N-HYDROXY-2-(ALKYL, ARYL OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF- alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF- alpha from membrane bound TNF- alpha 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- alpha 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 R<2> and R<3> form a heterocyclic ring and A is S, S(O), or S(O)2, and R<1> and R<4> are defined herein.

Description: N-HYDROXY-2-(ALKYL, ARYL, OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS BACKGROUND OF THE INVENTION Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. Of these classes, the gelatinases have been shown to be the MMPs most intimately involved with the growth and spread of tumors. It is known that the level of expression of gelatinase is elevated in malignancies, and that gelatinase can degrade 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 to its pathology. Furthermore, there is evidence to suggest that gelatinase is involved in plaque rupture associated with atherosclerosis. Other conditions mediated by MMPs are restenosis, MMP- mediated osteopenias, inflammatory diseases of the central nervous system, skin aging, tumor growth, osteoarthritis, rheumatoid arthritis, septic arthritis, comeal ulceration, abnormal wound healing, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, cirrhosis of the liver, glomerular disease of the kidney, premature rupture of fetal membranes, inflammatory bowel disease, periodontal disease, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neo- vascularization and corneal graft rejection. For recent reviews, see: (1) Recent Advances in Matrix Metalloproteinase Inhibitor Research, 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. TNF-α converting enzyme (TACE) catalyzes the formation of TNF-α from membrane bound TNF-α precursor protein. TNF-α is a pro-inflammatory cytokine that is now thought to have 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, insulin resistance and HTV infection in addition to its well documented antitumor properties. For example, research with anti- TNF-α antibodies and transgenic animals has demonstrated that blocking the formation of TNF-α inhibits the progression of arthritis. This observation has recently been extended to humans as well. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. While a variety of MMP and TACE inhibitors have been identified and disclosed in the literature, the vast majority of these molecules are peptidic and peptide-like compounds that one would expect to have bioavailability and pharmacokinetic problems common to such compounds that would limit their clinical effectiveness. Low molecular weight, potent, long acting, orally bioavailable inhibitors of MMPs and/or TACE are therefore highly desirable for the potential chronic treatment of the above mentioned disease states. Recently, two references have appeared (U.S. 5,455,258 and European Patent Appl. 606,046) that disclose arylsulfonamido-substituted hydroxyamic acids. These documents cover compounds exemplified by CGS 27023 A. These are the only non-peptide matrix metalloproteinase inhibitors disclosed to date. CGS 27023A Salah et al., Liebigs Ann. Chem. 195, (1973) discloses some aryl substituted thio and aryl substituted sulfonyl acetohydroxamic acid derivatives of general formula L These compounds were prepared to study the Mannich reaction. Subsequently, they were tested for their fungicidal activity. Some sulfone carboxylic acids are disclosed in U.S. patent 4,933,367. Those compounds were shown to exhibit hypoglycemic activity. SUMMARY OF THE INVENTION: The present invention relates to novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-α converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HTV infection. In accordance with this invention there is provided a group of compounds of general formula I I wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substituted with one or two groups selected independently from R 5 ; or heteroaryl-(CH2)o-6- wherein the heteroaryl group is 5 to 6 membered with one or two heteroatoms selected independently from O, S, and N and may be optionally substituted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO 2 -; R 2 and R 3 , taken with the carbon atom to which they are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 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 selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; phenyl or naphthyl optionally substituted with one or two groups selected independently from R 5 ; C 3 to Cβ cycloalkyl or bicycloalkyl optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substituted with one or two groups selected independently from R 5 ; R 5 is H, C -Cn aroyl, C2-C6 alkanoyl, to C12 alkyl, C 2 to 2 alkenyl, C2- 2 alkynyl, F, Cl, Br, I, CN, CHO, -C6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, -Cβ alkoxyaryl, C1-C6 alkoxyheteroaryl, -C6 alkylamino-Cι-C6 alkoxy, C1-C2 alkylene dioxy, aryloxy-Ci-Cό alkyl amine, -C12 perfluoro alkyl, S(O Ci-C 6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO C r C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO Cι-C 6 alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR6R6, SO 2 NR 6 R 6 , NR 6 SO 2 aryl, -NR*CONR 6 R 6 , NHSO 2 CF 3 , SO 2 NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -C C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -C 1 -C 6 alkyl, CONHSO 2 aryl, NH , OH, aryl, heteroaryl, C 3 to C 8 cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein -Cβ alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, -C 6 alkyl, Cι-C 6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted with OH; C 3 to C 6 alkenyl, C 3 to C 6 alkynyl, C1 to Cβ perfluoro alkyl, S(O) n -C 1 -C 6 alkyl S(O) n aryl where n is 0, 1 or 2;, or COheteroaryl, wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C 1 -C 6 alkyl, Cι-C 6 alkoxy, or hydroxy; and R 7 is C- 7 -C 11 aroyl, C 2 -C 6 alkanoyl, C r Cι 2 perfluoro alkyl, S(O) n -C 1 -C 6 -alkyl, S(O) n - aryl where n is 0, 1 or 2; COO-Cι-C 6 -alkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO 2 NR 6 R 6 , SO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO-Cι-C 6 -alkyl, CONHSO 2 aryl, aryl, or heteroaryl, where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, C 1 -C 6 alkyl, - alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or N- -Cβ alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionally substituted with one or two groups selected independently from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionally substituted with one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionally substituted with one or two groups selected independently from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated mono or bicyclic heterocycle containing one heteroatom selected from O, S or N-Cι-C 6 alkyl, optionally substituted with one or two groups selected independently from R 5 ; or R 8 R 9 N-C 1 -C 6 -alkoxyaryl-C 1 -C 6 -alkyl where R 8 and R 9 are independently selected from C1-C 6 alkyl or R 8 and R 9 together with the interposed nitrogen forms a 5-7 membered saturated heterocyclic ring optionally containing 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): la wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted with one to two groups selected independently from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one to two groups selected independently from R 5 ; saturated or unsaturated mono or bicyclic heterocycle of from 5 to 10 members containing one heteroatom selected from O, S or NR 7 , optionally substituted with one to two groups selected independently from R 5 ; or heteroaryl- (CH2)o-6- wherein the heteroaryl group is 5 to 6 membered with one or two heteroatoms selected independently from O, S, and N and may be optionally substituted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO2-; R 2 and R 3 , taken with the carbon atom to which they are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 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 selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; phenyl or naphthyl optionally substituted with one or two groups selected independently from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionally substituted with one or two groups selected independently from R 5 ; R 5 is H, F, Cl, Br, I, CN, CHO, C 7 -Cn aroyl, C 2 -Cό alkanoyl, d to C12 alkyl, C 2 to C12 alkenyl, C2- 2 alkynyl, -C6 alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, Cι-C 6 alkoxyaryl, -Cβ alkoxyheteroaryl, Cι-C6-alkylamino-Cι- C6 alkoxy, Cι-C2-alkylene dioxy, aryloxy-Cι-C6 alkyl amine, C1- 2 perfluoro alkyl, S(O) n -Cι-C 6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO-Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO-Ci-Ce alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR*R6, SO 2 NR 6 R 6 , NR 6 SO 2 aryl, NR 6 CONR 6 R 6 , NHSO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH 2 , OH, aryl, heteroaryl, C 3 to C 8 cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 ; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, -Cβ alkyl, Cι-C 6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted with OH; C3 to Cβ alkenyl, C3 to Q, alkynyl, to C 6 perfluoro alkyl, S(O)n alkyl or aryl where n is 0, 1, or 2; or COheteroaryl; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having lto 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Cι-C 6 alkyl, -Cβ alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C 2 -C6 alkanoyl, C1-C12 perfluoro alkyl, S(O) n -alkyl, S(O) n - aryl where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR 6 , CONR*R 6 , CONHOH, SO 2 NR 6 R 6 ,SO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO 2 alkyl, CONHSθ2aryl, aryl, heteroaryl; wherein Cι-C 6 alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, -Ce alkyl, Cι-C 6 alkoxy, or hydroxy; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionally substituted with one or two groups selected independently from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionally substituted with one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionally substituted with one or two groups selected independently from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein cycloalkyl or bicycloalkyl is optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated mono or bicyclic heterocycle containing one heteroatom selected from O, S or N- - alkyl, optionally substituted with one or two groups selected independently from R 5 ; R 8 R N-Cι-C 6 -alkoxyaryl-Cι-C 6 -alkyl where R 8 and R 9 are independently selected from Ci-Cβ alkyl or R 8 and R 9 together with the interposed nitrogen forms a 5-7 membered saturated 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 (lb): lb in which R 1 is phenyl, naphthyl, alkyl of 1-18 carbon atoms or heteroaryl such as pyridyl, thienyl, imidazolyl or furanyl, optionally substituted with Cι-C 6 alkyl, -CO alkoxy, C6-C10 aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, halogen; or S(O) π - -Ci-Cβal yl -Cβ alkoxyaryl or -Cβ alkoxyheteroaryl; A is -S-, -SO- or -SO 2 -; R 2 and R 3 , taken with the carbon atom to which they are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 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 selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; phenyl or naphthyl optionally substituted with one or two groups selected independently from R 5 ; C3 to Cs cycloalkyl or bicycloalkyl optionally substituted with one or two groups selected independently from R 5 ; R 5 is H, C7-C11 aroyl, C 2 -C6 alkanoyl, Ci to C i2 alkyl, C 2 to C12 alkenyl, C2-C12 alkynyl, F, Cl, Br, I, CN, CHO, Ci-Cό alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, Cι-C 6 alkylamino-Cι-C6 alkoxy, -C2 alkylene dioxy, aryloxy-Ci-Cό alkyl amine, -C12 perfluoro alkyl, S(O) n -Cι-C6 alkyl, S(O) n - aryl where n is 0, 1 or 2; OCOO Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO C r C 6 alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR R 6 , SO 2 NR6R 6 , NR6SO 2 aryl, -NR 6 CONR 6 R 6 , NHSO2CF3, SO2NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH2, OH, aryl, heteroaryl, C3 to Cs cycloalkyl; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein Ci-Cβ alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cό alkyl, Cι-C 6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted with OH; C3 to C alkenyl, C3 to Cβ alkynyl, Ci to Cβ perfluoro alkyl, S(O)n alkyl or aryl where n is 0, 1 or 2; or COheteroaryl; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cβ alkyl, C1-C6 alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C 2 -C 6 alkanoyl, -C12 perfluoro alkyl, S(O) n -alkyl, S(O) n - aryl where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR 6 , CONR6R6, CONHOH, SO 2 NR 6 R 6 ,SO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO2alkyl, CONHSQzaryl, aryl, or heteroaryl; where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, -C6 alkyl, Ci-Cβ alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or N- -C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR-Cι-C 6 alkyl, optionally substituted with one or two groups selected independently from R 5 ; R 8 R 9 N-Cι-C6-alkoxyaryl-Cι-C6-alkyl where R 8 and R 9 are independently selected from C1-C6 alkyl or R 8 and R 9 together with the interposed nitrogen forms a 5-7 membered saturated heterocyclic ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; and the pharmaceutically acceptable salts thereof. The most preferred matrix metalloproteinase and TACE inhibiting compounds of this invention are: 1 -benzyl-4- (4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- 1 -(3-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide, 1 -(3,4-dichlorobenzyl) -4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxamide, 4-(4-methoxy-benzenesulfonyl)- l-(4-methylbenzyl)-piperidine-4-carboxyUc acid hydroxamide, (4-methoxy-benzene-sulfonyl)-l-napthalene-2-yl-methylpiperidine-4-carboxyhc acid hydroxamide, l-biphenyl-4-ylmethyl-4-(4-methoxy-benzenesulfonyl)piperidine-4-carboxyhc acid hydroxamide, 4-(4-methoxy-benzene-sulfonyl)-l-(3-methyl-but-2-enyl)piperidine-4-carboxylic acid hydroxamide, l-(4-bromo-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- 1 -(3-phenyl-propyl)-piperidine-4-carboxylic acid hydroxyamide, 1 -tert-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxyamide, l-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide, l-cyclooctyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 1 -ethyl-4- (4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 1 -isopropyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, l-methyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 1 -benzyl-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, l-(4-fluoro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, l-(4-fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide, 4- (4-methoxy-benzenesulfonyl)- 1 - [2- (4-methoxyphenyl)-ethyl] -piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- l-(2-phenyl-ethyl)-piperidine-4-carboxylic acid hydroxyamide, 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 hydroxyamide, 4-(4-n-butoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-n-butoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxyUc acid hydroxyamide, 4-(4-methoxy-rjenzenesulfonyl)-l-[4-(2-piperiά n-l-yl-ethoxy)-benzyl]-piperidine-4- carboxyUc acid hydroxyamide, It is understood that the definition of the compounds of formulas I, la and lb, when R 1 , R 2 , R 3 and R 4 contains asymmetric carbons, encompass all possible stereoisomers and mixtures thereof which posses the activity discussed below. In particular, it encompasses racemic modifications and any optical isomers which possesses the indicated activity. Optical isomers may be obtained in pure form by standard separation techniques. Where not stated otherwise, the term "alkyl" refers to a straight or branched -C 6 alkyl group and 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, and similarly 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 compound of this invention and a pharmaceutically acceptable carrier. The compositions are preferably adapted for oral administration. However, they may be adapted for other modes of administration, for example, parenteral administration for patients. In order to obtain consistency of administration, it is preferred that a composition of the invention is in the form of a unit dose. Suitable unit dose forms include tablets, capsules, and powders in sachets or vials. Such unit dose 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 at a dose range of about 0.01 to 100 mg per kg. Such composition may be administered from 1 to 6 times a day, more usually from 1 to 4 times a day. The compositions of the invention may 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 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 may be prepared according to one of the general processes out lined below. The appropriately substituted mercaptan derivative was alkylated using either substituted (Scheme I) or unsubstituted ( Scheme 2) α-bromo acetic acid ester derivative in refluxing acetone using IC ^ as base. The sulphide derivative thus obtained was oxidized using m-chloroperbenzoic acid in CII,C1 2 or by using Oxone in methanol/ water. The sulfone obtained from the above mentioned process can be either further alkylated using variety of alkyl halides to obtain the disubstituted derivative or it can be hydrolyzed using NaOH/ MeOH at room temp. However instead of using the ethyl ester, if the tertiary butyl ester is present, the hydrolysis can be carried out with TFA/CHjClj at room temperature. Subsiquently, the carboxylic acid obtained was converted to the hydroxamic acid derivative by reaction with oxalyl chloride/ DMX (catalytic) and hydroxyl amine/ triethyl amine. SCHEME 1 SYNTHESIS: a. K 2 CO 3 / Acetone/ Reflux; b. m-Chloroperbenzoic acid; c. K 2 CO 3 / 18-Crown-6/ R 3 Br/Acetone/ Reflux/ d. NaOH MeOH/ THF/ RT e. (COCl) 2 /CH 2 CI 2 /Et 3 N/NH 2 OH HCI. SCHEME 2 SYNTHESIS: a. K 2 CO 3 / Acetone/ Reflux; b. m-Chloroperbenzoic acid; c. K 2 COj/ 18-Crown-6/ R 2 Br/Acetone/ Reflux/ d. R 3 Br/ 10 N NaOH/ BzN(Et)3/ CH 2 C1 2 / RT e. NaOH/ MeOH/ THF/ RT f. (COCI) 2 /CH 2 Cl 2 /Et 3 N/NH 2 OH.HCI. As outlined in Scheme 3, the sulfide derivative can be further alkylated using lithium bis(trimethyl silyl)amide in THF at 0° C. The alkylated or mono substituted compound was hydrolyzed and converted to the hydroxamic acid derivative. The sulfinyl derivatives were prepared by oxidizing the sulfide hydroxamic acid derivatives with H 2 O 2 in MeOH solution. SCHEME - 3 SYNTHESIS: a. K 2 CO 3 / Acetone/ Reflux; b. R 3 Br/ HMDS/ THF; c. NaOH/ MeOH/ THF/ RT d. (COCl) 2 /CH 2 Cl 2 /Et 3 N/NH 2 OH.HCI. e. MeOH/ H 2 O 2 / RT The corresponding l-substituted-4-(4-methoxy-benzenesulfonyl)-piperidine-4- carboxylic acid hydroxyamides were prepared starting from diethanolamine and appropriately substituted alkyl or aryl halides (Scheme 4). The N-substituted diethanol amine derivatives were converted to the dichloro compounds using thionyl chloride. The corresponding dichlorides were reacted with substituted sulfonyl acetic acid ethyl ester derivatives in the presence of K 2 Cθ 3 /18-Crown-6 in boiling acetone. l-substituted-4-(4-methoxy- benzenesulfonyl)-piperidine-4-carboxylic acid ethyl esters thus obtained were converted to the hydroxy amide as outlined in Scheme 4. Alternatively these classes of compounds and other hetrocycles can be prepared as indicated in Scheme 5 and 6. SCHEME 4 SCHEME 5 Y = N or CH a. RBr/ R^H/ CHCl 3 / Reflux; b. Oxone/MeOH; e. (COCl) 2 /NH 2 OH. HCl Et 3 N SCHEME 6 a. LiN(TMS) 2 /THF/ 0 °C/ C0 2 ; b. (COCl) 2 / NH 2 OH. HCI/ Et 3 N Alternatively, Schemes 7 to 11 show methods for the preparation of hydroxamic acid compounds using a solid phase support (P). Scheme 7 & 0 J " lqn Rl — * H Tθn Ri Reagents 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) Thiol (5.0 eq.); sodium iodide (5.0 eq.); l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 3.0 eq.); THF; 25°C; 12- 16 hours, c) 70% t -butylhydroperoxide (40 eq.); benzenesulfonic acid (2.0 eq.); DCM; 25°Q 12-24 hours, d) mCPBA (5.0 eq.); DCM; 25°C; 12-24 Hours, e) TFA : DCM (1:1); 25°C; 1 hour. The O-meΛylhydroxylarnine-phenoxymethyl-copoly(styrene-l%-divinylbenzene)- resin (hydroxylamine resin) may be coupled with a 2-halo acid to give the hydroxamate ester resin. The coupling reaction may be carried out in the presence of carbodiimide, such as DIC, in an inert solvent such as DMF at room temperature. The halogen group may 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 may be oxidized to the sulfoxide by reaction with an oxidizing agent such as ttfrt-butylhydroperoxide in the presence of an acid catalyst such as benzenesulfonic acid, in an inert solvent such as DCM at room temperature. Alternatively, the sulfide may be oxidized to the sulfone by reaction with an oxidizing agent such as etα-chloroperoxybenzoic acid, in an inert solvent such as DCM at room temperature. The sulfide, sulfoxide, or sulfone may be treated with and acid, such as trifluoroacetic acid, in and inert solvent such as DCM to liberate the free hydroxamic acid. Scheme 8 shows a method of preparing hydroxamic acids having alkoxy groups attached to the aromatic ring. Scheme 8 Reagents 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- Fluorobenzenethiol (5.0 eq.); sodium iodide (5.0 eq.); l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 3.0 eq.); THF; 25°C; 12-16 hours, c) Alcohol (15.0 eq.); sodium hydride (15.0 eq.); DMF; 80°C; 15 hours, d) 70% t -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. TFA : DCM (1:1); 25°C; 1 hour. The hydroxylamine resin may be coupled with the 2-halo acid and the halo group may be displaced by fluorobenzenethiol as previously described. The fluoro group may 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 may then be oxidized either to the corresponding sulfinyl or sulfonyl hydroxamate ester as previously described. The free hydroxamic acids may be liberated as previously described. Scheme 9 shows a method of preparing 2-bisarylsulfanyl-, sulfinyl-, and sulfonylhydroxamic acids. Scheme 9 Reagents 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- Bromobenzenethiol (5.0 eq.); sodium iodide (5.0 eq.); l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 3.0 eq.); THF; 25°C; 12-16 hours, c) 70% t -butylhydroperoxide (40 eq.); benzenesulfonic acid (2.0 eq.); DCM; 25°C; 12-24 hours, d) CPBA (5.0 eq.); DCM; 25°C; 12-24 hours, e) Arylboronic acid (2.0 eq.); tetrakis(triphenylphosρhine) palladium(O) (0.1 eq.); 10% aqueous sodium carbonate (10.0 eq.); DME; ; 80°C; 8 hours, f) TFA : DCM (1:1); 25°C; 1 hour. The hydroxylamine resin may be coupled with the 2-halo acid and the halo group may be displaced by bromobenzenethiol as previously described. The bromobenzenesulfanyl hydroxamate ester may then be oxidized either to the corresponding sulfinyl or sulfonyl hydroxamate ester as previously described. The bromo group may then be replaced with an aryl group by reaction with the arylboronic acid in the presence of a catalyst such as tetrakis(triphenylphosphine) palladium(O), and a base such as sodium carbonate, in an inert solvent such as DME at about 80°C. The free hydroxamic acids may be liberated as previously described. Scheme 10 shows a method of preparing hydroxamic acids having amine groups attached to the aromatic ring. Scheme 10 Reagents 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- Bromobenzenethiol (5.0 eq.); sodium iodide (5.0 eq.); l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 3.0 eq.); THF; 25° 12-16 hours, c) Amine (20.0 eq.); tris(dibenzylideneacetone)- diρalladium(0) (0.2 eq.); (S)-(-)-2,2'-bis(diphenylphosphimo)-l,l'-binaphthyl ((S)-BINAP, 0.8 eq.); sodium fc?rt-butoxide (18.0 eq.); dioxane; 80°C, 8 hours; d) TFA : DCM (1:1); 25° 1 hour. The hydroxylamine resin may be coupled with the 2-halo acid and the halo group may be displaced by bromobenzenethiol as previously described. The bromo group may then be displaced with an amine in the presence of a catalyst such as tris(dibenzylideneacetone)- dipalladium(O) and a hgand such as (S)-BINAP and a base such as sodium t -butoxide, in an inert solvent such as dioxane at about 80°C. The free hydroxamic acids may be liberated as previously described. 0 Scheme 11 shows a method of preparing hydroxamic acids having sulfonate groups attached to the aromatic ring. Scheme 11 j 5 Reagents 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- Hydroxybenzenethiol (5.0 eq.); sodium iodide (5.0 eq.); l,8-diazabicyclo[5.4.0]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 may be coupled with the 2-halo acid and the halo group may be displaced by hydroxybenzenethiol as previously described. The hydroxybenzenesulfanyl hydroxamate ester may then be oxidized either to the corresponding sulfinyl or sulfonyl hydroxamate ester as previously described. The hydroxy group may then be sulfonylated by reaction with a sulfonyl chloride in the presence of a base such as triethylamine, in an inert solvent such as DCM at about room temperature. The free hydroxamic acids may be Uberated as previously described. The following examples are presented to illustrate rather than limit the scope of the invention. HPLC purity of compounds prepared by combinatorial procedures is presented as area percentage at a prescribed wavelength (%@ nm). Example 1 N-Hydroxy-2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionamide To stirred solution of 4-methoxybenzenethiol (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 round bottom flask and the reaction mixture was heated at reflux for 8 hours with good stirring. At the end, reaction was allowed to cool and the potassium salts were filtered off and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H2O and 0.5 N NaOH solution. The organic layer was further washed well with water, dried over MgSO4, filtered and concentrated to afford 2-(4-methoxy-phenylsulfanyl)-propionic acid ethyl ester as a light yellow oil. Yield 4.5gms (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, lithium bis(trimethylsilyl)amide (1 M solution, 15 ml, 15 mmol) was added slowly. The orange colored reaction mixture was stirred at room temperature for 15 minutes and then it was 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 benzylbromide (1.72 gm, 10 mmol) was added dropwise in THF. The reaction was warmed to room temperature and stirred overnight before it was quenched with ice water, extracted with chloroform and washed with water. The organic layer was dried over MgSO 4 , filtered and concentrated and chromatographed on a silica-gel column with 10% ethyl acetate:hexane to afford 2-(4-methoxy- phenylsulfanyl)-2-methyl-3-phenyl-propionic acid ethyl ester as a colorless oil. Yield: 860 mg, (26%) ; MS: 331 (M+H) + . 2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionic acid ethyl ester (4.12 g, 12 mmol) 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 1:1 hexane:diethyl ether and extracted with H 2 O. The water layer was cooled with ice and acidified to pH 3. The acid was then extracted with chloroform and the organic layer was dried over MgSO4, filtered and concentrated to afford of 2-(4-methoxy-phenylsulfanyl)-2-methyl-3- phenyl-propionic acid as a low melting solid. Yield 580 mg, 16%; MS: 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 CH 2 C1 2 (100 ml) at O°C, oxalyl chloride (1.0 gm, 8 mmol) was added in a drop- wise manner. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, in a separate flask a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) was stirred in THF:water (5:1, 30 ml) at O°C for 1 hour. At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH 2 CI 2 and added slowly to the hydroxylamine at O°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 product obtained was purified by silica gel column chromatography and eluted with ethyl acetate. The N-hydroxy-2-(4-methoxyphenylsulfanyl)-2-methyl-3-phenyl- propionamide was isolated as a colorless solid, mp 88 °C; Yield, 300 mg, 57%; MS: 318 (M+H) + ; 1H NMR (300 MHz, CDC1 3 ): δ 1.32 (s, 3H), 3.07 (d, J =11 Hz, 1H), 3.23 (d, J =11 Hz, 1H), 3.79 (s, 3H), 6.83-7.36 (m, 9H). Example 2 N-Hydroxy-2-(4-methoxy-phenylsulfanyl)-2-phenyl-acetamide 2-(4-Methoxyphenylsulfanyl)-phenylacetic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from ethyl α-bromophenyl acetate (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%; MS: 303.1 (M+H) + . 2-(4-Methoxy-phenylsulfanyl)-2-phenyl acetic acid was prepared starting from 2-(4-methoxy- phenylsulfanyl)-phenyl-acetic acid ethyl ester (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. MS: 273 (M+H)+. Starting from 2-(4-methoxy-phenylsulfanyl)-phenyl acetic acid (1.05 g, 3.83 mmol) and following the procedure as outlined in Example 1, 154 mg of N-hydroxy-2-(4-methoxy- phenylsulfanyl)-2-phenyl-acetamide was isolated as a colorless solid, mp 155 °C; Yield 14%; MS: 290 (M+H) + ; *H NMR (300 MHz, DMSO-d6): δ 3.72 (s, 3H), 4.68 (s, 1H), 6.86-7.44 (m, 9H). Example 3 2-(4-Methoxy-phenylsulfanyl)-2,5-dimethyl-hex-4-enoic acid hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-2,5-dimethyl-hex-4-enoic acid ethyl ester was prepared following the procedure of Example 1, second paragraph. Starting from (4-methoxy- phenylsulfanyl)-propionic acid ethyl ester (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-enoic acid ethyl ester (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 outlined in Example 1. Yield is 1.9 g, 99% of low melting solid. MS: 280 (M+H) + . Starting from 2-(4-methoxy-phenylsulfanyl)-2,5-dimethyl-hex-4-enoic acid (1.67 g, 5.8 mmol) and following the procedure as outlined in Example 1, 1.5 g of 2-(4-methoxy- phenylsulfanyl)-2,5-dimethyl-hex-4-enoic acid hydroxyamide was isolated as a colorless solid, mp 89 °C; Yield 94%; MS: 296 (M+H) + ; Η NMR (300 MHz, CDC1 3 ): δ 1.34 (s, 3H), 1.61 (s, 3H), 1.74 (s, 3H), 2.41-2.58 (m, 2H), 3.80 (s, 3H), 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 2-(4-Methoxy-phenylsulfanyl)-3-methyl-butyric acid ethyl ester was prepared according to the general method of Example 1. Starting from ethyl 2-bromo-3-methyl-butanoate (20.9 g, 100 mmol) and 4-methoxybenzenethiol (14.0 g, 100 mmol), 30 g of the product was isolated. Yield 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 outlined in Example 1. Yield 5.0 g, 99%. Low melting solid. MS: 242 (M+H) + . Starting from 2-(4-methoxy-phenylsulfanyl)-3-methyl-butyric acid (4.39 g, 18.3 mmol) and following the procedure as outlined in Example 1 , 1.5 g of N-hydroxy-2-(4-methoxy- phenylsulfanyl)-3-methyl-butyramide was isolated as a colorless solid, mp 119 °C; Yield 33%; MS: 256 (M+H) + ; *H NMR (300 MHz, DMSO-d6): δ 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-benzenesulfinyl)-2-methyl-3-phenyl-propionamide N-hydroxy-2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionamide (400 mg, 1.26 mmol) (prepared in Example 1) was dissolved in methanol (100 ml) and 30% H2O 2 (10 ml) was added. The reaction mixture was stirred for 48 hours at room temperature at which time it was cooled to 0° C and quenched with saturated Na 2 SO 3 (20 ml) solution. The reaction mixture became cloudy. It was stirred for 4 hours before it was concentrated in a room temperature water bath, diluted with water, extracted with CHCI 3 and washed with H 2 O. The organic layer was dried over MgSO 4 , filtered and concentrated. The title compound was isolated by silica gel column chromatography, eluting with 75% ethylacetate:hexane. Low melting solid. Yield: 220 mg (52%); MS: 334.1 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): d 1.11 (s, 2H), 1.22 (s, 3H), 3.84 (s, 3H), 7.00-7.61 (m, 9H). Example 6 2-(4-Methoxy-benzenesulfinyl)-2,5-dimethyl-hex-4-enoic acid hydroxyamide Starting from 2-(4-methoxy-benzenesulfanyl)-2,5-dimethyl-hex-4-enoic hydroxamide (900 mg, 3.0 mmol) (prepared in Example 3) and following the procedure outlined in Example 5, 2- (4-methoxy-benzenesulfϊnyl)-2,5-dimethyl-hex-4-enoic acid hydroxyamide was isolated as a colorless solid. Yield: 104 mg (10%); mp 108 °C; MS: 312 (M+H)+; Η NMR (300 MHz, DMSO-d 6 ): δ 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-benzenesulfmyl)-3-methyl-butyramide Starting from N-hydroxy-2-(4-methoxy-phenylsulfanyl)-3-methyl-butyramide (1 g, 3.9 mmol) as 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: 420mg (40%); mp 163 °C; MS: 272 (M+H) + ; *H NMR (300 MHz, DMSO-d 6 ): δ 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 mmol) as prepared in Example 2, and following the procedure outlined in Example 5, N- hydroxy-2-(4-methoxy-benzenesulfιnyl)-2-phenyl-acetamide was isolated as colorless solid. Yield: lOOmg (40%); mp 135 °C; MS 304 (M+H) + ; Η NMR (300 MHz, DMSO-d ό ): δ 3.75 (s, 3H), 4.38 (s, 1H), 6.92-7.69 (m, 9H) Example 9 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-3-phenyl-propionamide. To a stirred solution of 4-methoxybenzenethiol (2.8 gm, 20 mmol) and anhydrous K 2 CO 3 (10 gm, excess) in dry acetone (100 ml), α-bromo ethyl acetate (3.3 gm, 20 mmol) was added in a round bottom flask and the reaction mixture was heated at reflux for 8 hours with good stirring. At the end, the reaction mixture was allowed to cool and the potassium salts were filtered off and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H 2 O and 0.5 N NaOH solution. The organic layer was further washed well with water, dried over MgSO 4 , filtered and concentrated. (4-methoxy- phenylsulfanyl)-acetic acid ethyl ester was isolated as 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 (4.4 g, 20 mmol) in CH 2 CI 2 (15 ml) was added slowly. The reaction mixture turned cloudy and was 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 off and Na 2 SO 3 solution was added to the organic layer which was stirred for at least 3 hours before the mixture was extracted with CHCI 3 and washed with H 2 O. 