United States Patent Application 08/987167 filed December 8,1997, teaches MMP inhibitors and their preparation and is hereby incorporated by reference.

Compounds which inhibit acyl-coenzyme A : cholesterol acyltransferase are known as ACAT inhibitors. Certain ACAT inhibitors and the methods for preparing them are taught in United States Patent 5, 491, 172 and its divisional 5, 633, 287 which are hereby incorporated by reference.

United States Patent 5, 756, 545 covers MMP inhibitors especially 2- (4'-Bromo-biphenyl-4-sulfonylamino) -3-methyl-butyric acid. This patent is hereby incorporated by reference.

United States Patent 5, 441, 975 teaches ACAT inhibitors, especially N-(2,6-Diisopropyl-phenyl)-2-(2-dodecyl-2H-tetrazol-5-yl)-2- phenyl-acetamide.

This and other patents in the same patent family : 5, 646, 170 ; 5, 693, 657 ; and 5, 366, 987 are hereby incorporated by reference.

SUMMARY OF THE INVENTION The instant invention is the coadministration of ACAT and MMP inhibitors for the reduction of both macrophage and smooth muscle cell components of atherosclerotic lesions in a mammal, particularly a human. The lesions are directly reduced, and so, the expansion of existing lesions and the development of new ones is impaired.

Certain ACAT inhibitors and certain MMP inhibitors are disclosed as suitable for coadministration.

Pharmaceutical compositions of the inhibitors are also included in the invention.

DETAILED DESCRIPTION OF THE INVENTION Coadministration of a bioavailable ACAT inhibitor with a matrix metalloproteinase (MMP) inhibitor can blunt the development of atherosclerotic lesions and promote development of a stable plaque morphology. ACAT inhibitors have been shown to reduce the accumulation of monocyte-macrophages within atherosclerotic lesions of rabbits. In addition, monocyte-macrophages have been reported to secrete such matrix metalloproteinases as MMP-7 and -9 while smooth muscle cells are noted to secrete MMP-1, -2, and -3. Inhibition of ACAT while directly reducing the accumulation of lipid-filled monocyte-macrophages will decrease the source of MMPs. Inhibition of MMPs will also limit the development of atherosclerotic lesions through reducing smooth muscle cell and monocyte migration into the development intima by limiting extracellular matrix remodeling. Coadministration of both agents will limit the development of new lesions by inhibiting cellular accumulation and stabilize the developed lesions by preventing both matrix remodeling and reducing the number of lipid-filled monocyte-macrophages, a source of MMP-7 and -9.

The instant invention is a method for treating and/or preventing atherosclerotic lesions comprising coadministrating one or more MMP inhibitors and one or more ACAT inhibitors.

The invention is further a method for preventing plaque rupture and for promoting lesion regression by administering a combination of an ACAT inhibitor and an MMP inhibitor.

The method is practiced by administering a chemical compound effective in inhibiting the biological activity of a matrix metalloproteinase such as collagenase, stromelysin, gelatinase, or elastase. The numerous compounds known to be matrix metalloproteinase inhibitors are useful in the practice of this invention.

The method is practiced by administering a chemical compound which inhibits the enzyme acyl-coenzyme A : cholesterol acyltransferase. The numerous compounds known as ACAT inhibitors are useful in the practice of this invention.

A 'matrix metalloproteinase inhibitor"as used herein is any chemical compound that inhibits by at least five percent the hydrolytic activity of at least one matrix metalloproteinase enzyme that is naturally occurring in a mammal.

Such compounds are also referred to as"MMP inhibitors."Numerous matrix metalloproteinase inhibitors are known, and all are useful in the method of this invention. For example, 4-biarylbutyric and 5-biarylpentanoic acid derivatives are described in United States Patent Application 339846 filed November 15,1994, which is incorporated herein by reference. The compounds are defined generally as (T) xA-B-D-E-G. Over 400 specific compounds are named, and each is incorporated herein and can be employed in this invention. Especially preferred compounds to be utilized include the following : [1,1 '-Biphenyl] -4-butanoic acid, 4'-chloro-oc-(2-methylpropyl)-^y-oxo-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-chloro-oc-(2-methylpropyl)-Y-oxo-, <BR> <BR> <BR> <BR> <BR> <BR> [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-α-(2-methylpropyl)-γ-oxo-, <BR> (R)-; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-ß-(2-methylpropyl)-γ-oxo-, (S);<BR> <BR> <BR> <BR> <BR> <BR> [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-ß-(2-methylpropyl)-γ-oxo-, <BR> (R)-; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> [1.1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-; [1,1 '-Biphenyl]-4-butanoic acid, 4'-bromo-y-oxo-;

[1,1 '-Biphenyl]-4-butanoic acid, 4'-fluoro-y oxo- ; [1,1 '-Biphenyl]-4-butanoic acid, 2'-fluoro-Y-oxo-; [l,l'-Biphenyl]-4-butanoic acid, 2'-chloro-y oxo- ; [1, 1'-Biphenyl] -4-butanoic acid, 2', 4'-difluoro-y oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 3'-chloro-γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, a- (2-methyl-propyl) -y oxo- ; [l,l'-Biphenyl]-4-butanoic acid, 4'-bromo-a- (2-methylpropyl) -y oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-fluoro-α-(2-methylpropyl)-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-ethyl-α-(2-methylpropyl)-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 2'-fluoro-α-(2-methylpropyl)-γ-oxo-; [1, 1'-Biphenyl]-4-butanoic acid, 2'-chloro-α-(2-methylpropyl)-γ-oxo-; [1, I'-Biphenyl] -4-butanoic acid, 4'-methoxy-a- (2-methylpropyl) -y-oxo- ; [1, 1'-Biphenyl] -4-butanoic acid, 2', 4'-difluoro-a- (2-methylpropyl) -y oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-methyl-α-(2-methylpropyl)-γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, a- (2-methyl-propyl) -y oxo-4'-pentyl- ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-oc-methylene-y oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 2'-chloro-α-methylene-γ-oxo-; [1,1 '-Biphenyl]-4-butanoic acid, 4'-chloro-a-methyl-y oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-pentyl-; Benzenebutanoic acid, 4-chloro-α-(2-methylpropyl)-γ-oxo-; Benzenebutanoic acid, 4-methyl-a-methylene-y-oxo- ; 2-Butenoic acid, 4-(4'-chloro[l,l'-biphenyl]-4-yl)-4-oxo-, (E)-; 2-Butenoic acid, 4-[4-(4-chlorophenyoxy)-phenyl]-4-oxo, (E)-; [1,1 '-Biphenyl] -4-butanoic acid, 4'-hydroxy-a- (2-methylpropyl) -y-oxo- ; [1,1 '-Biphenyl] -4-butanoic acid, 4'-chloro-ß-methylene-Y-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-hydroxy-α-(2-methylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-hydroxy-α-(2-methylpropyl)-; 2(3H)-Furanone, 5-(4'-chloro[1,1'-biphenyl]-4-yl)dihydro-3- (2-methylpropyl)-; 2(3H)-Furanone, 5-(4'-chloro[1,1'-biphenyl]-4-yl)dihydro-3-(2- methylpropyl)-;

[l,l'-Biphenyl]-4-butanoic acid, 3', 4'-dichloro-y-oxo-a- (3-phenylpropyl) - ; [1, 1'-Biphenyl] -4-butanoic acid, 3', 5'-dichloro-y-oxo-a- (3-phenylpropyl) - ; [l,l'-Biphenyl]-4-butanoic acid, 4'- (acetyloxy) -y-oxo-a- (3- phenylpropyl) - ; Benzenepentanoic acid, α-[2-[4-(5-chloro-2-thienyl)phenyl]-2-oxoethyl]-; 2-Furancarboxylic acid, 5-[4-(3-carboxy-1-oxo-6-phenylhexyl)phenyl]-; Benzenepentanoic acid, a- [2-oxo-2- [4- (3-pyridinyl) phenyl] ethyl] - ; Benzenepentanoic acid, a- [2-oxo-2- [4- [6- (pentyloxy) -3-pyridinyl] - phenyl] ethyl] - ; [1, 1'-Biphenyl] -4-butanoic acid, γ-oxo-4'-(pentylthio)-α-(3- <BR> <BR> <BR> <BR> phenylpropyl); <BR> <BR> <BR> <BR> <BR> [1, 1'-Biphenyl] -4-butanoic acid, 4"-methoxy-y-oxo-a- (3-phenylpropyl) - ; [l,l'-Biphenyl]-4-butanoic acid, 3'-chloro-4'-fluoro-γ-oxo-α-(3- phenylpropyl)-; [1,1 '-Biphenyl]-4-butanoic acid, 4'-ethoxy-γ-oxo-α-(3-phenylpropyl)-; Benzenepentanoic acid, a- [2-oxo-2- [4- (3-thienyl) phenyl] ethyl] - ; [1, 1'-Biphenyl] -4-butanoic acid, 2', 4'-dichloro-y-oxo-a- (3-phenylpropyl) - ; [1,1'-Biphenyl]-4-butanoic acid, 4'-formyl-γ-oxo-α-(3-phenylpropyl)-; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-ot-(3-phenylpropyl)-3',5'- bis (trifluoromethyl) - ; Benzenepentanoic acid, a- [2-oxo-2- [4- (2-thienyl) phenyl] ethyl] - ; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-α-(3 -phenylpropyl)-3'- (trifluoromethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 2'-formyl-γ-oxo-α-(3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4-hydroxy-γ-oxo-α-(3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-α-(3-phenylpropyl)-4'-propoxy-; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-4'-(pentyloxy)-a-(3- phenylpropyl) - ; [l,l'-Biphenyl]-4-butanoic acid, y-oxo-4'- (pentyloxy) -a- (3- phenylpropyl)-, (S)-;

[1,1'-Biphenyl]-4-butanoic acid, γ-oxo-4'-(pentyloxy)-α-(3- phenylpropyl)-, (R)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-(hexyloxy)-γ-oxo-α-(3-phenylpropyl)-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-butoxy-Y-oxo-(x-(3-phenylpropyl)-; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-4'-(3-phenylpropoxy)-oc- (3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-(1-methylethoxy)-γ-oxo-α- (3-phenylpropyl)-; [1,1 '-Biphenyl]-4-butanoic acid, 4'- (heptyloxy) -y-oxo-a- (3 -phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-(cyclohexyl-methoxy)-γ-oxo-α- (3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-(2-methyl-propoxy)-γ-oxo-α- (3-phenylpropyl)-; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-a-(3-phenylpropyl)-4'- (2-propenyloxy) - ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-oc-heptyl-y-oxo-; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a-decyl-y-oxo- ; [1, I'-Biphenyl] -4-butanoic acid, 4'-nitro-y-oxo-a- (2-phenylethyl) - ; [1, 1'-Biphenyl] -4-butanoic acid, 4'-cyano-y-oxo-a- (2-phenylethyl) - ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- (2-iodophenyl) ethyl] - y-oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[2-(3-iodophenyl)ethyl]- <BR> <BR> <BR> <BR> γ-oxo-; <BR> <BR> <BR> <BR> [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[2-(4-iodophenyl)ethyl]-<BR> <BR> <BR> <BR> <BR> <BR> γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-oc-[2-(3,5- dimethoxyphenyl)ethyl] -Y-oxo-; [1,1 '-Biphenyl]-4-butanoic acid, 4'-chloro-y-oxo-a-phenyl- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-(phenylmethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-(2-phenylethyl)-;

[1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-[(trimethylsilyl)- methyl]-; [1,1'-Biphenyl]-4-butanoic acid, 4'-bromo-γ-oxo-α-(3-phenylpropyl)-; [1, 1'-Biphenyl] -4-butanoic acid, -y-oxo-a- (3-phenylpropyl) - ; [1,1'-Biphenyl]-4-butanoic acid, 4'-amino-γ-oxo-α-(2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-α-(2-phenylethyl)-4'- [[(phenylmethoxy)carbonyl]amino]-; [1,1-Biphenyl]-4-butanoic acid, 4'-[[(1,1-dimethylethoxy)- carbonyl]amino]-γ-oxo-α-(2-phenylethyl)-; [1, I'-Biphenyl] -4-butanoic acid, 4'- (acetylamino) y-oxo-oc- (2-phenylethyl) - ; [1, 1'-Biphenyl] -4-butanoic acid, y-oxo-4'- [ ( 1 -oxopentyl) amino] -a- (2-phenylethyl) - ; [1,1'-Biphenyl]-4-butanoic acid, 4'-[(3,3-dimethyl-1-oxobutyl)amino]- γ-oxo-α-(2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[2-[2-(methoxycarbonyl)- phenyl]ethyl]-γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, a- [2- (2-carboxyphenyl) ethyl] -4'-chloro- y-oxo- ; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α- [2-[2-[(diethylamino)- carbonyl]phenyl]ethyl]-γ-oxo-; [I,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- [3- [ (diethylamino) carbonyl] phenyl] ethyl] -y-oxo-, (S) - ; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[2-[3- [(diethylamino)carbonyl]phenyl]ethyl]-γ-oxo-, (R)-; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[(phenylmethoxy)methyl]-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-(phenoxymethyl)-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2- [ (benzoyloxy) -methyl] -5- [ (4"-chloro [1, 1"- biphenyl] -4-yl) carbonyll -, (I cc, 2p, 5 P) - ;

1,2-Benzenedicarboxylic acid, 1-[[2-carboxy-3-[(4'-chloro [1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]-methyl]-2-methyl ester,( 1α,2ß,3α)-; Cyclopentanecarboxylic acid, 2- [ (4'-chloro [1, 1'-biphenyl] -4-yl) carbonyl] - 5- [ (2-thienylthio) methyl] -, (lu., 2p, 5p) - ; Cyclopentanecarboxylic acid, 2- [ (benzoylamino) methyl] -5- [ (4'- chloro [1, 1'-biphenylM-yOcarbonyl] -, (1 oc, 2p, 5p) - ; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[[(2-methoxyethoxy)methoxy]methyl]-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2- [ (4'-chloro [ 1, 1'-biphenyl] -4-yl) carbonyl] - 5- [ [ (phenylmethyl) thio] methyl] -, (loc, 20, 5p) - ; Cyclopentanecarboxylic acid, 2- [ (4'-chloro [1, 1'-biphenyl] -4-yl) carbonyl] - 5- [ (phenylthio) methyl] -, (I a, 2p, 5p) - ; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[(propylthio)methyl]-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2-[(2-benzothiazolylthio)methyl]-5-[(4'- chloro[1,1-biphenyl]-4-yl)carbonyl]-, (1α,2ß,5ß)-; Benzoic acid, 2- [ [ [2-carboxy-3- [ (4'-chloro [l, l'-biphenyl] - 4-yl) carbonyl] cyclopentyl] methyl] thio] -, 1-methyl ester, (1α,2ß,3α)-; Cyclopentanecarboxylic acid, 2- [ (4-chloro [1, 1'-biphenyl] -4-yl) carbonyl] - 5 - [ (phenylmethoxy) carbonyl] -amino] methyl] -, (I (x, 2p, 5p) - ; Benzoic acid, 2-methyl-, [2-carboxy-3-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-; Benzoic acid, 3-methyl-, [2-carboxy-3-[(4'-chloro [1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-; Benzoic acid, 4-methyl-, [2-carboxy-3-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-; Benzoic acid, 2-methoxy-, [2-carboxy-3-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-; Benzoic acid, 3-methoxy-, [2-carboxy-3-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-;

Benzoic acid, 4-methoxy-, [2-carboxy-3-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]cyclopentyl]methyl ester, (1α,2ß,3α)-; Cyclopentanecarboxylic acid, 2-[(2-benzoxazolylthio)methyl]-5-[(4'- chloro[1,1'-biphenyl]-4-yl)carbonyl]-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[(1,3-dihydro-4-nitro-1,3-dioxo-2H-isoindol-2-yl)methyl]-, (1α,2ß,5ß)-; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[(1,3-dihydro-5-nitro-1,3-dioxo-2H-isoindol-2-yl)methyl]-, (1α,2ß,5ß)-; 2H-Benz[f]isoindole-2-butanoic acid, α-[2- (4'-ethoxy [ 1, 1'-biphenyl] -4-yl) - 2-oxoethyl] -1, 3-dihydro-1, 3-dioxo- ; [1,1'-Biphenyl]-4-butanoic acid, α-(acetylamino)-4'-chloro-γ-oxo-; <BR> <BR> <BR> <BR> 2H-Isoindole-2-hexanoic acid, α-[2-(4'-chloro[1,1'-biphenyl]-4-yl)- <BR> <BR> <BR> <BR> <BR> 2-oxoethyl]-1,3-dihydro-1,3-dioxo-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-chloro-a- [ [ [3- (methoxycarbonyl) - <BR> <BR> <BR> <BR> phenyl] thio] methyl] -y-oxo- ; <BR> <BR> <BR> <BR> <BR> [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[[(2,6-(dimethylphenyl)- <BR> <BR> <BR> <BR> <BR> thio]methyl]-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [ [ [4-fluoro- <BR> <BR> <BR> <BR> 2- (methoxycarbonyl) phenyl] thio] methyl] -y-oxo- ; <BR> <BR> <BR> <BR> <BR> [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[[[3-[(diethylamino)- <BR> <BR> <BR> <BR> <BR> <BR> carbonyl]phenyl]thio]methyl]-γ-oxo-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-chloro-α-[[[2-[(dimethylamino)- carbonyl]phenyl]thio]methyl]-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[[[3-[(dimethylamino)- carbonyl]phenyl]thio]methyl-]-γ-oxo-; Bicyclo [2. 2. 1] hept-5-ene-2-carboxylic acid, 3- [ [4'- (pentyloxy) [ 1, 1'- biphenyl]-4-yl]carbonyl]-, (2-endo,3-exo)-; 1-Cyclopentene-1-carboxylic acid, 5-[(4'-chloro[1,1'-biphenyl]- 4-yl)carbonyl]-; Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 5-[(phenylmethyl)thio]-, (1α,2ß,5α)-;

Cyclopentanecarboxylic acid, 2-[(4'-chloro[1,1'-biphenyl-4-yl)carbonyl]- 5-[(phenylmethyl)thio]-, (1α,2ß,5ß)-; 1-Cyclopentene-1-carboxylic acid, 5-[[4'-(pentyloxy)[1,1'-biphenyl]- 4-yl]carbonyl]-; 1-Cyclopentene-1-carboxylic acid, 5- [ [4'- (hexyloxy) [I, I'-biphenyl] - 4-yl) ] carbonyl] - ; [l,l'-Biphenyl]-4-butanoic acid, 4'-hydroxy-y-oxo-a- [ (phenylthio) - methyl] - ; [1,1'-Biphenyl]-4-butanoic acid, α-[2-[2-[(butylamino)- carbonyl]phenyl]ethyl]-4'-chloro-γ-oxo-; [1, I'-Biphenyl] -4-butanoic acid, a- [2- (3-carboxyphenyl) ethyl] -4'-chloro- y-oxo- ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- [3- [ (diethylamino) - carbonyl] phenyl] ethyl] -y-oxo- ; [1,1'-Biphenyl]-4-butanoic acid, α-[2-[3-[(butylamino)carbonyl]- phenyl]ethyl]-4'-chloro-γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- [4- [ (diethylamino) - carbonyl] phenyl] ethyl] -y-oxo- ; [1,1'-Biphenyl]-4-butanoic acid, α-[2-[4-[(butylamino)- carbonyl]phenyl]ethyl]-4'-chloro-γ-oxo-; [l,l'-Biphenyl]-4-butanoic acid, oc- [2- (4-carboxyphenyl) ethyl] -4'-chloro- y-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-methoxy-γ-oxo-α-(2-phenylethyl)-; [l,l'-Biphenyl]-4-butanoic acid, 4'-hydroxy-y-oxo-a- (2-phenylethyl) - ; [1,1'-Biphenyl]-4-butanoic acid, 4'-ethoxy-γ-oxo-α-(2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-α-(2-phenylethyl)-4'-propoxy-; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-4'-(pentyloxy)-α-(2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-(hexyloxy)-γ-oxo-α-(2-phenylethyl)-; [l,l'-Biphenyl]-4-butanoic acid, 4'-butoxy-y-oxo-a- (2-phenylethyl) - ; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-ot-(2-phenylethyl)-4'- (phenylmethoxy) - ;

[1, 1'-Biphenyl] -4-butanoic acid, a- [2- (3-iodophenyl) ethyl) -y-oxo-4'- (pentyloxy) - ; [1,1'-Biphenyl]-4-butanoic acid, a-[2-(3-iodophenyl)ethyl]-Y-oxo-4'- (phenylmethoxy) - ; [1,1'-Biphenyl]-4-butanoic acid, α-[2-(3-[(diethylamino)carbonyl]- phenyl]ethyl]-γ-oxo-4'-(pentyloxy)-; [1, 1'-Biphenyll-4-butanoic acid, a- [2- (3- [ (diethylamino) carbonyl] - phenyl]ethyl]-Y-oxo-4'-(phenylmethoxy)-; 1, 2-Pyrrolidinedicarboxylic acid, 3- [ (4'-chloro [1, 1'-biphenyl] - 4-yl) carbonyl] -, 1- (phenylmethyl) ester, (2S-trans)-; 1, 2-Pyrrolidinedicarboxylic acid, 3-[(4'-chloro[ l,1 '-biphenyl]- 4-yl) carbonyl] -, 1- (phenylmethyl) ester, (2'R-trans) - ; L-Proline, 3-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]- 1-[[(phenylmethyl)amino]carbonyl]-, trans-; L-Proline, 3-[(4'-chloro[1,1'-biphenyl]-4-yl)carbonyl]-1-(1-oxo- 3-phenylpropyl)-, trans-; L-Proline, 3- [ (4'-chloro [1, I'-biphenyl] -4-yl) carbonyl] -1- (phenylacetyl) -, trans- ; L-Proline, 3- [ (4'-chloro [l, l'-biphenyl) -4-yl) carbonyl] -1- (3, 3-dimethyl- l-oxobutyl)-, trans-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-heptyl-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-decyl-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-nitro-γ-oxo-α-(2-phenylethyl)-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-cyano-y-oxo-a- (2-phenylethyl) - ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-oc- [2- (2-iodophenyl) ethyl] -y- oxo- ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- (3-iodophenyl) ethyl] -y- oxo- ; [1, 1'-Biphenyl] -4-butanoic acid, 4'-chloro-a- [2- (4-iodophenyl) ethyl] -y- oxo- ;

[1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-α-[2-(3,5- dimethoxyphenyl)ethyl]-γ-oxo-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-phenyl-; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-Y-oxo-(x-(phenylmethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-(2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-chloro-γ-oxo-α-[(trimethylsilyl)- methyl]-; [1,1'-Biphenyl]-4-butanoic acid, 4'-bromo-γ-oxo-α-(3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, y-oxo-ol-(3-phenylpropyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-amino-γ-oxo-α-(2-phenylethyl)-; [1,1 '-Biphenyl]-4-butanoic acid, y-oxo-(x-(2-phenylethyl)-4'- [[(phenylmethoxy)carbonyl]amino] -; [1,1'-Biphenyl]-4-butanoic acid, 4'-[[(1,1-dimethylethoxy)- carbonyl]amino]-γ-oxo-α-(2-phenylethyl)-; [1,1 '-Biphenyl]-4-butanoic acid, 4'- (acetylamino) -y-oxo-a- (2-phenylethyl) - ; [1,1'-Biphenyl]-4-butanoic acid, γ-oxo-4'-[(1-oxopentyl)amino]-α- (2-phenylethyl)-; [1,1'-Biphenyl]-4-butanoic acid, 4'-[(3,3-dimethyl-1-oxobutyl)amino]-γ- oxo-α-(2-phenylethyl)-; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-a- [2- [2-methoxycarbonyl) - phenyl] ethyl] -y-oxo- ; [1,1'-Biphenyl]-4-butanoic acid, α-[2-(2-carboxyphenyl)ethyl]-4'-chloro- γ-oxo-; [1, 1'-Biphenyl] -4-butanoic acid, 4'-chloro-a- [2- [2- [ (diethylamino) - carbonyl) phenyl] ethyl] -y-oxo- ; [l,l'-Biphenyl]-4-butanoic acid, 4'-chloro-ot-[2-[3-[(diethylamino)- carbonyl) phenyl] ethyl] -y-oxo-, (S) - ; and [1,1 '-Biphenyl]-4-butanoic acid, 4'-chloro-oc- [2- [3- [ (diethylamino) - carbonyl) phenyl] ethyl] -y-oxo-, (R) -.

Fenbufen and compounds related to fenbufen can be utilized. Such compounds are described in United States Patent Number 3, 784, 701 and by Child, et al., J. Pharm. Sci., 1977 ; 66 : 466-476, and Arzneim-Forsch, 1980 ; 30 (4A) : 695- 702, all of which are incorporated herein by reference. Preferred compounds from the fenbufen series to be utilized in this invention have the formula where R is 0 1 CCH2CH2COOH (fenbufen), COCH=CHCOOH, S02NH2, COCH2CHCOOH, CH3 Numerous peptides are known matrix metalloproteinase inhibitors. Typical of such peptides are those described in United States Patent Number 5, 300, 501 ; 5, 530, 128 ; 5, 455, 258 ; 5, 552, 419 ; WO 95/13289 ; and WO 96/11209, all of which are incorporated herein by reference. Such compounds are illustrated by the formula where each of the variable groups can include hydrogen alkyl, aryl, heteroaryl, alkenyl, alkynyl, carboxy, and the like. Preferred compounds from within this class which can be utilized in the method of this invention include the following :

N-[2,3-bis-Acetylmercaptopropanoyl)-L-leucyl-L-phenylalanine <BR> <BR> <BR> <BR> N-methylamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Acetylmercapto-3-methoxycarbonylpropanoyl] -L-leucyl-L- phenylalanine N-methylamide ; N- [2-Acetylmercapto-4-methoxycarbonylbutanoyl] -L-leucyl-L- phenylalanine N-methylamide ; N- [2-Acetylmercapto-5-methoxycarbonylpentanoyl] -L-leucyl-L- phenylalanine N-methylamide ; N- [2-Acetylmercapto-6-methoxycarbonylhexanoyl] -L-leucyl-L- phenylalanine N-methylamide ; <BR> <BR> <BR> <BR> N- [2-Acetylmercapto-4-phthalimidobutanoyl] -L-leucyl-L-phenylalanine<BR> <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Acetylmercapto-5-phthalimidopentanoyl] -L-leucyl-L-phenylalanine<BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Acetylmercapto-6-phthalimidohexanoyl] -L-leucyl-L-phenylalanine<BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; N-[2,3-bis-Mercaptopropanoyl]-L-leucyl-L-phenylalanine N-methylamide; N-[2-Mercapto-3-methoxycarbonylpropanoyl]-L-leucyl-L-phenyla lanine N-methylamide; N- [2-Mercapto-4-methoxycarbonylbutanyol] -L-leucyl-L-phenylalanine <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Mercapto-4-methoxycarbonylpentanoyl] -L-leucyl-L-phenylalanine<BR> <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Mercapto-6-methoxycarbonylhexanoyl] -L-leucyl-L-phenylalanine<BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Mercapto-4-phthalimidobutanoyl] -L-leucyl-phenyl-alanine<BR> <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Mercapto-5-phthalimidopentanoyl] -L-leucyl-L-phenylalanine <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide ; N- [2-Mercapto-6-phthalimidohexanyoyl] -L-leucyl-L-phenylalanine N-methylamide ; N-[2-Acetylmercapto-5-methoxycarbonylpentanoyl]-L-leucyl- L-phenylalanine N-methylamide;

N- [2-Acetylmercapto-6-methoxycarbonylhexanyol] -L-leucyl- L-phenylalanine N-methylamide ; N- [2-Acetylmercapto-6-methoxycarbonylhexanyol] -L-valinyl- L-phenylalanine N-methylamide ; N- [2-Acetylmercapto-6-methoxycarbonylhexanyol] -L-leucyl-L-tryptophan N-methylamide ; N- [2-Acetylmercapto-5-phthalimidopentanoyl] -L-leucyl-L-phenylalanine N-methylamide ; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-valinyl-L-phen ylalanine <BR> <BR> <BR> N-methylamide; <BR> <BR> <BR> N- [2-Acetylmercapto-5-phthalimidopentanoyl] -L-leucyl-L-tryptophan<BR> <BR> <BR> N-methylamide ; <BR> <BR> N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-L-[ß-( 4- thiazolyl)]alaine N-methylamide; <BR> <BR> <BR> N- [2-Acetylmercapto-5-phthalimidopentanoyl] -L-leucyl-L- (O- (2- <BR> <BR> <BR> pyridyl) alanine N-methylamide ; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-5-methy l-L- glutamicacid N-methylamide; N- [2-Acetylmercapto-6-phthalimidohexanoyl] -L-leucyl-L-phenylalanine N-methylamide ; N- [2-Acetylmercapto-2- (3-phthalimido) phenylacetyl] -L-leucyl- L-phenylalanine N-methylamide ; <BR> <BR> <BR> N- [2-Mercapto-5 -methoxycarbonylpentanoyl] -L-phenylalanine<BR> <BR> <BR> N-methylamide ; N- [2-Mercapto-6-methoxycarbonylhexanyol] -L-leucyl-L-phenylalanine N-methylamide ; N- [2-Mercapto-6-methoxycarbonylhexanyol] -L-leucyl-L-trptophan N-methylamide ; N- [2-Mercapto-5 -phthalimidopentanoyl] -L-leucyl-L-phenylalanine N-methylamide ; <BR> <BR> <BR> N- [2-Mercapto-5-phthalimidopentanoyl] -L-leucyl-L-tryptophan<BR> <BR> <BR> N-methylamide ;

N- [2-Mercapto-5-phthalimidopentanoyl] -L-leucyl-L- [ (3- (4-thiazolyl)alanine N-methylamide; N-[2-Mercapto-5-phthalimidopentanoyl]-L-leucyl-L-[ß-(2- pyridyl)]alanine N-methylamide; N- [2-Mercapto-5-phthalimidopentanoyl] -L-leucyl-5-methyl-L-glutamic acid N-methylamide ; N- [2-Mercapto-6-phthalimidohexanoyl] -L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> N- [N-Mercaptoacetyl) -L-leucyl] -L-phenylalanine N-methylamide ; <BR> <BR> <BR> N- [Acetomercaptoacyl) -L-leucyl-L-phenylalanine methylamide ; (RS)-2-(Acetylthio)pentanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)propanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)-3-methylbutanoyl-L-leucyl-L-phenylalanin e N-methylamide; (RS)-2-(Acetylthio)-2-phenylacetyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)-3-phenylpropanoyl-L-leucyl-L-phenylalani ne N-methylamide; (RS)-2-(Acetylthio)-4-phenylbutanoyl-L-leucyl-L-phenylalanin e N-methylamide; N- (Acetylmercaptoacyl) -L-threonyl-L-phenylalanine methylamide ; N- (Acetylmercaptoacyl) -L-leucyl-L-tryptophan methylamide ; (RS)-2-Mercaptopentanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-Mercaptopropanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS) -2-Mercapto-3-methylbutanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-2-phenylacetyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-3-phenylpropanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-4-phenylbutanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ;

