 2 H), 3.4 (m, 4H), 3.9 (s, 3H), 7.22 - 7.8 '(m, 9H), 10.6 (s, 1H), 11.2 (broad s, 1H).

Example 104 4- (4-n-Butoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide The 4- (4-n-butoxy-benzenesulfonyl) ethyl ester was prepared -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in Example 83. Starting with 4- (4-n-butoxy-benzenesulfonyl) -acetic acid ethyl ester (2.5 g, 10 mmol) and bis- (2-chloro ethyl) - (4-methoxy-benzyl) -amine (3.0 g, 10 mmol). Yield 3.5 g, (71%); low melting solid; MS: 490.5 (M + H) +. 4- (4-n-Butoxy-benzenesulfonyl) 1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-n-butoxy-benzenesulfonyl) -1- ethyl ester. (4-methoxy-benzyl) piperidine-4-carboxylic acid (3.0 g, 6.1 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (10 mL), tetrahydrofuran (20 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.5 g (53%), white solid, mp 207 ° C, MS: 462.5 (M + H) +. Starting with 4- (4-n-butoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid (1.0 g, 2.1 mmol) and following the procedure set forth in Example 83, 1.2 were isolated g of 4- (4-n-butoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide as a white solid, mp 173 ° C (HCl); Yield: 800 mg, 77%; MS: 477.5 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 0.9 (t, 3 H), 1.4 (m, 2 H), 1.7 (m, 2 H), 2.3 (m, 2 H), 2.5 (m, 2 H), 2.7 (m , 2H), 3.3 (m, 2H), 3.5 (m, 2H), 4.1 (t, 2H), 4.3 (m, 2H), 6.97 (d, 2H), 7.14 (d, 2H), 7.48 (d, 2H), 7.7 (d, 2H), 9.4 (broad s, 1H), 10.9 (broad s, 1H).

Example 105 4- (4-Methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (3-phenoxy-propyl)] -amino] -ethanol according to the general method set forth in Example 83. Starting with diethanolamine (15.8 g, 151 mmol) and 3-phenoxypropyl bromide (21.5 g, 100 mmol). Yield 21.31 g, (95%); yellow oil; MS: 238.1 (M + H) +. Bis- (2-chloro-ethyl) - (3-phenoxy-propyl) -amine was prepared according to the general method set forth in Example 83. Starting from 2- [(2-hydroxy-ethyl) - (3-phenoxy) propyl) -amino] -ethanol (20.0 g, 84 mmol). Yield 24.0 g, (91%); brown oil; MS: 277.8 (M + H) +. The 4- (methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting with ethyl ester (methoxy-benzenesulfonyl) -acetic (5.2 g, 20 mmol) and bis- (2-chloro-ethyl) - (3-phenoxy-propyl) -amine (7.0 g, 21 mmol). Yield 6.5 g, (70%); brown oil; MS: 432.5 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-) ethyl ester phenoxy-propyl) -piperidine-4-carboxylic acid (4.2 g, 9.1 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.0 g (75%), matt white powder, mp 195 ° C, MS: 434.5 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid (2.5 g, 5.77 mmol) and following the procedure set forth in the example 83, 1.2 g of 4- (4-methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide was isolated as a white off-white solid. Yield 46%; mp 101 ° C; MS: 448.5 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.18 (m, 2 H), 2.3 (m, 2 H), 2.58 (m, 2 H), 2.6-2.73 (m, 2 H), 3.0-3.06 (m, 2 H) , 3.60 (m, 2H), 3.87 (s, 3H), 4.01 (t, 2H), 6.9-7.77 (m, 9H), 9.33 (broad s, 1H), 10.28 (broad s, 1H).

Example 106 4- (4-n-Butoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide The 4- (4-n-butoxy-benzenesulfonyl) ethyl ester was prepared -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid according to the general method set forth in Example 83. Starting with 4- (butoxy-benzenesulfonyl) -acetic acid ethyl ester (3.0 g, 10 mmol) and bis- (2-chloroethyl) - (3-phenoxy-propyl) -amine (3.0 g, 11 mmol). Yield 4.5 g, (89%); brown oil; MS: 504.6 (M + H) +. 4- (4-n-Butoxy-benzenesulfonyl) 1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-n-butoxy-benzenesulfonyl) -1- ethyl ester. (3-phenoxy-propyl) piperidine-4-carboxylic acid (4.0 g, 7.9 mmol) dissolved in methanol: THF and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.0 g (79%), white matte powder, mp 191 ° C, MS: 476.5 (M + H) +. Starting with 4- (4-n-butoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid (700 mg, 1.4 mmol) and following the procedure set forth in Example 83, 300 were isolated mg of 4- (4-n-butoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide as a matt white solid. Performance 43%; mp 84 ° C; MS: 491.5 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 0.9 (t, 3 H), 1.5 (m, 2 H), 1.8 (m, 2 H), 2.18 (m, 2 H), 2.3 (m, 2 H), 2.58 (m , 2H), 2.6-2.73 (m, 2H), 3.2 (m, 2H), 3.40 (m, 6H), 3.97 (t, 2H), 4.1 (t, 2H), 6.9 - 7.7 (m, 9H), 10.7 (broad s, 1H), 11.28 (broad s, 1H).

Example 107 4- (4-Methoxy-benzenesulfonyl) -1- (2-phenoxyethyl) -piperidine-4-carboxylic acid hydroxyamide 2- [(2-hydroxy-ethyl) - (2-phenoxy-ethyl)] -amino] -ethanol according to the general method set forth in Example 83. Starting from diethanolamine (15.0 g, 150 mmol) and 2-chloro-phenethol (15.6 g, 100 mmol). Yield 18 g, (80%); Colorless oil; MS: 226 (M + H) +. Bis- (2-chloro-ethyl) - (2-phenoxy-ethyl) -amine was prepared according to the general method set forth in Example 83. Starting from 2- [(2-hydroxy-ethyl) - (2-phenoxy) ethyl) -amino] -ethanol (20.0 g, 88.8 mmol). Yield 25 g, (94%); brown oil; MS: 263.1 (M + H) +. The ethyl ester of the acid was prepared 4- (4-methoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid according to the general method set forth in Example 83. Starting from ethyl ester of 4- (methoxy-benzenesulfonyl) - acetic acid (5.0 g, 20 mmol) and bis- (2-chloro ethyl) - (2-phenoxy-ethyl) -amine (6.0 g, 20 mmol). Yield 5.8 g, (64%); brown oil; MS: 448.5 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (2- phenyl-ethoxy) -piperidine-4-carboxylic acid (5.0 g, 11.1 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 mL). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.0 g (63%), white matte powder, mp 235 ° C, MS: 420.5 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid (2.5 g, 5.9 mmol) and following the procedure set forth in Example 83, 1.3 g of 4- (4-methoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid hydroxyamide as a matt white solid. Yield 50%; mp 168-172 ° C (HCl); MS: 435.4 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 2.3 (m, 2 H), 2.5 (m, 2 H), 2.9 (m, 2 H), 3.4 (m, 4 H), 3.5 (m, 2 H), 3.7 (m , 2H), 3.9 (s, 3H), 4.4 (m, 2H), 6.9-7.8 (m, 9H), 9.3 (s, 1H), 10.2 (broad s, 1H), 11.3 (broad s, 1H).

Example 108 4- (4-n-Butoxy-benzenesulfonyl) -1- (2-phenoxyethyl) -piperidine-4-carboxylic acid hydroxyamide 4- (4-n-butoxy-benzenesulfonyl) ethyl ester was prepared -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (2.5 g, 10 mmol) and bis- (2-chloro ethyl) - (2-phenoxy-ethyl) -amine (2.98 g, 10 mmol). Performance 3.0 g, (69%); brown oil; MS: 490.6 (M + H) +. 4- (4-n-Butoxy-benzenesulfonyl) 1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-n-butoxy-benzenesulfonyl) -ethyl ethyl ester. (2-phenyl-ethoxy) -piperidine-4-carboxylic acid (2.5 g, 5.76 mmol) dissolved in methanol: THF and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.5 g (56%), white matte powder, mp 204 ° C, MS: 462.5 (M + H) +. Starting from 4- (4-n-butoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid (1.0 g, 2.16 mmol) and following the procedure set forth in Example 83, 600 were isolated mg of 4- (4-n-butoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid hydroxyamide as a white, off-white solid. Yield 58%; mp 112 ° C (HCl); MS: 477.4 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 0.942 (t, 3 H), 1.4 (m, 2 H), 1.7 (m, 2 H), 2.3 (m, 2 H), 2.5 (m, 2 H), 2.8 (m , 2H), 2.9-3.4 (m, 4H), 3.3 (m, 4H), 4.2 (t, 2H), 4.4 (m, 2H), 6.9 -7.7 (m, 9H), 9.4 (s, 1H), 10.5 (broad s, 1H), 11.3 (broad s, 1H).

Example 109 4- (4-Methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide Bis- (2-chloro-ethyl) was prepared ) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine according to the general method set forth in example 83. Starting from diethanolamine (15.0 g, 150 mmol) and 4- (2-) chloride piperidin-1-yl-ethoxy) -benzyl (5.9 g, 20 mmol). Yield 5.5 g, (85%); Brown semi-solid; MS: 323 (M + H) +. Bis- (2-chloro-ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine was prepared according to the general method set forth in example 83. Starting with 2- [(2 -hydroxy-ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine (3.22 g, 10 mmol). Performance. 4.0 g, (92%); brown semisolid; MS: 361.1 (M + H) +. The 4- (4-methoxy-benzenesulfonyl) -l- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83. Starting from 4- (methoxy-benzenesulfonyl) -acetic acid ethyl ester (5.0 g, 20 mmol) and bis- (2-chloro ethyl) - [4- (2-piperidin-1-yl-ethoxy) - benzyl] -amine (8.6 g, 20 mmol). Yield 6.0 g, (55%); brown oil; MS: 545.7 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 4- (4-) acid. methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid (5.4 g, 10 mmol) dissolved in THF: methanol 3: 1 and NaOH 10 N (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.0 g (77%), matt white powder, mp 174 ° C, MS: 517.6 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidin-4-carboxylic acid (3.5 g, 6.78 mmol) and following the procedure set forth in Example 83, 1.8 g of 4- (4-methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide was isolated as a Pale yellow white solid. Performance 49%; mp 114 ° C (HCl); EM: 532 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6): d 1.4-1.6 (m, 4H), 1.9 (m, 2H), 2.3 (m, 2H), 2.8 (m, 2H), 3.4 (m, 4H), 3.9 (s, 3H), 4.2 (m, 1H), 6.9-7.8 (m, 8H), 9.1 (s, 1H), 10.8 (s broad, 1H).

Example 110 N-Hydroxy-2- (4-methoxy-benzenesulfonyl) -propionamide Step A: Coupling of 2-bromo-propionic acid to the hydroxylamine resin. 4-O-methylhydroxylamino-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (2g, 1.1 meq / g) was placed in a peptide synthesis vessel (Chemglass Inc. Part Number CG-1866) and suspended in DMF (20 mL). 2-Bromopropionic acid (0.6 mL, 3.0 eq.), 1-hydroxybenzotriazole hydrate (HOBt, 1.8 g, 6.9 eq.) And 1,3-diisopropyl-carbodiimide (DIC, 1.4 mL, 4.0 eq) were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was removed and subjected to the Kaiser test. If the test showed the presence of free amine (blue resin) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM (2 x 20 mL). one wash consisted of the addition of the solvent and stirring by bubbling nitrogen or stirring in the orbital shaker for 1-5 minutes, then filtration under vacuum). The resin was dried in vacuo at room temperature. A resin sample (5-20 mg) was subjected to cleavage with DCM (0.5 mL) and TFA (0.5 mL) for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (1 x 1 mL). Filtering and washing were combined and concentrated in vacuo in a Savant SpeedVac Plus. Methane (1 mL) was added and the mixture was concentrated. The product was then characterized by H1 NMR, (DMSO d-6) d 4.54 (c, 1H), 1.83 (d, 3H).

Step B: Displacement of bromine with 4-methoxybenthiol. The N-hydroxy-2-bromo-propionamide resin prepared in Step A (0.35 g, 1.1 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 4-methoxybenthiol (0.23 mL, 5.0 eq.) Sodium iodide was added (288 mg, 5.0 eq.) And 1,8-diasabicyclo [5.4.0] undec-7-ene (DBU, 0. 17 mL, 3.0 eq. ). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into a barrel of a polypropylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL); DMF (2mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). the resin was dried in vacuo at room temperature.

Step C: Oxidation of sulfur to sulfoxide. The N-hydroxy-2- (4-methoxy-benzenesulfanyl) -propionamide resin prepared in Step B (175 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and 70% of tert-butylhydroxyperoxide ( 1.0 mL) and benzenesulfonic acid (50 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DCM (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step D: Oxidation of sulfur to sulfone. The N-hydroxy-2- (4-methoxy-benzenesulfanyl) -propionamide resin prepared in Step B (175 mg, 1: 1 meq / g) was suspended in DCM (3.0 mL) and added to m CPBA (180 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step E: Cleavage of the N-hydroxy-2- (4-methoxy-benzenesulfonyl) -propionamide from the resin. The N-hydroxy-2- (4-methoxy-benzenesulfonyl) -propionamide resin prepared in Step D (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness in a Savant Speed Plus. Methanol (1 mL) was added and the mixture was concentrated. 84% @ 215 nm; XH NMR (DMSO d-6) d 10.75 (broad s, 1H), 7.71 (dd, 2H), 7.16 (dd, 2H) 3.87 (s, 3 H), 3.83 (c, 1H), 1.26 (d, 3H) ). The hydroxamic acids of Examples 111-113 were synthesized using the appropriate materials and following the steps of example 110.

Example 111 N-Hydroxy-2- (4-methoxy-benzenesulfanyl) -propionamide. 72% @ 215 nm N-hydroxy-2 (4-methoxy-benzenesulfinyl) -propionamide. 76% = 215 nm; XH NMR (DMSO d-6) d 10.90 & 10.60 (broad s, 1H), 7.95 (broad s, 1H) 7.61 & 7.52 (dd, 2H), 7.15 & 7.10 (dd, 2H), 3.83 & 3.82 (s, 3H), 3.42 & 3.28 (c 1H), 1.23 & 0.97 (d, 3H).

Example 112 N-Hydroxy-2- (3-methyl-butane-l-sulfanyl) -propionamide. 74% @ 215 nm. N-Hydroxy-2- (3-methyl-butane-l-sulfanyl) -propionamide. 1 H NMR (DMSO d-6) d 10.8 (broad s, 1H), 7.95 (broad s, 1H) 3.45 & 3.31 (c, 1H), 2.71-2.50 (m, 2H), 1.71-1.46 (m, 3H), 1.33 & 1.25 (d, 3H), 0.94-0.82 (m, 6H) Example 113 N-Hydroxy-2- (3-methyl-butane-1-sulfonyl) -propionamide. 84% @ 215 nm.

Example 114 N-Hydroxy-3-methyl-2- (naphthalene-2-yl-sulfanyl) -butyramide Step A: Coupling of 2-bromo-3-methyl-butyric acid to the hydroxylamine resin. 4-O-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (5.9 g, 1.1 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2-Bromo-3-methyl-butyric acid (9.96 g, 10.0 eq), and DIC (9.04 mL, 10.5 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin turned blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM (2). x 20 mL). The resin was dried in vacuo at room temperature.

Step B Displacement of bromine with 2-naphthalethiol. The 2-bromohydroximate resin prepared in the Step A (0.15 g, 1.1 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). They added 2-naphthalethiol (138 mg, 5.0 eq.), Sodium iodide (129 mg, . 0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.078 mL, 3. 0 eq. ). The reaction was stirred at room temperature during 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2 mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The hydroxyamide resin of 2- (2-naphthalenesulfonyl) -N-hydroxypropionamide acid prepared in Step B (175 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and 70% tert-butylhydroperoxide (1.0 mL) benzenesulfonic acid (50 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours.

The reaction was filtered and washed with DCM ('2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. .

The 2- (2-Naphthalenesulfanyl) -N-hydroxy-propionamide resin prepared in step B (175 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and mCPBA (180 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of the N-hydroxy-3-methyl-2- (naphthalen-2-ylsulfanyl) butyramide from the resin. The resin of 2- (2-Naphthalenesulfanyl) -N- (hydroxypropionamide) prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 83% @ 215 nm; LCMS (electroraceum API) m / z 276 (M + H) +; XH NMR (DMSO d-6) d 10.7 (broad s, 1H), 7.91-7.81 (m, 4H) 7.55-7.45 (m, 3H), 3.41 (d, 1H), 2.09-1.97 (m, 3H), 0.97 (d, 3H).

The hydroxamic acids of Examples 115-118 were synthesized using appropriate starting materials and following the steps of Example 114.

Example 115 N-Hydroxy-3-methyl-2- (naphthalen-2-yl-sulfinyl) -butyramide. 67% @ 215 nm.

Example 116 N-Hydroxy-3-methyl-2- (naphthalen-2-ylsulfonyl) -butyramide. 97% @ 215 nm; LCMS (API electrorrocio) m / z 254 (M + H) +.

Example 117 N-Hydroxy-3-methyl-2-phenethylsulfinyl-butyramide. 93% @ 215 nm; LCMS (electroradio) m / z 254 (M + H) +.

Example 118 N-Hydroxy-3-methyl-2-phenethylsulfonyl-butyramide. 97% @ 215 nm; LCMS (electro-vacuum) m / z 286 (M + H) +.

Example 119 (1-Hydroxycarbamoyl-propan-1-sulfanyl) -acetic acid methyl ester Step A: Coupling of 2-bromobutyric acid to the hydroxylamine resin. 4-0-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (5 g, 1.1 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2-Bromobutyric acid (3.0 g, 3.0 eq) HOBt (4.86 g, 6.0 eq) and DIC (3.75 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin is blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM ( 2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with methyl thioglycolate. The 2-bromohydroximate resin prepared in Step A (0.45 g, 1.1 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). Methyl thioglycolate (286 mg, 5.0 eq.), Sodium iodide (404 mg) was added.5.0 eq. ) and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.24 mL, 3.0 eq.). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe. equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2 mL), MeOh (2 x 2 mL), and DCM ( 2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The (1-Hydroxycarbamoyl-propane-1-sulfanyl) -acetic acid methyl ester resin prepared in Step B (150 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and added 70% tert. butylhydroperoxide (1.0 mL) benzenesulfonic acid (50 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfur. The (1-Hydroxycarbamoyl-propan-1-sulfanyl) -acetic acid methyl ester resin prepared in step B (150 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and mCPBA (180 mg) was added. ). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of methyl ester of (1-Hydroxycarbamoyl-propane-1-sulfanyl) -acetic acid of the resin. The (1-Hydroxycarbamoyl-propane-1-sulfanyl) -acetic acid methyl ester resin prepared in step B (150 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. ). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. LCMS (electroraceum API) m / z 228 (M + Na) +. The hydroxamic acids of Examples 120-124 were synthesized using appropriate starting materials and following the steps of Example 119.