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. Yield: 100%; MS: 259.1 (M+H) + To stirred solution of the (4-methoxy-benzenesulfonyl)-acetic acid ethyl ester (2.5 g, 10 mmol), benzyl bromide ( 1.8 gm,10 mmol) and 18-Crown-6 (500 mg) in acetone (250 ml) was added K 2 CO 3 (lOgms, 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 MgSO 4 , filtered and concentrated. The product obtained was purified by silica-gel column chromatography, 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 gm 86%; Low melting solid; MS: 349 (M+H) + . To a stirred solution of 2-(4-methoxy-bεnzenesulfonyl)-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 HCI. The residue obtained was extracted with chloroform, washed well with water, dried and concentrated. The product obtained was purified by silica- gel column chromatography by eluting with ethyl acetate: methanol (95:5) to afford 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-propionic acid (200 mg, 0.625 mmol) and following the procedure as outlined in Example 1, 150 mg of N-hydroxy-2-(4-methoxy- benzenesulfonyl)-3-phenyl-propionamide was isolated as a brown solid. Yield: 71 ; mp 180 °C; MS: 336 (M+H) + ; l H NMR (300 MHz, CDC1 3 ): δ 3.2 (m, 1H), 3.8 (s, 3H), 4.0-4.2 (m, 2H), 7.0-8.0 (m, 9H). Example 10 2-(4-Methoxy-benzenesulfonyl)-hexanoic acid hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-hexanoic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from ethyl 2-bromo hexanoate (7 g, 32 mmol) and 4-methoxybenzenethiol (4.2 g, 30 mmol), 8.3 g of the product was isolated. Yield 98%; Light yellow oil; MS: 283 (M+H) + . Starting from 2-(4-methoxy-phenylsulfanyl)-hexanoic acid ethyl ester. (2.8 g 10 mmol) and following the procedure as outlined in Example 9, 3 g of 2-(4-methoxy-benzenesulfonyl)- hexanoic acid ethyl ester was isolated as a colorless sohd. 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 by following the procedure as outlined in Example 9. Mp 116 °C; MS: 287 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-hexanoic acid (1.0 g, 3.1 mmol) and following the procedure as outlined in Example 1, 700 mg of 2-(4-methoxy-benzenesulfonyl)-hexanoic acid hydroxyamide was isolated as a colorless solid. Yield: 60%; mp 130 °C; MS: 302 (M+H) + ; *H NMR (300 MHz, CDCI3): δ 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=ll Hz, 2H), 9.3 (s, 1H), 10.9 (s, 1H). Example 11 2-(4-Methoxy-benzene sulfonyl)-tetradecanoic hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-tetradecanoic acid ethyl ester was prepared according to the general method as outlined in Example 1. Starting from the corresponding ethyl -2- bromomyristate (5.0 g, 14.9 mmol) and 4-methoxythiophenol (1.9 g, 13.4 mmol), 5.0 g of the product was isolated. Yield 98%; 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 as outlined in Example 9, 3.2 g of 2-(4-methoxy- benzenesulfonyl)-tetradecanoic acid ethyl ester was isolated as a colorless solid, yield: 76%; Oil; MS: 425 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-tetradecanoic acid ethyl ester (2.5 g, 5.9 mmol), 2.0 g (85%) of 2-(4-methoxy-benzenesulfonyl)-tetradecanoic acid was isolated as a colorless sohd by following the procedure as outlined in Example 9. mp 82 °C; MS: 397 (M+H)+. Starting from 2-(4-methoxy-benzene sulfonyl)-tetradecanoic acid (1.14 g, 2.9 mmol) and following the procedure as outlined in Example 1, 670 mg of 2-(4-methoxy-benzenesulfonyl)- tetradecanoic hydroxyamide was isolated as an off-white solid. Yield: 57%; mp 114 °C; MS: 414 (M+H) + ; *H NMR (300 MHz, DMSO-dδ): δ 0.85 (t, J = 7 Hz, 3H), 1.16-1.27 (m, 20 H), 1.66 (m, 2H), 3.62-3.70 (m, 1H), 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 gm, 3mmol) (example 9), methyl iodide ( 1 ml, excess) and 18-Crown-6 (500 mg) in acetone (250 ml), K 2 CO 3 (10 gm, excess) was added and the reaction 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 MgSO 4 , filtered and concentrated. The product obtained was purified by sihca-gel column chromatography by eluting it with 30% ethyl acetate:hexanes to afford 2-(4-methoxy- benzenesulfonyl)-2-methyl-3-phenyl-propionic acid ethyl ester as a colorless oil. Yield 1.0 g, 98%; MS: 349 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-phenyl-propionic acid ethyl ester (900 mg, 2.7 mmol), 850 mg (quantitative) of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3- phenyl-propionic acid was isolated by following the procedure as outlined in Example 9. Colorless oil, MS 335 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-phenyl-propionic acid (900 mg, 2.7 mmol) and following the procedure as outlined in Example 1, 450 mg of N-hydroxy-2-(4- methoxy-benzenesulfonyl)-2-methyl-3-phenyl-propionamide was isolated as a brown solid. Yield: 48%; mp 58 °C; MS: 350 (M+H) + ; Η NMR (300 MHz, CDC1 3 ): δ 1.4 (s, 3H), 3.1 (d, J=9 Hz, 1H), 3.6 (d, J= 9 Hz, 1H), 3.9 (s, 3H), 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 as outlined in Example 9, 12 g of 2-(4-mefhoxy- benzenesulfonyl)-propionic acid ethyl ester was isolated as a semi-solid, yield 100%; MS: 256.1 (M+H) + . Following the procedure as outlined 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 2-(4- methoxy-benzenesulfony -propionic acid ethyl ester and isoprenyl bromide (1.0 g, 6 mmol). Yield 1.0 g, 81%; Colorless oil; MS: 341 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2,5-dimethyl-hex-4-enoic acid ethyl ester (900 mg, 2.6 mmol) 800 mg (96%) of 2-(4-methoxybenzenesulfonyl)-2,5-dimethyl-hex-4-enoic acid was isolated as a semi solid by following the procedure as outlined in Example 9. MS: 313 (M+H)+. Starting from 2-(4-methoxy-benzenesulfonyl)-2,5-dimethyl-hex-4-enoic acid (1.0 g, 3.2 mmol) and following the procedure as outlined in Example 1, 700 mg of 2-(4-methoxy- benzenesulfonyl)-2,5 dimethyl-hex-4-enoic acid hydroxyamide was isolated as a low melting solid. Yield: 67%; MS: 328 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.3 (s, 3H), 1.5 (d, J=6.2 Hz, 6H), 2.5 -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 as outlined in Example 12, 3-(biphenyl-4-yl)-2-(4-methoxy- benzenesulfonyl)-2-methyl-propionic acid ethyl ester was prepared, 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 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 was isolated as a colorless sohd by following the procedure as outlined in Example 9. mp 161 °C; MS: 411 (M+H) + . Starting from 3-(biphenyl-4-yl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid (2.0 g, 4.8 mmol) and following the procedure as outlined in Example 1, 1.2 g of 3-(biphenyl-4- yl)-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide was isolated as colorless solid. Yield: 58%; mp 177 °C; MS: 426 (M+H) + ; »H NMR (300 MHz, CDCI 3 ): δ 1.4 (s, 3H), 3.2 (d, J=9 Hz, IH), 3.7 (d, J= 9 Hz, IH), 3.9 (s, 3H), 7.0 - 7.8 (m, 13H), 9.7 (bs, IH). Example 15 2-(4-methoxy-benzenesulfonyl)-2,5,9-trimethyl-deca-4,8-dienoic acid hydroxyamide Following the procedure as outlined 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- (4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and geranyl bromide (3.0 g, 13 mmol). Yield 4.0 g, 98%; Colorless oil; MS : 409 (M+H) + . Starting from 2-(4-methoxy-r nzenesutfonyl)-2,5,9-trimethyl-deca-4,8-dienoic acid ethyl ester (3 g, 7.4 mmol), 2.8 g (96%) of 2-(4-methoxy-benzenesulfonyl)-2,5,9-trimethyl-deca-4,8- dienoic acid was isolated as a colorless oil by following the procedure as outlined in Example 9. MS: 379 (M-H)-. Starting from 2-(4-methoxy-benzenesulfonyl)-2,5,9-trimethyl-deca-4,8-dienoic acid (2.0 g, 5.2 mmol) and following the procedure as outlined in Example 1, 1.8 g of 2-(4-methoxy- benzenesulfonyl)-2,5,9-trimethyl-deca-4,8-dienoic acid hydroxyamide was isolated as a colorless oil. Yield: 88%; MS: 396 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.4 (s, 3H), 1.6 (s, 3H), 1.65 (s, 3H), 1.7 (s, 3H), 2.0- 3.1 (m,6 H), 3.9 (s, 3H), 5.5 (m, 2H), 6.98 (d, J= 9.0 Hz, 2H), 7.7 (d, J= 9.0 Hz, 2H). Example 16 3-Cyclohexyl-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide Following the procedure as outlined in Example 12, 3-cyclohexyl-2-(4-methoxy- benzenesulfonyl)-2-methyl-propionic acid ethyl ester was prepared, starting from (2.7 g, 10 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and bromometiiylcyclohexane (1.8 g, 10 mmol). Yield 3.5 g, 95%; Yellow oil; MS: 369 (M+H) + . Starting from 3-cyclohexyl-2-(4-methoxy-benzenesulfonyl)-2-methyl propionic acid ethyl ester (3 g, 8.1 mmol) 2.5 g (90%) of 3-cyclohexyl-2-(4-methoxy-benzenesulfonyl)-2-methyl propionic acid was isolated as colorless sohd by following the procedure as outlined in Example 9. mp 116 °C; MS: 341 (M+H) + . Starting from 3-cyclohexyl-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid (2.0 g, 5.8 mmol) and following the procedure as outlined in Example 1, 1.1 g of 3-cyclohexyl-N- hydroxy-2-( methoxy-benzenesulfonyl)-2-methyl-propionamide was isolated as colorless solid. Yield: 55%; mp 58 °C; MS: 356 (M+H) + ; Η NMR (300 MHz, CDCI 3 ) δ 1.4 (s, 3H), 2.3 -1.0 (m, 13 H), 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 as outlined in example 12, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-[4-(2-piperidin-l-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 the 4-(2- piperidin-l-yl-ethoxy)-benzyl chloride (2.9 g, 10 mmol). Yield 4.8 g, 98%; Brown oil; MS: 490 (M+H)+. Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-piperidin- 1 -yl-ethoxy)- phenylj-propionic acid ethyl ester (4.0 gm, 7.9 mmol) 3.5 g (Yield: 94 %) of 2-(4-methoxy- benzenesulfonyl)-2-methyl-3-[4-(2-piperidin-l-yl-ethoxy)-phenyl]-propionic acid was isolated as colorless crystals by following the procedure as outlined 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 as outlined in example 1, 1 g of N-hydroxy- 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-piperidin-l-yl- ethoxy)-phenyl] -propionamide was isolated as colorless solid. Yield: 1 g, 48%; mp 98°C; MS: 477 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.2 (s, 3H), 3.5 - 1.5 (m, 16 H), 3.9 (s, 3H), 4.4 (m, IH), 6.5 - 7.8 (m, 8H), 10.8 (bs, IH). Example 18 2-[4-(2-Azepan- 1 -yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-propionic acid hydroxyamide Following the procedure as outlined in example 12, 2-[4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4- methoxy-benzenesulfonyl)-propionic acid ethyl ester was prepared, starting from (2.7 g, 10 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and the l-[2-(4- chloromethyl-phenoxy)ethyl]-azepane (3.03 g, 10 mmol). Yield 4.5 g, 90%; Brown oil; MS: 504 (M+H)+. Starting from 2-[4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester (4.0 gm, 7.9 mmol) 3.5 g (Yield: 94 %) of 2-[4-(2-azepan-l-yl-ethoxy)- benzyl]-2-(4-methoxy-benzenesulfonyl)-propionic acid was isolated as semi-solid by following the procedure as outlined in example 9. MS: 476 (M+H) + . Starting from 2-[4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-propionic acid (2.0 g, 4.2 mmol) and following the procedure as outlined in example 1, 1 g of 2-[4-(2- azepan- 1 -yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-propionic acid hydroxyamide was isolated as colorless sohd. Yield: 1.8 g, 87%; mp 68°C; MS: 491 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.23 (s, 3H), 3.5 - 1.7 (m, 18 H), 3.8 (s, 3H), 4.2 (m, IH), 6.4 - 7.89 (m, 8H), 10.9 (bs, IH). Example 19 2-[4-(2-Azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-bεnzenesulfonyl)-pentanoic acid hydroxyamide 2-[4-(2-Azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-pentanoic acid ethyl ester was prepared according to the general method as outlined in example 12. Starting from 2- (4-methoxy-benzenesulfonyl)-pentanoic acid ethyl ester (3.5 g, 11.7 mmol) and l-[2-(4- chloromethyl-phenoxy)-ethyl]-azepane (3.9 g, 12.8 mmol). Yield 2.58 g (42%); brown oil; MS: 532.4 (M+H) + . 2-[4-(2-Azepan- 1 -yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-pentanoic acid was prepared starting from 2-[4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)- pentanoic acid ethyl ester (2 g, 3.76 mmol) dissolved in methanol (300 ml) and 10 N NaOH (15 ml). The resulting mixture was worked up as outlined in example 1. Yield 830 mg (44%); brown sohd; mp 55 °C; MS: 504.4 (M+H)+ Starting from 2-[4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-pentanoic acid (690 mg, 1.37 mmol) and following the procedure as outlined in example 1, 240 mg of 2- [4-(2-azepan-l-yl-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-pentanoic acid hydroxyamide was isolated as a yellow solid. Yield 34%; mp 85 °C; MS: 519.2 (M+H) + ; 1H NMR (300 MHz, DMSO-dβ): d 0.71 (t, J = 7.3 Hz, 3H), 0.78-1.77 (m, 16 H), 3.04-3.46 (m, 4H), 3.87 (s, 3H), 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, IH), 10 (s, IH). Example 20 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diisopropyl amino- ethoxy )-phenyl] -propionamide Following the procedure as outhned in example 12, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-[4-(2-N,N-diisopropyl amino-ethoxy)-phenyl] -propionic acid ethyl ester was prepared, starting from (5.4 g, 20 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and the 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 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diisopropyl amino- ethoxy)-phenyl]-propionic acid ethyl ester (4.0 gm, 7.9 mmol) 3.5 g (Yield: 92 %) of 2-(4- methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-dΕrøpropyl arnino-ethoxy)-phenyl]- propionic acid was isolated as colorless crystals by following the procedure as outhned in example 9. Mp 68 °C; MS: 478.6 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-dhsopropyl amino- ethoxy)-phenyl] -propionic acid (2.0 g, 4.1 mmol) and following the procedure as outhned 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 colorless solid. Yield: 1 g, 49%; mp 98°C (Hcl Salt); MS: 493 (M+H) + ; Η NMR (300 MHz, CDC1 3 ): δ 1.2 (s, 3H), 1.3 (d,6H), 1.4 (d,6H), 3.5 - 1.5 (m, 6 H), 3.9 (s, 3H), 4.4 (s, 2H), 6.5 - 7.8 (m, 8H), 10.8 (bs, IH). Example 21 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl]-propionamide Following the procedure as outhned 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, 20 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and the 4- (2-N,N-diethyl amino-ethoxy)-benzyl chloride (5.5 g, 20 mmol). Yield 8.5 g, 89%; Brown oil; MS: 478.6 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl] -propionic acid ethyl ester (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 was isolated as colorless crystals by following the procedure as outhned 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 as outlined in example 1, 1 g of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenylj-propionamide was isolated as colorless sohd. Yield: 1 g, 48%; mp 56-59°C (HCI Salt); MS: 465.5 (M+H) + ; l U NMR (300 MHz, CDC1 3 ): δ 1.1 (t, 6H), 1.3 (s,3H), 3.2 - 3.9 (m, 8 H), 3.9 (s, 3H), 4.3 (s, 2H), 6.5 - 7.8 (m, 8H), 10.8 (bs, IH). Example 22 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-piperidin-l-yl-ethoxy)-phenyl]- propionamide Following the procedure as outhned in example 12, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-[3-(2-piperidin-l-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 the 3-(2- piperidin-l-yl-ethoxy)-benzyl chloride (6.0 g, 20 mmol). Yield 8.2 g, 83%; Brown oil; MS: 490 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-piperidin- 1 -yl-ethoxy)- phenyl] -propionic acid ethyl ester (6.0 gm, 12.2 mmol) 4.9 g (Yield: 79 %) of 2-(4-methoxy- benzenesulfonyl)-2-methyl-3-[3-(2-piperidin-l-yl-ethoxy)-phenyl]-propionic acid was isolated as colorless crystals by following the procedure as outlined 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 as outlined in example 1 , 1.8 g of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3- [3-(2-piperidin- 1 -yl-ethoxy)-phenyl] - propionamide was isolated as colorless solid. Yield: 1.8 g, 58%; mp 74°C; MS: 477 (M+H) + ; Η NMR (300 MHz, CDCI3): δ 1.25 (s, 3H), 1.6-1.8 (m, 6 H), 2.5 - 3.7 (m, 8H), 3.9 (s, 3H), 4.4 (t, 2H), 6.7 - 7.8 (m, 8H), 10.8 (bs, IH). Example 23 3-(4- { 3-[4-(3-Chloro-phenyl)-piperazin- 1 -yl]-propoxy } -phenyl)-N-hydroxy-2-(4-m ethoxy-benzenesulfonyl)-2-methyl-propionamide Following the procedure as outlined in example 12, 3-(4-{3-[4-(3-chloro-phenyl)-piperazin-l- yl]-propoxy}-phenyl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid ethyl ester was prepared, starting from (2.72 g, 10 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and the l-[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 3-(4- { 3-[4-(3-chloro-phenyl)-piperazin-l -yl]-propoxy } -phenyl)-2-(4-methoxy- benzenesulfonyl)-2-methyl-propionic acid ethyl ester (4.0 gm, 6.5 mmol) 3.0 g (Yield: 78 %) of 3-(4- { 3-[4-(3-chloro-phenyl)-piperazin- l-yl]-propoxy } -phenyl)-2-(4-methoxy-ben zenesulfonyι)-2-methyl-propionic acid was isolated as colorless crystals by following the procedure as outhned in example 9. Mp 196 °C; MS: 588.1 (M+H)+. Starting from 3-(4- { 3-[4-(3-chloro-phenyl)-piperazin- l-yl]-propoxy } -phenyl)- 2-(4-methoxy- benzenesulfonyl)-2-methyl-propionic acid (3.0 g, 5.1 mmol) and following the procedure as outlined in example 1, 1.8 g of 3-(4-{3-[4-(3-chloro-phenyl)-piperazin-l-yl]-propoxy}- phenyl)-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide was isolated as pale yellow sohd. Yield: 1.8 g, 55%; mp 122°C (HCI Salt); MS: 640 (M+H) + ; ] H NMR (300 MHz, CDC1 3 ): δ 1.2 (s, 3H), 3.4 - 1.5 (m, 14 H), 3.9 (s, 3H), 4.5 (m, 2H), 6.5 - 8.2 (m, 12H), 10.3 (bs, IH). Example 24 2-(4-Methoxy-benzenesulfonyl)-5-methyl-2-[4-(2-morphohn-4-yl-ethoxy)-benzyl]- hex-4-enoic acid hydroxyamide To a stirred solution of (4-methoxy-benzenesulfonyl)-acetic acid ethyl ester (5.16 g, 20 mmol), isoprenyl bromide (3.0 g, 20 mmol) and 18-Crown-6 (500 mg) in acetone (250 ml) was added K2CO3 (10 gms, excess) and the mixture refluxed foe 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 sihca-gel column chromatography, eluting with 30% ethy acetate: hexane. The product 2-(4-methoxy-benzenesulfonyl)-5-methyl-hex-4- enoic acid ethyl ester was isolated as a colourless oil. Yield: 3.0 g, 93%. Following the procedure as outlined in example 12, 2-(4-Methoxy-benzenesulfonyl)-5-methyl- 2-[4-(2-morphohn-4-yl-ethoxy)-benzyl]-hex-4-enoic acid ethyl ester was prepared, starting from (3.26 g, 10 mmol) of 2-(4-methoxy-benzenesulfonyl)-5-methyl-hex-4-enoic acid ethyl ester and 4-(2-mo holin-l-yl-ethoxy)-benzyl chloride (3.0 g, 11 mmol). Yield 4.5 g, 82%; Brown oil; MS: 546 (M+H)+. Staιtmg from 2-(4-Methoxy-benzenesulfonyl)-5-methyl-2-[4-(2-morphohn-4-yl-ethoxy)- benzyl]-hex-4-enoic acid ethyl ester (3.0 gm, 5.5 mmol) 2.1 g (Yield: 75 %) of 2-(4- Methoxy-benzenesulfonyl)-5-methyl-2-[4-(2-morphohn-4-yl-ethoxy)-benzyl]-hex-4-enoic acid was isolated as semi-solid by following the procedure as outlined 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 as outhned in example 1, 450 mg of 2-(4-Methoxy-benzenesulfonyl)-5-methyl-2-[4-(2-moφhohn-4-yl- ethoxy )-benzyl]-hex-4-enoic acid hydroxyamide was isolated as pale yellow solid. Yield: 450 mg, 45%; mp 92°C (HCI Salt); MS: 570 (M+H) + ; Η NMR (300 MHz, CDC1 3 ): δ 1.3 (d, 3H), 1.65 (d, 2H), 3.5 - 1.8 (m, 14 H), 3.9 (s, 3H), 4.5 (m, 2H), 5.4 (m, IH), 6.5 - 7.9 (m, 8H), 11.5 (bs, IH). Example 25 N-Hydroxy-2-(4-ethoxy-r nzenesulfonyl)-2-memyl-3-[4-(2-N,N-diethyl amino-ethoxy)- 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) 2-bromo ethylpropionate (18. 2 g, 100 mmol) was added drop wise. The reaction mixture was refluxed for 1 hr 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 colorless oil. Yield: 22.0 g, 99%, MS: 227 (M+H). To stirred solution of 2-(4-hydroxy-phenylsulfanyl)-propionic acid ethyl ester (11.3 g, 50 mmol), and K 2 CO 3 (50 g, excess) in acetone (300 ml) ethyl iodide (20 ml, excess) was added and refluxed for 8 hrs. At the end, reaction mixture was filtered and concentrated. The residue obtained was extracted with chloroform and washed well with water. It was dried and concentrared. The product, 2-(4-ethoxy-phenylsulfanyl)-propionic acid ethyl ester was isolated as colorless oil. Yield: 12.0 g , 98%; MS: 255 (M+H). 2-(4-Ethoxy-phenylsulfanyl)-propionic acid ethyl ester was converted to 2-(4-ethoxy- phenylsulfonyl)-propionic acid ethyl ester by following the procedure as described in example 9, paragraph 2. Following the procedure as outlined in 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 the 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 2-(4-ethoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl]-propionic acid ethyl ester (4.0 gm, 8.1 mmol) 3.2 g (Yield: 80 %) of 2-(4-ethoxy- benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)-phenyl] -propionic acid was isolated as colorless semi-solid by following the procedure as outlined 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 as outlined in example 1, 1.2 g of 2-(4-ethoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl] -propionamide was isolated as colorless low melting sohd. Yield: 1.2 g, 57%; (HCI Salt); MS: 478.5 (M+H) + ; ! H NMR (300 MHz, CDC1 3 ): δ 0.9 (t, 3H), 1.1 (t, 6H), 1.3 (s,3H), 3.2 - 3.9 (m, 8 H), 3.9 (s, 3H), 4.3 (s, 2H), 6.5 - 7.8 (m, 8H), 10.8 (bs, IH). Example 26 (4E)-2-(4-Methoxy-benzenesulfonyl)-5,9-dimethyl-2-[4-(2-moφholin-4-yl-ethoxy) -benzyl]-deca-4,8-dienoic acid hydroxyamide To a stirred solution of (4-methoxy-benzenesulfonyl)-acetic acid ethyl ester (5.16 g, 20 mmol), geranyl bromide (4.2g, 20 mmol) and 18-Crown-6 (500 mg) in acetone (250 ml) was added K2CO3 (10 gms, excess) and the mixture refluxed foe 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 MgSO 4 , filtered and concentrated. The product obtained was purified by sihca-gel column chromatography, eluting with 30% ethy acetate: hexane. The product 2-(4-methoxy-benzenesulfonyl)-5,9-dimethyl- deca-4,8-dienoic acid ethyl ester was isolated as a colourless oil. Yield: 7.0 g, 89%. Following the procedure as outlined in example 12, 2-(4-Methoxy-benzenesulfonyl)-5,9- dimethyl-2-[4-(2-morpholin-4-yl-ethoxy)-benzyl]-deca-4,8-dienoic acid ethyl ester was prepared, starting from (1.0 g, 2.5 mmol) of 2-(4-methoxy-benzenesulfonyl)-5,9-dimethyl- deca-4,8-dienoic acid ethyl ester and 4-(2-moφholin-l-yl-ethoxy)-benzyl chloride (800 mg, 2.5 mmol). Yield 1.2 g, 76%; Brown oil; MS: 614 (M+H) + . Starting from 2-(4-Methoxy-benzenesulfonyl)-5,9-dimethyl-2-[4-(2-moφholin-4-yl-ethoxy)- benzyl]-deca-4,8-dienoic acid ethyl ester (2.0 gm, 3.2 mmol) 1.5 g (Yield: 80 %) of 2-(4- Methoxy-benzenesulfonyl)-5,9-dimethyl-2-[4-(2-moφholin-4-yl-ethoxy)-benzyl]-deca-4,8- dienoic acid was isolated as semi-solid by following the procedure as outlined in example 9. MS: 586.6 (M+H)+. Starting from 2-(4-Methoxy-benzenesulfonyl)-5,9-dimethyl-2-[4-(2-moφholin-4-yl-ethoxy)- benzyl]-deca-4,8-dienoic acid (1.0 g, 1.7 mmol) and following the procedure as outlined in example 1, 550 mg of (4E)-2-(4-Methoxy-benzenesulfonyl)-5,9-dimethyl-2-[4-(2-moφholin- 4-yl-ethoxy)-benzyl]-deca-4,8-dienoic acid hydroxyamide was isolated as pale yellow solid. Yield: 550 mg, 53%; mp 61°C (HCI Salt); MS: 638 (M+H) + . Example 27 2-[4-(2-Diemylaπώno-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-hexanoic acid hydroxyamide 2-[4-(2-DieΛylammo-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-hexanoic acid ethyl ester was prepared according to the general method as outlined 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-Diethylammc>-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-hexanoic acid was prepared starting from 2-[4-(2-diethylamino-ethoxy )- benzyl] -2-(4-methoxy-benzenesulfonyl)- hexanoic acid ethyl ester (8 g, 15.4 mmol) dissolved in methanol (200 ml) and 10 N NaOH (30 ml). The resulting mixture was worked up as outlined in example 1. Yield 3.88 g crude (51%); brown oil; MS: 492 (M+H) + . Starting from 2-[4-(2-diethylarnino-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-hexanoic acid (3.88 g, 7.89 mmol) and following the procedure as outlined in example 1, 800 mg of 2- [4-(2-diethylamino-ethoxy)-benzyl]-2-(4-methoxy-benzenesulfonyl)-hexanoic acid hydroxyamide was isolated as a yellow powder. Yield 20%; mp 67 °C; MS: 507.4 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 10.1 (s, IH) Example 28 N-Hydroxy-2-(4-n-butoxy-benzenesulfonyl)-2-methyl-3-[4-(2-piperidin-l-yl-ethoxy)-phenyl]- propionamide Following the procedure as outlined in example 12, 2-(4-n-butoxy-benzenesulfonyl)-2-methyl- 3-[4-(2-piperidin-l-yl-ethoxy)-phenyl]-propionic acid ethyl ester was prepared, starting from (3.1 g, 10 mmol) of 2-(4-n-butoxy-benzenesulfonyl)-propionic acid ethyl ester (Prepared from 2-(4-hydroxy-phenylsulfanyl)-propionic acid ethyl ester and n-butylbromide foUowing the procedure outlined in example 27 )the 4-(2-piperidin-l-yl-ethoxy)-benzyl chloride (3.0 g, 10.1 mmol). Yield 4.5 g, 84%; Brown oil; MS: 532.7 (M+H) + . Starting from 2-(4-n-butoxy-benzenesulfonyl)-2-methyl-3- [4-(2-piperidin- 1 -yl-ethoxy)- phenyl] -propionic acid ethyl ester (5.0 gm, 9.4 mmol) 4.2 g (Yield: 88 %) of 2-(4-n-butoxy- benzenesuhOnyl)-2-methyl-3-[4-(2-piperidin-l-yl-ethoxy)-phenyl]-propionic acid was isolated as colorless solid by following the procedure as outlined in example 9. MS: 504.6 (M+H) + Starting from 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 procedure as outlined in example 1, 1.3 g of 2-(4-n-butoxy-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine-l-yl-ethoxy)- phenyl] -propionamide was isolated as colorless solid. MP. 65 C, Yield: 1.3 g, 42%; (HCI Salt); MS: 478.5 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 0.9 (t, 3H), 1.2 (s, 3H), 1.3 - 1.9 (m,10H), 2.8 - 4.5 (m, 12 H), , 6.8 - 7.8 (m, 8H), 10.8 (bs, IH). Example 29 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-N,N-diethyl amino-ethoxy)- phenyl] -propionamide Following the procedure as outhned in example 12, 2-(4-methoxy-benzenesuh°onyl)-2-methyl- 3-[3-(2-N,N-diethyl amino-ethoxy)-phenyl]-propionic acid ethyl ester was prepared, starting from (5.0 g, 18 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and the 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 2-(4-methoxy-bεnzenesulfonyl)-2-methyl-3-[3-(2-N,N-diethyl amino-ethoxy)- phenyl]-propionic acid ethyl ester (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 was isolated as colorless semi-solid by following the procedure as outlined in example 9. MP: 78- 81; 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 as outlined 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 colorless low melting sohd. Yield: 1.5 g, 21%; (HCI Salt); MS: 450.5 (M+H)+; Η NMR (300 MHz, DMSO-d 6 ): δ 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 (bs, IH). Example 30 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-moφhoUn-l-yl-ethoxy)- phenyl] -propionamide Following the procedure as outhned in example 12, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-[3-(2-moφholin-l-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 the 3-(2- moφholin-l-yl-ethoxy)-benzyl chloride (6.0 g, 20 mmol). Yield 9.1 g, 93%; Brown oil; MS: 492 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-moφholin- 1 -yl-ethoxy)- phenyl]-propionic acid ethyl ester (10.0 gm, 20.3 mmol) 8.0 g (Yield: 86 %) of 2-(4-methoxy- benzenesulfonyl)-2-methyl-3-[3-(2-moφhohn-l-yl-ethoxy)-phenyl]-propionic acid was isolated as colorless crystals by following the procedure as outhned in example 9.; MS: 464.5 (M+H) + . Start g from 2-(4-methoxy-benzenesuUOnyl)-2-methyl-3-[3-(2-moφholin-l-yl-ethoxy)- phenyl] -propionic acid (4.55 g, 9.8 mmol) and following the procedure as outUned in example 1, 440 mg of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[3-(2-moφholi-l-yl-ethoxy)- phenyl] -propionamide was isolated as colorless sohd. Yield: 440 mg, 9%; mp 63°C; MS: 479.5 (M+H) + ; *H NMR (300 Mhz, DMSO-de): δ 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 (bs, IH). Example 31 6-(l,3-Dioxo-l,3-dihydro-isoindol-2-yl)-2-(4-methoxy-benzenesulfonyl)-2-methyl -hexanoic acid hydroxyamide Following the procedure as outlined in Example 9, 6-(l,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-phathalimido bromobutane (5.66 g, 20 mmol). Yield 8.4 g, 97%; Colorless oil; MS: 474 (M+H). Starting from 6-(l ,3-Dioxo- 1 ,3-dihydro-isoindol-2-yl)-2-(4-methoxy-benzenesulfonyl)-2- methyl-hexanoic acid ethyl ester (8.4 g, 17.7 mmol) 6.95 g (88%) of 6-(l,3-Dioxo-l,3- dihydro-isoindol-2-yl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-hexanoic acid was isolated as colorless oil by following the procedure as outlined in Example 9. MS: 446 (M-H)-. Starting from 6-(l ,3-Dioxo- 1 ,3-dihydro-isoindol-2-yl)-2-(4-methoxy-benzenesulfonyl)-2- methyl-hexanoic acid (4.9 g, 11 mmol) and following the procedure as outhned in Example 1, 3.1 g of 6-(l,3-Dioxo-l,3-dihydro-isoindol-2-yl)-2-(4-methoxy-benzenesulfonyl)-2-methyl -hexanoic acid hydroxyamide was isolated as a Ught brown solid; Yield: 46%; mp 146- 148 °C; MS: 461.2 (M+H) + ; *H NMR (300 MHz, DMSO-dβ): δ 1.55 (s, 3H), 1.61- 3.77 (m, 8H), 3.82 (s, 3H), 6.92-8.21 (m, 8H), 10.70 (bs,lH), 11.20 (bs,lH). Example 32 3-[4-(2-Diethylamino-ethoxy)-phenyl]-2-(4-furan-2-yl-benzenesulfonyl)-N-hydroxy-2- methyl-propionamide To a stirred solution of 4-bromo thiophenol (19.0 g, 100 mmol) and triethyl amine (15.0 g, 150 mmol) in chloroform (400 ml) 2-bromo ethylpropionate (18. 2 g, 100 mmol) was added drop wise. The reaction mixture was refluxed for 1 hr and cooled to room temperature. The reaction mixture was washed with water, dried and concentrated. 2-(4-bromo-phenylsulfanyl)- propionic acid ethyl ester was isolated as colorless oil. Yield: 28.0 g, 99%, MS: 290 (M+H). 