N-[N-(Mercaptoacetyl)-L-threonyl]-L-phenylalanine methylamide; N-[N-(Mercaptoacetyl)-L-leucyl]-L-tryptophan methylamide; [4-(N-Hydroxyamino)-2(R)-cyclohexylmethylsuccinyl]-L-ß- cyclohexylalanine-N-(2-phenylethyl)amide; [4-N-(Hydroxyamino)-2R-isobutylsuccinyl]-L-ß-cyclohexylalan ine-N- (2-phenylethyl)amide; [4-(N-hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-(2-phenylethyl)amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-[2-(N,N-dimethylamino]ethyl)amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-[2-(p-sulphonamidophenyl)ethyl)amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-(2-(p-sulphonylphenyl)ethyl)amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-[2-(2-pyridyl)ethyl]amide; [4-(N-Hydroxyamino)-2R-pentylsuccinyl]-L-ß-cyclohexylalanin e-N- <BR> <BR> <BR> <BR> (2-phenylethyl)amide; <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isoamylsuccinyl]-L-ß-cycloheXylalani ne-N- (2-phenylethyl) amide ; [4-(N-Hydroxyamino)-2R-phenylbutylsuccinyl]-L-ß-cyclohexyla lanine-N- (2-phenylethyl)amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- N-[3-(4-morpholinyl)propyl]amide; [4-(N-Hydroxyamino)-2R-phenylpropylsuccinyl]-L-ß-cyclohexyl alanine- <BR> <BR> <BR> <BR> N-[ß-alanine]amide; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-ß-cycloheXylalan ine amide; [4-(N-Hydroxyamino)-2R-(3-phenylpropyl)succinyl]-L-ß- cyclohexylalanine amide; [4-(N-Hydroxyamino)-2R-(3-phenylbutyl)succinyl]-L-ß- cyclohexylalanine amide;

[4-N- (Hydroxyamino) -2R-phenylethylsuccinyl] -L-leucine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-phenylethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-phenylpropylsuccinyl] -L-leucine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-phenylethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R) -isobutylsuccinyl] -L-tryptophan amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R) -isobutylsuccinyl] -L-valine amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [3-Phosphono-2R,S-phenylpropyl- 1 -oxopropyl]-L-ß-cyclohexylalanine-N- <BR> <BR> <BR> <BR> <BR> <BR> (2-phenylethyl) amide, dimethylester ; [3-Phosphono-2R-phenylpropyl-l-oxopropyl] -L-p-cyclohexylalanine-N- <BR> <BR> <BR> <BR> (2-phenylethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [3-Phosphono-2S-phenylpropyl-l-oxopropyl] -L-p-cyclohexylalanine-p- <BR> <BR> <BR> <BR> <BR> <BR> <BR> alanine ; [3-Phosphono-2R-phenylpropyl-l-oxopropyl] -L-p-cyclohexylalanine ; [3-Phosphono-2S-phenylpropyl-1-oxopropyl]-L-ß-cyclohexylala nine-ß- alanine, methyl ester; [3-Phosphono-2R, S-phenylpropyl-l-oxopropyl] -L-p-cyclohexylalanine-N- [4 (3-aminopropyl) morpholine] amide, bromine salt ; <BR> <BR> <BR> <BR> [3-Phosphono-2R,S-(4-methylphenyl)propyl- 1 -oxopropyl]-L-ß- <BR> <BR> <BR> <BR> <BR> <BR> cyclohexylalanine-N- (2-phenylethyl) amide, diethylester ; [3-Phosphono-2R,S-(4-methylphenyl)propyl-1-oxopropyl]-L-ß- cyclohexylalanine-N-(2-phenylethyl)-amide; 4-t-Butoxy-2(R)-[3-(2-phenoxyethyl)succinyl]-L-ß-cyclohexyl alanine-N- (2-phenylethyl)amide; 4-Hydroxy-2(R)-[3-(2-phenoxyethyl)succinyl]-L-ß-cyclohexyla lanine-N- <BR> <BR> (2-phenylethyl)amide; <BR> <BR> <BR> <BR> <BR> <BR> 4-(N-Hydroxyamino-2(R)-[3-(2-phenoxyethyl)succinyl] -L-ß- <BR> <BR> <BR> <BR> <BR> <BR> cyclohexylalanine-N- (2-phenylethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> {4-Hydroxy-2 (R) - [3- (4-pyridinium) propyl] succinyl} -L-p- <BR> <BR> <BR> <BR> <BR> <BR> cyclohexylalanine-N- (2-phenylethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> {4-(N-Hydroxyamino)-2(R)-[3-(4-pyridinium)propyl]succinyl} -L-ß- <BR> <BR> <BR> <BR> <BR> <BR> cyclohexylalanine-N- (2-phenylethyl) amide ;

{4-(N-Hydroxyamino)-2(R)-[3-(N-methyl-4-pyridinium)propyl]su ccinyl}- L-ß-cyclohexylalanine-N-(2-phenylethyl)amide; {4-Hydroxy-2-(R)-[3-(4-methylphenyl)propyl]succinyl}-L-ß- cyclohexylalanine-N-[(2-morpholine-sulphonylamino)ethyl]amid e; {4-(N-Hydroxyamino)-2-(R)-[3-(4-methylphenyl)propyl]succinyl }-L-ß- cyclohexylalanine-N-[(2-morpholinesulphonylamino)ethyl]amide ; {4-(N-Hydroxyamino)-2-(R)-[3-(4-chlorophenyl)propyl]succinyl }-L-ß- cyclohexylalanine-N-[(2-morpholinesulphonylamino)ethyl]amide ; {4-N-Hydroxyamino)-2-(R)-[3-(4-methylphenyl)propyl]succinyl} -L-ß- <BR> <BR> <BR> <BR> cyclohexylalanine-N-[(2-dimethylsulphonylamino)propyl]amide; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R) - [3- (4-chlorophenyl) propyl] succinyl] -L- [S- <BR> <BR> <BR> <BR> <BR> <BR> (methyl) penicillamine] -N-methylamide ; [4-(N-Hydroxyamino)-2(R)-[3-(4-chlorophenyl)propyl]succinyl] -L-[S- (methyl)penicillamine]amide; [4-(N-Hydroxyamino)-2(R)-[3-(4-chlorophenyl)propyl]succinyl] -L- penicillamine]amide; {4- (N-Hydroxyamino) -2 (R) - [3- (4-chlorophenyl) propyl] succinyl} -L- [S- (methyl) penicillaminesulphone] -N-methylamide ; {4-(N-Hydroxyamino)-2(R)-[3-(4-chlorophenyl)propyl]succinyl} -L-[S- <BR> <BR> <BR> <BR> (methyl)penicillaminesulphoxide]-N-methylamide; <BR> <BR> <BR> <BR> <BR> {4- (N-Hydroxyamino) -2 (R) - [3- (4-chlorophenyl) propyl] succinyl} -L-<BR> <BR> <BR> <BR> <BR> <BR> penicillamine-N-methylamide ; [4-(N-Hydroxyamino)-2(R)-3-(2-methylpropyl)succinyl]-L-[S- methyl)penicillamine]-N-methylamide; N4-Hydroxy-N¹-(1-(S)-carbamoyl-2,2-dimethylpropyl)-2-(R)-4- <BR> <BR> <BR> <BR> (chlorophenylpropyl)succinamide; <BR> <BR> <BR> <BR> <BR> <BR> N4-Hydroxy-N 1- (1- (S) -carbamoyl-2, 2-dimethylpropyl) -2- (R) - (4- <BR> <BR> <BR> <BR> <BR> <BR> <BR> methylphenylpropyl) succinamide ; N4-Hydroxy-N 1- (1- (S) -carbamoyl-2, 2-dimethylpropyl) -2- (R) - (4- <BR> <BR> methoxyphenylpropyl) succinamide ; <BR> <BR> <BR> <BR> <BR> <BR> N4-Hydroxy-N 1- (1- (S) -carbamoyl-2, 2-dimethylpropyl) -2- (R) - (4- <BR> <BR> <BR> <BR> <BR> <BR> trifluoromethylphenylpropyl) succinamide ;

N4-Hydroxy-N 1- (1- (S) -carbamoyl-2, 2-dimethylpropyl) -2- (R) - (4- <BR> <BR> <BR> chloromethylphenylpropyl) succinamide ; N-[N-(Mercaptoacetyl)-L-leucyl]-L-phenylalanine methylamide; N- (Acetomercaptoacyl) -L-leucyl] -L-phenylalanine methylamide ; (RS)-2-(Acetylthio)pentanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)propanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)-3-methylbutanoyl-L-leucyl-L-phenylalanin e N-methylamide; (RS)-2-(Acetylthio)-2-phenylacetyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-(Acetylthio)-3-phenylpropanoyl-L-leucyl-L-phenylalani ne N-methylamide; (RS)-2-(Acetylthio)-4-phenylbutanoyl-L-leucyl-L-phenylalanin e N-methylamide; <BR> <BR> <BR> N- (Acetylmercaptoacyl) -L-threonyl-L-phenylalanine methylamide ; <BR> <BR> <BR> N- (Acetylmercaptoacyl) -L-leucyl-L-tryptophan methylamide ; (RS)-2-Mercaptopentanoyl-L-leucyl-L-phenylalanine N-methylamide; (RS)-2-Mercaptopropanoyl-L-leucyl-L-phenylalanine N-methylamide; <BR> <BR> <BR> (RS) -2-Mercapto-3-methylbutanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-2-phenylacetyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-3-phenylpropanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> (RS) -2-Mercapto-4-phenylbutanoyl-L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; N-[N-(Mercaptoacetyl)-L-threonyl]-L-phenylalanine methylamide; N-[N-(Mercaptoacetyl)-L-leucyl]-L-tryptophan methylamide; <BR> <BR> <BR> N [2, 3-bis-Acetylmercaptopropanoyl] -L-leucyl-L-phenylalanine <BR> <BR> <BR> N-methylamide ; N-[2-Acetylmercapto-3-methoxycarbonylpropanoyl]-L-leucyl-L- phenylalanine N-methylamide;

N-[2-Acetylmercapto-4-methoxycarbonylbutanoyl]-L-leucyl-L- phenylalanine N-methylamide; N-[2-Acetylmercapto-5-methoxycarbonylpentanoyl]-L-leucyl-L- phenylalanine N-methylamide; N-[2-Acetylmercapto-6-methoxycarbonylhexanoyl]-L-leucyl-L- phenylalanine N-methylamide; N-[2-Acetylmercapto-4-phthalimidobutanoyl)-L-leucyl-L-phenyl alanine N-methylamide; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-L-pheny lalanine <BR> <BR> <BR> <BR> N-methylamide; <BR> <BR> <BR> <BR> <BR> N [2-Acetylmercapto-6-phthalimidohexanoyl] -L-leucyl-L-phenylalanine <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide; N-[2,3-bis-Mercaptopropanoyl]-L-leucyl-L-phenylalanine N-methylamide; N-[2-Mercapto-3-methoxycarbonylpropanoyl]-L-leucyl-L-phenyla lanine N-methylamide; N [2-Mercapto-4-methoxycarbonylbutanoyl] -L-leucyl-L-phenylalanine N-methylamide; N-[2-Mercapto-5-methoxycarbonylpentanoyl]-L-leucyl-L-phenyla lanine N-methylamide; N [2-Mercapto-6-methoxycarbonylhexanoyl] -L-leucyl-L-phenylalanine N-methylamide; N-[2-Mercapto-4-phthalimidobutanoyl]-L-leucyl-L-phenylalanin e <BR> <BR> <BR> <BR> N-methylamide; <BR> <BR> <BR> <BR> <BR> N [2-Mercapto-5-phthalimidopentanoyl] -L-leucyl-L-phenylalanine <BR> <BR> <BR> <BR> <BR> <BR> N-methylamide; N [2-Mercapto-6-phthalimidohexanoyl] -L-leucyl-L-phenylalanine N methylamide ; N-[2-Acetylmercapto-5-methoxycarbonylpentanoyl]-L-leucyl-L- phenylalanine N-methylamide; N [2-Acetylmercapto-6-methoxycarbonylhexanoyl] -L-leucyl-L- phenylalanine N-methylamide; N-[2-Acetylmercapto-6-methoxycarbonylhexanoyl] -L-valinyl-L- phenylalanine N-methylamide ;

N [2-Acetylmercapto-6-methoxycarbonylhexanoyl] -L-leucyl-L-tryptophan N-methylamide; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-L-pheny lalanine N-methylamide; N [2-Acetylmercapto-5-phthalimidopentanoyl] -L-valinyl-L-phenylalanine <BR> <BR> <BR> N-methylamide; <BR> <BR> <BR> N [2-Acetylmercapto-5-phthalimidopentanoyl] -L-leucyl-L-tryptophan <BR> <BR> <BR> N-methylamide; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-L-[ß- (4-thiazolyl)]alanine N-methylamide; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-L-[ß- (2-pyridyl)alanine N-methylamide; N-[2-Acetylmercapto-5-phthalimidopentanoyl]-L-leucyl-5-methy l-L- glutamic acid N-methylamide; N-[2-Acetylmercapto-6-phthalimidohexanoyl]-L-leucyl-L-phenyl alanine N-methylamide; N-[2-Acetylmercapto-2-(3-phthalimido)phenylacetyl]-L-leucyl- L- phenylalanine N-methylamide; N-[2-Mercapto-5-methoxycarbonylpentanoyl]-L-leucyl-L-phenyla lanine N-methylamide; N-[2-Mercapto-6-methoxycarbonylhexanoyl]-L-leucyl-L-phenylal anine N-methylamide; N-[2-Mercapto-6-methoxycarbonylhexanoyl]-L-leucyl-L-tryptoph an N-methylamide; N-[2-Mercapto-5-phthalimidopentanoyl)-L-leucyl-L-phenylalani ne N-methylamide; N-[2-Mercapto-5-phthalimidopentanoyl]-L-leucyl-L-tryptophan N-methylamide; N-[2-Mercapto-5-phthalimidopentanoyl]-L-leucyl-L-[(ß- (4-thiazolyl)alanine N-methylamide; N-[2-Mercapto-5-phthalimidopentanoyl]-L-leucyl-L-[ß-(2-pyri dyl)]alanine N-methylamide;

N-[2-Mercapto-5-phthalimidopentanoyl]-L-leucyl-5-methyl-L-gl utamic acid N-methylamide; N-[2-Mercapto-6-phthalimidohexanoyl]-L-leucyl-L-phenylalanin e N-methylamide; <BR> <BR> <BR> <BR> N-Hydroxy-2 (R) - [ [4-methoxybenzenesulfonyl] - (3-picolyl) aminoJ- <BR> <BR> <BR> <BR> <BR> <BR> 3-methylbutanamide ; N-Hydroxy-2(R)-[[4-methoxybenzenesulfonyl]-3-picolyl)amino]- <BR> <BR> <BR> <BR> 2-cyclohexylacetamide; <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2 (R) - [ [4-methoxybenzenesulfonyl] - (benzyl) amino] - <BR> <BR> <BR> <BR> <BR> <BR> 4-methylpentanamide ; N-Hydroxy-2(R)-[[4-methoxybenzenesulfonyl]-(benzyl)amino]-6- [(N,N- dimethylglycyl)amino]hexanamide hydrochloride; <BR> <BR> <BR> <BR> N-Hydroxy-2(R)-[[4-methoxybenzenesulfonyl] -(3 -picolyl)amino]- <BR> <BR> <BR> <BR> <BR> <BR> 3-methylbutanamide ; <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2(R)-[[4-methoxybenzenesulfonyl]-(4-picolyl)amino] - <BR> <BR> <BR> <BR> <BR> <BR> 2-cyclohexylacetamide ; N-Hydroxy-2(R)-[(4-methoxybenzenesulfonyl]-(4-picolyl)amino] - <BR> <BR> <BR> <BR> 2-(2-tetrahydrofuranyl)acetamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2 (R) - [ [4-methoxybenzenesulfonyl] - (3-picolyl) amino] - <BR> <BR> <BR> <BR> <BR> <BR> 3 -methylbutanamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S-methylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-isobutyl-3S-benzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3S-methoxyphenylsuccinyl]-NÂ ²-(S)- piperazic acid N-methyl amide; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methoxybenzylsuccinyl] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-thiophenylsuccinyl]-N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-isobutyl-3S-methyl-thiobenzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ;

[4- (N-Hydroxyamino) -2R-isobutyl-3S- (methylthio-2-thienyl) succinyl] - N2- (S) -piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylacetate] -N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-isopropanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-thioacetate] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-thioisopropanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-(2-pyridyl)] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-(3-pyridyl)]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-(4-pyridyl)] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3S-methyl thio-tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylsuccinyl] -N2-(S)-piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-hexyl-3 S-benzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-hexyl-3S-methoxyphenylsuccinyl] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methoxybenzylsuccinyl]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylthiophenylsuccinyl]-N2-(S)- piperazic acid N-methyl amide ;

[4- (N-Hydroxyamino) -2R-hexyl-3S-methylthiobenzylsuccinyl] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-(methylthio-2-thienyl)succinyl]-N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-hexyl-3 S-benzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-hexyl-3 S-methyl acetate] -N2- (S) -piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylisopropanoate] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3S-methyl tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylthioacetate]-N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylthioisopropanoate] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methylthio-tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methyl-(2-pyridyl)]-N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methyl-(3-pyridyl)]-N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-hexyl-3 S-methyl-(4-pyridyl)]-N2,(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-ethylphenyl-3S-methylsuccinyl] N2-(S)- piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-benzylsuccinyl] -N2- (S) - piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3 S-methoxyphenylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ;

[4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methoxybenzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methylthiophenylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methylthiobenzylsuccinyl] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S- (methylthio-2-thienyl) - succinyl] -N2- (S) -piperazic acid N-methyl amide; [4-(N-Hydroxyamino)-2R-ethylphenyl-3 S -benzylsuccinyl] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-ethylphenyl-3S-methyl acetate]-N2-(S)- piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methylisopropanoate] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-ethylphenyl-3 S-methyl-tert-butanoate] -N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-ethylphenyl-3 S-methylthioacetate] -N2-(S)- piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methylthioisopropanoate] -N2- (S) -piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-ethylphenyl-3S-methylthio-tert-butanoate] -N2- (S) -piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3S-methylsuccinyl]-N2-(S)-piper azic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-octyl-3S-methylthiophenylsuccinyl] -N2- (S) - piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-octyl-3S-methylthiobenzylsuccinyl] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S-methylthio-2-thienyl)succinyl]-N 1 (S) -piperazic acid N-methyl amide ;

[4-(N-Hydroxyamino)-2R-octyl-3S-methyl acetate]-N2-(S)-piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-octyl-3S-methylisopropanoate] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3S-methyl tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S-methylthioacetate] -N2-(S)-piperazic acid N-methyl amide ; [4- (N-Hydroxyamino) -2R-octyl-3S-methylthioisopropanoate] -N2- (S) - piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S-methylthio-tert-butanoate]-N2-(S)- piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S -methyl-(2-pyridyl)] -N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S-methyl-(3 -pyridyl)] -N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-octyl-3 S-methyl-(4-pyridyl)]-N2-(S)-piperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-N2-(S)-4'(S/R)- benzylpiperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-N2-(S)-5'(S/R)- benzylpiperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl] -N2-(S)-6'(S/R)- benzylpiperazic acid N-methyl amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-N2-S)- [5', 6'jbenzopiperazic acid N-methyl amide ; N-[1 (R)-Carboxy-ethyl] -a-(S)-isobutylglycine-(S)-N2-piperazic acid methyl amide ; N-[l(R)-Carboxy-ethyl]-oc-(S)-hexylglycine-(S)-N2-piperazic acid methyl amide ;

N-[1(R)-Carboxy-ethyl]-α-(S)-heptylglycine-(S)-N²-piperazi c acid methyl amide; N- [1 (R) -Carboxy-ethyl] -oc- (S) -octylglycine- (S) -N2-piperazic acid methyl amide ; N- [l (R) -Carboxy-ethyl] -a- (S) -ethylphenylglycine- (S) -N2-piperazicacid methyl amide ; N-[1(R)-Carboxy-ethyl]-α-(S)-propylphenylclycine-(S)-N²-pi perazic acid methyl amide; N-[1(R)-Carboxy-ethylthiobenzyl]-α-(S)-isobutylglycine-(S)- N²-piperazic acid methyl amide; N-[1(R)-Carboxy-ethylthiobenzyl]-α-(S)-hexylglycine-(S)-N² -piperazic acid methyl amide; N-[1(R)-Carboxy-ethylthiobenzyl]-α-(S)-ethylphenylglycine-( S)-N²- piperazic acid methyl amide; N-[1(R)-Carboxy-ethylthiobenzyl]-α-(S)-propylphenylglycine- (S)-N²- piperazic acid methyl amide; N-[1(R)-Carboxy-ethyloxybenzyl]-α-(S)-isobutylglycine-(S)-N ²-piperazic acid methyl amide; N- [I (R) -Carboxy-ethyloxybenzyl] -u- (S) -hexylglYcine- (S) -N2-piperazic acid methyl amide ; N-[1(R)-Carboxy-ethyloxybenzyl]-α-(S)-ethylphenylglycine-(S )-N²- piperazic acid methyl amide; N-[1(R)-Carboxy-ethyloxybenzyl]-α-(S)-propylphenylglycine-( S)-N²- piperazic acid methyl amide; N- [1 (R)-Carboxy-4-(p-toluenesulfonyl)butyl] -(x-(S)-phenethylglycyl-(S)- N2-piperazic acid methyl amide ; N-[1(R)-Carboxyethyl]-α-[2-(4-phenylphenoxy)ethyl]-glycyl-( S)-N²- piperazic acid methyl amide; 2-[2(R)-[2-[1,1'-Biphenyl)yl]ethyl]-4-butyl-4(S)-carboxy-1-o xobutyl]- 3(S)-methylaminocarbonyl-hexahydropyridazine;

2- [2 (R) - [2- [ 1, 1'-Biphenyl) yl] ethyl] -4-methyl-4 (S) -carboxy-1-oxobutyl] - 3 (S) -methylaminocarbonyl-hexahydropyridazine ; 2- [2 (R) - [2- [ 1, 1'-Biphenyl) yl] propyl] -4-butyl-4 (S) -carboxy-1-oxobutyl] - 3 (S) -methylaminocarbonyl-hexahydropyridazine ; <BR> <BR> <BR> 2-[2(R)-[2-(4-Propylphenyl)ethyl]-4-butyl-4(S)-carboxy- 1 -oxobutyl]-3(S)- <BR> <BR> <BR> methylaminocarbonyl-hexahydropyridazine ; 2-[2(R)-[2-(4-Butylphenyl)ethyl]-4-butyl-4(S)-carboxy-1-oxob utyl]-3(S)- methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-(4-t-Butylphenyl)ethyl)-4-butyl-4(S)-carboxy-1-ox obutyl]- 3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[4-(4-Fluorophenyl)phenyl]ethyl]-4-butyl-4(S)-car boxy- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[4-(4-Fluorophenyl)phenyl]ethyl]-4-methyl-4(S)-ca rboxy- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-n-Octyl-4-methyl-4(S)-carboxy-1 oxobutyl]-3(S)- <BR> <BR> <BR> methylaminocarbonyl-hexahydropyridazine; <BR> <BR> <BR> 2-[2(R)-[2-[(4-Thiazolyl)phenyl]ethyl]-4-butyl-4(S)-carboxy- 1 -oxobutyl]- 3 (S) -methylaminocarbonyl-hexahydropyridazine ; 2-[2(R)-[2-[(4-Thiazolyl)phenyl]ethyl]-4-methyl-4(S)-carboxy - 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; <BR> <BR> <BR> 2- [2 (R) - [2- [ (4-Thiazolyl) phenyl] ethyl] -4- [3- (phenylsulfonyl) propyl-4 (S) - <BR> <BR> <BR> carboxy-1-oxobutyl] -3 ( S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[(4-Thiazolyl)phenyl]ethyl]-4-(3-phenylpropyl)-4( S)-carboxy- <BR> <BR> <BR> 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; <BR> <BR> <BR> 2-[2(R)-[2-[(4-Oxazolyl)phenyl]ethyl]-4-butyl-4(S)-carboxy-1 -oxobutyl]- 3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[(4-Oxazolyl)phenyl]ethyl]-4-methyl-4(S)-carboxy- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; 2- [2 (R) - [2- [ (4-Oxazolyl) phenyl] ethyl] -4- [3- (phenylsulfonyl) propyl-4 (S) - carboxy-1-oxobutyl] -3 (S) -methylaminocarbonyl-hexahydropyridazine ; 2-[2(R)-[2-[(4-Oxazolyl)phenyl]ethyl]-4-(3-phenylpropyl)-4(S )-carboxy- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine;

2-[2(R)-[2-[4-(Dimethylamino)methylphenyl]ethyl]-4-butyl-4(S )-carboxy- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[4-(Dimethylamino)methylphenyl]ethyl]-4-methyl-4( S)- carboxy-1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyrida zine; 2-[2(R)-[2-[4-(Dimethylamino)methylphenyl]ethyl]-4-[3- (phenylsulfonyl)propyl-4(S)-carboxy-1-oxobutyl]-3(S)-methyla minocarbonyl- hexahydropyridazine; 2-[2(R)-[2-[4-(Dimethylamino)methylphenyl]ethyl]-4-(3-phenyl propyl)- 4(S)-carboxy-1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydrop yridazine; 2-[2(R)-[2-[(4-Imidazolyl)phenyl]ethyl]-4-butyl-4(S)-carboxy - 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; 2-[2(R)-[2-[(4-Imidazolyl)phenyl]ethyl]-4-methyl-4(S)-carbox y- 1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyridazine; <BR> <BR> <BR> <BR> <BR> 2- [2 (R) - [2- [ (4-Imidazolyl) phenyl] ethyl] -4- [3- (phenylsulfonyl) propyl-4 (S) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> carboxy-1-oxobutyl] -3 (S) -methylaminocarbonyl-hexahydropyridazine ; 2-[2(R)-[2-[(4-Imidazolyl)phenyl]ethyl]-4-[3-(phenylpropyl)- 4(S)- carboxy-1-oxobutyl]-3(S)-methylaminocarbonyl-hexahydropyrida zine; <BR> <BR> <BR> <BR> <BR> HS (CH2) 2- (S-D-Leu) -Phe-NHMe ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> HS(S)CHMeCH2-(S -D-Leu)-Phe-NHMe; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> HS(S)CH(PhtNBu)CH2-(S-D-Leu)-Phe-NHMe; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> HS(S)CH(PhtNEt)CH2-(S-D-Leu)-Phe-NHMe; HS(1,2-Cyclopentyl)(S-D-Leu)-Phe-NHMe <BR> <BR> <BR> <BR> <BR> Me-S (NH) 2- (CH2-DL-Leu) -Trp-NHBn ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> n-Bu-S (NH) 2- (CH2-DL-Leu) -Trp-NHBn ; n-Bu-S(NH)2-(CH2-DL-TyrOCH3)-Trp-NHBn; <BR> <BR> Me-RS-SO (NH) - (CH2-L-Leu) -Phe-Ala-NH2 ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> n-Bu-RS-SO (NH) - (CH2-L-Leu) -Phe-Ala-NH2 ; HO-NH-CO-CH2-CH- (CH2-CH (CH3) 2-CO-Nal-Pro-NH2 ;

HO-NH-CO-CH(CH3-CH(CH2)-CH(CH3)2)-CO-Nal-Ala-NH2; wherein Pal is 3-pyridylalanine ; HO-NH-CO-CH2-CH(CH2CH(CH3)2)-CONal-(CH2NH)-Ala-NH2;

4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(2-morpholin-4-ylethyl)amino]carbonyl]butyl]amino]-b utanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[methylamino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (lH-imidazol-2-ylmethyl) amino] carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (lH-tetrazol-5-ylmethyl) amino] carbonyl] butyl] amino] -butanoicacid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[[2-(phenyl)ethyl]amino]carbonyl]butyl]amino]-butanoi c acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(pyridin-3-ylmethyl)amino]carbonyl]butyl]amino]-buta noic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(2-methyl-2H-tetrazo-5-ylmethyl)amino]carbonyl]butyl ]amino]-butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (4-hydroxy-2-methyl-pyrimidm-5-ylmethyl) amino] carbonyl] butyl] - amino] -butanoic acid ; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[[2-(2-pyridin-3-yl)ethyl]amino]carbonyl]butyl]amino] -butanoic acid; <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [l- (lH-tetrazol-5-yl) ethyl] amino] carbonyl] butyl] amino] -butanoic acid ;

4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(5-amino-4H-[1,2,4]-triazol-3-ylmethyl)amino]carbony l]butyl]amino]- butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[[1 -(6-oxo- 1,6-dihydro-pyridazin-3-yl)ethyl]amino]carbonyl]butyl]- <BR> <BR> <BR> <BR> <BR> <BR> <BR> amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (I, 3-Dihydro-1, 3-dioxo-2H-benz [f] isoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[[(phenyl)amino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(benzyl)amino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(pyridin-4-ylmethyl)amino]carbonyl]butyl]amino]-buta noic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ [2- (lH-imidazol-4-yl) ethyl] ammo] carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[[(pyridin-2-ylmethyl)amino]carbonyl]butyl]amino]-buta noic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(4-sulfamoyl-phenyl)amino]carbonyl]butyl]amino]-buta noic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- (l, 3-Dihydro-l, 3-dioxo-2H-benz [f] isoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (3-sulfamoyl-phenyl) amino] carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (l, 3-Dihydro-l, 3-dioxo-2H-benz [f|isoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[[(4-dimethylamino-benzyl)amino]carbonyl]butyl]amino]- butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz [f]isoindol-2-yl)-2-(R)-[[3-methyl- 1-(S)-[[[1-(S)-phenyl-ethyl]amino]carbonyl]butyl]amino]-buta noic acid; <BR> <BR> <BR> <BR> 4- (l, 3-Dihydro-l, 3-dioxo-2H-benz [f|isomdol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(1,1 -dioxo-tetrahydro-thiophen-3 -yl)amino]carbonyl]butyl]amino]- butanoic acid ; 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[[(4-sulfamoyl-benzyl)amino]carbonyl]butyl]amino]-buta noic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[[1-(R)-phenyl-ethyl]amino]carbonyl]butyl]amino]-buta noic acid; <BR> <BR> 4-(1,3 -Dihydro- 1,3-dioxo-2H-benz[fgisoindol-2-yl)-2-(R)-[[3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(3-fluorobenzyl)amino]carbonyl]butyl]amino]-butanoic acid;

4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [f] isoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> l-(S)-[[(furan-2-ylmethyl)amino]carbonyl]butyl]amino]-butano ic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(1 -methyl- 1 H-tetrazol-5-ylmethyl)amino]carbonyl]butyl]amino]-butanoic <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> 4- (l, 3-Dihydro-l, 3-dioxo-2H-benz [f|isoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(1,2,3,4-tetrahydro-naphthalen- 1 -yl)amino]carbonyl]butyl]amino]- butanoic acid ; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(2,4-difluoro-benzyl)amino]carbonyl]butyl]amino]-but anoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [f] isoindol-2-yl) -2- (R) - [ [3 -methyl- <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(3-nitrobenzyl)amino]carbonyl]butyl]amino]-butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- <BR> <BR> <BR> <BR> 1-(S)-[[(4-nitrobenzyl)amino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(4-methanesulfonylamino-benzyl)amino]carbonyl]butyl]a mino]-butanoic <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(3-methanesulfonylamino-benzyl)amino]carbonyl]butyl] amino]-butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)- [[3-methyl- 1-(S)-[[(3,4-difluoro-benzyl)amino]carbonyl]butyl]amino]-but anoic acid; 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[[(3-trifluoromethyl-benzyl)amino]carbonyl]butyl]amino ]-butanoic acid; <BR> <BR> <BR> <BR> 4- [2-(S)- [1 -(R)-Carboxy-3 -(1,3 -dioxo- 1,3 -dihydro-benzo [f] isoindol-2-yl)- <BR> <BR> <BR> <BR> <BR> propylamino] -4-methyl-pentanoylamino-methyl) -benzoic acid ; 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[f] isoindol-2 -yl)-2-(R)-[[3 -methyl- <BR> <BR> <BR> <BR> 1 -(S)-[[(2-hydroxy- 1,1 -bis-hydroxymethyl-ethyl)amino]carbonyl]butyl]amino]- butanoic acid ; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(3,5-difluoro-benzyl)amino]carbonyl]butyl]amino]-but anoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[benzylmethyl-amino]carbonyl]butyl]amino]-butanoic acid;