Example 120 (1-Hydroxycarbamoyl-propan-1-sulfonyl) -acetic acid hydroxyamide. LCMS (API electrorrocio) m / z 224 (M + H) +.

Example 121 (1-Hydroxycarbamoyl-propan-1-sulfinyl) -acetic acid hydroxyamide. 100% @ 220 nm; LCMS (API electrorrocio) m / z 240 (M + H) +.

Example 122 Hydroxyamide of (1-Hydroxycarbamoyl-propan-1-sulfonyl) -propionic acid. lti NMR (DMSO d-6) d 10.7 (broad s, 1H), 4.03 (st, 2H), 2.95 (c, 1H), 2.75-2.70 (m, 1H), 2.60-2.54 (m, 1H), 1.74 -1.66 (m, 2H), 1.58-1.50 (m, 4H), 1.32 (sextet, 2H), 0.88 (t, 3H), 0.85 (t, 3H); LCMS (electro-vacuum API) m / z 264 (M + H) +.

Example 123 Hydroxyamide of (1-Hydroxycarbamoyl-propan-1-sulfinyl) -propionic acid. 83% @ 220 nm; LCMS (API electrorrocio) m / z 280 (M + H) +.

Example 124 Hydroxyamide of (1-Hydroxycarbamoyl-propan-1-sulfonyl) propionic acid. 100% = 220 nm.

EXAMPLE 125 2- (4-Hydroxybenzenesulfanyl) -N-hydroxy-3-phenyl-propionamide Step A: Coupling of 2-bromo-3-phenylpropidic acid to the hydroxylamine resin. 4-O-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1- (5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2-Bromo-3-phenylpropidnico acid (3.5 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin turned blue) the described / above coupling was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM ( 2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 4-hydroxythiophenol. The 2-bromohydroximate resin prepared in the Step A (0.33 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 4-Hydroxythiophenol (250 mg, 5.0 eq.), Sodium iodide (297 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.18 mL, 3.0 eq. ). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2). mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The resin of 2- (4-Hydroxybenzenesulfanyl) -N-hydroxy-3-phenyl-propionamide prepared in Step B (110 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and 70% tert- butylhydroperoxide (0.73 mL) benzenesulfonic acid (36 mg).

The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The resin of 2- (4-Hydroxybenzenesulfanyl) -N-hydroxy-3-phenyl-propionamide prepared in step B (110 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and mCPBA (132 mg) was added. ). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 2 mL), MeOH (2 x 2 L), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of 2- (4-Hydroxybenzenesulfanyl) -N-hydroxy-3-phenyl-propionamide from the resin. The resin of 2- (4-Hydroxybenzenesulfanyl) -N-hydroxy-3-phenyl-propionamide prepared in step B (110 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. ). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 84% @ 215 nm; XH NMR (DMSO d-6) d 10.41 (broad s, 1H), 7.95 (broad s (1H), 7.30-7.15 (m, 5H), 7.10 (dd, 2H), 6.75 (dd, 2H), 3.53 ( c, 1H), 3.05 (dd, 1H), 2.79 (dd, 1H) The hydroxamic acids of Examples 126-130 were synthesized using appropriate starting materials and following the steps of Example 125.

Example 126 2- (4-Hydroxybenzenesulfinyl) -N-hydroxy-3-phenyl-propionamide. 73% @ 215 nm.

EXAMPLE 127 2- (4-Hydroxybenzenesulfonyl) -N-hydroxy-3-phenyl-propionamide. 77% @ 215 nm; XH NMR (DMSO d-6) d 10.50 (broad s, 1H), 7.95 (broad s, 1H), 7.68-7.57 (m, 2H), 7.28- 7.17 (m, 3H), 7.08-7.98 (m, 2H) ), 6.95-6.87 (m, 2H), 3.96 (t, 1H), 3.02 (d, 2H). Example 128 2- (4-Acetylamino-benzenesulfanyl) -N-hydroxy-3-phenyl-propionamide. 86% @ 215 nm; H NMR (DMSO d-6) d 10.50 (broad s, 1H), 10.03 (broad s, 1H), 8.13 (broad s, 1H), 7.56-7.12 (m, 9H), 3.67 (c, 1H), 3.08 (dd, 1H), 2.84 (dd, 1H), 2.04 (s, 3H).

Example 129 2- (4-Acetylamino-benzenesulfinyl) -N-hydroxy-3-phenyl-propionamide. 73% @ 215 nm.

EXAMPLE 130 2- (4-Acetylamino-benzenesulfinyl) -N-hydroxy-3-phenyl-propionamide. 95% @ 215 nm.

Example 131 (4-Hydroxycarbamoyl) -4- (4-methanesulfanyl-phenylsulfanyl) -butyric acid methyl ester Step A: Coupling of 2-bromo-5-methyl-glutamic acid to the hydroxylamine resin. 4-O-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (4.5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). S-2-Bromo-5-methyl glutarate (3.87 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin is blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM ( 2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 4-hydroxythiophenol. The 2-bromohydroximate resin prepared in the Step A (0.22 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 4- (Methylthio) thiophenol (206 mg, 5.0 eq.), Sodium iodide (197 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.12 mL, 3.0 eq.). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was vented in the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2). mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The 4-hydroxycarbamoyl-4- (4-methanesulfanyl-phenylsulfanyl) -butyric acid methyl ester resin prepared in Step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and 70% strength was added. tert-butylhydroperoxide (0.49 mL) benzenesulfonic acid (36 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step D: Oxidation of sulfur to sulfone. The 4-hydroxycarbamoyl-4- (4-methanesulfanyl-phenylsulfanyl) -butyric acid methyl ester resin prepared in step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and mCPBA ( 87 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of methyl ester of 4-hydroxycarbamoyl-4- (4-methanesulfanyl-phenylsulfanyl) -butyric acid of the resin. The 4-hydroxycarbamoyl-4- (4-methanesulfanyl-phenylsulfanyl) -butyric acid methyl ester resin prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA ( 1.0 mL). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 77% @ 215 mn; LCMS (electro-vacuum API) m / z 316 (M + H) +. The hydroxamic acids of Examples 132-139 were synthesized using appropriate starting materials and following the steps of Example 131.

EXAMPLE 132 (4-Hydroxycarbamoyl-4- (4-methanesufinyl-phenylsulfinyl) -butyric acid hydroxyamide 79% @ 215 nm; LCMS (API electroderoxide) m / z 348 (M + H) +.

Example 133 (4-Hydroxycarbamoyl-4- (4-methanesulfonyl-phenylsulfinyl) -butyric acid hydroxyamide: 78% @ 215 nm; LCMS (API electroderoxide) m / z 380 (M + H) +.

Example 134 (4-Hydroxycarbamoyl-4- (4-bromobenzenesulfanyl) -butyric acid hydroxyamide 93% @ 215 nm.

Example 135 (4-Hydroxycarbamoyl-4- (4-bromobenzenesulfinyl) -butyric acid hydroxyamide 80% @ 215 nm.

Example 136 (4-Hydroxycarbamoyl-4- (4-bromobenzenesulfonyl) -butyric acid hydroxyamide 77% @ 215 nm.

Example 137 (4-Hydroxycarbamoyl-4- (2-trifluoromethyl-benzenesulfanyl) -butyric acid hydroxyamide 93% @ 215 nm.

Example 138 (4-Hydroxycarbamoyl-4- (2-trifluoromethyl-benzenesulfinyl) -butyric acid hydroxyamide 72% @ 215 nm.

Example 139 (4-Hydroxycarbamoyl-4- (2-trifluoromethyl-benzenesulfonyl) -butyric acid hydroxyamide 90% @ 215 nm.

Example 140 2- (3-Methoxy-benzenesulfanyl) decanoic acid hydroxyamide Step A: Coupling of 2-bromo decanoic acid to the hydroxylamine resin. 4-O-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (4.5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2-Bromo-decanoic acid (4.07 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin is blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM ( 2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 3-methoxy-benzothiol. The 2-bromo hydroximate resin prepared in Step A (0.22 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 3-methoxy-benzothiol (185 mg, 5.0 eq.), Sodium iodide (197 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.12 mL, 3.0) were added. eq.). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2). mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The hydroxamide resin of 2- (3-methoxy-benzenesulfanyl) decanoic acid prepared in Step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and 70% tert-butylhydroperoxide (0.49 mL) was added. ) benzenesulfonic acid (24 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The hydroxamide resin of 2- (3-methoxy-benzenesulfanyl) decanoic acid prepared in step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 L) and mCPBA (87 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Hydroxamide incision of 2- (3-methoxy-benzenesulfanyl) decanoic acid from the resin. The hydroxamide resin of 2- (3-methoxy-benzenesulfanyl) decanoic acid prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 89% = 215 nm.

The hydroxamic acids of Examples 141-145 were synthesized using appropriate starting materials and following the steps of example 140.

Example 141 2- (3-Methoxy-benzenesulfinyl) decanoic acid hydroxyamide. 96% @ 215 nm.

Example 142 2- (3-Methoxy-benzenesulfonyl) decanoic acid hydroxyamide. 96% @ 215 nm.

EXAMPLE 143 2- (4-Methanesulfanyl-benzenesulfanyl) decanoic acid hydroxyamide. 85% @ 215 nm; LCMS (electroraceum API) m / z 342 (M + H) +.

Example 144 2- (4-Methanesulfinyl-benzenesulfinyl) decanoic acid hydroxyamide. 86% @ 215 nm; LCMS (electro-vacuum API) m / z 374 (M + H) +.

EXAMPLE 145 2- (4-Methanesulfonyl-benzenesulfonyl) decanoic acid hydroxyamide. 92% @ 215 nm.

EXAMPLE 146 3-Benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide Step A: Coupling of 2-bromo-3-benzyloxy propionic acid to the hydroxylamine resin. 4-O-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (4.5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2-bromo-3-benzyloxy propionic acid (4.2 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin turned blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM (2). x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 4- (methylthio) thiophenol.

The 2-bromo hydroximate resin prepared in Step A (0.22 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 4- (Methylthio) thiophenol (206 mg, 5.0 eq.), Sodium iodide (197 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.12 mL, 3.0 eq.). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2). mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The resin of 3-Benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide prepared in Step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and 70% of tert-butylhydroperoxide (0.49 mL) benzenesulfonic acid (24 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The resin of 3-Benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide prepared in step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and mCPBA ( 87 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of 3-Benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide from the resin. The resin of 3-Benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA ( 1.0 mL). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 76% @ 215 nm; LCMS (electro-vacuum API) m / z 350 (M + H) +. The hydroxamic acids of Examples 147-151 were synthesized using appropriate starting materials and following the steps of Example 146.

EXAMPLE 147 3-Benzyloxy-N-hydroxy-2- (4-methanesul inyl-benzenesulfinyl) -propionamide. 70% @ 215 nm; LCMS (electro-vacuum API) m / z 382 (M + H) +.

EXAMPLE 148 3-Benzyloxy-N-hydroxy-2- (4-methanesulfonyl-benzenesulfonyl) -propionamide. 63% @ 215 nm. LCMS (electro-vacuum API) m / z 414 (M + H) +.

Example 149 3-benzyloxy-N-hydroxy-2- (4-methanesulfanyl-benzenesulfanyl) -propionamide. 90% @ 215 nm.

Example 150 3-benzyloxy-N-hydroxy-2- (2-chloro-benzylsulfinyl) propionamide. 70% @ 215 nm.

Example 151 3-Benzyloxy-N-hydroxy-2- (2-chloro-benzylsulfonyl) propionamide. 72% @ 215 nm.

Example 152 2- (2-Bromo-benzenesulfanyl) -N-hydroxy-3- (3H-imidazole) -propionamide Step A: Coupling of 2-bromo-3- (3H-imidazol-4-yl) -propionic acid to the hydroxylamine resin. 4-0-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (4.5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF. (40 mL). S-2-bromo-3- (3H-imidazol-4-yl) -propidnic acid (3.55 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin turned blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM (2). x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 2-bromothiophenol. The 2-bromo hydroximate resin prepared in Step A (0.22 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 2-Bromothiophenol (249 mg, 5.0 eq.), Sodium iodide (197 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.12 mL, 3.0 eq. ). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2). mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The resin of 2- (2-bromo-benzenesulfanyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide prepared in Step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and 70% tert-butylhydroperoxide (0.49 mL) benzenesulfonic acid (24 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The resin of 2- (2-bromo-benzenesulfanyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide prepared in step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 L) and mCPBA (87 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Incision of 2- (2-bromo-benzenesulfanyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide from the resin. The resin of 2- (2-bromo-benzenesulfanyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL).; and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 86% @ 215 nm. The hydroxamic acids of Examples 153-154 were synthesized using appropriate starting materials and following the steps of Example 152.

Example 153 2- (4-Bromo-benzenesulfinyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide. 69% @ 215 nm.

EXAMPLE 154 2- (4-Chloro-benzenesulfonyl) -N-hydroxy-3- (3H-imidazol-4-yl) -propionamide.

EXAMPLE 155 2- (3-Fluorophenylsulfanyl) -5-guanidino-pentanoic acid hydroxyamide Step A: Coupling of 2-bromo-5-guanidino-pentane acid to the hydroxylamine resin. 4-0-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (4.5 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF. (40 mL). S-2-bromo-5-guanidino-pentane acid (3.85 g, 3.0 eq) HOBt (4.4 g, 6.0 eq.) And DIC (3.4 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin turned blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM (2). x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 3-fluorothiophenol. The 2-bromo hydroximate resin prepared in Step A (0.22 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (2 mL). 3-Fluorothiophenol (169 mg, 5.0 eq.), Sodium iodide (197 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.12 mL, 3. 0 eq.). The reaction was stirred at room temperature during 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF (2 mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The 2- (3-fluorophenylsulfanyl) -5-guanidino-pentanoic resin prepared in Step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and 70% tert-butylhydroperoxide (0.49 mL) was added. ) benzenesulfonic acid (24 mg).

The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The 2- (3-fluorophenylsulfanyl) -5-guanidino-pentanoic resin prepared in step B (73 mg, 1.1 meq / g) was suspended in DCM (1.5 mL) and mCPBA (87 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Hydroxyamide incision of 2- (3-fluorophenylsulfanyl) -5-guanidino-pentanoic acid from the resin. The hydroxyamide resin of 2- (3-fluorophenylsulfanyl) -5-guanidino-pentanoic acid prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. . The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 93% @ 215 nm. The hydroxamic acids of Examples 156-159 were synthesized using appropriate starting materials and following the steps of Example 155.

Example 156 2- (3-Fluorophenylsulfinyl) -5-guanidino-pentanoic acid hydroxyamide. 80% @ 220 nm; LCMS (electroraceous API) m / z 317 (M + H) +.

Example 157 2- (2-Bromosulfanyl) -5-guanidino-pentanoic acid hydroxyamide. 92% @ 220 nm; lti NMR (DMSO d-6) d 10.90 (broad s, 2H), 10.41 (broad s, 1H), 7.95 (s broad 1H), 7.66-7.14 (m, 5H), 3.72 (c, 1H), 3.13 ( c, 2H), 1.90-1.66 (m, 2H), 1.58-1.43 (2H).

Example 158 2- (2-Bromosulfinyl) -5-guanidino-pentanoic acid hydroxyamide. 79% @ 220 nm; LCMS (electro-vacuum API) m / z 379 (M + H) +.

Example 159 2- (2-Bromosulfonyl) -5-guanidino-pentanoic acid hydroxyamide. : H NMR (DMSO d-6) d 8.03-7.45 (m, 5H), 4.52 (c, 1H), 3.16 (c, 2H), 2.07-1.90 (m, 2H), 1.66-1.59 (2H).

EXAMPLE 160 2- (2,5-Dichlorobenzenesulfanyl) -octanoic acid hydroxyamide Step A: Coupling of 2-bromo-octanoic acid to the hydroxylamine resin. 4-0-Methylhydroxylamine-phenoxymethyl-copoly (styrene-1% -divinylbenzene) -resin1 (10.0 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in DMF (80 mL). 2-Bromo octanoic acid (8.8 g, 3.0 eq) HOBt (8.8 g, 6.0 eq.) And DIC (7.2 mL, 4.0 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 2-16 hours. The reaction was filtered and washed with DMF (3 x 20 mL). A sample of resin was subjected to the Kaiser test. If the test shows the presence of amine (the resin is blue) the coupling described above was repeated, otherwise the resin was washed with DCM (3 x 20 mL), MeOH (2 x 20 mL), and DCM ( 2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Displacement of bromine with 2,5-dichlorothiophenol. The 2-bromohydroximate resin prepared in Step A (0.45 g, 1.2 meq / g) was placed in a flask flask of 20 mL and suspended in THF (6 mL). 2, 5-Dichlorothiophenol (483 mg, 5.0 eq.), Sodium iodide (404 mg, 5.0 eq.) And 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 0.24 mL, 3.0) were added. eq.). The reaction was stirred at room temperature for 12-16 hours. The reaction mixture was poured into the barrel of a propylene syringe equipped with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 2 mL), DMF ( 2 mL), MeOh (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step C: Oxidation of sulfur to sulfoxide. The hydroxyamide resin of 2- (2, 5-dichlorobenzenesulfanyl) -octanoic acid prepared in Step B (150 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and 70% tert-butylhydroperoxide (1.0 mL) was added. mL) benzenesulfonic acid (50 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step D: Oxidation of sulfur to sulfone. The hydroxyamide resin of 2- (2, 5-dichlorobenzenesulfanyl) -octanoic acid prepared in step B (150 mg, 1.1 meq / g) was suspended in DCM (3.0 mL) and mCPBA (180 mg) was added. The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Hydroxyamide incision of 2- (2, 5-dichlorobenzenesulfanyl) -octanoic acid from the resin. The hydroxyamide resin of 2- (2, 5-dichlorobenzenesulfanyl) -octanoic acid hydroxyamide resin prepared in step B (73 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. ). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. 92% @ 215 nm; XH NMR (DMSO d-6) d 10.96 (broad s, 1H), 9.26 (broad s, 1H), 7.93-7.76 (m, 3H), 4.07 (c, 1H), 2.04-1.85 (m, 1H), 1.78-1.64 (m, 1H), 1.32-1.09 (m, 8H), 0.81 (t, 3H).

The hydroxamic acids of Examples 161-167 were synthesized using appropriate starting materials and following the steps of example 160.