2-(4-bromo-phenylsulfanyl)-propionic acid ethyl ester was converted to 2-(4-bromo- phenylsulfonyl)-propionic acid ethyl ester by following the procedure as described in example 9, paragraph 2. A mixture of 2-(4-bromo-phenylsulfonyl)-propionic acid ethyl ester (6.4 g, 20 mmol), 2- (tributyl stannyl)furan (7.5g, 21 mmol) and (Ph 3 P) 4 Pd (500 mg) was refluxed in degassed tolune (250 ml) for 8 hrs. At the end reaction mixture was filtered through Cehte and concentrated. The product was purified by sihca gel column chromatography by eluting it with 50% ethylacetate : hexane. Colorless oil. Yield: 5.9 g, 95%, MS: 309 (M+H). Following the procedure as outhned in example 12, 2-(4-(2-furanyl-benzenesulfonyl)-2- methyl-3-[4-(2-N,N-diethyl amino-ethoxy)-phenyl]-propionic acid ethyl ester was prepared, starting from (3.08 g, 10.0 mmol) of 2-(4-(2-furanyl-benzenesulfonyl)-propionic acid ethyl ester and the 4-(2-N,N-diethyi amino-ethoxy)-benzyl chloride (3.5 g, 12.2 mmol). Yield 5.0 g, 97%; Brown oil; MS: 514.6 (M+H)+. Starting from 2-(4-(2-furanyl-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl]-propionic acid ethyl ester (5.1 gm, 10.0 mmol) 3.8 g (Yield: 78 %) of 2-(4-(2- furanyl-r^nzenes fonyl)-2-methyl-3-[4-(2-N,N-ώethyl ammo-ethoxy)-phenyl]-propionic acid was isolated as colorless solid by following the procedure as outlined in example 9. MP: 58 C, MS: 486.5 (M+H) + . Starting from 2-(4-(2-furanyl-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl] -propionic acid (5.0 g, 10.3 mmol) and foUowing the procedure as outUned in example 1 , 1.2 g of 2-(4-ethoxy-benzenesulfonyl)-2-methyl-3-[4-(2-N,N-diethyl amino-ethoxy)- phenyl]-propionamide was isolated as colorless low melting sohd. Yield: 3.2 g, 62%; (HCI Salt); MS: 502 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.23 (t, 6H), 1.4 (s, 2H), 2.8 (q,4H), 3.0 (t, 2 H), 4.1 (t, 2H), 6.5 - 8.0 (m, 7H). Example 33 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-[4-(2-moφholin-4-yl-ethoxy)-benzyl]- butyramide 2-(4-Methoxy-phenylsulfanyl)-butyric acid ethyl ester was prepared according to the general method as outUned in example 9. Starting from ethyl 2-bromobutyrate (10.71 g, 55 mmol) and 4-methoxythiophenol (7 g, 50 mmol), 5.19 g (40%); clear oU; MS: 255.2 (M+H) + . 2-(4-Methoxy-benzenesulfonyl)-butyric acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 2-(4-methoxy-phenylsulfanyl)-butyric acid ethyl ester (5 g, 20 mmol). Yield 5.74 g (100%); clear oU; MS: 287.1 (M+H) + . Following the procedure as outlined in example 12, 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2- moφholin-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 the 4-[2- (chloromethyl-phenoxy)-ethyl]-moφholine (2.34 g, 6.7 mmol). Yield 5.7 g, 100%; Brown oil; MS: 506.4 (M+H) + . Startmg from 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2-moφhohn-4-yl-ethoxy)-benzyl]-butyric acid ethyl ester (5.54 gm, 11 mmol) 2.9 g (Yield: 55 %) of 2-(4-Methoxy-benzenesulfonyl)-2- [4-(2-moφhohn-4-yl-ethoxy)-benzyl]-butyric acid was isolated as colorless semi-solid by following the procedure as outlined in example 9. MS: 478.3 (M+H) + . Startmg from 2-(4-methoxy-tenzenesulfonyl)-2-[4-(2-rrκ)φhohn-4-yl-ethoxy)-benzyl]-butyric acid (2.6 g, 5.4 mmol) and following the procedure as outhned in example 1, 510 mg of N- hydroxy-2-(4-methoxy-rjenzenesulfonyl)-2-[4-(2-moφhoUn-4-yl-ethoxy)-benzyl]-butyramide was isolated as a brown solid. Yield 2%; mp 51 °C; MS: 493.3 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.90 (t, J = 7.2 Hz, 3H), 1.69-1.96 (m, 4 H), 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, IH), 10.8 (s, IH). Example 34 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-2-[4-(2-piperidin-l-yl-ethoxy)-benzyl]- butyramide Following the procedure as outlined in example 12, 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2- piperidin-l-yl-ethoxy)-benzyl] -butyric acid ethyl ester was prepared, starting from (1.0 g, 3.33 mmol) of 2-(4-methoxy-benzenesuh c onyl)-butyric acid ethyl ester and the 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-l-yl- ethoxy )-benzyl] -butyric acid ethyl ester (3.7 gm, 7.3 mmol) 2.2 g (Yield: 63 %) of 2-(4-Methoxy-benzenesulfonyl)-2- [4-(2-piperidin-l-yl- ethoxy)-benzyl]-butyric acid was isolated as colorless semi-soUd by following the procedure as outlined in example 9. MS: 476 (M+H) + . Starting from 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2-piperidin-l-yl- ethoxy )-benzyl] -butyric acid (2.2 g, 4.63 mmol) and following the procedure as outlined in example 1, 360 mg of N- Hydroxy-2-(4-rrιethoxy-benzenesuhonyl)-2-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-butyrarmde was isolated as a brown solid. Yield 16%; mp 75 °C; MS: 491.3 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.90 (t, J = 7.1 Hz, 3H), 1.36-1.96 (m, 4 H), 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, IH), 10.8 (s, IH) Example 35 2-(4-Methoxy-benzenesuh c bnyl)-2-[4-(2-moφhohn-4-yl-ethoxy)-benzyl]-pentanoic acid hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-pentanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from ethyl 2-bromovalerate (8.23 g, 39.3 mmol) and 4-methoxythiophenol (5 g, 35.7 mmol), 10.46 g (100%); clear oU; MS: 269 (M+H) + . 2-(4-Methoxy-benzenesulfonyl)-pentanoic acid ethyl ester was prepared according to the general method as outhned in example 9. Starting from 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 as outlined in example 12, 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2- morphohn-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 the 4-[2- (chloromethyl-phenoxy)-ethyl]-moφholine (3.45 g, 11.9 mmol). Yield 3.08 g, 62%; Brown oil; MS: 520.4 (M+H)+. Startmg from 2-(4-Methoxy-benzenesulfonyl)-2-[4-(2-moφholin-4-yl-ethoxy)-benzyl]- pentanoic acid ethyl ester (2.73 gm, 5.27 mmol) 1.45 g (Yield: 56 %) of 2-(4-Methoxy- benzenesulfonyl)-2-[4-(2-moφhohn-4-yl-ethoxy)-benzyl]-pentanoic acid was isolated as colorless semi-solid by following the procedure as outlined in example 9. MS: 492.3 (M+H)+. Starting from 2-(4-methoxy-benzenesulfonyl)-2-[4-(2-moφhoUn-4-yl-ethoxy)-benzyl]- pentanoic acid (1.01 g, 2.05 mmol) and following the procedure as outlined in example 1, 190 mg of 2-(4-methoxy-benzenesulfonyl)-2-[4-(2-moφhoUn-4-yl-ethoxy)-benzyl]-pentanoic acid hydroxyamide was isolated as a brown solid. Yield 18%; mp 101 °C; MS: 507.4 (M+H) + ; ! H NMR (300 MHz, DMSO-d 6 ): δ 0.71 (t, J = 7 Hz, 3H), 1.58-1.82 (m, 4 H), 3.12-3.98 (m, 12H), 3.87 (s, 3H), 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, IH). Example 36 2-[4-(2-Azepan-l-yl-ethoxy)-benzyl]-2-(4-Methoxy-benzenesulfonyl)-octanoic acid hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 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)\ 2-(4-Methoxy-benzenesulfonyl)-octanoic acid ethyl ester was prepared according to the general method as outUned in example 9. Starting from 2-(4-methoxy-phenylsulfanyl)-octanoic acid ethyl ester (4.0 g, 13.6 mmol). Yield 3.7 g (83%); clear oil; MS: 343.3 (M+H) + . Following the procedure as outlined in example 12, 2-[4-(2-Azepan-l-yl-ethoxy)-bεnzyl]-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 the l-[2-(4- chloromethyl-phenoxy)-ethyl]-azepane (1.73 g, 6.0 mmol). Yield 4.86 g, 99%; Brown oil; MS: 574.5 (M+H) + . Starting from 2-[4-(2-Azepan-l-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-Azepan- 1 -yl-ethoxy)- benzyl]-2-(4-Methoxy-benzenesulfonyl)-octanoic acid was isolated as colorless semi-solid by following the procedure as outhned in example 9. MS: 551 (M+H) + . Starting from 2-[4-(2-Azepan- 1 -yl-ethoxy)-benzyl]-2-(4-Methoxy-benzenesulfonyl)-octanoic acid (1.09 g, 2.0 mmol) and following the procedure as outlined in example 1, 300 mg of 2-[4- (2-Azepan- l-yl-ethoxy)-benzyl]-2-(4-Methoxy-benzenesulfonyl)-octanoic acid hydroxyamide was isolated as a yellow solid. Yield 27%; mp 65 °C; MS: 561.6 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.81 (t, J = 6.6 Hz, 3H), 1.08-1.82 (m,14H), 3.13-3.51 (m, 12H), 3.87 (s, 3H), 4.33 (t, 2H) 6.88 (d, J = 8.7 Hz, 2H),7.14 (m,4H), 7.7 (d, J=9Hz, 2H), 9.06 (s, IH), 10.28 (s, IH). Example 37 2-(4-Methoxy-benzenesulfanyl)-octanoic acid hydroxyamide 2-(4-Methoxy-phenylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 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) + . 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 colorless semi-solid by following the procedure as outlined in example 9. MS: 283 (M+H) + . Starting from 2-(4-Methoxy-benzenesulfanyl)-octanoic acid (4.25 g, 16 mmol) and following the procedure as outlined in example 1, 3.64 g of 2-(4-Methoxy-benzenesulfanyl)-octanoic acid hydroxyamide was isolated as colorless solid. Yield: 76%, MP: 90 C; MS: 298.2 (M+H). Example 38 2-(4-Fluoro-phenylsulfanyl)-octanoic acid hydroxyamide 2-(4-Fluoro-phenylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from ethyl 2-bromooctanoate (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 2-(4-fluoro-benzenesulfanyl)-octanoic acid ethyl ester (3.1 gm, 10 mmol) 2.89 g (Yield: 100 %) of 2-(4-fluoro-benzenesulfanyl)-octanoic acid was isolated as colorless semi- solid by foUowing the procedure as outlined in example 9. MS: 268.9 (M+H) + . Starting from 2-(4-fluoro-benzenesulfanyl)-octanoic acid (2.49 g, 9.2 mmol) and foUowing the procedure as outlined in example 1, 2.72 g of 2-(4-fluoro-benzenesulfanyl)-octanoic acid hydroxyamide was isolated as colorless solid. Yield: 99%, MP: 58 C; MS: 284(M-H). Example 39 2-(l-methyl-lH-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide 2- (1 -methyl- lH-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from ethyl 2-bromooctanoate (12.1 g, 48 mmol) and l-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oh; MS: 285 (M+H)\ Starting from 2-(l -methyl- lH-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester (12 gm, 42.2 mmol) 10.2 g (Yield: 95 %) of 2-(l -methyl- lH-imidazol-2-ylsulfanyl)-octanoic acid was isolated as colorless sohd by following the procedure as outlined in example 9. MP: 95 C, MS: 257.1 (M+H) + . Starting from 2- (1 -methyl- lH-imidazol-2-ylsulfanyl)-octanoic acid (7.84 g, 30.6 mmol) and following the procedure as outlined in example 1, 2.77 g of 2-(l -methyl- lH-imidazol-2- ylsulfanyl)-octanoic acid hydroxyamide was isolated as colorless solid. Yield: 33%, MP: 125 C; MS: 272.2 (M+H). Example 40 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-3-naphthalen-2-yl-propionamide Following the procedure as outlined in Example 9, 2-(4-methoxy-benzensulfonyl)-3- naphthalen-2-yl-propionic acid ethyl ester was prepared, 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-propionoic acid ethyl ester (3.7 g, 9 mmol) 3.3g (96%) of 2-(4-methoxy-benzenesulfonyl)-3-naphthalen-2-yl-propionoic acid was isolated as colorless oU by following the procedure as outlined in Example 9. MS: 369.1 (M-H)-. Starting from 2-(4-methoxy-benzenesulfonyl)-3-naphthalen-2-yl-propionic acid (2.2 g, 5.9 mmol) and foUowing the procedure as outhned in Example 1, 820 mg of N-hydroxy-2-(4- methoxy-benzenesulfonyl)-3-naphthalen-2-yl-propionamide was isolated as a light brown solid; Yield: 36%; mp 161- 163 °C; MS: 385.9 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 3.32 (d, J=7.0 Hz, IH), 3.69 (d, J= 7.0 Hz, IH), 3.82 (s, 3H), 5.02 (s, IH), 6.92-7.89 (m, 11H). Example 41 N-Hydroxy-2-(4-methoxy-phenylmethanesulfonyl)-2-methyl-3-phenyl propionic acid hydroxamide A mixture of 4-methoxybenzyl mercaptan ( 7.0g, 45 mmol), ethyl 2-bromopropionate (8.2 g, 46 mmol) and powdered oven dried potassium carbonate ( lOg, 72 mmol) in 150 mL of acetone was heated at reflux for 18 h. The mixture was cooled, filtered, and the filtrate concentrated. The residue was taken up in 150 mL of methylene chloride, washed with water (150 mL), dried over anhydrous sodium sulfate and evaporated to yield 12 g (99%); colorless liquid; MS 255.1 (M+H). This product is used without further purification. To an ice cold (5 °C) solution of 2-(4-methoxy-phenylmethanesulfanyl)-propionic acid ethyl ester (5.7g, 21 mmol) in 100 mL CH 2 CI 2 was added portionwise (7.2g, 40 mmol) of m- chloroperbenzoic acid and the mixture was stirred for 1 h. The reaction was diluted with hexanes (500 mL) and stirred at 25 C° for 30 minute at room temperature. The mixture was filtered and the organic layer treated with saturated aqueous sodium bisulfite (200 mL). The hexanes solution containing the product was washed with water, dried (Na 2 SO 4 ) and concentrated. Yield 5.5g (91%); colorless oil; MS 287.1 (M+H) + . Following the procedure as outlined in Example 9, 2-(4-Methoxy-phenylmethanesulfonyl)-2- methyl-3-phenyl-propionic acid ethyl ester was prepared, starting from 2-(4-Methoxy- phenylmethanesulfonyl)-propionic acid ethyl ester (2g, 7 mmol) and benzyl bromide (1.3g, 7.7 mmol). Yield 3.0 g, 100%; Low melting solid; MS: 377 (M+H) + . 2-(4-Methoxy-phenylmethanesulfonyl)-2-methyl-3-phenyl-propionic acid was prepared starting from 2-(4-Methoxy-phenylmethanesuhOnyl)-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 outlined in Example 9. Yield 930 mg, 31%. Colorless sohd, mp: 106-108 C;. MS: 347 (M-H)+. Starting from 2-(4-Methoxy-phenylmethanesulfonyl)-2-methyl-3-phenyl-propionic acid (2.7 g, 7.0 mmol) and foUowing the procedure as outlined in example 1, 266 mg of N-Hydroxy-2-(4- πιethoxy-phenylmethanesulfonyl)-2-methyl-3-phenyl propionic acid hydroxamide was isolated as light colorless solid; Yield: 10%; mp 58-59 °C; MS: 364.2 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 1.28 (s, 3H), 2.84-2.88 (d, IH), 3.75 (s, 3H), 3.81-3.86 (d, IH), 4.59-4.63 (d, IH), 4.69-4.74 (d, IH), 6.94-6.98 (d, 2H), 7.19 (m, 2H), 7.29-7.33 (d, 4H), 9.24 (s, IH), 10.88 (s, IH). Example 42 5-Methyl-2-(3-methyl-but-2-enyl)-2-(toluene-4-sulfonyl)-hex-4-enoic acid hydroxyamide 5-Methyl-2-(3-methyl-but-2-enyl)-2-(toluene-4-sulfonyl-hex-4-enoic acid ethyl ester was prepared according to general method as outlined in example 9. Starting from ethyl α-(p- tolylsulfonyl)acetate (2.9g, 10.9 mmol and 4-bromo-2-methyl butene (3.42g, 23 mmol). Yield 4.6g ; tan oil; 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 general method as outlined in example 9. Starting from 5-methyl-2-(3-methyl-but- 2-enyl)-2-(toluene-4-sulfonyl-hex-4-enoic acid ethyl ester (4.5g, 11 mmol), ethanol (15 mL) and 10 N sodium hydroxide. Starting from 5-methyl-2-(3-methyl-but-2-enyl)-2-(toluene-4-suh c onyl)-hex-4-enoic acid (4.1 g, 11 mmol) and following the procedure as oudined in example 1, 1.07 g of 5-Methyl-2-(3- methyl-but-2-enyl)-2-(toluene-4-sulfonyl)-hex-4-enoic acid hydroxyamide was isolated as colorless sohd; Yield: 30%; mp 108-110 °C; MS: 366.2 (M+H)+; Η NMR (300 MHz, DMSO-d 6 : δl.49 (s, 6H), 1.62 (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, IH), 10.80 (s, IH). Example 43 2-Methyl-2-(2-methyl-furan-3-suh c onyl)-3-phenyl-propionic acid hydroxamide 2-Methyl-2-(2-methyl-furan-3-sulfonyl)-3-phenyl-propionic acid ethyl ester (Prepared from 3- mercapto-2-methylfuran) was prepared according to the general method as outlined in example 9. Starting from 2-(2-methyl-furan-3-ylsulfanyl)-propionic acid ethyl ester (2.9g, 11.9 mmol), benzyl bromide (2.22g, 13 mmol) and potassium carbonate (lOg) in acetone (75 mL). Yield (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 as outhned in example 9. Starting from 2-(2-rnethyl-furan-3-ylsulfanyl)- propionic acid ethyl ester (4.8g, 14.3 mmol), dissolved in ethanol (25 mL and 10 N sodium hydroxide (10 mL). Yield 3.7g (84 %), , white solid, MS 307.4 (M-H). Starting from 2-Methyl-2-(2-methyl-furan-3-sulfonyl)-3-phenyl-propionic acid (3.58 g, 12 mmol) and following the procedure as outhned in example 1, 1.078 g of 2-Methyl-2-(2- methyl-furan-3-sulfonyl)-3-phenyl-propionic acid hydroxyamide was isolated as orange color solid; Yield: 29%; mp 68-70 °C; MS: 324 (M+H) + ; Η NMR (300 MHz, DMSO-d*): δ 1.27 (s, 3H), 2.81-2.86 (d, IH), 3.33 (s, 3H), 3.61-3.66 (d, IH), 6.66 (s, IH), 7.19-7.25 (m, 5H), 7.76 (s, IH), 9.09 (s, IH), 10.81 (s, IH) Example 44 2-Methyl-2-(2-memyl-furan-3-suhOnyl)-3-[4-(2-piperidin-l-yl-ethoxy)-phenyl]-propionic acid hydroxamide 2-Memyl-2-(2-methyl-furan-3-sulfonyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 2-(2-methyl-furan-3-sulfonyl)-propionic acid ethyl ester (2.4g, 9.8 mmol) and l-[2-(4- chloromethylphenoxy)-ethyl]-piperidine (2.96g, 10.7 mmol); Yield 2.4g (92%); amber oh; MS 464.2 (M+H) + . 2-Methyl-2-(2-methyl-furan-3-sulfonyl)-3-[4-(2-piperimn-l-yl-ethoxy)-phenyl]-propionic acid was prepared according to the general method as outUned in example 1. Starting from 2- methyl-2-(2-methyl-furan-3-sulfonyl)-3-[4-(2-piperidin- l-yl-ethoxy)-phenyl] -propionic acid ethyl ester (2.01g, 4.5 mmol), dissolved in ethanol (20 mL) and 10 N sodium hydroxide (10 mL). The resulting mixture was worked up as outhne in example 9. Yield 2.03g; amber crystals mp 66-68 °C; MS 434 (M-H). Starting from 2-Methyl-2-(2-methyl-f uran-3-sulfonyl)-3-[4-(2-piperidin- 1 -yl-ethoxy)-phenyl]- propionic acid (2.03 g, 6.0 mmol) and foUowing the procedure as outlined in example 1, 1.36 g of 2-Methyl-2-(2-methyl-furan-3-sulfonyl)-3-[4-(2-piperidin- 1 -yl-ethoxy)-phenyl] -propionic acid hydroxyamide was isolated as amber color sohd; Yield: 32%; mp 115-117 °C; MS: 451.1 (M+H) + ; Η NMR (300 MHz, DMSO-cLJ: δ 1.15-1.22 (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, IH), 6.87-6.90 (d, 2H), 7.12- 7.17 (d, 2H), 10.35 (s, IH), 10.60 (s, IH), 11.70 (s, IH). Example 45 2-Methyl-3-[4-(2-piperidm-l-yl-ethoxy)-phenyl-2-(thiophene-2-sulfonyl)-propionic acid hydroxamide 2-Methyl-3-[4-(2-piperidm-l-yl-ethoxy)-phenyl2-(thiophene-2-sulfonyl)-propionic acid ethyl ester was prepared acording to the general method as outhned in example 9. Starting from 2- (thiophene-2-sulfonyl)-propionic acid ethyl ester( prepared from 2-mercaptothiophene and 2- bromopropionic acid ethylester) (4.4g, 17.7 mmol) and l-[2-(4-chloromethylphenoxy)-ethyl]- piperidine (5.3g, 19.5 mmol); Yield (96%); semi-solid; MS 466. 2-Methyl-3-[4-(2-piperidin- 1 -yl-ethoxy)-phenyl-2-(thiophene-2-sulfonyl)-propionic acid was prepared acording to the general method as outhned in example 9. Starting from 2-methyl-3- [4-(2-piperidin-l-yl-ethoxy)-phenyl-2-sulfonyl)-propionic acid ethyl ester (9.8g, 20 mmol), dissolved in ethanol (20 mL) and 10 N sodium hydroxide (20 mL). The resulting mixture was worked up as outline in example 1. Yield 4.5g (49 %); white sohd mp 170-172 °C; MS 436.3 (M-H). Starting from 2-Methyl-3-[4-(2-piperidin- l-yl-ethoxy)-phenyl-2-(thiophene-2-sulfonyl)- propionic acid (3.6 g, 8.0 mmol) and following the procedure as outhned in example 1, 345 mg of 2-Memyl-3-[4-(2-piperidin-l-yl-ethoxy)-phenyl-2-(thiophene-2-sulfonyl)-propionic acid hydroxyamide was isolated as light colorless soUd; Yield: 10 %; mp 115-118 °C; MS: 451.2 (M+H)+; Η NMR (300 MHz, DMSO-d 6 ): δl.29 (s, 3H), 1.66-1.78 (m, 6H), 2.81-2.86 (d, IH), 2.96-3.99 (m, 4H), 3.39-3.47 (m, 2H), 3.51-3.59 (d, IH), 4.32 (m, 2H),6.72-6.74 (d IH), 6.87-6.96 (d, 2H), 7.01-7.20 (m, 3H), 7.31-7.33 (m, IH), 7.69-7.72 (m, IH), 7.83- 7.84 (m, IH), 8.07-8.08 (dd, IH), 8.17 (dd, IH), 9.0 (s, IH) 10.0 (s, IH), 10.78 (s, IH). Example 46 2-(octane- l-sulfonyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]propionic acid hydroxamide 5 2-(Octane- l-sulfonyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid ethyl ester was prepared according to the general method as outlined in example 9 . Starting from 2-(octane-l- sulfonyl)-propionic acid ethyl ester (5.0g, 18 mmol) and l-[2-(4-chloromethylphenoxy)-efhyl]- piperidine (5.6g, 19.7 mmol); Yield 8.9g (96%); amber oil, MS 495. l o 2-(Octane- l-sulfonyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid was prepared according to the general method as outlined in example 9. Starting from 2-(octane-l-sulfonyl)- 3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid ethyl ester (8.9g, 18 mmol), ethanol (25 mL) and 10 N sodium hydroxide (25 mL). Yield 6.0g (72 %). 15 Starting from 2-(Octane-l-suh c onyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid (3.6 g, 7.7 mmol) and foUowing the procedure as outhned in example 1, 3.3 g of 2-(Octane-l- sulfonyl)-3-[4-(2-piperidin-yl-ethoxy)-phenyl]-propionic acid hydroxyamide was isolated as tan solid; Yield: 89%; mp 69-70 °C; MS: 483.2 (M+H)+; Η NMR (300 MHz, DMSO-c .): δ .687 (t, 3H), 1.27-1.69 (m, 15H), 2.71-2.75 (d, IH), 3.51 (s, 3H), 3.65-3.69 (d, IH), 6.86- 20 6.89 (d, 2H), 7.08-7.11 (d, 2H), 9.16 (s, IH), 10.70 (s, IH). Example 47 3-Biphenyl-4-yl-2-methyl-2-(l-methyl-lH-imidazole-2-suh c onyl)-propionic acid hydroxyamide 25 3-Biphenyl-4-yl-2-methyl-2-(l -methyl- lH-imidazole-2-sulfonyl)-propionic acid ethyl ester was prepared according to the general method as outhned in example 9. Starting from 2- methyl-(l -methyl- lH-imidazolesulfonyl)-propionic acid ethyl ester Prepared from (l-Methyl-2- mercapto imidazole and 2-bromo ethyl propionate) (3.0g, 12.2 mmol) and 4- 30 chloromethylbiphenyl (2.97g, 15 mmol). Yield 5.0g ( 99 %); low melting sohd; MS 413 (M+H)+. 3-Biphenyl-4-yl-2-methyl-2-(l-methyl-lH-imidazole-2-sulfonyl)-propionic acid was prepared according to the general method as outhned in example 9. Starting from 3-biphenyl-4-yl-2- 35 methyl2-(l -methyl- lH-imidazole-2-sulfonyl)-propionic acid ethyl ester (5.0g, 11.9 mmol), ethanol (15 mL) and 10 N sodium hydroxide (10 mL). Yield 2.8g (61 %); brown solid mp 119-122 °C; MS 385.2 (M+H). Starting from 3-Biphenyl-4-yl-2-me yl-2-(l-methyl-lH-imidazole-2-sulfonyl)-propionic acid (2.8 g, 7.0 mmol) and following the procedure as outhned in example 1, 112 mg of 3- Biphenyl-4-yl-2-memyl-2-(l-methyl-lH-imidazole-2-sulfonyl)-propionic acid hydroxyamide was isolated as tan colored solid; Yield: 4%; mp 112 °C; MS: 399.0 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.911 (s, 3H), 3.3 (s, 3H), 3.5 (d, IH), 4.2 (d, IH), 6.8 (d, IH), 6.9 (d, IH), 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-suh c onyl)-propionic acid hydroxamide 2-Methyl-3-phenyl-2-(thiophene-2-sulfonyl)-propionic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 2-(thiophen-2-sulfonyl)- propionic acid ethyl ester (3.0g, 12 mmol) and benzyl bromide (2.48g, 15 mmol). Yield 5.2 g ( %); tan oil; MS 339.1 (M+H). 2-Methyl-3-phenyl-2-(thiophene-2-sulfonyl)-propionic acid was prepared according to the general method as outlined in example 9. Starting from 2-methyl-3-phenyl-2-(thiophen-2- sulfonyl)-propionic acid ethyl ester (5.0 g, 15 mmol), ethanol (30 mL) and 10 N sodium hydroxide (10 mL). Yield 5.6g MS 310.0 (M+H). Starting from 2-Methyl-3-phenyl-2-(thiophene-2-sulfonyl)-propionic acid (5.0 g, 16 mmol) and following the procedure as outlined in example 1, 1.8 g of 2-Methyl-3-phenyl-2- (thiophene-2-sulfonyl)-propionic acid hydroxyamide was isolated as colorless sohd; Yield: 40%; mp 116-117 °C; MS: 325.9 (M+H)+; Η NMR (300 MHz, DMSO-d 6 ): δ 1.29 (s, 3H), 3.33 (d, IH), 3.69 (d IH), 7.18-7.30 (m, 5H), 7.74 (m, IH), 8.22 (m, IH), 9.13 (s, IH), 10.80 (s, IH). Example 49 2-[8-(l-carboxy-ethanesulfonyl)-octane-l-sulfonyl]-propionic acid hydroxyamide 2-[8-(l-Carboxyl-ethanesulfonyl)-octane-l-sulfonyl]-propionic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from 2-[8-(l- ethoxycarbonyl-ethylsulfanyl)-octylsulfanyl] -propionic acid ethyl ester (10.2g, 26 mmol) and sodium peroxymonopersulfate (64g, 104 mmol). Yield 9.87g (86%); colorless liquid; MS 442.9 (M+H). 2-[8-(l-Carboxy-ethanesulfonyl)-octane-l-suhOnyl]-propionic acid was prepared according to general method as outline in example 1. Starting from 2-[8-(l-carboxy-ethanesulfonyl)-octane- 1 -sulfonyl] -propionic acid ethyl ester (3.0g, 6.8 mmol), ethanol (15 mL) and 10 N sodium hydroxide (15 mL). Yield 2.7g (98 %); white solid mp 99-102 °C; MS 387 (M+NH3) + . Starting from 2-[8-(l-Carboxy-ethanesulfonyl)-octane-l-sulfonyl]-propionic acid (2.5 g, 6.5 mmol) and following the procedure as outhned in example 1, 641 mg of 2-[8-(l-Carboxy- ethanesulfonyl)-octane-l -sulfonyl] -propionic acid hydroxyamidewas isolated as amber coloured oil.; Yield: 23%; MS: 434.0 (M+NH4)+; Η NMR (300 MHz, DMSO-d 6 ): δ 1.27- 3.23 (m, 22H), 3.33 (m, 2H), 8.9 (s, IH), 9.28 (s, IH). Example 50 2-(4-Bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine-l-yl-ethoxy)-phenyl]-propionic acid hydroxamide 2-(4-Bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine-l-yl-ethoxy)-phenyl]-propionic acid ethyl ester was prepared according to general method as outlined in example 9. Starting from ethyl α-(4-bromophenyl-sulfonyl) acetate (5.0g, 16 mmol) and l-[2-(4- chloromethylphenoxy)-ethyl]-piperidine (4.97g, 16 mmol). Yield 6.1g (71 %); tan oU; MS 541.1 (M+H) + . 2-(4-Bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine-l-yl-ethoxy)-phenyl]-propionic acid was prepared according to general method as outlined in example 9. Starting from2-(4- bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine- 1 -yl-ethoxy)-phenyl]-propionic acid ethyl ester (6.5g, 20 mmol), ethanol (30 mL) and 10 N sodium hydroxide (15 mL). Yield 6.3g (100 %); yellow solid mp 125-127 °C; MS 512.5 (M+H) + . Starring from 2-(4-Bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine- 1 -yl-ethoxy)-phenyl]- propionic acid (6.1 g, 612 mmol) and foUowing the procedure as outlined in example 1, 1.07 g of 2-(4-Bromo-benzenesulfonyl)-2-methyl-3-[4-(2-piperidine-l-yl-ethoxy)-phenyl]-propionic acid hydroxyamide was isolated as Ught yellow solid; Yield: 17%; MS: 525.4 (M+H) + . Example 51 3-(4-Brorno-phenyl)-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide Following the procedure as outhned in Example 9, 3-(4-bromo-phenyl)-2-(4-methoxy- benzensulfonyl)-2-methyl-propionic acid ethyl ester was prepared, starting from (3.0 g, 11 mmol) 2-(4-methoxy-benzenesuhOnyl)-propionic acid ethyl ester and 4-bromobenzyl bromide (3.0 g, 12 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 3-(4-bromo-phenyl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid ethyl ester (4.0 g, 9.0 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 3.0 g, 78%. Low melting soUd. MS: 413 (M+H) + . Starting from 3-(4-bromo-phenyl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid (2.7 g, 6.5 mmol) and foUowing the procedure as outlined in example 1, 2.26 g of 3-(4- bromophenyl)-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide was isolated as hght colorless solid; Yield: 81%; mp 86-88 °C; MS: 429.8 (M+H)+; Η NMR (300 MHz, CDC1 3 ): δ 1.42 (s,3H), 1.77 (bs, IH), 3.26 (d, J=7.0 Hz, IH), 3.68 (d, J= 7.0 Hz, IH), 3.85 (s, 3H), 7.01 -7.76 (m,8H), 9.71 - 9.88 (bs, IH). Example 52 N-hydroxy-2-(4-n ethoxy-benzenesulfonyl)-2-methyl-3-naphthalen-2-yl-propionarnide Following the procedure as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-naphthalen-2-yl-propionic acid ethyl ester was prepared, starting from (5.4 g, 20 mmol) 2- (4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and 2-bromomethyl 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) 4.2g (98%) of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-naphthalen- 2-yl-propionic acid was isolated as colorless crystals by following the procedure as outUned in Example 9. mpl44-146 °C; MS: 384.9 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-naphthalen-2-yl-propionic acid (2.4 g, 6.2 mmol) and following the procedure as outlined in Example 1, 1.6 g of N-hydroxy-2-(4- methoxy-benzenesuUOnyl)-2-methyl-3-naphthalen-2-yl-propionamide was isolated as a light colorless solid; Yield: 64%; mp 185 -187 °C; MS: 400.2 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.56 (s,3H), 3.28 (d, J= 8.0 Hz, IH), 3.81 (d, J=8Hz,lH), 3.93 (s,3H), 4.88 (bs, IH), 7.02 - 7.92 (m, 11H). Example 53 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-3-methyl-butyramide 2-(4-Methoxy-phenylsuh c anyl)-3-methyl-butyric acid ethyl ester was prepared according to the general method as outhned in Example 1. Starting from ethyl 2-bromo-3-methyl-butanoate (20.9 g, 100 mmol) and 4-methoxybenzenethiol (14.0 g, 100 mmol), 30 g of 2-(4-methoxy- phenylsulfanyl)-3-methyl-butyric acid ethyl ester was isolated. Yield 99%; Light yellow oU; MS: 269 (M+H)+. Starting from 2-(4-methoxy-phenylsulfanyl)-3-methyl-butyric acid ethyl ester. (2.68 g 10 mmol) and following the procedure as outUned in Example 9 for oxidation, 3 g of 2-(4- methoxy-benzenesulfonyl)-3-methyl-butyric acid ethyl ester was isolated as a colorless solid, yield: 99%; mp 53 °C; MS: 273 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-3-methyl-butyric acid ethyl ester (3 g, 10 mmol) 2.7 g (96%) of 2-(4-methoxy-benzenesulfonyl)-3-methyl-butyric acid was isolated as a colorless solid by foUowing the procedure as outlined in Example 9. Mp 96 °C; MS: 273 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-3-methyl-butyric acid (2.0 g, 7.34 mmol) and following the procedure as outUned in Example 9, 590 mg of N-hydroxy-2-(4-methoxy- benzenesulfonyl)-3-methyl-butyramide was isolated as a colorless sohd. Mp 220 °C; Yield 28%; MS: 288 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.88 (d, J = 6.7 Hz, 3H), 1.07 (d, J = 6.7 Hz, 3H), 2.09-2.20 (bs, IH), 3.53 (d, J = 9, IH), 7.12-7.17 (m, 2H), 7.74-7.79 (m, 2H). ' Example 54 l-(4-Methoxy-benzenesuh c Onyl)-cyclopentanecarboxyUc acid hydroxyamide Following the procedure as outlined in Example 9, l-(4-methoxy-benzenesulfonyl)- cyclopentanecarboxylic acid ethyl ester was prepared, starting from (3.0 g, 11.6 mmol) of 2- (4-methoxy-benzenesulfonyl)-acetic acid ethyl ester and 1,4-dibromobutane ( 2.4 g, 7.6 mmol). Yield 2.4 g, 78%; Colorless sohd, mp 86-88 °C; MS: 313 (M+H) + . l-(4-Methoxy-benzenesulfonyl)-cyclopentanecarboxylic acid was prepared starting from l-(4-methoxy-benzenesulfonyl)-cyclopentanecarboxylic acid ethyl ester (2.2 g, 7.0 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 1.66 g, 83%. Colorless solid; mp 112-115 °C; MS: 285 (M+H) + . Starting from l-(4-methoxy-benzenesutfonyl)-cyclopentanecarboxylic acid (442 mg, 1.5 mmol) and following the procedure as outlined in Example 1, 410 mg of l-(4- methoxy-benzenesulfonyl)cyclopentanecarboxylic acid hydroxyamide was isolated as a colorless solid, mp 89-91 °C; Yield 88%; MS: 300 (M+H) + ;iH NMR (300 MHz, CDC1 3 ): δ 1.65-1.82 (m, 4H), 2.17-2.42 (m, 4H), 3.87 (s, 3H), 7.0 (d, J= 8Hz, 2H), 7.7 (bs, IH), 7.72 (d, J=8 Hz, 2H), 9.73 (bs, IH). Example 55 3-(2-Bromo-phenyl)-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionamide Following the procedure as outhned in Example 9, 3-(2-bromo-phenyl)-2-(4-methoxy- benzenesulfonyl)-2-methyl-propionic acid ethyl ester was prepared, starting from (2.0 g, 7.3 mmol) of 2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester and 2-(bromo)benzyl bromide (2.0 g, 8 mmol). Yield 3.1 g, 87%; Colorless oil; MS: 441 (M+H) + . 3-(2-Bromo-phenyl)-2-(4-methoxy-bεnzenesulfonyl)-2-methyl-propionic acid was prepared starting from 3-(2-bromo-phenyl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid ethyl ester (3.0 g, 68 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 1.7 g, 63%. Waxy solid; MS: 414 (M+H)+. Starting from 3-(2-bromo-phenyl)-2-(4-methoxy-benzenesulfonyl)-2-methyl-propionic acid (470 mg, 1.1 mmol) and following the procedure as outlined in Example 9, 380 mg of 3-(2- bromo-phenyl)-N-hyd^oxy-2-(4-rnethoxy-benzenesulfonyl)-2-methyl-propionamide was isolated as a colorless solid, mp 93-96 °C; Yield 77%; MS: 429 (M+H) + ; W NMR (300 MHz, CDC1 3 ): δ 1.3 (s, 3H), 3.32 (d, J=7.0 Hz, IH), 3.69 (d, J= 7.0 Hz, IH), 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 as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 5-phenyl-pent-4-enoic acid ethyl ester was prepared, starting from (3.0 g, 11 mmol) 2-(4- methoxy-benzenesulfonyl)-propionic acid ethyl ester and cinnamyl bromide (2.1 g, 11 mmol). Yield 3.51 g, 82%; Colorless oil; MS: 389 (M+H)+. 2-(4-Methoxy-benzenesulfonyl)-2-methyl-5-phenyl-pent-4-enoic acid was prepared starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-5-phenyl-pent-4-enoic acid ethyl ester (3.0 g, 11 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 1.9 g, 68%; yellowish oU; 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 as outlined in Example 1, 420 mg of 2-(4-methoxy- benzenesulfonyl)-2-methyl-5-phenyl-pent-4-enoic acid hydroxyamide was isolated as a colorless solid, mp 162-164 °C; Yield 92%; MS: 376 (M+H)+; Η NMR (300 MHz, CDCI 3 ): δ 1.41 (s, 3H), 3.0-3.16 (m, IH), 3.30 (d, J= 11 Hz, 2H), 3.92 (s, 3H), 5.9 - 6.1 (m, IH), 6.53 (d, J=l lHz, IH), 7.1-7.72 (m, 9H), 9.12 (bs,lH). Example 57 2-(4-methoxy-benzenesulfonyl)-5-phenyl-2-(3-phenyl-propyl)-pentanoic acid hydroxyamide Following the procedure as outhned in Example 9, 2-(4-mefhoxy-benzenesulfonyl)-5-phenyl- 2-(3-phenyl-propyl)-pentanoic acid ethyl ester was prepared, starting from (4.0 g, 15.8 mmol) 2-(4-methoxy-benzenesulfonyl)-acetic acid ethyl ester and 3-bromopropyl benzene (6.4 g, 32 mmol). Yield 3.7 g, 47%; Colorless oil; MS: 495 (M+H) + . 2-(4-Methoxy-benzenesulfonyl)-5-phenyl-2-(3-phenyl-propyl)-pentanoic acid was prepared starting from 2-(4-methoxy-benzenesulfonyl)-5-phenyl-2-(3-phenyl-propyl)-pentanoic acid ethyl ester (2.0 g, 4 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 1.18 g, 63%. Waxy soUd; MS: 449.2 (M+H-H 2 O) + . Starting from 2-(4-methoxy-benzenesulfonyl)-5-phenyl-2-(3-phenyl-propyl)-pentanoic acid (600 mg, 1.2 mmol) and following the procedure as outlined in Example 1, 420 mg of 2-(4- methoxy-benzenesulfonyl)-5-phenyl-2-(3-phenyl-propyl)-pentanoic acid hydroxyamide was isolated as a colorless solid. Mp 118-120 °C; yield 68%; MS: 482 (M+H)+; *H NMR (300 MHz, CDC1 3 ): δ 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=ll Hz, 2H). Example 58 2-aUyl-2-(4-methoxy-tenzenesulfonyl)-pent-4-enoic acid hydroxyamide Following the procedure as outhned in Example 9, 2-allyl-2-(4-methoxy-benzenesulfonyl)- pent-4-enoic acid ethyl ester was prepared, starting from (3.0 g, 11.6 mmol) 2-(4-methoxy- benzenesulfonyl)-acetic acid ethyl ester and aUyl bromide (4 ml, excess). Yield 3.6 g, 92%; YeUow oil; MS: 338 (M+H)+. 