4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(2-dimethylaminoethyl)-methyl-amino]carbonyl]butyl]am ino]-butanoic <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (l-azabicyclo [2. 2. 2] -oct-3 (R) -amino] carbonyl] butyl] amino] -butanoicacid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-(1,3-Dihydro-1,3-dioxo-2H-benz [f]isoindol-2-yl)-2-(R)-[[3-methyl- 1-(S)-[[(1-azabicyclo[2.2.2]oct-3-(S)-yl)amino]carbonyl]buty l]amino]-butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (3- (R) -4- (S) -5- (R) -6-tetrahydrox-tetrahydra-pyran-2- (R) -ylmethyl) amino] -<BR> <BR> <BR> <BR> <BR> <BR> carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(N,N'-dimethyl-hydrazino)carbonyl]butyl]amino]-butan oic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[flisoindol-2-yl)-2-(R)-[[3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(methylmethoxy)amino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(dimethyl)amino]carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(2-oxo-tetrahydro-thiophen-3 -(R)-yl)amino] carbonyl]butyl]amino]- butanoic acid ; 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[fl isoindol-2-yl)-2-(R)- [ [3 -methyl- 1 - (S) - [ [ (2-oxo-tetrahydro-thiophen-3 - (S) -yl) amino] carbonyl] butyl] amino] - butanoic acid ; <BR> <BR> 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[0 isoindol-2-yl)-2-(R)-[[3 -methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(3 -(R)-acetylamino-4-(S)-5-(S)-dihydroxy-6-(R)-hydroxymethyl- <BR> <BR> <BR> <BR> <BR> <BR> tetrahydro-pyran-2-yl) amino] carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[[benzyl(2-hydroxyethyl)amino]carbonyl]butyl]amino]-b utanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[p isoindol-2-yl)-2-(R)-[[3 -methyl - <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[3,4-dihydro- 1 H-isoquinoline-2-carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> I - (S) - [4-methylpiperazine- I -carbonyl] butyl] amino] -butanoic acid ;

4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[1-oxo-[1,4]thiazinane-4-carbonyl]butyl]amino]-butanoi c acid; 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[morpholine-4-carbonyl]butyl]amino]-butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[4-(2-3-dihydroxy-propyl)-piperazine- 1 -carbonyl]butyl]amino]-butanoic <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[3,4,5,6-tetrahydro-H-[2,3]bipyridinyl-1)carbonyl)buty l]amino]-butanoic acid; <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(1 -methyl-8-oxo- 1,7-diazacyclotridec-9-yl)amino]carbonyl]butyl]amino]- butanoic acid ; <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[methyl- 1 -methyl-piperidin-4-yl)amino]carbonyl]butyl]amino]-butanoic <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[(4-hydroxy- 1,1 -dioxo-tetrahydro-thiophen-3 -yl)amino]carbonyl]butyl]- amino] -butanoic acid ; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-(4-ethoxycarbonylmethyl-piperazine-1-carbonyl)butyl]am ino]-butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[[(1,1-dioxo-tetrahydro-thiophen-3-yl)-methyl-amino]ca rbonyl]butyl]- amino]-butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[2-(R)-(pyridin-3-yl)-pyrrolidinecarbonyl]butyl]amino] -butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[2-(S)-(pyridin-3-yl)-pyrrolidinecarbonyl]butyl]amino] -butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)-2-(R)-[[3- methyl- 1-(S)-[3-oxo-2-(R)-phenyl-piperazine-1-carbonyl]butyl]amino] -butanoic acid; 4-(1,3-Dihydro-1,3-dioxo-2H-benz [f]isoindol-2-yl)-2-(R)-[[3-methyl- 1-(S)-[3-oxo-2-(S)-phenyl-piperazine-1-carbonyl]butyl]amino] -butanoic acid;

4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- l-(S)-[(pyridine-3-carbonyl-hydrazino)carbonyl]butyl]amino]- butanoic acid; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> l-(S)-[[(benzenesulfonyl)amino]carbonyl]butyl]amino]-butanoi c acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> I - (S) - [ (3 -aminobenzyl) amino] carbonyl] butyl] amino] -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> I - (S) - [ [4- (trifluoro-methanesulfonylamino) benzyl] amino] carbonyl] butyl] amino] - butanoic acid ; <BR> <BR> <BR> <BR> 4- (l, 3-Dihydro-l, 3-dioxo-2H-benz [f) isoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[[2-hydroxy-(R)-bicyclo[4.3.0]nona-3,6(1)-diene]amino] carbonyl]butyl]- amino] -butanoic acid ; <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro-1, 3-dioxo-2H-benz [f] isoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[[[2-hydroxy-(S)-bicyclo[4.3.0]nona-3,6(1)-diene]amino] carbonyl]butyl]- amino] -butanoic acid ; <BR> <BR> <BR> <BR> 4-(1,3 -Dihydro- 1,3 -dioxo-2H-benz[fl isoindol-2-yl)-2-(R)- [ [3 -methyl - <BR> <BR> <BR> <BR> <BR> <BR> l- (S) - [ [ (N-methyl-pyrrolidine) -methyl-amino] carbonyl] butyl] amino] -butanoic<BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (1, 3-Dihydro- 1, 3-dioxo-2H-benz [flisoindol-2-yl) -2- (R) - [ [3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> 1 -(S)-[(N-ethoxycarbonylmethyl-piperazine)- 1 -carbonyl]butyl]amino]-butanoic acid ; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- bromo- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- propoxy- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- nitro- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- amino- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- methyl- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- methoxy- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid;

2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- phenyl- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; <BR> <BR> <BR> <BR> 2-(R)-[1 -(S)-(Benzylamino)carbonyl-3 -methylbutylamino]-4-(1,3 -dioxo- <BR> <BR> <BR> <BR> <BR> <BR> 1, 3-dihydro-isoindol-2-yl) -butanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- methanesulfonylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-bu tanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- benzenesulfonylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-bu tanoic acid; 2-(R)-[1-(S)-(Benzylamino)carbonyl-3-methylbutylamino]-4-(5- hydroxy- 1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butanoic acid; 2-(R)-[[3-Methyl- 1 -(S)-[[(pyridin-3-ylmethyl)amino]carbonyl]- butyl] amino] -4- (1, 3, 5, 7-tetraoxo-3, 5, 6-tetrahydro- I H-pyrolo [3, 4-fl isoindol- 2-yl) butanoic acid ; <BR> <BR> <BR> <BR> EtONHCONMe-CH2CH (iBu) -CO-L-Trp-NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> EtCONOH-CH2CH (iBu) -CO-L-Trp-NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> n-PrCONOEt-CH2CH (iBu) -CO-L-Trp-NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> EtNHCONOMe-CH2CH (iBu) -CO-L-Trp-NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> MeNHCONOH-CH2CH (iBu) -CO-L-Trp-NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> EtONHCONMe-CH2CH (iBu) -CO-L-Ala (2-naphthyl) -NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> EtCONOH-CH2CH (iBu) -CO-L-Ala (2-naphthyl) -NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> n-PrCONOEt-CH2CH (iBu) -CO-L-Ala (2-naphthyl) -NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> EtNHCONOMe-CH2CH (iBu) -CO-L-Ala (2-naphthyl) -NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> MeNHCONOH-CH2CH (iBu) -CO-L-Ala (2-naphthyl) -NHEt ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> HONHCONHCH2CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> HONHCONHCH2CH2CH (iBu) -CO-L-TrpNHMe ; HONHCONHCH(iBu)-CO-L-TrpNHMe; <BR> <BR> H2NCON (OH) CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N (OH) CH2CH (iBu) -CO-L-TrpNHMe ;

H2NCON (OH) CH2CH2CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> CH3CON (OH) CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> CH3CON (OH) CH2CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> CH3CON (OH) CH2CH2CH (iBu) -CO-L-TrpNHMe ; <BR> <BR> NHOHCOCH2CH (i-Bu) CO-L-Trp-NHMe ; N-{D,L-2-(Hydroxyaminocarbonyl)methyl-4-methylpentanoyl}-L-3 -(2'- <BR> <BR> <BR> naphthyl)alanyl-L-alanine, 2-(amino)ethyl amide; <BR> <BR> <BR> N- {D, L-2- (Hydroxyaminocarbonyl) methyl-4-methylpentanoyl -L- 3-amino-2-dimethylbutanoyl-L-alanine, 2- (amino) ethyl amide ; 4 (S) - [3-Hydroxyaminocarbonyl-2 (R) - (2-methylpropyl) propanoyl] amino- 1,2,3,4,5-tetrahydro-3H-2-benzazepin-3-one; [4-(N-Hydroxyamino)-(2R)-isobutyl-3-methylsuccinyl]-L-phenyl glycine- N-methylamide; 4(S)-[2(R)-[1(R)-Hydroxycarbamoyl-2-morpholinoethyl]- 4-methylvaleryl]amino-1,2,4,5-tetrahydro-3H-2-benzazepine-3- one; (1R,4S)-4-[(2R)-Hydroxycarbamoylmethyl-4-methylvaleryl]amino -3-oxo- 1,2,4,5-tetrahydro-3H-2-benzazepine-1-carboxylic acid; 3-[2-(N-Methylcarbamoyl)ethylsulfinyl]-5-methylhexanohydroxa mic acid; <BR> <BR> <BR> N- [ (2-Thenoylmercapto-3-methyl) -butanoyl] -homocysteine thiolactone ; <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-is oleucine, N-phenylamide; N- [1 (R) -Carboxy-ethyl] -oc- (S) - (2-phenyl-ethyl) glycine- (L) -alanine, N-phenylamide ;

N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-ph enylalanine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-se rine-O- benzyl ether, N-phenylamide; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -tryptophan, N-phenylamide ; <BR> <BR> <BR> <BR> N- [l (R) -Carboxy-ethyl] - (x- (S) - (2-phenyl-ethyl) glycine-a- (S) - (2-phenyl- <BR> <BR> <BR> <BR> <BR> <BR> ethyl) glycine, N-phenylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -norleucine, N-phenylamide ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -valine, N-phenylamide ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -serine, N-phenylamide hydrochloride ; N- [I (R) -Carboxy-ethyl] - (x- (S) - (2-phenyl-ethyl) glycine- (L) -asparagine, N-phenylamide ; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-th reonine, N-phenylamide hydrochloride; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -lysine, N-phenylamide ; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-gl utamic acid, N-phenylamide; N- [I (R) -Carboxy-ethyl] - (x- (S) - (2-phenyl-ethyl) glycine- (L) -tyrosine, N-phenylamide hydrochloride ; N- [1 (R) -Carboxy-5- ( 1, 3-dioxo-isoindolin-2-yl) pentyl] -oc- (S) - (2-phenyl- ethyl) glycine- (L) -leucine, N-phenylamide ; N- [l (R) -Carboxy-5- (l-oxo-isoindolin-2-yl) pentyl] -a- (S) - (2-phenyl-ethyl) - glycine- (S) -leucine, N-phenylamide hydrochloride ; N-[1(R)-Carboxy-5-(1-oxo-isoindolin-2-yl)pentyl]-α-(S)-(2-p henyl-ethyl)- glycine-(S)-arginine, N-phenylamide;

N- [1 (R) -Carboxy-ethyl] -a- (S) - (2- (3-hydroxyphenyl) -ethyl) glycine- (S) - leucine, N-phenylamide hydrochloride ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2- (4-methylphenyl) -ethyl) glycine- (S) - leucine, N-phenylamide hydrochloride ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2- (2'-thienyl) ethyl) glycine- (L) -leucine, N-phenylamide ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2- (4-ethylphenyl) ethyl) glycine- (L) - leucine, N-phenylamide ; <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-5-(1-oxo-isoindolin-2-yl)pentyl]-α-(S)-(2-( 4- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> propylphenyl)ethyl)glycine-(L)-leucine, N-phenylamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [1 (R)-Carboxy-ethyl] -(x-(S)-(2-(4-chlorophenyl)ethyl)glycine-(L)- leucine, N-phenylamide ; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-α-(S) - (2-cyclohexyl-ethyl)glycine, N-phenylamide; N- [1 (R) -Carboxy-ethyl] -oc- (S) - (2-phenyl-ethyl) glycine-a- (S) - <BR> <BR> <BR> <BR> <BR> (cyclohexyl) glycine, N-phenylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-α-(S) - (cyclohexylmethyl)glycine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-ß - naphthylalanine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-α - naphthylalanine, N-phenylamide; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- [ (L) -glutamic acid, <BR> <BR> <BR> <BR> <BR> a, 8-bis-N-phenylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-cyclohexylamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[(1(R)-Carboxy-ethyl)]-α-(S)-(2-phenyl-ethyl)glycine-α-( S)- (4-hydroxyphenyl-ethyl)glycine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-ph enylglycine, N-phenylamide;

N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-gl utamic acid, N#-benzylamide, Nα-phenylamide; N- [I (R) -Carboxy-ethyl] -oc- (S) - (2-phenyl-ethyl) glycine- (L) -ornithine, N-phenylamide ; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine- (L) -arginine, N-phenylamide ; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-α-(S) - (3-phenylpropyl)glycine, N-phenylamide; N- [1 (R) -Carboxy-ethyl] -a- (S) - (2-phenyl-ethyl) glycine-a- (S) -n- octylglycine, N-phenylamide ; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, N-(4-carboxyphenyl)amide; <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-(4-trifluoromethylphenyl)amide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-(3-pyridyl)amide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[1(R)-Carboxy-ethyl]-α-(S)-(2-phenyl-ethyl)glycine-(L)-le ucine, N-(benzothiazol-2-yl)amide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-(4-n-propylphenyl)ethyl)gly cine-(L)- leucine, N-phenylamide; N-[1(R)-Carboxy-ethyl]-α-(S)-(2-4-propylphenyl)ethyl)glycin e-(L)- arginine, N-phenylamide; N- [l (R) -Carboxy-ethyl] -a- (S) - (2- (3, 4-dimethylphenyl-ethyl) glycine- (L) - leucine, N-phenylamide ; <BR> <BR> <BR> <BR> (2- ( ( (4- ( 1, 3-Dihydro-1, 3-dioxo-2H-isoindol-2-yl) butyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> hydroxyphosphinyl) methyl) -4-phenylbutanoyl) -L-leucine, N-phenylamide ; (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)- hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine, N-phenylamide; (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl- 1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl) -L-leucine, N-phenylamide;

(2- ( (Hydroxy (methyl) phosphinyl) methyl) -4-phenylbutanoyl) -L-leucine, N-phenylamide ; <BR> <BR> <BR> <BR> [ [Hydroxy [l (R) - [N- (N-acetyl-L-prolyl-L-alanyl) -amino] -ethyl] -<BR> <BR> <BR> <BR> <BR> <BR> phosphinyl] -methyl] -4-phenyl-butanoyl-L-leucyl, N-phenylamide ; [Hydroxy-[N-(N-(benzoyl)-L-prolyl)aminobutyl]phosphinyl]meth yl]- 4-phenyl-butanoyl-L-leucine, N-phenylamide; [Hydroxy-[2-Methylpropyloxycarbonyl-aminobutyl]-phosphinyl]m ethyl]- 4-phenylbutanoyl-L-leucine, N-phenylamide; [Hydroxy-[ l -Methylethylarninocarbonyl-aminobutyl]-phosphinyl]methyl]- 4-phenylbutanoyl-L-leucine, N-phenylamide ; N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -leucinamide ; N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -leucine, N-phenylamide ; N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -leucine, N-benzylamide ; N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -leucine, N- (2-phenylethyl) amide ; N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -phenylalaninamide ; <BR> <BR> <BR> <BR> N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -phenylalanine N-phenylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N-(2-Thiomethyl-4-phenylbutanoyl)-(L)-phenylalanine N-benzylamide; <BR> <BR> <BR> <BR> <BR> N- (2-Thiomethyl-4-phenylbutanoyl) - (L) -phenylalanine-b-alanine ; 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)- 1,5-pentanedioic acid 1 -(L-leucine, N-phenylamide) amide ; 2ER)-(2-(4-(1 -n-Propyl)phenyl)ethyl)- 1,5-pentanedioic acid 1 - (2 (S) -t- butyl) glycine, N-phenylamide) amide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-1,5-pentanedioic acid 1-(2(S)-t- <BR> <BR> <BR> <BR> butyl)glycine, N-(4-pyridylamide)amide; <BR> <BR> <BR> <BR> <BR> <BR> 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)- 1,5-pentanedioic acid 1 -(L-arginine, <BR> <BR> <BR> <BR> <BR> N-methylamide) amide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-methyl-1,5-pentanedio ic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-methyl-1,5-pentanedio ic acid 1-(2(S)-t-butyl)glycine, N-phenylamide)amide; 2 (R) - (2- (4- (1 -n-Propyl) phenyl) ethyl) -4-methyl-1, 5-pentanedioic acid 1-(2(S)-(4-thiazolylmethyl)glycine, N-phenylamide)amide;

2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-methyl- 1,5 -pentanedioic acid 1-(2(S)-(3-pyridylmethyl)glycine, N-phenylamide)amide; 2(D-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-methyl- 1,5-pentanedioic acid l-(L-leucine, N-(4-pyridyl)amide)amide; 2ER)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-methyl- 1,5 -pentanedioic acid 1-(2(S)-(2-pyridylmethyl)glycine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-methyl-1,5-pentanedio ic acid 1-(L-arginine, N-phenylamide)amide; 2ER)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-methyl- 1,5-pentanedioic acid 1-(L-phenylalanine, N-4-pyridylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(1-(4-(N-(2-oxoisoind olinyl))- butyl))-l,5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(1-(4-(N-(2-oxoisoind olinyl))-but- 2-enyl))-1,5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; <BR> <BR> <BR> <BR> 2eR)-(2-(4-(4-Fluorophenyl)phenyl)ethyl)-4-methyl-1,5-pentan edioic acid <BR> <BR> <BR> <BR> <BR> <BR> 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(Phenyl)phenyl)ethyl)-4-methyl-1,5-pentanedioic acid 1-(L- leucine, N-phenylamide) amide ; 2 (R) - (2- (4- (4-Methoxyphenyl) phenyl) ethyl) -4-methyl-1, 5-pentanedioic acid 1- (L-leucine, phenylamide) amide ; 2 (R) - (2- (4- (4-Methylphenyl) phenyl) ethyl) -4-methyl-1, 5-pentanedioic acid 1- (L-leucine, phenylamide) amide ; 2 (R) - (2- (4- (4-Hydroxy-n-butyl) -phenyl) -ethyl) -4-methylpentanedioic acid 1-(S-leucine, phenylamide)amide; 2 (R), 4 (S) - (2- (4- (3-Hydroxy-n-propyl) phenyl) ethyl) -4-methyl- 1, 5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-Phenylethyl)-4-methyl-1,5-pentanedioic acid 1- (L-leucine, N-phenylamide) amide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-1,5-pentanedioic acid 1-(L-leucine, N-ethylamide) amide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-1,5-pentanedioic acid 1-(L-leucine, N-isopropylamide) amide ;

2ER)-(2-(4-(1 -n-Propyl)phenyl)propyl)- 1,5-pentanedioic acid 1- (2 (S) -Lert- butyl-glycine, N-4-pyridyl) amide) amide ; 2(R)-(3-(4-(1-n-Propyl)phenyl)propyl)-1,3-pentanedioic acid 1 -(L-leucine, N-phenylamide) amide ; 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-hexyl- 1,5-pentanedioic acid 1 -(L- leucine, N-phenylamide) amide ; 2R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-butyl-1,5-pentanedioic acid 1 -(L- leucine, N-phenylamide) amide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(3-methylbenzyl)-1,5- pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-(2-benzimidazolyl) butyl)- 1, 5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2 (R) - (2- (4- (l-n-Propyl) phenyl) ethyl) -4- (4- (2-benzthiazolyl) butyl) - 1, 5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-(2-benzoxazolyl)bu tyl)- 1, 5-pentanedioic acid 1-(L-leucine, N-phenylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedio ic acid 1- (L-leucine, N-phenylamide) amide 9-piperidineamide ; 2(R)-(2-(4-(1-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedioic acid 1- (L- leucine, N-methylamide) amide 9-phenylamide ; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedio ic acid 1-(L-leucine, N-methylamide)amide 9-tert-butylamide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy- 1,9-nonanedioic acid 1 - (L-leucine, N-methylamide) amide 9-benzylamide ; 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-carboxy- 1,9-nonanedioic acid 1-(L-leucine, N-methylamide)amide 9-morpholineamide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedio ic acid 1-(L-leucine, N-methylamide)amide 9-(1(R)-phenylethyl)amide; 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-carboxy- 1,9-nonanedioic acid 1-(L-leucine, N-methylamide)amide 9-(1(S)-phenylethyl)amide; 2R)-(2-(4-(1 -n-Propyl)phenyl)ethyl)-4-carboxy- 1,9-nonanedioic acid 1-(L-leucine, N-methylamide)amide 9-(N-methyl-N-phenyl)amide;

2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedio ic acid 1-(L-leucine, N-methylamide)amide 9-(N'-methylpiperazine)amide trifluoroacetic acid salt 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedio ic acid 1-(L-leucine, N-methylamide)amide 9-(3-pyridyl)amide; 2(R)-(2-(4-(1-Propyl)phenyl)ethyl)-4-carboxy-1,9-nonanedioic acid 1 -(L- leucine, N-methylamide) amide ; 2(R)-(2-(4-(1-Propyl)phenyl)ethyl)-1,5-pentanedioic acid 1-((R)-(S-p- methoxybenzyl) penicillamine, N-phenylamide) amide ; 2(R)-(2-(4-(1-Propyl)phenyl)ethyl)-1,5-pentanedioic acid 1 -(R)-(S-p- methoxybenzyl) penicillamine sulfone, N-phenylamide) amide ; 2-(2-(4-(1-Propyl)phenyl)ethyl)-4-(1-(4-(2-phthalimido))buty l)- 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-benzoylamino-1-but yl)- 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-pivaloylamino-1-bu tyl)- 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-phenylsulfonylamin o-1-butyl)- 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-(N'-phenylureido)- 1-butyl)- 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2 (R) - (2- (4- (l-n-Propyl) phenyl) ethyl) -4- (4-phenyloxycarbonylamino- 1-butyl) -1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-N'-benzyloxycarbon ylamino-L- prolylamino)-1-butyl)-1,5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2 (R) - (2- (4- ( 1 -n-Propyl) phenyl) ethyl) -4- (4-cyclopentylamino-1 -butyl) - 1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2 (R) - (2- (4- (l -n-Propyl) phenyl) ethyl) -4- (4- (2-carboxybenzoylamino) - 1-butyl) -1, 5-pentandioic acid 1-(L-leucine, N-methylamide)amide; 2(R)-(2-(4-(1-n-Propyl)phenyl)ethyl)-4-(4-cyano-1-butyl)-1,5 -pentandioic acid 1-(L-leucine, N-phenylamide)amide;

N-[1(R)-Carboxyethyl]-α-(S)-(9-amino-n-nonyl)]glycine-(L)-l eucine, N-phenylamide ; N- [1 (R) -Carboxyethyl] -a- (S) - (n-octyl)] glycine- (L) -leucine, N-phenylamide ; N- [1 (R) -Carboxyethyl] -a- (S) - (n-octyl)] glycine- (L) -arginine, N-phenylamide ; N-[1(R)-Carboxyethyl]-α-(S)-(9-amino-n-nonyl)]glycine-(L)-a rginine, N-phenylamide ; N- [1 (R) -Carboxyethyl] -a- (S) - (n-decyl)] glycine- (L) -leucine, N-phenylamide ; 1-(2-(4-Propylphenyl)ethyl)cyclopentane-1,3-dicarboxylic acid 1- (L- leucine, N-phenylamide) amide ; 1-(2-(4-Propylphenyl)ethyl)cyclohexane-1,3-dicarboxylic acid 1-(L- leucine, N-phenylamide) amide ; <BR> <BR> <BR> <BR> N- [1 (R) -Carboxyethyl] -a- (S) -2- (4-fluorobiphenyl) -glycyl- (S) -2- (tert- <BR> <BR> <BR> <BR> <BR> <BR> butyl) glycine, N-phenylamide ; 3S-[4-(N-Hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxy- 3, 4-dihydrocarbostyril ; 3S-[4-(N-Hydroxyamino)-2R-isobutyl-3S-acetylthiomethylsuccin yl]- amino-3, 4-dihydrocarbostyril ; 3S-[4-(N-Hydroxyamino)-2R-isobutyl-3S-methylsuccinyl]amino- 1-methoxy-3,4-dihydrocarbostyril; 3S-[4-(N-Hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxyme thyl- 3, 4-dihydrocarbostyril ; 1-Carboxymethyl-3S-[4-N-hydroxyamino)-2R-isobutyl-3S- methylsuccinyl]amino-3,4-dihydrocarbostyril; <BR> <BR> <BR> <BR> 3 S- [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] amino- <BR> <BR> <BR> <BR> <BR> <BR> 1 -methoxyethoxymethyl -3,4-dihydrocarbostyril; <BR> <BR> <BR> <BR> <BR> <BR> 3 S- [4-(N-Hydroxyamino)-2R-heptylsuccinyl] amino - 1 -methoxy- <BR> <BR> <BR> <BR> <BR> <BR> 3, 4-dihydrocarbostyril ; 7-Chloro-3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl]amino- 1-methoxymethyl-3, 4-dihydrocarbostyril ;

3 S- [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] amino-1 -methoxyethyl- <BR> <BR> <BR> <BR> 3, 4-dihydrocarbostyril ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3 S- [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] amino-1-methoxyethyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 6, 7-methylenedioxy-3, 4-dihydrocarbostyril ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3R- [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] amino-1 -methoxyethyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 6,7-methylenedioxy-3,4-dihydrocarbostyril; 2-(R)-N-Hydroxy-2-[(4-methoxybenzenesulfonyl) (3-morpholin- 4-yl-3-oxopropyl)amino]-3-methyl-butyramide; 2-(R)-2-[(2-Benzylcarbamoylethyl)(4-methoxy-benzenesulfonyl) - amino] -N-hydroxy-3 -methylbutyramide ; 2-(R)-N-Hydroxy-2-((4-methoxybenzenesulfonyl)(2-[(pyridin-3- ylmethyl) carbamoyl] ethyl) amino) -3 -methylbutyramide ; 2-(R)-N-Hydroxy-2-([4-methoxybenzenesulfonyl]-[2-(methylpyri din- 3-ylmethylcarbamoyl)ethyl]amino)-3-methylbutyramide; 4-(3 - [1 -(R)- 1 -Hydroxycarbamoyl-2-methylpropyl)- (4-methoxybenzenesulfonyl)amino]propionyl)piperazine-1-carbo xylic acid, tert-butyl ester ; 2-(R)-N-Hydroxy-2-[(4-methoxybenzenesulfonyl)(3-oxo-3- piperazin-1-ylpropyl)amino)-3-methylbutyramide hydrochloride; 2- (R) -2- [ (Benzylcarbamoylethyl) (4-methoxy-benzenesulfonyl) amino] - N-hydroxy-3 -methylbutyramide; 2-(R)-N-Hydroxy-2-[(4-methoxybenzenesulfonyl][(2-morpholin-4 - <BR> <BR> <BR> <BR> ylethylcarbamoyl) methyl] amino] -3 -methylbutyramide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2- (R) -N-Hydroxy-2- ( (4-methoxybenzenesulfonyl) ( [ (pyridin-3-ylmethyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> carbamoyl] methyl) amino) -3-methylbutyramide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2- (R) -3, 3, 3, -Trifluoro-N-hydroxy-2- [ (methoxy-benzenesulfonyl) (3- morpholin-4-yl-3-oxopropyl)amino]propionamide; 2- (R) -N-Hydroxy-2- ( (4-phenoxybenzenesulfonyl) [2-methylpyridin- 4-ylmethylcarbamoyl)ether]amino)-3-methylbutyramide; 4- [4-Methoxybenzenesulfonyl) (3-morpholin-4-yl-3-oxopropyl) amino] -l- methylpiperidene-4-carboxylic acid hydroxyamide ; 2-(R)-N-Hydroxy-2-((4-methoxybenzenesulfonyl)-[3-(4-methylpi perazin- I-yl) -3- oxopropyl] amino) -3-methylbutyramide ;

2- (R) -2- [ (2-Carboxyethyl) (4-methoxybenzene-sulfonyl) amino) - N-hydroxy-3 -methylbutyramide; [ (2-Carboxyethyl) (3, 4-dimethoxybenzene-sulfonyl) amino] -N-hydroxy- acetamide ; <BR> <BR> <BR> <BR> 2- (R) -2- [ (2-Carbamoylethyl) (4-methoxybenzene-sulfonyl) amino] -N- <BR> <BR> <BR> <BR> <BR> hydroxy-3-methylbutyramide ; 2-(R), 3-(R)-3, N-Dihydroxy-2-[(4-methoxybenzenesulfonyl)(3-oxo-3- piperidin-1-ylpropyl)amino]-butyramide; 2-(R)-N-Hydroxy-2-((4-methoxybenzenesulfonyl)[3-(methylpyrid in- 3-ylmethylcarbamoyl)propyl]amino)-3-methylbutyramide; 2- (R) -N-Hydroxy-2- ( (4-methoxybenzenesulfonyl) [2- (methylcarboxymethylcarbamoyl)ethyl]amino)-3-methyl-butyrami de; 2-(R)-N-Hydroxy-2-((4-methoxybenzenesulfonyl)[(1- methylpiperidin-4-ylcarbamoyl)methyl]amino)-3-methylbutyrami de; 2-(R)-N-Cyclohexyl-N-hydroxy-2-((4-methoxy-benzenesulfonyl)- [3-(4-methylpiperazin- 1 -yl)-3-oxopropyl]amino)-acetamide; 2-(R)-N-Hydroxy-2-[(methoxybenzenesulfonyl)(3-morpholin-4-yl - [3 -oxopropyl)amino] -4-(morpholin-4-yl)butyramide; [4-N-Benzyloxyamino) -2 (R) -isobutylsuccinyl] -L-leucyl-L-alanine ethyl ester ; <BR> <BR> <BR> <BR> [4-N-Benzyloxyamino) -2 (R) -isobutylsuccinyl] -3 (RS) -aminolaurolactam ; <BR> <BR> <BR> <BR> <BR> <BR> Na-[4-(N-Benzyloxyamino)-2(R)-isobutylsuccinyl]-Ne-(N- benzyloxycarbonylglycyl) -L-lysyl-L-alanine ethyl ester ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylglycine ethyl ester ; <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylglycine<BR> <BR> <BR> <BR> <BR> <BR> isopentylamide ; <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-valylglycine ethylamide ; <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylglycine<BR> <BR> <BR> <BR> <BR> <BR> ethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> Na- [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -Ne- <BR> <BR> <BR> <BR> <BR> tert. butoxycarbonyl-L-lysylglycine ethylamide ;

[4-(N-Hydroxyamino)-2(RS)-isobutylsuccinyl]-O-methyl-L- tyrosinylglycine ethyl ester ; [4-(N-Hydroxyamino)-2(RS)-isobutylsuccinyl]-O-methyl-L- tyrosinylglycine ethylamide ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucyl-L-alanine ethyl ester ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylglycine isopentyl ester ; [4- (N-Hydroxyamino) -2 (R) -propylsuccinyl] -L-leucylglycine ethyl ester ; [4-(N-Hydroxyamino)-2(RS)-sec.butylsuccinyl]-L-leucylglycine ethyl ester ; [4- (N-Hydroxyamino) -2 (R) -isobutylsuccinyl] -L-leucyl-L-alanine ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylglycine methyl ester ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucylsarconsine ethyl ester ; [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucyl-L-proline ethyl ester ; <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucine-L-alanine<BR> <BR> <BR> <BR> <BR> <BR> isopropyl ester ; [4-(N-Hydroxyamino)-2(RS)-isobutylsuccinyl] -L-leucine-2- <BR> <BR> <BR> <BR> oxopropylamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucine-2-<BR> <BR> <BR> <BR> <BR> <BR> methoxyethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-leucine-2, 2- <BR> <BR> <BR> <BR> <BR> dimethoxyethylamide ; Na- [4-(N-Hydroxyamino)-2(R)-isobutylsuccinyl] -Ne-glycyl-L-lysine methylamide ; Na- [4-(N-Hydroxyamino)-2(R)-isobutylsuccinyl] -Ne- (4-carboxybenzoyl) -L-lysl-L-alanine ethyl ester ; <BR> <BR> Na- [4- (N-Hydroxyamino) -2 (R) -isobutylsuccinyl] -Ne-<BR> <BR> <BR> <BR> <BR> <BR> (4-carboxybenzoyl) -L-lysyl-L-aline ;