Example 161 2- (2,5-Dichlorobenzenesulfonyl) -octanoic acid hydroxyamide. 96% @ 215 nm.

Example 162 2- (3-Methoxybenzenesulfanyl) -octanoic acid hydroxyamide. 86% @ 220 nm: LCMS (electroraceous API) m / z 298 (M + H) +.

Example 163 2- (3-Methoxybenzenesulfinyl) -octanoic acid hydroxyamide. 96% @ 220 nm.

Example 164 2- (3-Methoxybenzenesulfonyl) -octanoic acid hydroxyamide. 83% @ 220 nm.

Example 165 2- (3,4-Dimethoxybenzenesulfanyl) -octanoic acid hydroxyamide. 87% @ 215 nm; LMCS (electroacoustic API) m / z 328 (M + H) +.

Example 166 2- (3,4-Dimethoxybenzenesulfinyl) -octanoic acid hydroxyamide. 90% @ 215 nm. Example 167 2- (3,4-Dimethoxybenzenesulfonyl) -octanoic acid hydroxyamide. 87% @ 215 nm.

The hydroxamic acid compounds of Examples 168-198 were synthesized using the appropriate starting materials and following the steps of Example 160. The crude products were dissolved in DMSO: methanol (1: 1 mL) and purified by low reverse phase CLAP. the conditions described below: Column: ODS-A, 20 mm x 50 mm, particle size 5 μm (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL / min.

Example 168 2- (2-Benzimidazol-2-ylsulfanyl) -octanoic acid hydroxyamide 81% @ 215 nm; LCMS (electroraceum API) m / z 308 (M + H) +.

Example 169 2- (2-Benzooxazol-2-ylsulfanyl) -octanoic acid hydroxyamide 72% @ 215 nm; LCMS (electroraceous API) m / z 309 (M + H) +.

Example 170 2- (2-Benzothiazol-2-ylsulfanyl) -octanoic acid hydroxyamide 72% @ 215 nm; LCMS (electroraceum API) m / z 325 (M + H) +.

Example 171 2- (2-Pyridine-2-sulfanyl) -octanoic acid hydroxyamide 76% @ 215 nm; LCMS (electro-vacuum API) m / z 269 (M + H) +.

Example 172 2- (4-Phenyl-thiazole-2-sulfanyl) -octanoic acid hydroxyamide 97% @ 215 nm; LCMS (electro-vacuum API) m / z 336 (M + H) +.

Example 173 2- (2-Pyridin-2-yl-ethylsulfanyl) -octanoic acid hydroxyamide 84% @ 215 nm; LCMS (electroraceum API) m / z 297 (M + H) +.

Example 174 2- (2-Phenyl-5H-tetrazol-5-ylsulfanyl) -octanoic acid hydroxyamide 67% @ 215 nm; LCMS (electro-vacuum API) m / z 338 (M + H) +.

Example 175 2- (2-Pyrazin-2-yl-ethylsulfanyl) -octanoic acid hydroxyamide 98% @ 215 nm; LCMS (electroraceum API) m / z 298 (M + H) +.

Example 176 2- (l-Methyl-lH-tetrazol-5-ylsulfanyl) -octanoic acid hydroxyamide 66% @ 215 nm; LCMS (electroraceum API) m / z 274 (M + H) +.

Example 177 2- (2-Benzimidazol-2-ylsulfinyl) -octanoic acid hydroxyamide 81% @ 215 nm.

Example 178 2- (2-Pyridin-2-sulfinyl) -octanoic acid hydroxyamide 76% @ 215 nm; .

Example 179 2- (4-Phenyl-thiazole-2-sulfinyl) -octanoic acid hydroxyamide 78% @ 215 nm.

Example 180 Hydroxyamide of 2- (2-pyrazine-2-ethylsulfinyl) -octanoic acid 96% @ 215 nm; LCMS (electro-vacuum API) m / z 314 (M + H) +.

Example 181 2- (3-Oxy-lH-benzimidazole-2-sulfonyl) -octanoic acid hydroxyamide 63% @ 215 nm; LCMS (electroraceum API) m / z 356 (M + H) +.

Example 182 2- (4-Phenyl-thiazole-2-sulfonyl) -octanoic acid hydroxyamide 70% @ 215 nm; LCMS (electro-vacuum API) m / z 383 (M + H) +.

Example 183 2- [2- (Oxy-pyridin-2-yl) -ethanesulfonyl] -octanoic acid hydroxyamide 77% @ 215 nm; LCMS (electroraceum API) m / z 345 (M + H) +.

Example 184 3- (1-Hydroxycarbamoyl-heptylsulfanyl) -benzoic acid hydroxyamide 100% @ 220 nm; LCMS (electroraceous API) m / z 312 (M + H) +.

Example 185 Hydroxyamide of 3- [4- (1-hydroxycarbamoyl-heptylsulfanyl) -phenyl] -propionic acid 90% @ 220 nm; LCMS (electroraceous API) m / z 340 (M + H) +.

Example 186 2- (Thiazol-2-ylsulfanyl) -octanoic acid hydroxyamide 75% @ 215 nm; LCMS (electroraceous API) m / z 275 (M + H) +.

Example 187 2- (2, 5-Dioxo-imidazolidin-4-ylmethylsulfanyl) -octanoic acid hydroxyamide 98% @ 215 nm; LCMS (electroraceous API) m / z 304 (M + H) +.

Example 188 3- (1-Hydroxycarbamoyl-heptylsulfinyl) -benzoic acid hydroxyamide 84% @ 220 nm; LCMS (electroraceous API) m / z 328 (M + H) +.

Example 189 3- [4- (1-Hydroxycarbamoyl-heptylsulfinyl) -phenyl] -propionic acid hydroxyamide 78% @ 220 nm; LCMS (electroraceum API) m / z 356 (M + H) +.

Example 190 Hydroxyamide of 2- (quinoline-8-sulfinyl) -octanoic acid 87% @ 220 nm; LCMS (electroraceous API) m / z 335 (M + H) +.

Example 191 2- (Naphthalen-2-ylcarbamoylmetansulfinyl) -octanoic acid hydroxyamide 83% @ 220 nm; LCMS (electroraceum API) m / z 391 (M + H) +.

Example 192 3- (1-Hydroxycarbamoyl-heptylsulfonyl) -benzoic acid hydroxyamide 72% @ 215 nm.

Example 193 3- [4- (1-Hydroxycarbamoyl-heptylsulfonyl) -phenyl] -propionic acid hydroxyamide 67% @ 215 nm.

Example 194 Hydroxyamide 2- (1H-imidazole-2-sulfonyl) -octanoic acid 95% @ 215 nm; LCMS (electroraceum API) m / z 290 (M + H) +.

Example 195 2- (Thiazol-2-ylsulfonyl) -octanoic acid hydroxyamide 91% @ 215 nm; LCMS (electro-vacuum API) m / z 307 (M + H) +.

Example 196 Hydroxyamide 2- (quinoline-8-sulfonyl) -octanoic acid 94% @ 220 nm; LCMS (electro-vacuum API) m / z 351 (M + H) +.

Example 197 2- (Naphthalen-2-ylcarbamoylmetanesulfonyl) -octanoic acid hydroxyamide 79% @ 220 nm; LCMS (electroraceous API) m / z 407 (M + H) +.

Example 198 2- (2, 5-Dioxo-imidazolidin-4-ylmethylsulfonyl) -octanoic acid hydroxyamide 97% @ 215 nm.

Example 199 Step A: Displacement of bromine with 4-fluorothiophenol. The 2-bromohydroximate resin prepared in Example 160, Step A (9.4 g, 1.2 meq / g) was placed in a peptide synthesis vessel and suspended in THF (50 mL). 4-Fluorothiophenol (6.6 g, 5.0 eq.), Sodium iodide was added (7.7 g, 5.0 eq.) And 1,8-diazabicyclo [5. 0] undec-7- ene (DBU, 4. 6 L, 3.0 eq. ). The reaction was stirred at room temperature for 12-16 hours, then filtered and washed with DMF (2 x 30 mL), DMF: water 9: 1 (2 x 30 mL), DMF (30 mL), MeOH (2 x 30 mL), and DCM (2 x 20 mL). The resin was dried in vacuo at room temperature.

Step B: Coupling of the hydroxyamide resin of 2- (4-fluorobenzenesulfanyl) -octanoic acid with benzyl alcohol. The hydroxyamide resin of 2- (4-fluorobenzenesulfanyl) -octanoic acid prepared in Step A (330 mg, 1.1 meq / g) was suspended in DMF (2.0 mL) and benzyl alcohol (731 mg, 15 eq. ) and sodium hydride (327 mg, 15 eq.). The reaction was heated at 80 ° C for 15 hours while stirring in an orbital shaker. After cooling to room temperature the mixture was filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 3 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL) . The resin was dried in vacuo at room temperature.

Step C: Oxidation of Sulfide to Sulfoxide The hydroxyamide resin of 2- (4-benzyloxy-phenylsulfanyl) -octanoic acid prepared in Step B (110 mg, 1.1 meq / g) was suspended in DCM (2.2 mL) and added 70% of tert-butylhydroperoxide (0.73 mL) and benzenesulfonic acid (36 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step D: Oxidation of Sulfide to Sulfone The hydroxyamide resin of 2- (4-benzyloxy-phenylsulfanyl) -octanoic acid prepared in Step B (110 mg, 1.1 meq / g) was suspended in DCM (2.2 mL) and added mCPBA (132 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 2 mL), DMF (2 x 2 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step E: Cleavage of the 2- (4-benzyloxy-benzenesulfanyl) -octanoic acid hydroxyamide from the resin The 2- (4-benzyloxy-phenylsulfanyl) -octanoic acid hydroxyamide resin prepared in Step B (110 mg, 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL), DMF (2 x 2 mL). The filtrate and washing were concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. The crude product was dissolved in DMSO: methanol (1: 1, 2 mL) and purified by reverse phase CLAP under the conditions described below: Column: ODS-A, 20 mm x 50 mm, particle size 5 μm (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL / min. Hydroxyamide of 2- (4-benzyloxy-phenylsulfanyl) -octanoic acid 100% @ 215 nm; LCMS (electro-vacuum API) m / z 374 (M + H) +.

The hydroxamic acid compounds of Examples 200-220 were synthesized using the appropriate starting materials and following the steps of Example 199.

Example 200 2- (4-Butoxy-benzenesulfanyl) -octanoic acid hydroxyamide 100% @ 215 nm; LCMS (electro-vacuum API) m / z 374 (M + H) +.

Example 201 2- [4- (2-Piperazin-1-yl-ethoxy) -benzenesulfanyl] -octanoic acid hydroxyamide 98% @ 215 nm; LCMS (electroraceous API) m / z 340 (M + H) +.

Example 202 2- [4- (5-Hydroxy-pentyloxy) -phenylsulfanyl] -octanoic acid hydroxyamide 65% @ 215 nm; LCMS (electro-vacuum API) m / z 370 (M + H) +.

Example 203 2- [4- (3-pyridin-2-yl-propoxy) -benzenesulfanyl] -octanoic acid hydroxyamide 95% @ 215 nm; LCMS (electro-vacuum API) m / z 403 (M + H) +.

EXAMPLE 204 2- (4-Benzyloxy-phenylsulfinyl] -octanoic acid hydroxyamide 100% @ 215 nm.

Example 205 2- (4-Butoxy-benzenesulfinyl] -octanoic acid hydroxyamide 98% @ 215 nm.

EXAMPLE 206 2- [4- (2-Piperazin-1-yl-benzenesulfinyl] -octanoic acid 98% @ 215 nm hydroxyamide.

Example 207 2- [4- (3-Piperidin-2-yl-propoxy) -benzenesulfinyl] -octanoic acid hydroxyamide 99% @ 215 nm.

EXAMPLE 208 2- (4-Benzyloxy-phenylsulfonyl] -octanoic acid hydroxyamide 100% @ 215 nm.

Example 209 2- (4-Butoxy-benzenesulfonyl] -octanoic acid hydroxyamide 100% @ 215 nm.

EXAMPLE 210 2- [4- (2-Piperazin-1-yl-benzenesulfonyl] -octanoic acid 97% Hydroxyamide @ 215 nm.

Example 211 2- [4- (3-pyridin-2-yl-propoxy) -benzenesulfonyl] -octanoic acid hydroxyamide 100% @ 215 nm.

Example 212 2- [4- (1-Methyl-pyrrolidin-3-yloxy) -benzenesulfanyl] -octanoic acid hydroxyamide 91% @ 215 nm; LCMS (electro-vacuum API) m / z 367 (M + H) +.

Example 213 2- [4- (1-Ethyl-propoxy) -benzenesulfanyl] -octanoic acid hydroxyamide 100% @ 215 nm; LCMS (electroraceum API) m / z 354 (M + H) +.

Example 214 2- [4- (Tetrahydro-pyran-4-yloxy) -benzenesulfanyl] -octanoic acid hydroxyamide 97% @ 215 nm; LCMS (electroraceum API) m / z 368 (M + H) +.

Example 215 2- [4- (1-Methyl-pyrrolidin-3-yloxy) -benzenesulfinyl] -octanoic acid hydroxyamide 96% @ 215 nm.

Example 216 2- [4- (1-Ethyl-propoxy) -benzenesulfinyl] -octanoic acid hydroxyamide 97% @ 215 nm.

Example 217 2- [4- (Tetrahydro-pyran-4-yloxy) -benzenesulfinyl] -octanoic acid hydroxyamide 97% @ 215 nm.

Example 218 2- [4- (1-Methyl-pyrrolidin-3-yloxy) -benzenesulfonyl] -octanoic acid hydroxyamide 96% @ 215 nm.

Example 219 2- [4- (1-Ethyl-propoxy) -benzenesulfonyl] -octanoic acid hydroxyamide 100% @ 215 nm.

Example 220 2- [4- (Tetrahydro-pyran-4-yloxy) -benzenesulfonyl] -octanoic acid hydroxyamide 100% @ 215 nm.

Example 221 Step A: Displacement of bromine with 4-bromothiophenol. The 2-bromo-octanoic acid hydroxymate resin prepared in Example 160, Step A (5.0 g, 1.1 meq / g) was placed in a peptide synthesis vessel and suspended in THF (60 mL). 4-Bromothiophenol (5.2 g, 5.0 eq.), Sodium iodide (4.1 g, 5.0 eq.) And 1,8-diazabicyclole were added. [5.40] undec-7- ene (DBU, 2.5 mL, 3.0 eq.). The reaction was stirred at room temperature for 12-16 hours, then filtered and washed with DMF (2 x 30 mL), DMF: water 9: 1 (2 x 30 mL), DMF (30 mL), MeOH (2 x 30 mL), and DCM (2 x 30 mL). The resin was dried in vacuo at room temperature.

Step B: Oxidation of Sulfide to Sulfoxide The hydroxyamide resin of 2- (4-bromobenzenesulfanyl) -octanoic acid prepared in Step A (4.4 g, 1.1 meq / g) was suspended in DCM (60 mL) and 70 was added. % of tert-butylhydroperoxide (30 mL) and benzenesulfonic acid (1.5 g). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 30 mL), DMF (2 x 30 mL), MeOH (2 x 30 mL), and DCM (2 x 30 mL). The resin was dried in vacuo at room temperature.

Step C: Oxidation of Sulfide to Sulfone The hydroxyamide resin of 2- (4-bromobenzenesulfanyl) -octanoic acid prepared in Step B (4.4 g, 1.1 meq / g) was suspended in DCM (60 mL) and mCPBA was added. (5.2 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 30 mL), DMF (2 x 30 mL), MeOH (2 x 30 mL), and DCM (2 x 30 mL). The resin was dried in vacuo at room temperature.

Step D: Coupling of the hydroxyamide resin of 2- (4-bromobenzenesulfinyl) -octanoic acid with 4-chlorobenzeneboronic acid. The hydroxyamide resin of 2- (4-bromobenzenesulfinyl) -octanoic acid prepared in Step B (150 mg, 1.1 meq / g) was suspended in DME (2.0 mL) and nitrogen gas was bubbled through the suspension for 1- 2 minutes. 4-Chlorobenzeneboronic acid (51.6 mg, 2 eq.), Tetracis (triphenylphosphine) palladium (0) (19.07 mg, 0.1 eq.) And sodium carbonate (2M solution, 0.825 mL, 10 eq) were added. The reaction was heated at 80 ° C for 8 hours while stirring in an orbital shaker. After cooling to room temperature the mixture was filtered and washed with DME (2 x 2 mL), DMF: water 9: 1 (2 x 3 mL), MeOH (2 x 2 mL), and DCM (2 x 2 L) . The resin was dried in vacuo at room temperature.

Step E: Cleavage of 2- (4'-chloro-biphenyl-yl-sulfinyl) -octanoic acid hydroxyamide from the resin. The resin of the hydroxyamide of 2- (4'-chloro-biphenyl-yl-sulfinyl) -octanoic acid prepared in Step D (150 mg, 1.1 meq / g) was suspended in DCM (1.0 mL) and TFA was added. (1.0 mL). The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were concentrated to dryness in a Savant? PeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. The crude product was dissolved in DMSO: methanol (1: 1, 2 mL) and purified by reverse phase CLAP under the conditions described below: Column: ODS-A, 20 mm x 50 mm, particle size 5 μm (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL / min. Hydroxyamide of 2- (4'-chloro-biphenyl-4-sulfinyl) -octanoic acid 96% @ 215 nm; LCMS (electroraceum API) m / z 394 (M + H) +.

The hydroxamic acid compounds of Examples 222-224 were synthesized using the appropriate starting materials and following the steps of Example 221.

Example 222 2- [4- (5-Chloro-thiophen-2-yl) -benzenesulfinyl] -octanoic acid hydroxyamide 100% @ 215 nm; LCMS (electroacoustic API) m / z 400 (M + H) +.

Example 223 2- (4-Chloro-biphenyl-4-sulfonyl) -octanoic acid hydroxyamide 94% @ 215 nm; LCMS (electro-vacuum API) m / z 410 (M + H) +.

Example 224 2- [4- (5-Chloro-thiophen-2-yl) -benzenesulfonyl] -octanoic acid hydroxyamide 85% @ 215 nm; LCMS (electro-vacuum API) m / z 416 (M + H) +.

Example 225 Step A: Coupling of the hydroxyamide resin of 2- (4-bromobenzenesulfanyl) -octanoic acid with N- (3-aminopropyl) -morpholine.