2-Allyl-2-(4-methoxy-benzenesulfonyl)-pent-4-enoic acid was prepared starting from 2-aUyl-2- (4-methoxy-benzenesulfonyl)-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 oudined in Example 9. Yield 1.76 g, 87%; yellowish oil; MS: 311 (M+H) + . Starting from 2-aUyl-2-(4-methoxy-benzenesulfonyl)-pent-4-enoic acid (1.5 g, 4.8 mmol) and following the procedure as outhned in Example 1, 1.5 g of 2-aUyl-2-(4-methoxy- benzenesulfonyl)-pent-4-enoic acid hydroxyamide was isolated as colorless solid. Mp 114-116 °C; Yield 99%; MS: 326 (M+H) + ; *H NMR (300 MHz, CDCI 3 ): δ 1.62 (s, IH), 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-propyl-pentanoic acid hydroxyamide 2-ahyl-2-(4-rnethoxy-benzenesulfonyl)-pent-4-enoic acid hydroxyamide (326 mg, 1.0 mmol) (example 26) was dissolved in methanol (50 ml) and hydrogenated over 10% Pd/C (100 mg) at room temperature, under 49 psi pressure for 4 hours. At the end, the reaction mixture was filtered and methanol was removed. The resulting solid was crystaUized from methanol. Yield: 250 mg, 75%; MS: 330 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 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 (bs, IH), 6.97 (d, J=9Hz, 2H), 7.76 (d,J=9 Hz, 2H). Example 60 2-benzyl-N-hydroxy-2-(4-methoxy-benzenesulfonyl)-3-phenyl-propionamide Following the procedure as outlined in Example 9, 2-benzyl-2-(4-methoxy-benzenesulfonyl)- 3-phenyl-propionic acid ethyl ester was prepared, starting from (1.0 g, 3.8 mmol) of 2-(4- nιethoxy-benzenesulfonyl)-acetic acid ethyl ester and benzylbromide (4 ml, excess). Yield 1.2 g, 72%; YeUow oil; MS: 439 (M+H) + . 2-Benzyl-2-(4-methoxy-benzenesulfonyl)-3-phenyl-propionic acid was prepared starting 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 outhned 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 as outhned in Example 1, 225 mg of 2-benzyl-N- hydroxy-2-(4-methoxy-benzenesulfonyl)-3-phenyl-propionamide was isolated as a waxy solid. Yield 52%; MS: 426 (M+H) + ; ! H NMR (300 MHz, CDCI 3 ): δ 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=4Hz, IH), 9.58 (bs, IH). Example 61 N-hydroxy-2-(4-methoxy-benzenesuh°onyl)-2-methyl-3-pyridin-3-yl-propionamide To a stirred solution of 2-(4-methoxy-benzenesulfonyl)propionic acid ethyl ester (2.7 gm, 10 mmol), 3-picolyl chloride hydrochloride (3.2 g, 20 mmol). and triethyl benzylammonium chloride (1 g) in methylene chloride (400 ml), 10 N NaOH ( 30 ml) was added. The reaction was continued at room temp for 48 hours. At the end, the organic layer was separated and washed weU with water. The organic layer was dried, filtered and concentrated. The crude product obtained was purified by silica- gel column chromatography. The column was eluted with 50% ethyl acetate: hexane. 2-(4-Methoxy-benzensulfonyl)-2-methyl-3-pyridin-3-yl- propionic acid ethyl ester was isolated as brown oU. Yield 3.0 g, 82%; Brown oh; MS: 364 (M+H) + Starting from 2-(4-methoxy-benzenesuhOnyl)-2-methyl-3-pyridin-3-yl-propionic acid ethyl ester (2.5 g, 6.8 mmol) 1.8 g (79%) of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-pyridin-3- yl-propionic acid was isolated as a colorless sohd by foUowing the procedure as outlined 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 as outlined in Example 1, 225 mg of N-hydroxy-2- (4-methoxy-benzenesulfonyl)-2-methyl-3-pyridin-3-yl-propionamide was isolated as a colorless sohd. Yield 52%; mp 98 °C; MS: 351 (M+H) + ; »H NMR (300 MHz, CDC1 3 ): δ 1.4 (s, 3H), 3.1 (d, J=9.0, IH), 3.65 (d, J= 9.1, IH), 3.9 (s, 3H), 7-8.5 (m, 8H). Example 62 2-(4-Methoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-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) 8 g of the mono octylated compound 2-(4-methoxy- benzenesulfonyl)-decanoic acid ethyl ester was isolated by following the procedure outlined in Example 9. Yield: 8.0 g 74%; MS: 370 (M+H) + . Following the procedure as outlined in example 29, 2-(4-methoxy-benzenesulfonyl)-2- pyridin-3-ylmethyl-decanoic acid ethyl ester was prepared, starting from (8.0 g, 21.6 mmol) of 2-(4-methoxy-benzenesulfonyl)-decanoic acid ethyl ester and 3-picolyl chloride hydrochloride (4.1 g, 25 mmol). Yield 6.5 g, 68%; Brown oil; MS: 462 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-2-pyricUn-3-yhτiethyl-decanoic acid ethyl ester 5 (5.0 g, 11 mmol), 4.5g (91%) of 2-(4-medιoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl- decanoic acid was isolated as a colorless sohd by following the procedure as outUned in Example 9. Mp 159 °C; MS: 434 (M+H) + . Starting from 2-(4-methoxy-benzenesuh c onyl)-2-pyridin-3-ylmethyl-decanoic acid (2.5 g, 5.7 l o mmol) and foUowing the procedure as outhned in Example 1 , 1.4 g of 2-(4-methoxy- benzenesulfonyl)-2-pyridin-3-ylmethyl-decanoic acid hydroxyamide was isolated as colorless solid. Yield: 50%; mp 62 °C; MS: 448 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 0.86 (t, 6.9 Hz, 3H), 1.25-2.17 (m, 14 H), 3.3 (d, J=14 Hz, IH), 3.5 (d, J= 14 Hz, IH), 3.9 (s, 3H), 6.8 - 8.6 (m, 8H). 15 Example 63 2-(4-Methoxy-benzenesdfonyl)-5-methyl-2-pyridin-3-ylmethyl-hex-4-enoic acid hydroxyamide 20 Following the procedure as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-5-methyl- hex-4-enoic acid ethyl ester was prepared, starting from (6.0 g, 23 mmol) 2-(4-methoxy- benzenesulfonyl)-acetic acid ethyl ester and isoprenyl bromide (3.0 g, 20 mmol). Yield 6.52 g, 86%; Colorless oU; MS: 327 (M+H) + . 25 Following the procedure as outUned in Example 29, 2-(4-methoxy-benzenesulfonyl)-5-methyl- 2-pyridin-3-ylmethyl-hex-4-enoic acid ethyl ester was prepared, starting from (4.0 g, 12.2 mmol) of 2-(4-methoxy-benzenesulfonyl)-5-methyl-hex-4-enoic acid ethyl ester and 3- picolylchloride hydrochloride (2.1 g, 13 mmol). Yield 4.14 g, 81%; Brown oil; MS: 418 30 (M+H)+. 2-(4-Methoxy-benzenesuh c onyl)-5-methyl-2-pyridin-3-ylmethyl-hex-4-enoic acid was prepared starting from 2-(4-methoxy-benzenesulfonyl)-5-methyl-2-pyridin-3-ylmethyl-hex-4-enoic acid ethyl ester (4.0 g, 9.5 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The 35 resulting reaction mixture was worked up as outhned in Example 9. Yield 3.2 g, 87%; ivory sohd; mp 117-119 °C; MS: 390 (M+H) + . Starting from 2-(4-me oxy-benzenesuhOnyl)-5-methyl-2-pyridm-3-ylmethyl-hex-4-enoic acid (2.1 g, 5.4 mmol) and following the procedure as outhned in Example 1, 1.82 g of 2-(4- methoxy-benzenesιdfonyl)-5-meuιyl-2-pyridin-3-ylmethyl-hex-4-enoic acid hydroxyamide was isolated as a colorless sohd. Yield: 82%; mp 89 - 92 °C; MS: 405 (M+H) + ; l H NMR (300 MHz, CDC1 3 ): δ 1.63 (s, 3H), 1.76 (s, 3H), 2.62-2.78 (m, 2H), 3.3 (d, J=4.0 Hz, IH), 3.63 (d, J= 4.0 Hz, IH), 3.82 (s, 3H), 5.26 (m, IH), 7.12-7.88 (m, 6H), 8.27-8.33 (m, 2H). Example 64 2-Benzyl-4-dhsopropylarrιinc)-N-hyά^xy-2-(4-methoxy-benzenesιUfonyl)-butyramide Following the procedure as outUned in Example 29, 2-benzyl-4-diisopropylamino-2-(4- methoxy-benzenesulfonyl)-butyric acid ethyl ester was prepared, starting from (3.0 g, 8.5 mmol) of 2-(4-methoxy-benzenesulfonyl)-3-phenyl-propionic acid ethyl ester (Example 9) and 2-diisopropylaminoethyl chloride hydrochloride (4.0 g, 20 mmol). Yield 3.2 g, 79%; Ivory solid, mp 89-91 °C; MS: 476.4 (M+H)+. Starting from 2-benzyl- ά isopropylamino-2-(4-methoxy-benzenesulfonyl)-butyric acid ethyl ester (3.53 gm, 7.5 mmol) 2.8 g (86%) of 2-benzyl-4-diisopropylamino-2-(4-methoxy- benzenesulfonyl)-butyric acid was isolated as colorless crystals by following the procedure as outlined in Example 9. Mp 136-138 °C; MS: 448.5 (M+H)+. Starting from 2-benzyl-4-dhsopropylamino-2-(4-methoxy-benzenesulfonyl)-butyric acid (1.85 g, 4.1 mmol) and foUowing the procedure as outUned in Example 1, 1.3 g of 2-benzyl-4- dhsopropylamino-N-hydroxy-2-(4-methoxy-benzenesuh c onyl)-butyramide was isolated as a low melting waxy solid; Yield: 68%; MS: 463.3 (M+H)+; IH NMR (300 MHz, CDCI 3 ): δ 0.98 (d, J = 11 Hz, 6H), 1.16 (d, J=ll Hz, 6H), 1.92 (m, 2H), 2.46 (m, 2H), 2.71 (m, 2H), 3.18 (m, IH), 3.48 (m, IH), 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, IH). Example 65 3-Cyclohexyl-N-hydroxy-2-(4-rneuhoxy-benzenesdfonyl)-2-pyrio n-3-ylmemyl-propionamide Following the procedure as outhned in Example 9, 3-cyclohexyl-2-(4-methoxy- benzenesulfonyl)-propionic acid ethyl ester was prepared, starting from (4.0 g, 15 mmol) 2-(4- methoxy-benzenesulfonyl)-acetic acid ethyl ester and 1-bromomethyl cyclohexane (2.7 g, 15 mmol). Yield 5.0 g, 94%; Colorless oil; MS: 355 (M+H) + . Following the procedure as outhned in Example 29, 3-cyclohexyl-2-(4-methoxy- benzenesuhOnyl)-2-pyridin-3-ylmethyl-propionic acid ethyl ester was prepared, starting from 3-cyclohexyl-2-(4-methoxy-benzenesulfonyl)-propionic acid ethyl ester(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 3-cyclohexyl-2-( methoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-propionic acid ethyl ester (1.3 g, 2.9 mmol) l.Og (83%) of 3-cyclohexyl-2-(4-methoxy- benzenesulfonyl)-2-pyridin-3-ylmethyl-propionic acid was isolated as colorless crystals by foUowing the procedure as outlined in Example 9. Mp 92 °C; MS: 417.5 (M+H) + Starting from 3-cyclohexyl-2-(4-methoxy-bεnzenesulfonyl)-2-pyridin-3-yhnethyl-propionic acid (1.0 g, 2.4 mmol) and following the procedure as outhned in Example 1, 80 mg of 3- cyclohexyl-N-hyό^xy-2-(4-methoxy-benzenesιdfonyl)-2-pyridin-3-ylmethyl-propionamide was isolated as acoloriess hydrochloride salt; Yield: 71%; mp 57-60 °C; MS: 433 (M+H) + ; l NMR (300 MHz, CDC1 3 ): δ 0.8-2.08 (m, 13 H), 3.3 (d, J=14 Hz, IH), 3.7 (d, J= 14 Hz, IH), 3.9 (s, 3H), 7.0 - 8.5 (m, 8H). Example 66 2-(4-Methoxy-benzenesuhOnyl)-4-methyl-2-pyridin-3-ylmethyl-pentanoic acid hydroxyamide Following the procedure as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-4-methyl- pentanoic acid ethyl ester was prepared, starting from (5.0 g, 20 mmol) 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 as outlined in Example 29, 2-(4-rnethoxy-benzenesulfonyl)-4- methyl-2-pyridin-3-ylmethyl-penanoic acid ethyl ester was prepared, starting from (3.1 g, 10 mmol) of 2-[(4-methoxy-benzenesuh c onyl)-4-methyl pentanoic acid ethyl ester and 3-picolyl chloride hydrochloride (1.8 g, 11 mmol). Yield 3.0 g, 75%; Colorless oil; MS: 406 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)- meΛyl-2-pyridin-3-ylιrιethyl-pentanoic acid ethyl ester (1.2 g, 2.9 mmol) l.Og (91%) of 2-(4-methoxy-benzenesulfonyl)-4-methyl-2- pyridin-3-ylmethyl-pentanoic acid was isolated as colorless crystals by foUowing the procedure as outhned 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 as outlined in Example 1, 180 mg of 2-(4- methoxy-benzenesulfonyl)-4-methyl-2-pyridin-3-ylmethyl-pentanoic acid hydroxyamide was isolated as a colorless solid; Yield: 21%; mp 78 °C; MS: 393.4 (M+H)+; *H NMR (300 MHz, CDC1 3 ): δ 0.65 (d, 6.3 Hz, 3H), 0.89 (d, J=6.2 Hz, 3H), 1.7 (m, IH), 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 as outhned in Example 29, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-quinolin-6-yl-propionic acid ethyl ester was prepared, 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 yeUow sohd; 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) 2.5g (90%) of 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-quinolin- 6-yl-propionic acid was isolated as colorless crystals by following the procedure as outUned in Example 9. mp 106-108 °C; MS: 386.4 (M+H) + . Starting from 2-(4-methoxy-benzenesuhOnyl)-2-methyl-3-quinolin-6-yl-propionic acid (2.0 gm, 5.2 mmol) and following the procedure as outlined in Example 1, 1.2 g of N-hydroxy-2- (methoxy-rjenzenesιdfonyl)-2-methyl-3-quinohn-6-yl-propionamide was isolated as a colorless solid; Yield: 57%; mp 206 °C; MS: 401.4 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 1.4 (s, 3H), 3.19 (m, IH), 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 as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-6- phenoxy-hexanoic acid ethyl ester was prepared, starting from (2.5 g, 10 mmol) 2-(4- methoxy-benzenesulfonyl)-acetic acid ethyl ester and l-bromo-4-phenoxy butane ( 2.2 , 10 mmol). Yield 3.8 g, 93%; Colorless oil; MS: 407 (M+H) + . Following the procedure as outUned 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) 2-( memoxy-benzenesulfonyl)-6-phenoxy-hexanoic acid ethyl ester and 3-picolyl chloride (1.8 g, 11 mmol). Yield 3.5 g, 71%; Colorless oU; 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), 2.8g (Yield: Quantitative) of 2-(4-methoxy-benzenesulfonyl)-6- phenoxy-2-pyridin-3-ylmethyl-hexanoic acid was isolated as colorless crystals by following the procedure as outhned 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 foUowing the procedure as outlined in Example 1 , 1.5 g of 2-(4- methoxy-benzenesulfonyl)-6-phenoxy-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide was isolated as a colorless solid; Yield: 72%; mp 68 °C; MS: 485.5 (M+H)+; *H NMR (300 MHz, CDCI 3 ): δ 1.5 - 2.5 (m, 8H), 3.4 (bs, 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 as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-5-hexanoic acid ethyl ester was prepared, starting from (10.0 g, 39 mmol) 2-(4-methoxy- benzenesulfonyl)-acetic acid ethyl ester and 1 -bromo- 3-methyl butane ( 6.0 g, 40 mmol). Yield 8.5 g, 62%; Colorless oil; MS: 329 (M+H) + . Following the procedure as outUned in Example 9, 2-(4-methoxy-benzenesulfonyl)-5-methyl- 2-pyridin-3-yhnethyl-hexanoic acid ethyl ester was prepared, starting from (6.0 g, 18 mmol) of 2-(4-methoxy-benzenesulfonyl)-5-methyl-hexanoic acid ethyl 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-me oxy-benzenes fonyl)-5-methyl-2-pyridin-3-ylmethyl-hexanoic acid ethyl ester (3.0 g, 7.1 mmol) 2.6g (92%) of 2-(4-methoxy-benzenesulfonyl)-5-methyl-2- pyridin-3-ylmethyl-hexanoic acid was isolated as a colorless sohd by following the procedure as outlined 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 as outlined in Example 1, 800 mg of 2-(4- methoxy-benzenesuUOnyl)-5-methyl-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide was isolated as a colorless solid; The hydrochloride was prepared by passing hydrogen chloride gas through methanol solution of the hydroxyamide. Yield: 72%; mp 62 °C (HCI salt); MS: 408 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): δ 0.76 (m, 6H), 1.2 -2.0 (m, 5H), 3.5 (bq, 2H), 7.1 - 8.8 (m, 8H), 11.1 (bs.lH). Example 70 2-(4-Methoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide (4-Methoxy-phenylsulfanyl) -acetic acid tert-butyl ester was prepared according to the general method as oudined in Example 1. Starting from the corresponding 1 -bromo tert-butyl acetate (5.3 g, 27 mmol) and 4-methoxybenzenethiol (3.7 g, 27 mmol), 6.4 g of the product was isolated. Yield 98%; Light yellow oU; MS: 255 (M+H)+. 2-(4-Methoxy-benzenesulfonyl)-acetic acid tert-butyl ester was prepared according to the general method as outhned in Example 9. Starting from 2-(4-methoxy-benzenesulfanyl)-acetic acid tert-butyl ester (5.0 g, 20 mmol) and 3-chloroperoxybenzoic acid 57% (12.0g, 40 mmol), 5.3 g of the product was isolated. Yield 92%; Waxy sohd; MS: 287.1 (M+H)+. 2-(4-Methoxy-benzenesulfonyl)-pyridin-3-ylpropionic acid tert-butyl ester was prepared according to the procedure as outUned in Example 9. Starting from 2-(4-methoxy- benzenesulfonyl)acetic acid tert-butyl ester (20.0 g, 70.0 mmol) and 3-picolyl chloride (7.28 g, 44.4 mmol), 10.5 g of the product was isolated by silica gel chromatography (50% ethyl acetate: hexane). Yield 63%; white sohd; mp 93-94 °C; MS: 378.0 (M+H) + . 2-( Methoxy-benzenesvu'fonyl)-2-pyridin-3-ylmethyl-hexanoic acid tert-butyl ester was prepared according to the procedure as outlined in Example 9. Starting from 2-(4-methoxy- benzenesulfonyl)-pyridin-3-ylpropionic acid tert-butyl ester (2.0 g, 5.3 mmol) and n-butyl bromide (0.73 g, 5.3 mmol), 1.20 g of the product isolated. Yield 52%; yellowish gum; MS: 434.3 (M+H) + . A mixture of the 2-(4-Memoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-hexanoic acid tert-butyl ester (1.1 g, 2.5 mmol), in methylene chloride/ TFA (l:l)was stirred at room temperature for about 2 hours. The solvents were then evaporated and the 2-(4-methoxy-benzenesulfonyl)-2- pyridin-3-ylmethyl-hexanoic acid was purified by sUica gel chromatography (30% methanol/methylene chloride). Yield 0.90 g, 94%; white solid; mp 70 'C; MS: 376.1 (M-H)-. 2-(4-Methoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-hexanoic acid hydroxyamide was prepared according to the method as outhned in Example 1. Starting from 2-(4-methoxy- benzenesuh 0 onyl)-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 isolated. Yield 37%; pale yellowish sohd; mp 65 °C; MS: 392.9 (M+H) + ; *H NMR (300 MHz, DMSO-d 6 ) δ 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, IH), 3.62 (d, J = 14.4 Hz, IH), 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, IH), 8.40-8.45 (m, IH), 8.70-8.85 (m, 2H), 11.0 (brs, IH); IR (KBr, cm-i): 3064m, 2958s, 2871m, 1671m. Example 71 2- (4-methoxy-benzenesulf onyl)-2-oct-2-ynyl-dec-4-ynoic acid hydroxyamide. The title compound was prepared according to the procedure as outlined in example 9. Starting from 2-(4-methoxy-benzenesulfonyl)-acetic acid tert-butyl ester (2.86 g, 10 mmol) and 1- bromo-2-octyne (3.80 g, 20 mmol), 4.4 g of the product isolated. Yield 100%; yeUowish gum; MS: 446.9 (M+H) + . 2-(4-Methoxy-benzenesuh°onyl)-2-oct-2-ynyl-dec-4-ynoic acid was prepared according to die method as outhned in example 70. Starting from 2-(4-methoxy-benzenesulfonyl)-2-oct-2-ynyl- dec-4-ynoic acid tert-butyl ester (4.40 g, 10.0 mmol), 2.0 g of the product isolated. Yield 49%; white solid; mp 61°C; MS: 345.1 (M-H)-. 2-(4-Methoxy-benzenesulfonyl)-2-oct-2-ynyl-dec-4-ynoic acid hydroxyamide was prepared according to the mediod as outlined in example 1. Starting from 2-(4-methoxy- benzenesulfonyl)-2-oct-2-ynyl-dec-4-ynoic acid (0.36 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.25 g of the product isolated. Yield 62%; white solid; mp 83-84 β C; 462.0 (M+H) + ; Η NMR (300 MHz, DMSO-dβ) δ 0.82-0.90 (m, 6H), 1.15-1.45 (m, 12H), 1.90-2.05 (m, 4H), 2.86 (brd, J = 17.0 Hz, 2H), 3.00 (brd, J = 17.0 Hz, 2H), 3.87 (s, 3H), 7.15 (d, J = 10.0 Hz, IH), 7.71 (d, J = 10.0 Hz, IH), 9.20 (brs, IH), 10.90 (brs, IH); IR (KBr, cm 1 ): 3344s, 3208m, 2930m, 2870m, 1677s, 1592s; Anal. Calc'd for C 25 H 35 NO 5 S: 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 2-(4-Methoxy-benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid tert-butyl ester was prepared according to the procedure as outlined in Example 9. Starting from 2-(4-methoxy- benzenesulfonyl)-acetic acid tert-butyl ester (2.86 g, 10 mmol) and l-bromo-2-butyne (2.68 g, 20 mmol), 3.50 g of the product was 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 as outhned in example 70. Starting from 2-(4-methoxy-benzenesulfonyl)-2-but-2- ynyl-hex-4-ynoic acid tert-butyl ester (3.0 g, 7.7 mmol), 2.5 g of the product isolated. Yield 97%; white solid; mp 141-143 °C; MS: 333.1 (M-H)-. 2-(4-Methoxy-benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid hydroxyamide was prepared according to the mediod as outlined in example 1. Starting from 2-(4-methoxy- benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid (0.27 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.23 g of the product was isolated. Yield 89%; white solid; mp 135-137°C; MS: 349.9 (M+H) + l; *H NMR (300 MHz, DMSO-d 6 ) δ 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 (brs, IH), 10.90 (brs, IH); 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 2-(4-Methoxy-benzenesuh c onyl)-2-prop-2-ynyl-pent-4-ynoic acid tert-butyl ester was prepared according to the procedure as outlined in Example 9. Starting from 2-(4-methoxy- benzenesulfonyl)-acetic acid tert-butyl ester (2.0 g, 7.0 mmol) and propargyl bromide (1.77 g, 15 mmol), 1.90 g of the product was isolated. Yield 75%; white sohd; p 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 as outlined in Example 70. Starting from 2-(4-methoxy-benzenesulfonyl)-2- prop-2-ynyl-pent-4-ynoic acid tert-butyl ester (1.70 g, 4.7 mmol), 1.30 g of the product isolated. Yield 90%; white solid; mp 156°C; MS: 305.1 (M-H)-. 2-(4-Methoxy-benzenesulfonyl)-2-prop-2-ynyl-pent-4-ynoic acid hydroxyamide was prepared according to the method as outlined in Example 1. Starting from (4-methoxy- benzenesulfonyl)-2-prop-2-ynyl-pent-4-ynoic acid (0.25 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.22 g of the product was isolated. Yield 85%; white solid; mp 156°C; MS: 321.9 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ) δ 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 (brs, IH), 10.65 (brs, IH); IR (KBr, cm-1): 3392s, 3293s, 3271m, 2955m, 1650s, 1594s; Anal. Calc'd for C 15 H 1 5NO5S: 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 as outlined in Example 38. Starting from 2-(4-methoxy-benzenesulfonyl)-pyridin-3-ylpropionic acid tert-butyl ester (2.20 g, 5.8 mmol) and 1 -bromo- 2-octyne (1.14 g, 6 mmol), 2.60 gm of the product isolated. Yield 92%; yellowish gum; MS: 486.0 (M+H) + . A mixture of the 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) is stirred at room temperature for about 2 hours. (Ref. example 70) The solvents are then evaporated and the 2- (4-methoxy-benzenesulfonyl)-2-pyridin-3-ylmedιyl-dec-4-ynoic acid was purified by silica gel chromatography (-30% methanol/methylene chloride). Yield: 2.0 g, 87%; White solid; mp 146°C; MS: 428.1 (M-H)-. 2-(4-Medιoxy-benzenesulfonyl)-2-pyridin-3-ylmed yl-dec-4-ynoic acid hydroxyamide was prepared according to the procedure outlined in Example 1. Starting from 2-(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 was isolated. Yield 67%; off-white solid; mp 65°C; MS: 445.0 (M+H) + ; *H NMR (300 MHz, DMSO-de) δ 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, IH), 2.90 (d, J = 17.9 Hz, IH), 3.50 (d, J = 13.7 Hz, IH), 3.74 (d, J = 13.7 Hz, IH), 3.89 (s, 3H), 7.19 (d, J = 9.0 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.85-7.89 (m, IH), 8.37-8.40 (m, IH), 8.70-8.80 (m, 2H), 11.0 (brs, IH); IR (KBr, cm-1): 3157m, 3095m, 2954s, 2932s, 2858m, 1671m, 1593s; Anal. Calc'd for C23H28N2O5S HCI O.9H2O: 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-ylmetiιyl-pent-4-ynoic acid hydroxyamide 2-(4-Methoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-pent-4-ynoic acid tert-butyl ester was prepared according to the procedure as outlined in Example 38. Starting from 2-(4-methoxy- benzenesulfonyl)-pyridin-3-ylpropionic acid tert-butyl ester (3.77 g, 10 mmol) and propargyl bromide (1.74 g, 13 mmol), 2.50 g of the product was isolated. Yield 60%; yellowish soUd; 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 as outUned in Example 70. Starting from 2-(4-methoxy- benzenesulfonyl)-2-pyridin-3-ylmethyl-pent-4-ynoic acid tert-butyl ester (2. 0 g, 4.8 mmol), 1.2 g of the product isolated. Yield 69%; white solid; mp 119-121°C; MS: 358.1 (M-H)-. 2-(4-Medιoxy-benzenesulfonyl)-2-pyridin-3-ylmethyl-pent-4-ynoic acid hydroxyamide was prepared according to the method as outhned in Example 1. Starting from 2-(4-methoxy- benzenesulfonyl)-2-pyridin-3-ylmethyl-pent-4-ynoic acid (0.29 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 m, 10 mmol), 0.065 g of the product was isolated. Yield 25%; off-white solid; mp 70°C; MS: 375.0 (M+H) + ; Η NMR (300 MHz, DMSO-dό) δ 1.19 (brs, IH), 2.90-3.00 (m, 2H), 3.55 (d, J = 13.8 Hz, IH), 3.67 (d, J = 13.8 Hz, IH), 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, IH), 8.35-8.40 (m, IH), 8.70-8.80 (m, 2H), 11.1 (brs, IH); IR (KBr, cm-1): 3168m, 3095s, 1670m, 1593s. Example 76 2-(4-Fluoro-benzenesulfonyl)-2-pyridin-3-ylmethyl-hex-4-ynoic acid hydroxyamide 2-(4-Fluoro-benzenesulfanyl)-acetic acid tert-butyl ester was prepared according to the procedure as outlined in Example 1. Starting from 4-fluorothiophenol (30.0 g, 230 mmol) and tert-butyl bromoacetate (45.67 g, 230 mmol), 53.4 g of the product was isolated. Yield 100%; pale yellowish oil; MS: 243.1 (M+H) + . 2-(4-Fluoro-berιzenesulfonyl)-acetic acid tert-butyl ester was prepared according to the general method as outlined in Example 9. Starting from 2-(4-fluoro-benzenesulfanyl)-acetic acid tert- butyl ester (48.4 g, 200 mmol) and 3-chloroperoxybenzoic acid (121.3g (57%), 400 mmol ), 48.0 g of the product was isolated. Yield 88%; pale yellowish oil; MS: 275.1 (M+H)+. The title compound was prepared according to the procedure as outlined in Example 70. Starting from 2-(4-fluoro-benzenesulfonyl)-3-pyridin-3-ylpropionic acid tert-butyl ester (1.83 g, 5.0 mmol) and l-bromo-2-butyne (0.67 g, 5.0 mmol), 2.18 g of the product was isolated. Yield 100%; 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 as outlined in Example 38. Starting from 2-(4-fluoro-benzenesulfonyl)-2- pyridin-3-ylmethyl-hex-4-ynoic acid tert-butyl ester (2.1 g, 5.0 mmol), 1.20 g of the product was isolated. Yield 67%; off-white solid; mp 150°C; MS: 360.2 (M-H)-. 2-(4-Fluoro-benzenesulfonyl)-2-pyridin-3-ylmethyl- hex-4-ynoic acid hydroxyamide was prepared according to the method as outhned in Example 1. Starting from 2-(4-fluoro- benzenesulfonyl)-2-pyridin-3-ylmethyl-hex-4-ynoic acid (0.29 g, 0.81 mmol) and hydroxylamine hydrochloride ( 0.70 g, 10 mmol), 0.15 g of the product was isolated. Yield 45%; white soUd; mp 190°C; MS: 377.2 (M+H) + ; l H NMR (300 MHz, DMSO-d 6 ) δ 1.60 (s, 3H), 2.70-3.00 (m, 2H), 3.53 (d, J = 13.8 Hz, IH), 3.74 (d, J = 13.8 Hz, IH), 7.50-7.58 (m, 2H), 7.80-7.95 (m, 3H), 8.35-8.40(m, IH), 8.74-8.79 (m, 2H), 11.1 (brs, IH); IR (KBr, cm-1): 3154m, 3105s, 3068s, 2875m, 1696s, 1630w, 1590s; Anal. Calc'd for Ci 8 Hι 7 FN 2 O 4 S-HCl- 0.5H 2 O: 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 as outhned in Example 9. Starting from 2-(4-fluoro-benzenesulfonyl)-3-pyridin-3-ylpropionic acid tert-butyl ester (1.83 g, 5.0 mmol) and l-bromo-2-octyne (0.95 g, 5.0 mmol), 1.80 g of the product was isolated. 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 as outlined in Example 70. Starting from 2-(4-fluoro-benzenesulfonyl)-2- pyridin-3-ylmethyl-dec-4-ynoic acid tert-butyl ester (1.80 g, 3.8 mmol), 1.40 g of the product was isolated. Yield 88%; off-white solid; mp 123-124°C; MS: 416.3 (M-H)-. 2-(4-Ruoro-benzenesulfonyl)-2-pyridin-3-ylmethyl-dec-4-ynoic acid hydroxyamide was prepared according to the method as outhned in Example 1. Starting from 2-(4-fluoro- benzenesulfonyl)-2-pyridin-3-ylmethyl-dec-4-ynoic acid (0.67 g, 1.62 mmol) and hydroxylamine hydrochloride (1.39 g, 20 mmol), 0.22 g of the product was isolated. Yield 29%; white solid; mp 180-182°C; MS: 433.2 (M+H)+; Η NMR (300 MHz, DMSO-a ) δ 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, IH), 2.94 (d, J = 19.9 Hz, IH), 3.54 (d, J = 13.7 Hz, IH), 3.75 (d, J = 13.7 Hz, IH), 7.40- 7.60(m, 2H), 7.70-8.00 (m, 3H), 8.30-8.40 (m, IH), 8.70-8.80 (m, 2H), 11.1 (brs, IH); IR (KBr, cm-1): 3154m, 3105s, 3067m, 2957s, 2933s, 2873m, 1690s, 1631m. Anal. Calc'd for C 2 2H 25 FN 2 O 4 S HCI: C, 56.34; H, 5.59; N, 5.97. Found: C, 56.18; H, 5.54; N,5.76. Example 78 2-(4-Fluoro-benzenesuh c onyl)-2-but-2-ynyl-hex-4-ynoic acid hydroxyamide 2-(4-Fluoro-benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid tert-butyl ester was prepared according to the procedure as outhned in Example 9. Starting from 2-(4-fluoro- benzenesulfonyl)-acetic acid tert-butyl ester (4.87 g, 20 mmol) and l-bromo-2-butyne (5.36 g, 40 mmol), 6.0 g of the product was isolated. Yield 77%; white sohd; 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 as outlined in Example 70, starting from 2-(4-fluoro-benzenesulfonyl)-2-but-2-ynyl- hex-4-ynoic acid tert-butyl ester (3.50 g, 8.47 mmol), 2.35 g of the product was isolated. Yield 79%; white solid; mp 129-131°C; MS: 642.8 (2M-H)-. 2-(4-Fluoro-benzenesuh c onyl)-2-but-2-ynyl-hex-4-ynoic acid hydroxyamide was prepared according to the method as outlined in Example 1. . Starting from 2-(4-fluoro- benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid (0.26 g, 0.81 mmol) and hydroxylamine hydrochloride (0.70 g, 10 mmol), 0.21 g of the product was isolated. Yield 77%; white solid; mp 161-163°C; MS:338.1(M+H) + ; *H NMR (300 MHz, DMSO-d 6 ) δ 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 (brs, IH), 10.95 (brs, IH); IR (KBr, cm-1): 3336s, 3245m, 1681s, 1589m, 1493m; Anal. Calc'd for Cι 6 H 16 FNO 4 S: 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 as outhned in Example 9, 2-(4-methoxy-benzenesulfonyl)-5-methyl- 2-(3-methyl-but-2-enyl)-hex-4-enoic acid ethyl ester was prepared, starting from (5.0 g, 20 mmol) 2-(4-methoxy-benzenesulfonyl)-acetic acid ethyl ester and isoprenyl bromide (6.0 g, 40 mmol). Yield 7.0 g, 88%; Colorless oil; MS: 395 (M+H) + . Starting from 2-(4-methoxy-benzenesulfonyl)-5-methyl-2-(3-methyl-but-2-enyl)-hex-4-enoic acid ethyl ester (3.5 g, 9 mmol), 3.3g (97%) of 2-(4-methoxy-benzenesulfonyl)-5-methyl-2- (3-methyl-but-2-enyl)-hex-4-enoic acid was isolated as a colorless oU by following the procedure as oudined 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 as outhned 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 sohd. Yield: 67%; mp 93 - 96 °C; MS: 383 (M+H) + ; J H NMR (300 MHz, CDC1 3 ): δ 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 (bs, IH), 7.72 (d, J=8 Hz, 2H), 9.71 (bs, IH). 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 as outlined in example 1 starting from ethyl 2- bromoheptanoate (11 g, 47 mmol) and 4-methoxythiophenol (6g, 42.8 mmol), as a yellow oil; MS: 297.2 (M+H) + . 2-(4-Methoxy-phenylsulfanyl)-heptanoic acid was prepared starting with 2-(4-methoxy- phenylsulfanyl)-heptanoic acid ethyl ester (4 g, 13.5 mmol) dissolved in methanol (300 ml) and 10 N NaOH (25 ml). The resulting reaction mixture was worked up as outlined in example 1. Yield 3 g (83%). yeUow oil. MS: 267.1 (M-H)\ Starting from 2-(4-methoxy-phenylsulfanyl)-heptanoic acid (2.49 g, 9.32 mmol) and following the procedure as outhned in example 1, 1.83 g of 2-4-(methoxy-phenylsulfanyl)-heptanoic acid hydroxyamide was isolated as an off white solid. Mp 90-95 °C; Yield 70%; MS: 284.0 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.826 (t, J= 6.9 Hz, 3H), 1.135-1.76 (m, 8H), 3.35 (m, IH), 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 from 2-(4-methoxy-phenylsulfanyl)-heptanoic acid hydroxyamide (1.69 g, 6 mmol) and following the procedure outhned in example 5, the two diastereomers of 2-(4-methoxy- phenylsulfinyl)-heptanoic acid hydroxyamide were separated on a silica gel column using 75% etiiyl acetate:hexanes. The less polar isomer, 2R*-(4-methoxy-phenyl- S*- sulfinyl)-heptanoic acid hydroxyamide 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, IH), 3.82 (s, 3H), 7.09-7.61 (m, 4H). The more polar isomer, 2S*-(4-methoxy-phenyl- R*- sulfinyl)-heptanoic acid hydroxyamide was isolated as a gray solid. Yield: 200 mg (11%); mp 112 °C; MS: 300.0 (M+H) + , Η NMR (300 MHz, DMSO-d 6 ): δ 0.754 (t, J= 6.9 Hz, 3H), 1.014-1.121 (m, 6H), 1.58-1.89 (m, 2H), 3.10-3.15 (m, IH), 3.834 (s, 3H), 7.13-7.65 (m, 4H). Example 82 2-(4-methoxy-benzenesuU r onyl)-2-methyl-3-[4-(2-moφholin-4-yl-ethoxy)-phenyl]-propionic hydroxyamide hydrochloride. Following the procedure as outhned in example 12, 2-(4-methoxy-benzenesulfonyl)-2-methyl- 3-[4-(2-moφholin-l-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- (moφholin-l-yl-ethoxy)-benzyl chloride hydrochloride (2.9 g, 10 mmol). Yield 4.8 g, 98%; Brown oil; MS: 492 (M+H) + . Starting from 2-( methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-moφholin- 1 -yl-ethoxy)- phenyl]-propionic acid ethyl ester (4.0 gm, 8.1 mmol) 3.2 g (Yield: 84 %) of 2-(4-methoxy- benzenesulfonyl)-2-methyl-3-[4-(2-moφhohn- 1 -yl-etiιoxy)-phenyl] -propionic acid was isolated as colorless crystals by following the procedure as outhned in example 9. Mp 171 °C; MS: 464 (M+H)+. Starting from 2-(4-methoxy-benzenesulfonyl)-2-methyl-3-[4-(2-moφholin-l-yl-ethoxy)- phenyl] -propionic acid (4.0 g, 8.6 mmol) and following the procedure as outlined in example 1, 2.5 g of 2-(4-methoxy-bεnzenesulfonyl)-2-methyl-3-[4-(2-moφholin-l-yl-ethoxy)- phenyl] -propionic hydroxyamide was isolated as colorless solid. The hydrochloride salt was prepared by reacting the free base with methanoUc hydrogen chloride at 0 °C. Yield: 2.5 g, 60%; mp 98°C; MS: 479 (M+H) + ; *H NMR (300 MHz, CDC1 3 ): 1.36 (s, 3H), 3.8 - 12.6 (m, 16 H), 3.9 (s, 3H), 4.1 - 4.3 (m, IH), 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 (bs, IH). Example 83 l-Benzyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc Acid hydroxyamide To a stirred solution of 4-methoxybenzenethiol (2.8 gm, 20 mmol) and anhydrous K 2 CO 3 (10 gm, excess) in dry acetone (100 ml), α-bromo ethyl acetate (3.3 gm, 20 mmol) was added in a round bottom flask and the reaction mixture was heated at reflux for 8 hours with good stirring. At the end, the reaction mixture was allowed to cool and the potassium salts were filtered off and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H 2 O and 0.5 N NaOH solution. The organic layer was further washed well with water, dried over MgSO 4 , filtered and concentrated. (4-methoxy- phenylsulfanyl)-acetic acid ethyl ester was isolated as 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 (4.4 g, 20 mmol) in CH 2 CI 2 (15 ml) was added slowly. The reaction mixture turned cloudy and was 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 off and Na 2 SO 3 solution was added to the organic layer which was stirred for at least 3 hours before the mixture was extracted with CHCI 3 and washed with H 2 O. 