[4- (N-Hydroxyamino) -2 (R) -isobutylsuccinyl] -3 (RS) -aminooctahydro- <BR> <BR> <BR> <BR> <BR> 2H-azonin-2-one ; [4-(N-Hydroxyamino)-3(S)-methyl-2(R)-isobutyl-succinyl]-L- leucylglycine ethyl ester ; [(3-Aminophthalimido)methyl] [(RS)-4-methyl-2-[[(S)3-methyl- 1 - (methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid; <BR> <BR> <BR> [(RS)-4-Methyl-2-[[(S)-3-methyl- 1 -(methyl-carbamoyl)butyl]- <BR> <BR> <BR> <BR> carbamoyl]pentyl](1,8-naphthalenedi-carboximidomethyl)phosph inic acid; [ (R or S) -4-Methyl-2- [ [ (R or S) -2-oxo-3-azacyclotridecyl] - carbamoyl]pentyl](1.8-naphthalenedicarboximidomethyl)phosphi nic acid; N- [N- [ (R or S)-2[[[[[N-[1-(Benzyloxy)carbonyl]-L-prolyl]-L- leucyl] amino] methyl] hydroxyphosphinyl] -methyl] -4-methylvaleryl] -L- leucyl] -L-alanine; [[1,4-Dihydro-2,4-dioxo-3(2H)-quinazolinyl]-methyl][[(R or S) -4- methyl-2- [ [ (R or S) -2-oxo-3-azacyclotridecyl] carbamoyl] pentyl] phosphinic acid ; <BR> <BR> <BR> N2- [(R)-Hydroxycarbamoylmethyl] -4-methylvaleryl] -N 1,3 <BR> <BR> <BR> <BR> <BR> dimethyl-L-valinamide ; N2- [2 (R or S)-[[[(5-Bromo-2,3-dihydro-6-hydroxy)- 1,3-dioxo- 1 H- benz[d,e]isoquinol-2-yl)methyl]-[(hydroxy)phosphinyl]methyl] -4-methylvaleryl]- N 1,3-dimethyl-L-valinamide; N2- [ (R or S) - [ [ (R) - (Amino) [ (5-bromo-2, 3-dihydro-6-hydroxy-1, 3-dioxo- 1 H-benz[d,e]isoquinol-2-yl)methyl](hydroxy)phosphinyl]methyl] -4- methylvaleryl]-N3,1-dimethyl-L-valinamide hydrobromide; N2- [2 (R or S)-[l(S)-(Hydroxycarbamoyl)ethyl-4-methylvaleryl]- N 1,3-dimethylvalinamide; <BR> <BR> <BR> N2- [2 (R) - [1 (R or S) - (Hydroxycarbamoyl) -2-phthalimidoethyl] -4- <BR> <BR> <BR> <BR> <BR> methylvaleryl]-N 1,3 -dimethyl-L-valinamide; N²-[2(R)- [1(R or S) - (Hydroxycarbamoyl) -4- (methoxy- carbonyl) butyl] -4-methylvaleryl] -N 1, 3-dimethyl-L-valinamide ; M²-[2(R)-[1 (R or S) - (Hydroxycarbamoyl) -4-phenyl-butyl] - 4-methylvaleryl]-N¹,3-dimethyl-L-valinamide;

N2-[2(R)-[1(R or S)-(Hydroxycarbamoyl)-2-succinimidoethyl]-4- methylvaleryl]-N 1,3-dimethyl-L-valinamide; 4-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -2-phthalimidoethyl] -4- methylvaleryl] morpholine ; 4-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -2-phthalimidoethyl] -4- methylvaleryl]tetrahydro- 1,4-thiazine; 1-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -2-phthalimidoethyl] -4- methylvaleryl] -4-piperidinol; 1 -[2(R)-[1 (R or S)-(Hydroxycarbamoyl)-2-(1,2-dimethyl-3,5- dioxo- l ,2,4-triazolidin-4-yl)ethyl] -4-methylvaleryl]piperidine; 4-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -2- (3-methyl-2, 5-dioxo- 1-imidazolidinyl)ethyl]-4-methylvaleryl]tetrahydro-1,4-thiaz ine; Hexahydro-2-[2(R)-[1 (R or S)-(hydroxycarbamoyl)-2-phthalimidoethyl]- 4-methylvaleryl] -N-methyl-3 (S) -pyridazinecarboxamide ; 1- [2 (R) - (R or S) - (Hydroxycarbamoyl) -2- (3, 4, 4-trimethyl-2, 5- dioxo-1-imidazolidinyl)ethyl]-4-methylvaleryl]-4-piperidinol ; [4- (N-Hydroxyamino) -2 (R or S) -heptylsuccinyl] -L-leucyl-L-leucine ethylamide ; [4- (N-Hydroxyamino) -2 (R or S) -nonylsuccinyl] -L-leucyl-L-leucine ethylamide ; [4- (N-Hydroxyamino) -2 (R or S) -heptyl-3 (S) -methylsuccinyl] -L- leucyl-L-leucine ethylamide ; [4- (N-Hydroxyamino) -2 (R) -heptyl-3 (R or S) - (phthalimidomethyl) - succinyl] -L-leucyl-L-leucine ethylamide ; [4-(N-Hydroxyamino)-2(RS)-nonylsuccinyl]-L-tert. butylglycine <BR> <BR> <BR> <BR> methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-phenylalanine <BR> <BR> <BR> <BR> <BR> <BR> <BR> methylamide ; [4- (N-Hydroxyamino) -2 (R) -heptyl-3 (R or S) -phthalimidomethyl) - succinyl]-L-tert.butylglycine methylamide; [4- (N-Hydroxyamino) -2 (R) -heptyl-3 (R or S)-(3-phenylpropyl)-succinyl]- L-leucyl-L-leucine ethylamide ;

[4-(N-Hydroxyamino)-2(RS)-heptylsuccinyl]-L-leucine methylamide; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-leucine neopentylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-alanyl-L-leucine<BR> <BR> <BR> ethylamide ; [4-(N-Hydroxyamino)-2(RS)-heptylsuccinyl] -L-(Ne-phthaloyl)- lysyl-L-leucine ethylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -undecylsuccinyl] -L-leucyl-L-leucine <BR> <BR> <BR> ethylamide ; [4-(N-Hydroxyamino)-2(RS)-heptylsuccinyl]-L-phenylalanyl-L-l eucine <BR> <BR> <BR> ethylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-nonalyl-L-leucine<BR> <BR> <BR> ethylamide ; [4-(N-Hydroxyamino)-2(RS)-heptylsuccinyl]-phenylalanine tert. butylamide ; [4-(N-Hydroxyamino)-2(RS)-heptylsuccinyl]-L-tert.butylglycin e <BR> <BR> <BR> methylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-neopentylglycine<BR> <BR> <BR> methylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-homophenylalanyl-L- leucine ethylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -heptylsuccinyl] -L-cyclohexylalanine<BR> <BR> <BR> methylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isooctylsuccinyl] -L-phenylalanine<BR> <BR> <BR> methylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R) -heptylsuccinyl] -L-neonpentylglycine<BR> <BR> <BR> methylamide ; [4- (N-Hydroxyamino) -2 (R) -heptylsuccinyl] - (D or L) - ß,ß-dimethylphenylalanine methylamide; [4- (N-Hydroxyamino) -2 (R) -heptylsuccinyl] - (D or L) -threo- p-methylphenylalanine methylamide ; <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R) -heptylsuccinyl] -DL-erthro-<BR> <BR> <BR> p-methylphenylalanine methylamide ;

[4- (N-Hydroxyamino) -2 (R) -heptyl-3 (R or S) - [ (3-methyl-2, 5-dioxo- 1-imidazolidinyl)methyl]succinyl]-L-leucyl-L-leucine ethylamide; N2-[3-Cyclobutyl-2(R or S) - [ (hydroxycarbamoyl) -methyl] -propionyl] - N 1, 3-dimethyl-L-valinamide ; N2- [3-Cyclopropyl-2 (R or S) - [ (hydroxycarbamoyl) -methyl] - propionyl]-N 1,3 -dimethyl-L-valinamide; N2- [3-Cyclopentyl-2 (R or S) - [ (hydroxycarbamoyl) -methyl] - <BR> <BR> <BR> <BR> propionyl] -NI, 3-dimethyl-L-valinamide ; <BR> <BR> <BR> <BR> <BR> <BR> N2- [3-Cyclopropyl-2 (R) - [l (RorS) - [ (hydroxy-carbamoyl) -2- (3, 4, 4- <BR> <BR> <BR> <BR> <BR> <BR> trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-N 1,3-dimethyl- <BR> <BR> <BR> <BR> <BR> L-valinamide ; N2- [3-Cyclopropyl-2 (R) - [l (R or S)-[(hydroxy-carbamoyl)- 4-phenylbutyl)]propionyl]-N¹,3-dimethyl-L-valinamide; N2-[3-Cyclobutyl-2(R)-[1 (R or S) - (hydroxy-carbamoyl) - 4-phenylbutyl]propionyl]-N¹,3-dimethyl-L-valinamide; N2-[3-Cyclopentyl-2(R)-[1 (R or S) - (hydroxycarbamoyl) - 4-phenylbutyl]propionyl]-N¹,3-dimethyl-L-valinamide; 1-[3-Cyclopropyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2, 5-dioxo-l-imidazolidinyl) ethyl] propionyl] piperidine ; 1-[3-Cyclopropyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]-4-pipe ridinol; l- [3-Cyclobutyl-2 (R) - [l (R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2, 5-dioxo-1-imidazolidinyl) ethyl] propionyl] piperidine ; 1-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-4-piperidinol; 1-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-4-piperidinol; 1-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]piperid ine; 3-[3-Cyclobutyl-2(R)-[1(R or S)-(hydroxycarbamoyl)-2-(3,4,4-trimethyl- 2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-3-azabicyclo[3.2.2]nonane;

3-[3-Cyclopropyl-2(R)-[1 (R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]-3-azab icyclo[3.2.2]nonane; 3-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]-3-azab icyclo[3.2.2]nonane; 1-[3-Cyclohexyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]piperidine; 4-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]tetrahy dro-1,4-thiazine; 4- [3-Cyclopentyl-2 (R) - [ 1 (R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- <BR> <BR> <BR> <BR> trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]tetrahydro- 1,4-thiazine <BR> <BR> <BR> <BR> <BR> <BR> S, S-dioxide ; 4-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]tetrahy dro-1,4-thiazine; 3-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]-5,5-di methyl-N-propyl- [4 (R) -thiazolidinecarboxamide ; 4-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]morphol ine; 3-[3-Cyclopentyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- <BR> <BR> <BR> <BR> trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-N,5,5-trimethyl-4(R)- <BR> <BR> <BR> <BR> <BR> thiazolidinecarboxamide ; 4-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]-4-phen ylpiperazine; 4-[3-Cyclobutyl-2(R)-[1 (R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]morphol ine; 1-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxy-carbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]propionyl]pyrroli dine; 8-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- <BR> <BR> <BR> <BR> trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]- 1,4-dioxa-8- <BR> <BR> <BR> <BR> <BR> <BR> azaspiro [4, 5] decane ; 1- [3-Cyclobutyl-2 (R) - [ I (R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]-4-methoxypiperidine;

1 -[3-Cyclobutyl-2(R)-[1 (R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]octahydroazocine; 1-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (5, 5- dimethyl-2,4-dioxo-3-oxazolidinyl)ethyl]propionyl]piperidine ; 1-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- (3, 4, 4- trimethyl-2,5-dioxo- 1 -imidazolidinyl)ethyl]propionyl]hexahydroazepine; 1-[3-Cyclobutyl-2(R)-[2-(hexahydro-1,3-dioxo-pyrazolo[1,2-a] [1,2,4]- triazol-2-yl) -1 (R or S) - (hydroxycarbamoyl) ethyl] propionyl] piperidine ; 1-[3-Cyclobutyl-2(R)-[1(R or S) - (hydroxycarbamoyl) -2- phthalimidoethyl] propionyl] piperidine ; 2-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -4-phenylbutyl] nonanoyl] - hexahydro-N-methyl-3 (S) -pyridazinecarboxamide ; N-Cyclohexyl-hexahydro-2-[2(R)-[1(RS)-(hydroxycarbamoyl)-4- phenylbutyl] nonanoyl] -3 (S) -pyridazinecarboxamide ; Hexahydro-2-[2(R)-[1(RS)-(hydroxycarbamoyl)-4-phenylbutyl]no nanoyl]- N- (2, 2, 6, 6-tetramethyl-4-piperidinyl) -3 (S) -pyridazinecarboxamide ; 1-[2(R)-[1(R or S) -Hydroxycarbamoyl) -4-phenylbutyl] nonanoyl] - <BR> <BR> <BR> <BR> <BR> piperidine ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N2- [2 (R) - [l (RS) - (Hydroxycarbamoyl) -2- (3, 4, 4-trimethyl-2, 5-dioxo-l- imidazolidinyl)ethyl]nonanoyl]-N¹-methyl-L-prolinamide; 1-[2(R)-[1(R or S) - (Hydroxycarbamoyl) -2- (3, 4, 4-trimethyl-2, 5-dioxo-l- imidazolidinyl) ethyl] nonanoyl] piperidine ; Hexahydro-2- [2 (R) -1 (R or S) - (hydroxycarbamoyl) -2- (3, 4, 4-trimethyl-2, 5- dioxo-1-imidazolidinyl)ethyl]nonanoyl]-N-methyl-3(S)-pyridaz inecarboxamide; Hexahydro-2- [2 (R or S)-[l(S)-(hydroxycarbamoyl)-3-phenylpropyl]- undecanoyl] -N-methyl-3 (S) -pyridazinecarboxamide ; Hexahydro-2- [2 (R or S)-[1 (S)-(hydroxycarbamoyl)-3-phenylpropyl]- undecanoyl] -N-methoxy-N-methyl-3 (S) -pyridazinecarboxamide ; Hexahydro-2- [2 (R or S)-[(1(S)-(hydroxycarbamoyl)-3-phenylpropyl]- undecanoyl]-N-(1,2,2,6,6-pentamethyl-4-piperidinyl)-3(S)- pyridazinecarboxamide ;

Hexahydro-2- [2 (R or S)-[1 (S)-(hydroxycarbamoyl)ethyl]undecanoyl]-N- methyl-3 (S) -pyridazinecarboxamide ; Hexahydro-2- [2 (R or S)-[1(S)-(hydroxycarbamoyl)-3-phenylpropyl]- nonanoyl] -N-methyl-3 (S) -pyridazinecarboxamide ; Hexahydro-2- [2 (R or S) - [l (S) - (hydroxycarbamoyl) ethyl] nonanoyl] -N- methyl-3 (S) -pyridazinecarboxamide ; 1- [2 (R or S)-[1(S)-(Hydroxycarbamoyl)ethyl]undecanoyl]piperidine; 1- [2- (R or S) - [ 1 (S) - (Hydroxycarbamoyl) -3-phenylpropyl] undecanoyl] - piperidine ; Hexahydro-2- [2 (R or S)-[l(S)-(hydroxycarbamoyl)-3-phenylpropyl]- undecanoyl] -N- (2, 2, 6, 6-tetramethyl-4-piperidinyl) -3 (S) -pyridazinecarboxamide ; Hexahydro-2- [2 (R or S) - [l (S) - (hydroxycarbamoyl) ethyl] undecanoyl] -N- (2,2,6,6-tetramethyl-4-piperidinyl)-3(S)-pyridazinecarboxami de; 1-[2(R or S)-[1(S)-(hydroxycarbamoyl)-4-phenylbutyl]undecanoyl]- piperidine ; 4-[2(R or S)-[1(S)-(hydroxycarbamoyl)-4-phenylbutyl]undecanoyl]- morpholine ; 1-(Benzyloxycarbonyl)-hexahydro-2-[2(R)-[(R or S) - (hydroxycarbamoyl) - <BR> <BR> <BR> <BR> 4-phenylbutyl]nonanoyl]-N-(α(S)-methylbenzyl)-3(S)-pyridazi necarboxamide; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -5 -(carboxy)pentanoyl] - L-phenylalanine N-methylamide ; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (phenylmethoxy)hexanoyl]-L-phenylalanine N-methylamide; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (propylamino) - 6-(oxo)hexanoyl]-L-phenylalanine N-methylamide; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] - (6RS) -6- (hydroxy)heptanoyl]-L-phenylalanine N-methylamide; (2S)-N-2-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (hydroxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; (2S)-N-2-[(2'R)-2'-[2'-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ;

N-[(2'R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl]-6-(4'- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> oxobutylamino) hexanoyl] -L-phenylalanineN-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2(S)-N-2-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-(oXo )-6'- (propylamino)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; N-[(2R)-2-[(1 'S)- 1 '-(Methyl)-2'-(hydroxyamino)-2'-(oxo)ethyl]-6- (phenylmethoxy)hexanoyl]-L-phenylalanine N-methylamide; N- [(2R)-2- [(1 'S)- 1 '-(Methyl)-2'-(hydroxyamino)-2'-(oxo)ethyl] -6- (oxo)-6-(propylamino)hexanoyl]-L-phenylalanine N-methylamide; (2S)-N-2[(2'R)-[(1"R)-1"-(1,3-Dihydro-1,3-dioxo-2H-isoindol- 2- yl) methyl-2"- (hydroxyamino) -2"- (oxo) ethyl] -6'- (phenylmethoxy) hexanoyl] - amino-3, 3-dimethylbutanoic acid N-methylamide ; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (oxo) -6- (propylamino)hexanoyl]-L-phenylalanine N-2-phenylethylamide; (2 S)-N-2- [(2'R)-2'- [(1 "S)- 1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6- (phenylmethoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid <BR> <BR> <BR> <BR> N-2-phenylethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)- 1 "-(Methyl)-2"-(hyroxyamino)-2"- (oXo)ethyl]-6'-(oXo)-6'-(propylamino)hexanoyl]amino-3,3-dime thylbutanoic acid <BR> <BR> <BR> <BR> <BR> N-2-phenylethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)- 1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6'- (oxo) -6'- (propylamino) hexanoyl] amino-3, 3-dimethylbutanoic acid N-2- (4'-sulfamoyl) phenylethylamide ; (2S)-N-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3-cyclohexylpropionic acid N-2- (4'- <BR> <BR> <BR> <BR> <BR> sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[2R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl]-6'-(phenylmethoxy )- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> hexanoyl]-L-(3,5-dimethyl)phenylalanine N-2-(4'-sulfamoyl)phenylethylamide; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(4 - methoxy) phenoxy] hexanoyl] amino-3, 3 -dimethylbutanoic acid N-2- (4'- sulfamoyl) phenylethylamide ;

(2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [(4-methyl)phenoxy]hexanoyl]amino-3,3-dimethylbutanoic acid N-2- (4"-sulfamoyl) phenylethylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [(l-oXo)butylamino]hexanoyl]amino-3-cyclohexylpropionic acid <BR> <BR> <BR> <BR> N-2- (4'-sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)- 1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6- (phenylmethoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2-[(2'R)-2'-[(1"S)-1"-(2-Methylpropyl)-2"-(hydroxyami no)- 2"- (oxo) ethyl] -6- (phenylmethoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (phenoxy) hexanoyl] -L- phenylalanine N-methylamide ; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -7-(phenoxy)heptanoyl] -L- phenylalanine N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-2- phenylethylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-2- (4'- <BR> <BR> <BR> <BR> sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -5- (phenylmethoxy) - pentanoyl]-L-phenylalanine N-methylamide; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -7- (phenylmethoxy) - heptanoyl] -L-phenylalanine N-methylamide ; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (phenyloxy) hexanoyl] - L-phenylalanine N-methylamide ; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -7- [(phenyloxy)heptanoyl] - L-phenylalanine N-methylamide ;

(2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(2 - phenethylamino)-6'-(oxo)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [ (4-methylphenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [ (4-chlorophenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [ (3-methylphenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-(carboxymethyl)-6'-(3-methylphenoxy)hexa noyl]- amino-3, 3-dimethylbutanoic acid N-methylamide ; N-[(2R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl]-5-(carboxy)penta noyl]- L-phenylalanine N-methylamide ; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -6-(phenylmethoxy)- hexanoyl]-L-phenylalanine N-methylamide; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -6-(propylamino)-6- (oxo)hexanoyl]-L-phenylalanine N-methylamide; <BR> <BR> <BR> <BR> N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -(6RS)-6-(hydroxy)- <BR> <BR> <BR> <BR> <BR> <BR> <BR> heptanoyl]-L-phenylalanine N-methylamide; (2S)-N-2-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (hydroxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; (2S)-N-2-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; N- [ (2'R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (4'- <BR> <BR> <BR> <BR> oxobutylamino) hexanoyl] -L-phenylalanine N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2(S)-N-2-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl] -6'-(oxo)-6'- (propylamino)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; N- [ (2R) -2- [ ( 1'S) -1'- (Methyl) -2'- (hydroxyamino) -2'- (oxo) ethyl] - 6- (phenylmethoxy) hexanoylJ-L-phenylalanine N-methylamide ; N- [ (2R) -2- [ ( 1'S) -1'- (Methyl) -2'- (hydroxyamino) -2'- (oxo) ethyl] - 6-(oxo)-6-(propylamino)hexanoyl]-L-phenylalanine N-methylamide;

(2S) -N-2 [ (2'R) - [ ( 1"R) -1"- (1, 3-dihydro-1, 3-dioxo-2H-isoindol-2- <BR> <BR> <BR> <BR> <BR> <BR> yl)methyl -2"-(hydroxyamino)-2"-(oxo)ethyl] -6'-(phenylmethoxy)hexanoyl] - amino-3, 3-dimethylbutanoic acid N-methylamide ; N-[(2R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl] -6-(oxo)-6- (propylamino)hexanoyl]-L-phenylalanine N-2-phenylethylamide; (2S)-N-2-[(2'R)-2'-[(1 "S)- 1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6- (phenylmethoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid <BR> <BR> <BR> <BR> N-2-phenylethylamide ; <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)-1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6'- (oxo) -6'- (propylamino) hexanoyl] amino-3, 3-dimethylbutanoic acid <BR> <BR> <BR> <BR> N-2-phenylethylamide ; <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)- 1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo) ethyl] -6'- (oxo) -6'- (propylamino) hexanoyl] amino-3, 3-dimethylbutanoic acid N-2- (4'-sulfamoyl) phenylethylamide ; (2S)-N-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- <BR> <BR> <BR> <BR> (phenylmethoxy)hexanoyl]amino-3-cyclohexylpropionic acid N-2-(4'- <BR> <BR> <BR> <BR> <BR> <BR> sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -6'-(phenylmethoxy) -<BR> <BR> <BR> <BR> <BR> <BR> hexanoyl]-L-(3,5-dimethyl)phenylalanine N-2-(4'-sulfamoyl)phenylethylamide; <BR> <BR> <BR> <BR> <BR> <BR> (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- [ (4- <BR> <BR> <BR> <BR> <BR> methoxy)phenoxy]hexanoyl]amino-3,3-dimethylbutanoic acid N-2-(4'- sulfamoyl) phenylethylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(4 - methyl) phenoxy] hexanoyl] amino-3, 3-dimethylbutanoic acid N-2- (4'- sulfamoyl) phenylethylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(1 - oxo) butylamino] hexanoyl] amino-3-cyclohexylpropionic acid N-2- (4'- <BR> <BR> <BR> <BR> sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> (2S)-N-2-[(2'R)-2'-[(1 "S)-1 "-(Methyl)-2"-(hydroxyamino)-2"- (oxo)ethyl]-6-(phenylmethoxy)hexanoyl]amino-3,3-dimethylbuta noic acid N-methylamide ;

(2S)-N-2-[(2'R)-2'-[(1"S)-1"-(2-Methylpropyl)-2"-(hydroxyami no)- 2//- (oxo) ethyl] -6- (phenylmethoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid <BR> <BR> <BR> <BR> N-methylamide ; <BR> <BR> <BR> <BR> <BR> N-[(2R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl]-6-(phenoxy)hexan oyl]- L-phenylalanine N-methylamide ; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -7-(phenoxy)heptanoyl] -L- phenylalanine N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-2-phenylethylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'- (phenylmethoxy)hexanoyl]amino-3,3-dimethylbutanoic acid N-2- (4'- <BR> <BR> <BR> <BR> sulfamoyl) phenylethylamide ; <BR> <BR> <BR> <BR> <BR> N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -5- (phenylmethoxy)pentanoyl]-L-phenylalanine N-methylamide; N-[(2R)-2-[2'-(Hydroxyamino)-2'-(oxo)ethyl]- 7- (phenylmethoxy) heptanoyl] -L-phenylalanine N-methylamide ; N- [ (2R) -2- [2'- (Hydroxyamino) -2'- (oxo) ethyl] -6- (phenyloxy)hexanoyl]-L-phenylelanine N-methylamide; N- [(2R)-2- [2'-(Hydroxyamino)-2'-(oxo)ethyl] -7- [(phenyloxy)heptanoyl]-L-phenylalanine N-methylamide; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(2 - phenethylamino)-6'-(oxo)hexanoyl]amino-3,3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(4 - methylphenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(4 - chlorophenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ; (2S)-N-2'-[(2'R)-2'-[2"-(Hydroxyamino)-2"-(oxo)ethyl]-6'-[(3 - methylphenoxy) hexanoyl] amino-3, 3-dimethylbutanoic acid N-methylamide ;

(2S)-N-2'-[(2'R)-2'-(Carboxymethyl)-6'-(3-methylphenoxy)hexa noyl]- amino-3, 3-dimethylbutanoic acid N-methylamide ; (3R,10S)-5-Methyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0]nonade ca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanoic acid; (3R,10S)-N-Hydroxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.0]- nonadeca-12 (19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) hexanamide ; (3R,11S)-N-Hydroxy-5-methyl-3-(10-oxo-1,9-diazatricyclo[11.6 .1.0]- eicosa-13(20),14(19),15,17-tetraen-11-ylcarbamoyl)hexanamide ; (3R,9S)-5-Methyl-3-(8-oxo-i,7-diazatricyclo[9.6.1.0]octadeca - 11 (18),12(17),13,15 -tetraen-9-ylcarbamoyl)hexanoic acid; (3R,9S)-N-Hydroxy-5-methyl-3-(8-oxo-1,7-diazatricyclo[9.6.1. 0]octadeca- 11(18),12(17),13,15-tetraen-9-ylcarbamoyl)hexanamide; <BR> <BR> <BR> <BR> (105)-[4-Methyl-2-(9-oxo-1,8-diazatricyclo[10.6.1.0]nonadeca - <BR> <BR> <BR> <BR> <BR> <BR> 12(19),13(18),14,16-tetraen- 10-ylcarbamoyl)pentyl] -(quinolin-2- <BR> <BR> <BR> <BR> <BR> <BR> ylthiomethyl) phosphinic acid ; (3R,10S)-N-Hydroxy-5-methyl-2-methoxycarbonyl-3-(9-oxo-1,8- <BR> <BR> <BR> <BR> diazatricyclo [10. 6. 1. 0] nonadeca-12 (19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) - <BR> <BR> <BR> <BR> <BR> <BR> hexanamide ; N (4-Methyl-2-carboxymethylpentanoyl) -L-leucine-N'- (4-methoxycarbonylphenyl)carboxamide; N (4-Methyl-2- (N"-hydroxycarbamoyl) methylpentanoyl) -L-leucine- N'- (4-methoxycarbonylphenyl) carboxamide ; N (4-Methyl-2- (N"-hydroxycarbamoyl) methylpentanoyl) -L-leucine-N'- (4-carboxyphenyl)carboxamide; N(4-Methyl-2-(N"-hydroxycarbamoyl)methylpentanoyl)-L- <BR> <BR> <BR> <BR> tryptophan-N'- (4-carboxyphenyl) carboxamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N (4-Methyl-2- (N"-hydroxycarbamoyl) methylpentanoyl) - L-cyclohexylglycine-N'- (4-methoxycarbonylphenyl) carboxamide ; N (4-Methyl-2- (N"-hydroxycarbamoyl) methylpentanoyl) -L-t-leucine-N'- (4-methoxycarbonylphenyl)carboxamide; (3R,10S)-6-Biphenyl-4-yl)-3-(9-oxo-1,8-diazatricyclo[10.6.1. 0]onadeca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanoic acid;

(3R,10S)-3-(9-Oxo-1,8-diazatricyclo[10.6.1.0]nonadeca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)-5-(thiophen-2-yl )pentanoic acid; (3R,10S)-3-Cyclopentyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0]n onadeca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)propionic acid; (3R,10S)-4-Cyclopentyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0]n onadeca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)butanoic acid; (3R,10S)-4-Cyclopropyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0]n onadeca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)butanoic acid; (3R,10S)-5-Methyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0]nonade ca- 12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanoic acid; (3R,10S)-N-Hydroxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.0]- nonadeca-12 (19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) hexanamide ; (3R,11S)-N-Hydroxy-5-methyl-3-(10-oxo-1,9-diazatricyclo[11.6 .1.0]- eicosa-13(20),14(19),15,17-tetraen- 11 -ylcarbamoyl)hexanamide; (3R,9S)-N-5-Methyl-3-(8-oxo-1,7-diazatricyclo[9.6.1.0]octade ca- 11 (18),12(17),13,15-tetraen-9-ylcarbamoyl)hexanoic acid; (3R,9S)-N-Hydroxy-5-methyl-3-(8-oxo-1,7-diazatricyclo[9.6.1. 0]octadeca- II (18), 12 (17), 13, 15-tetraen-9-ylcarbamoyl) hexanamide ; (10S)-2-Mercaptomethyl-4-methyl-N-(9-oxo-1,8-diazatricyclo[1 0.6.1.0]- nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)pentanam ide; (10S)-2-Acetylthiomethyl-4-methyl-N-(9-oxo-1,8-diazatricyclo [10.6.1.0]- nonadeca-12 (19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) pentanamide ; <BR> <BR> <BR> <BR> (3R,10S)-2-(Methanesulfonamidomethyl)-5-methyl-3 -(9-oxo- 1,8- <BR> <BR> <BR> <BR> <BR> <BR> diazatricyclo [10. 6. 1. 0] nonadeca-12 ( 19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) - hexanoic acid ; (3R,10S)-2-(3 -Ethylureidomethyl)-5-methyl-3-(9-oxo-1,8- diazatricyclo [10. 6. 1. 0] nonadeca-12 (19), 13 (18), 14, 16-tetraen-10- <BR> <BR> <BR> <BR> ylcarbamoyl) hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> (3R,9S)-N-Hydroxy-2-hydroxy-5-methyl-3-(8-oxo- 1,7- diazatricyclo[9.6.1.0]octadeca-11(18),12(17),14,16-tetraen-9 - ylcarbamoyl) hexanamide or its (2S, 3R, 9S) stereoisomer ;