The hydroxyamide resin of 2- (4-bromobenzenesulfanyl) -octanoic acid prepared in Example 199, Step A (100 mg, 1.1 meq / g) was suspended in dioxane (2.0 L) and nitrogen gas was bubbled through the suspension. for 1-2 minutes. N- (3-aminopropyl) -morpholine (346 mg, 20 eq.), Tris (dibenzylidenaceton) -dipaladium (0) (22 mg, 0.2 eq.), (S) - (-) - 2,2 'were added. bis (diphenylphosphino) -l, 1-binaphthyl ((S) -BINAP, 60 mg, 0.8 eq.) and sodium tert-butoxide (207 mg, 18 eq.). the reaction was heated to 80CC for 8 hours while stirring in an orbital shaker. After cooling to room temperature the mixture was filtered and washed with DMF (2 x 2 mL), DMF: water 9: 1 (2 x 3 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step B: Cleavage of 2- [4- (3-morpholin-4-i1-propylamino) -phenylsulfanyl] -octanoic acid hydroxyamide. The hydroxyamide resin of 2- [4- (3-morpholin-4-yl-propylamino) -phenylsulfanyl] -octanoic acid prepared in Step A (100 mg, 1.1 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL). The filtrate and washing were combined and concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. The crude product was dissolved in DMSO: methanol (1: 1, 2 mL) and purified by reverse phase CLAP under the conditions described below: Column: ODS-A, 20 mm x 50 mm, particle size 5 μm (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL / min. Hydroxyamide of 2- [4- (3-morpholin-4-yl-propylamino) -phenylsulfanyl] -octanoic acid 88% @ 215 nm; LCMS (electro-vacuum API) m / z 410 (M + H) +. The hydroxamic acid compounds of Examples 226-231 were synthesized using the appropriate starting materials and following the steps in this example: Example 226 2- [4- (Biphenyl-4-ylamino) -phenylsulfanyl] -octanoic acid hydroxyamide 95% @ 215 nm; LCMS (electroraceum API) m / z 435 (M + H) +.

Example 227 2- [4- (Pyridin-4-ylamino) -phenylsulfanyl] -octanoic acid hydroxyamide 97% @ 215 nm; LCMS (electro-vacuum API) m / z 360 (M + H) +.

Example 228 2- (4-Cyclopentylamino-phenylsulfanyl] -octanoic acid hydroxyamide 77% @ 215 nm; LCMS (API electro-dew) m / z 351 (M + H) +.

Example 229 2- (4-Methylamino-phenylsulfanyl] -octanoic acid hydroxyamide 99% @ 215 nm; LCMS (API electro-dew) m / z 297 (M + H) +.

EXAMPLE 230 2- (4-Piperidin-1-yl-phenylsulfanyl] -octanoic acid hydroxyamide 72% @ 215 nm; LCMS (API electro-chemical) m / z 351 (M + H) +.

EXAMPLE 231 2- (4-Piperazin-1-yl-phenylsulfanyl] -octanoic acid hydroxyamide 74% @ 215 nm; LCMS (API electro-dew) m / z 352 (M + H) +.

Example 232 Step A: Displacement of the bromine with 4-hydroxythiophenol. The 2-bromo-octanoic resin prepared in Example 160, Step A (15.0 g, 1.1 meq / g) was placed in a peptide synthesis vessel and suspended in THF (120 mL). 4-Hydroxythiophenol (11.3 g, 5.0 eq.), Sodium iodide (13.5 g, 5.0 eq.) And 1,8-diazabicyclo [5.40] undec-7- ene (DBU, 8.1 mL, 3.0 eq.) Were added. The reaction was stirred at room temperature for 12-16 hours, then filtered and washed with DMF (2 x 60 mL), DMF: water 9: 1 (2 x 60 mL), DMF (30 mL), MeOH (2 x 60 mL), and DCM (2 x 60 mL). The resin was dried in vacuo at room temperature.

Step B: Coupling of the hydroxyamide resin of 2- (4-hydroxybenzenesulfanyl) -octanoic acid with benzene sulfonyl choride The hydroxyamide resin of 2- (4-hydroxybenzenesulfanyl) -octanoic acid prepared in Step A (240 mg, 1.2 meq / g) was suspended in DCM (3.0 mL). Benzene sulfonyl chloride (225 mg, 5 eq.) And triethylamine (0.06 mL, 2 eq.) Were added. The reaction was stirred on an orbital shaker at room temperature for 8 hours, then filtered and washed with DME (2 x 2 mL), DMF: water 9: 1 (2 x 3 mL), MeOH (2 x 2 mL), and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature.

Step C: Oxidation of sulfide to sulfoxide The 4- (1-hydroxycarbamoyl-heptylsulfanyl) -phenylbenzenesulfonic acid resin prepared in Step B (80 mg, 1.2 meq / g) was suspended in DCM (3 mL) and added 70% tert-butylhydroperoxide (1 mL) and benzenesulfonic acid (23 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 3 mL), DMF (2 x 3 mL), MeOH (2 x 3 mL), and DCM (2 x 3 mL). The resin was dried in vacuo at room temperature.

Step D: Oxidation of Sulfide to Sulfone The 4- (1-hydroxycarbamoyl-heptylsulfanyl) -phenyl ester benzenesulfonic acid resin prepared in Step B (80 mg, 1.2 meq / g) was suspended in DCM (3 mL) and added mCPBA (84 mg). The reaction mixture was stirred on an orbital shaker at room temperature for 12-24 hours. The reaction was filtered and washed with DCM (2 x 3 mL), DMF (2 x 3 mL), MeOH (2 x 3 mL), and DCM (2 x 3 mL). The resin was dried in vacuo at room temperature.

Step E: Cleavage of 4- (l-hydroxycarbamoyl-heptylsulfanyl) -benzenesulfonic acid phenyl ester from the resin, 4- (l-hydroxycarbamoyl-heptylsulfanyl) -benzenesulfonic acid phenyl ester resin prepared in Step B (80 mg , 1.2 meq / g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was stirred for 1 hour at room temperature. The reaction was filtered and the resin was washed with DCM (2 x 1 mL), DMF (2 x 2 mL). The filtrate and washing were concentrated to dryness in a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture was concentrated. The crude product was dissolved in DMSO: methanol (1: 1, 2 mL) and purified by reverse phase CLAP under the conditions described below: Column: ODS-A, 20 mm x 50 mm, particle size 5 μm (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL / min. 4- (1-Hydroxycarbamoyl-heptylsulfanyl) -benzenesulfonic acid phenyl ester 91% @ 215 nm; LCMS (electro-vacuum API) m / z 424 (M + H) +.

The hydroxamic acid compounds of Examples 233-240 were synthesized using the appropriate starting materials and following the steps of Example 232.

Example 233 4- (1-hydroxycarbamoyl-heptylsulfanyl) -hydroxyamide of 2, 5-dichloro-thiophen-3-sulfonic acid 98% @ 215 nm; LMCS (electroraceum API) m / z 498 (M + H) +.

Example 234 4- (1-hydroxycarbamoyl-heptylsulfanyl) -hydroxyamide of ethanesulfonic acid 78% @ 215 nm; LMCS (electroacoustic API) m / z 376 (M + H) +.

Example 235 4- (1-hydroxycarbamoyl-heptyl-sulfinyl) -hydroxyamide of 5-chloro-l, 3-dimethyl-lH-pyrazole-4-sulfonic acid 99% @ 215 nm; LMCS (electroraceous API) m / z 492 (M + H) +.

Example 236 4- (1-hydroxycarbamoyl-heptylsulfinyl) -hydroxyamide of 2, 5-dichloro-thiophene-3-sulfonic acid 96% @ 215 nm; LMCS (electroacoustic API) m / z 514 (M + H) +.

Example 237 4- (1-hydroxycarbamoyl-heptylsulfinyl) -hydroxyamide of 5-pyridin-2-yl-thiophene-2-sulfonic acid 96% @ 215 nm; LMCS (electroacoustic API) m / z 523 (M + H) +.

Example 238 4- (1-hydroxycarbamoyl-heptylsulfonyl) -hydroxyamide of 2-nitro-benzenesulfonic acid 97% @ 215 nm; LMCS (electroacoustic API) m / z 501 (M + H) +.

Example 239 4- (1-hydroxycarbamoyl-heptyl-sulfonyl) -hydroxyamide of 3-bromo-2-chloro-thiophene-2-sulfonic acid 97% @ 215 nm; LMCS (electroacoustic API) m / z 576 (M + H) +.

Example 240 4- (1-hydroxycarbamoyl-heptylsulfonyl) -hydroxyamide of benzo [1, 2, 5] thiadiasol-4-sulfonic acid 83% @ 215 nm; LMCS (electroacoustic API) m / z 514 (M + H) +.

EXAMPLE 241 l-Benzyl-4- (4-benzyloxy-benzenesulfonyl-piperidine-4-carboxylic acid hydroxy) To a stirred solution of 4-methoxybenzthiol (2.8 gm, 20 mmol) and anhydrous K2CO3 (10 gm, excess) in dry acetone (100 ml), a-bromo ethyl acetate (3.3 gm, 20 mmol) was added in a round bottom flask and the reaction mixture was heated to reflux for 8 hours with good agitation. The reaction mixture was allowed to cool and the potassium salts were filtered and the reaction mixture was concentrated.The residue was extracted with chloroform and washed with H20 and 0.5 N NaOH solution. The organic layer was further washed well with water, dried on MgSO4, filtered and concentrated, (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester was isolated as a pale yellow oil Yield: 4.4 g (100%); MS: 227 (M + H) +. stirring solution of (4-methoxy-phenylsulfanyl) -acetic acid ethyl ester (4.4, 20 mmol), anhydrous K2C03 (10 gm, ex dried) in dry acetone (100 ml), benzyl bromide (3.5 g, 20 mmol) was added to reflux for 4 hours. At the end, the reaction mixture was filtered, concentrated and the residue was extracted with chloroform. This was washed well with water, dried and concentrated. The crude product obtained was converted to the ethyl ester of (4-benzyloxy-phenylsulfonyl) -acetic acid by oxidizing with m-chloroperbenzoic acid as described in Example 83. Low melting solid. Yield: 6.6 g, 97%; MS: 335 (M + 1). To a stirring solution of bis- (2-chloro-ethyl) -benzyl amine hydrochloride (6.6 gm, 24.7 mmol), 18-Corona-6 (500 mg), and anhydrous K2C03 (30 gm, excess) in acetone dried (250 ml), (4-benzyloxy-phenylsulfonyl) -acetic acid ethyl ester (8.01 gm, 24 mmol) was added in a spherical bottom flask and the reaction mixture was heated to reflux for 16 hours with good agitation. At the end, the reaction mixture was cooled and the potassium salts were filtered and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H20. The organic layer was further well washed with water, dried over MgSO4, filtered and concentrated. The dark brown reaction mixture was purified by column chromatography on silica gel eluting it with 30% ethyl acetate: hexane and the product of 4- (4-benzyloxy-benzenesulfonyl) -l-benzyl acid ethyl ester was isolated -piperidine-4-carboxylic acid as a brown oil. Yield: 6.5 g, 55%; MS: 494 (M + H). 4- (4-Benzyloxy-benzenesulfonyl) -l-benzyl-piperidine-4-carboxylic acid ethyl ester (5.0 g, 10.1 mmol) was dissolved in MeOH / THF (1: 1, 200 mL) and stirred at room temperature for 72 hours. At the end the reaction mixture was concentrated and the product was neutralized with HCl by dissolving it in water (200 ml). After neutralization, the reaction mixture was concentrated to dryness. Ice cold water (100 ml) was added to the solid and filtered. The product, 4- (4-benzyloxy-benzenesulfonyl) -1-benzyl-piperidine-4-carboxylic acid was dried at 50 C and taken for the next step without any purification. Colorless solid, mp 66-68 ° C; Yield: 4.3 g, 91%; MS: 466 (M + H). Starting with 4- (4-benzyloxy-benzenesulfonyl) -l-benzyl-piperidine-4-carboxylic acid (4.65 g, 10.0 mmol) and following the procedure set forth in Example 83, 1.1 g of hydroxyamide of 4- ( 4-benzyloxy-benzenesulfonyl) -1-benzyl-piperidine-4-carboxylic acid as a colorless solid. Performance 21%; mp 89 ° C; MS: 48.1 1 H NMR (300 MHz, DMSO-d 6): d 2.27 (m, 3 H), 2.76-2.79 (m, 2 H), 3.43 (m, 4 H), 4.30 (s, 2 H), 7.14-7.17 (d , 2H), 7.50-7.73 (m, 5H), 9.37 (s, 1H), 10.53 (s, 1H), 11.18 (s, 1H).

Example 242 4- (4-Butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide. 2- [(2-hydroxy) ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine according to the general method set forth in example 83 starting from diethanolamine (15.0 g, 150 mmol) and 4- (2-) chloride piperidin-1-yl-ethoxy) -benzyl (5.9 g, 20 mmol). Yield 5.5 g, (85%); Brown semi-solid; MS: 323 (M + H) +. Bis- (2-chloro-ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine was prepared according to the general method set forth in example 83 starting from 2- [(2- hydroxy-ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl] -amine (3.22 g, 10 mmol). Yield 4.0 g, (92%); brown semisolid; MS: 361.1 (M + H) +. The 4- (4-butoxy-benzenesulfonyl) -l- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in example 83 starting with 4- (butoxy-benzenesulfonyl) -acetic acid ethyl ester (5.0 g, 20 mmol) and bis- (2-chloro ethyl) - [4- (2-piperidin-1-yl-ethoxy) -benzyl ] -amine (8.6 g, 20 mmol). Yield 6.0 g, (68%); brown oil; MS: 587.7 (M + H) +. 4- (4-Butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid was prepared starting from ethyl ester of 4- (4-) acid. butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid (5.8 g, 10 mmol) dissolved in THF: methanol 3: 1 and NaOH 10 N (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.8 g (86%), fluffy brown solid, mp 98 ° C, MS: 559.6 (M + H) +.

Starting from 4- (4-butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid (5.5 g, 10 mmol) and following the procedure set forth in Example 83, 2.4 g of 4- (4-butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide was isolated as a Pale yellow solid. Yield 41%; mp 155 ° C (HCl); MS: 574 (M + H) +; XH NMR (300 MHz, DMSO-d6): d 0.9 (t, 3H), 1.1-1.8 (m, 6H), 1.9 (m, 4H), 2.3 (m, 4H), 2.8 (m, 6H), 3.2- 3.6 (m, 8H), 4.2 (m, 2H), 6.9-7.8 (m, 8H), 9.1 (s, 1H), 10.8 (s broad, 1H).

Example 243 4- (4-Butoxy-benzenesulfonyl) -1- [3- (2-morpholinyl-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide Bis- (2-hydroxyethyl) was prepared ) - [3- (2-morpholinyl-1-yl-ethoxy) -benzyl] -amine according to the general method set forth in example 83 starting from diethanolamine (15.0 g, 150) and 3- (2-morpholine) chloride 1-yl-ethoxy) -benzyl (5.9 g, 20 mmol). Yield 6.2 g, (95%); Brown semi-solid; MS: 325 (M + H) +. Bis- (2-chloro-ethyl) - [3- (2-morpholin-1-yl-ethoxy) -benzyl] -amine was prepared according to the general method set forth in Example 83 starting from bis- (2-hydroxy) ethyl) - [3- (2-morpholin-1-yl-ethoxy) -benzyl] -amine (3.24 g, 10 mmol) yield 4.0 g (92%); brown semisolid; EM 361.1 (M + H) +.

The 4- (butoxy-benzenesulfonyl) -l- [4- (2-morpholinyl-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in Example 83 starting with 4- (butoxy-benzenesulfonyl) acetic acid ethyl ester (6.0 g, 20 mmol) and bis- (2-chloro-ethyl) - [3- (2-morpholin-1-yl-ethoxy) -benzyl] - amine (8.6 g, 20 mmol). Yield 8.5 g (72%); brown oil; MS: 589.7 (M + H) +. 4- (4-Butoxy-benzenesulfonyl) -1- [3- (2-morpholinyl-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid was prepared starting from 4- (4-butoxy) ethyl ester -benzenesulfonyl) -1- [3- (2-morpholin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid (5.8 g, 10 mmol) dissolved in THF: methanol 3: 1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.8 g (85%), fluffy brown solid; MS: 561.6 (M + H) +. Starting with 4- (4-butoxy-benzenesulfonyl) -1- [3- (2-morpholin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid (5.6 g, 10 mmol) and following the procedure set forth in Example 83, 4.02 g of 4- (4-butoxy-benzenesulfonyl) -1- [3- (2-morpholinyl-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide were isolated as a Pale yellow solid. Yield 62%; mp 123 ° C (HCl); MS: 576 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.9 (t, 3 H), 1.4 (m, 2 H), 1.8 (t, 2 H), 2.3-4.7 (m, 23 H), 7.0-7.8 (m, 8 H) , 9.1 (s, 1H), 10.8 (s broad, 1H).

Example 244 l-Methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The l-methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester was prepared according to the general method set forth in example 83 starting from 4- (butoxy-benzenesulfonyl) acetic acid ethyl ester (3 g, 10 mmol) and methyl-bis- (2-chloro ethyl) -amine (2.2 g, 11.6 mmol ). Yield 4.0 g, (98%); solid brown low melting; MS: 384 (M + H) +. L-Methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from l-methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid ethyl ester (7.6 g, 20 mmol) dissolved in methanol (300 ml) and 10 N NaOH (35 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 6.0 g (84%), white solid; mp 195 ° C, MS: 356.4 (M + H) +. Starting from l-methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (4.0 g, 11.2 mmol) and following the procedure set forth in Example 83, 3.9 g of l-methyl hydroxyamide were isolated. -4- (4-Butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a yellow powder. Yield 85%; mp 118 ° C; MS: 371 (M + H) +; H NMR (300 MHz, DMSO-d6): d 0.9 (t, 3H), 1.45 (c, 2H), 1.8 (c, 2H), 2.1 (s, 3H), 2.3 (d, J = 11.4 Hz, 2H), 2.5-3.7 (m, 8H), 4.1 (t, 2H), 7.16 (d, 2H), 7.67 (d, 2H).

Example 245 l-Ethyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-ethyl-4- (4-butoxy-benzenesulfonyl) -piperidin-4-carboxylic acid was prepared according to the general method set forth in example 83 starting from 4- (butoxy-benzenesulfonyl) acetic acid ethyl ester (3 g, 10 mmol) and ethyl-bis- (2-chloro ethyl) -amine (2.2 g, 10.6 mmol ). Yield 3.5 g, (88%); solid brown low melting; MS: 398 (M + H) +. The l-ethyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from ethyl ester of l-ethyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (7.94 g, 20 mmol) dissolved in methanol (300 ml) and 10 N NaOH (35 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 6.5 g (88%), white solid; mp 162 ° C, MS: 370 (M + H) +. Starting from l-ethyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (3.7 g, 10 mmol) and following the procedure set forth in Example 83, 3.2 g of l-ethyl hydroxyamide were isolated. -4- (4-Butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a yellow powder. Performance 76%; mp 98 ° C; MS: 385 (M + H) +; X H NMR (300 MHz, DMSO-de): d 0.9 (t, 3 H), 1.2 (t, 3 H), 1.46 (c, 2 H), 1.9 (c, 2 H), 2.3 (d, J = 11.4 Hz, 2 H ), 2.5-3.6 (m, 10H), 4.1 (t, 2H), 7.16 (d, 2H), 7.67 (d, 2H).