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. Yield: 100%; MS: 259.1 (M+H) + . To a stirred solution of diethanol amine (10.5 g, 100 mmol), and anhydrous K 2 CO 3 (30 gm, excess) in dry acetone (250 ml), benzyl bromide (17.2 gm, 100 mmol) was added in a round bottom flask and the reaction mixture was heated at reflux for 8 hours with good stirring. At the end, the reaction mixture was aUowed to cool and the potassium salts were filtered off and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H 2 O . The organic layer was further washed well with water, dried over MgSO 4 , filtered and concentrated. Colorless oil. Yield: 19.0 g, 97%; MS: 196 (M+H). N-Benzyldiedianolamine (9.75 g, 50 mmol) was dissolved in saturated methanolic hydrochloric acid and concentrated to dryness. The hydrochloride thus formed was dissolved in methylene chloride (300 ml) and thionyl chloride (20 g, excess) was added dropwise and stirred at room temperature for 1 hr. At the end reaction mixture was concentrated to dryness and the product bis-(2-chloro-ethyl)-benzyl amine hydrochloride was used for further transformation with out 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 g, 24.7 mmol), 18-Crown-6 (500 mg), and anhydrous K 2 CO3 (30 gm, excess) in dry acetone (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 at reflux for 16 hours with good stirring. At the end, the reaction mixture was aUowed to cool and the potassium salts were filtered off and the reaction mixture was concentrated. The residue was extracted with chloroform and washed with H 2 O . The organic layer was further washed well with water, dried over MgSO 4 , filtered and concentrated. The dark brown reaction mixture was purified by sihca gel coumn chromatography by eluting it with 30% ethylacetate: hexane and the product 4-(4-Methoxy- benzenesulfonyl)-l-benzyl-piperidine-4-carboxylic acid ethyl ester was isolated as Brown oil. Yield: 6.0 g, 60%; MS: 418 (M+H). 4-(4-Methoxy-benzenesuh c Onyl)-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 for 72 hrs. At the end reaction mixture was concentrated and the product was nuetralised with con. Hcl by dissolving it in water (200 ml). After the nuetraUzation reaction mixture was concentrated to dryness. Ice cold water (100 ml) was added to the solid and filtered. The product 4-(4- Methoxy-benzenesulfonyl)-l-benzyl-piperidine-4-carboxyhc acid was dried at 50 C and taken to next step with out 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 CH 2 C1 2 (100 ml) at O°C, oxalyl chloride (1.0 gm, 8 mmol) was added in a drop-wise manner. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, in a separate flask a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) was stirred in THF:water (5:1, 30 ml) at O°C for 1 hour. At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH 2 CI 2 and added slowly to me hydroxylamine at O°C. The reaction mixture was stirred at room temperature for 24 hours and concentrated. The residue obtained was extracted with chloroform and washed weU with water. The product obtained was purified by sUica gel column chromatography and eluted with chloroform the product 4-(4-Methoxy-benzenesulfonyl)-l-benzyl-piperidine-4-carboxy c acid hydroxyamide was isolated as a colorless solid, mp 90-95 °C; Yield, 1.2 g, 48%; MS: 405 (M+H) + ; IH NMR (300 MHz, DMSO-d*;): δ 2.29 (m, 3H), 2.76-2.79 (m, 2H), 3.43 (m, 5 4H),4.30 (s, 2H), 7.14-7.17 (d,2H), 7.50-7.73 (m, 5H), 9.37 (s,lH), 10.53 (s,lH), 11.18 (s,lH). Example 84 l o 4-(4-methoxy-benzenesulfonyl)- 1 -(3-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(3-methoxy-benzyl)-amino]-ethanol was prepared according to the 15 general method as outhned in example 83. Starting from 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-Methoxybεnzyl-bis-(2-chloro-ethyl)-amine was prepared according to the general method as 20 outhned in example 83. Starting from 3-Methoxy-benzyl diethanolamine (4.4 g, 20 mmol). Yield 4.5 g (93 %); yellow solid mp 86 -88 C; MS: 263. (M+H)\ 4-(4-Methoxy-benzenesulfonyl)-l-(3-methoxy-benzyl)piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4- 25 (methoxy-benzenesulfonyl)-acetic acid ethyl ester (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 30 prepared starting from 4-(4-Methoxy-benzenesulfonyl)- 1 -(3-methoxy-benzyl)piperidine-4- carboxyhc acid ethyl ester (2.4g, 5.36 mmol) dissolve in methanol (30 mL) , 10 N sodium hydroxide (10 mL), tetrahydrohydrofuran (20 mL). The resulting reaction mixture was worked up as outlined in example 83. Yield 710 mg (32 %). white sohd mp 199 °C , MS: 419.9 (M+H)\ 35 Starting from 4-(4-methoxy-benzenesulfonyl)-l-(3-methoxy-benzyl)-piperidine-4-carboxylic acid (830 mg, 1.98 mmol) and following the procedure as outlined in example 83, 190 mg of 4-(4-methoxy-benzenesulfonyl)- 1 -(3-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxamide was isolated as a white solid, mp 130 °C; Yield 20.4%; MS: 435.0 (M+H) + ; Η NMR (300 MHz, DMSO-c ): δ 2.24-2.32 (m, 2H), 2.5 l(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, 1H0, 10.1 (s, IH). Example 85 1 -(3,4-dichlorobenzyl) -4-(4-methoxy-benzenesuhOnyl)-piperidine-4-carboxylic acid hydroxamide 2-[(2-Hydroxy-ethyl)-(3,4-dichloro-benzyl)-amino]-ethanol was prepared according to the general method as outlined in example 83. Starting from diethanolamine (4.84 g, 46 mmol) and 3,4-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 as outlined in example 83. Starting from 3,4-dichlorobenzyl diethanolamine (10.7 g, 41 mmol). Yield 99%; yellow solid mp 218-220 °C; MS: 301.8 (M+H) + . l-(3,4-Dichloro-benzyl)-4-(methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4- (methoxy-benzenesulfonyl)-acetic acid ethyl ester (2.9 g, 11 mmol) and 3,4-dichlorobenzyl- bis(2-chloroethyl)-amine (3.4 g, 11 mmol). Yield 5.9g (60 %); brown oU; MS: 494.5 (M+H) + . l-(3,4-Dichloro-benzyl)-4-(4-methoxy-benzenesuU ' ulfonyl)-piperidine-4-carboxyUc acid was prepared starting from l-(3,4-dichloro-benzyl)-4-(methoxy-benzenesulfonyl)-piperidine-4- carboxylic acid ethyl ester (5.0 g, 10 mmol) dissolved in methanol (50 mL), IO N sodium hydroxide (15 mL) and tetrahydrofuran (75 mL). The resulting reaction mixture was worked up as outlined 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-carboxyUc acid (2.67g, 5.8 mmol) and following the procedure as outlined in example 83, .2 g of l-(3,4- dichlorobenzyl) -4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxamide was isolated as a white solid, mp 192- 195 °C; Yield 10%; MS 472.9 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 7.65-7.68 (d, J=.029, 2H), 7.72-7.75 (d, J=.027, 2H), 7.87 (s, IH), 9.37 (s, IH), 10.53 (s, IH), 11.18 (s, IH). Example 86 4-(4-methoxy-benzenesulfonyl)- 1 -(4-methylbenzyl)-piperidine-4-carboxylic acid hydroxamide 2-[(2-Hydroxy-ethyl)-(4-methyl-benzyl)- aminoj-ethanol was prepared according to the general method as oudined in example 83. Starting from 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-chIoro-ethyl)-amine was prepared according to the general method as outlined in example 83. Starting from 4-methyl-benzyl diethanolamine (6 g, 20 mmol). Yield 5.2 g (84 %); yellow solid mp 145-147 °C; MS: 245.9 (M+H) + . 4-(4-Methoxy-benzenesulfonyl)-l-(4-methyl-benzyl)piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4- (methoxy-benzenesulfonyl)-acetic acid ethyl ester (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-benzenesuh c onyl)l-(4-methyl-benzyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester (4.3g, 9.9 mmol) dissolve in methanol (30 mL) , 10 N sodium hydroxide (10 mL), tetrahydrohydrofuran (20 mL). The resulting reaction mixture was worked up as outhned in example 83. Yield 1.6 g (40 %). white solid mp 207-208 °C , MS: 404.3 (M+H) + . Starting from 4-(4-methoxy-benzenesulfonyl)-l-(4-methylbenzyl)-piperidine-4-carboxyUc acid (1.59g, 3.9 mmol) and following the procedure as outlined in example 83, .505 g of 4-(4- methoxy-benzenesulfonyl)-l-(4-methylbenzyl)-piperidine-4-carboxylic acid hydroxamide was isolated as a white solid, mp 176-177 °C; Yield 32%; MS: 419.0 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 2.24-2.32 (m, 2H), 2.5 l(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-rrιethoxy-benzene-sulfonyl)- 1 -napthalene-2-yl-methylpiperidine-4-carboxyUc acid hydroxamide 2-[(2-Hydroxy-ethyl)-(2-napthyl-2-ylme yl)-aminoj-ethanol was prepared according to the general method as outlined in example 83. Starting from diethanolamine (6.18 g, 59 mmol) and 2-(bromomethyl)napthalene (10 g, 45 mmol). Yield 12.7 g (96 %); yeUow soUd mp 162-164 °C; MS: 246.0 (M+H) + . 2-Napthyl-2-ylmethyl-bis-(2-chloro-ethyl)-amine was prepared according to the general method as outlined in example 83. Starting from 2-napthyl-ylmethyl-diethanol amine (10 g, 36 mmol). Yield 9.1 g (79 %); brown solid mp 124-126 °C; MS: 281.9 (M+H) + . 4-( Methoxy-benzenesuhonyl)--napthalene-ylmethyl-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4- (methoxy-benzenesulfonyl)-acetic acid ethyl ester (8.4 g, 32 mmol) and 1-napthalene-ylmethyl- bis-(2-chloro-ethyl)-amine ((8.6 g, 27 mmol). Yield 6.5 g (52 %); low melting solid; MS: 440.0 (M+H) + . 4-(4-Methoxy-benzenesulfonyl)- 1 -napthalene-ylmethyl-piperidine-4-carboxylic acid was prepared starting from 4-(4-methoxy-benzenesulfonyl)-napthalene-ylmethyl-piperidine-4- carboxylic acid ethyl ester (6.3g, 13 mmol) dissolved in methanol (30 mL), 10 N sodium hydroxide (30 mL) and tetrahydrofuran (30 mL). The resulting reaction mixture was worked up as outlined 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 -napthalene-2-yl-methylpiperidine-4-carboxylic acid (2.18g, 5.0 mmol) and following the procedure as outlined in example 83, .753 g of 4-(4- methoxy-benzene-sulfonyl)- 1 -napthalene-2-yl-methylpiperidine-4-carboxylic acid hydroxamide was isolated as a off white solid, mp 168-170 °C; Yield 31%; MS 455.0 (M+H) + ; 'H NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 10.70 (s, IH), 11.20 (s, IH). Example 88 l-Biphenyl-4-yhτιethyl-4-(4-methoxy-benzenesuhonyl)piperidine-4-carboxylic acid hydroxamide 2- [(2-Hydroxy-ethyl)-(l-biphenyl-4-ylmethyl))-amino] -ethanol was prepared according to the general method as outlined in example 83. Starting from diedianol amine (5.2 g, 49 mmol) and 4-(chloromethyl)biphenyl (10 g, 49 mmol). Yield 9.98 g (66 %); white sohd mp 160-162 °C; MS: 271.9 (M+H) + . This was converted to the dichloride as outhned in example 83 l-Biphenyl-4-ylmeuιyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4- (methoxy-benzenesulfonyl)-acetic acid etiiyl ester (2.85 g, 11 mmol) and l-biphenyl-4- ylmethyl-bis-(2-chloro-ethyl)-amine (3.4 g, 11 mmol). Yield 2.1 g, (39 %); beige solid, mp 176-178 °C, MS: 494.1 (M+H) + . 1 -Biphenyl-4-ylmethyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid was prepared starting from l-biphenyl-4ylmethyl-(4-methoxy-benzenesulfonyl)-piperidine-4- carboxylic acid ethyl ester (5.7g, 12 mmol) dissolved in ethanol (20 mL), tetrahydrofuran (20 mL) and 10 N sodium hydroxide (10 mL). The resulting reaction mixture was worked up as outhned in example 83. Yield 2.1g (39% ) MS: 465.8 (M+H) + . Starting from 1 -biphenyl-4-ylmethyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid (l.Og, 2.2 mmol and following the procedure as outlined in example 83, .132g of 1- biphenyl-4-ylmethyl-4-(4-methoxy-benzenesulfonyl)piperidine-4-carboxylic acid hydroxamide was isolated as a tan solid. mpl68 °C; Yield 20%; MS: 440.9 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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=.059 Hz, 2H), 7.49-7.65 (m, 5H), 7.68-7.74 (d, J=.06 Hz, 2H), 9.3 (s, IH), 10.3 (s, IH), 11.15 (s, IH). Example 89 4- (4-methoxy-benzene-sulfonyl)- 1 -(3-methyl-but-2-enyl)piperidine-4-carboxylic acid hydroxamide 5 2-[(2-Hydroxy-ethyl)-l-(3-methyl-but-2-enyl)-amino]-ethanol was prepared according to the general method as outlined in example 83. Starting from died anol amine (4.1 g, 39 mmol) and 4-bromo-2-methyl-butene (6.0 g, 40 mmol). Yield ( 98 %); brown oil; MS: 173.8 (M+H) + . l o 1 -(3-methyl-but-2-enyl)]-bis-(2-chloro-ethyl)-amine was prepared according to the general method as outlined in example 83. Starting from 2-[(2-hydroxy-ethyl)-l-(3-methyl-but-2- enyl)-amino]-ethanol (10.4g, 50 mmol). Yield 10.5g (99%); brown solid; MS: 210.3 (M+H) 4-(4-Methoxy-benzenesulfonyl)- 1 -(3-methyl-but-2-enyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outhned in example 1. Starting from 4- 15 (memoxy-benzenesulfonyl)-acetic acid ethyl 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)- l-(3-methyl-but-2-enyl)-piperidine-4-carboxylic acid was 20 prepared starting from 4-(4-methoxy-benzenesulfonyl)- 1 -(3-methyl-but-2-enyl)-piperidine-4- carboxylic acid ethyl ester (6.2g, 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 outlined in example 83. Yield 1.2 g (21 %). brown solid mp 196-197 °C, MS: 367.9 (M+H) + . 25 Starting from 4-(4-methoxy-benzenesuh c bnyl)-l-(3-methyl-but-2-enyl)-piperidine-4-carboxyhc acid (l.Og. 3.0 mmol) and following the procedure as outlined in example 83, .110 mg of 4- (4-methoxy-benzene-sulfonyl)- 1 -(3-methyl-but-2-enyl)piperidine-4-carboxyhc acid hydroxamide was isolated as a yellow solid, mp 142-145 °C; Yield 12%; MS: 382.9 (M+H) + ; 30 Η NMR (300 MHz, DMSO-d 6 ): δ 1.67 (s, 3H), 1.79 (s, 3H), 2.18-2.23 (m, 2H), 2.66- 2.73 (m, 2 H), 3.37-3.46 (m, 2H), 3.67-3.69 (m, 2H), 5.19-5.24 (m, IH), 7.15-7.18 (d, J=.03, 2H), 7.67-7.70 (d, J=.030, 2H), 9.34 (s, IH), 9.88 (s, IH), 11.15 (s, IH). Example 90 1 -(4-Brorrκ)-benzyl)-4-( methoxy-benzenesuhonyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(4-Brornobenzyl)-(2-hydroxy-ethyl)-amino]-ethanol was prepared according to the general mediod as oudined in example 83. Starting from diethanolamine (22.5 g, 150 mmol). and 4- bromobenzyl bromide (25 g, 100 mmol). Yield 33.66g, (99%); yellow oil; MS: 273.8 (M+H) + . (4-Bromo-benzyl)-bis-(2-chloro-ethyl)-amine was prepared according to the general method as outhned in example 83. Starting from 2-[(4-bromobenzyl)-(2-hydroxy-ethyl)-amino]-ethanol (33.28 g, 122 mmol). Yield 47 g, (99%); brown solid; mp 125 °C; MS: 309.8 (M+H) + . l-(4-Bromo-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 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) + . l-(4-Brorrκ)-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid was prepared starting from l-(4-bromo-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4- carboxylic acid ethyl ester (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 outhned in example 83. Yield 6.18 g (40%); tan solid; mp 215 °C; MS: 469.7 (M+H) + . Starting from l-(4-Bromo-benzyl)-4-(4-methoxy-benzenesuh c onyl)-piperidine-4-carboxylic acid (1.95 g, 4.2 mmol) and following the procedure as outlined in example 83, 1.29 g of 1- (4-bromo-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxyamide was isolated as an off white solid. Yield 60%; mp 180 °C; MS: 484.7 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 10.5 (s, IH). Example 91 4-(4-methoxy-benzenesulfonyl)- 1 -(3-phenyl-propyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(3-phenyl-propyl)-aminoj-ethanol was prepared according to the general method as outlined in example 83. Starting from diethanolamine (15.8 g, 151 mmol). and 1- bromo-3-ρhenylpropane (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 as outlined in example 83. Starting from 2-[(2-hydroxy-ethyl)-(3-phenyl-propyl)-aminoj- ethanol (20.32 g, 90.7 mmol). Yield 24.9 g (92%); brown oil; MS: 259.8 (M+H)\ 4-(4-Methoxy-benzenesulfonyl)- 1 -(3-phenyl-propyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outUned in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid ethyl ester (12 g, 46.5 mmol) and bis-(2-chloro- ethyl)-(3-phenyl-propyl)-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 4-(4-Methoxy-benzenesulfonyl)-l-(3-phenyl-propyl)-piperidine-4- carboxylic acid ethyl ester (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 outhned in example 83. Yield 4.67 g (47%); off white powder; mp 203 °C; MS: 418.2 (M+H) + . Starting from 4-(4-methoxy-benzenesulfonyl)- 1 -(3-phenyl-propyl)-piperidine-4-carboxyhc acid (4.37 g, 10.4 mmol) and foUowing the procedure as outlined in example 83, 1.64 g of 4- (4-methoxy-benzenesulfonyl)-l-(3-phenyl-propyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white solid. Yield 37%; mp 143 °C; MS: 432.9 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 1.92-1.97 (m, 2H), 2.18-2.29 (m, 2H), 2.47 (d, 2H), 2.58 (t, J = 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, 7 H), 7.68, (d, J = 9 Hz, 2H), 9.3 (s, IH), 10.1 (s, IH). Example 92 1 -Tert-butyl-4-(4-meu oxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide tert-Butyl-bis-(2-chloro-emyl)-amine was prepared according to me general method as outhned 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) + . l-tert-Butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid ethyl ester was prepared according to the general method as outhned in example 83. Starting from 4- (methoxy-benzenesulfonyl) acetic acid ethyl ester (10 g, 38.76 mmol) and tert-butyl-bis-(2- chloro-ethyl)-amine (5.25 g, 22.53 mmol). Yield 5.37 g, (62%); brown oil; MS: 384 (M+H) + . l-tert-Butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid was prepared starting from l-tert-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester (5.37 g 14 mmol) dissolved in methanol (300 ml) and 10 N NaOH (23 ml). The resulting reaction mixture was worked up as outlined in example 83. Yield 1.52 g (30.6%); white powder, mp 204 °C; MS: 356 (M+H) + . Starting from l-tert-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid (320 mg, 0.9 mmol) and foUowing me procedure as outlined in example 83, 190 mg of 1-tert-butyl- 4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as a green solid. Yield 52%; mp 40 °C; MS: 371.1 (M+H) + ; 'H NMR (300 MHz, DMSO-d 6 ): δ 1.29 (s, 9H), 1.54 (m, 2H), 1.66 (m, 2H), 2.39 (m, 2H), 2.98 (m, 2H), 3.88 (s, 3H), 7.18 (d, 2H), 7.67 (d, 2H). Example 93 1 -Butyl-4-( med oxy-benzenesuhOnyl)-piperidine-4-carboxylic acid hydroxyamide Butyl-bis-(2-chloro-ethyl)-amine was prepared according to the general method as outhned 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) + . 1 -Butyl-4-(4-methoxy-benzenesuh c Onyl)-piperidine-4-carboxyUc acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from 4-(methoxy- benzenesulfonyl) acetic acid ethyl ester (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-carboxyhc acid was prepared starting from l-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc 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 outhned 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 foUowing the procedure as outlined in example 83, 200 mg of l-butyl-4-(4- methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide was isolated as an off white solid. Yield 9.3%; mp 75 °C; MS: 371.1 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.87 (t, J = 7.2 Hz, 3H), 1.27 (m, 2H), 1.59 (m, 2H), 2.27 (m, 2H), 2.45 (m, 2H), 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 1 -Cyclooctyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide Cyclooctyl-bis-(2-chloro-ethyl)-amine was prepared according to the general method as outhned in example 83. Starting from N-cyclooctyldiethanolamine (6 g, 28 mmol). Yield 10 g, (99%); off white solid; mp 158 °C; MS: 251.9 (M+H) + . l-Cyclooctyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outhned in example 83. Starting from 4- (methoxy-benzenesulfonyl) acetic acid ethyl ester (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-carboxyhc 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 outhned 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-carboxyhc acid (2.26 g, 5.53 mmol) and following the procedure as outlined in example 83, 570 mg of 1- cyclooctyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as a white powder. Yield 22%; mp >200 °C; MS: 425 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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). 5 Example 95 l-Ethyl-4-(4-medιoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide l o 1 -Ethyl-4- (4-methoxy-benzenesuhOnyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outhned in example 83. Starting from 4-(methoxy- benzenesulfonyl) acetic acid ethyl ester (3 g, 11.6 mmol) and ethyl-bis-(2-chloro-ethyl)-arnine (2.39g, 11.6 mmol). Yield 3.09 g, (75%); low melting brown solid; MS: 356 (M+H) + . 15 1 -Ethyl-4-(4-methoxy-bεnzenesulf onyl)-piperidine-4-carboxylic acid was prepared starting from l-ethyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester (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 outlined in example 83. Yield 1.29 g (58%); white sohd; mp 209 °C; MS: 328 (M+H) + . 20 Starting from l-ethyl-4-(4-methoxy-benzenesuhonyl)-piperidine-4-carboxylic acid (1.23 g, 3.76 mmol) and following the procedure as outlined in example 83, 1.02 g of l-ethyl-4-(4- methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide was isolated as an off white powder. Yield 80%; mp 85 °C; MS: 343 (M+H) + ; Η NMR (300 MHz, DMSO-d g ): δ 25 0.926 (t, J =7.1 Hz, 3H), 1.68-1.89 (m, 4H), 2.05-2.24 (m, 4H), 2.73 (q, 2H), 3.85 (s, 3H), 7.07 (d, 2H), 7.64 (d, 2H). Example 96 30 l-Isopropyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide l-Isopropyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outhned in example 83. Starting from 4- (methoxy-benzenesulfonyl) acetic acid ethyl ester (5.7 g, 22.2 mmol) and isopropyl-bis-(2- 35 chloro-ethyl)-amine (4.9 g, 22.2 mmol). Yield 5.64 g, (68%); low melting brown solid; MS: 370 (M+H)\ l-Isopropyl-4-(4-methoxy-benzenesuUOnyl)-piperidine-4-carboxyhc acid was prepared starting from l-isopropyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid etfiyl 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 outlined 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-benzenesuh 0 onyl)-piperidine-4-carboxyhc acid (2.13 g, 6.25 mmol) and following the procedure as outhned in example 83, 590 mg of 1-isopropyl- 4-(4-methoxy-benzenesuh c onyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as a white powder. Yield 2.4%; mp 75 °C; MS: 357 (M+H) + ; 'H NMR (300 MHz, DMSO-d 6 ): δ 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 1 -Methyl-4- (4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide l-Methyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outUned in example 83. Starting from 4-(methoxy- benzenesulfonyl) acetic acid ethyl ester (3 g, 11.6 mmol) and methyl-bis-(2-chloro-efhyl)- amine (2.2g, 11.6 mmol). Yield 3.09 g, (75%); low melting brown solid; 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-carboxyhc 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 oudined in example 83. Yield 3.23 g (41%); white sohd; 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 as outhned in example 83, 1.10 g of l-methyl-4-(4- methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as a yeUow powder. Yield 53%; mp 89 °C; MS: 329 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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 1 -Benzyl-4-(4-butoxy-benzenesuh c onyl)-piperidine-4-carboxyUc acid hydroxyamide l-Benzyl-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from from 4-(butoxy- benzenesulfonyl) acetic acid ediyl ester (6 g, 20 mmol) and bis-(2-chloro-ethyl)-benzylamine (10 g, 30 mmol). Yield 5.15 g (56%); 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:metiιanol 3:1 and 10 N NaOH (10 ml). The resulting reaction mixture was worked up as outlined in example 83. Yield 2.66 g (56%); off white solid; mp 210 °C; MS: 432 (M+H) + . Starting from l-benzyl-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid (2.61 g, 6.06 mmol) and following the procedure as outhned in example 83, 860 mg of l-bεnzyl-4-(4- butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white powder. Yield 32%; mp 144 °C; MS: 446.9 (M+H) + ; Η NMR (300 MHz, DMSO-d : δ 0.94 (t, J = 7.3 Hz, 3H), 1.44 (q, J = 7.5 Hz, 2H), 1.70 (q, 2H), 2.28-2.32 (m, 2H), 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, IH), 10.7 (s, IH). Example 99 l-(4-Huoro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide l-(4-Huoro-benzyl)-4-(4-medιoxy-benzenesuU ? onyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to die general mediod as outlined in example 83. Starting from 4- (med oxy-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 oh; MS: 436.9 (M+H)\ l-(4-Huoro-benzyl)-4-(4-methoxy-benzeriesulfonyl)-piperidine-4-carboxylic acid was prepared starting from l-(4-fluoro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4- carboxylic acid ethyl ester (17.4 g, 40 mmol) dissolved in THF:med anol 3:1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as outhned in example 83. Yield 10.8 g (66%); colorlesssohd; mp 154 °C; MS: 408 (M+H) + . Starting from l-(4-Huoro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid (8.14 g, 20 mmol) and following the procedure as outhned in example 83, 4.3 g of l-(4- fluoro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white solid. Yield 51%; mp 176-178 °C; MS: 484.7 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 9.75 (s, IH). Example 100 1 -(4-Fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide l-(4-Fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to me general method as outhned in example 83. Starting from from 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) + . l-(4-Ruoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid was prepared starting from l-(4-Fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid ethyl ester (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 oudined in example 83. Yield 3.5 g (79%); off white solid; mp 114 °C; MS : 450 (M+H) * . Starting from l-(4-Fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid (2.24 g, 5.0 mmol) and following the procedure as outlined in example 83, 200 mg of l-(4- Fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxyamide was isolated as an off white powder. Yield 9%; mp 112 °C; MS: 465.9 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 10.55 (s, IH). Example 101 4-(4-methoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(4-methoxy-benzyl)-amino]-ethanol was prepared according to the general method as outhned in example 83. Starting from diethanolamine ( 12.0 g, 114 mmol) and 4-methoxybenzyl chloride ( 14.2 g, 100 mmol). Yield 17.5 g, (77 %); yeUow oil; MS: 226 (M+H). 4-Methoxybenzyl-bis-(2-chloro-ethyl)-amine was prepared according to d e general method as outhned in example 83. Starting from 4-Methoxy-benzyl diedianolamine (10 g, 44 mmol). Yield 10 g (75 %); yellow solid mp 55 C; MS: 263.1 (M+H) + . 4-(4-Medιoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)piperidine-4-carboxyUc acid eti yl ester was prepared according to die general method as outlined in example 83. Starting from 4- (metiιoxy-benzenesulfonyl)-acetic acid ethyl ester (5.0 g, 20 mmol) and bis- (2-chloro ediyl)- (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-benzenesulfony 1) 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-Methoxy-benzenesulfonyl)-l-(4-methoxy-benzyl)piperidine-4- carboxylic acid ethyl ester (4.2g, 10 mmol) dissolve in methanol (30 mL) , 10 N sodium hydroxide (10 mL), tetrahydrohydrofuran (20 mL). The resulting reaction mixture was worked up as outlined in example 83. Yield 3.0 g (71 %). white solid mp 190 °C , MS: 420.4 (M+H)\ Starting from 4-(4-methoxy-benzenesulfonyl)- l-(4-medιoxy-benzyl)-piperidine-4-carboxylic acid (2.0 g, 4.7 mmol) and following the procedure as oudined in example 83, 1.2 g of 4-(4- methoxy-benzenesulfonyl)-l-(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxamide was isolated as a white solid, mp 175 °C (HCI); Yield: 1.2 g, 59 %; MS: 433.0 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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 (bs, IH), 10.9 (bs, IH). Example 102 4-(4-methoxy-benzenesulfonyl)- 1 -[2-(4-methoxyphenyl)-ethyl] -piperidine-4-carboxyUc acid hydroxyamide 2- {(2-Hydroxy-ethyl)-[2-(4-methoxy-phenyl)-ethyl]-amino} -ethanol was prepared according to the general method as outhned in example 83. Starting from diedianolamine (10.0 g, excess), and l-(2-chloroethyl)-4-methoxybenzene (8.5 g, 50 mmol). Yield 11 g, (92%); yeUow oil; MS: 240 (M+H) + . The corresponding dichloride, bis-(2-chloro-ethyl)-(4-methoxyphenyl-2-edιyl)-amine was prepared according to the general mediod as outiined in example 83. Starting from 2- { (2- hydroxy-edιyl)-[2-(4-methoxy-phenyl)-ethyl]-amino} -ethanol (10 g, 41.8 mmol). Yield 11 g (95%); brown oil; MS: 277.2 (M+H) + . 4-(4-medιoxy-benzenesulfonyl)- 1 -[2-(4-methoxyphenyl)-ethyl]-piperidine-4-carboxyhc acid ediyl ester was prepared according to the general method as outhned in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid ethyl ester (5.0 g, 20 mmol) and bis-(2- chloro-ethyl)-(4-methoxyphenyl-2-ethyl)-amine (6.4 g, 20 mmol). Yield 6.0 g (65%); brown oil; MS: 462.5 (M+H) + . 4-(4-methoxy-benzenesulfonyl)- 1 -[2-(4-medιoxyphenyl)-ethyl]-piperidine-4-carboxyhc acid was prepared starting from 4-(4-methoxy-benzenesulfonyl)-l-[2-(4-methoxyphenyl)-ethyl]- piperidine-4-carboxylic acid ethyl ester (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 outiined in example 83. Yield 4.0 g (85%); off white 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 as outlined in example 83, 900 mg of 4-(4-methoxy-benzenesulfonyl)-l-[2-(4-methoxyphenyl)-ethyl]-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white solid. Yield 58%; mp 206 °C (HCI); MS: 449.5 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 2.3 (m, 2H), 2.5 (m, 3H), 2.8 (m, 2H), 2.95 (m, 2H), 3.25 ( , 2H), 3.4 (m,4H), 3.60 (d, J = 12.3 Hz, 2H), 3.77 (s, 3H),3.99 (s, 3H), 6.9 (d, 2 H), 7.1 - 7.25, (q, 4H), 7.7 (d, 2H), 9.3 (s, IH), 10.6 (s, IH). Example 103 4-(4-medιoxy-benzenesulfonyl)- 1 -(2-phenyl-ethyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(2-phenyl-ethyl)-aminoj-ethanol was prepared according to the general method as outlined in example 1. Starting from diethanolamine (6.0 g, 57). and 2-bromo- ethylbenzene (9.0 g, 48.3 mmol). Yield 9 g, (90%); yellow ott; MS: 210 (M+H) + . Bis-(2-Chloro-emyl)-(2-phenyl-ethyl)-amine was prepared according to die general method as outhned in example 83. Starting from 2-[(2-Hydroxy-emyl)-(2-phenyl-ethyl)-amino]-ethanol (8.5 g, 40.6 mmol). Yield 11 g (95%); brown oil; MS: 247.1 (M+H) + . 4-(4-methoxy-benzenesulfonyl)- 1 -(2-phenyl-ed yl)-piperidine-4-carboxylic acid etiiyl ester was prepared according to the general method as outhned in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid etiiyl 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 oU; MS: 432.5 (M+H) + . 