(3R,10S)-N-Hydroxy-5-methyl-2-methoxycarbonyl-3-(9-oXo- 1,8- diazatricyclo [10. 6. 1. 0] nonadeca-12 ( 19), 13 (18), 14, 16-tetraen-10-ylcarbamoyl) - hexanamide ; (3R,9S)-5-Methyl-3-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]oc tadeca- 11 (18),12,14,16-tetraen-9-ylcarbamoyl)hexanoic acid; (3R,9S)-3-Cyclobutylmethyl-N-(8-oxo-4-oxa-1,7-diazatricyclo[ 9.6.1.0]- octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) succinamic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11(18),12,14,16-tetraen-9-ylcarbamoyl)-5-phenoxy-pentanoic acid; (3R,9S)-5-(4-Chlorophenoxy)-3-(8-oxo-4-oxa-1,7-diazatricyclo [9.6.1.0] - octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) pentanoic acid ; (3R,9S)-5-(4-Chlorophenoxy)-3-(8-oxo-4-oxa-1,7-diazatricyclo [9.6.1.0]- octadeca-l l (18),12,14,16-tetraen-9-ylcarbamoyl)pentanoic acid ethyl ester ; (3R,9S)-3-(8-Oxo-1,7-diazatricyclo[9.6.1.0]octadeca-11(18),1 2,14,16- tetraen-9-ylcarbamoyl) pentanoic acid ethyl ester ; (3R,9S)-6-(4-Hydroxy-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricycl o[9.6.1.0]- octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11(18),12,14,16-tetraen-9-ylcarbamoyl)-6-pyridin-4-yl-hexano ic acid; (3R,9S)-6-[4-(3-Hydroxy-propoxy)-phenyl]-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca-11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) -5- (4-phenoxy-phenyl) pentanoic acid ; (3R,9S)-6-[4-(2-Hydroxy-ethoxy)-phenyl]-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18),12,14,16-tetraen-9-ylcarbamoyl) -6 -[4 -(2 -pyrrolidin- 1 -yl - ethoxyphenyl]hexanoic acid; (3R,9S)-6-(4-Methoxy-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricycl o[9.6.1.0]- octadeca- 11 (18),12,14,16-tetraen-9-ylcarbamoyl)hexanoic acid;

(3R,9S)-6-[4-(2-Methoxy-ethoxy)-phenyl]-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- I l (18), 12, 14, 16-tetraen-9-ylcarbamoyl) -5-phenyl-pentanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- II (18), 12, 14, 16-tetraen-9-ylcarbamoyl) -6-phenyl-hexanoic acid ; (3R,9S)-6-(3-Hydroxy-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricycl o[9.6.1.0]- octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11(18),12,14,16-tetraen-9-ylcarbamoyl)-6-[4-(3-piperidin-1-y l- propoxy) phenyl] hexanoic acid ; (3R,9S)-6-[4-(3-Dimethylamino-propoxy)-phenyl]-3-(8-oxo-4-ox a- 1,7-diazatricyclo[9.6.1.0]octadeca-11 (18),12,14,16-tetracn- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-6-[4-(2-Dimethylamino-ethoxy)-phenyl]-3-(8-oXo-4-oxa - 1,7-diazatricyclo[9.6.1.0]octadeca-11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-6-(4-Cyano-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricyclo[ 9.6.1.0]- octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) hexanoic acid ; (3R,9S)-6-Naphthalen-2-yl-3-(8-oxo-4-oxa-1,7-diazatricyclo[9 .6.1.0]- octadeca-11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) hexanoic acid ; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18),12,14,16-tetraen-9-ylcarbamoyl)-6-(4-pyrrol- 1 -yl)hexanoic acid; (3R,9S)-6-(4-Hydroxy-3-methyl-phenyl)-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca-11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-6-(4-Benzyloxy-phenyl)-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ; (3R,9S)-6-[4-(4-Aminobutoxy-phenyl)]-3-(8-oxo-4-oxa- 1,7-diazatricyclo[9.6.1.0]octadeca-11 (18),12,14,16-tetraen- 9-ylcarbamoyl) hexanoic acid ;

(3R,9S)-5-(4-Methoxy-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricycl o[9.6.1.0]- octadeca- 11 (18),12,14,16-tetraen-9-ylcarbamoyl)pentanoic acid; (3R,9S)-6-(4-Amino-phenyl)-3-(8-oxo-4-oxa-1,7-diazatricyclo[ 9.6.1.0]- octadeca- 11 (18),12,14,16-tetracn-9-ylcarbamoyl)hexanoic acid; (3R,9S)-3-(8-Oxo-4-oxa-1,7-diazatricyclo[9.6.1.0]octadeca- 11 (18), 12, 14, 16-tetraen-9-ylcarbamoyl) -6- [4- (pyridin-4-ylmethoxy) phenyl] - hexanoic acid ; (3R,9S)-6-(4-Acetylamino-phenyl)-3-(8-oxo-4-oxa- 1,7- diazatricyclo[9.6.1.0]octadeca-11(18),12,14,16-tetraen-9-ylc arbamoyl)hexanoic acid ; Na-[[3-(N-Hydroxycarbamoyl)-4-methylthio-2-propoxymethyl]but ylyl]- <BR> <BR> <BR> <BR> N, O-dimethyltyrosine amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> Nα-[[3-(N-Hydroxycarbamoyl)-4-isopropylthio-2-propoxymethyl ]- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> butylyl] -N, O-dimethyltyrosine amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> Na- [ [3- (N-Hydroxycarbamoyl) -2-propylthio] butylyl] -N, O- dimethyltyrosine amide ; <BR> <BR> <BR> <BR> <BR> N- [N-(1 -Phosphono-3 -phenylpropyl)-(S)-leucyl] -(S)-phenylalanine-N- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[N-(1 -Phosphono-3-(4-bromo- 1,8-naphthalene-dicarboximido)propyl)- (S)-leucyl]-(S)-phenylalanine methylamide; N-[N-(1-Phosphono-3-(benzyloxycarbonylamino)propyl)-(S)-leuc yl]-(S)- phenylalanine methylamide ; N-[N-(1-Phosphono-3-(2-hydroxyphenyl)propyl)-(S)-leucyl]-(S) - phenylalanine methylamide ; N-[N-(1-Phosphono-3-(methylmercapto)propyl)-(S)-leucyl]-(S)- phenylalanine-N-methylamide ; N-[N-(1-Phosphono-3-(methylsulphinyl)propyl)-(S)-leucyl]-(S) - phenylalanine-N-methylamide ; N-[N-(1-Phosphono-3-(methylsulphonyl)propyl)-(S)-leucyl]-(S) - <BR> <BR> phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[N-(1 -Phosphono-3-(1,8-naphthalenedicarboximido)propyl)-(S)-leucy l]- <BR> <BR> <BR> <BR> <BR> <BR> <BR> (S) -tryptophan-N-methylamide ;

N-[N-(1 -Phosphono-3-(1,8-naphthalenedicarboximido)propyl)-(S)-leucy l]- <BR> <BR> <BR> <BR> <BR> <BR> (S) -lysine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-[N-(1 -Phosphono-3-(1,8-naphthalenedicarboximido)propyl)-(S)-leucy l]- <BR> <BR> <BR> <BR> <BR> <BR> <BR> (-) -aminoazacyclotridecan-2 -one ; <BR> <BR> <BR> <BR> <BR> <BR> N- [N-(1 -Phosphono-3 -(1,8-naphthalenedicarboximido)propyl)-(S)-leucyl] - (S)-lysine-N-(aminoethyl)amide; N- [N- (l -Phosphono-3- (1, 8-naphthalenedicarboximido) propyl) - (S) -leucyl] - (S)-lysine-N-(ethylpyrrolidine)amide; N-[N-(1 -Phosphono-3-(1,8-naphthalenedicarboximido)propyl)-(S)-leucy l]- (S)-lysine-N-(ethyl-N-methylpiperazine)amide; N-[N-(1-Phosphono-3-[8-(7,9-dioxo-8-azaspiro[4,5]decyl)]prop yl)-(S)- leucyl] - (S) -phenylalanine-N-methylamide ; and N- [N- (l -Phosphono-3- [8- (7, 9-dioxo-8-azaspiro [4, 5] decyl)] propyl) - (S) - leucyl] - (S) -lysine-N-methylamide.

As noted above, numerous inhibitors of matrix metalloproteinases are known. A large number of inhibitors are characterized as hydroxamic acid-based and/or carboxylic acid-based compounds. Typical of such compounds are those described in the following references, all of which are incorporated herein by reference, since all of the disclosed compounds can be used in the method of this invention.

US 4, 599, 361 (Searle) US 4,771,038 (ICI) US 4, 996, 358 (Roche) US 4, 918, 105 (Bellon) US 5, 304, 604 ; US 5, 514, 677 (British Biotechnology) US 5, 240, 958 ; US 5, 310, 763 ; US 5, 530, 161 (British Biotechnology) US 5, 453, 438 (British Biotechnology) US 5, 239, 078 (Glycomed) US 5, 183, 900 (Glycomed) US 5, 270, 326 (Glycomed) WO 92/17460 (Smith-Kline Beecham) US 5, 300, 501 (Celltech) US 5, 304, 549 (Roche)

US 5, 256, 657 (Sterling Winthrop) US 5, 300, 674 ; US 5, 412, 145 (British Biotechnology) US 5, 387, 610 ; US 5, 616, 605 (Research Corporation Technologies) US 5, 442, 110 ; US 5, 473, 100 (Yamanouchi) US 5, 643, 908 (Sankyo) US 5, 525, 629 (British Biotechnology) US 5, 569, 665 (Celltech) US 5, 530, 128 (Celltech) US 5, 318, 964 ; US 5, 447, 929 (Roche) US 5, 643, 964 ; US 5, 700, 838 (British Biotechnology) WO 97/27174 (Shionogi) An especially preferred group of compounds to be employed in the present method are those described in WO 95/35275 and WO 95/35276, both of which are incorporated herein by reference. Typical compounds from within these groups to be employed include : N-Hydroxy-2- [ [ (2- (4-methoxy-phenoxy) -ethyl- (toluene-4-sulfonyl) - amino] -acetamide; N-Hydroxy-2-[(4-phenoxy-ethyl)-toluene-4-sulfonyl) amino]-acetamide; N-Hydroxy-2- [ (4-methoxy-benzenesulfonyl) -nonyl-amino] -acetamide ; <BR> <BR> <BR> 2- [-Decyl- (toluene-4-sulfonyl) -amino] -N-hydroxy-acetamide ; <BR> <BR> <BR> <BR> <BR> 2-Benzyl-(octane- 1 -sulfonyl)-amino]-N-hydroxy-acetamide; <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ (2-methoxy-benzyl) - (octane-l-sulfonyl) -amino] -acetamide ; 2- [ (2-Ethoxy-benzyl) - (octane-l-sulfonyl) -amino] -N-hydroxy-acetamide ; N-Hydroxy-2-[(naphthalen-2-yl-methyl)-(octane- 1 -sulfonyl)-amino]- acetamide ; 2- [(4-Chloro-benzyl)-(octane- 1 -sulfonyl)-amino] -N-hydroxy-acetamide, and salts, solvates, or hydrates thereof.

Another class of matrix metalloproteinase inhibitors are aryl sulfonamides of the formula

where Ar is carbocyclic or heterocyclic aryl, and R, R 1, and R2 include hydrogen, alkyl, aryl, heteroaryl, amino, substituted and disubstituted amino. These compounds are disclosed in European Patent Number 0606046, incorporated herein by reference. Specific compounds to be employed in the present method include : <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (isobutyl) amino] acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (cyclo-hexylmethyl) amino] - acetamide ; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (cyclo-hexyl) amino] - acetamide ; <BR> <BR> <BR> N-Hydroxy-2-[[4-methoxybenzenesulfonyl](phenethyl)amino]acet amide; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (3-methylbutyl) amino] - acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (sec-butyl) amino] acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (tert-butyl) amino] acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (4-fluorobenzyl) amino] - acetamide ; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (4-chlorobenzyl) amino] - acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (isopropyl) -amino] acetamide ; <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (4-methylbenzyl) amino] - acetamide ; 4-N-Hydroxy-carbamoyl]-4-[[4-methoxybenzene-sulfonyl(benzyl) - amino]- 1 -[dimethylaminoacetyl]-piperidine hydrochloride; <BR> <BR> <BR> 4-N-Hydroxy-carbamoyl] -4- [ [4-methoxybenzene-sulfonyl (benzyl) - <BR> <BR> <BR> amino] - I - [3-picolyl] -piperidine dihydrochloride ; <BR> <BR> <BR> 4-N-Hydroxy-carbamoyl] -4- [ [4-methoxybenzene-sulfonyl (benzyl) - <BR> <BR> <BR> amino]-1-[carbomethoxymethyl]-piperidine hydrochloride;

4-N-Hydroxy-carbamoyl]-4-[[4-methoxybenzene-sulfonyl(benzyl) - amino]-1-piperidine trifluoroacetate; 4-N-Hydroxy-carbamoyl]-4-[[4-methoxybenzene-sulfonyl(benzyl) - <BR> <BR> <BR> <BR> amino] - I - [t-butoxycarbonyl] -piperidine ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-N-Hydroxycarbamoyl] -4-[[4-methoxybenzene-sulfonyl(benzyl)-amino] - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1- [methylsulfonyl] -piperidine ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxycarbamoyl] -4- [ [4-methoxybenzene-sulfonyl (benzyl) -amino] - 1-[4-picoly]-piperidine hydrochloride; N-Hydroxycarbamoyl]-4-[[4-methoxybenzene-sulfonyl(benzyl)ami no]- 1-[morpholinocarbonyl]-piperidine hydrochloride; and N- (t-Butyloxy) -2- [ [4-methoxybenzenesulfonyl (benzyl) amino] -2- [2- (4- morpholino) ethyl] acetamide.

The following compounds are prepared similarly to Example 7 : <BR> <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (isobutyl) -amino-2- (2- (4- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> morpholino) ethyl] acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (2-picoly) -amino-2- (2- (4- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> morpholino) ethyl] acetamide dihydro-chloride ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (3-picolyl) amino] -2- [2- (4- morpholino)ethyl]acetamide dihydrochloride; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (2-methyl-thiazol- 4-ylmethyl)amino]-2-[2-(4-morpholino)ethyl]acetamide dihydrochloride; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] benzyl) amino] -2- [2- (4- thiomorpholino] ethyl] acetamide ; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl](benzyl)amino]-2-[2-(4- methylthiazol-4-ylmethyl]acetamide; <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl (benzyl) amino] -2- [ (6- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> chloropiperonyl] acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ [4-methoxybenzenesulfonyl (benzyl) amino] -2- [(1 - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> pyrazolyl) methyl] acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2-[[4-methoxybenzenesulfonyl(3-picolyl)amino]-2-[3 - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> picolyl] acetamide ; N-Hydroxy-2-[[4-methoxybenzenesulfonyl(benzyl)-amino]-2-[(1- methyl- 4-imidazolyl)methyl]acetamide hydrochloride;

N-Hydroxy-2- [ [4-methoxybenzenesulfonyl (isobutyl) amino] -2- [ (l-methyl- 4-imidazolyl)methyl]acetamide hydrochloride; N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (3 -picolyl)amino] -2- [(1 - methyl-4-imidazolyl)methyl]acetamide hydrochloride; N-Hydroxy-2-[[4-methoxybenzenesulfonyl(2-picolyl)amino]-2-[( 1 - methyl-4-imidazolyl)methyl]-acetamide hydrochloride; and N-Hydroxy-2- [ [4-methoxybenzenesulfonyl] (2-methylthiazol- 4-ylmethyl)amino-2-[(1-methyl-4-imidazolyl)methyl]acetamide hydrochloride.

Another group of small peptide matrix metalloproteinase inhibitors are described in United States Patent Numbers 5, 270, 326, 5, 530, 161, 5, 525, 629, and 5, 304, 604 (incorporated herein by reference). The compounds are hydroxamic acids defined by the formula where R1, R2, R3, and R4 can be hydrogen or alkyl and X is OR5 or NHR5 where R5 includes hydrogen, alkyl and aryl, A includes alkyl, and n is 0 to 2. Typical compounds to be employed in the instant method include the following : N- [2-Isobutyl-3 -(N'-hydroxycarbonylamido)-propanoyl] -D-tryptophan <BR> <BR> <BR> <BR> methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Isobutyl-3- (N'-hydroxycarbonylamido) -propanoyl] -N-methyl-L- tryptophan methylamide ; N-[2-Isobutyl-3-(N-hydroxycarbonylamido)-propanoyl]-L-3-(2- <BR> <BR> naphthyl) -alanine methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [2-Isobutyl-3- (N'-hydroxycarbonylamido) -propanoyl] -L-tryptophan <BR> <BR> <BR> <BR> <BR> <BR> 2-hydroxyethylamide ;

N-[2-Isobutyl-3-(N'-hydroxycarbonylamido)-propanoyl]-L-trypt ophan <BR> <BR> <BR> <BR> amylamide ; <BR> <BR> <BR> <BR> <BR> N- [2-Isobutyl-3- (N'-hydroxycarbonylamido) -propanoyl] -L-tryptophan <BR> <BR> <BR> <BR> <BR> piperidinamide ; N-[2-Isobutyl-3-(N'-hydroxycarbonylamido)-propanoyl-L-trypto phan dodecylamide ; N- [2-Isobutyl-3 -(N'-hydroxycarbonylamido)-propanoyl] -L- tryptophan (S) -methylbenzylamide ; N-[L-2-Isobutyl-3-(N'-hydroxycarbonylamido)-propanoyl]-L- tryptophan (6-phenylmethoxycarbonyl-amino-hexyl-1) amide ; 2S-Hydroxy-3R-[1S-(3-methoxy-2,2-dimethyl-propylcarbamoyl)- <BR> <BR> <BR> 2,2-dimethyl-propylcarbamoyl]-5-methyl-hexanohydroxamic acid; <BR> <BR> <BR> <BR> 2 S -Hydroxy-3 R- [1 S-(methylcarbamoyl)-2,2 -dimethyl -propylcarbamoyl] - 6-(4-chloro)phenyl-hexanohydroxamic acid; 2S-Hydroxy-3R- [l S- (methylcarbamoyl) -2, 2-dimethyl-propylcarbamoyl] - octanohydroxamic acid ; 2 S-Hydroxy-3 R- [1 S -(pyridin-2-ylmethylcarbamoyl)-2,2-dimethyl- propylcarbamoyl]-5-methyl-hexanohydroxamic acid; 2S-Hydroxy-3R-[1S-(pyridin-3-ylmethylcarbamoyl)-2,2-dimethyl - propylcarbamoyl]-5-methyl-hexanohydroxamic acid; 2S-Hydroxy-3R-[1 S-(pyridin-4-ylmethylcarbamoyl)-2,2-dimethyl- propylcarbamoyl]-5-methyl-hexanohydroxamic acid; 2S-Hydroxy-3R-[1 S-(methylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]- 4-methoxy-butanohydroxamic acid ; 2S-Hydroxy-3R- [lS- (methylcarbamoyl) -2, 2-dimethyl-propylcarbamoyl] - 4-benzyloxy-butanohydroxamic acid ; 2S-Hydroxy-3R- [1 S- (methylcarbamoyl) -2, 2-dimethyl-propylcarbamoyl] - 4-benzylthio-butanohydroxamic acid; 2S-Hydroxy-3R-[1 S-(methylcarbamoyl)-2,2-dimethyl-buten- 3-ylcarbamoyl]-5-methyl-hexanohydroxamic acid; 2S-Hydroxy-3R-[1 S-(tert-butylcarbamoyl)-2,2-dimethyl- propylcarbamoyl]-5-methyl-hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(N,N-dimethyl-carbamoyl)-2,2-dimethyl- propylcarbamoyl]-5-methyl-hexanohydroxamic acid; 2S-Hydroxy-3R-[1S-(3-hydroxy-2,2-dimethyl-propylcarbamoyl)- 2, 2-dimethyl-propylcarbanoyl] -5-methyl-hexanohydroxamic acid ; 2S-Hydroxy-3R-[1 S-(methylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]- 6-phenyl-hexanohydroxamic acid ; 2S-Hydroxy-3R- [lS- (methylcarbamoyl) -2, 2-dimethyl-butylcarbamoyl] - 5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> (2-hydroxyethyl) -amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalaninyl-proline ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-hydroxyethyl) -N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-phenylalaninyl-D- prolinol; <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-phenylalaninyl-L-prolinol; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N- (5-N- <BR> <BR> <BR> <BR> <BR> <BR> methyl-pentylcarboxamide) amide ; <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-ethylthioethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> (2-methoxyethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-phenylalanine-N-(2-N- <BR> <BR> <BR> <BR> <BR> <BR> acetylethyl) amide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-phenylalanine-N- (3 -(2-pyrrolidone)propyl)amide; [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N- (3-(2-pyrrolidone)propyl)amide sodium salt ; <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-acetoxyethyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S-methylsuccinyl] -L-phenylalanine- <BR> <BR> <BR> <BR> <BR> N- (3- (2-pyrrolidone) propyl) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-L-phenylalanine- <BR> <BR> <BR> <BR> <BR> <BR> N-methyl-N- (2-hydroxyethyl) amide ;

[4- (N-Hydroxyamino) -2R-isobutyl-3 S-methylsuccinyl] -L-phenylalanine- <BR> <BR> <BR> <BR> <BR> N- (2-hydroxyethyl) amide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-L-phenylalaninyl- D-prolinol ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl]-L-phenylalanine- N- (3- (2-pyrrolidone) propyl) amide sodium salt ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl] -L-phenylalanine- <BR> <BR> <BR> N- (3- (2-pyrrolidone) propyl) amide ; <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methylsuccinyl] -L-phenylalanine- N- (3- (2-pyrrolidone) propyl) amide or a salt thereof ; N2- [4- (N-Hydroxyamino) -3S- (4-hydroxyphenylthiomethyl) -2R- isobutylsuccinyl] -N6-tert-butyloxycarbonyl-L-lysine-N 1-methylamide ; N2- [4- (N-Hydroxyamino) -3S- (4-hydroxyphenylthiomethyl) -2R- <BR> <BR> <BR> isobutylsuccinyl] -N6-tert-butyloxycarbonyl-N6-(4-hydroxyphenylthiomethyl)-L- lysine-N 1 -methylamide; N2- [4-(N-Hydroxyamino)-3 S -(2-thienylthiomethyl)-2R-isobutylsuccinyl] - N6-tert-butyloxycarbonyl-L-lysine-N 1-methylamide ; N2- [4- (N-Hydroxyamino) -3S- (4-hydroxyphenylthiomethyl) -2R- isobutylsuccinyl] -O-tert-butyl-L-threonine-N 1-methylamide ; N2- [4- (N-Hydroxyamino) -3S- (4-hydroxyphenylthiomethyl) -2R- isobutylsuccinyl]-L-glutamine-N 1,N5-dimethylamide; <BR> <BR> <BR> N2- [4- (N-Hydroxyamino) -3S- (4-hydroxyphenylsulphonylmethyl) -2R- <BR> <BR> <BR> <BR> <BR> isobutylsuccinyl]-N6-acetyl-L-lysine-N 1 -methylamide; 3R-(3-Methoxycarbonyl-1S-methylcarbamoyl-propylcarbamoyl)- 5-methyl-2S-2-propenyl-hexanohydroxamic acid ; 3R-(1S-Methylcarbamoyl-2-thien-2-yl-ethylcarbamoyl)-5-methyl -2S- 2-propenyl-hexanohydroxamic acid ; 3R-(3-Methyl-1S-methylcarbamoyl-butylcarbamoyl)-5-methyl-2S- 2-propenyl-hexanohydroxamic acid ; 2 S-[1 S-Methylcarbamoyl-2-oxadiazol-5 -yl -ethylcarbamoyl)-5 -methyl-2S- 2-propenyl-hexanohydroxamic acid ;

[4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-(4-oxymethylcarbo xylic acid) phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-(4-oxymethylcarbo xy-N- methylamide) phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-(4-oxymethylcarbo xy-beta- <BR> <BR> <BR> <BR> alanine) phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L- (4-oxymethylcarboxyglycine)phenylalanine-N-methylamide; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-(4-oxymethylcarbo xy-N- benzylamide) phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-(4-cyano)phenylal anine-N- <BR> <BR> <BR> <BR> methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L- (4-acetamido) - <BR> <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-<BR> <BR> <BR> <BR> <BR> <BR> (4-oxymethylcarboxamide) -henylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (2-thienylthiomethylsuccinyl] -L- <BR> <BR> <BR> <BR> <BR> <BR> <BR> (4-N-acetylamino) -henylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutyl-3S-(2-thienylthiomethylsucci nyl]-L- (4-N-methylsuccinylamide)phenylalanine-N-methylamide; <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (4-aminophenylthiomethyl) - <BR> <BR> <BR> <BR> <BR> <BR> succinyl] -L- (4-N- (methylsuccinylamide) phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (4- <BR> <BR> <BR> <BR> <BR> <BR> aminophenylthiomethylsuccinyl] -L- (4-N- (4- (4-oxobutanoic acid) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> aminophenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (4-hydroxyphenylthiomethyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> succinyl] -L- (4-N-methylsuccinylamido) phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (4-hydroxyphenylthiomethyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> succinyl] -L- (4-N- (4- (4-oxobutanoic acid) aminophenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (2-thienylthiomethyl) -succinyl] -L- (4-oxymethylcarboxymethyl)phenylalanine-N-methylamide; <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(2-thienylthiomethyl)-succinyl]-L- <BR> <BR> <BR> <BR> <BR> <BR> <BR> (4-N- (oxymethylcarboxylic acid) phenylalanine-N-methylamide ;

[4-(N-Hydroxyamino)-2R-isobutyl-3 S-(2-thienylthiomethyl)-succinyl]-L- 4-oxymethylcarboxyglycyl methyl ester) -phenylalanine-N-methylamide ; [4- (N-Hydroxyamino) -2R-isobutyl-3S- (2-thienylthiomethyl) -succinyl] -L- 4-oxymethylcarboxyglycine)phenylalanine-N-methylamide; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl-succinyl] -L- 4- (oxymethylcarboxyglycyl methyl ester) -phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-methyl)-succinyl]-L- 4-(oxymethylcarboxyglycine)-phenylalanine-N-methylamide; <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-4-oxymethylnitrile)- <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-3-(1 -(2- <BR> <BR> <BR> <BR> <BR> <BR> methyloxycarbonyl) -ethyl) -4-methoxyphenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-3- (hydroxymethyl) - <BR> <BR> <BR> <BR> <BR> 4-methoxyphenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-3-methyl- 4-methoxyphenylalanine-N-methylamide ; 2-[Benzyl-(octane-1-sulfonyl)-amino]-N-hydroxy-acetamide; <BR> <BR> <BR> <BR> N-Hydroxy-2-[(2-methoxy-benzyl)-(octane- 1 -sulfonyl)-amino]-acetamide; <BR> <BR> <BR> <BR> <BR> <BR> 2-[(2-Ethoxy-benzyl)-(octane- 1 -sulfonyl)-amino]-N-hydroxy-acetamide; N-Hydroxy-2-[(naphthalen-2-yl-methyl)-(octane-1-sulfonyl)-am ino]- acetamide ; 2-[(4-Chloro-benzyl)-(octane-1-sulfonyl)-amino]-N-hydroxy-ac etamide; N2-[3 S-Hydroxy-4-(N-hydroxyamino)-2R-isobutylsuccinyl]-L-leucine- N 1 -methylamide ; N2-[3 S-Hydroxy-4-(N-hydroxyamino)-2R-isobutylsuccinyl)]-5-methyl- L- glutamic acid-N1-methylamide; N2- [3 S -Hydroxy-4-(N-hydroxyamino)-2R-isobutylsuccinyl)] -L- phenylalanine-N 1-methylamide ; <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(thienylthiomethyl)succinyl] -L- <BR> <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S-phenylthiomethyl) succinyl] -L- <BR> <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ;

2S-(4-Methoxyphenylsulfanylmethyl)-3R-(2-phenyl- 1 S-methylcarbamoyl- <BR> <BR> <BR> <BR> <BR> ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2S-(3 -Chlorophenylsulfanylmethyl)-3R-(2-phenyl- 1 S-methylcarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S- (Phenylsulfanylmethyl) -3R- (2-phenyl-1 S- (pyrid-3- ylmethylcarbamoyl) -ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(3-Methylphenylsulfanylmethyl)-3R-(2-phenyl-1S-methylcarb amoyl- ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S- (Thien-2-ylsulfanylmethyl) -3R- (2- (4-carboxymethoxyphenyl) -1 S- <BR> <BR> <BR> <BR> methylcarbamoyl-ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2 S-(Thien-2-ylsulfanylmethyl)-3 R-(2-phenyl- 1 S-(pyrid-3 - <BR> <BR> <BR> <BR> <BR> <BR> ylmethylcarbamoyl) -ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxyphenylsulfanylmethyl)-3R-(2-phenyl-1S-(pyrid-3- <BR> <BR> <BR> <BR> ylmethylcarbamoyl) -ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2S- (Thien-2-ylsulfanylmethyl) -3R- (2-naph-2-yl-lS-methylcarbamoyl- ethylcarbamoyl) -5-methyl-hexanohydroxamicacid ; 2S- (4-Hydroxyphenylsulfanylmethyl) -3R- (2R-hydroxy-1 S- methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxyphenylsulfanylmethyl)-3R-(5-acetamido-1S- methylcarbamoyl-pentylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxyphenylsulfanylmethyl)-3R-(3-[1,1- dimethylethoxycarbonyl] -lS-methylcarbamoyl-propylcarbamoyl) -5-methyl- hexanohydroxamic acid ; 2S- (Thien-2-ylsulfonylmethyl) -3R- (2-phenyl-1 S-methylcarbamoyl- <BR> <BR> <BR> <BR> ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> 3S- (2- [4-Acetamido-phenyl] -lS-methylcarbamoyl-ethylcarbamoyl) - 5-methyl-hexanohydroxamic acid ; 2S-(4-Phthalimido-butyl)-3R-(3-methyl-1S- <BR> <BR> <BR> <BR> ethoxycarbonylmethylcarbamoyl-butylcarbamoyl) -5-methyl-hexanohydroxamic <BR> <BR> <BR> <BR> <BR> <BR> acid ; 3R-(2-[4-Methoxy-phenyl]-1S-methylcarbamoyl-ethylcarbamoyl)- 2S,5-dimethyl-hexanohydroxamic acid;

3R-(2-Phenyl- 1 S-[2-oxo-pyrolid- 1 -yl]-propylcarbamoyl-ethylcarbamoyl)- 5-methyl-hexanohydroxamic acid ; 3R-(2-[4-Methoxy-phenyl]-1S-methylcarbamoyl-ethylcarbamoyl)- 5-methyl-hexanohydroxamic acid ; 3R-(2-Phenyl-1S-[pyrid-3-ylmethylcarbamoyl]-ethylcarbamoyl)- 5-methyl- hexanohydroxamic acid ; 3R-(2,2-Dimethyl-1S-methylcarbamoyl-propylcarbamoyl)-5-methy l- hexanohydroxamic acid ; Isobutylmalonoyl-L-alanine-furfurylamide hydroxamate ; 2-Isobutyl-3-carbonyl-3'-(4-acetylaniline)propionic acid; N-Benzyloxycarbonyl-a-phosphonoglycyl-L-alanine furfurylamide ; <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (phenylthiomethyl) succinyl] -L- <BR> <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(4-methoxyphenylthiomethyl)- succinyl] -L-phenylalanine-N-methylamide; <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- (4-hydroxyphenylthiomethyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> succinyl] -L-phenylalanine-N-methylamide; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(2,4-dimethylphenylthiomethyl)- succinyl] -L-phenylalanine-N-methylamide; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(3-bromophenylthiomethyl)- <BR> <BR> <BR> <BR> succinyl] -L-phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3 S- (3 -chlorophenylthiomethyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> succinyl] -L-phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(3-methylphenylthiomethyl)- succinyl] -L-phenylalanine-N-methylamide ; [4-(N-Hydroxyamino)-2R-isobutyl-3 S-(4-(N-acetyl)-amino- <BR> <BR> <BR> <BR> phenylthiomethyl) succinyl] -L-phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutyl-3 S-phenylsulphinylmethylsuccinyl]-L- <BR> <BR> <BR> <BR> <BR> <BR> <BR> phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3R- (3-Methoxycarbonyl-1 S-methylcarbamoyl-propylcarbamoyl) - 5-methyl-2S-phenylsulfanylmethyl- hexanohydroxamic acid ; 3R-(3-Methoxycarbonyl-1S-methylcarbamoyl-propylcarbamoyl)- 5-methyl-2S-(thien-2-ylsulfanylmethyl)-hexanohydroxamic acid;

2S- (4-Methoxy-phenylsulfanylmethyl) -3R- (3-methoxycarbonyl-1 S- <BR> <BR> <BR> <BR> <BR> <BR> methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamicacid ; 2S- (4-Amino-phenylsulfanylmethyl) -3R- (3-methoxycarbonyl-1 S- <BR> <BR> <BR> <BR> methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> 2S-(Ethylsulfanylmethyl)-3R-(3-methoxycarbonyl- 1 S-methylcarbamoyl- propylcarbamoyl) -5-methyl-hexanohydroxamicacid ; <BR> <BR> <BR> <BR> 2S-(Acetylsulfanylmethyl)-3R-(3-methoxycarbonyl- 1 S-methylcarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> 2S-(Benzylsulfanylmethyl)-3R-(3-methoxycarbonyl- 1 S-methylcarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(tert-Butylsulfanylmethyl)-3R-(3-methoxycarbonyl-1S- methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-Thiomethyl-3R- (3-methoxycarbonyl-1 S-methylcarbamoyl- propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxy-phenylsulfanylmethyl)-3R-(2-tert-butoxycarbony l-1S- methylcarbamoyl-ethylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxy-phenylsulphinylmethyl)-3R-(3-methoxycarbonyl-1 S- methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; 2S-(4-Hydroxy-phenylsulphonylmethyl)-3R-(3-methoxycarbonyl-1 S- <BR> <BR> <BR> <BR> methylcarbamoyl-propylcarbamoyl) -5-methyl-hexanohydroxamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-phenylalanine-N- [1 -(2- <BR> <BR> <BR> <BR> <BR> aminoethyl) -pyrrolidine] amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4-(N-Hydroxyamino)-2R-isobutylsuccinyl]-L-phenylalanine-N-[ 1 -(3 - <BR> <BR> <BR> <BR> <BR> <BR> aminopropyl) -2 (RS) -methylpiperidine] amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N- [2- (2- <BR> <BR> <BR> <BR> <BR> aminoethyl)- 1 -methylpyrrole]amide; [4-(N-Hydroxyamino)-2R-isobutylsuccinyl] -L-phenylalanine-N-(3 - <BR> <BR> <BR> <BR> aminomethylpyridine) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> (2-aminomethylpyridine) amide ; <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-phenylalanine-N- (4-aminomethylpyridine)amide;

[4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> (1 -(3-aminopropyl)-imidazole)amide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (RS) -isobutylsuccinyl] -L-phenylalanine-N- <BR> <BR> <BR> <BR> <BR> <BR> <BR> (2-aminomethylbenzimdazole) amide ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S-methylsuccinyl] -L-phenylalanine-<BR> <BR> <BR> <BR> <BR> <BR> <BR> N- [4- (2-aminoethyl) -morpholino] amide ;<BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N-<BR> <BR> <BR> <BR> <BR> <BR> [4- (2-aminoethyl) -morpholine] amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2 (R, S) -isobutylsuccinyl] -L-phenylalanine-N- [2-(2-aminoethyl)-pyridine]amide; [4-(N-Hydroxyamino)-2(R,S)-isobutylsuccinyl]-L-phenylalanine -N- <BR> <BR> <BR> <BR> [4- (2-aminopropyl) -morpholine] amide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N- (3-aminomethylpyridine) amide hydrochloride ; and [4- (N-Hydroxyamino) -2R-isobutylsuccinyl] -L-phenylalanine-N- [4- (2-aminoethyl) -morpholine] amide hydrochloride.