Example 246 ln-Butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared according to the general method set forth in example 83 starting from 4- (butoxy-benzenesulfonyl) acetic acid ethyl ester (3 g, 10 mmol) and n-butyl-bis- (2-chloro ethyl) -amine (2.0 g, 10.1 mmol). Yield 3.8 g, (89%); solid brown low melting; MS: 426 (M + H) \ l-Butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid starting from ethyl ester of l-butyl-4- (4-butoxy-benzenesulfonyl) ) -piperidine-4-carboxylic acid (8.5 g, 20 mmol) dissolved in methanol (300 ml) and 10 N NaOH (35 ml). The resulting reaction mixture was worked up as discussed in Example 83.

Yield 7.5 g (88%), white solid; mp 182 ° C, MS: 398 (M + H) +. Starting from l-butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (3.9 g, 10 mmol) and following the procedure set forth in Example 83, 1.8 g of l-butyl hydroxyamide were isolated. -4- (4-Butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid as a yellow powder. Performance 40%; mp 121 ° C; MS: 413 (M + H) +; 1H NMR (300 MHz, DMSO-de): d 0.9-1.0 (m, 6H), 1.2-1.8 (m, 8H), 2.2-2.8 (m, 8H), 3.0-3.6 (m, 4H), 4.2 (t, 2H), 7.16 (d, 2H), 7.67 (d, 2H), 9.3 (broad s, 1H), 10.3 (broad s, 1H), 11.1 (broad s, 1H).

Example 247 [4- (4-Chloro-phenoxy) -phenylsulfanyl] -acetic acid ethyl ester A mixture of 4-bromochlorobenzene (1.92 g, 10 mmol), (4-hydroxy-phenylsulfanyl) -acetic acid ethyl ester ( 2.12 g, 10 mmol), sodium hydride (460 mg, 10 mmol) and copper (II) chloride (500 mg) were refluxed in anhydrous pyridine (50 ml) for 12 hours. The reaction mixture was carefully cooled with cold ice water and acidified with concentrated HCl. The product was extracted with chloroform, washed well with water; dried and concentrated. The product was purified by column chromatography on silica gel eluting with 30% ethyl acetate: hexane. Yield 2.5 g (77%); Colorless low melting solid; MS: 323 (M + H) +. Alternatively, the title compound was prepared from 4- (4-chloro-phenoxy) -benzthiol and bromo ethyl acetate as described in Example 83.

Example 248 [4- (4-Chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester [4- (4-Chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester was prepared according to the general method set forth in Example 83 starting from [4- (4-chloro-phenoxy) -benzenesulfanyl] -acetic acid ethyl ester (3.23 g, 10 mmol) and oxone (10 g). Yield 3.5 g, (99%); oil; MS: 356 (M + H) +.

Example 249 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -1-methyl-piperidine-4-carboxylic acid hydroxyamide The 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] ethyl ester was prepared ] -l-methyl-piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester (2.0 g, 5.6 mmol ) and mechlorethannin hydrochloride (Aldrich), (1.9 g, 10 mmol). Yield 2 g, (81%); brown oil; MS: 438 (M + H) +. 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -l-methyl-piperidine-4-carboxylic acid was prepared starting from 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] ethyl ester] -1-methyl-piperidine-4-carboxylic acid (4.3 g, 10 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (100 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.5 g (86%), white solid; mp 185 ° C, MS: 410 (M + H) +. Starting from 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -l-methyl-piperidine-4-carboxylic acid (1.0 g, 2.4 mmol) and following the procedure set forth in Example 83, 460 mg of hydroxyamide were isolated 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -l-methyl-piperidine-4-carboxylic acid as a HCl salt, a white powder. Yield 41%; mp 52 ° C; MS: 426 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 1.3 (s, 3 H), 2.2 - 2.9 (m, 6 H), 3.5 (broad d, 2 H), 7.2 - 7.9 (m, 8 H), 8.1 (s, 1 H) ), 11.0 (broad s, 1H).

Example 250 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -1-ethyl-piperidine-4-carboxylic acid hydroxyamide The 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] ethyl ester was prepared ] -l-ethyl-piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester (4 g, 11.3 mmol ) and ethyl-bis- (2-chloro-ethyl) -amine (2.32 g, 16.9 mmol). Yield 3.36 g, (66%); brown oil; MS: 452.0 (M + H) +. 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -l-ethyl-piperidine-4-carboxylic acid was prepared starting from ethyl 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -1-ethyl-piperidine-4-carboxylic acid (3.02 g, 6.7 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.8 g (65%), white solid; mp 184 ° C, MS: 423.9 (M + H) +. Starting with 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -l-ethyl-piperidine-4-carboxylic acid (1.75 g, 4.14 mmol) and following the procedure set forth in Example 83, 650 mg of 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -l-ethyl-piperidine-4-carboxylic acid hydroxyamide as a HCl salt, a white solid. Performance 33%; mp 158 ° C; MS: 438.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 1.78 (t, J = 7.23 Hz, 3 H), 2.23-2.27 (m, 2 H), 2.51-2.73 (m, 4 H), 3.04 (m, 2 H), 3.81 (d, J = 24 Hz, 2H), 7.16-7.27 (m, 4H), 7.50-7.57 (m, 2H), 7.76 (d, J = 7 Hz, 2H), 9.34 (s, 1H), 9.85 ( s, 1H).

Example 251 l-Butyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-butyl-4- [4- (4-chloro) was prepared -phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [4- (4-chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester (6 g, 18.3 mmol) and butyl-bis- (2-chloro-ethyl) -amine (5.2 g, 22 mmol). Yield 3.3 g, (38%); yellow oil; MS: 480 (M + H) +. L-Butyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid was prepared starting from l-butyl-4- [4- (4-chloro-phenoxy) ethyl ester. ) -benzenesulfonyl] -piperidine-4-carboxylic acid (3.3 g, 6.9 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (25 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 2.08 g (67%), white solid; mp 201 ° C, MS: 451.9 (M + H) +.

Starting with l-butyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid (2 g, 4.43 mmol) and following the procedure set forth in Example 83, 630 mg of hydroxyamide of l-butyl-4- [4- (4-chlorophenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid as a salt of HCl, a white solid. Performance 31%; mp 212 ° C; MS: 466.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.87 (t, J = 7.3 Hz, 3 H), 1.32 (m, 2 H), 1.60 (m, 2 H), 2.21 (m, 2 H), 2.50 (m, 2 H) ), 2.70 (c, 2H), 3.00 (m, 2H), 3.57 (d, 2H), 7.16-7.26 (m, 4H), 7.49-7.56 (m, 2H), 7.77 (d, J = 9 Hz, 2H), 9.34 (s, 1H), 10.13 (s, 1H).

Example 252 l-Benzyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-benzyl-4- [4- (4-chloro) was prepared -phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [4- (4-chloro-phenoxy) -benzenesulfonyl] -acetic acid ethyl ester (6 g, 16.9 mmol) and bis- (2-chloro-ethyl) -benzyl amine (6.44 g, 24 mmol). Yield 2.21 g, (25%); yellow oil; MS: 513.9 (M + H) +. L-benzyl 4 - [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid was prepared starting from l-benzyl-4- [4- (4-chloro-phenoxy) -ethyl ethyl ester - benzenesulfonyl] -piperidine-4-carboxylic acid (2.11 g, 4.1 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.11 g (56%), white solid; mp 201 ° C, MS: 485.9 (M + H) +. Starting from l-benzyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid (1 g, 2.06 mmol) and following the procedure set forth in Example 83, 430 mg of hydroxyamide of l-benzyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid as a HCl salt, a matt white solid. Performance 39%; mp 90.4 ° C; MS: 500.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.18-2.30 (m, 2H), 2.73-2.81 (m, 4H), 3.36 (d, 2H), 4.28 (d, J = 4.5 Hz, 2H), 7.15 -7.25 (m, 4H), 7.43-7.48 (m, 3H), 7.51-7.56 (m, 4H), 7.74 (d, J = 9 Hz, 2H), 9.53 (s, 1H), 10.47 (s, 1H) ).

Example 253 [4- (3-Methyl-butoxy) -phenylsulfanyl] -acetic acid ethyl ester To a stirred solution of [4-hydroxy-phenylsulfanyl] -acetic acid ethyl ester (2.12 g, 10 mmol) was added K2C03 (anhydrous, 10 g) and l-bromo-3-methyl butane (3 g, in excess) and boiling acetone. The reaction mixture was refluxed for 24 hours and cooled to room temperature. The reaction mixture was filtered and concentrated. The residue obtained was extracted with chloroform; washed well with water and concentrated. The obtained crude product was taken for the next step without purification. Yield 2.7 g, (94%); (M + H) + 283.

Example 254 [4- (3-Methyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester [4- (3-Methyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester was prepared according to the general method set forth in Example 83 starting from [4- (3-methyl-butoxy) -benzenesulfanyl] -acetic acid ethyl ester (2.8 g, 10 mmol) and oxone (10 g). Yield 3.0 g, (99%); oil; MS: 341EI (M + H) +.

Example 255 l-Benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-benzyl-4- [4- (3-methyl) was prepared -butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [4- (3-methyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester (6.2 g, 20 mmol) and bis- (2-chloro-ethyl) -benzyl amine (6.44 g, 24 mmol). Yield 8 g, (84%); yellow oil; MS: 474 (M + H) +. L-Benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid was prepared starting from l-benzyl-4- [4- (3-methyl-butoxy acid ethyl ester. ) -benzenesulfonyl] -piperidine-4-carboxylic acid (4.7 g, 10 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3 g (67%), white solid; mp 182 ° C, MS: 446 (M + H) +. Starting with l-benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid (2.2 g, 5 mmol) and following the procedure set forth in Example 83, 1.82 g of hydroxyamide of l-benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid as a salt of HCl, a matt white solid. Performance 73%; pf 106 ° C; MS: 498 (M + H) +; ? ti NMR (300 MHz, DMSO-d6): d 0.8 (d, 6H), 1.5 (m, 1H), 1.6-2.0 (m, 6H), 2.73-2.81 (m, 4H), 3.5 (d, 2H ), 4.28 (d, J = 4.5 Hz, 2H), 7.15-7.25 (m, 4H), 7.43-7.48 (m, 3H), 7.51-7.56 (m, 4H), 7.74 (d, J = 9 Hz, 2H), 9.53 (s, 1H), 10.47 (s, 1H).

Example 256 l-Butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide The l-butyl-4- [4- (3-methyl) ethyl ester was prepared -butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [4- (3-methyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester (6.2 g, 20 mmol) and bis- (2-chloro-ethyl) -benzyl amine (5.2 g, 22 mmol). Yield 7 g, (79%); yellow oil; MS: 440 (M + H) +. L-Butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid was prepared starting from l-butyl-4- [4- (3-methyl-butoxy acid ethyl ester. ) -benzenesulfonyl] -piperidine-4-carboxylic acid (4.4 g, 10 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 3.2 g (77%), white solid; mp 188 ° C, MS: 412 (M + H) +. Starting with l-butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid (2.0 g, 5 mmol) and following the procedure set forth in Example 83, 1.6 g of hydroxyamide of l-butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid as a HCl salt, a matt white solid. Performance 69%; mp 201 ° C; MS: 464 (M + H) +.

Example 257 [4- (2-Ethyl-butoxy) -phenylsulfanyl] -acetic acid ethyl ester To a stirred solution of [4-hydroxy-phenylsulfanyl] -acetic acid ethyl ester (2.12 g, 10 mmol) was added K2C03 (anhydrous, 10 g) and l-bromo-2-ethyl butane (3 g, in excess) and boiling acetone. The reaction mixture was refluxed for 24 hours and cooled to room temperature. The reaction mixture was filtered and concentrated. The residue obtained was extracted with chloroform; washed well with water and concentrated. The obtained crude product was taken for the next step without purification. Yield 2.8 g, (94%); (M + H) + 297.

Example 258 [4- (2-Ethyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester [4- (2-Ethyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester was prepared according to the general method set forth in Example 83 starting from [4- (2-ethyl-butoxy) -benzenesulfanyl] -acetic acid ethyl ester (2.96 g, 10 mmol) and oxone (10 g). Yield 3.1 g, (99%); oil; MS: 329EI (M + H) +.

Example 259 l-Benzyl-4- [4- (2-ethyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide The ethyl ester of l-benzyl-4- [4- (2-ethyl) was prepared -butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [4- (2-ethyl-butoxy) -benzenesulfonyl] -acetic acid ethyl ester (6.4 g, 20 mmol) and bis- (2-chloro-ethyl) -benzyl amine (6.44 g, 24 mmol). Yield 8 g, (84%); yellow oil; MS: 488 (M + H) +. L-benzyl-4- [4- (2-ethyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid was prepared starting from l-benzyl-4- [4- (2-ethyl-butoxy acid ethyl ester. ) -benzenesulfonyl] -piperidine-4-carboxylic acid (4.8 g, 10 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4 g (87%), Semi-solid; MS: 460 (M + H) +. Starting with l-benzyl-4- [4- (2-ethyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid (2.2 g, 5 mmol) and following the procedure set forth in Example 83, 1.02 g of hydroxyamide of l-benzyl-4- [4- (2-ethyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid as a HCl salt, a white, off-white solid. Performance 40%; mp 114 ° C; MS: 512 (M + H) +.

EXAMPLE 260 4- (4-Butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide The 4- (4-butoxy-benzenesulfonyl) -1- (4- (4-butoxy-benzenesulfonyl) ethyl ester was prepared. 3-methoxy-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- (4-butoxy-benzenesulfonyl) -acetic acid ethyl ester (20 g, 77.5 mmol) and bis- ( 2-chloro-ethyl) - (3-methoxy-benzyl) -benzyl amine (34 g ,.116 mmol). Yield 9.53 g, (25%); brown oil; MS: 490.2 (M + H) +. 4- (4-Butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1- (3-) ethyl ester methoxy-benzyl) -piperidine-4-carboxylic acid (2.61 g, 5.34 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (15 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1 g (41%), brown solid; mp 175 ° C, MS: 462.0 (M + H) +. Starting with 4- (4-butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid (900 mg, 1.95 mmol) and following the procedure set forth in Example 83, 200 mg of 4- (4-Butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide as an HCl salt, a brown powder. Yield 20%; mp 137 ° C; MS: 477.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.96 (t, J = 7.11 Hz, 3 H), 1.48 (m, 2 H), 1.73 (m, 2 H), 2.27 (m, 2 H), 2.47 (m, 2 H) ), 2.78 (m, 2H), 3.35 (m, 2H), 3.77 (s, 2H), 4.08 (t, J = 6.3 Hz, 3H), 4.32 (s, 2H), 7.03 (t, 2H), 7.15 (m, 3H), 7.36 (t, J = 7.8 Hz, 1H), 7.64 (d, J = 9 Hz, 2H), 9.36 (s, 1H), 10.22 (s, 1H).

Example 261 4- (4-Methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide 4- (4-methoxy-benzenesulfonyl) ethyl ester -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic starting from ethyl ester of l- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4- carboxylic acid (3 g, 6.05 mmol) and 2- (tributylstannyl) -thiophene (6.8 g, 18.14 mmol) in the presence of tetracis palladium (0) in boiling toluene. Yield 1.58 g, (52%); solid brown; mp 130 ° C; MS: 500 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1 ethyl ester - (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid (1.3 g, 2.61 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 950 mg (77%), brown solid; mp 235 ° C, MS: 471.8 (M + H) +. Starting from 4- (4-methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid (920 mg, 1.95 mmol) and following the procedure set forth in Example 83, isolated 510 mg of 4- (4-methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide as a salt of HCl, a brown solid. Yield 50%; mp 166 ° C; MS: 486.9 (M + H) +; 1 H NMR (300 MHz, DMSO-de): d 2.12-2.21 (m, 2H), 2.50 (m, 2H), 2.78 (m, 2H), 3.39 (m, 2H), 3.87 (s, 3H), 4.29 (d, 2H), 7.17 (m, 3H), 7.54-7.75 (m, 8H), 9.36 (s, 1H), 10.07 (s, 1H).

Example 262 4- (4-Methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide The 4- (4-methoxy-benzenesulfonyl) ethyl ester was prepared -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in Example 261. Starting with ethyl ester of l- (4-bromo-benzyl) -4- ( -methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (4.65 g, 9.38 mmol) and 2- (tributylstannyl) -pyridine (12.08 g, 32.8 mmol). Yield 2.79 g, (60%); brown oil; MS: 495.1 (M + H) +. 4- (4-Methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-methoxy-benzenesulfonyl) -1 ethyl ester - (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid (1.83 g, 3.7 mmol) dissolved in THF: methanol (3: 1 150 ml) and 10 N NaOH (10 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.38 g (80%), matt white solid; mp 217 ° C, MS: 466.9 (M + H) +. Starting with 4- (4-methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid (1.32 g, 2.83 mmol) and following the procedure set forth in Example 83, isolated 480 mg of 4- (4-methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide as an HCl salt, a white powder. Performance 33%; mp 214 ° C; MS: 482.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.30 (m, 2 H), 2.80 (m, 2 H), 3.42 (d, J = 12.5 Hz, 2 H), 3.75 (m, 2 H), 3.88 (s, 3 H) ), 4.36 (s, 2H), 7.15 (d, J = 8.9 Hz, 2H), 7.59-7.74 (m, 4H), 7.84-7.95 (m, 3H), 8.55 (d, J = 8.1 Hz, 1H) , 8.79 (s, 1H), 9.14 (s, 1H), 10.68 (s, 1H), 11.17 (s, 1H).