4-(4-methoxy-benzenesulfonyl)-l-(2-phenyl-ethyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-methoxy-bεnzenesulfonyl)- l-(2-phenyl-edιyl)-piperidine-4-carboxylic acid ethyl ester (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 outiined in example 83. Yield 2.0 g (72%); off white powder, mp 208 °C; MS: 404.5 (M+H) + . Starting from 4-(4-methoxy-bεnzenesulfonyl)- 1 -(2-phenyl-ethyl)-piperidine-4-carboxylic acid (1.5 g, 3.7 mmol) and following the procedure as outlined in example 83, 900 mg of 4-(4- methoxy-benzenesulfonyl)-l-(2-phenyl-ethyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white solid. Yield 58%; mp 205 °C (HCI); MS: 419.4 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 2.3 (m, 2H), 2.5 (m, 3H), 2.8 (m, 2H), 2.95 (m, 2H), 3.25 (m, 2H), 3.4 (m,4H), 3.9 (s, 3H),7.22 - 7.8 (m, 9H), 10.6 (s, IH), 11.2 (bs, IH). Example 104 4-(4-n-Butoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide 4-(4-n-Butoxy-benzenesulfonyl)-l-(4-methoxy-benzyl)piperidine-4-carboxyhc acid etiiyl ester was prepared according to the general mediod as outlined in example 83. Starting from 4-(n- Butoxy-benzenesulfonyl)-acetic acid etiiyl ester (2.5 g, 10 mmol) and bis- (2-chloro etfιyl)-(4- medioxy-benzy -amine (3.0 g, 10 mmol). Yield 3.5 g (71 %); low melting sohd; MS: 490.5 (M+H) + . 4-(4-n-Butoxy-benzenesulfonyl) 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-Butoxy-benzenesuh c onyl)-l-(4-methoxy-benzyl)piperidine-4- carboxyhc acid ethyl ester (3.0g, 6.1 mmol) dissolve in methanol (30 mL) , 10 N sodium hydroxide (10 mL), tetrahydrohydrofuran (20 mL). The resulting reaction mixture was worked up as outlined in example 83. Yield 1.5 g (53 %). white solid mp 207 °C , MS: 462.5 (M+H)\ Starting from 4-(4-n-Butoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)-piperidine-4-carboxyhc acid (1.0 g, 2.1 mmol) and following the procedure as outlined in example 83, 1.2 g of 4-(4- Butoxy-benzenesulfonyl)- l-(4-methoxy-benzyl)-piperidine-4-carboxyhc acid hydroxamide was isolated as a white solid, mp 173 °C (HCI); Yield: 800 mg, 77 %; MS: 477.5 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.9 (t, 3H), 1.4 (m, 2H), 1.7 (m,2H), 2.3 (m, 2H), 2.5 (m, 2H), 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 (bs, IH), 10.9 (bs, IH). Example 105 4-(4-Methoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(3-phenoxy-propyl)-amino]-ethanol was prepared according to the general mediod as outhned in example 83. Starting from diethanolamine (15.8 g, 151 mmol). and 3-Phenoxypropyl bromide (21.5 g, 100 mmol). Yield 21.31 g, (95%); yellow oU; MS: 238.1 (M+H) + . Bis-(2-Chloro-ethyl)-(3-phenoxy-propyl)-amine was prepared according to the general method as outlined in example 83. Starting from 2-[(2-hydroxy-ethyl)-(3-phenoxy-propyl)-aminoj- ethanol (20.0 g, 84 mmol). Yield 24.0 g (91%); brown oh; MS: 277.8 (M+H) + . 4-(4-Medιoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperidine-4-carboxyhc acid etiiyl ester was prepared according to the general method as outhned in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid ethyl ester (5.2 g, 20 mmol) and bis-(2-chloro-ethyl)- (3-phenoxy-propyl)-amine (7.0 g, 22 mmol). Yield 6.5 g (70%); brown oil; MS: 462.5 (M+H) + . 4-(4-Medιoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-Methoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperidine-4- carboxylic acid ethyl ester (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 outhned in example 83. Yield 3.0 g (75%); off white powder; mp 195 °C; MS: 434.5 (M+H) + . Startmg from 4-( methoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperid ή ιe-4-carboxylic acid (2.5 g, 5.77 mmol) and following the procedure as outhned in example 83, 1.2 g of 4-(4- methoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxylic acid hydroxyamide was isolated as an off white solid. Yield 46%; mp 101 °C; MS: 448.5 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 2.18 (m, 2H), 2.3 (m, 2H), 2.58 (m, 2H), 2.6-2.73 (m, 2H), 3.0-3.06 (m, 2H), 3.60 (m 2H), 3.87 (s, 3H), 4.01 (t, 2H), 6.9 - 7.7 (m, 9H), 9.33 (bs, IH), 10.28 (bs, IH). Example 106 4-(4-n-Butoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperidine-4-carboxylic acid hydroxyamide 4-(4-n-Butoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in example 83. Starting from from 4-(butoxy-benzenesulfonyl) acetic acid ethyl ester (3.0 g, 10 mmol) and bis-(2-chloro-edιyl)- (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-carboxyhc acid was prepared starting from 4-(4-n-Butoxy-benzenesulfonyl)-l-(3-phenoxy-propyl)-piperidine-4- carboxylic acid ethyl ester (4.0 g, 7.9 mmol) dissolved in THRMethanol 3: 1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as outhned in example 83. Yield 3.0 g (79%); off white powder, mp 191 °C; MS: 476.5 (M+H) + . Starting from 4-(4-n-butoxy-benzenesulfonyl)- l-(3-phenoxy-propyl)-piperidine-4-carboxylic acid (700 mg, 1.4 mmol) and following the procedure as outiined in example 83, 300 mg of 4- (4-n-butoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxyhc acid hydroxyamide was isolated as an off white soUd. Yield 43%; mp 84 °C; MS: 491.5 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.9 (t, 3H), 1.5 (m, 2H), 1.8 (m, 2H), 2.18 (m, 2H), 2.3 (m, 2H), 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 (bs, IH), 11.28 (bs, IH). Example 107 4-(4-methoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxylic acid hydroxyamide 2-[(2-Hydroxy-ethyl)-(2-phenoxy-edιyl)-amino]-ethanol was prepared according to the general mediod as outiined in example 83. Starting from diethanolamine (15.0 g, 150). and 2-chloro- phenetol (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 as outlined 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)\ 4-(4-methoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxylic acid etiiyl ester was prepared according to the general method as outiined in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid ethyl ester (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)- l-(2-phenoxy-ethyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-methoxy-benzenesulfonyl)-l-(2-phenyl-ethoxy)-piperidine-4- carboxylic acid ethyl ester (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 outhned in example 83. Yield 3.0 g (63%); off white powder, mp 235 °C; MS: 420.5 (M+H) + . Starting from 4-(4-methoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxylic acid (2.5 g, 5.9 mmol) and following the procedure as outhned in example 83, 1.3 g of 4-(4- methoxy-benzenesulfonyl)- 1 -(2-phenoxy-edιyl)-piperidine-4-carboxyhc acid hydroxyamide was isolated as an off white sohd. Yield 50%; mp 168-172 °C (HCI); MS: 435.4 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 2.3 (m, 2H), 2.5 (m, 2H), 2.9 (m, 2H), 3.4 (m, 4H), 3.5 (m, 2H), 3.7 (m,2H), 3.9 (s, 3H), 4.4 (m, 2H), 6.9 - 7.8 (m, 9H), 9.3 (s, IH), 10.2 (bs, IH), 11.3 (s, IH). Example 108 4-(4-n-Butoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxylic acid hydroxyamide 4-(4-Butoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-ρiperidine-4-carboxy c acid ethyl ester was prepared according to the general method as outiined in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid etiiyl ester (2.5 g, 10 mmol) and bis-(2- chloro-ethyl)-(2-phenoxy-ethyl)-amine (2.98 g, 10 mmol). Yield 3.0 g (69%); brown oil; MS: 490.6 (M+H) + . 4-(4-n-Butoxy-benzenesulfonyl)-l-(2-phenoxy-ethyl)-piperidine-4-carboxylic acid was prepared starting from 4-(4-n-butoxy-benzenesulfonyl)-l-(2-phenyl-ethoxy)-piperidine-4- carboxylic acid ethyl ester (2.5 g, 5.76 mmol) dissolved in THF:methanol 3:1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as outlined in example 83. Yield 1.5 g (56%); off white 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 as outhned in example 83, 600 mg of 4- (4-butoxy-benzenesulfonyl)- 1 -(2-phenoxy-ethyl)-piperidine-4-carboxyhc acid hydroxyamide was isolated as an off white sohd. Yield 58%; mp 112 °C (HCI); MS: 477.4 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 0.942 (t, 3H), 1.4 (m, 2H), 1.7 (m, 2H), 2.3 (m, 2H), 2.5 (m, 4H), 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, IH), 10.5 (bs, IH), 11.3 (s, IH). Example 109 4-(4-Methoxy-benzenesulfonyl)-l-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-piperidin e-4-carboxylic acid hydroxyamide Bis-(2-chloro-ethyl)-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-amine was prepared according to the general method as outiined in example 83. Starting from diethanolamine (15.0 g, 150). and 4- (2-piperidin-l-yl-ethoxy)- benzyl chloride (5.9 g, 20 mmol). Yield 5.5 g, (85%); Brown semi- solid; MS: 323 (M+H) + . Bis-(2-chloro-ethyl)-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-amine was prepared according to die general method as outhned in example 83. Starting from 2-[(2-Hydroxy-ethyl)- [4-(2- piperidin-l-yl-ethoxy)-benzyl]-amine (3.22 g, 10 mmol). Yield 4.0 g (92%); brown semi- solid; MS: 361.1 (M+H) + . 4-(4-Methoxy-benzenesulfonyl)- 1 -[4-(2-piperidin- 1 -yl-ethoxy)-benzyl] -piperidin e-4-carboxylic acid ethyl ester was prepared according to the general method as outhned in example 83. Starting from from 4-(methoxy-benzenesulfonyl) acetic acid ethyl ester (5.0 g, 20 mmol) and Bis-(2-chloro-ethyl)-[4-(2-piperidin-l-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)-l-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-piperidine-4- carboxylic acid was prepared starting from 4-(4-Metiιoxy-benzenesuhOnyl)-l-[4-(2-piperidin- l-yl-ethoxy)-benzyl]-piperidine-4-carboxylic acid ethyl ester (5.4 g, 10 mmol) dissolved in THF:methanol 3:1 and 10 N NaOH (40 ml). The resulting reaction mixture was worked up as outlined in example 83. Yield 4.0 g (77%); off 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 e-4-carboxyhc acid (3.5 g, 6.78 mmol) and following the procedure as outlined in example 83,1.8 g of 4-(4-Methoxy-benzenesulfonyl)-l-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-piperidin e-4-carboxylic acid hydroxy amidewas isolated as an pale yeUow soUd. Yield 49%; mp 114 °C (HCI); MS: 532 (M+H) + ; Η NMR (300 MHz, DMSO-d 6 ): δ 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, IH), 6.9 - 7.8 (m, 8H), 9.1 (s, IH), 10.8 (bs, IH). Example 110 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-propionamide Step A: Coupling of 2-bromo-propionic acid to hydroxylamine resin. 4-O-Medιymydroxylarnme-phenoxymethyl-copoly(styrene-l %-divinylbenzene)-resin 1 (2 g , 1.1 meq/g) was placed in a peptide syndiesis 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, 6.0 eq.) and 1,3-dUsopropylcarbodhmide (DIC, 1.4 mL, 4.0 eq.) were added. The reaction was shaken 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 (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). (A wash consisted of addition of the solvent and agitation either by nitrogen bubbling or shaking on the orbital shaker for 1-5 minutes, then filtration under vacuum). The resin was dried in vacuo at room temperature. A sample of resin (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 washed with DCM (1 x 1 mL). The filtrate and the washing were combined and concentrated in vacuo on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. The product was then characterized by H'NMR, (DMSO d-6) δ 4.54 (q, IH), 1.83 (d, 3H). Step B: Displacement of bromide with 4-methoxybenzenethiol. The N-Hydroxy-2-bromo-propionamide resin prepared in Step A (0.35 g, 1.1 meq/g) was placed in a 20 mL scintiUation vial and suspended in THF (2 mL). 4-Methoxybenzenethiol (0.23 mL, 5.0 eq.), sodium iodide (288 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.17 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 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% tert-butylhydroperoxide (1.0 mL) and benzenesulfonic acid (50 mg) were added. The reaction mixture was shaken 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. 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 mCPBA (180 mg) was added. The reaction mixture was shaken 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 N-Hydroxy-2-(4-methoxy-benzenesulfonyl)-propionamide from 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed with DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and d e mixture concentrated. 84% @ 215 nm; Η ΝMR (DMSO d-6) δ 10.75 (brs, 1 H), 7.95 (brs, 1 H), 7.71 (dd, 2 H), 7.16 (dd, 2 H), 3.87 (s, 3 H), 3.83 (q, 1 H), 1.26 (d, 3 H). The hydroxamic acids of Examples 111-113 are synthesized using appropriate starting materials and foUowing the steps in example 110. Example 111 N-Hydroxy-2-(4-methoxy-benzenesulfanyl)-propionamide. 72% @ 215 nm N-Hydroxy-2-(4-methoxy-benzenesulfinyl)-propionamide. 76% @ 215 nm; Η ΝMR (DMSO d-6) δ 10.90 &10.60 (brs, 1 H), 7.95 (brs, 1 H) 7.61 & 7.52 (dd, 2 H), 7.15 & 7.10 (dd, 2 H), 3.83 & 3.82 (s, 3 H), 3.42 & 3.28 (q IH), 1.23 & 0.97 (d, 3 H). Example 112 N-Hydroxy-2-(3-methyl-butane-l-sulfanyl)-propionamide. 74% @ 215 nm. N-Hydroxy-2-(3-methyl-butane-l-sulfinyl)-propionamide. 'H ΝMR (DMSO d-6) δ 10.8 (brs 1 H), 7.95 (brs, 1 H), 3.45 & 3.31 (q, 1 H), 2.71 -2.50 (m, 2 H), 1.71-1.46 (m, 3 H), 1.33 & 1.25 (d, 3 H), 0.94-0.82 (m, 6 H) Example 113 N-Hydroxy-2-(3-methyl-butane-l-sulfonyl)-propionamide. 84% @ 215 nm. Example 114 Ν-hydroxy-3-methyl-2-(naphthalen-2-ylsulfanyl)-butyramide Step A: Coupling of 2-bromo-3-methyl-butyric acid to hydroxylamine resin. 4-O-Medιymydroxylamme-phenoxymethyl-copoly(styrene-l%-divinylbenzene)-resin 1 (5 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 shaken 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 (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 bromide with 2-naphthalenethiol. The 2-bromo hydroxymate resin prepared in Step A (0.15 g, 1.1 meq/g) was placed in a 20 mL scintillation vial and suspended in THF (2 mL). 2-Naphthalenethiol (138 mg, 5.0 eq.), sodium iodide (129 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.078 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 2-(2-Naphthalenesulfanyl)-N-hydroxypropionamide resin 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) were added. The reaction mixture was shaken 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. 2-(2-Naphthalenesuh c anyl)-N-hydroxypropionamide 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 shaken 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 N-Hydroxy-3-methyl-2-(naphthalen-2-ylsulfanyl)-butyramide from resin. The 2-(2-Νaphthalenesuh c anyl)-N-hydroxypropionamide 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed witii DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 83% @ 215 nm; LCMS (API-electrospray) mz 276 (M+H) + ; Η ΝMR (DMSO d-6) δ 10.7 (brs, 1 H), 7.91 (brs, 1 H), 7.91-7.81 (m, 4 H), 7.55-7.45 (m, 3 H), 3.41 (d, 1 H), 2.09- 1.97 (m, 1 H), 1.05 (d, 3 H), 0.97 (d, 3 H). The hydroxamic acids of Examples 115-118 are synthesized using appropriate starting materials and foUowing the steps in example 114: Example 115 N-Hydroxy-3-methyl-2-(naphthalen-2-ylsulfinyl)-butyramide. 67% @ 215 nm. Example 116 N-Hydroxy-3-methyl-2-(naρhthalen-2-ylsulfonyl)-butyramide. 97% @ 215 nm; LCMS (API- electrospray) m z 308 (M+H) + . Example 117 N-Hydroxy-3-methyl-2-phenethylsulfinyl-butyramide. 93% @ 215 nm; LCMS (API- electrospray) m/z 254 (M+H) + . Example 118 N-Hydroxy-3-medιyl-2-phenethylsulfonyl-butyramide. 97% @ 215 nm; LCMS (API- electrospray) m/z 286 (M+H) + . Example 119 (l-Hydroxycarbamoyl-propane-l-sulfanyl)-acetic acid methyl ester Step A: Coupling of 2-bromobutyric acid to hydroxylamine resin. 4-O-Methy ydroxylamine-phenoxymedιyl-copoly(styrene- 1 %-divinylbenzene)-resin 1 (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 shaken 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 die presence of free amine (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 bromide with methyl thioglycolate. The 2-bromo hydroxymate resin prepared in Step A (0.45 g, 1.1 meq/g) was placed in a 20 mL scintiUation vial and suspended in THF (2 mL). Metiiyl thioglycolate (286 mg, 5.0 eq.), sodium iodide (404 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.24 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. (l-Hydroxycarbamoyl-propane-l-sulfanyl)-acetic acid methyl ester resin prepared in Step B (150 mg, 1.1 meq/g) was suspended in DCM (3.0 mL) and 70% t -butylhydroperoxide (1.0 mL) benzenesulfonic acid (50 mg) were added. The reaction mixture was shaken 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. (l-Hydroxycarbamoyl-propane-l-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 shaken 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 (l-Hydroxycarbamoyl-propane-l-sulfanyl)-acetic acid methyl ester from resin The (l-Hydroxycarbamoyl-propane-l-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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed witii DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. LCMS (API-electrospray) m/z 228 (M+Na) + . The hydroxamic acids of Examples 120-124 are synthesized using appropriate starting materials and foUowing the steps in example 119. Example 120 (l-Hydroxycarbamoyl-propane-l-sulfonyl)-acetic acid hydroxyamide. LCMS (API- electrospray) m/z 224 (M+H) + . Example 121 (l-Hydroxycarbamoyl-propane-l-sulfιnyl)-acetic acid hydroxy amide. 100% @ 220 nm; LCMS (API-electrospray) m/z 240 (M+H)\ Example 122 (l-Hydroxycarbamoyl-propane-l-sulfanyl)-propionic acid hydroxyamide. Η NMR (DMSO d-6) δ 10.7 (brs, 1 H), 4.03 (t, 2 H), 2.95 (q, 1 H), 2.75-2.70 (m, 1 H), 2.60-2.54 (m, 1 H), 1.74-1.66 (m, 2 H), 1.58-1.50 (m, 4 H), 1.32 (sextet, 2 H), 0.88 (t, 3 H), 0.85 (t, 3 H); LCMS (API-electrospray) m z 264 (M+H) + . Ill Example 123 (l-Hydroxycarbamoyl-propane-l-sulfinyl)-propionic acid hydroxyamide. 83% @ 220 nm; LCMS (API-electrospray) m/z 280 (M+H) + . Example 124 (l-Hydroxycarbamoyl-propane-l-sulfonyl)-propionic acid hydroxyamide. 100% @ 220 nm; Example 125 2-(4-Hydroxybenzenesulfanyl)-N-hydroxy-3-phenyl-propionamide Step A: Coupling of 2-bromo-3-phenyl-propionic acid to hydroxylamine resin. 4-O-Medιy ydroxylam e-phenoxymethyl-copoly(styrene- 1 %-divinylbenzene)-resin' (5 g , 1.2 meq/g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). 2- Bromo-3-phenyl-propionic 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 shaken 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 die test showed die presence of free amine (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 bromide with 4-hydroxythiophenol. The 2-bromo hydroxymate resin prepared in Step A (0.33 g, 1.2 meq/g) was placed in a 20 mL scintillation vial and suspended in THF (2 mL). 4-Hydroxythiophenol (250 mg, 5.0 eq.), sodium iodide (297 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.18 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 2-(4-Hydroxybenzenesulfanyl)-N-hydroxy-3-phenyl-propionamide resin prepared in Step B (110 mg, 1.1 meq/g) was suspended in DCM (3.0 mL) and 70% rt-butylhydroperoxide (0.73 mL) benzenesulfonic acid (36 mg) were added. The reaction mixture was shaken 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. 2-(4-Hydroxybenzenesulfanyl)-N-hydroxy-3-phenyl-propionamide resin 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 shaken 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 2-(4-Hydroxybenzenesulfanyl)-N-hydroxy-3-phenyl-propionamide from resin. The 2-(4-Hydroxybenzenesuh c anyl)-N-hydroxy-3-phenyl-propionamide 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed witii DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 84% @ 215 nm; ! H ΝMR (DMSO d-6) δ 10.41 (brs, 1 H), 7.95 (brs (1 H), 7.30-7.15 (m, 5 H), 7.10 (dd, 2 H), 6.75 (dd, 2 H), 3.53 (q, 1 H), 3.05 (dd, 1 H), 2.79 (dd, 1 H). The hydroxamic acids of Examples 126-130 are synthesized using appropriate starting materials and foUowing the steps in 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; Η ΝMR (DMSO d-6) δ 10.50 (brs, 1 H), 7.95 (brs, 1 H), 7.68-7.57 (m, 2 H), 7.28-7.17 (m, 3 H), 7.08-7.98 (m, 2 H), 6.95-6.87 (m, 2 H), 3.96 (t, 1 H), 3.02 (d, 2 H). Example 128 2-(4-Acetylamino-benzenesuh c anyl)-N-hydroxy-3-phenyl-propionamide. 86% @ 215 nm; Η ΝMR (DMSO d-6) δ 10.50 (brs, 1 H), 10.03 (brs, 1 H), 8.13 (brs, 1 H), 7.56-7.12 (m, 9 H), 3.67 (q, 1 H), 3.08 (dd, 1 H), 2.84 (dd, 1 H), 2.04 (s, 3 H) Example 129 2-(4-Acetylamino-benzenesulfinyl)-N-hydroxy-3-phenyl-propionamide. 73% @ 215 nm. Example 130 2-(4-Acetylammo-rjen2enesulfonyl)-N-hydroxy-3-phenyl-propionamide. 95% @ 215 nm; Example 131 4-Hydroxycarbamoyl-4-(4-methanesulfanyl-phenylsulfanyl)-butyric acid methyl ester Step A: Couphng of 2-bromo-5-methyl glutaric acid to hydroxylamine resin. 4-O-Methy ydroxylarnine-phenoxymethyl-copoly(styrene- 1 %-divinylbenzene)-resin 1 (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 shaken 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 (resin turned blue) the coupling described above was repeated, odierwise 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 bromide with 4-hydroxythiophenol. The 2-bromo hydroxymate resin prepared in Step A (0.22 g, 1.2 meq/g) was placed in a 20 mL scintiUation vial and suspended in THF (2 mL). 4-(Medιylthio)thiophenol (206 mg, 5.0 eq.), sodium iodide (197 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted with a polypropylene frit, filtered and washed with DMF (2 x 2 mL), DMRwater 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 sulfide to sulfoxide. 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% tert- butylhydroperoxide (0.49 mL) benzenesulfonic acid (24 mg) were added. The reaction mixture was shaken 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. 4-Hydroxycarbamoyl-4-(4-methanesulfanyl-phenylsulfanyl)-butyric acid metiiyl ester 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 shaken 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 4-Hydroxycarbamoyl-4-(4-methanesulfanyl-phenylsulfanyl)-butyric acid methyl ester from 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) was added. The reaction was shaken for 1 hour at room temperature. The reaction was filtered and die resin washed with DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Metiianol (1 mL) was added and the mixture concentrated. 77% @ 215 nm; LCMS (API-electrospray) m/z 316 (M+H) + . The hydroxamic acids of Examples 132-139 are synthesized using appropriate starting materials and foUowing the steps in example 131. Example 132 4-Hydroxycarbamoyl-4-(4-methanesulfinyl-phenylsuUϊnyl)-butyric acid hydroxyamide. 79% @ 215 nm; LCMS (API-electrospray) m/z 348 (M+H) + . Example 133 4-Hydroxycarbamoyl-4-(4-methanesulfonyl-phenylsulfonyl)-butyric acid hydroxyamide. 78% @ 215 nm; LCMS (API-electrospray) m/z 380 (M+H) + . Example 134 4-Hydroxycarbamoyl-4-(4-bromo-benzenesuh c anyl)-butyric acid hydroxyamide. 93% @ 215 nm. Example 135 4-Hydroxycarbamoyl-4-(4-bromo-benzenesuh c inyl)-butyric acid hydroxyamide. 80% @ 215 nm. Example 136 4-Hydroxycarbamoyl-4-(4-bromo-benzenesulfonyl)-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-trifluoromed yl-benzenesulfinyl)-butyric acid hydroxyamide. 72% @ 215 nm. Example 139 4-Hyά^xycarbamoyl-4-(2-trifluorornethyl-benzenesuhOnyl)-butyric acid hydroxyamide. 90% @ 215 nm. Example 140 2-(3-methoxy-benzenesulfanyl)decanoic acid hydroxamide Step A:CoupUng of 2-bromo-decanoic acid to hydroxylamine resin. 4-O-Methylhyd^xylamine-phenoxymethyl-copoly(styrene- 1 %-divinylbenzene)-resin 1 (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 shaken 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 die Kaiser test. If die test showed die presence of free amine (resin turned blue) the coupling described above was repeated, otherwise die resin was washed widi 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 bromide widi 3-methoxy-benzenethiol. The 2-bromo hydroxymate resin prepared in Step A (0.22 g, 1.2 meq/g) was placed in a 20 mL scintiUation vial and suspended in THF (2 mL). 3-Methoxy-benzenethiol (185 mg, 5.0 eq.), sodium iodide (197 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 2-(3-Med oxy-benzenesulfanyl)decanoic acid hydroxamide 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) benzenesulfonic acid (24 mg) were added. The reaction mixture was shaken 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. 2-(3-Medιoxy-benzenesulfanyl)decanoic acid hydroxamide 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 shaken 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 2-(3-methoxy-benzenesulfanyl)decanoic acid hydroxamide from resin. The 2-(3-methoxy-benzenesulfanyl)decanoic acid hydroxamide 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed with DCM (2 x 1 mL). The filtrate and die washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 89% @ 215 nm. The hydroxamic acids of Examples 141-145 are synthesized using appropriate starting materials and foUowing die steps in example 140. Example 141 2-(3-Methoxy-benzenesulfinyl)decanoic acid hydroxamide. 96% @ 215 nm. Example 142 2-(3-Methoxy-benzenesulfonyl)decanoic acid hydroxamide. 96% @ 215 nm. Example 143 2-(4-methanesulfanyl-benzenesulfanyl)decanoic acid hydroxamide. 85% @ 215 nm; LCMS (API-electrospray) m/z 342 (M+H)\ Example 144 2-(4-methanesulfinyl-benzenesuUϊnyl)decanoic acid hydroxamide. 86% @ 215 nm; LCMS (API-electrospray) m/z 374 (M+H) + . Example 145 2-(4-medιanesulfonyl-benzenesuUOnyl)decanoic acid hydroxamide. 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 hydroxylamine resin. 4-O-Medιy ydroxylamme-phenoxymed yl-copoly(styrene-l%-divinylbenzene)-resin 1 (4.5 g, 1.2 meq/g) was placed in a peptide synthesis vessel and suspended in DMF (40 mL). S-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 shaken 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 die Kaiser test. If the test showed die presence of free amine (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 bromide with 4-(methylthio)d iophenol. The 2-bromo hydroxymate resin prepared in Step A (0.22 g, 1.2 meq/g) was placed in a 20 mL scintillation vial and suspended in THF (2 mL). 4-(Methyldιio)thiophenol (206 mg, 5.0 eq.), sodium iodide (197 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 3-Benzyloxy-N-hydroxy-2-(4-methanesulfanyl-benzenesulfanyl)-propionamide 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) benzenesulfonic acid (24 mg) were added. The reaction mixture was shaken 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. 3-Benzyloxy-N-hydroxy-2-(4-methanesulfanyl-benzenesulfanyl)-propionamide 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 shaken 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 3-benzyloxy-N-hydroxy-2-(4-meti anesulfanyl-benzenesulfanyl)- propionamide from resin. The 3-benzyloxy-N-hydroxy-2-(4-memanes fanyl-benzenesulfanyl)-propionamide 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed with DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 76% @ 215 nm; LCMS (API-electrospray) m/z 350 (M+H) + . The hydroxamic acids of Examples 147-151 are synthesized using appropriate starting materials and foUowing die steps in example 146. Example 147 3-Benzyloxy-N-hydroxy-2-(4-methanesulfinyl-benzenesuhϊnyl)-propionamide. 70% @ 215 nm; LCMS (API-electrospray) m/z 382 (M+H) + . Example 148 3-Benzyloxy-N-hydroxy-2-(4-methanesulfonyl-benzenesulfonyl)-propionamide. 63% @ 215 nm; LCMS (API-electrospray) m/z 414 (M+H) + . Example 149 3-Benzyloxy-N-hydroxy-2-(2-chloro-benzylsulfanyl)-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. 5 Example 152 2-(2-bromo-benzenesuhanyl)-Ν-hydroxy-3-(3H-imidazol-4-yl)-propionamide l o Step A: Coupling of 2-bromo-3-(3H-imidazol-4-yl)-propionic acid to hydroxylamine resin. 4-O-Me y ydroxylamine-phenoxymethyl-copoly(styrene- 1 %-divinylbenzene)-resin 1 (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)-propionic 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 shaken on an orbital shaker at room 15 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 d e Kaiser test. If d e test showed die presence of free amine (resin turned blue) the couphng 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. 20 Step B: Displacement of bromide with 2-bromothiophenol. The 2-bromo hydroxymate resin prepared in Step A (0.22 g, 1.2 meq/g) was placed in a 20 mL scintiUation vial and suspended in THF (2 mL). 2-Bromodιiophenol (249 mg, 5.0 eq.), sodium iodide (197 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 25 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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. 30 Step C: Oxidation of sulfide to sulfoxide. 2-(2-Bromo-benzenesulfanyl)-N-hydroxy-3-(3H-imidazol-4-yl)-propionamide 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) benzenesulfonic acid (24 mg) were added. The reaction mixture was shaken on an orbital shaker at room temperature for 12 - 24 hours. The reaction 35 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. 2-(2-Bromo-benzenesdfanyl)-N-hyαtoxy-3-(3H-imidazol-4-yl)-propionarrude 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 shaken on an orbital shaker at room temperature for 12 - 24 hours. The reaction was fdtered 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 2-(2-bromo-benzenes fanyl)-N-hyαVoxy-3-(3H-imidazol-4-yl)- propionamide from resin. The 2-(2-bromo-r^nzenesmfanyl)-N-hydroxy-3-(3H-imidazol-4-yl)-propionamide 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 shaken for 1 hour at room temperature. The reaction was filtered and the resin washed widi DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 86% @ 215 nm. The hydroxamic acids of Examples 153-154 are synthesized using appropriate starting materials and foUowing d e steps in example 152. Example 153 2-(4-bromo-benzenesulfmyl)-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-pentanic acid to hydroxylamine resin. 4-O-Medιy ydroxylamine-phenoxymed yl-copoly(styrene- 1 %-divinylbenzene)-resin 1 (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-pentanic 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 shaken on an orbital shaker at room temperature for 2 - 16 hours. The reaction was filtered and washed witi DMF (3 x 20 mL). A sample of resin was removed and subjected to the Kaiser test. If die test showed die presence of free amine (resin turned blue) die 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 bromide with 3-fluorodιiophenol. The 2-bromo hydroxymate resin prepared in Step A (0.22 g, 1.2 meq/g) was placed in a 20 mL scintillation vial and suspended in THF (2 mL). 3-Fluorothiophenol (169 mg, 5.0 eq.), sodium iodide (197 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.12 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 2-(3-Fluorophenylsuh c anyl)-5-guanidino-pentanoic acid hydroxyamide 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) benzenesulfonic acid (24 mg) were added. The reaction mixture was shaken 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. 2-(3-Fluorophenylsuh c anyl)-5-guanidino-pentanoic acid hydroxyamide 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 shaken 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 2-(3-fluorophenylsulfanyl)-5-guanidino-pentanoic acid hydroxyamide from resin. The 2-(3-fluorophenylsulfanyl)-5-guanidino-pentanoic 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 shaken for 1 hour at room temperature. The reaction was filtered and die resin washed widi DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. 93% @ 215 nm. The hydroxamic acids of Examples 156-159 are synthesized using appropriate starting 5 materials and foUowing d e steps in example 155: Example 156 2-(3-Fluorophenylsulfinyl)-5-guanidino-pentanoic acid hydroxyamide. 80% @ 220 nm; l o LCMS (API-electrospray) m/z 317 (M+H) + . Example 157 2-(2-Bromosulfanyl)-5-guanidino-pentanoic acid hydroxyamide. 92% @ 220 nm; ! H NMR 15 (DMSO d-6) δ 10.90 (brs, 2 H), 10.41 (brs, IH), 7.95 (brs, 1 H), 7.66-7.14 (m, 5 H), 3.72 (q, 1 H), 3.13 (q, 2 H), 1.90-1.66 (m, 2 H), 1.58-1.43 (2 H). Example 158 20 2-(2-Bromosulfinyl)-5-guanidino-pentanoic acid hydroxyamide.79% @ 220 nm; LCMS (API- electrospray) m/z 379 (M+H) + . Example 159 25 2-(2-Bromosulfonyl)-5-guanidino-pentanoic acid hydroxyamide. H NMR (DMSO d-6) δ 8.03-7.45 (m, 5 H), 4.52 (q, 1 H), 3.16 (q, 2 H), 2.07-1.90 (m, 2 H), 1.66-1.59 (2 H). Example 160 30 2-(2,5-dichlorobenzenesulfanyl)-octanoic acid hydroxyamide Step A: CoupUng of 2-bromo-octanoic acid to hydroxylamine resin. 