In a preferred embodiment, tricyclic butyric acid derivatives which are inhibitors of matrix metalloprotienases are employed in the instant invention. A preferred group of tricyclic butyric acid derivatives are defined by the formula : wherein one of R¹ or wherein X is O, N-OR6 wherein R6 is hydrogen, - (CH2) n-aryl wherein n is zero or an integer of 1 to 5, alkyl, or -(CH2)n-cycloalkyl wherein n is as defined above, or

N-N-R6 wherein R6a R6 and R6a are each the same or different and each is as defined above for R6 ; R and Ra are each the same or different and each is hydrogen, - (CH2) n-aryl wherein n is as defined above, - (CH2) n-heteroaryl wherein n is as defined above, -(CH2)p-R7-(CH2)q-aryl wherein R7 is O or S and p or q is each zero or an integer of 1 to 5 and the sum of p + q equals an integer of 5, -(CH2)p-R7~(CH2)q-heteroaryl wherein p, q, and R7 are as defined above, alkyl, -(CH2)n-cycloalkyl wherein n is as defined above, or -(CH2)r-NH2 wherein r is an integer of 1 to 9 ; a is zero or an integer of 1 to 3 ; R5 is OH, OR6 wherein R6 is as defined above, wherein R6 and R6a are each the same or different and are as defined above for R6, or NH-OR6 wherein R6 is as defined above ; R3 and R4 are each the same or different and each is hydrogen, alkyl, N02, halogen, OR6 wherein R6 is as defined above, CN, CO2R6 wherein R6 is as defined above, S03R6 wherein R6 is as defined above, CHO,

wherein R is as defined above, wherein R6 and R6a are each the same or different and are as defined above for R6, or wherein R6 and R6a are each the same or different and are as defined above for R6 ; W, W 1, Z, and Z I are each the same or different and each is CR3 wherein R3 is as defined above, or N providing only one of W or W l is N and/or only one of Z or Z I is N ; and Y is -N- wherein R R is as defined above, -o- -S- (O) m- wherein -CH2-, m is zero or an integer of 1 or 2, - C- wherein R6 N-OR6 is as defined above, - CH- wherein R6 I OR6 is as defined above,

- C- wherein R6 N-N-R6 R6a and R6a are the same or different and are as defined above for R6, - C-N- wherein o R6 R6 is as defined above, - N-C- wherein R60 -C-O-, II -O-C-, II R6 is as defined above, -CH2-O-, -O-CH2-, -CH2-S(O)m- wherein m is as defined above, -S(O)m-CH2- wherein m is as defined above, -CH2-N- wherein R6 R6 is as defined above, -N-CH2- wherein R6 R6 is as defined above, - CH=N-, or - N=CH- ; with the proviso that when X is O, and R5 is not NH-OR6, at least one of R or Ra is not hydrogen ; and corresponding isomers thereof ; or a pharmaceutically acceptable salt thereof.

Typical compounds from this class include : 4-Dibenzofuran-2-yl-4-hydroxyimino-butyric acid ;

2-(2-Dibenzofuran-2-yl-2-hydroxyimino-ethyl)-4-methyl-pentan oic acid; 2-(2-Dibenzofuran-2-yl-2-hydroxyimino-ethyl)-5-phenyl-pentan oic acid; 4-Dibenzofuran-2-yl-4-hydroxyimino-2-phenethyl-butyric acid ; 5- (4-Chloro-phenyl) -2- (2-dibenzofuran-2-yl-2-hydroxyimino-ethyl) - pentanoic acid ; 2- (2-Dibenzofuran-2-yl-2-hydroxyimino-ethyl) -5- (4-fluoro-phenyl) - pentanoic acid ; 2- (2-Dibenzofuran-2-yl-2-hydroxyimino-ethyl) -5- (4-methoxy-phenyl) - pentanoic acid ; 2-(2-Dibenzofuran-2-yl-2-hydroxyimino-ethyl)-5-p-tolyl-penta noic acid; <BR> <BR> <BR> <BR> 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -5-methyl-hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -6-phenyl-hexanoic acid ; <BR> <BR> <BR> <BR> <BR> 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -5-phenyl-pentanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6- (4-Chloro-phenyl) -3- (dibenzofuran-2-yl-hydroxyimino-methyl) - hexanoic acid ; 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -6- (4-fluoro-phenyl) - hexanoic acid ; 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -6- (4-methoxyphenyl) - hexanoic acid ; and 3- (Dibenzofuran-2-yl-hydroxyimino-methyl) -6-p-tolyl-hexanoic acid ; and corresponding isomers thereof ; or a pharmaceutically acceptable salt thereof.

Tricyclic butyric acids having an a-amino substituent are defined by the formula : wherein : X is 0, NOR9, S, OH, SH, or

R7 and R7a independently are hydrogen, C1-C20 alkyl or substituted C1-C20 alkyl, (CH2) 0-6-arYl, (CH2)0-6-heteroaryl, or (CH2)0-6-cycloalkyl; R 1 and R2 independently are hydrogen, C 1 -C20 alkyl or substituted C 1 -C20 alkyl, halo, N02, CN, CHO, COR6, COOR6, S03R6, OR6, CONR4R5, (CH2)0-6-aryl, (CH2)0-6-heteroaryl, or (CH2)0-6-cycloalkyl; R6 is hydrogen, C1-C20 alkyl or substituted C 1 -C20 alkyl; aryl is phenyl or substituted phenyl ; R3 is hydroxy, O-C1-C20 alkyl or substituted O-C I -C20 alkyl, O-(CH2)1-3 aryl, or NHOR6 ; R4 and RS independently are hydrogen,

C1-C20 alkyl or substituted C1-C20 alkyl, (CH2)0-6-aryl, (CH2)0-6-heteroaryl; or one of R4 and R5 is hydrogen and the other is: COR8, <BR> <BR> <BR> <BR> CSRg, <BR> <BR> <BR> <BR> <BR> CONRgR9, CSNR8R9, COORg, COSRg, -O-, -S(O)0,1 or 2, -CH2-,

-CH2-O-, -O-CH2-, -CH2S(O)0,1 or 2, -S(O)0,1 or 2-CH2-, - CH=N, or -N=CH-; R8 and R9 independently are hydrogen, C1-C20 alkyl or substituted C1-C20 alkyl

(CH2) 0-6-aryl, (CH2)0-6-heteroaryl, or (CH2)0-6-cycloalkyl; W, W1, Z, and Z1 independently are CR1 or N ; and the pharmaceutically acceptable salts, isomers, stereoisomers, and solvates thereof.

Specific examples of compounds to be employed in the present method include : (S)-4-Dibenzofuran-2-yl-4-oxo-2-(2,2,2-trifluoroacetylamino) -butyric acid ; (R)-4-Dibenzofuran-2-yl-4-oxo-2-(2,2,2-trifluoroacetylamino) -butyric acid ; (S)-2-Amino-4-dibenzofuran-2-yl-4-oxo-butyric acid; (S)-2-Acetylamino-4-dibenzofuran-2-yl-4-oxo-butyric; (S)-4-Dibenzofuran-2-yl-2- [3 -(2,6-diisopropyl-phenyl)-ureido] -4-oxo- butyric acid ; (S)-2-Benzoylamino-4-dibenzofuran-2-yl-4-oxo-butyric acid; <BR> <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2-phenylacetylamino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2- (3-phenyl-propionylamino) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2- (7-phenyl-heptanoylamino) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> (S)-2-[(Biphenyl-4-carbonyl)-amino] -4-dibenzofuran-2-yl -4-oxo-butyric <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2- (dodecanoylamino) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2- (dodecanoyl-amino) -butyric acid ; (S)-4-Dibenzofuran-2-yl-4-oxo-2-(2,2,2-trifluoroacetylamino) -butyric acid ; (R)-4-Dibenzofuran-2-yl-4-oxo-2-(2,2,2-trifluoroacetylamino) -butyric acid ; (S)-2-Amino-4-dibenzofuran-2-yl-4-oxo-butyric acid; (S)-2-Acetylamino-4-dibenzofuran-2-yl-4-oxo-butyric acid; (S) -4-Dibenzofuran-2-yl-2- [3- (2, 6-diisopropyl-phenyl) -ureido] -4-oxo- butyric acid ;

(S)-2-Benzoylamino-4-dibenzofuran-2-yl-4-oxo-butyric acid; <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2-phenylacetylamino-butyric acid ; <BR> <BR> <BR> (S) -4-Dibenzofuran-2-yl-4-oxo-2- (3-phenyl-propionylamino) -butyric acid ; (S)-4-Dibenzofuran-2-yl-4-oxo-2-(7-phenyl-heptanoylamino)-bu tyric acid; (S) -2- [ (Biphenyl-4-carbonyl) -amino] -4-dibenzofuran-2-yl-4-oxo-butyric acid ; (S) -4-Dibenzofuran-2-yl-4-oxo-2- (octanoylamino) -butyric acid ; and (S)-4-Dibenzofuran-2-yl-4-oxo-2-(dodecanoylamino)-butyric acid.

Tricyclic sulfonamide matrix metalloproteinase inhibitors include compounds of the formula wherein M is a natural (L) alpha amino acid derivative having the structure X is O, S, S (O) n, CH2, CO, or NH ; R is a side chain of a natural alpha amino acid ; R1 is Cl-ces alkoxy, hydroxy, or -NHOR5 ; R2 and R4 are independently hydrogen, -C 1 -Cs alkyl, -NO2, halogen, -OR5, -CN, -C02R5, -S03R5, -CHO, -COR5, -CONR5R6, - (CH2) nNR5R6, -CF3, or -NHCoR5; each R5 and R6 are independently hydrogen or C I -C5 alkyl ; and n is 0 to 2, and the pharmaceutically acceptable salts, ester, amides, and prodrugs thereof.

Specific compounds from this class to be employed include : (L)-2-(Dibenzofuran-2-sulfonylamino)-4-methyl-pentanoic acid; (L) -2- (Dibenzofuran-2-sulfonylamino) -3-methyl-pentanoicacid ; (L) -2- (Dibenzofuran-2-sulfonylamino) -3-phenyl-propionicacid ;

(L)-2-(Dibenzofuran-2-sulfonylamino)-propionic acid; (L)-2-(Dibenzofuran-2-sulfonylamino)-3-methyl-butyric acid; (Dibenzofuran-2-sulfonylamino) -acetic acid ; (L)-2-(Dibenzofuran-2-sulfonylamino)-succinic acid; <BR> <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -3-tritylsulfanyl-propionic acid ; <BR> <BR> <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -3-mercapto-propionic acid ; (L)-2-(Dibenzofuran-2-sulfonylamino)-3-methyl-pentanoic acid hydroxyamide ; <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -4-methyl-pentanoic acid ; <BR> <BR> <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -3-methyl-pentanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -3-phenyl-propionic acid ; (L)-2-(Dibenzofuran-2-sulfonylamino)-propionic acid; <BR> <BR> <BR> <BR> (L) -2- (Dibenzofuran-2-sulfonylamino) -3-methyl-butyric acid ; <BR> <BR> <BR> <BR> <BR> (Dibenzofuran-2-sulfonylamino) -acetic acid ; (L)-2-(Dibenzofuran-2-sulfonylamino)-succinic acid; (L) -2- (Dibenzofuran-2-sulfonylamino) -3-tritylsulfanyl-propionic acid ; (L)-2-(Dibenzofuran-2-sulfonylamino)-3-mercapto-propionic acid; and (L)-2-(Dibenzofuran-2-sulfonylamino)-3-methyl-pentanoic acid hydroxyamide.

Additional tricyclic sulfonamides are defined by the formula : wherein Q is an un-natural amino acid ; X is O, S, S (O) n, CH2, CO, or NH ; R2 and R4 are independently hydrogen, Cl-C5 alkyl, -N02, halogen, -OR5, -CN, - C02R5, -S03R5, -CHO, -COR5, -CONR5R6, - (CH2) nNR5R6, -CF3, or -NHCoR5; each R5 and R6 are independently hydrogen or C l-Cs alkyl; and

n is 0 to 2, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.

Specific examples of such compounds include : (S) -2- (Dibenzofuran-2-sulfonylamino) -4-phenyl-butyric acid ; 2 (S)-3-[(Dibenzofuran-2-sulfonylamino)-methyl]-5-methyl-hexan oic acid; (S) -2- (Dibenzofuran-2-sulfonylamino) -4-phenyl-butyric acid ; and 2(S)-3-[(Dibenzofuran-2-sulfonylamino)-methyl]-5-methyl-hexa noic acid.

Another general class of matrix metalloproteinase inhibitors, which are useful to treat and prevent heart failure and ventricular dilatation, are biphenyl butyric acid derivatives, including compounds of the formula : wherein R and R 1 are the same or different and are hydrogen, alkyl, halogen, nitro, cyano, trifluoromethyl, -OR6 wherein R6 is hydrogen, alkyl, aryl, arylalkyl, heteroaryl, or cycloalkyl, wherein R6 and R6a are the same or different and are as defined above for R6,

wherein R6 is as defined above, wherein R6 is as defined above, wherein R6 is as defined above, -SR6 wherein R6 is as defined above, wherein R6 is as defined above, -CH2-OR6 wherein R6 is as defined above, wherein R6 and R6a are the same or different and are as defined above for R6, wherein R6 and R6a are the same or different and are as defined above for R6, wherein R6 is as defined above, cycloalkyl, or heteroaryl, with the proviso that R and R I are not both hydrogen ; R2 is -OR6 wherein R6 is as defined above, or wherein R6 and R6a are the same or different and are as defined above for R6 ;

R3, R3a, R4, and R4a are the same or different and are hydrogen, fluorine, alkyl, - (CH2) n-aryl wherein n is an integer from 1 to 6, - (CH2) n-heteroaryl wherein n is as defined above, - (CH2) n-cycloalkyl wherein n is as defined above, -(CH2)p-X-(CH2)q-aryl wherein X is O, S, SO, S02, or NH, and p and q are each zero or an integer of 1 to 6, and the sum of p + q is not greater than six, -(CH2)p-X-(CH2)q-heteroaryl wherein X, p, and q are as defined above, or - (CH2) n-R7 wherein R7 is N-phthalimido, N-2, 3-naphthyimido, - OR6 wherein R6 is as defined above, wherein R6 and R6a are the same or different and are as defined above for R6, - SR6 where R6 is as defined above, wherein R6 is as defined above, wherein R6 is as defined above, wherein R6 is as defined above,

wherein R6 and R6a are the same or different and are as defined above for R6, wherein R6 is as defined above, wherein R6 is as defined above, wherein R6 is as defined above, or wherein R6 and R6a are the same or different and are as defined above for R6, and n is as defined above ; R5 is OH or SH ; with the proviso that R3, R3a, R4, and R4a are hydrogen or at least one of R3, R3a, R4, or R4a is fluorine ; and corresponding isomers thereof ; or a pharmaceutically acceptable salt thereof.

Typical compounds from this class that are routinely utilized to treat atherosclerosis include : <BR> <BR> <BR> <BR> 4- (4'-Chloro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 4- (4'-Bromo-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; 4-(4'-Chloro-biphenyl-4-yl)-4-(dimethylhydrazono)-butyric acid; <BR> <BR> <BR> <BR> 4- (4'-Fluoro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -4-hydroxy-butyric acid ; <BR> <BR> <BR> <BR> <BR> 4- (4'-Bromo-2'-fluoro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -3-fluoro-4-oxo-butyric acid ; 4-(2',4'-Dichloro-biphenyl-4-yl)-4-hydroxyimino-butyric acid;

4-(2',4'-Difluoro-biphenyl-4-yl)-4-hydroxyimino-butyric acid; <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -4-hydroxyimino-2-fluoro-2- (3- <BR> <BR> <BR> <BR> <BR> phenylpropyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2 -fluoro-2 -(2 - <BR> <BR> <BR> <BR> <BR> phenylethyl) -butyric acid ; ()-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-(3- <BR> <BR> <BR> <BR> phthalimidopropyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -4-hydroxyimino-2-fluoro-2- <BR> <BR> <BR> <BR> <BR> (phenylthiomethyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> 4- (4'-Chloro-2'-fluoro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; 4-Hydroxyimino-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid; 4-(4'-Chloro-biphenyl-4-yl)-4-methoxyimino-butyric acid; <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-2-fluoro-2-{2-(1,3-dioxo-1,3 -dihydro- <BR> <BR> <BR> <BR> <BR> isoindol-2-yl) -ethyl] -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-(1 H-indol- <BR> <BR> <BR> <BR> <BR> 3-yl) methyl-butyric acid ; <BR> <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2 -fluoro-2-methyl- butyric acid ; <BR> <BR> <BR> () -2- [2- (4'-Chloro-biphenyl-4-yl) -2-hydroxyiminoethyl] -2-fluoro- <BR> <BR> <BR> <BR> <BR> 6-phenyl-hexanoic acid ; <BR> <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-2-fluoro-2-[2-(1,3-dioXo- 1,3-dihydro- <BR> <BR> <BR> <BR> <BR> benzo [F] isoindol-2-yl) -ethyl] -4-hydroxyimino-butyricacid ; <BR> <BR> <BR> <BR> <BR> () -2- [2- (4'-Chloro-biphenyl-4-yl) -2-hydroxyiminoethyl] -6- (1, 3-dioxo- <BR> <BR> <BR> <BR> <BR> 1, 3-dihydro-isoindol-2-yl) -2-fluoro-hexanoic acid ; <BR> <BR> <BR> <BR> <BR> (+)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-[2 -(phenyl- <BR> <BR> <BR> <BR> <BR> ethylcarbamoyl) -ethyl] -butyric acid ; <BR> <BR> <BR> <BR> <BR> 4- (4'-Chloro-biphenyl-4-yl) -3, 3-difluoro-4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-3,3-dimethyl-2-fluoro-4-hydr oxyimino- butyric acid ; ()-4-(4'-Chloro-biphenyl-4-yl)-2,2-dimethyl-3-fluoro-4-hydro xyimino- butyric acid ;

4- (4'-Chloro-biphenyl-4-yl) -2, 2-difluoro-4-hydroxyimino-butyric acid ; and 4- (4'-Chloro-biphenyl-4-yl) -2, 2, 3, 3-tetrafluoro-4-hydroxyimino-butyric acid.

A compound selected from the group consisting of : <BR> <BR> <BR> <BR> 4- (4'-Chloro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (4'-Bromo-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (4'-Chloro-biphenyl-4-yl) -4- (dimethylhydrazono) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4-(4'-Fluoro-biphenyl-4-yl)-4-hydroxyimino-butyric acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -4-hydroxy-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- (4'-Bromo-2'-fluoro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biphenyl-4-yl) -3-fluoro-4-oxo-butyric acid ; 4-(2',4'-Dichloro-biphenyl-4-yl)-4-hydroxyimino-butyric acid; 4-(2',4'-Difluoro-biphenyl-4-yl)-4-hydroxyimino-butyric acid; <BR> <BR> <BR> <BR> () -4- (4'-Chloro-biPhenyl-4-yl) -4-hydroxyimino-2-fluoro-2- (3- <BR> <BR> <BR> <BR> <BR> <BR> <BR> phenylpropyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-(2 - <BR> <BR> <BR> <BR> <BR> <BR> <BR> phenylethyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (+)-4-(4'-Chloro-biphenyl -4-yl)-4-hydroxyimino -2 -fluoro-2 -(3 - <BR> <BR> <BR> <BR> <BR> <BR> <BR> phthalimidopropyl) -butyric acid ; ()-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2- <BR> <BR> <BR> <BR> (phenylthiomethyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 4- (4'-Chloro-2'-fluoro-biphenyl-4-yl) -4-hydroxyimino-butyric acid ; 4-Hydroxyimino-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid; 4-(4'-Chloro-biphenyl-4-yl)-4-methoxyimino-butyric acid; <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-2-fluoro-2-[2-(1,3-dioXo- 1,3-dihydro- <BR> <BR> <BR> <BR> <BR> <BR> <BR> isoindol-2-yl) -ethyl] -4-hydroxyimino-butyricacid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-(1 H-indol- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3-yl) methyl-butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2-me thyl- butyric acid ;

() -2- [2- (4'-Chloro-biphenyl-4-yl) -2-hydroxyiminoethyl] -2-fluoro- 6-phenyl-hexanoic acid ; <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-2-fluoro-2-[2-(1,3-dioXo- 1,3-dihydro- <BR> <BR> <BR> <BR> <BR> benzo[F]isoindol-2-yl)-ethyl]-4-hydroxyimino-butyric acid; <BR> <BR> <BR> <BR> <BR> () -2- [2- (4'-Chloro-biphenyl-4-yl) -2-hydroxyiminoethyl] -6- (1, 3-dioxo- <BR> <BR> <BR> <BR> <BR> 1,3-dihydro-isoindol-2-yl)-2-fluoro-hexanoic acid; <BR> <BR> <BR> <BR> <BR> (_)-4-(4'-Chloro-biphenyl-4-yl)-4-hydroxyimino-2-fluoro-2 -[2 -(phenyl- <BR> <BR> <BR> <BR> <BR> ethylcarbamoyl) -ethyl] -butyric acid ; <BR> <BR> <BR> <BR> <BR> 4- (4'-Chloro-biphenyl-4-yl) -3, 3-difluoro-4-hydroxyimino-butyric acid ; <BR> <BR> <BR> <BR> <BR> (#)-4-(4'-Chloro-biphenyl-4-yl)-3,3-dimethyl-2-fluoro-4-hydr oxyimino- butyric acid ; ()-4-(4'-Chloro-biphenyl-4-yl)-2,2-dimethyl-3-fluoro-4-hydro xyimino- butyric acid ; 4- (4'-Chloro-biphenyl-4-yl) -2, 2-difluoro-4-hydroxyimino-butyric acid ; and 4- (4'-Chloro-biphenyl-4-yl) -2, 2, 3, 3-tetrafluoro-4-hydroxyimino-butyric acid.

Biphenyl sulfonamides are also particularly good in the present method.

Such compounds include those of the formula : wherein : R1 is Ci-Ce alkyi, halo, nitro, NR4R5, cyano, OR4, and COOL4; R2 is Cj-Cg alkyi, optionally substituted by phenyl, substituted phenyl, NR4R5, OR6, carboxy, carboxamido, thio, methylthio, indole, imidazole, phthalimido, phenyl, and substituted phenyl ; R3 is OH, OC1-C6 alkyl, or NHOH; R4 is hydrogen, C1-C6 alkyl, or Cl-C6 alkanoyl;

R5 is hydrogen or C 1 -C6 alkyl; and R6 is hydrogen, C1-C6 alkyl, C1-C6 alkanoyl, phenyl, or substituted phenyl.

Specific compounds which can be employed include a compound of the above formula wherein R I is at the 47 position.

Another class of matrix metalloproteinase inhibitors useful in the present method are the heterocyclic substituted phenyl butyric acid derivatives, for example those defined by the formula : Ar is selected from phenyl, phenyl substituted with alkyl, N02, halogen, OR5 wherein R5is hydrogen or alkyl, CN, CO2R5 wherein R5 is as defined above, S03R5 wherein R5 is as defined above, CHO, COR5 wherein R5 is as defined above, CONHR5 wherein R5 is as defined above, or NHCOR5 wherein R5 is as defined above, 2-naphthyl, or heteroaryl ; R1 is selected from hydrogen, methyl, ethyl, N02,

halogen, OR5 wherein R5 is as defined above, CN, CO2R5 wherein R5 is as defined above, S03R5 wherein R5 is as defined above, CHO, or COR5 wherein R5 is as defined above; R2 and R3 are the same or different and independently selected from hydrogen, alkyl, -(CH2)v-aryl wherein v is an integer from 1 to 5, -(CH2)v-heteroaryl wherein v is as defined above, -(CH2)v-cycloalkyl wherein v is as defined above, - (CH2) p-X- (CH2) q-aryl wherein X is O or S and p and q is each zero or an integer of 1 to 5, and the sum of p + q is not greater than an integer of 5, -(CH2)p-X-(CH2)q-heteroaryl wherein X, p, and q are as defined above, -(CH2)tNR6R6a, wherein t is zero or an integer of from 1 to 9 and R6 and R6a are each the same or different and are as defined above for R5, -(CH2)VSR5, wherein v and R5 are as defined above, -(CH2)VCO2R5, wherein v and R5 are as defined above, or -(CH2)VCONR6R6a, wherein R6 and R6a are the same or different and are as defined above for R5 and v is as defined above; R3 is additionally -(CH2)rR7 wherein r is an integer from 1 to 5 and R7 is 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl, or 1, 3, -dihydro-1, 3-dioxo- benzo [f] isoindol-2-yl ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> YisCHorN;

Z is wherein R10 is as defined above for R2 and R3, and is independently the same or different from R2 and R3 provided that when Z is then R4 must be OH, C=O, C=NOR5 wherein R5 is as defined above, or C=N-NR6R6a wherein R6 and R6a are the same or different and are as defined above for R5 ; W is -CHRS wherein R5 is as defined above ; n is zero or an integer of 1 ; R4 is OH, NR6R6a wherein R6 and R6a are the same or different and are as defined above for R5, when R4is NR6R6a then Z must be C=O or NHOR9 wherein R9 is hydrogen, alkyl, or benzyl ; and corresponding isomers thereof ; or a pharmaceutically acceptable salt thereof.

Especially preferred MMP inhibitors have the formula Ar is selected from phenyl, phenyl substituted with alkyl, N02, halogen, OR. 5 wherein R5 is hydrogen or alkyl, CN, CO2R5 wherein R5 is as defined above,

S03R5 wherein R5 is as defined above, CHO, COR5 wherein R5 is as defined above, CONHR5 wherein R5 is as defined above, or NHCOR5 wherein R5 is as defined above, 2-naphthyl, or heteroaryl ; Rl is selected from hydrogen, methyl, ethyl, N02, halogen, OR5 wherein R5 is as defined above, CN, CO2R5 wherein R5 is as defined above, S03R5 wherein R5 is as defined above, CHO, or COR5 wherein R5 is as defined above ; R2 and R3 are the same or different and independently selected from hydrogen, alkyl, -(CH2)v-aryl wherein v is an integer from 1 to 5, -(CH2)v-heteroaryl wherein v is as defined above, - (CH2) v-cycloalkyl wherein v is as defined above, -(CH2)p-X-(CH2)q-aryl wherein X is O or S and p and q is each zero or an integer of 1 to 5, and the sum of p + q is not greater than an integer of 5, -(CH2)p-X-(CH2)q-heteroaryl wherein X, p, and q are as defined above,

-(CH2)tNR6R6a, wherein t is zero or an integer of from 1 to 9 and R6 and R6a are each the same or different and are as defined above for R5, -(CH2)vSR5, wherein v and R5 are as defined above, -(CH2)vCO2R5, wherein v and R5 are as defined above, or -(CH2)VCONR6R6a, wherein R6 and R6a are the same or different and are as defined above for R5 and v is as defined above ; R3 is additionally -(CH2)rR7 wherein r is an integer from 1 to 5 and R7 is 1,3-dihydro- 1,3-dioxo-2H-isoindol-2-yl, or 1,3,-dihydro- 1,3-dioxo- benzo[f]isoindol-2-yl; YisCHorN; wherein R10 is as defined above for R2 and R3, and is independently the same or different from R2 and R3 provided that when then R4 must be OH, C=O, C=NOR5 wherein R5 is as defined above, or C=N-NR6R6a wherein R6 and R6a are the same or different and are as defined above for R5; W is -CHRS wherein R5 is as defined above ; n is zero or an integer of 1 ; R4 is OH, NR6R6a wherein R6 and R6a are the same or different and are as defined above for R5, when R4 is NR6R6a then Z must be C=O or NHOR9 wherein R9 is hydrogen, alkyl, or benzyl ;

and corresponding isomers thereof ; or a pharmaceutically acceptable salt thereof.