Example 263 (1- (3,4-Dichlorobenzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide 4- (4-butoxy-benzenesulfonyl) -1- ethyl ester (3,4-dichloro-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83. Starting from (4-butoxy-benzenesulfonyl) -acetic acid ethyl ester (13.2 g, 44 mmol), (3) , 4-dichloro-benzyl) -bis- (2-chloro-ethyl) -amine (14.3 g, mmol) Yield 14.1 g, (60%), white solid, PF 86 ° C, MS: 527.9 (M + H ) + (1- (3,4-Dichlorobenzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid was prepared starting from 4- (4-butoxy-benzenesulfonyl) -1 ethyl ester - (3,4-dichloro-benzyl) -piperidine-4-carboxylic acid (14.0 g, 26.5 mmol) dissolved in THF: methanol (100: 50 ml) and 10 N NaOH (20 ml) The resulting reaction mixture was worked up as shown in Example 83. Yield 7.87 g (60%), matt white solid, mp 239 ° C, MS: 501.9 (M + H) +. 1- (3,4-dichlorobenzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid (7.7 g, 15.5 mmol) and following the procedure set forth in the example 83, 4.05 mg of 1- (3,4-dichloro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide was isolated as an HCl salt, white solid. Performance 48%; mp 256.8 ° C; MS: 514.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.94 (t, 3 H), 1.38-1.48 (c, 2 H), 1.68-1.75 (c, 2 H), 2.27 (m, 4H), 2.72 (m, 2H), 4.10 (t, 2h), 4.24 (s, 2H), 7.12-7.15 (d, J = 8.9, 2H), 7.51-7.53 (d, J = 8.1, U), 7.63-7.65 (d, J = 8.8, 2H), 7.72-7.75 (d, J = 9.9, 2H), 7.87 (s, 1H), 9.36 (s, 1H), 10.5 (s, 1H), 11.2 (s, 1H).

Example 264 [4- (4-Chloro-benzyloxy) -benzenesulfonyl] -1-methylpiperidine-4-carboxylic acid hydroxyamide [4- (4-Chloro-benzyloxy) -benzenesulfonyl] -l-methyl-piperidinic acid ethyl ester was prepared -4-carboxylic acid according to the general method set forth in example 83 starting from [4- (4-chloro-benzyloxy) -benzenesulfonyl] -acetic acid ethyl ester (13.79 g, 37 mmol) and [4- (4-chloro -benzyloxy) -bis- (2-chloro-ethyl) -amine (8.7 g, 45 mmol). Yield 10.9 g, (65%); brown oil; MS: 451.9 (M + H) +. [4- (4-Chloro-benzyloxy) -benzenesulfonyl] -l-methylpiperidine-4-carboxylic acid was prepared starting from [4- (4-chloro-benzyloxy) -benzenesulfonyl] -l-methyl-piperidin-4-ethyl ester. carboxylic acid (10.7 g, 24 mmol) dissolved in THF: methanol (75:75 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.9 g (50%), matt white solid; MS: 426.2 (M + H) +.

Starting from [4- (4-chloro-benzyloxy) -benzenesulfonyl] -l-methylpiperidine-4-carboxylic acid (4.9 g, 12 mmol) and following the procedure set forth in Example 83, 1.2 g of acid hydroxyamide were isolated [ 4- (4-chloro-benzyloxy) -benzenesulfonyl] -l-methyl-piperidine-4-carboxylic acid as a HCl salt, off-white solid. Performance 24%; mp 117.8 ° C; MS: 438.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 2.2 (m, 2 H), 2.49 (m, 4 H), 2.5 (s, 3 H), 2.6 (m, 2 H), 5.2 (s, 2 H), 7.25-7.23 (d, t = 8.7, 2H), 7.5 (d, t = 2.7, 4H), 7.68-7.71 (d, t = 9.6, 2H), 9.33 (s, 1H), 10.11 (s, 1H).

EXAMPLE 265 4- (4-Butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide The 4- (4-butoxy-benzenesulfonyl) -1- (4- (4-butoxy-benzenesulfonyl) ethyl ester was prepared. 3-phenoxy-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting with 4- (4-butoxy-benzenesulfonyl] -acetic acid ethyl ester (10.1 g, 34 mmol) and l- ( 3-phenoxy-benzyl) -bis- (2-chloro-ethyl) -amine (818 g, 50 mmol) Yield 8.9 g, (49%), brown oil, MS: 552.1 (M + H) +. 4- (4-Butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-carboxylic acid starting from 4- (4-butoxy-benzenesulfonyl) -1- (3-phenoxy) ethyl ester benzyl) -piperidine-4-carboxylic acid (10.7 g, 24 mmol) dissolved in THF: methanol (75:50 ml) and 10 N NaOH (20 ml) The resulting reaction mixture was worked up as described in example 83. Yield 5.0 g (76%), matt white solid; MS: 524.3 (M + H) +. Starting with 4- (4-butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-carboxylic acid (5.9 g, 11 mmol) and following the procedure set forth in Example 83, 0.39 g of 4- (4-Butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide as an HCl salt, brown solid. Yield 11%; mp 92.5 ° C; MS: 539.1 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d 0.93-0.97 (t, J = 3.7, 3 H), 1.49 (m, 2 H), 1.73 (m, 2 H), 2.51 (m, 4 H), 4.09 (t, 2H), 4.29 (broad s, 2H), 7.06-7.10 (d, J = 12, 2H), 7.13-7.15 (m, 3H), 7.39-7.42 (d, 2H), 7.63-7.66 (d, 2H) 9.50 (s, 1H), 9.98 (s, 1H).

EXAMPLE 266 [4- (4-Chloro-benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide [4- (4-Chloro-benzyloxy)] ethyl ester was prepared benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from [l- (4-chloro-benzyloxy) -benzenesulfonyl] -acetic acid ethyl ester (5.47 g , 15 mmol) and l- (4-methyl-benzyl) -bis- (2-chloro-ethyl) -amine (5.23 g, 18 mmol). Yield 8.0 g, (96%); brown oil; MS: 542.0 (M + H) +. [4- (4-Chloro-benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid was prepared starting from [4- (4-chloro-benzyloxy) -benzenesulfonyl] ethyl ester] -1- (4-methylbenzyl) -piperidine-carboxylic acid (7.9 g, 124 mmol) dissolved in THF: methanol (50:50 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 4.6 g (61%), off white solid; mp 204 ° C; MS: 514.1 (M + H) +. Starting from [4- (4-chloro-benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid (4.2 g, 8 mmol) and following the procedure set forth in Example 83, 1.3 were isolated g of [4- (4-chloro-benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide as a HCl salt, yellow solid. Yield 29%; mp 172 ° C; MS: 528.9 (M + H) +; XH NMR (300 MHz, DMSO-de): d.

Example 267 4- (4-Butoxy-benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide The 4- (4-butoxy-benzenesulfonyl) -1- (4-) ethyl ester was prepared methylbenzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- (4-butoxy-benzenesulfonyl) -acetic acid ethyl ester (5.47 g, 15 mmol) and l- (4-methyl- benzyl) -bis- (2-chloro-ethyl) -amine (15.3 g, 51 mmol) Yield 10.1 g, (57%), white solid, MP 93 ° C, MS: 474.1 (M + H) +. prepared 4- (4-butoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid starting from ethyl 4- (4-butoxy-benzenesulfonyl) -1- (4-methylbenzyl) - piperidine-4-carboxylic acid (10.0 g, 22 mmol) dissolved in THF: methanol (50:50 ml) and 10 N NaOH (20 ml) The resulting reaction mixture was worked up as described in example 83. Yield 7.2 g (72%), matt white solid, mp 244 ° C; MS: 446.3 (M + H) +. Starting from 4- (4-butoxy-benzenesul acid fonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid (6.6 g, 1.5 mmol) and following the procedure set forth in Example 83, 2.06 g of 4- (4-butoxy-benzenesulfonyl) hydroxamide were isolated) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid as a HCl salt, yellow solid. Performance 28%; mp 137 ° C; MS: 461 (M + H) +; ? R NMR (300 MHz, DMSO-d6): d 0.91-0.964 (t, J = 7.3, 3H), 1.41 (m, 2H), 1.70 (m, 4H), 1.79 (t, s, 3H), 2.52 (m, 2H), 2.76 (m, 2H), 3.33 (broad d, 2H), 4.10 (t, 2H), 4.22 (d, 2H), 7.12-7.14 (d, J = 8.7, 2H), 7.25- 7.28 (d, J = 8.1, 2H), 7.42-7.45 (d, J = 7.8, 2H), 7.63-7.65 (d, J = 8.7, 2H), 10.31 (s, 1H), 10.75 (s broad, 1H ).

Example 268 4- (4-Butoxy-benzenesulfonyl] -1- (4-cyanobenzyl) -piperidine-4-carboxylic acid hydroxamide The 4- (4-butoxy-benzenesulfonyl) -1- (4- (4-butoxybenzenesulfonyl) ethyl ester was prepared. 4-cyano-benzyl) -piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- (4-butoxy-benzenesulfonyl) -acetic acid ethyl ester (5.29 g, 17.6 mmol) and l- ( 4-cyano-benzyl) -bis- (2-chloro-ethyl) -amine (6.19 g, 21 mmol) Yield 6.8 g, (80%), brown solid, MS: 485.0 (M + H) +. 4- (4-butoxy-benzenesulfonyl) -1- (4-cyanobenzyl) -piperidine-4-carboxylic acid starting from 4- (4-butoxy-benzenesulfonyl) -1- (4-cyano-benzyl) ethyl ester -piperidine-4-carboxylic acid (10.0 g, 124 mmol) dissolved in THF: methanol (75:50 ml) and 10 N NaOH (20 ml) The resulting reaction mixture was worked up as described in example 83. Yield 7 g (11%), matt white solid, MS: 456.0 (M + H) +. Starting from 4- (4-butoxy-benzenesulfonyl) -1- (4-cyano-b) encyl) -piperidine-4-carboxylic acid (.600 g, 1.2 mmol) and following the procedure set forth in Example 83, 83.21 g of 4- (4-butoxy-benzenesulfonyl) -1- (4-cyano) hydroxyamide were isolated. -benzyl) -piperidine-4-carboxylic acid as a HCl salt, matt white solid. Performance 34%; mp 241.6 ° C; MS: 472.0 (M + H) +; X H NMR (300 MHz, DMSO-d 6): d .915-964 (t, J = 7.2, 3 H), 1.51 (c, 2 H), 1.75 (c, 2 H), 2.27 (m, 2 H), 2.49 ( m, 4H), 4.11-4.19 (t, 2H), 4.37 (s, 1H), 7.12-7.15 (d, J = 8.7, 2H), 7.63-7.66 (d, J = 9, 2H), 7.72-7.74 (d, J = 7.8, 2H), 9.36 (s, 1H), 10.23 (s, 1H), 11.16 (s, 1H).

Example 269 4- (4-Butoxy-benzenesulfonyl] -1-pyridin-4-ylmethyl-piperidine-4-carboxylic acid hydroxamide The 4- (4-butoxy-benzenesulfonyl) -1-pyridin-4-ethyl ester was prepared -ylmethyl-piperidine-4-carboxylic acid according to the general method set forth in example 83 starting from 4- (4-butoxy-benzenesulfonyl) -acetic acid ethyl ester (6.0 g, 20.0 mmol) and l-pyridin-4-ylmethyl -bis- (2-chloro-ethyl) -amine (4.89 g, 21 mmol) Yield 4.5 g, (48%), brown oil, MS: 461.0 (M + H) +. 4- (4-Butoxy-benzenesulfonyl) -1-pyridin-4-ylmethyl-piperidine-4-carboxylic acid was prepared starting from 4- (4-butoxy-benzenesulfonyl) -l-pyridin-4-ylmethyl ethyl ester. -piperidine-4-carboxylic acid (3.0 g, 6.5 mmol) dissolved in THF: methanol (75:50 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as set forth in Example 83. Yield 1.2 g (42%), matt white solid; MS: 433.0 (M + H) +. Starting from 4- (4-butoxy-benzenesulfonyl) -1-pyridin-4-ylmethyl-piperidine-4-carboxylic acid (0.864 g, 2.0 mmol) and following the procedure set forth in Example 83, 600 mg of hydroxyamide was isolated 4- (4-Butoxy-benzenesulfonyl) -l-pyridin-1-methylmethyl-piperidinecarboxylic acid as a HCl salt, white, off-white solid. Performance 67%; mp 118 ° C; MS: 447.9 (M + H) +; X H NMR (300 MHz, DMSO-d 6): dO .94 (t, 3 H), 1.11 (t, 1 H), 1.23 (t, 1 H), 1.44 (m, 1 H), 1.73 (m, 1 H), 2.34 ( m, 2H), 2.78 (m, 2H), 3.10 (m, 2H), 3.38 (m, 2H), 4.08 (t, 2H), 4.42 (broad s, 2H), 7.13 (d, 2H), 7.64 ( d, 2H), 7.94 (d, 2H), 8.82 (d, 2H), 11.2 (broad s, 1H), 11.4 (broad s, 1H).

References: 1 Rickter, L. S .; Desai, M. C. Tetrahedron Let ters, 1997, 38, 231-322.

The compounds object of the present invention were tested for biological activity according to the following procedures.

In Vitro Gelatinase Assay The assay was based on the incision of the thiopeptide substrate ((Ac-Pro-Leu-Gli (2-mercapto-4-metyl-pentanoyl) -Leu-Gly-OEt), Bache Bioscience) by the enzyme , gelatinase, releasing the product from the substrate that reacts colorimetrically with DTNB ((5, 5'-dithio-bis (2-nitro-benzoic acid)) .The enzymatic activity was measured by the speed of color increase.The thiopeptide substrate was It was made fresh as a standard of mM in 100% DMSO and the DTNB was dissolved in 100% DMSO as a standard at 100 mM and stored in the dark at room temperature Both the substrate and the DTNB were diluted together to lmM with buffer of substrate (50mM HEPES pH 7.5, 5mM CaCl2) before use The gelatinase B standard of human neutrophils was diluted with assay buffer (50 mM HEPES pH 7.5, 5mM CaCl2, 0.02% Brij) to a final concentration of 0.15 nM The test buffer, the enzyme, the DTNB / substrate (final concentration 500 μM) and the vehicle or inhibitor were added to a 96-well plate (total reaction volume of 200 μM) and the increase in color was verified spectrophotometrically for 5 minutes at 405 nm in a reader of plates. The increase in DO405 was plotted and the slope of the line was calculated, which shows the reaction rate. The linearity of the reaction rate was confirmed (r2> 0.85). The mean (x ± sem) of the control rate was calculated and statistical significance was compared (p <0.05) with drug-treated rates using Dunnet's multiple comparison test. A dose-response relationship can be generated using multiple doses of the drug and IC 50 values with a 95% Cl were estimated using linear regression (IPRED, HTB). References: Weingarten, H and Feder, J., Spectrophotometric assay for vertebrate collagenase, Anal. Biochem. 147, 437-440 (1985).

In Vitro Collagenase Assay The assay was based on the incision of a peptide substrate (Dnp-Pro-Cha -Gly-Cys (Me) -His-Ala-Lys (NMA) -NH2), International Peptide, Inc.) by the collagenase releasing the fluorescent NMa group which was quantified in the fluorometer. The Dnp absorbs the fluorescence of the NMa in the intact substrate. The test was carried out in HCBC assay buffer (50 mM HEPES), pH 7.0, Ca + 2 5 mM, Brij 0.02% Cysteine 0.05%), with collagenase from human recombinant fibroblasts (truncated, mw = 18, 828, WAR, Radnor). The substrate was dissolved in methanol and stored frozen in 1 mM aliquots. The collagen was stored frozen in buffer in aliquots of 25 μM. For the assay the substrate was dissolved in a HCBC buffer to a final concentration of 10 μM and the collagenase to a final concentration of 5 nM. The compounds were dissolved in methanol, DMSO, or HCBC. Methanol and DMSO were diluted in HCBC to <; 1.0%. The compounds were added to the 96-well plate containing the enzyme and the reaction was initiated by the addition of the substrate. The reaction was read (excitation at 340 nm, emission at 444 nm) for 10 minutes and the increase in fluorescence over time was plotted as a linear line. The slope of the line was calculated and represents the reaction rate. The linearity of the reaction rate was confirmed (r2> 0.85). The mean (x ± sem) of the control rate was calculated and compared by statistical significance (p <0.05) with drug-treated velocities using Dunnet's multiple comparison test. Dose-response relationships can be generated using multiple doses of drug and IC 50 values with a Cl 95% were estimated using linear regression (IPRED, HTB). References: Bickett, D.M. et al., A high-performance fluorogenic substrate for collagenase (MMP-1) and gelatinase (MMP-9) interstitial, Anal. Biochem. 212, 58-64 (1993).

Procedure for Measuring Inhibition of TACE Using 96-well black microtiter plates, each well receives a solution composed of lOμlL of TACE (Immunex, final concentration of lμg / mL), 70μL of Tris buffer, pH 7.4 with a content of 10% of glycerol (final concentration of lOmM), and lOμL of test compound solution in DMSO (final concentration of lM, concentration of DMSO <1%) and incubated for 10 minutes at room temperature. The reaction was initiated by the addition of a fluorescent peptidyl substrate (final concentration of 100μM) to each well and then shaking on a shaker for 5 seconds. The reaction was read (excitation at 340 nm, emission at 420 nm) for 10 minutes, and the increase in fluorescence was plotted over time as a linear line. The slope of the line was calculated and represents the reaction rate.

The linearity of the reaction rate was confirmed (r2> 0.85). The mean (x ± sem) d the control rate was calculated and compared to determine its statistical significance (p <0.05) with the drug-treated rates using Dunnett's multiple comparison test. Dose-response relationships can be generated using multiple doses of drug and IC 50 values with an estimated 95% Cl using linear regression. The results obtained after these standard experimental test procedures are presented in the following table.

IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) Example MMP 1 MMP 9 MMP 13 TACE ? NT 559.6 193.3 31.62% 2 NT 10.50% 0% 403 3 NT 308.9 169.4 27.43% 4 371 22.20% 17.10% 21% 5 NT 7.7 4.7 25% 6 267 21.4 15.6 40.43% 7 844 72.9 42.1 33% 8 NT 346 307.9 47% IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 9 313 107 NT 20.30% 8% 128 64 54.75% 11 18.8% 2925 319 942 12 100 10.8 11 15.50% 13 239 11 14 626 14 158 23 8 17.18% 285 17 4 137 16 325 9 24 # 180 17 238.6 8.9 1.4 41.00% 18 540 18.9 11.5 29.2% 19 446 95.8 4.8 33.1% 423 14.6 18.7 31% 21 318 13.2 15.3 39% 22 219 3.2 2.5 30% 23 593 7.9 4.0 40.6% 24 413 20.9 31.3 47.5 262 26.7 8.0 NT 26 304.6 6.3 3.2 34.6% 27 629 106 30.1 NT 28 761 3.1 2.0 30.6% 29 297 4.3 3.6 41% IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 397 8.1 5.7 25.2% 31 162 15.2 5.7 688 32 13.7 3.7 1.0 NT 33 318 53.9 18.4 23.9% '34 519.8 34.7 26.1 28.1% 455.8 233.6 48.2 44.9 36 622 83.8 20.7 826 37 9% 31.6% 14.3% 87 38 48.3% 1.7% 5.8% 55.1% 39 29.4% 35.2% 26.6% 69.4 40 583 197 14 160 41 100 10.8 11 15.50% 42 262 50.9 6.2 36.5 43 66.1% 34.7% 0 D • D "6 46.6% 44 47.1% 36.9% 39.5% 14.9% 45 49% 48.6% 36.7% 20.4% 46 78.9% 79.12% 84.7% 1.4% 47 17.1% 12.9% 7.12 3.3% 48 99.1% 79.1% 85.4% 51.1% 48 10.1% 23.7% 54.6% NT 50 51.1 58.4 10.6 NT IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 51 178.1 10.4 13.1 48.14% 52 139.3 7.9 9.1 NT 53 647.9 27.80% 188 52.57% 54 110 66 21 55.10% 55 303 10 7 21.70% 56 299 16 12 65% 57 258 332 191 16.57% 58 211 35 39 7.70% 59 30.20% 447 141 24.86% 60 NT 184 NT 23.60% 61 258 38 22 17.21% 62 522 174 43 669 63 156 9 3 203 64 40.90% 25.60% 36.70% 29.70% 65 1000 63 13 42.21% 66 1600 131 226 42.33% 67 364 2.3 43.7 690 68 297 29 27 522 69 574.5 120.2 90 41.32% 70 1139 88.80% 127 764 71 1000 63 13 42.21% IC 50 (nM or% Inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 72 117 11 1 51.64% 73 300 141 12 20.17% 74 138.1 9.2 4.3 47.86% 75 672.3 83.4 32.7 23.77% 76 805 NT 500 NT 77 205.5 NT 170 NT 78 262 560 34 24.58% 79 25 0.54 0.4 805 80 22.1% 26% 63.6% 191 81a 2036 230.9 43.9 27.1 81b 3765 154 15.7 228 82 237.6 19.4 5.1 34.5% 83 492 10.2 2.0 229 84 519 8.8 2.0 213 85 450 5.8 1.5 115 86 494 16.8 1.5 222 87 368 5.0 1.6 170.7 88 1329 12.8 3.1 610 89 1389 38.6 7.0 49% 90 598 10.3 2.2 71.9 91 1929 13.3 10.8 503 IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 92 59.6% 649 148 9.7 93 56.3% 452 38 15.8% 94 2640 138 28.6 22.9 95 3681 364 33.1 25.4% 96 4437 374 33.8 18.1 97 5109 484 43.7 20.20% 98 2383 3.8 1.2 154 99 656 16.2 2.4 250 100 4729 19.1 5.3 39.5% 101 642 12.3 2.1 197 102 662 33.7 1.9 53% 103 1306 45.1 8.8 470 104 2610 3.1 1.4 208 105 1214 44.2 4.1 50.2% 106 3788 5.1 0.9 631 107 629 26.8 2.5 293 108 2896 5.4 1.7 270 109 393 2.7 2.5 386 241 48.2% * 2.7 15.8 277 242 1950 2 1.3 581 243 2181 1.9 1.5 506 IC 50 (nM or% inhibition at 1 micromolar or 10 micromolar (*)) (continued) Example MMP 1 MMP 9 MMP 13 TACE 244 3417 9.8 1.5 594 245 7062 43.4 2.2 51.95% * 246 50.30% * 28.3 2.4 880 249 1412 2 1.6 270 250 1717 1.6 0.8 413 251 1067 0.8 0.9 301 252 801 1.1 0.9 278 255 2558 3.6 1.5 565 256 10000 7.2 2.9 43.01% * 259 3160 14.3 5.3 39% * 260 1495 2.9 1.3 272 261 513 10.9 2.7 273 262 422 6.1 2.3 298 263 3669 20.3 5.2 57.70% * 264 4293 2.9 3.1 182 265 1944 9.3 7.8 1037 266 4746 6 5.7 421 267 3620 5.4 2.3 508 268 2292 2.8 1.1 278 269 2071 2.2 1.4 296 Data of the compounds prepared by solid phase synthesis: for Examples 110 to 240 Example MMP 1 MMP 9% inhibition% inhibition% inhibition No. of MMP 13 a of MMP 13 a of TACE at 1 mM 0.02 μM (HTS) 0.2 μK (manual) ñ? 75 17.6 111 10 40.4 112 '50 33.7 113 0 13.1 114 0 - 0 115 0 0 116 0 9.1 117 7 8.1 118 24 16.7 119 0 7.8 120 31 19.9 121 0 6.1 122 0 3.1 123 0 2.5 124 0 0 125 5 2.3 126 25 10.4 127 47 29.2 Example MMP 1 MMP 9% inhibition% inhibition% inhibition No. of MMP 13 a of MMP 13 a of TACE at 1 mM 0.02 μM (HTS) 0.2 μMember (manual) 128 1.9 mM 213nM 91 255nM 19.31 129 90 32.77 130 28 27.9 131 71 20.73 132 71 20.76 133 53 22.04 134 25 -9.31 135 79 42.67 136 89 42.69 137 83 13.35 138 20 5.284 139 28.05 140 29 -4.22 141 32 11.76 142 69 54.27 143 53 43.9 144 38 19.7 145 45 2.5 146 68 7.317 147 73 11.95 Example MMP 1 MMP 9% inhibition% inhibition% inhibition No. of MMP 13 a of MMP 13 a of TACE at 1 mM 0.02 μM (HTS) 0.2 μMember (manual) 148 15 43.46 149 13 4.408 150 54 1,818 151 6 5,927 152 9 10.03 153 12 11.8 154 89 13.14 155 31 18.62 156 23 -2.09 Example MMP 1 MMP 9% inhibition% inhibition% inhibition No. of MMP 13 a of MMP 13 a of TACE at 1 mM 0.2 μM (HTS) 0.2 μMember (manual) 157 19 13.7 158 33 -7.48 159 49 5.852 160 14 -3.57 161 0 12.7 162 13 0 163 84 9.515 Example MMP 1 MMP 9% inhibition% inhibition% inhibition No. of MMP 13 a of MMP 13 a of TACE to 1 mM 0.2 μM (HTS) 0.2 μMember (manual) 164 74 62.69 165 71 73.7 166 9 4.16 167 27 8.961 168 21 3,688 Example%%% of ICS0 of% of No. inhibition of inhibition inhibition TACE inhibition MMP 13 to 36nM MMP 13 to 0.36 of MMP 13 to of TACE to 1 (HTS) mM (HTS) 3.6 mM Mm (HTS) 169 28 40 72 41.7 170 32 49 90 25.5 171 31 38 48 16.6 172 34 32 42 29.4 173 18 46 56 25.5 174 10 19 40 27.7 175 16 20 37 32.9 176 6 5 16 26.6 177 5 1 9 38.5 178 -. 178 -10 74 39 26 Example%%% C50%% No. inhibition of inhibition of inhibition TACE inhibition MMP 13 to 36nM MMP 13 to 0.36 of MMP 13 a of TACE to 1 (HTS) mM (HTS) 3.6 M Mm (HTS) 179 12 32 60 42.7 180 14 19 45 34.4 181 6 35 62 15.7 182 -. 182 -9 -8 7 28.6 183 -. 183 -6 12 70 34.6 184 16 24 44 24.8 185 9 0 23 7.21 186 -. 186 -14 -4 35 19.5 187 -. 187 -14 -12 20 85.5 188 -. 188 -27 -24 A- 16.2 189 -. 189 -30 -18 -9 14 190 -. 190 -35 -28 -13 38.3 191 -. 191 -45 -3 22 2.9 192 -. 192 -32 5 61 33.2 193 -. 193 -32 -15 56 14.9 194 -. 194 -17 -8 5 5.4 195 -. 195 -9 -2 10 27.0 196 -. 196 -18 1 11 35.7 197 -. 197 -33 -26 -3 17.8 Example%%% IC50%% No. inhibition of inhibition of inhibition TACE inhibition MMP 13 to 36nM MMP 13 to 0.36 of MMP 13 a of TACE to 1 (HTS) mM (HTS) 3.6 mM Mm (HTS) 198 -. 198 -39 -7 15 17.1 199 -. 199 -10 -7 30 -1.0 200 37.9 201 50.9 202 10.6 203 32.8 204 7.75 205 84.0 206 89.8 207 -. 207 -6.3 208 67.7 209 31.2 210 52.2 211 20.7 212 56.0 213 -. 213-17.5 214 11.03 215 895 60.12 216 2.49 Example% of% of ICS0 of% of No. inhibition of inhibition of inhibition TACE inhibition MMP 13 to 36nM MMP 13 to 0.36 of MMP 13 to of TACE to 1 (HTS) M (HTS) 3.6 BM Mm (HTS) 217 55.1 218 380 68.7 219 7.3 220 256 53.1 221 146 98.9 222 212 89.3 2223 22 + 6 107.3 224 -. 224 -404 75.0 225 96.6 114.3 226 28 22 28 2.2 227 15 -16 -22 7.3 228 37 28 65 6.8 229 29 17 33 34.4 230 29 31 26 700 72.1 231 23 13 '5 41.6 232 30 17 42 20.8 233 33 29 46 19.8 234 26 28 40 18.4 235 59 70 70 48.3 236 44 44 64 35 Example%%% IC50%% Do not . inhibition of inhibition of inhibition TACE inhibition MMP 13 to 36nM MMP 13 to 0.36 of MMP 13 a of TACE to 1 (HTS) mM (HTS) 3.6 mM Mm (HTS) 237 55 65 72 38.2 238 22 11 24 54.4 239 54 74 83 45.9 240 48 51 4 6 40.3 Pharmaceutical Composition The compounds of this invention can be administered pure or with a pharmaceutical carrier to a patient in need thereof. The pharmaceutical carrier can be solid or liquid. Applicable solids may include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet disintegrating agents or an encapsulating material. In powders, the carrier is a finely divided solid which is a mixture with the finely divided active ingredient. In tablets, the active ingredient is mixed in a carrier having the necessary compression properties in suitable proportions and compacted in desired shape and size. The powders and tablets preferably contain up to 99% active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting point waxes, and ion exchange resins. . The liquid carriers can be used in the preparation of solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid carrier may contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing the above additives, for example, cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, for example, glycols ) and its derivatives, and oils (for example, fractionated coconut oil or arachis oil). For parenteral administration the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. Liquid pharmaceutical compositions that are sterile solutions or suspensions can be used, for example, by intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. The oral administration may be in the form of a liquid or solid composition. The compounds of this invention can be administered rectally in the form of a conventional suppository. For administration by inhalation or intranasal or intrabronchial insufflation, the compounds of this invention can be formulated in an aqueous or partially aqueous solution, which can then be used in the form of an aerosol. The compounds of this invention can also be administered transdermally through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, that is not toxic to the skin, and that allows the release of the agent for systemic absorption towards the blood flow of the skin. The carrier can also take any number of forms such as creams and ointments, pastes, gels and occlusive devices. The creams and ointments can be a viscous liquid or semi-solid emulsions of any type of oil in water or water in oil. Pastes comprised of absorbent powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable. A variety of occlusive devices can be used to release the active ingredient into the bloodstream such as a semipermeable membrane that covers a reservoir containing the active ingredient with or without the carrier, or a matrix containing the active ingredient. Other occlusive devices are known in the literature. The dose to be used in the treatment of a specific patient who suffers from a disease or condition in which the MMP and TACE are involved must be administered subjectively by the attending physician. The variables involved include the severity of the dysfunction, and the patient's size, age, and response pattern. The treatment will generally be initiated with small doses, less than the optimum dose of the compound. Subsequently, the dose is increased until the optimum effect is reached under the circumstances. The precise doses for oral, parenteral, nasal or intrabronchial administration will be determined by the doctor who administers them based on the experience with the individual subject treated and the standard medical principles. Preferably the pharmaceutical composition is a unit dosage form, for example, as tablets or capsules. In such form, the composition is subdivided into unit doses containing appropriate amounts of the active ingredient; the unit dosage form may be packaged compositions, for example packaged powders, flasks, ampoules, pre-filled syringes or sacks containing liquids. The unit dosage form can be, for example, a capsule or a tablet itself, or it can be an appropriate number of any such compositions in packaged form. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (42)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: A compound according to formula I characterized in that: R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6- where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from 0, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; cycloalkyl or bicycloalkyl of C3 to Cg optionally substituted with one or two groups independently selected from R5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cn aroyl, C2-C6 alkanoyl, Ci to C2 alkyl, C2-C2 alkenyl, C2-C12 alkynyl, F, Cl, Br, I, CN, CHO, C.sub.1 -C.sub.6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, C? -C6 alkoxyaryl, C? -C6 alkoxyheteroaryl, C? -C6 alkylamino Ci-C? alkoxy, alkylene dioxy of C? -C2, aryloxy-alkyl amine of C? -C6, perfluoro alkyl of C? -C? 2, S (0) n-alkyl of C? -C6, S (0) n-aryl where n is 0, 1 or 2; OCOO C? -C6 alkyl, OCOOaryl, OCONR6, COOH, COO-Ci-C6 alkyl, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, NR6CONR6R6, NHS02CF3, S02NHheteroaryl ?, S02NHCOaryl, CONHS02- C? C6, CONHS02-aryl, S02NHCOaryl, CONHS02-C6-C6 alkyl, CONHS02-aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; or saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, wherein the C6-C6 alkyl is linear or branched, the heteroaryl is a mono or bicyclic heteroaryl group of 5-10 members that have from 1 to 3 heteroatoms selected independently of O, S or NR7, -Q and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 to C6 alkenyl, C3 to C6 alkynyl, 15 perfluoro alkyl of Ci to C6, S (O) n-alkyl of C? -C6, S (0) n aryl where n is 0, 1 or 2, or COheteroaryl, where the heteroaryl is a mono or bicyclic heterocycle group of 5-10 members having 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or Naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cß alkyl, C?-C6 alkoxy, or hydroxy; and R7 is C7-Cu aroyl, C6-C6 alkanoyl, Ci-Ci perfluoroalkyl, S (O) n C-C6 alkyl, S (0) n-aryl 5 where n is 0.1 or 2; COO-C de-C6 alkyl, COOaryl, CONHR6, CONR6R6, C0NH0H, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHSO-C?-C6 alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano, amino, nitro, Ci-Cß alkyl, C?-C6 alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or N-Ci-Cß alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from O, S or N and is optionally substituted with one or two groups independently selected from R 5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups independently selected from R5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from O, S or N-Ci-Cß alkyl, optionally substituted with one or two groups independently selected from R 5; or R8R9N-C6-C6-alkoxyaryl-C6-alkyl wherein R8 and R9 are independently selected from Ci-C3 alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring which optionally it contains an oxygen atom, where the 'aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
2. 2. The compound according to claim 1, characterized in that: R 1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6- where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from O, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 which optionally has one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; cycloalkyl or bicycloalkyl of C to C8 optionally substituted with one or two groups independently selected from R5; R5 is H, F, Cl, Br, I, CN, CHO, C7-Cp aroyl, C2-C6 alkanoyl, Ci to C2 alkyl, C2 to C2 alkenyl, C2-C12 alkynyl, C 1 -C 6 alkoxy, aryloxy, heteroaryloxy, C 3 -C 6 alkenyloxy, C 3 -C 6 alkynyloxy, C 6 -C 6 alkoxy, C 1 -C 6 alkoxy heteroaryl, C 1 -C 6 alkylamino C 6 -C 6 alkoxy, alkylene dioxide of C? -C2, aryloxy-alkyl amine of C? ~ C6, perfluoro alkyl of C? -C? 2, S (0) n-alkyl of C? -C6, S (0) n-aryl where n is 0, 1 or 2; OCOO-C 1 -C 6 alkyl, OCOOaryl, OCONR 6, COOH, C 1 -C 6 alkyl, COOaryl, CONR 6 R 6, CONHOH, NR 6 R 6, * S 0 2 NR 6 R 6, NR 6 S0 2 aryl, NR 6 CONR 6 R 6, NH S0 2 CF 3, S 0 2 NHheteroaryl, S 0 2 NHCOaryl, CONHS 2 -C 6 alkyl ? -C6, CONHS02-aryl, S02NHCOaryl, C0NHS02-C? -C6 alkyl, CONHS02aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; or saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7; wherein the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen , cyano, amino, nitro, Ci-Ce alkyl, Ci-Cβ alkoxy, or hydroxy; R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 alkenyl to Ce, C3 alkynyl to Ce, perfluoro alkyl of Ci to e, S (0) nalkyl or aryl where n is 0, 1 or 2; or COheteroaryl; wherein the heteroaryl is a 5-10 membered mono- or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from 0, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; and R7 is C7-Cn aroyl, C2-C6 alkanoyl, C?-C? 2, S (0) n-alkyl, S (0) n-aryl o-fluorine, where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR6, C0NR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHC0aril, C0NHS02alkyl, CONHS02aryl, aryl, or heteroaryl; where the C? -C6 alkyl is linear or branched, the heteroaryl is a 5-10 membered mono- or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or NR7 and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Ce alkyl, C? -C6 alkoxy, or hydroxy; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from O, S or N and is optionally substituted with one or two groups independently selected from R 5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl is optionally substituted with one or two groups independently selected from R6; saturated or unsaturated mono- or bicyclic heterocycle containing a heteroatom selected from O, S or N-C6-C6alkyl, optionally substituted with one or two groups independently selected from R5; or R8R9N-C6-C6-alkoxyaryl-C6-C6 alkyl where R8 and R9 are independently selected from Ci-Cß alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
3. 3. The compound according to claim 2, characterized in that R1 is phenyl, naphthyl, alkyl of 1-18 carbon atoms or heteroaryl such as pyridyl, thienyl, imidazolyl or furanyl, optionally substituted with C? -C6 alkyl, alkoxy Ci-Ce, C6-C6 aryloxy or heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, halogen; or S (0) C -C6-C6-alkoxyaryl-C6-C6alkyl, or C6-C6alkoxyheteroaryl; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing O, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two "groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; C3 to C8 cycloalkyl or bicycloalkyl optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cn aroyl, C2-C6 alkanoyl, Ci to Ci2 alkyl, C2 to C12 alkenyl, C2-C2 alkynyl, F, Cl, Br, I, CN, CHO, C? -C6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C? -C6 alkynyloxy, Ci-Ce alkylamino Ci-C? Alkoxy, alkylene dioxy of C? ~ C2, aryloxy-alkyl amine of Ci-Ce, perfluoro alkyl of C1-C12, S (O) n-alkyl of C? -C6, S (0) n-aryl where n is 0, 1 or 2; OCOO alkyl of C? -C6, OCOOaryl, OCONR6, COOH, COO alkyl of C? ~ C6, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, -NR6C0NR6R6, NHS02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02-C?-C6 alkyl, CONHS02aryl, S02NHCOaryl, CONHS02-C?-C6 alkyl, CONHS02aryl, NH 2, OH, aryl, heteroaryl, C 3 to C 8 cycloalkyl; mono or bicyclic heterocycle of 5 to 10 saturated or unsaturated member containing a heteroatom selected from O, S or NR7, wherein the C? -C6 alkyl is linear or branched, the heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from 0, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cß alkyl, Ci-Cβ alkoxy, or hydroxy; R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 al alkenyl, C3 to C6 alkynyl, perfluoro alkyl of Ci to Ce, S (0) nalkyl or aryl where n is 0, 1 or 2, or COheteroaryl, where the heteroaryl is a mono or bicyclic heterocycle of 5- 10 members having 1 to 3 heteroatoms independently selected from 0, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, Ci-Ce alk or hydr and R7 is C7-Cn aroyl, C2-C6 alkanoyl, perfluoro C-C12 alkyl, S (O) n-alkyl, S (O) n-aryl where n is 0, 1 or 2; COO-alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano , amino, nitro, C? -C6 alkyl, Ci-C? alk or hydr and the heteroaryl is a 5-10 membered mono- or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or N-Ci-Cg alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from O, S or N and is optionally substituted with one or two groups independently selected from R 5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from 0, S or N-C 1 -C 6 alkyl, optionally substituted with one or two groups independently selected from R 5; R8R9N-C6-C6-alkoxyaryl-C6-C6alkyl wherein R8 and R9 are independently selected from C6-C6 alkyl or R8 and R9 together with the interposed nitrogen form a 5-7 membered saturated heterocyclic ring which optionally it contains an oxygen atom, where the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