4-O-Methylhydroxylarnine-phenoxymethyl-copoly(styrene- 1 %-divinylbenzene)-resin 1 ( 10.0 g , 1.2 meq/g) was placed in a peptide synthesis vessel and suspended in DMF (80 mL). 2- 35 Bromo-octanoic acid (8.4 g, 3.0 eq.) HOBt (8.8 g, 6.0 eq.) and DIC (7.2 mL, 4.0 eq.) were added. The reaction was shaken on an orbital shaker at room temperature for 2 - 16 hours. The reaction was filtered and washed widi DMF (3 x 20 mL). A sample of resin was removed and subjected to die Kaiser test. If the test showed the presence of free amine (resin turned blue) die coupling described above was repeated, odierwise d e resin was washed widi 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 bromide with 2,5-dichlorothiophenol. The 2-bromo hydroxymate resin prepared in Step A (0.45 g, 1.2 meq/g) was placed in a 20 mL scintillation vial and suspended in THF (6 mL). 2,5-Dichlorothiophenol (483 mg, 5.0 eq.), sodium iodide (404 mg, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.24 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours. The reaction mixture was poured into a polypropylene syringe barrel fitted 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 sulfide to sulfoxide. 2-(2,5-Dichlorobenzenesulfanyl)-octanoic acid hydroxyamide resin prepared in Step B (150 mg, 1.1 meq/g) was suspended in DCM (3.0 mL) and 70% tert-butylhydroperoxide (1.0 mL) benzenesulfonic acid (50 mg) were added. The reaction mixture was shaken on an orbital shaker at room temperature for 12 - 24 hours. The reaction was filtered and washed widi 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. 2-(2,5-Dichlorobenzenesulfanyl)-octanoic acid hydroxyamide 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 shaken 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 2-(2,5-dichlorobenzenesuh c anyl)-octanoic acid hydroxyamide from resin. The 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 shaken for 1 hour at room temperature. The reaction was filtered and die resin washed with DCM (2 x 1 mL). The filtrate and die washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Metiianol (1 mL) was added and the mixture concentrated. 92% @ 215 nm; Η NMR (DMSO d-6) δ 10.96 (brs, 1 H), 9.26 (brs, 1 H), 7.93-7.76 (m, 3 H), 4.07 (q, 1 H), 2.04-1.85 (m, 1 H), 1.78-1.64 (m, 1 H), 1.32-1.09 (m, 8 H), 0.81 (t, 3 H). The hydroxamic acids of Examples 161-167 are synthesized using appropriate starting materials and foUowing die steps in example 160. Example 161 2-(2,5-Dichlorobenzenesulfonyl)-octanoic acid hydroxyamide. 96% @ 215 nm. Example 162 2-(3-Medιoxybenzenesulfanyl)-octanoic acid hydroxyamide 86% @ 220 nm; LCMS (API- electrospray) m/z 298 (M+H) + . Example 163 2-(3-Medιoxybenzenesulfinyl)-octanoic acid hydroxyamide 96% @ 220 nm. Example 164 2-(3-Medιoxybenzenesulfonyl)-octanoic acid hydroxyamide 83% @ 220 nm. Example 165 2-(3,4-Dimethoxybenzenesulfanyl)-octanoic acid hydroxyamide 87% @ 215 nm; LCMS (API- electrospray) m z 328 (M+H) + . Example 166 2-(3,4-Dimethoxybenzenesulfinyl)-octanoic acid hydroxyamide 90% @ 215 nm. Example 167 2-(3,4-Dimedιoxybenzenesulfonyl)-octanoic acid hydroxyamide 87% @ 215 nm. The hydroxamic acid compounds of Examples 168-198 are synthesized using appropriate starting materials and foUowing the steps in example 160. The crude products are dissolved in DMSO:methanol (1:1, 2 mL) and purified by reverse phase HPLC under die conditions described below: Column: ODS-A, 20 mm x 50 mm, 5 μm particle size (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 (API- electrospray) m/z 308 (M+H) + . Example 169 2-(2-Benzooxazol-2-ylsulfanyl)-octanoic acid hydroxyamide 72% @ 215 nm; LCMS (API- electrospray) m/z 309 (M+H) + . Example 170 2-(2-Benzodιiazol-2-ylsulfanyl)-octanoic acid hydroxyamide 72% @ 215 nm; LCMS (API- electrospray) m/z 325 (M+H) + . Example 171 2-(2-Pyridine-2-sulfanyl)-octanoic acid hydroxyamide 76% @ 215 nm; LCMS (API- electrospray) m/z 269 (M+H)\ Example 172 2-(4-Phenyl-thiazole-2-suh°anyl)-octanoic acid hydroxyamide 97% @ 215 nm; LCMS (API- electrospray) m/z 336 (M+H) + . Example 173 2-(2-Pyridin-2-yl-ethylsuUanyl)-octanoic acid hydroxyamide 84% @ 215 nm; LCMS (API- electrospray) m/z 297 (M+H) + . Example 174 2-(2-Phenyl-5H-tetrazol-5-ylsulfanyl)-octanoic acid hydroxyamide 67% @ 215 nm; LCMS (API-electrospray) m/z 338 (M+H) + . Example 175 2-(2-Pyrazin-2-yl-ethylsulfanyl)-octanoic acid hydroxyamide 98% @ 215 nm; LCMS (API- electrospray) m/z 298 (M+H) + . Example 176 2-(l-Methyl-lH-tetrazol-5-ylsulfanyl)-octanoic acid hydroxyamide 66% <§> 215 nm; LCMS (API-electrospray) m/z 274 (M+H) + . Example 177 2-(2-Benzimidazol-2-ylsulfinyl)-octanoic acid hydroxyamide 81% @ 215 nm. Example 178 2-(2-Pyridine-2-sulfinyl)-octanoic acid hydroxyamide 76% @ 215 nm;. Example 179 2-(4-Phenyl-thiazole-2-sulfinyl)-octanoic acid hydroxyamide 78% @ 215 nm. Example 180 2-(2-Pyrazin-2-yl-emylsulfinyl)-octanoic acid hydroxyamide 96% @ 215 nm; LCMS (API- electrospray) m/z 314 (M+H) + . Example 181 2-(3-Oxy-lH-benzimidazole-2-sulfonyl)-octanoic acid hydroxyamide 63% @ 215 nm; LCMS (API-electrospray) m/z 356 (M+H) + . Example 182 2-(4-Phenyl-thiazole-2-sulfonyl)-octanoic acid hydroxyamide 70% @ 215 nm; LCMS (API- electrospray) m/z 383 (M+H) + . Example 183 2-[2-(l-Oxy-pyridin-2-yl)-edιanesulfonyl]-octanoic acid hydroxyamide 77% @ 215 ran; LCMS (API-electrospray) m/z 345 (M+H) + . Example 184 3-(l-Hydroxycarbamoyl-heptylsulfanyl)-benzoic acid hydroxyamide. 100% @ 220 nm; LCMS (API-electrospray) m/z 312 (M+H) + . Example 185 3-[4-(l-Hydroxycarbamoyl-heptylsulfanyl)-phenyl]-propionic acid hydroxyamide. 90% @ 220 nm; LCMS (API-electrospray) m/z 340 (M+H) + . Example 186 2-(Thiazol-2-ylsulfanyl)-octanoic acid hydroxyamide. 75% @ 215 nm; LCMS (API- electrospray) m/z 275 (M+H) + . Example 187 2-(2,5-Dioxo-imidazolidin-4-ylmethylsulfanyl)-octanoic acid hydroxyamide. 98% @ 215 nm; LCMS (API-electrospray) m/z 304 (M+H) + . Example 188 3-(l-Hydroxycarbamoyl-heptylsulfinyl)-benzoicacid hydroxyamide. 84% @ 220 ran; LCMS (API-electrospray) m/z 328 (M+H) + . Example 189 3-[4-(l-Hydroxycarbamoyl-heptylsulfinyl)-phenylj-propionic acid hydroxyamide. 78% @ 220 nm; LCMS (API-electrospray) m/z 356 (M+H) + . Example 190 2-(Quinohne-8-sulfinyl)-octanoic acid hydroxyamide. 87% @ 220 nm; LCMS (API- electrospray) m/z 335 (M+H) + . Example 191 2-(Naphmalen-2-ylcarbamoylmethanesulfinyl)-octanoic acid hydroxyamide. 83% @ 220 ran; LCMS (API-electrospray) m/z 391 (M+H) + . Example 192 3-(l-Hydroxycarbamoyl-heptylsulfonyl)-benzoic acid hydroxyamide. 72% @ 215 nm. Example 193 3-[4-(l-Hydroxycarbamoyl-heptylsulfonyl)-phenyl]-propionic acid hydroxyamide. 67% @ 215 nm. Example 194 2-(lH-Imidazole-2-sulfonyl)-octanoic acid hydroxyamide. 95% @ 215 nm; LCMS (API- electrospray) m/z 290 (M+H) + . Example 195 2-(Thiazol-2-ylsulfonyl)-octanoic acid hydroxyamide. 91% @ 215 nm; LCMS (API- electrospray) m/z 307 (M+H) + . Example 196 2-(QuinoUne-8-sulfonyl)-octanoic acid hydroxyamide. 94% @ 220 nm; LCMS (API- electrospray) m/z 351 (M+H) + . Example 197 2-(Naphthalen-2-ylcarbamoylmethanesulfonyl)-octanoic acid hydroxyamide. 79% @ 220 nm; LCMS (API-electrospray) m/z 407 (M+H) + . Example 198 2-(2,5-Dioxo-imidazohdin-4-ylmedιylsulfonyl)-octanoic acid hydroxyamide. 97% @ 215 nm. Example 199 Step A: Displacement of bromide with 4-fluorothiophenol. The 2- bromo hydroxymate 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 (7.7 g, 5.0 eq.) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 4.6 mL, 3.0 eq.) were added. The reaction was shaken 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 20 mL), and DCM (2 x 20 mL). The resin was dried in vacuo at room temperature. Step B: Couphng of 2-(4-fluorobenzenesulfanyl)-octanoic acid hydroxyamide resin with benzyl alcohol. 2-(4-Fluorobenzenesulfanyl)-octanoic acid hydroxyamide resin 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 (237 mg, 15 eq.) were added. The reaction was heated to 80°C for 15 hours while shaking on an orbital shaker. After cooling to room temperature die mixture was filtered and washed widi 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. 2-(4-Benzyloxy-phenylsulfanyl)-octanoic acid hydroxyamide resin prepared in Step B (110 mg, 1.1 meq/g) was suspended in DCM (2.2 mL) and 70% tert-butylhydroperoxide (0.73 mL) 5 benzenesulfonic acid (36 mg) were added. The reaction mixture was shaken 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. l o Step D: Oxidation of sulfide to sulfone. 2-(4-Benzyloxy-phenylsulfanyl)-octanoic acid hydroxyamide resin prepared in Step B (110 mg, 1.1 meq g) was suspended in DCM (2.2 mL) and mCPBA (132 mg) was added. The reaction mixture was shaken 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), 15 and DCM (2 x 2 mL). The resin was dried in vacuo at room temperature. Step E: Cleavage of 2-(4-benzyloxy-benzenesuh c anyl)-octanoic acid hydroxyamide from 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 20 was shaken for 1 hour at room temperature. The reaction was filtered and die resin washed with DCM (2 x 1 mL). The filtrate and die washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Medianol (1 mL) was added and die mixture concentrated. The crude product was dissolved in DMSO:methanol (1:1, 2 mL) and purified by reverse phase HPLC under die conditions described below: 25 Column: ODS-A, 20mm x 50 mm, 5 μm particle size (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 30 25 min. 5 95 Flow Rate: 15 mL/min. 2-(4-Benzyloxy-phenylsulfanyl)-octanoic acid hydroxyamide 100% @ 215 nm; LCMS (API- electrospray) m/z 374 (M+H) + . 35 The hydroxamic acid compounds of Examples 200-220 are synthesized using appropriate starting materials and foUowing the steps in example 199: Example 200 2-(4-Butoxy-benzenesulfanyl)-octanoic acid hydroxyamide 100% @ 215 nm; LCMS (API- electrospray) m/z 374 (M+H) + . Example 201 2-[4-(2-Piperazine-l-yl-ethoxy)-benzenesulfanylj-octanoic acid hydroxyamide 98% @ 215 nm; LCMS (API-electrospray) m/z 340 (M+H) + . Example 202 2-[4-(5-Hydroxy-pentyloxy)-phenylsulfanyl]-octanoic acid hydroxyamide 65% @ 215 nm.; LCMS (API-electrospray) m/z 370 (M+H) + . Example 203 2-[4-(3-Pyridin-2-yl-propoxy)-benzenesulfanyl]-octanoic acid hydroxyamide 95% @ 215 ran; LCMS (API-electrospray) 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-Piperazine-l-yl-ethoxy)-benzenesulfinyl]-octanoic acid hydroxyamide 98% @ 215 nm. Example 207 2-[4-(3-Pyridin-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-Piperazine-l-yl-edioxy)-benzenesulfonyl]-octanoic acid hydroxyamide 97% @ 215 nm. Example 211 2-[4-(3-Pyridin-2-yl-propoxy)-benzenesulfonyl]-octanoic acid hydroxyamide 100% @ 215 nm. Example 212 2-[4-(l-Metiιyl-pyrrolidin-3-yloxy)-benzenesulfanyl]-octanoic acid hydroxyamide 91% @ 215 nm; LCMS (API-electrospray) m/z 367 (M+H) + . Example 213 2-[4-(l-Ethyl-propoxy)-benzenesulfanyl]-octanoic acid hydroxyamide 100% @ 215 nm; LCMS (API-electrospray) m/z 354 (M+H) + . Example 214 2-[4-(Tetrahydro-pyran-4-yloxy)-benzenesulfanyl]-octanoic acid hydroxyamide 97% @ 215 nm; LCMS (API-electrospray) m/z 368 (M+H) + . Example 215 2-[4-(l-Methyl-pyrrohdin-3-yloxy)-benzenesulfinyl]-octanoic acid hydroxyamide 96% @ 215 nm. Example 216 2-[4-(l-Edιyl-propoxy)-benzenesulfinyl]-octanoic acid hydroxyamide 97% @ 215 nm. Example 217 2-[4-(Terrahydro-pyran-4-yloxy)-benzenesulfinyl]-octanoic acid hydroxyamide 97% @ 215 nm. Example 218 2-[4-(l-Med yl-pyrrolidin-3-yloxy)-benzenesulfonyl]-octanoic acid hydroxyamide 96% @ 215 nm. Example 219 2-[4-(l-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 bromide 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- diazabicyclo[5.4.0]undec-7-ene (DBU, 2.5 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours, then filtered and washed with DMF (2 x 30 mL), DMRwater 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. 2-(4-Bromobenzenesulfanyl)-octanoic acid hydroxyamide resin prepared in Step A (4.4 g, 1.1 meq/g) was suspended in DCM (60 mL) and 70% tert-butylhydroperoxide (30 mL) benzenesulfonic acid (1.5 g) were added. The reaction mixture was shaken 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. 2-(4-Bromobenzenesulfanyl)-octanoic acid hydroxyamide resin prepared in Step B (4.4 g, 1.1 meq/g) was suspended in DCM (60 mL) and mCPBA (5.2 g) was added. The reaction mixture was shaken 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 2-(4-bromobenzenesulfinyl)-octanoic acid hydroxyamide resin with 4- chlorobenzeneboronic acid. 2-(4-Bromobenzenesulfinyl)-octanoic acid hydroxyamide resin prepared in Step B (150 mg, 1.1 meq/g) was suspended in DME (2.0 mL) and nitrogen gas bubbled d rough die suspension for 1-2 minutes. 4-Chlorobenzeneboronic acid (51.6 mg, 2 eq.), tetrakis(triphenylphosphine) paUadium(0) (19.07 mg, 0.1 eq.) and sodium carbonate (2 M solution, 0.825 mL, 10 eq.) were added. The reaction was heated to 80°C for 8 hours whde shaking on an orbital shaker. After cooling to room temperature the mixture was filtered and washed widi 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 E: Cleavage of 2-(4'-chloro-biphenyl-4-sulfinyl)-octanoic acid hydroxyamide from resin. The 2-(4'-chloro-biphenyl-4-sulfinyl)-octanoic acid hydroxyamide resin prepared in Step D (150 mg, 1.1 meq/g) was suspended in DCM (1.0 mL) and TFA (1.0 mL) was added. The reaction was shaken for 1 hour at room temperature. The reaction was filtered and the resin washed with DCM (2 x 1 mL). The filtrate and die washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Methanol (1 mL) was added and the mixture concentrated. The crude product was dissolved in DMSO:methanol (1:1, 2 mL) and purified by reverse phase HPLC under d e conditions described below: Column: ODS-A, 20mm x 50 mm, 5 μm particle size (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL/min. 2-(4'-Chloro-biphenyl-4-sulfinyl)-octanoic acid hydroxyamide 96% @ 215 nm; LCMS (API- electrospray) m/z 394 (M+H) + . The hydroxamic acid compounds of Exmples 222-224 are synthesized using appropriate starring materials and foUowing the steps in example 221 : Example 222 2-[4-(5-Chloro-dιiophen-2-yl)-benzenesulfinyl]-octanoic acid hydroxyamide 100% @ 215 nm; LCMS (API-electrospray) m/z 400 (M+H) + . Example 223 2-(4'-Chloro-biphenyl-4-sulfonyl)-octanoic acid hydroxyamide 94% @ 215 nm; LCMS (API- electrospray) m/z 410 (M+H) + . Example 224 2-[4-(5-Chloro-thiophen-2-yl)-benzenesulfonyl]-octanoic acid hydroxyamide 85% @ 215 ran; LCMS (API-electrospray) m/z 416 (M+H) + . Example 225 Step A: Coupling of 2-(4-bromobenzenesulfanyl)-octanoic acid hydroxyamide resin with N-(3- aminopropyl)-moφhoUne. 2-(4-Bromobenzenesulfanyl)-octanoic acid hydroxyamide resin prepared in Example 199, Step A (100 mg, 1.1 meq/g) was suspended in dioxane (2.0 mL) and nitrogen gas bubbled through die suspension for 1-2 minutes. N-(3-Aminopropyl)-moφhohne (346 mg, 20 eq.), tris(dibenzyUdeneacetone)-dipalladium(0) (22 mg, 0.2 eq.), (S)-(-)-2,2'- bis(diphenylphosphino)-l,l'-binaphthyl((S)-BIΝAP, 60 mg, 0.8 eq.) and sodium tert- butoxide (207 mg, 18 eq.) were added. The reaction was heated to 80°C for 8 hours while shaking on 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-[ (3-moφhohn-4-yl-propylarnino)-phenylsulfanyl]-octanoic acid hydroxyamide from resin. The 2-[4-(3-moφholin-4-yl-propylamino)-phenylsulfanyl]-octanoic acid hydroxyamide resin 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 shaken for 1 hour at room temperature. The reaction was filtered and die resin washed widi DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Metiianol (1 mL) was added and the mixture concentrated. The crude product was dissolved in DMSO:methanol (1:1, 2 mL) and purified by reverse phase HPLC under the conditions described below: Column: ODS-A, 20mm x 50 mm, 5 μm particle size (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 rnL/min. 2-[4-(3-moφholin-4-yl-propylamino)-phenylsulfanyl]-octanoic acid hydroxyamide 88% @ 215 nm; LCMS (API-electrospray) m/z 410 (M+H) + . The hydroxamic acid compounds of Examples 226-231 are synthesized using appropriate starting materials and foUowing the steps in this example: Example 226 2-[4-(Biphenyl-4-ylamino)-phenylsulfanyl]-octanoic acid hydroxyamide 95% @ 215 ran; LCMS (API-electrospray) m/z 435 (M+H) + . Example 227 2-[4-(Pyridin-4-ylamino)-phenylsulfanyl]-octanoic acid hydroxyamide 97% @ 215 nm; LCMS (API-electrospray) m/z 360 (M+H) + . Example 228 2-(4-Cyclopentylamino-phenylsulfanyl)-octanoic acid hydroxyamide 77% @ 215 nm; LCMS (API-electrospray) m/z 351 (M+H) + . Example 229 2-(4-Methylamino-phenylsulfanyl)-octanoic acid hydroxyamide 99% @ 215 nm; LCMS (API- electrospray) m/z 297 (M+H) + . Example 230 2-(4-Piperidin-l-yl-phenylsuU " anyl)-octanoic acid hydroxyamide 72% @ 215 nm; LCMS (API- electrospray) m/z 351 (M+H) + . Example 231 2-(4-Piperazin-l-yl-phenylsulfanyl)-octanoic acid hydroxyamide 74% @ 215 nm; LCMS (API-electrospray) m/z 352 (M+H) + . Example 232 Step A: Displacement of bromide with 4-hydroxythiophenol. The 2-bromo-octanoic acid hydroxymate 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[5.4.0]undec-7-ene (DBU, 8.1 mL, 3.0 eq.) were added. The reaction was shaken at room temperature for 12 - 16 hours, then filtered and washed wid DMF (2 x 60 mL), DMF: water 9:1 (2 x 60 mL), DMF (60 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 2-(4-hydroxybenzenesulfanyl)-octanoic acid hydroxyamide resin with benzene sulfonyl chloride. 2-(4-Hydroxybenzenesulfanyl)-octanoic acid hydroxyamide resin 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 triediylamine (0.06 mL, 2 eq.) were added. The reaction was shaken 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. Benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfanyl)-phenyl ester resin prepared in Step B (80 mg, 1.2 meq/g) was suspended in DCM (3 mL) and 70% tert-butylhydroperoxide (1 mL) benzenesulfonic acid (23 mg) were added. The reaction mixture was shaken 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. Benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfanyl)-phenyl ester resin prepared in Step B (80 mg, 1.2 meq/g) was suspended in DCM (3 mL) and mCPBA (84 mg) was added. The reaction mixture was shaken 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 benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsuhanyl)-phenyl ester resin. The benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfanyl)-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 shaken for 1 hour at room temperature. The reaction was filtered and die resin washed widi DCM (2 x 1 mL). The filtrate and the washing were combined and concentrated to dryness on a Savant SpeedVac Plus. Medianol (1 mL) was added and the mixture concentrated. The crude product was dissolved in DMSO:methanol (1:1, 2 mL) and purified by reverse phase HPLC under the conditions described below: Column: ODS-A, 20mm x 50 mm, 5 μm particle size (YMC, Inc. Wilmington, North Carolina) Solvent Gradient Time Water Acetonitrile 0.0 95 5 25 min. 5 95 Flow Rate: 15 mL/min. Benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfanyl)-phenyl ester 91% @ 215 nm; LCMS (API-electrospray) m/z 424 (M+H) + . The hydroxamic acid compounds of Examples 233-240 are synthesized using appropriate starting materials and foUowing the steps in example 232: Example 233 2,5-Dichloro-thiophene-3-sulfonic acid ^(l-hydroxycarbamoyl-heptylsutfany -hydroxyarnide 98% @ 215 nm; LCMS (API-electrospray) m/z 498 (M+H) + . Example 234 Etiianesulfonic acid 4(l-hydroxycarbamoyl-heptylsulfanyl)-hydroxyamide. 72% @ 215 nm; LCMS (API-electrospray) m/z 376 (M+H) + . Example 235 5-Chloro-l,3-dimethyl-lH-pyrazole-4-sulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfinyl)- hydroxyamide 99% <α> 215 nm; LCMS (API-electrospray) m/z 492 (M+H) + . Example 236 2,5-Dichloro-thiophene-3-sulfonic acid 4-(l -hydroxycarbamoyl-heptylsulfinyl)-hydroxyamide 96% @ 215 nm; LCMS (API-electrospray) m/z 514 (M+H) + . Example 237 5-Pyridin-2-yl-thiophene-2-suh c onic acid 4(1 -hydroxycarbamoyl-heptylsulfinyl)-hydroxy amide 96% @ 215 nm; LCMS (API-electrospray) m/z 523 (M+H) + . Example 238 2-Nitro-benzenesulfonic acid 4-(l-hydroxycarbamoyl-heptylsulfonyl)-hydroxyamide 97% @ 215 nm; LCMS (API-electrospray) m/z 501 (M+H) + . Example 239 3-Bromo-2-chloro-thiophene-2-sulfonic acid 4-( 1 -hydroxycarbamoyl-heptylsulfonyl)- hydroxyamide 97% @ 215 nm; LCMS (API-electrospray) m/z 576 (M+H)\ Example 240 Benzo[ 1 ,2,5]thiadiazole-4-sulfonic acid 4-( 1 -hyclroxycarbamoyl-heptylsulfonyl)- hydroxyamide 83% @ 215 nm; LCMS (API-electrospray) m/z 514 (M+H) + . References: 1 Rickter, L. S.; Desai, M. C. Tetrahedron Letters, 1997, 38, 321-322. The subject compounds of die present invention were tested for biological activity according to the following procedures. In Vitro Gelatinase Assay The assay is based on die cleavage of die tiiiopeptide substrate ((Ac-Pro-Leu-Gly(2 mercapto-4 methyl-pentanoyl)-Leu-Gly-OEt), Bachem Bioscience) by die enzyme, gelatinase, releasing the substrate product which reacts colorimetrically with DTNB ((5,5'-dithio-bis(2-nitro-benzoic acid)). The enzyme activity is measured by the rate of die color increase. The thiopeptide substrate is made up fresh as a 20 mM stock in 100% DMSO and die DTNB is dissolved in 100% DMSO as a 100 mM stock and stored in dark at room temperature. Both die substrate and DTNB are diluted together to 1 mM with substrate buffer (50 mM HEPES pH 7.5, 5 mM CaCl 2 ) before use. The stock of human neutrophU gelatinase B is diluted with assay buffer (50 mM HEPES pH 7.5, 5 mM CaCl 2 , 0.02% Brij) to a final concentration of 0.15 nM. The assay buffer, enzyme, DTNB/substrate (500 μM final concentration) and vehicle or inhibitor are added to a 96 well plate (total reaction volume of 200μl) and the increase in color is monitored spectrophotometrically for 5 minutes at 405 nm on a plate reader. The increase in OD405 is plotted and d e slope of die line is calculated which represents die reaction rate. The linearity of the reaction rate is confirmed (r^ >0.85). The mean (x ± sem) of die control rate is calculated and compared for statistical significance (p <0.05) with drug- treated rates using Dunnett's multiple comparison test. Dose-response relationships can be generated using multiple doses of drug and IC 50 values widi 95% CI are estimated using linear regression (IPRED, HTB). References: Weingarten, H and Feder, J., Spectrophotometric assay for vertebrate coUagenase, Anal. Biochem. 147, 437-440 (1985). In Vitro CoUagenase Assay The assay is based on die cleavage of a peptide substrate ((Dnp-Pro-Cha-Gly-Cys(Me)-His- Ala-Lys(NMa)-NH2), Peptide International, Inc.) by coUagenase releasing the fluorescent NMa group which is quantitated on die fluorometer. Dnp quenches the NMa fluorescence in the intact substrate. The assay is run in HCBC assay buffer (50 mM HEPES, pH 7.0, 5 mM Ca +2 , 0.02% Brij, 0.5% Cysteine), with human recombinant fibroblast coUagenase (truncated, mw=18,828, WAR, Radnor). Substrate is dissolved in medianol and stored frozen in 1 mM aliquots. CoUagenase is stored frozen in buffer in 25 μM aliquots. For the assay, substrate is dissolved in HCBC buffer to a final concentration of 10 μM and coUagenase to a final concentration of 5 nM. Compounds are dissolved in methanol, DMSO, or HCBC. The methanol and DMSO are ctiluted in HCBC to < 1.0%. Compounds are added to die 96 weU plate containing enzyme and the reaction is started by die addition of substrate. The reaction is read (excitation 340 nm, emission 444 nm) for 10 min. and the increase in fluorescence over time is plotted as a Unear line. The slope of the line is calculated and represents the reaction rate. The linearity of the reaction rate is confirmed (r 2 >0.85). The mean (x ± sem) of the control rate is calculated and compared for statistical significance (p <0.05) with drug-treated rates using Dunnett's multiple comparison test. Dose-response relationships can be generated using multiple doses of drug and IC50 values widi 95% CI are estimated using Unear regression (IPRED, HTB) . References: Bickett, D. M. et al., A high throughput fluorogenic substrate for interstitial coUagenase (MMP-1) and gelatinase (MMP-9), Anal. Biochem. 212,58-64 (1993). Procedure for Measuring TACE Inhibition Using 96-weU black microtiter plates, each weU receives a solution composed of 10 μL TACE (Immunex, final concentration lμg/mL), 70μL Tris buffer, pH 7.4 containing 10% glycerol (final concentration 10 mM), and 10 μL of test compound solution in DMSO (final concentration lμM, DMSO concentration <1%) and incubated for 10 minutes at room temperature. The reaction is initiated by addition of a fluorescent peptidyl substrate (final concentration 100 μM) to each well and tiien shaking on a shaker for 5 sec. The reaction is read (excitation 340 nm, emission 420 nm) for 10 min. and the increase in fluorescence over time is plotted as a Unear line. The slope of the line is calculated and represents the reaction rate. The linearity of the reaction rate is confirmed (r^ >0.85). The mean (x±sem) of the control rate is calculated and compared for statistical significance (p<0.05) with drug-treated rates using Dunnett's multiple comparison test. Dose-response relationships can be generate using multiple doses of drug and IC50 values with 95% CI are estimated using linear regression The results obtained foUowing tiiese standard experimental test procedures are presented in die foUowing table. IC 50 (nM or % inhibition at 1 micromolar) Example MMP 1 MMP 9 MMP 13 TACE 1 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% 9 313 107 NT 20.30% 10 8% 128 64 54.75% 11 18.80% 2925 319 942 12 100 10.8 11 15.50% 13 239 11 14 626 14 158 23 8 17.18% 15 285 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% 20 423 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 25 262 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% 30 397 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% 35 455.8 233.6 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% 55.5% 46.6% 44 47.1% 36.9% 39.5% 14.9% Example MMP 1 MMP 9 MMP 13 TACE 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% 49 10.1% 23.7% 54.6% NT 50 51.1 58.4 10.6 NT 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 57415 120.2 90 41.32% 70 1139 88.80% 127 764 71 1000 63 13 42.21% 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 Example MMP 1 MMP 9 MMP 13 TACE 89 1389 38.6 7.0 49% 90 598 10.3 2.2 71.9 91 1929 13.3 10.8 503 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 Compounds prepared by solid phase synthesis Data: for Examples 110 to 240 Example MMP 1 MMP 9 MMP 13 % MMP 13 % TACE % No inhibition at 0.2 inhibition at inhibition at 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 29.2 128 1.9 mM 213 nM 91 255 nM 19.31 129 90 32.77 Example MMP 1 MMP 9 MMP 13 % MMP 13 % TACE % N o inhibition at 0.2 inhibition at inhibition at μM (HTS) 0.2 μM I mM (manual) 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 8 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 11.95 148 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 -2.09 157 19 13.7 158 33 -7.48 159 49 5.852 160 14 -3.57 161 0 12.7 162 13 0 163 84 9.515 164 74 62.69 165 71 73.7 166 9 4.16 167 27 8.961 168 21 3.688 Example MMP 13 % MMP 13 MMP 13 TACE TACE N o . inhibition at % inhibition ; it % inhibition at IC 50 nM % inhibition at 36 nM (HTS) 0.36 mM 3.6 mM (HTS) I 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 Example MMP 13 % MMP 13 MMP 13 TACE TACE No . inhibition at % inhibition at % inhibition at IC 50 nM % inhibition at 36 nM (HTS) 0.36 mM 3.6 mM (HTS) I mM (HTS) 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 -10 74 39 26 179 12 32 60 42.7 180 14 19 45 34.4 181 6 35 62 15.7 182 -9 -8 7 28.6 183 -6 12 70 34.6 184 16 24 44 24.8 185 9 0 23 7.21 186 -14 -4 35 19.5 187 -14 -12 20 85.5 188 -27 -24 4 16.2 189 -30 -18 -9 14. 190 -35 -28 -13 38.3 191 -45 -3 22 2.9 192 -32 5 61 33.2 193 -32 -15 56 14.9 194 -17 -8 5 5.4 195 -9 -2 10 27.0 196 -18 1 11 35.7 197 -33 -26 -3 17.8 198 -39 -7 15 17.1 199 -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 -6.3 208 67.7 209 31.2 210 52.2 211 20.7 212 56.0 213 -17.5 214 11.03 215 895 60.12 216 2.49 217 55.1 218 380 68.7 219 7.3 220 256 53.1 221 146 98.9 222 212 89.3 223 226 107.3 224 404 75.0 Example MMP 13 % MMP 13 MMP 13 TACE TACE No . inhibition at % inhibition at % inhibition at IC 50 nM % inhibition at 36 nM (HTS) 0.36 mM 3.6 mM (HTS) I mM (HTS) 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 35 237 55 65 72 38.2 238 22 11 24 930 54.4 239 54 74 83 45.9 240 48 51 46 40.3 Pharmaceutical Composition Compounds of tiiis invention may be administered neat or with a pharmaceutical carrier to a patient in need thereof. The pharmaceutical carrier may be solid or Uquid. AppUcable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubdizers, suspending agents, fiUers, glidants, compression aids, binders or tablet-disintegrating agents or an encapsulating material. In powders, die carrier is a finely divided sohd which is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the 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 waxes and ion exchange resins. Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of this invention can be dissolved or suspended in a pharmaceuticaUy acceptable Uquid carrier such as water, an organic solvent, a mixture of both or pharmaceuticaUy acceptable oils or fat. The liquid carrier can contain other suitable pharmaceutical additives such a solubihzers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of hquid carriers for oral and parenteral administration include water (particularly containing additives as above, e.g., ceUulose derivatives, preferable sodium carboxymethyl ceUulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g., glycols) and their derivatives, and oils (e.g., fractionated coconut oU and arachis oU). For parenteral administration the carrier can also be an ody ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Oral be eidier ;quid or solid composition form. The compounds of this invention may be administered rectaUy in die form of a conventional suppository. For administration by intranasal or intrabronchial inhalation or insufflation, the compounds of this invention may be formulated into an aqueous or partiaUy aqueous solution, which can then be utilized in die form of an aerosol. The compounds of this invention may also be administered transdermally through die use of a transdermal patch containing the active compound and a carrier tiiat is inert to die active compound, is non-toxic to the skin, and aUows deUvery of die agent for systemic absoφtion into die blood stream via the skin. The carrier may take any number of forms such as creams and ointments, pastes, gels, and occlusive devices. The creams and ointments may be viscous liquid or semi-solid emulsions of either d e od in water or water in oil type. Pastes comprised of absoφtive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable. A variety of occlusive devices may be used to release the active ingredient into the blood stream such as a semipermeable membrane covering a reservoir containing die active ingredient with or without a carrier, or a matrix containing d e active ingredient Other occlusive devices are known in the literature. The dosage to be used in the treatment of a specific patient suffering from a disease or condition in which MMPs and TACE are involved must be subjectively determined by the attending physician. The variables involved include die severity of die dysfunction, and die size, age, and response pattern of the patient. Treatment will generally be initiated with smaU dosages less than the optimum dose of die compound. Thereafter die dosage is increased until tiie optimum effect under die circumstances is reached. Precise dosages for oral, parenteral, nasal, or intrabronchial administration wiU be determined by die administering physician based on experience widi die individual subject treated and standard medical principles. Preferably the pharmaceutical composition is in unit dosage form, e.g., as tablets or capsules. In such form, the composition is sub-divided in unit dose containing appropriate quantities of die active ingredient; the unit dosage form can be packaged compositions, for example packed powders, vials, ampoules, prefilled syringes or sachets containing hquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.