Preferred compounds to be employed include : 4-Oxo-4- [4- (4-phenyl-piperidin-1-yl) -phenyl] -butyric acid ; 4-Oxo-4-[4-(4-phenyl-piperidin-1-yl)-phenyl]-butyric acid, potassium salt ; <BR> <BR> <BR> N-Hydroxy-4-oxo-4- [4- (4-phenyl-piperidin-1-yl) -phenyl] -butyramide ; <BR> <BR> <BR> E/Z-4-Hydroxyimino-4-[4-(4-phenyl-piperidin-1-yl)-phenyl]-bu tyric acid; <BR> <BR> <BR> E/Z-4-Benzyloxyimino-4-[4-(4-phenyl-piperidin- 1 -yl)-phenyl]-butyric <BR> <BR> <BR> acid ; 4-Oxo-4-[4-(4-phenyl-piperazin-1-yl)-phenyl]-butyric acid; <BR> <BR> <BR> () 3-Methyl-5-oxo-5- [4- (4-phenyl-piperidin-1-yl) -phenyl] -pentanoic acid ; <BR> <BR> <BR> 4-Oxo-4- [4- (4-phenyl-piperidin-1-yl) -phenyl] -butyric acid ; <BR> <BR> <BR> 4-0xo-4- [4- (4-phenyl-piperidin-l-yl) -phenyl] -butyric acid, potassium salt ; <BR> <BR> <BR> N-Hydroxy-4-oxo-4-[4-(4-phenyl-piperidin- 1 -yl)-phenyl]-butyramide; <BR> <BR> <BR> E/Z-4-Hydroxyimino-4- [4- (4-phenyl-piperidin-1 -yl) -phenyl] -butyric acid ; E/Z-4-Benzyloxyimino-4- [4- (4-phenyl-piperidin-1-yl) -phenyl] -butyric acid ; 4-Oxo-4- [4- (4-phenyl-piperazin-1-yl) -phenyl] -butyric acid ; and () 3-Methyl-5-oxo-5- [4- (4-phenyl-piperidin-1-yl) -phenyl] -pentanoic acid.

A compound which is 4-oxo-4-[4-(4-phenyl-piperidin-1-yl)-phenyl]- butyric acid.

Similar compounds which are sulfonamide derivatives have the formula : wherein : Ar is selected from phenyl ; phenyl substituted with alkyl, -NO-2, halogen, -OR5, -CN, -C02R5, -S03R5, -CHO, -COR5, -CONHR5, -NHR5, or-NHCOR5; heteroaryl ; or 2-naphthyl ;

R1 is hydrogen, methyl, -N02, -Cl, -NH2, -NHC02CH3, -OH, or -CO2H; R2 and R3 are the same or different and are independently selected from hydrogen, alkyl, -(CH2)v-aryl, -(CH2)v-heteroaryl, -(CH2)v-cycloalkyl, - (CH2) p-X- (CH2) q-aryl, - (CH2) p-X- (CH2) q-heteroaryl, - (CH2) tNR6R6a, -(CH2)vR7, -(CH2)vCO2R5, -(CH2)vCONR6R6a, or-(CH2)vSR5; m is zero or 1 ; Y is CH or N ; provided that when m = 1, Y does not = N ; z is zero or 1 ; W is -CHR8 ; n is zero or 1 ; R4 is -OH, -NR6R6a, or-NHOR9; R5 is hydrogen or alkyl ; <BR> <BR> <BR> v is 1 to 5 ; <BR> <BR> <BR> <BR> X is 0 or S ; p and q are independently 1 to 5, provided that p + q is not greater than 5 ; t is 1 to 9 ; R6 and R6a are each the same or different and are hydrogen or alkyl ; R7 is 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl, or 1, 3-dihydro-1, 3-dioxo- benzo[f]isoindol-2-yl; R8 is hydrogen or alkyl ; and R9 is hydrogen, alkyl, or benzyl ; or a pharmaceutically acceptable salt thereof.

Specific sulfonamide derivatives to be employed in the present method include : <BR> <BR> <BR> <BR> [4-(4-Phenyl-piperidin-l-yl)-benzenesulfonylamino]-acetic acid; <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [4- (4-phenyl-piperidin-1 -yl) -benzenesulfonylamino] - acetamide ; 3-[4-(4-Phenyl-piperidin-l-yl)-benzenesulfonylamino]-propion ic acid;

(R)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; (S)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; (S)-3-Phenyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- propionic acid ; (R)-3-Phenyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyla mino]- propionic acid ; (S)-3 -(1 H-Indol-3 -yl)-2- [4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino]-propionic acid; () -5-Phenyl-2- [4- (4-phenyl-piperidin-1-yl) -benzenesulfonylamino] - pentanoic acid ; [4-(4-Phenyl-piperazin-1-yl)-benzene-sulfonylamino]-acetic acid; {Isobutyl-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyl]amino }-acetic acid ; (S)-4-Phenyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyla mino]- butyric acid ; (R)-2-[4-(4-Phenyl-piperidin- 1 -yl)-benzenesulfonylamino]-3- tritylsulfanyl-propionic acid, sodium salt ; (R)-3 -(1 H-Indol-3 -yl)-2- [4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino] -propionic acid, disodium salt, monohydrate ; (S)-2- {4-[-4-(4-Hydroxy-phenyl)-piperazin- 1 -yl] - benzenesulfonylamino}-3-phenyl-propionic acid; (S)-2- {4-[-4-(4-Chloro-phenyl)-piperazin- 1 -yl]- benzenesulfonylamino}-3-phenyl-propionic acid, hydrochloride ; (R)-3-Mercapto-2-[4-(4-phenyl-piperidin-1-yl)- benzenesulfonylamino] -propionic acid, trifluoracetic acid salt ; <BR> <BR> <BR> <BR> (S)-2- [4-(4-Benzyl-piperidin- 1 -yl)-benzenesulfonylamino] -3 -phenyl- <BR> <BR> <BR> <BR> <BR> <BR> propionic acid ; (S)-3 -(4-Benzyloxy-phenyl)-2-[4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino] -propionic acid ;

(S)-3 -(4-Hydroxy-phenyl)-2-[4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino]-propionic acid; (S)-3-Phenyl-2-[4-(4-phenyl-piperazin-1-yl)-benzenesulfonyla mino]- <BR> <BR> <BR> <BR> propionic acid ; <BR> <BR> <BR> <BR> <BR> <BR> (S)-2- {4-[-4-(3-Methoxy-phenyl)-piperazin- 1 -yl]-benzenesulfonylamino} - 3-phenyl-propionic acid ; (S)-2-{4-[-4-(3-Hydroxy-phenyl)-piperazin- 1 -yl]-benzenesulfonylamino} - 3-phenyl-propionic acid hydrobromide ; (S)-2- {4-[-4-(4-Methoxy-phenyl)-piperazin- 1 -yl]-benzenesulfonylamino} - 3-phenyl-propionic acid ; (R)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; (S)-4-Methyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyla mino]- pentanoic acid ; (S)-3 -Phenyl-2- [4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino] - propionic acid ; <BR> <BR> <BR> <BR> (R)-3-Phenyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- <BR> <BR> <BR> <BR> <BR> propionic acid ; (S)-3-(1H-Indol-3-yl)-2-[4-(4-phenyl-piperidin-1-yl)- <BR> <BR> <BR> <BR> benzenesulfonylamino] -propionic acid ; <BR> <BR> <BR> <BR> <BR> <BR> [4- (4-Phenyl-piperidin-1-yl) -benzenesulfonylamino] -acetic acid ; N-Hydroxy-2- [4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino] - acetamide ; 3- [4- (4-Phenyl-piperidin-1-yl) -benzenesulfonylamino] -propionic acid ; (R)-4-Methyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyla mino]- pentanoic acid ; (S)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; <BR> <BR> <BR> <BR> (S)-3-Phenyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- <BR> <BR> <BR> <BR> <BR> <BR> propionic acid ; <BR> <BR> <BR> <BR> <BR> (R)-3-Phenyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- propionic acid ;

(S)-3 -(1 H-Indol-3 -yl)-2-[4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino]-propionic acid; () -5-Phenyl-2- [4- (4-phenyl-piperidin- I -yl) -benzenesulfonylamino] - pentanoic acid ; [4-(4-Phenyl-piperazin-1-yl)-benzene-sulfonylamino]-acetic acid ; <BR> <BR> <BR> <BR> <BR> { Isobutyl-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonyl]amino} -acetic <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; (S)-4-Phenyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- butyric acid ; (R)-2-[4-(4-Phenyl-piperidin- 1 -yl)-benzenesulfonylamino]-3- tritylsulfanyl-propionic acid, sodium salt ; (R)-3-(1 H-Indol-3-yl)-2-[4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino) -propionic acid, disodium salt, monohydrate ; <BR> <BR> <BR> <BR> <BR> (S)-2- {4-[-4-(4-Hydroxy-phenyl)-piperazin- 1 -yl]- <BR> <BR> <BR> <BR> <BR> <BR> <BR> benzenesulfonylamino}-3-phenyl-propionic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> (S)-2- {4-[-4-(4-Chloro-phenyl)-piperazin- 1 -yl]- benzenesulfonylamino} -3-phenyl-propionic acid, hydrochloride ; (R)-3-Mercapto-2-[4-(4-phenyl-piperidin-1-yl)- benzenesulfonylamino] -propionic acid, trifluoracetic acid salt ; (S)-2-[4-(4-Benzyl-piperidin- 1 -yl)-benzenesulfonylamino]-3-phenyl- propionic acid ; <BR> <BR> <BR> <BR> <BR> (S)-3 -(4-Benzyloxy-phenyl)-2-[4-(4-phenyl-piperidin- 1 -yl)- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> benzenesulfonylamino]-propionic acid; (S)-3 -(4-Hydroxy-phenyl)-2- [4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino]-propionic acid; (S)-3 -Phenyl-2-[4-(4-phenyl-piperazin- 1 -yl)-benzenesulfonylamino]- propionic acid ; (S)-2-{4-[-4-(3 -Methoxy-phenyl)-piperazin- I -yl]-benzenesulfonylamino } - 3-phenyl-propionic acid ; (S)-2- {4-[-4-(3-Hydroxy-phenyl)-piperazin- 1 -yl]-benzenesulfonylamino} - 3-phenyl-propionic acid hydrobromide ;

(S)-2- {4-[-4-(4-Methoxy-phenyl)-piperazin- 1 -yl] -benzenesulfonylamino} - 3-phenyl-propionic acid ; (R)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; (S)-4-Methyl-2-[4-(4-phenyl-piperidin- 1 -yl)-benzenesulfonylamino]- pentanoic acid ; (S)-3-Phenyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyla mino]- <BR> <BR> <BR> <BR> propionic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> (R) -3-Phenyl-2- [4- (4-phenyl=piperidin-1-yl) -benzenesulfonylamino] - propionic acid ; and (S)-3-(1 H-Indol-3-yl)-2-[4-(4-phenyl-piperidin- 1 -yl)- benzenesulfonylamino] -propionic acid.

Additional specific compounds which can be used include : <BR> <BR> <BR> <BR> 2- (Dibenzofuran-2-sulfonylamino) -3- (4-fluoro-phenyl) -propionic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2- (Dibenzofuran-2-sulfonylamino) -3-phenyl-propionic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3- (4-tert-Butoxy-phenyl) -2- (dibenzofuran-2-sulfonylamino) -propionic <BR> <BR> <BR> <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (Dibenzofuran-2-sulfonylamino) -phenyl-acetic acid ; 3-tert-Butoxy-2-(dibenzofuran-2-sulfonylamino)-propionic acid; 2- (Dibenzofuran-2-sulfonylamino) -3- ( 1 H-imidazol-4-yl) -propionic acid ; 2- (Dibenzofuran-2-sulfonylamino) -3-hydroxy-propionic acid ; 3-Benzyloxy-2-(dibenzofuran-2-sulfonylamino)-propionic acid; 6-Benzyloxycarbonylamino-2- (dibenzofuran-2-sulfonylamino) -hexanoic acid ; 5-Benzyloxycarbonylamino-2-(dibenzofuran-2-sulfonylamino)-pe ntanoic acid ; (Dibenzofuran-2-sulfonylamino) - (4-methoxy-phenyl) -acetic acid ; 3-Chloro-2-(dibenzofuran-2-sulfonylamino)-propionic acid; 3- (4-Benzyloxy-phenyl) -2- (dibenzofuran-2-sulfonylamino) -propionic acid ; 2- (Dibenzofuran-2-sulfonylamino) -5-p-tolyl-sulfanylamino-pentanoic acid ; 2- (Dibenzofuran-2-sulfonylamino) -4-mercapto-butyric acid ;

3-(4-Bromo-phenyl)-2-(dibenzofuran-2-sulfonyl-amino)-propion ic acid; 2- (Dibenzofuran-2-sulfonylamino) -butyric acid ; 1-(Dibenzofuran-2-sulfonylamino)-cyclopropane-carboxylic acid; 3- (4-Chloro-phenyl) -2- (dibenzofuran-2-sulfonyl-amino) -propionic acid ; 2-(Dibenzofuran-2-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid; <BR> <BR> <BR> <BR> 2 -(4'-Bromo-biphenyl-4-sulfonylamino)-6-(4-fluoro- <BR> <BR> <BR> <BR> <BR> <BR> benzenesulfonyl amino) -hexanoic-acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl -4-sulfonylamino)-6 -(4-methoxy- <BR> <BR> <BR> <BR> <BR> <BR> benzenesulfonylamino) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6- (4-Bromo-benzenesulfonylamino) -2- (4'-bromo-biphenyl-4- <BR> <BR> <BR> <BR> <BR> <BR> sulfonylamino) -hexanoic-acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6- (2-Acetylamino-thiazole-5-sulfonylamino) -2- (4'-bromo-biphenyl- <BR> <BR> <BR> <BR> <BR> <BR> 4-sulfonylamino) -hexanoic-acid ; 6-(4-Acetylamino-benzenesulfonylamino)-2-(4'-bromo-biphenyl- 4-sulfonylamino) -hexanoic-acid ; 6-Benzenesulfonylamino-2-(4'-bromo-biphenyl-4-sulfonylamino) - hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (pentane-1-sulfonylamino) - hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(naphthalene-2-sulfo nylamino)- hexanoic-acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (naphthalene-1- <BR> <BR> <BR> <BR> sulfonylamino) -hexanoic-acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-phenyl- <BR> <BR> <BR> <BR> <BR> <BR> ethenesulfonylamino) -hexanoic-acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-phenyl-acetylamino-h exanoic <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- [2- (4-chloro-phenoxy) - <BR> <BR> <BR> <BR> <BR> <BR> acetylamino] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- [2- (4-chloro-phenoxy) - <BR> <BR> <BR> <BR> <BR> <BR> 2-methyl-propionylamino] -hexanoic acid ;

2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- [2- (pyridin-4-ylsulfanyl) - <BR> <BR> <BR> <BR> <BR> <BR> acetylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(2,4-dichloro-phe noxy)- <BR> <BR> <BR> acetylamino] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-thiophen-2-yl- <BR> <BR> <BR> <BR> <BR> acetylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(3 -phenyl-acryloylamino)- hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (7-phenyl-heptanoylamino) - hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6- [2 -(2 -trifluoromethyl-phenyl)- acetylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2 -phenoxy-butyrylamino)- hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-phenyl-sulfanyl- <BR> <BR> <BR> acetylamino) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-phenoxy-acetylamino) - hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(3,4-dimethoxy-ph enyl)- acetylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6- [2-(4-tert-butyl-phenoxy)- <BR> <BR> <BR> acetylamino] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6- [3 -(3,4-dimethoxy- <BR> <BR> <BR> <BR> <BR> phenyl) -propionylamino] -hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-cyclopent-1-enyl- acetylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6- [2-(4-methoxy-phenoxy)- <BR> <BR> <BR> acetylamino] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(naphthalen- 1 -yloxy)- acetylamino]-hexanoic acid;

2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(4-nitro-phenoxy) - acetylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[4-(4-chloro-3-methy l- phenoxy) -butyrylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(4-methoxy-phenyl )- propionylaminoj-hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-pyridin-3-yl-acetylamino) - hexanoic acid ; 6-(2-Benzo[1,3]dioxol-5-yl-acetylamino)-2-(4'-bromo-biphenyl -4- sulfonylamino) -hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-pyridin-2-yl-acetylamino) - hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6- [2 -(4-tert-butyl-phenoxy)- acetylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(3,4-dimethoxy-ph enyl)- propionylamino]-hexanoic acid; <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-cyclopent- 1 -enyl- <BR> <BR> <BR> <BR> <BR> <BR> acetylamino) -hexanoic acid ; 2 -(4'-Bromo-biphenyl-4-sulfonylamino)-6- [2-(4-methoxy-phenoxy)- acetylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(naphthalen-1-ylo xy)- acetylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(4-nitro-phenoxy) - acetylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[4-(4-chloro-3-methy l- phenoxy) -butyrylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(4-methoxy-phenyl )- propionylamino] -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-pyridin-3-yl-acet ylamino)- hexanoic acid ;

6-(2-Benzo[1,3]dioxol-5-yl-acetylamino)-2-(4'-bromo-biphenyl -4- sulfonylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-pyridin-2-yl-acet ylamino)- hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[4-(4-nitro-phenyl)- butyrylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(4-tert-butyl-phe noxy)- acetylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(3,4-dimethoxy-ph enyl)- propionylamino] -hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-cyclopent-1-enyl- acetylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[2-(4-methoxy-phenox y)- acetylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(4-phenyl-butyrylami no)- hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[4-(4-chloro-3-methy l- phenoxy)-butyrylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(4-chloro-phenyl) - propionylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(4-methoxy-phenyl )- propionylamino]-hexanoic acid; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2-pyridin-3-yl-acet ylamino)- hexanoic acid ; 6-(2-Benzo[1,3]dioxol-5-yl-acetylamino)-2-(4'-bromo-biphenyl -4- sulfonylamino) -hexanoic acid ; 2- (4'-Bromo-biphenyl-4-sulfonylamino) -6- (2-naphthalen-1-yl- acetylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-[3-(4-chloro-phenoxy )- propionylamino] -hexanoic acid ;

2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(6-phenyl-hexanoylam ino)- hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(4-thiophen-2-yl- butyrylamino) -hexanoic acid ; 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(2,4,6-triisopropyl- <BR> <BR> <BR> <BR> <BR> benzoylamino) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-isobutoxycarbonylami no- hexanoic acid ; <BR> <BR> <BR> <BR> <BR> 2-(4'-Bromo-biphenyl-4-sulfonylamino)-6-(9H-fluoren-9- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> ylmethoxycarbonylamino) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 6-(Adamantan- 1 -yloxycarbonylamino)-2-(4'-bromo-biphenyl-4- sulfonylamino) -hexanoic acid ; and 6-Allyloxycarbonylamino-2- (4'-bromo-biphenyl-4-sulfonylamino) - hexanoic acid.

Numerous succinamide MMP inhibitors are known and can be utilized in the method of this invention. Typical succinamides include : 2S,Nl-Dihydroxy-3R-isobutyl-N4-{ 1 S-[2-(2-methoxy-ethoxymethoxy)- ethylcarbamoyl] -2, 2-dimethyl-propyl} -succinamide ; 2S-Allyl-Nl-hydroxy-3R-isobutyl-N4- {1 S- [2- (2-methoxy- ethoxymethoxy)ethylcarbamoyl] -2-phenyl -ethyl } -succinamide; 2S-Allyl-Nl-hydroxy-3R-isobutyl-N4- {1 S- [2- (2-methoxy- <BR> <BR> <BR> <BR> ethoxymethoxy)ethylcarbamoyl]-2,2-dimethyl-propyl } -succinamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2S-Allyl-N 1 -hydroxy-3R-isobutyl-N4-(1 S-{2-[2-(2-methoxy-ethoxy)- ethoxy] -ethylcarbamoyl] -2, 2-dimethyl-propyl} -succinamide ; 2S-Allyl-N4- { 1 S-[2,2-di-(methoxymethyl)-propylcarbamoyl } -2,2- <BR> <BR> <BR> <BR> dimethyl-propyl]-N 1 -hydroxy-3R-isobutyl-succinamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 28-Allyl-N4- {1 S- [2, 2-di- (methoxymethyl) -butylcarbamoyl] -2, 2-dimethyl- propyl }-N¹-hydroxy-3R-isobutyl-succinamide; N4-Hydroxy-2R-isobutyl-N¹-{1S-[2-(2-methoxy-ethoxy)- ethylcarbamoyl]-2,2-dimethyl-propyl}-3S-(thiophen-2-yl-sulfa nylmethyl)- succinamide ;

N4-Hydroxy-2R-isobutyl-N¹-(1S-{2-[2-methoxy-ethoxy)ethoxy]- <BR> <BR> <BR> ethylcarbamoyl } -2,2-dimethyl-propyl)-3 S-(thiophen-2-yl -sulfanylmethyl)- <BR> <BR> <BR> <BR> succinamide ; N1{1S-[2,2-Di-(methoxymethyl)-propylcarbamoyl]-2,2-dimethyl- <BR> <BR> <BR> propyl} -N4-hydroxy-3R-isobutyl-3 S-(thiophen-2-yl-sulfanylmethyl)- <BR> <BR> <BR> <BR> succinamide ; N4-Hydroxy-2R-isobutyl-N¹-{1S-[2-(2-methoxy-ethoxy)- <BR> <BR> <BR> ethylcarbamoyl]-2,2-dimethyl-propyl } -3 S-propyl-succinamide; <BR> <BR> <BR> <BR> N4-(1 S-Cyclobutylcarbamoyl-2,2-dimethyl-propyl)-2S,N 1 -dihydroxy-3R- <BR> <BR> <BR> <BR> <BR> isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> N4-(1 S-Cyclopropylcarbamoyl-2,2-dimethyl-propyl)-2S,N I -dihydroxy- <BR> <BR> <BR> <BR> 3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> N4-(1 S-Cyclopentylcarbamoyl-2,2-dimethyl-propyl)-2S,N 1 -dihydroxy- <BR> <BR> <BR> <BR> <BR> 3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> N4-(1 S-Cyclohexylcarbamoyl-2,2-dimethyl-propyl)-2S ,N 1 -dihydroxy-3R- <BR> <BR> <BR> <BR> <BR> isobutyl-succinamide ; <BR> <BR> <BR> <BR> N4-(1 S-Cycloheptylcarbamoyl-2,2-dimethyl-propyl)-2S,N 1 -dihydroxy- <BR> <BR> <BR> <BR> <BR> 3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> N4- (l S-Cyclopropylcarbamoyl-2-mercapto-2-methyl-propyl) -2S, N I - <BR> <BR> <BR> <BR> dihydroxy-3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> N4-(1 S-Cyclopropylcarbamoyl-2,2-dimethyl-propyl)-2S,N 1 -dihydroxy- 3R-(3-phenyl-propenyl)-succinamide; N4-(1 S-Cyclopropylcarbamoyl-2,2-dimethyl-propyl)-2 S ,N 1 -dihydroxy- 3R-(3-phenyl-propyl)-succinamide; N4-[2,2-Dimethyl- 1 S-(2-phenyl-cyclopropylcarbamoyl)-propyl]-2S,N 1 <BR> <BR> <BR> <BR> dihydroxy-3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> 2S-Allyl-N4-(1 -cyclopropylcarbamoyl-2,2-dimethyl-propyl)-N 1 -hydroxy- <BR> <BR> <BR> <BR> 3R-isobutyl-succinamide ; <BR> <BR> <BR> <BR> <BR> 2S-Allyl-N4-(1 S-cyclopropylcarbamoyl-2-mercapto-2-methyl-propyl)-N 1 <BR> <BR> <BR> <BR> <BR> hydroxy-3R-isobutyl-succinamide ;

N4- (1 S-Cyclopropylcarbamoyl-2, 2-dimethyl-propyl) -N 1-hydroxy-3R- <BR> <BR> <BR> <BR> <BR> isobutyl-2S- (thiophen-2-ylsulfanylmethyl) -succinamide ; <BR> <BR> <BR> <BR> <BR> N4- (1 S-Cyclopropylcarbamoyl-2, 2-dimethyl-propyl) -N 1 -hydroxy-2S- (4-hydroxy-phenylsulfanylmethyl) -3R-isobutyl-succinamide ; and N4-(1 S-Cyclopropylcarbamoyl-2,2-dimethyl-propyl)-2S-(1,3-dioXo- 1,3-dihydro-isoindol-2-ylmethyl)-N¹-hydroxy-3R-isobutyl-suc cinamide.

Another especially preferred group of MMP inhibitors to be utilized in the method of this invention are the sulfonated amino acid derivatives described in WO 97/27174, incorporated herein by reference. Those compounds have the general structure where Rl l is substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroaryl alkyl ; R12 is hydrogen, or a group as defined for R11; R13 is a single bond, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene ; R14 is a single bond, -(CH2)1 or 2-, -CH=CH-, -C#C-, -CO-, -CONH-, -N=N-, NH, N-alkyl, -NHCONH-, -NHCO-, -O-, -S-, -S02NH-, -S02NH-N=CH-, or tetrazoldiyl ; R15 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted non-aromatic heterocyclic group ; and Y is NHOH or OH.

Especially preferred compounds to be employed in the method of this invention have the above formula wherein R13 is phenylene or substituted phenylene. Typical of such compounds that can be employed have the formula

where R1 l and R. 12 are as defined above, and R 17 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

Especially preferred are compounds of the formula wherein R¹¹ and R18 are as follows :

The following patents and applications covering MMP inhibitors are incorporated herein by reference : United States 5, 753, 653 ; WO 96/16027 ; WO 97/20824; WO 98/50348; WO 98/43963; WO 9832748; WO 98/17643; and EP 0780386. These include compounds such as shown below.

4-[2-(2-Carboxymethyl-4-phenyl-butylamino)-3- cyclohexylpropionylamino]benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4-phenyl-butyrylamino) -3, 3 -methyl- butyrylamino] -benzoic acid methyl ester ;

4- [2- (2-Carboxymethyl-4-phenyl-butyrylamino) -3, 3-dimethyl- butyrylamino] -benzoic acid methyl ester ; 4- [2- (2-Hydroxaminocarbonylmethyl-4-phenyl-butyrylamino) -3, 3- dimethyl-butyrylamino] -benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4-methyl-valerylamino) -3, 3-dimethyl- butyrylamino]-benzoic acid methyl ester ; 4- [2- (2-Hydroxaminocarbonylmethyl-5-methyl-valerylamino) -3, 3- dimethyl-butyrylamino]-benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4-phenyl-butylamino) -2- cyclohexylpropionylamino]benzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-4-methyl-valerylamino)-4-methyl-valery lamino]- benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5-phenyl-valerylamino) -3, 3-dimethyl- butyrylamino]-benzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-4-methyl-pentanoylamino)-3-(1H-indol-3 -yl)- propionylamino-benzoic acid methyl ester ; 5-Methyl-3-(9-oxo-1,8-diaza-tricyclo[10.6.1.0,13,18]nonadeca - 12(19),13,15,17-tetraen-10-ylcarbamoyl)-hexanoic acid; 4- [2- (2-Hydroxaminocarbonylmethyl-4-phenyl-butyrylamino) -3, 3-methyl- butyrylaminoj-benzoic acid methyl ester ; 4- [2- (2-Hydroxaminocarbonylmethyl-4-phenyl-butyrylamino) -2- cyclohexylpropionylamino]-benzoic acid methyl ester benzoic acid methyl ester ; 4-[2-(2-Hydroxaminocarbonylmethyl-4-methyl-valerylamino)-4-m ethyl- valerylamino] -benzoic acid methyl ester ; 4-[2-(2-Hydroxaminocarbonylmethyl-4-phenyl-butylamino)-3- cyclohexylpropionylamino] benzoic acid methyl ester ; 4-[2-(2-Methoxyaminocarbonylmethyl-4-phenyl-butylamino)-3- cyclohexylpropionylamino]benzoic acid methyl ester ; 4- [2- (2-Hydroxaminocarbonylmethyl-5-phenyl-valerylamino) -3, 3- dimethyl-butyrylamino] -benzoic acid methyl ester ; 5-Methyl-3-(9-oxo-1,8-diaza-tricyclo[10.6.1.0 13,18]nonadeca- 12(19),13,15,17-tetraen-10-ylcarbamoyl)-1-hexylhydroxamic acid;

4-[2-(2-Hydroxaminocarbonylmethyl-4-methyl-pentanoylamino)-3 -(1H- indol-3-yl) -propionylamino] -benzoic acid methyl ester ; 3 - [2-(4-Methoxy-benzylsulfanyl)-2-methyl - 1 -phenylcarbamoyl- propylcarbamoyl]-5-methyl-hexanoic acid; 3- [2- (4-Methoxy-benzylsulfanyl) -2-methyl-1 -phenylcarbamoyl- propylcarbamoyl]-5-methyl-hexanoic acid N-hydroxyamide ; 4- [2-(2-Hydroxaminocarbonylmethyl-4-methyl-pentanoylamino)-2- cyclohexyl-acetylamino] -benzoic acid methyl ester ; 2- (Phenyl-2-ethyl) benzoic acid N-hydroxy amide ; 4-[2-(2-Acylhyrdazinomethyl-4-methyl-pentanoylamino)-3-(1H-i ndol-3- yl) -propionylamino] -benzoic acid methyl ester ; 2-(Propylthio)-pyridine-3-N-(hydroxy)carboxamide; 4- [2- (2-Carboxymethyl-5-phenyl-pentanoylamino) -2- cyclohexylacetylamino] benzoic acid methyl ester ; <BR> <BR> <BR> <BR> [4- (N-Hydroxyamino) -2R-isobutyl-3S- ( (thien-2-ylthio) methyl) succinyl] -<BR> <BR> <BR> <BR> <BR> L-phenylalanine-N-methylamide ; <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-5-phenylpentanamide ; 4-[2-(2-Carboxymethyl-5-(3-hydroxyphenyl)-valeroyl)amino)-4- methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (3-hydroxyphenyl) -4-pentenoyl) amino) -4- methyl-valeroyl] aminobenzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-5-(3-aminophenyl)-4-pentenoyl)amino)-4 -methyl- valeroyl] aminobenzoic acid methyl ester, trifluoroacetate salt ; 2- (Phenyl-2-ethyl) pyridine-3-N-hydroxycarboxamide ; 4-[2-(2-Carboxymethyl-5-(3-aminophenyl)-valeroyl)amino)-4-me thyl- valeroyl] aminobenzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-5-(3-aminophenyl)acetyl)amino)-4-methy l- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (3-aminophenyl) acetyl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 2- [3- (3-Hydroxy-phenyl) -propyl] -benzohydroxamic acid ; 2- (Thiobenzyl) benzoic acid N-hydroxy amide ; 1 - (3-Phenyl-propyl) -pyrrolidine-2-hydroxamic acid ;

4- [2- (2-Carboxymethyl-5- (5-hydroxyvaleroyl) amino) -4-methyl- valeroyl]aminobenzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-5-(N'-methylureido)valeroyl)amino)-4-m ethyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (triflouroacetamido) valeroyl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-2-phenylacetylamino)-4-methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Hydroxaminocarbonylmethyl-2-phenylacetylamino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4-methyl-pentanoylamino) -2-cyclohexyl- acetylamino] -benzoic acid methyl ester ; 2- [3- (3-Amino-phenyl) -propyl] -benzohydroxamic acid ; cis-4-Benzyloxy-pyrrolidine-2-carboxylic acid ; 4- [2- (2-Carboxymethyl-5- (3-amino-4- (trifluoromethyl) phenyl) - valeroyl) amino) -4-methyl-valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (methanesulfamido) valeroyl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; <BR> <BR> <BR> <BR> N-Cbz-L-Tyrosine ; <BR> <BR> <BR> <BR> <BR> <BR> N-Boc-L-Tryptophan ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- [2- (Carboxy-2-o-tolyl-propionylamino-4-methyl-pentanoylamino] - benzoic acid methyl ester ; 4-[2-(Carboxymethyl-hepanoylamino)-4-methyl-pentanoylamino]- benzoic acid methyl ester ; 4-[2-(2-Carboxymethyl-5-(4-n-butylphenyl)-valeroyl)amino)-4- methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (4-n-butylphenyl) -4-pentenoyl) amino) -4- methyl-valeroyl]aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-2- (2-thienyl) acetylamino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4- (3-aminophenyl) -butyryl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ;