4. 4. The compound according to claim 1, characterized in that it is hydroxyamide of l-benzyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide, or a pharmaceutically acceptable salt thereof .
6. 6. The compound according to claim 1, characterized in that it is 1- (3, -dichlorobenzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -l-naphthalen-2-yl-methyl-piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
9. 9. The compound according to claim 1, characterized in that it is l-biphenyl-4-ylmethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
10. 10. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- (3-methyl-but-2-enyl) piperidine-4-carboxylic acid hydroxamide or a salt pharmaceutically acceptable thereof.
11. 11. The compound according to claim 1, characterized in that it is 1- (4-bromo-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
13. The compound according to claim 1, characterized in that it is hydroxyamide of l-benzyl-4- (4-benzyloxy-benzenesulfonyl) -piperidine-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
14. 14. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide, 15.
15. The compound in accordance with claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- ['3- (2-morpholinyl-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically salt acceptable of it.
16. The compound according to claim 1, characterized in that it is l-methyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
17. 17. The compound according to claim 1, characterized in that it is hydroxyamide of l-ethyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
18. 18. The compound according to claim 1, characterized in that it is l-n-butyl-4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
19. 19. The compound according to claim 1, characterized in that it is 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -1-methyl-piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
20. The compound according to claim 1, characterized in that it is 4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -1-ethyl-piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
21. 21. The compound according to claim 1, characterized in that it is l-butyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
22. 22. The compound according to claim 1, characterized in that it is hydroxyamide of l-benzyl-4- [4- (4-chloro-phenoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
23. 23. The compound according to claim 1, characterized in that it is l-benzyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
24. 24. The compound according to claim 1, characterized in that it is l-butyl-4- [4- (3-methyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
25. 25. The compound according to claim 1, characterized in that it is l-benzyl-4- [4- (2-ethyl-butoxy) -benzenesulfonyl] -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
26. 26. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- (3-methoxy-benzyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
27. 27. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- (4-thiophen-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof. same.
28. The compound according to claim 1, characterized in that it is 4- (4-methoxy-benzenesulfonyl) -1- (4-pyridin-2-yl-benzyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically salt acceptable of it.
29. 29. The compound according to claim 1, characterized in that it is 1- (3,4-dichlorobenzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
30. 30. The compound according to claim 1, characterized in that it is [4- (4-chloro-benzyloxy) -benzenesulfonyl] -1-methylpiperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
31. 31. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- (3-phenoxy-benzyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
32. 32. The compound according to claim 1, characterized in that it is [4- (4-chloro-benzyloxy) -benzenesulfonyl] -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
33. 33. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- (4-methylbenzyl) -piperidine-4-carboxylic acid hydroxamide or a pharmaceutically acceptable salt thereof.
34. 34. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -1- (4-cyano-benzyl) -piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
35. 35. The compound according to claim 1, characterized in that it is 4- (4-butoxy-benzenesulfonyl) -l-pyridin-4-ylmethyl-piperidine-4-carboxylic acid hydroxyamide or a pharmaceutically acceptable salt thereof.
36. 36. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of: 4- (4-methoxy-benzenesulfonyl) -1- (3-phenyl-propyl) hydroxyamide ) -piperidine-4-carboxylic acid, l-tert-butyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-butyl-4- (4-methoxy-benzenesulfonyl) hydroxyamide - piperidine-4-carboxylic acid, l-cyclooctyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-ethyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-hydroxyamide carboxylic acid, l-isopropyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-methyl-4- (4-methoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, l-benzyl-4- (4-butoxy-benzenesulfonyl) -piperidine-carboxylic acid hydroxyamide, 1- (4-fluoro-benzyl) -4- (4-methoxy-benzenesulfonyl) -piperidin-4-hydroxyamide carboxylic, 1- (4-fluoro-benzyl) -4- (4-butoxy-benzenesulfonyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-methoxy-benzenesulfonyl) -1- (4-methoxy) hydroxyamide benzyl) -piperidine-4-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1- [2- (4-methoxyphenyl) -ethyl] -piperidine-4-carboxylic acid hydroxyamide, 4- (4-hydroxyamide) -methoxy-benzenesulfonyl) -1 - (2-phenyl-ethyl) -piperidine-4-carboxylic acid, 4- (4-n-butoxy-benzenesulfonyl) -1- (4-methoxy-benzyl) -piperidin-4-hydroxyamide -carboxylic acid 4- (4-methoxy-benzenesulfonyl) -1- (3-phenoxy-propyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-n-butoxy-benzenesulfonyl) -1- ( 3-Phenoxy-propyl) -piperidine-4-carboxylic acid, 4- (4-methoxy-benzenesulfonyl) -1- (2-phenoxyethyl) hydroxyamide) -piperidine-4-carboxylic acid, 4- (4-n-butoxy-benzenesulfonyl) -1- (2-phenoxy-ethyl) -piperidine-4-carboxylic acid hydroxyamide, 4- (4-methoxy-benzenesulfonyl) hydroxyamide ) -1- [4- (2-piperidin-1-yl-ethoxy) -benzyl] -piperidine-4-carboxylic acid.
37. 37. A method for inhibiting pathological changes mediated by matrix metalloproteinases in mammals, characterized in that it comprises administering to a mem- rapher in need thereof a therapeutically effective amount of a compound that inhibits the metalloproteinase of the matrix of the formula I characterized in that: R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from 0, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) 0-6- where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from 0, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; cycloalkyl or bicycloalkyl of C to C8 optionally substituted with one or two groups independently selected from R5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; R5 is H, aroyl of C-Cn, C2-C6 alkanoyl, Ci to C2 alkyl, C2-C2 alkenyl, C2-C2 alkynyl, F, Cl, Br, I, CN, CHO , C 1 -C 6 alkoxy, aryloxy, heteroaryloxy, C 3 -C 6 alkenyloxy, C 3 -C 2 alkynyloxy, Ci-Cβ alkoxyaryl, Ci-Ce alkoxyheteroaryl, Ci-Cß alkylamino-Ci-Ce alkoxy, alkylene dioxy C 1 -C 2 / aryloxy-Ci-Cß arylamino, perfluoro C de-C? 2 alkyl, S (0) n-C?-C6 alkyl, S (0) n-aryl where n is 0, 1 or 2; OCOO C 1 -C 6 alkyl, OCOOaryl, OCONR 6, COOH, C 1 -C 6 alkyl, COOaryl, CONR 6 R 6, CONHOH, NR 6 R 6, S 0 2 NR 6 R 6, NR 6 S0 2 aryl, NR 6 CN 0 R 6 R 6, NH S0 2 CF 3, S 0 2 NHheteroaryl, S 0 2 NHCOaryl, CONHS 0 2 -C 1 alkyl C6, CONHS02-aryl, S02NHCOaryl, CONHS02-C6-C6 alkyl, CONHS02-aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; 5- or 10-membered saturated or unsaturated mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, where the C? -C6 alkyl is linear or branched, the heteroaryl is a mono or bicyclic heteroaryl group of 10 members having 1 to 3 heteroatoms independently selected from 0, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, Ci-Cß alkoxy, or hydroxy; R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 to C6 alkenyl, C3 alkynyl to Ce, C3 a, S (0) n-Ci-Cß alkyl, C (O) n aryl orthofluoro where n is 0, 1 or 2, or COheteroaryl, where heteroaryl is a 5-10 membered mono- or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cd alkyl, C? -C6 alkoxy, or hydroxy; and R7 is C-Cn aroyl, C2-C6 alkanoyl, perfluoro C? -C? 2 alkyl, S (0) n-Ci-C? alkyl, S (0) n-aryl where n is 0.1 or 2; COO-C? -C6 alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHC0aril, CONHSO-C? -C6alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano, amino, nitro, C? -C6 alkyl, Ci-Ce alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono- or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from 0, S or N-C6-C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from 0, S or N and is optionally substituted with one or two groups independently selected from R5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R6; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from 0, S or N-Ci-Cß alkyl, optionally substituted with one or two groups independently selected from R 5; or R8R9N-C6-C6-C6-C6-alkyl-C6alkyl wherein R8 and R9 are independently selected from Ci-Ce alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring which optionally it contains an oxygen atom, where the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
38. 38. The method according to claim 37, characterized in that the condition treated is atherosclerosis, formation of atherosclerotic plaque, reduction of coronary thrombosis of rupture of atherosclerotic plaque, restenosis, osteopenias mediated by MMP, inflammatory diseases of the central nervous system, skin aging, angiogenesis, tumor metastasis, tumor growth, osteoarthritis, rheumatoid arthritis, septic arthritis, corneal ulceration, abnormal wound healing, bone diseases, proteinuria, aneurysmal aortic disease, degenerative cartilaginous loss after traumatic joint injury, demyelinating diseases of the nervous system, cirrhosis of the liver, glomerular disease of the kidney, premature rupture of the fetal membranes, inflammatory bowel disease or periodontal disease.
39. 39. The method according to claim 37, characterized in that the treated condition is related to age-related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, premature retinopathy, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis / neovascularization and corneal graft rejection.
40. 40. A method for inhibiting pathological changes mediated by the enzyme that converts TNF-a (TACE) in mammals, characterized in that it comprises administering to the mammal in need thereof a therapeutically effective amount of the compound that inhibits TACE of the formula characterized in that: R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6- where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from O, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; C3 to C8 cycloalkyl or bicycloalkyl optionally substituted with one or two groups independently selected from R5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from 0, S or NR7, optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cu aroyl, C2-C6 alkanoyl, Ci to C2 alkyl, C2-C12 alkenyl, C2-C2 alkynyl, F, Cl, Br, I, CN, CHO, C.sub.1 -C.sub.6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, C? -C6 alkoxyaryl, C? -C6 alkoxyheteroaryl, C? -C6 alkylamino Ci-Ce alkoxy, alkylene dioxy of C? -C2, aryloxyalkylamine of Ci-Ce, perfluoro > C? -C? 2 alkyl, S (0) n-Ct.-C6 alkyl, S (0) n-aryl where n is 0, 1 or 2; OCOO C? -C6 alkyl, OCOOaryl, OCONR6, COOH, COO-C? -Calkyl, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, NR6C0NR6R6, NHS02CF3, S02NHheteroaryl, S02NHCOaryl, CONHS02-C? C6, CONHS02-aryl, S02NHCOaryl, CONHS02-C6-C6 alkyl, CONHS02-aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; or 5- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, wherein the Ci-Ce alkyl is linear or branched, the heteroaryl is a mono or bicyclic heteroaryl group of 5-10 members having 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cß alkyl, -alkoxy of Ci-Ce, or hydroxy; ' R 6 is H, C 1 to C 8 alkyl optionally substituted with OH; C3 alkenyl to Ce, C3 alkynyl to Ce, perfluoro C6 to C6 alkyl, S (O) n C to C6 alkyl, S (0) n aryl where n is 0, 1 or 2, or COheteroaryl , wherein the heteroaryl is a 5-10 membered mono- or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen , cyano, amino, nitro, Ci-Cd alkyl, Ci-Cß alkoxy, or hydroxy; and R7 is C7-Cn aroyl, C2-C6 alkanoyl, perfluoro C? -C? 2 alkyl, S (O) n-Ci-Ce alkyl, S (0) n-aryl where n is 0.1 or 2; COO-C? -C6 alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHSO-C? -C6 alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano, amino, nitro, Ci-Ce alkyl, C? -Ce alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono- or bicyclic heteroaryl group having from 1 to 3 heteroatoms independently selected from O, S or N-C6-C6alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from 0, S or N and is optionally substituted with one or two groups independently selected from R5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups independently selected from R5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from 0, S or N-C 1 -C 6 alkyl, optionally substituted with one or two groups independently selected from R 5; or R8R9N-C6-C6-alkoxyaryl of Ct.-C6 alkyl wherein R8 and R9 are independently selected from C-C alkyl & or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
41. 41. The method according to claim 40, characterized in that the condition treated is rheumatoid arthritis, graft rejection, cachexia, anorexia, inflammation, fever, insulin resistance, septic shock, congestive heart deficiency, inflammatory disease of the central nervous system , inflammatory bowel disease or HIV infection.
42. 42. A pharmaceutical composition comprising a pharmaceutical carrier and a therapeutically effective amount of a metalloproteinase of the matrix or compound that inhibits TACE according to the formula I characterized in that: R1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups independently selected from R5; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups independently selected from R 5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, optionally substituted with one or two groups independently selected from R5; or heteroaryl- (CH2) or -6 where the heteroaryl group is from 5 to 6 members with one or two heteroatoms independently selected from O, S and N and may be optionally substituted with one or two groups independently selected from R5; A is -S-, -SO- or -S02-; R2 and R3, taken with the carbon atom to which they are attached, form a 5- to 7-membered heterocyclic ring containing 0, S, or N-R7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; phenyl or naphthyl optionally substituted with one or two groups independently selected from R5; C3 to C8 cycloalkyl or bicycloalkyl optionally substituted with one or two groups independently selected from R5; saturated or unsaturated 5- to 10-membered mono- or bicyclic heterocycle containing a heteroatom selected from 0, S or NR7, optionally substituted with one or two groups independently selected from R5; R5 is H, C7-Cn aroyl, C2-C6 alkanoyl, Ci to C12 alkyl, C2-C2 alkenyl, C2-C alkynyl2 / F, Cl, Br, I, CN, CHO, C? -C6 alkoxy, aryloxy, heteroaryloxy, C3-Ce alkynyloxy, C3-C6 alkynyloxy, C? -C6 alkoxyaryl, Ci-Ce alkoxy heteroaryl, Ci-Cd alkylamino Ci-C? alkoxy, alkylene dioxy of C? -C2, Ci-C? aryloxyalkylamine, perfluoro C? -C? 2 alkyl, S (0) n-Ct.-C6 alkyl, S (0) n-aryl where n is 0, 1 or 2; OCOO C? -C6 alkyl, OCOOaryl, OCONR6, COOH, COO-C6-C6 alkyl, COOaryl, CONR6R6, CONHOH, NR6R6, S02NR6R6, NR6S02aryl, NR6C0NR6R6, NHS02CF3, S02NHheteroaryl ?, S02NHCOaryl ?, CONHS02- C-alkyl? ~ C6, CONHS02-aryl, S02NHCOaryl, CONHS02-C6-C6 alkyl, CONHS02-aryl, NH2, OH, aryl, heteroaryl, C3 to C8 cycloalkyl; 5- or 10-membered saturated or unsaturated mono- or bicyclic heterocycle containing a heteroatom selected from O, S or NR7, where the C? -Ce alkyl is linear or branched, the heteroaryl is a mono or bicyclic heteroaryl group of 10 members having 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C6-C6 alkoxy, or hydroxy; R6 is H, Ci to C18 alkyl optionally substituted with OH; alkenyl of C3 to Ce, C3 to C6 alkynyl, perfluoro alkyl of Cx to C6, S (O) n-C alquilo-C6 alkyl, S (0) n aryl where n is 0, 1 or 2, or COheteroaryl, where the heteroaryl is a 5-10 membered mono- or bicyclic heterocycle group having from 1 to 3 heteroatoms independently selected from O, S or NR7, and the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cd alkyl, C? -C6 alkoxy, or hydroxy; and R7 is C7-Cu ayl, C2-C6 alkanoyl, perfluoro C1-C12 alkyl, S (O) n Ci-Cß alkyl, S (0) n-aryl where n is 0, 1 or 2; COO-Ci-Ce alkyl, COOaryl, CONHR6, CONR6R6, CONHOH, S02NR6R6, S02CF3, S02NHheteroaryl, S02NHCOaryl, CONHSO-C?-C6 alkyl, CONHS02aryl, aryl, or heteroaryl, where the aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups independently selected from halogen, cyano, amino, nitro, C? -C6 alkyl, C? -C6 alkoxy, or hydroxy; and the heteroaryl is a 5-10 membered mono- or bicyclic heteroaryl group having 1 to 3 heteroatoms independently selected from O, S or N-C6-C6alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups independently selected from R 5; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups independently selected from R 5; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups independently selected from R 5; arylalkyl of 7 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; heteroarylalkyl wherein the alkyl is from 1 to 6 carbon atoms and the heteroaryl contains 1 or 2 heteroatoms selected from 0, S or N and is optionally substituted with one or two groups independently selected from R5; biphenylalkyl of 13 to 18 carbon atoms, wherein the biphenyl is optionally substituted with one or two groups independently selected from R5; arylalkenyl of 8 to 16 carbon atoms, wherein the aryl is optionally substituted with one or two groups independently selected from R5; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups independently selected from R5; saturated or unsaturated mono or bicyclic heterocycle containing a heteroatom selected from 0, S or N-Ci-Cß alkyl, optionally substituted with one or two groups independently selected from R 5; or R8R9N-C6-C6-alkoxy-C6-C6alkyl wherein R8 and R9 are independently selected from Ci-C3 alkyl or R8 and R9 together with the interposed nitrogen form a saturated 5-7 membered heterocyclic ring which optionally it contains an oxygen atom, where the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.