Claims: What is claimed is: 1. A compound according to formula I I wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionaUy substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionaUy substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substituted with one or two groups selected independently from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substituted widi one or two groups selected independently from R 5 ; or heteroaryl- (CH 2 )o- 6 - wherein the heteroaryl group is 5 to 6 membered widi one or two heteroatoms selected independently from O, S, and N and may be optionally substituted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO2-; R 2 and R 3 , taken with die carbon atom to which tiiey are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionaUy having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionaUy substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon ..toms having 1 to 3 double bonds, optionally substituted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substituted with one or two groups selected independently from R 5 ; phenyl or naphthyl optionaUy substituted widi one or two groups selected independently from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionaUy substituted with one or two groi selected independently from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substituted with c^e or two groups selected independendy from R 5 ; R 5 is H, C7-C11 aroyl, C -C6 alkanoyl, Ci to C12 alkyl, C 2 to C12 alkenyl, C2-C12 alkynyl, F, Cl, Br, I, CN, CHO, Cι-C 6 alkoxy, aryloxy, heteroaryloxy, C3-C alkenyloxy, C3-C6 alkynyloxy, C -Cβ alkoxyaryl, Cι-^6 alkoxyhei roaryl, -C6 alkylamino-Cι-C6 alkoxy, Ci-C ..Ikylene dioxy, aryloxy-Cι-C6 alkyl amine, C1-C12 perfluoro alkyl, S(O)n-Cι-C6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO Ci- alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR6R6, S0 2 NR 6 R 6 , NR 6 SO 2 aryl, -NR 6 CONR 6 R 6 , NHSO 2 CF 3 , SO2NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH , OH, aryl, heteroaryl, C3 to Cβ cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein Ci-Cό alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C \ -Cβ alkyl, C1-C6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted widi OH; C3 to Cβ alkenyl, C3 to Cβ alkynyl, to C perfluoro alkyl, S(O)n-Cι-C6 alkyl S(O) n aryl where n is 0, 1 or 2;, or COheteroaryl, wherein heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphtiiyl, optionaUy substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C1-C6 alkyl, Cι-C 6 alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C2- alkanoyl, C1-C12 perfluoro alkyl, S(O) n -Cι-C6-alkyl, S(O) n - aryl where n is 0, 1 or 2; COO-Cι-C 6 -alkyl, COOaryl, CONHR 6 , CONR*R 6 , CONHOH, SO2NR 6 R 6 , SO2CF3, SC^NHheteroaryl, SO 2 NHCOaryl, CONHSO-Cι-C 6 -alkyl, CONHSC^aryl, aryl, or heteroaryl, where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, -C6 alkyl, - alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicycUc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or N- -Ce alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionaUy substituted widi one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independently from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionaUy substituted widi one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionally substituted with one or two groups selected independendy from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionaUy substituted with one or two groups selected independently from R 5 ; saturated or unsaturated mono or bicychc heterocycle containing one heteroatom selected from O, S or N-Ci-Cδ alkyl, optionally substituted widi one or two groups selected independently from R 5 ; or R 8 R 9 N-Cι-C6-alkoxyaryl-Cι-C6-alkyl where R 8 and R 9 are independendy selected from C1-C6 alkyl or R 8 and R 9 together with the inteφosed nitrogen forms a 5-7 membered saturated heterocycUc ring optionaUy containing an oxygen atom, wherein the aryl group is phenyl or naphtiiyl; or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1 wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionaUy substituted widi one or two groups selected independendy from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionaUy substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substituted widi one or two groups selected independently from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted widi one to two groups selected independently from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one to two groups selected independently from R 5 ; saturated or unsaturated mono or bicychc heterocycle of from 5 to 10 members containing one heteroatom selected from O, S or NR 7 , optionaUy substituted with one to two groups selected independently from R 5 ; or heteroaryl-(CH2)o-6- wherein the heteroaryl group is 5 to 6 membered with one or two heteroatoms selected independently from O, S, and N and may be optionally substituted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO 2 -; R 2 and R 3 , taken with the carbon atom to which tiiey are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionaUy substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substituted with one or two groups selected independently from R 5 ; phenyl or naphdiyl optionaUy substituted with one or two groups selected independently from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionaUy substituted with one or two groups selected independently from R 5 ; R 5 is H, F, Cl, Br, I, CN, CHO, C7-C11 aroyl, C2-C 6 alkanoyl, Ci to C alkyl, C to C12 alkenyl, C2-C12 alkynyl, Cι-Cβ alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, alkoxyaryl, C1-C6 alkoxyheteroaryl, Ci-C δ -alkylamino-Ci- Cβ alkoxy, Cι-C2-alkylene dioxy, aryloxy-Ci-Cβ alkyl amine, C1-C12 perfluoro alkyl, S(O) n -Cι-C 6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO-Q-Ce alkyl, OCOOaryl, OCONR 6 , COOH, COO-Ci- alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR 6 R 6 , SO 2 NR 6 R 6 , NR 6 SO 2 aryl, NR 6 CONR6R*, NHSO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO2-C1-C6 alkyl, CONHSO 2 aryl, NH 2 , OH, aryl, heteroaryl, C 3 to C 8 cycloaU yl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 ; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independendy from halogen, cyano, amino, nitro, Cι-C 6 alkyl, Cι-C 6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted with OH; C3 to β alkenyl, C3 to Cβ alkynyl, C \ to Cβ perfluoro alkyl, S(O)n alkyl or aryl where n is 0, 1, or 2; or COheteroaryl; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having lto 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, -Cβ alkyl, -Cβ alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C 2 -C6 alkanoyl, -C12 perfluoro alkyl, S(O) n -alkyl, S(O) n - aryl where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO2NR 6 R 6 ,SO CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO2alkyl, CONHSθ2aryl, aryl, heteroaryl; wherein -Cό alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicycUc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cό alkyl, - β alkoxy, or hydroxy; alkyl of 1 to 18 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substituted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substituted widi one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionaUy substimted with one or two groups selected independendy from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionaUy substituted with one or two groups selected independendy from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionally substimted with one or two groups selected independently from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein cycloalkyl or bicycloalkyl is optionally substimted with one or two groups selected independendy from R 5 ; saturated or unsaturated mono or bicychc heterocycle containing one heteroatom selected from O, S or N- -Cβ alkyl, optionally substimted widi one or two groups selected independendy from R 5 ; R 8 R 9 N-Cι-C 6 -alkoxyaryl-Cι-C 6 -alkyl where R 8 and R 9 are independendy selected from C 1 -C 6 alkyl or R 8 and R 9 togedier with the inteφosed nitrogen forms a 5-7 membered saturated heterocyclic ring optionally containing an oxygen atom, wherein die aryl group is phenyl or naphd yl; or a pharmaceutically acceptable salt diereof. 3. A compound according to claim 2 wherein R 1 is phenyl, naphthyl, alkyl of 1-18 carbon atoms or heteroaryl such as pyridyl, thienyl, imidazolyl or furanyl, optionally substituted with -Cβ alkyl, -C 6 alkoxy, Ce- o aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C 3 -C 6 alkynyloxy, halogen; or S(O) n - -Ci-Cβalkyl alkoxyaryl or C 1 -C 6 alkoxyheteroaryl; A is -S-, -SO- or -SO 2 -; R 2 and R 3 , taken with die carbon atom to which they are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionally having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionaUy substimted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independendy from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substituted with one or two groups selected independently from R 5 ; phenyl or naphtiiyl optionaUy substituted with one or two groups selected independently from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionaUy substituted with one or two groups selected independently from R 5 ; R 5 is H, C7-C11 aroyl, C 2 -C6 alkanoyl, d to C12 alkyl, C2 to C12 alkenyl, C2-C12 alkynyl, F, Cl, Br, I, CN, CHO, Ci-Cβ alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, C1-C6 alkylamino-Cι-C6 alkoxy, C1-C2 alkylene dioxy, aryloxy-Ci-Ce alkyl amine, -C12 perfluoro alkyl, S(O) n -Cι-C6 alkyl, S(O) n - aryl where n is 0, 1 or 2; OCOO C r C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO - C 6 alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR 6 R 6 , SO NR 6 R 6 , NR 6 SO 2 aryl, -NR 6 CONR 6 R 6 , NHSO2CF3, SO2NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -C C 6 alkyl, CONHSO aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH2, OH, aryl, heteroaryl, C3 to C» cycloalkyl; saturated or unsaturated 5 to 10 membered mono or bicychc heterocycle containing one heteroatom selected from O, S or NR 7 , wherein -C6 alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cβ alkyl, -C6 alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted widi OH; C3 to C6 alkenyl, C3 to Cβ alkynyl, C \ to Cβ perfluoro alkyl, S(O)n alkyl or aryl where n is 0, 1 or 2; or COheteroaryl; wherein heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphdiyl, optionaUy substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, - alkyl, C1-C6 alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C 2 -C6 alkanoyl, -C12 perfluoro alkyl, S(O) n -alkyl, S(O) n - aryl where n is 0, 1 or 2; COOalkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO2NR 6 R 6 ,SO 2 CF 3 , SO2NHheteroaryl, SC^NHCOaryl, CONHSO2aUcyl, CONHSθ2aryl, aryl, or heteroaryl; where aryl is phenyl or naphthyl, optionaUy substituted by 1 or 2 groups selected independendy from halogen, cyano, amino, nitro, -C6 alkyl, C1-C6 alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or N-C1-C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted widi one or two groups selected independendy from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substimted with one or two groups selected independendy from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substimted with one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, optionally substituted widi one or two groups selected independendy from R 5 ; arylalkenyl of 8 to 16 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, optionally substituted with one or two groups selected independently from R 5 ; saturated or unsaturated mono or bicychc heterocycle containing one heteroatom selected from O, S or NR-C1-C6 alkyl, optionally substituted with one or two groups selected independently from R 5 ; R 8 R 9 N-Cι-C6-alkoxyaryl-Cι-C6-alkyl where R 8 and R 9 are independendy selected from C1-C6 alkyl or R 8 and R 9 together with the interposed nitrogen forms a 5-7 membered saturated heterocyclic ring optionaUy containing an oxygen atom, wherein die aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt tiiereof. 4. A compound according to claim 1 which is l-benzyl-4-(4-methoxy-benzenesulfonyl)- piperidine-4-carboxyhc acid hydroxyamide or a pharmaceutically acceptable salt thereof. 5. A compound according to claim 1 which is 4-(4-methoxy-benzenesulfonyl)-l-(3-methoxy- benzyl)-piperidine-4-carboxyhc acid hydroxyamide or a pharmaceutically acceptable salt thereof. 6. A compound according to claim 1 which is l-(3,4-dichlorobenzyl) -4-(4-metiιoxy- benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxamide or a pharmaceuticaUy acceptable salt thereof. 7. A compound according to claim 1 which is 4-(4-metiιoxy-benzenesulfonyl)-l-(4- medιylbenzyl)-piperidine-4-carboxyhc acid hydroxamide or a pharmaceuticaUy acceptable salt thereof. 8. A compound according to claim 1 which is 4-(4-memoxy-benzene-sulfonyl)-l-napthalene- 2-yl-medιylpiperidine-4-carboxyhc acid hydroxamide or a pharmaceutically acceptable salt thereof. 9. A compound according to claim 1 which is l-biphenyl-4-ylmemyl-4-(4-medιoxy- benzenesulfonyl)piperidine-4-carboxyhc acid hydroxamide or a pharmaceuticaUy acceptable salt thereof. 10. A compound according to claim 1 which is 4-(4-methoxy-benzene- sulfonyl)- l-(3-methyl- but-2-enyl)piperidine-4-carboxyhc acid hydroxamide or a pharmaceutically acceptable salt thereof. 11. A compound according to claim 1 which is l-(4-bromo-benzyl)-4-(4-methoxy- benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide or a pharmaceuticaUy acceptable salt thereof. 12. A compound according to claim 1 which is 4-(4-methoxy-benzenesulfonyl)-l-[4-(2- piperidin-l-yl-edιoxy)-benzylj-piperidine-4-carboxylic acid hydroxy amide or a pharmaceuticaUy accepted saltthere of. 13. A compound according to claim 1 or a pharmaceutically acceptable salt thereof which is selected from die group of compounds consisting of: -(4-methoxy-benzenesulfonyl)- 1 -(3-phenyl-propyl)-piperidine-4-carboxylic acid hydroxyamide, l-tert-butyl-4-( medιoxy-benzenesuU r onyl)-piperidine-4-carboxyhc acid hydroxyamide, l-butyl-4-(4-rnethoxy-benzenesuUOnyl)-piperidine-4-carboxyUc acid hydroxyamide, l-cyclooctyl-4-(4-medιoxy-benzenesulfonyl)-piperidine-4-carboxy c acid hydroxyamide, l-edιyl-4-(4-medιoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, l-isopropyl-4-(4-rnethoxy-benzenesulfonyl)-piperidine-4-carboxyUc acid hydroxyamide, 1 -methyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide, 1 -benzyl-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, l-(4-fluoro-benzyl)-4-(4-rnedιoxy-benzenesulfonyl)-piperidine-4-carboxyhc acid hydroxyamide, 1 -(4-fluoro-benzyl)-4-(4-butoxy-benzenesulfonyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-memoxy-benzenesuhonyl)-l-(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-medιoxy-benzenesulfonyl)- 1 -[2-(4-medιoxyphenyl)-ethylJ-piperidine-4-carboxyUc acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)-l-(2-phenyl-edιyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-n-butoxy-benzenesulfonyl)- 1 -(4-methoxy-benzyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)-l-(3-phenoχy-propyl)-piperidine-4-carboxyhc acid hydroxyamide, 4-(4-n-butoxy-benzenesulfonyl)- 1 -(3-phenoxy-propyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-methoxy-benzenesulfonyl)- l-(2-phenoxy-ethyl)-piperidine-4-carboxylic acid hydroxyamide, 4-(4-n-butoxy-benzenesulfonyl)- 1 -(2-phenoxy-ed yl)-piperidine-4-carboxylic acid hydroxyamide, and 4-(4-methoxy-benzenesulfonyl)- 1 -[4-(2-piperidin- 1 -yl-edιoxy)-benzylj-piperidine-4-carboxylic acid hydroxy amide. 14. A mediod of inhibiting pathological changes mediated by matrix metaUoproteinases in mammals which comprises administration to a mammal in need thereof a therapeuticaUy effective amount of a matrix metaUoproteinase inhibiting compound of die formula 5 wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionaUy substituted with one or two groups selected independendy from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionaUy substituted l o with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substituted widi one or two groups selected independendy from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; 15 cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted witii one or two groups selected independently from R 5 ; 20 or heteroaryl-(CH2)o-6- wherein the heteroaryl group is 5 to 6 membered widi one or two heteroatoms selected independently from O, S, and N and may be optionally substimted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO 2 -; 25 R 2 and R 3 , taken with the carbon atom to which tiiey are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionally having one or two double bonds; R 4 is hydrogen, 30 alkyl of 1 to 6 carbon atoms, optionaUy substimted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substimted wid one or two groups selected independently from R 5 ; phenyl or naphthyl optionaUy substituted with one or two groups selected independendy from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionaUy substituted with one or two groups selected independendy from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted with one or two groups selected independendy from R 5 ; R 5 is H, C7-C11 aroyl, C 2 -C 6 alkanoyl, Ci to C12 alkyl, C 2 to C12 alkenyl, C 2 -Cι 2 alkynyl, F, Cl, Br, I, CN, CHO, Ci-Cβ alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, alkoxyaryl, Ci-Ce alkoxyheteroaryl, C1-C6 aU ylamino-Cι-C6 alkoxy, C1-C2 aU ylene dioxy, aryloxy-Cι-C6 alkyl amine, -C12 perfluoro alkyl, S(O)n-Cι-C6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO d-C 6 alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR6R6, SO 2 NR 6 R6, NR6SO 2 aryl, -NR 6 CONR*R6, NHSO2CF3, SO2NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH 2 , OH, aryl, heteroaryl, C3 to Cβ cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein -C6 alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Q-Cό alkyl, -Cβ alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted widi OH; C3 to C6 alkenyl, C3 to Cβ alkynyl, to C6 perfluoro alkyl, S(O)n-Cι-C6 alkyl S(O) n aryl where n is 0, 1 or 2;, or COheteroaryl, wherein heteroaryl is a 5- 10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphtiiyl, optionaUy substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, -Cβ alkyl, Cι-C 6 alkoxy, or hydroxy; and R 7 is C 7 -C 11 aroyl, C 2 -C 6 alkanoyl, -C12 perfluoro alkyl, S(O) n -Cι-C 6 -alkyl, S(O) n - aryl where n is 0, 1 or 2; COO-Cι-C 6 -alkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO2NR 6 R 6 , SO 2 CF3, SC^NHheteroaryl, SO 2 NHCOaryl, CONHSO-Cι-C 6 -alkyl, CONHSC^aryl, aryl, or heteroaryl, where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independendy from halogen, cyano, amino, nitro, - alkyl, - alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or N- -Cβ alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substimted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substimted with one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independendy from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionaUy substituted widi one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independendy from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionaUy substimted with one or two groups selected independendy from R 5 ; saturated or unsaturated mono or bicychc heterocycle containing one heteroatom selected from O, S or N-C 1 -C 6 alkyl, optionally substimted widi one or two groups selected independently from R 5 ; or R 8 R 9 N-Cι-C 6 -alkoxyaryl-Cι-C 6 -alkyl where R 8 and R 9 are independendy selected from C 1 -C 6 alkyl or R 8 and R 9 togetiier widi die inteφosed nitrogen forms a 5-7 membered saturated heterocycUc ring optionaUy containing an oxygen atom, wherein die aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof. 15. A method according to claim 14 wherein die condition treated is atherosclerosis, atherosclerotic plaque formation, reduction of coronary thrombosis from atherosclerotic plaque rupture, restenosis, MMP-mediated osteopemas, 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 disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint 5 injury, demyelinating diseases of the nervous system, cirrhosis of the liver, glomerular disease of the kidney, premature rupture of fetal membranes, inflammatory bowel disease, or periodontal disease. 16. A mediod according to claim 14 wherein die condition treated is age related macular l o degeneration, diabetic retinopathy, proliferative vitreoretinopathy , retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neovascularization and corneal graft rejection. 17. A method of inhibiting pathological changes mediated by TNF-α converting enzyme 15 (TACE) in mammals which comprises administration to a mammal in need thereof a therapeuticaUy effective amount of a TACE inhibiting compound of the formula 20 wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionaUy substituted with one or two groups selected 25 independendy from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionaUy substimted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substimted with one or two groups selected independently from R 5 ; 30 aryl of 6 to 10 carbon atoms, optionally substituted witii one or two groups selected independently from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted with one or two groups selected independendy from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted widi one or two groups selected independendy from R 5 ; or heteroaryl-(CH 2 )o-6- wherein the heteroaryl group is 5 to 6 membered widi one or two heteroatoms selected independendy from O, S, and N and may be optionally substimted with one or two groups selected independently from R 5 ; A is -S-, -SO- or SO 2 -; R 2 and R 3 , taken with the carbon atom to which tiiey are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionaUy having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionaUy substimted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substimted with one or two groups selected independently from R 5 ; phenyl or naphthyl optionaUy substituted with one or two groups selected independently from R 5 ; C3 to Cβ cycloalkyl or bicycloalkyl optionaUy substituted widi one or two groups selected independently from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted wid one or two groups selected independendy from R 5 ; R 5 is H, C 7 -C 11 aroyl, C 2 -C 6 alkanoyl, d to 2 alkyl, C 2 to C alkenyl, C -Cι alkynyl, F, Cl, Br, I, CN, CHO, -C 6 alkoxy, aryloxy, heteroaryloxy, C 3 -C 6 alkenyloxy, C3-C6 alkynyloxy, C1-C6 alkoxyaryl, Ci-Cβ alkoxyheteroaryl, Ci-Cβ alkylamino-Cι-C6 alkoxy, C1-C2 alkylene dioxy, aryloxy-Cι-C 6 alkyl amine, C 1 - 2 perfluoro alkyl, S(O)n-Cι-C 6 alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO Cι-C 6 alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR 6 R 6 , SO 2 NR 6 R 6 , NR 6 SO 2 aryl, -NR 6 CONR 6 R 6 , NHSO 2 CF 3 , SO 2 NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO 2 -Cι-C 6 alkyl, CONHSO 2 aryl, NH 2 , OH, aryl, heteroaryl, C3 to Cβ cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein - alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, -Cβ alkyl, Q-Cβ alkoxy, or hydroxy; R 6 is H, Ci to Cis alkyl optionally substituted widi OH; C3 to Cβ alkenyl, C3 to Cβ alkynyl, to Cβ perfluoro alkyl, S(O)n-Cι-C6 alkyl S(O) n aryl where n is 0, 1 or 2;, or COheteroaryl, wherein heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionaUy substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, Ci-Cβ alkyl, Q-Cβ alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C2-C6 aUcanoyl, Q-C12 perfluoro alkyl, S(O) n -Cι-C 6 -alkyl, S(O) n - aryl where n is 0, 1 or 2; COO-Cι-C 6 -alkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO 2 NR 6 R 6 , SO2CF3, SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO-Cι-C 6 -alkyl, CONHSO 2 aryl, aryl, or heteroaryl, where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, C1-C6 alkyl, -Cβ alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or N-C1-C6 alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substimted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substimted with one or two groups selected independendy from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionally substituted widi one or two groups selected independendy from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionally substituted widi one or two groups selected independently from R 5 ; arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independendy from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein the cycloalkyl or bicycloalkyl group is optionaUy substimted widi one or two groups selected independendy from R 5 ; saturated or unsaturated mono or bicycUc heterocycle containing one heteroatom selected from O, S or N-Ci-Ce alkyl, optionally substimted widi one or two groups selected independendy from R 5 ; or R 8 R 9 N-Cι-C6-alkoxyaryl-Cι-C6-alkyl where R 8 and R 9 are independendy selected from C r C6 alkyl or R 8 and R 9 togetiier with the inteφosed nitrogen forms a 5-7 membered saturated heterocycUc ring optionaUy containing an oxygen atom, wherein die aryl group is phenyl or naphdiyl; or a pharmaceutically acceptable salt diereof. 18. The mediod according to claim 14 wherein the condition treated is rheumatoid arthritis, graft rejection, cachexia, anorexia, inflammation, fever, insuUn resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, or HIV infection. 19. A pharmaceutical composition comprising a pharmaceutical carrier and a therapeuticaUy effective amount of a matrix metaUoproteinase or TACE inhibiting compound according to die formula I wherein: R 1 is alkyl of 1 to 18 carbon atoms, optionaUy substituted with one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionaUy substituted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionaUy substimted with one or two groups selected independently from R 5 ; aryl of 6 to 10 carbon atoms, optionally substituted widi one or two groups selected independendy from R 5 ; cycloalkyl of 3 to 8 carbon atoms, optionally substituted widi one or two groups selected independendy from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted widi one or two groups selected independendy from R 5 ; or heteroaryl-(CH2)o-6- wherein the heteroaryl group is 5 to 6 membered widi one or two heteroatoms selected independendy from O, S, and N and may be optionally substimted widi one or two groups selected independently from R 5 ; A is -S-, -SO- or SO2-; R 2 and R 3 , taken with the carbon atom to which they are attached, form a 5 to 7 membered heterocyclic ring containing O, S or N-R 7 optionaUy having one or two double bonds; R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, optionaUy substimted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having 1 to 3 double bonds, optionally substituted with one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having 1 to 3 triple bonds, optionally substimted widi one or two groups selected independendy from R 5 ; phenyl or naphtiiyl optionaUy substituted widi one or two groups selected independently from R 5 ; C3 to Cδ cycloalkyl or bicycloalkyl optionaUy substituted with one or two groups selected independently from R 5 ; saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , optionally substimted with one or two groups selected independendy from R 5 ; R 5 is H, C7-C11 aroyl, C2-C6 alkanoyl, Ci to C12 alkyl, C 2 to C12 alkenyl, C2-C12 alkynyl, F, Cl, Br, I, CN, CHO, Cι-Cβ alkoxy, aryloxy, heteroaryloxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, -Cό alkoxyaryl, C1-C6 alkoxyheteroaryl, Ci-Cό alkylamino-Cι-C6 alkoxy, C1-C2 alkylene dioxy, aryloxy-Cι-C 6 alkyl amine, -C12 perfluoro alkyl, S^- -Ce alkyl, S(O) n -aryl where n is 0, 1 or 2; OCOO Cι-C 6 alkyl, OCOOaryl, OCONR 6 , COOH, COO Ci- alkyl, COOaryl, CONR 6 R 6 , CONHOH, NR 6 R 6 , SO2NR6R 6 , NR6SO 2 aryl, -NR 6 CONR 6 R 6 , NHSO 2 CF 3 , SO 2 NHheteroaryl,SO 2 NHCOaryl, CONHSO 2 -C r C 6 alkyl, CONHSO 2 aryl, SO 2 NHCOaryl, CONHSO2-C1-C6 alkyl, CONHSOzaryl, NH 2 , OH, aryl, heteroaryl, C3 to Cβ cycloalkyl; or saturated or unsaturated 5 to 10 membered mono or bicyclic heterocycle containing one heteroatom selected from O, S or NR 7 , wherein - alkyl is straight or branched, heteroaryl is a 5-10 membered mono or bicyclic heteroaryl group having 1 to 3 heteroatoms selected independendy from O, S or NR 7 and aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, alkyl, Ci-Cβ alkoxy, or hydroxy; R 6 is H, Ci to Ci δ alkyl optionally substituted widi OH; C3 to Cβ alkenyl, C3 to Cβ alkynyl, Ci to Cβ perfluoro alkyl, S(O)n-Cι-C6 alkyl S(O) n aryl where n is 0, 1 or 2;, or COheteroaryl, wherein heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or NR 7 and aryl is phenyl or naphthyl, optionaUy substituted by 1 or 2 groups selected from halogen, cyano, amino, nitro, C1-C6 alkyl, C1-C6 alkoxy, or hydroxy; and R 7 is C7-C11 aroyl, C2-C 6 alkanoyl, C1-C12 perfluoro alkyl, S(O) n -Cι-C 6 -alkyl, S(O) n - aryl where n is 0, 1 or 2; COO-Cι-C 6 -alkyl, COOaryl, CONHR 6 , CONR 6 R 6 , CONHOH, SO 2 NR6R6, SO 2 CF 3 , SO 2 NHheteroaryl, SO 2 NHCOaryl, CONHSO-Cι-C 6 -alkyl, CONHSO 2 aryl, aryl, or heteroaryl, where aryl is phenyl or naphthyl, optionally substituted by 1 or 2 groups selected independently from halogen, cyano, amino, nitro, -Cβ alkyl, -Cβ alkoxy, or hydroxy; and heteroaryl is a 5-10 membered mono or bicychc heteroaryl group having 1 to 3 heteroatoms selected independently from O, S or N- -Cβ alkyl; alkyl of 1 to 18 carbon atoms, optionally substituted widi one or two groups selected independently from R 5 ; alkenyl of 3 to 18 carbon atoms having from 1 to 3 double bonds, optionaUy substimted widi one or two groups selected independently from R 5 ; alkynyl of 3 to 18 carbon atoms having from 1 to 3 triple bonds, optionally substimted widi one or two groups selected independently from R 5 ; arylalkyl of 7 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independendy from R 5 ; biphenylalkyl of 13 to 18 carbon atoms, wherein biphenyl is optionaUy substituted widi one or two groups selected independendy from R 5 ; 5 arylalkenyl of 8 to 16 carbon atoms, wherein aryl is optionaUy substituted with one or two groups selected independendy from R 5 ; cycloalkylalkyl or bicycloalkylalkyl of 4 to 12 carbon atoms, wherein die cycloalkyl or bicycloalkyl group is optionaUy substimted with one or two groups selected independendy from R 5 ; l o saturated or unsaturated mono or bicychc heterocycle containing one heteroatom selected from O, S or N- -C6 alkyl, optionally substimted with one or two groups selected independently from R 5 ; or R 8 R 9 N-Cι-C 6 -alkoxyaryl-Cι-C 6 -alkyl where R 8 and R 9 are independendy selected from C 1 -C 6 alkyl or R 8 and R 9 together with the interposed nitrogen forms a 15 5-7 membered saturated heterocycUc ring optionally containing an oxygen atom, wherein the aryl group is phenyl or naphthyl; or a pharmaceutically acceptable salt tiiereof.

Inventors: BAKER JANNIE LEA, DAVIS JAMIE MARIE, GROSU GEORGE THEODORE, VENKATESAN ARANAPAKAM MUDUMBAI, BAKER, JANNIE, LEA, DAVIS, JAMIE, MARIE, GROSU, GEORGE, THEODORE, VENKATESAN, ARANAPAKAM, MUDUMBAI
Applicants: AMERICAN CYANAMID CO, AMERICAN CYANAMID COMPANY
Application year: 1998
Main classification: A61K31
IPC codes: A61K31, A61P1, A61P3, A61P9, A61P17, A61P19, A61P29, A61P31, A61P35, A61P37, C07C317, C07C323, C07D207, C07D209, C07D211, C07D213, C07D215, C07D231, C07D233, C07D235, C07D241, C07D257, C07D263, C07D277, C07D285, C07D295, C07D307, C07D309, C07D333, C07D409