4- [2- (2-Carboxymethyl-5- (biphen-4-yl) -valeroyl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; cis-4-Benzylsulfanyl-pyrrolidine-2-carboxylic acid ; 2-Cyclohexylmethyl sulfonyl-benzoic acid ; Pyrrolidine-1-carbothioic acid phenethyl-amide ; <BR> <BR> <BR> <BR> 3- (2-Methyl-thiazol-4-yl) -N-phenethyl-propionamide ; <BR> <BR> <BR> <BR> <BR> <BR> N-Phenyl-3 - [1 -(2-trimethylsilanyl-ethoxymethyl)- 1 H-imidazol-4-yl] -<BR> <BR> <BR> <BR> <BR> <BR> propionamide ; <BR> <BR> <BR> <BR> <BR> <BR> 3- (3H-Imidazol-4-yl) -N-phenethyl-propionamide ; <BR> <BR> <BR> <BR> <BR> 4- [2- (2-Carboxymethyl-5- (formamido) valeroyl) amino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 2-Cyclohexylmethyl sulfonyl-benzohydroxamic acid ; [2-Oxo-3-(3-phenyl-propyl)-tetrahydro-furan-3-yl]-acetic acid; 4-[2-(2-Carboxymethyl-5-(fluoren-2-yl)valeroyl)amino)-4-meth yl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-2- (3-thienyl) acetylamino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 4- [2- (2-Benzylthio-3-carboxy-propionylamino) -4-methylpentanoylamino] - benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-4- (2-indolyl) butyrylamino) -4-methyl- valeroyl]aminobenzoic acid methyl ester ; 1-Allyl-3-(2-hydroxyethyl)-2-thiourea; 3-(1-Hydroxyimino-propyl)-6-phenyl-hexanoic acid; 2- (3H-Imidazol-4-ylmethyl) -N 1, N 4-diphenethyl-succinamide ; <BR> <BR> <BR> <BR> 3- (2-Hydroxymethyl-3H-imidazol-4-yl) -N-phenethyl-propionamide ; <BR> <BR> <BR> <BR> <BR> 6-Phenyl-3-propionyl-hexanoic acid ; 4- {2-([2-Hydroxyamino-2-hydroxyimino-ethyl]-5-phenyl- pentanoylamino)-4-methyl-pentanoylamino}-benzoic acid methyl ester ; 4- [2- (2- (2-Phenylcyclopropyl) succinylamino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; 6-Biphenyl-4-yl-[2,2-dimethyl-1-(pyridin-4-ylcarbamoyl)- propylcarbamoyl] -hexanoic acid trifluoroacetate salt ;

3- [1 - (5, 6-Dichloro-1 H-benzoimidazol-2-yl) -3-methyl-butylcarbamoyl] -5- methyl-hexanoic acid ; 6-Biphenyl-4-yl-3-[1 -(5,6-dichloro-1H-benzoimidazol-2-yl)-3-methyl- butylcarbamoyl]-5-methyl-hexanoic acid; <BR> <BR> <BR> <BR> 2-Carboxymethyl-heptanoyl-2- (N-methylcarboxamide) piperidine ; <BR> <BR> <BR> <BR> <BR> 4- [2- (2- (2-Phenylcyclopropyl) succinylamino) -4-methyl- valeroyl] aminobenzoic acid methyl ester ; <BR> <BR> <BR> <BR> 2-Carboxymethyl-heptanoyl-3- (N-methylcarboxamide) - <BR> <BR> <BR> <BR> <BR> <BR> hexahydropyridazine ; <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3 -[1 -[3 -(3 -hydroxy-ethyl)-phenylcarbamoyl] -2,2- <BR> <BR> <BR> <BR> <BR> <BR> dimethyl-propylcarbamoyl] -hexanoic acid ; 2R-(3-(4-Biphenyl)propyl-N-(2R-hydroxy-3-(2-hydroxyphenyl)-5 -methyl- 3 S-hexyl) succinamide ; <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3 -[1 -[3-(2-aminoethyl)-phenylcarbamoyl] -2,2-dimethyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2R- (3- (4-Biphenyl) propyl) -N- (diphenylmethyl) succinamide ; <BR> <BR> <BR> <BR> <BR> <BR> 2R- (3- (4-Biphenyl) propyl) -N- (phenylmethyl) succinamide ; <BR> <BR> <BR> <BR> <BR> 2- (2-Oxo-imidazolidin-4-ylmethyl) -5-phenyl-pentanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2-(3-Biphenyl-4-yl-propyl)-N 1 -[1 -(5,6-dichloro- 1 H-benzoimidazol-2-yl)- 3-methyl-butyl]-N4-hydroxy-succinamide hexanoic acid ; 6-Biphenyl-4-yl-[2,2-dimethyl-1-(pyridin-4-ylcarbamoyl)- propylcarbamoyl] -hexanoic acid, N-hydroxyamide ; <BR> <BR> <BR> <BR> 2R-(3 -(4-Biphenyl)propyl)-N-((1 -hydroxy- 1 -methylethyl)phenylmethyl)- <BR> <BR> <BR> <BR> <BR> <BR> succinamide ; <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [1-phenylcarbamoyl-2- (4-cyano-benzylsulfanyl) -2- methyl-propylcarbamoyl]-hexanoic acid; 4- {2- [2-Carboxymethyl-5- (4'-hydroxy-biphenyl-4-yl) -pentanoylamino] -4- methyl-pentanoylamino} -benzoic acid methyl ester ; 1-(N-Methyl-N-phenethylthiocarbomyl)-pyrrolidine-2-carboxyli c acid; 6-Biphenyl-4-yl-3 -({ cyclohexyl-[2-(4-sulfanoyl-phenyl)-ethylcarbamoyl]- methyl}-carbamoyl)-hexanoic acid; 3R(6-(4-Biphenyl)-3-(N-benzylcarbamoyl))-hexanoic acid N-hydroxyamide ;

[3- (3-Biphenyl-4-yl-propyl) -2-oxo-pyrrolidin-3-yl] -acetic acid ; 2-Benzylsulfonyl-cyclopent-1-ene-carboxylic acid hydroxamide ; [2-Oxo-3-(3-phenyl-propyl)-pyrrolidin-3-yl]-acetic acid; [3-(3-Naphthalen-2-yl-propyl)-2-oxo-pyrrolidin-3-yl]-acetic acid; 2-Benzylsulfonyl-cyclohex-1-enecarboxylic acid hydroxy amide ; 6-Benzylsulfonyl-cyclohex-1-enecarboxylic acid hydroxy amide ; <BR> <BR> <BR> <BR> 2R- (3- (4-Biphenyl) propyl) -N- (3-methylpyridine) succinamide ; <BR> <BR> <BR> <BR> <BR> <BR> { 3 - [3 -(3 -Hydroxy-phenyl)-propyl] -2-oxo-pyrrolidin-3 -yl } -acetic acid; 6-Biphenyl-4-yl-{[cyclohexyl-(3-morpholin-4-yl-propylcarbamo yl)- methyl] -carbamoyl} hexanoic acid ; [2-Oxo-3-(3-biphenyl-propyl)-tetrahydro-furan-3-yl]-acetic acid; 4-[2-(2-Thioamidomethyl-5-phenyl-valerylamino)-4-methyl- valeroylamino] -benzoic acid methyl ester ; 4- [2- (2-Amino-2-hydroxyimino-ethyl-5-phenyl-valerylamino) -4-methyl- valeroylamino] -benzoic acid methyl ester ; 6-Biphenyl-4-yl-3-[2,2-dimethyl-1-(4-methylsulfamoyl- phenylcarbamoyl) -propylcarbamoyl] -hexanoic acid ; 6-Biphenyl-4-yl-3-[2,2-dimethyl-1-(2-hydroxyethylsulfamoyl- <BR> <BR> <BR> phenylcarbamoyl) -propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> I -(N-Hydroxy)-3 -(2-bibenzyl)urea; <BR> <BR> <BR> <BR> <BR> <BR> 4-(2- { 5 - [7-(2-Amino-acetylamino)-9H-fluoren-2-yl] -2-carboxymethyl - pentanoylamino} -4-methyl-pentanoylamino) -benzoic acid methyl ester TFA salt ; 3R-(6-(4-Biphenyl)propyl)-N-(3-methylpyridinecarbamoyl)-hexa noic acid N-hydroxy amide ; <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [cyclohexyl- (4- (2-hydroxy-ethylsulfamoyl) - <BR> <BR> <BR> <BR> <BR> phenylcarbamoyl) -methylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [cyclohexyl- (4- (2-dimethylamino-ethylsulfamoyl) - phenylcarbamoyl) -methylcarbamoyl] -hexanoic acid, trifluoroacetate salt ; 4-(2-{2-Carboxymethyl-5-[4-(1H-tetrazol-5-yl)-phenyl]-pentan oylamino}- 4-methyl-pentanoylamino) -benzoic acid methyl ester ; 4- [2- (2-Carboxymethyl-5- (4- (2-hydroxy-ethyl) -phenyl) -pentanoylamino) - 4-methyl-pentanoylamino] -benzoic acid methyl ester ;

4- (2- { [5-Hydroxyamino-3- (3-phenyl-propyl) -3, 4-dihydro-2-H-pyrrole-3- carbonyl] -amino} -4-methyl-pentanoylamino) benzoic acid methyl ester ; 5-Hydroxyamino-3-(3-phenyl-propyl)-3,4-dihydro-2-H-pyrrole-3 - carboxylic acid(2-cyclohexyl-1-methylcarbamoyl-ethyl)amide; <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [2, 2-dimethyl-l- (4- (3-morpholin-4-yl-sulfamoyl) - <BR> <BR> <BR> <BR> <BR> phenylcarbamoyl) -propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [2, 2-dimethyl-l- (4-methylsulfanyl-phenylcarbamoyl) - propylcarbamoyl]-hexanoic acid; 6-Biphenyl-4-yl-3-[2,2-dimethyl-1-(4-methylsulfonyl-phenylca rbamoyl)- propylcarbamoyl]-hexanoic acid; 4- [2- (5-Biphenyl-4-yl-2-carboxymethyl-pentanoylamino) -pent-4- enoylamino] -benzoic acid methyl ester ; 6-Biphenyl-4-yl-3-[2,2-dimethyl-1-(4-methylsulfinyl-phenylca rbamoyl)- propylcarbamoyl] -hexanoic acid ; 4- (2-{[5-Hydroxyamino-3-(3-pentyl)-3,4-dihydro-2-H-pyrrole-3- carbonyl] -amino} -4-methyl-pentanoylamino) benzoic acid methyl ester ; 5-Hydroxyamino-3-(3-pentyl)-3,4-dihydro-2-H-pyrrole-3-carbox ylic acid(2-cyclohexyl- 1 -methylcarbamoyl-ethyl)amide; 6-Biphenyl-4-yl-[2,2-dimethyl-1-(pyridin-4-ylcarbamoyl)- <BR> <BR> <BR> <BR> propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 4- [2- (2-Carboxymethyl-5- (4-cyano-biphenyl-4-yl) -pentanoylamino) -4- methyl-pentanoylamino] -benzoic acid methyl ester ; 6-Biphenyl-4-y-3-(R)-(2-hydroxy-1-(S)-phenyl-ethylcarbamoyl) -hexanoic acid ; 3-(R)-(1-(R)-Benzyl-2-hydroxy-ethylcarbamoyl)-6-biphenyl-4-y l-hexanoic acid ; 6-Biphenyl-4-yl-3-(R)-(2-hydroxy-1-hydroxymethyl-ethylcarbom yl)- hexanoic acid ; 4-[2-(2-Carboxymethyl-5-(4-pyridin-4-yl-phenyl)-pentanoylami no)-4- methyl-pentanoylamino] benzoic acid methyl ester ; 6-Biphenyl-4-yl(2-hydroxy-2-methyl-1-phenylcarbamoyl- propylcarbamoyl) -hexanoic acid ;

6-Biphenyl-4-yl(2-hydroxy-2-methyl- 1 -phenylcarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 3- {2-Allylsufamyl-2-methyl-l- [2- (4-sulfamoyl-phenyl) -ethylcarbamoyl] - <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl}-6-biphenyl-4-yl-hexanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 4- [2- (5-Biphenyl-4yl-2-carboxymethyl-pentanoylamino) -4, 5-dihydroxy- pentanoylamino]-benzoic acid methyl ester ; 4- (2- {5- [4'- (2-Amino-ethoxy) -biphenyl-4-yl] -2-carboxymethyl- pentanoylamino} -4-methyl-pentanoylamino) -benzoic acid methyl ester ; 6-Biphenyl-4-y-3-(R)-(2-hydroxy- 1 -(S)-phenyl-ethylcarbamoyl)- hexanehydroxamic acid ; 3-(R)-(1-(R)-Benzyl-2-hydroxy-ethylcarbamoyl)-6-biphenyl-4-y l- hexanehydroxamic acid ; N- [5- (Biphenyl-4-yl) -2- (N-hydroxyformamido) methylpentanoyl] -tert- leucine, N- (pyrid-4-yl) amide ; <BR> <BR> <BR> <BR> [3- (3-Naphthalen-2-yl-propyl) -2-oxo-tetrahydro-furan-3-yl] -acetic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- (R) - (2-hydroxy-l-hydroxymethyl-ethylcarbomyl) - hexanehydroxamic acid ; 4- [2- (2-Carboxymethyl-5-naphthalen-2-yl-pentanoylamino) -4-methyl- pentanoylamino] -benzoic acid methyl ester ; <BR> <BR> <BR> <BR> 3 - [2,2-Dimethyl- I -(pyridin-4-ylcarbamoyl)-propylcarbamoyl] -5-methyl- <BR> <BR> <BR> <BR> <BR> <BR> hexanoicacid ; N 1 - [2, 2-Dimethyl-1 - (pyridin-4-ylcarbamoyl) -propyl] -N4-hydroxy-2- isobutyl-succinamide ; 4-{2-[2-Carboxymethyl-5-(2-fluoro-biphenyl-4-yl)-pentanoylam ino]-4- methyl-pentanoylamino} -benzoic acid methyl ester ; 6-Biphenyl-4-yl-3(R)-(1(S)-hyroxymethyl-2,2-dimethyl- propylcarbamoyl) -hexanoic acid ; 4-{2-[5-Biphen-4-yl-2-(1-carboxy-ethylamino)-pentanoylamino] -4- methyl-pentanoylamino} -benzoic acid methyl ester ; 6-Biphenyl-4-yl-3(R)-(1(S)-hyroxymethyl-2,2-dimethyl- propylcarbamoyl)-hexanehydroxamic acid;

6-Biphenyl-4-yl-3 - [2,2-dimethyl- 1 -(4-methylsulfinyl-phenylcarbamoyl)- propylcarbamoyl]-hexanoic acid; 2-(Biphenyl-4-ylsulfonyl)-cyclohex-1-enecarboxylic acid hydroxyamide ; 6-(Biphenyl-4-ylsulfonyl)-cyclohex-1-enecarboxylic acid hydroxyamide ; 2-Phenethylsulfanyl-cyclohex-l-enecarboxylic acid hydroxyamide ; 6-(4'-cyano-biphenyl-4-yl)-3-[2-hydroxy-1-(4-methylsulfinyl- <BR> <BR> <BR> <BR> <BR> phenylcarbamoyl) -propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1- {1- [ 1- (4-Methoxycarbonyl-phenylcarbamoyl) -3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> butylcarbamoyl]-3-methyl-butylcarbamoyl}-pyrrolidine-2-carbo xylic acid; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3- [2, 2-dimethyl-l- (4S-methylsulfinyl-phenylcarbamoyl) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl] -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- [2- (2-Carboxymethyl-5- (4- (2-hydroxy-3, 3, 3-trifluoropropyl) -phenyl) - pentanoylamino) -4-methyl-pentanoylamino] -benzoic acid methyl ester ; 2-Benzylsulfanyl-cyclohexancarboxylic acid hydroxamide ; <BR> <BR> <BR> <BR> <BR> 1- {1- [1- (4-Methoxycarbonyl-phenylcarbamoyl) -3-methyl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> butylcarbamoyl] -3-methyl-butylcarbamoyl} -pyrrolidine-2-carboxylic acid ; trans-2-Benzylsulfanyl-cyclohexancarboxylic acid hydroxamide ; 4- [2- (2-Carboxymethyl-5- (4- (2-methylthiazol-4- yl)phenyl)valeroyl)amino)-4-methyl-valeroyl]aminobenzoic acid methyl ester ; 1-{1-[1-(4-Methoxycarbonyl-phenylcarbamoyl)-3-methyl- butylcarbamoyl]-3-methyl-butylthiocarbamoyl}-pyrrolidine-2-c arboxylic acid; 3- [ (Cyclohexyl- (4- (2-hydroxy-ethylsulfamoyl) -phenylcarbamoyl) - methyl) -carbamoyl] -6- (4-pyridin-4-yl-phenyl) -hexanoic acid trifluoroacetate salt ; trans-2- (Biphenyl-4-yl-methylsulfanyl) -cyclohexancarboxylic acid hydroxamide ; 6-Biphenyl-4-yl-3-(1-hydroxymethyl-2,2-dimethyl-but-3-enylca rbamoyl)- hexanoic acid ; 6-Biphenyl-4-yl-3-(1-hydroxymethyl-2,2-dimethyl-but-3-enylca rbamoyl)- hexanoic acid ; 6-Biphenyl-4-yl-3-(R)-(1-hydroxymethyl-2-(S)-(1H-imidazol-4- yl)- ethylcarbamoyl) -hexanoic acid ;

3-(R)-(2-(R)-Benzyloxy-1-(S)-hydroxymethyl-propylcarbamoyl)- 6- biphenyl-4-yl-hexanoic acid ; 4- [4-Methyl-2- (2-nitromethyl-5-phenyl-pentanoylamino) - pentanoylamino] -benzoic acid methyl ester ; 6-Biphenyl-4-yl-3-[3-methyl-1-(4-(2-hydroxyethylsulfamoyl)- phenylcarbamoyl) -butylcarbamoyl] -hexanoic acid ; 6-Biphenyl-4-yl-3-(1-hydroxymethyl-2-phenyl-ethylcarbamoyl)- hexanoic acid ; N1-(1-Benzyl-2-hydroxy-ethyl)-2-(3-biphenyl-4-yl-propyl)-N4- hydroxy- succinamide ; 6-Biphenyl-4-yl-3-(R)-(1-hydroxymethyl-2-(S)-(1H-imidazol-4- yl)- <BR> <BR> <BR> ethylcarbamoyl) -hexanehydroxamic acid ; <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [2-Oxo-3- (3-phenyl-propyl) -tetrahydro-furan-3-yl] - acetamide ; 4- [2- (2-Carboxymethyl-5- (2-hydroxy-biphen-4-yl) -valeroylamino) -4- methyl-valeroylamino]-benzoic acid methyl ester ; N1-(2-Benzyloxy-1-hydroxymethyl-propyl)-2-(3-biphenyl-4-yl-p ropyl)- N4-hydroxy-succinamide; trans-2-(4-Phenoxy-benzylsulfanyl)-cyclohexancarboxylic acid hydroxamide ; 2-(4-Indol-1-yl-benzylsulfanyl)-cyclohexancarboxylic acid hydroxamide ; 6-Biphenyl-4-yl-3-[2-hydroxy-2-methyl-1-(4S-methylsulfinyl- phenylcarbamoyl) -propylcarbamoyl] -hexanoic acid ; 6-Biphenyl-4-yl-3-(2,4,5-trihydroxy-6-hydroxymethyl-tetrahyd ro-pyran-3- <BR> <BR> <BR> ylcarbamoyl) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> 5-Biphenyl-4-yl-2- [(formyl-hydroxy-amino)-methyl]-pentanoic acid{1-[4- (2-dimethylamino-ethylsulfamoyl)-phenylcarbamoyl]-3-methyl-b utyl}-amide; 2-(3-Biphenyl-4-yl-propyl)-N4-hydroxy-N1-(2,4,5-trihydroxy-6 - hydroxymethyl-tetrahydro-pyran-3-yl)-succinamide; 6-Biphenyl-4-yl-3-(2,4,5-trihydroxy-6-hydroxymethyl-tetrahyd ro-pyran-3- ylcarbamoyl) -hexanoic acid ;

N-[2,2-Dimethyl-1S-(pyridin-4-ylcarbamoyl)-propyl]-3R-thioph en-3-yl- succinamic acid ; 4-[2S-(2R-(3-Biphenyl-4-yl-pyrrol- 1 -yl)-3 -carboxy-propionylamido)-4- methyl-pentanoylamino]-benzoic acid methyl ester ; 3-(R)-(2-Benzyloxy-phenyl)-1-(S)-hydroxymethyl-ethylcarbamoy l)-6- biphenyl-4-yl-hexanoic acid ; 6-Biphenyl-4-yl-3-(R)-(2-hydroxy-1-(S)-(4-hydroxy-benzyl)- ethylcarbamoyl)-hexanoic acid; 6-Biphenyl-4-yl-3- (l -hydroxyimino-ethyl) -hexanoic acid ; N-[2-(3-(4-biphenyl)propyl)-5,5-difluoro-4-oxopentanoyl)-L-t -leucine, N'- 4-(methylthio)phenyl amide; 6-Biphenyl-4-yl-3-(R)-(2-hydroxy-1-(S)-(4-hydroxy-benzyl)- ethylcarbamoyl) -hexanehydroxamicacid ; 4- {2-[2-carboxymethyl-5-(4'-sulfamoyl-biphenyl-4-yl)-pentanoyl amino]- 4-methyl-pentanoylamino}-benzoic acid methyl ester ; 2- (2-Biphenyl-4-yl-ethylsulfanyl) -cyclohexane carboxylic acid hydroxyamide ; 3-Acetyl-6-biphenyl-4-yl-3-hexanoic acid ; N-[5-(Biphen-4-yl)-2-(1-carboxy-2-hydroxybut-1-yl)pentanoyl] -t-L- leucine, N'-(4-methylthiophenyl)amide; 6-Biphenyl-4-yl-3-(2-hydroxy-cyclohexylcarbamoyl)-hexanoic acid; 2-(3-Biphenyl-4-yl-propyl)-N4-hydroxy-N1-(2-hydroxy-cyclohex yl)- succinamide ; 6-Biphenyl-4-yl-3-(1-hydroxyimino-ethyl)-hexanoic acid hydroxamide ; 6-Biphenyl-4-yl-3-(2-Hydroxy-cyclohexylcarbamoyl)-hexanoic acid; 6-Biphenyl-4-yl-3-[2,2-dimethyl-1-(pyridin-4-ylcarbamoyl)- propylcarbamoyl]-hexanoic acid ethyl ester ; 2-(3-Biphenyl-4-yl-pyrrol-1-yl)-3-carboxy-N-(1-hydroxy-3-phe nyl-prop- 2-yl) -propionamide ; N-[5-(Biphen-4-yl)-2-(1-carboxy-2-hydroxyethyl)pentanoyl]-L- t-leucine, N'-(4 -methylthiophenyl)amide;

3 -(R)-(2-Hydroxy- 1 -(S)-(1 H-imidazol-4-yl)-ethylcarbamoyl)-6-(4-(2- <BR> <BR> <BR> <BR> <BR> <BR> methyl-thiazol-4-yl)-phenyl)-hexanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 3- (R) - (2-Hydroxy-l- (S) - (lH-imidazol-4-yl) -ethylcarbamoyl) -6- (4- (2- <BR> <BR> <BR> <BR> <BR> <BR> methyl-thiazol-4-yl) -phenyl) -hexanehydroxamic acid ; 5-Biphenyl-4-yl-2-(1-hydroxymethyl-3-methylsulfanyl-propylca rbamoyl)- pentanoic acid ; 2-(3-Biphenyl-4-yl-propyl)-N-hydroxy-N'-(1-hydroxymethyl-3- methylsulfanyl-propyl) malonamide ; 6-Biphenyl-4-yl-3-(3-hydroxy-piperidine-1-carbonyl)-hexanoic acid; 6-Biphenyl-4-yl-3-(3-hydroxy-piperidine-1-carbonyl)-hexanoic acidhydroxyamide ; 1-(4-Methoxy-benzenesulfonyl)-piperidine-2-carboxylic acid hydroxyamide ; 1- [4-Bromo-phenoxy) -benzenesulfonyl) -piperidine-2-carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> N- (I -Benzyl-2-methoxy-ethyl) -3- (3-biphenyl-4-yl-pyrrol-1-yl) -succinamic <BR> <BR> <BR> <BR> <BR> <BR> acid ; N- (1-Benzyl-2-methoxy-ethyl) -3- (3-biphenyl-4-yl-pyrrol-1-yl) -succinamic hydroxamic acid ; <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3(R)-2(S)-hydroxy-(1 (S)-hydroxymethyl-2,2-dimethyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl) -hexanoic acid ; 3-(1-Benzyl-2-hydroxy-ethylcarbamoyl)-5-methyl-hexanoic acid; N 1 -(1 -benzyl-2-hydroxy-ethyl)-N4-hydroxy-2-isobutyl-succinamide; 6-Biphenyl-4-yl-3(R)-2(S)-hydroxy-(1(S)-hydroxymethyl-2,2-di methyl- propylcarbamoyl) -hexanoic hydroxamic acid ; 1- [4-Bromo-phenoxy) -benzenesulfonyl) -piperidine-2-carboxylic acid ; 6-Biphenyl-4-yl-3-(2-hydroxy-1-hydroxmethyl-propylcarbamoyl) - hexanoic acid ; 6-Biphenyl-4-yl-3-(R)-(2-oxo-cyclohexyl-1-(S)-carbamoyl)-hex anoic acid; 6-Biphenyl-4-yl-3-(2-hydroxy-1-hydroxmethyl-propylcarbamoyl) - hexanoichydroxamic acid ;

2S-[(1 S-Benzyl-2-hydroxyethylcarbamoyl)-3R-biphenyl-4-yl-pyrrol- 1 -yl- methyl]-pentanoic acid; 3R-(3-Biphenyl-4-yl-pyrrol- 1 -yl)-N-(2R-hydroxy-cyclohexyl- 1 R-yl)- succinamic acid ; 2-(3-Biphenyl-4-yl-pyrrol-1-yl)-3-carboxamate-N-(1-hydroxy-3 -phenyl- prop-2 -yl) -propionamide; trans-2-(3-Biphenyl-4-yl-propyl)-cyclohexane carboxylic acid ; <BR> <BR> <BR> <BR> trans-2- (3-Biphenyl-4-yl-propyl) -cyclohexanecarboxylic <BR> <BR> <BR> <BR> <BR> <BR> acidhydroxyamide ; <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-3 -(R)-(1 -(S)-hydroxymethyl-2-(3 -pyridyl)- <BR> <BR> <BR> <BR> <BR> <BR> ethylcarbamoyl) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 6-Biphenyl-4-yl-2-(S)-hydroxy-3 -(R)-(1 -hydroxymethyl-2-(S)-( l H- <BR> <BR> <BR> <BR> <BR> <BR> imidazol-4-yl) -ethylcarbamoyl) -hexanoic acid ; <BR> <BR> <BR> <BR> <BR> 1- [4-Biphenyl-4-yloxy) -benzenesulfonyl) -piperidine-2-carboxylic acid ; 1 - [4-Biphenyl-4-yloxy)-benzenesulfonyl)-piperidine-2-carboxyli c <BR> <BR> <BR> <BR> acidhydroxamide ; <BR> <BR> <BR> <BR> <BR> <BR> 1-(4-Phenoxy-benzenesulfonyl)-piperidine-2-carboxylic acidhydroxamide; 6-Biphenyl-4-yl-2S-hydroxy-3R-(1S-hydroxymethyl-3-methylsulf anyl- propylcarbamoyl) -hexanoic acid ; 6-Biphenyl-4-yl-3-(R)-(1-(S)-hydroxymethyl-2-(3-pyridyl)- ethylcarbamoyl) -hexanehydroxamic acid ; 6-Biphenyl-4-yl-2S-hydroxy-3R-(1S-hydroxymethyl-3-methylsulf anyl- propylcarbamoyl) -hexanoic hydroxamic acid ; 1 -[4-(4-Bromo-phenoxy)-benzenesulfonyl] -4-(tert-butoxycarbonyl)- piperazine-2-carboxylic acidhydroxyamide; l- [4- (4-Bromo-phenoxy) -benzenesulfonyl] -piperazine-2-carboxylic acidhydroxyamide ; 3R-(3-Biphenyl-4-yl-pyrrol-1-yl)-N-[2-hydroxy-1S-(1H-imidazo l-4-yl- methyl) -ethyl] -succinamic acid trifluoroacetate ; 3R-(3-Biphenyl-4-yl-pyrrol-1-yl)-N-[1S-(methoxy-methylcarbam oyl)-3- methyl-butyl]-succinamic acid; N-(1-Acetyl-3-methyl-butyl)-3-(3-biphenyl-4-yl-pyrrol-1-yl)- succinamic acid ;

6-Biphenyl-4-yl-3-(R)-(2-oxo-1-tetrahydrofuran-3-(S)-ylcarba moyl)- hexanoic acid ; 3-[2,2-Dimethyl-1-(pyridin-4-ylcarbamoyl)-propylcarbamoyl]-2 -hydroxy- 5-methyl-hexanoic acid-hydrochloride salt ; N4-(2,2-Dimethyl-1-methylcarbamoyl-propyl)-2,N¹-dihydroxy-3 - <BR> <BR> <BR> isobutyl-succinamide ; <BR> <BR> <BR> 6-Biphenyl-4-yl-3-(R)-(2-oxo-azepan-3-(S)-ylcarbamoyl)-hexan oic acid; <BR> <BR> <BR> N-( l -Benzyl-2-hydroxy-ethyl)-3 -(4-biphenyl-4-yl-pyrazol- 1 -yl)- succinamic acid ; N-(8-Oxo-4-oxa-1,7-diaza-tricyclo[9.6.1.0 12,17]octadeca- 11 (18),12(17),13,15 -tetraen-9R-yl)-3 S-(3 -phenyl-pyrrol- 1 -yl)-succinamic acid; 4-Acetyl-1-[4-phenoxy-benzenesulfonyl]-piperazine-2-carboxyl ic acid, N-hydroxyamide ; l-(Diphenylphosphinic)-piperidine-2-carboxylic acid hydroxamide ; 3R-(3-Biphenyl-4-yl-pyrrol-1-yl)-N-[3S-(2RS-hydroxy-5-methyl )-hexyl]- succinamic acid ; <BR> <BR> <BR> N-( l -(S)-Benzyl-2-hydroxy-ethyl)-3-(R)-(2-biphenyl-4-yl- <BR> <BR> <BR> cyclopropylmethyl) -succinamic acid ; 6-Biphenyl-4-yl-3-(R)-(2-oxo-1-tetrahydrofuran-3-(S)-ylcarba moyl)- hexanehydroxamic acid ; 1 -[4-(4-Bromo-phenoxy)-benzenesulfonyl]-4-methyl-piperazine-2 - carboxylic acid N-hydroxyamide ; <BR> <BR> <BR> 4- (4-Methoxy-benzenesulfonyl) -thiomorpholine-3-carboxylic <BR> <BR> <BR> acidhydroxyamide ; 3-(Diphenylphosphinic)-propanoic acid; 3- (Diphenylphosphinic) -propanoic acid hydroxyamide ; 4- [2- (2-Carboxymethyl-5- (4- (3-hydroxy-propyl) -phenyl) - pentanoylamino) -4-methyl-pentanoylamino] -benzoic acid methyl ester ; <BR> <BR> <BR> 1 - [4-(4-Chlorophenoxy)benzenesulfonyl] -N-hydroxy-4-(N- <BR> <BR> <BR> methylcarbamoyl) piperazine-2-carboxamide ; <BR> <BR> <BR> 4- [4- (4-Bromo-phenoxy) -benzenesulfonyl] -thiomorpholine-3-carboxylic acid N-hydroxyamide ;

3-(3-Biphenyl-4-yl-pyrrol- 1 -yl)-N-(2,2-dimethyl- 1 -methylcarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> propyl) -succinamic acid ; 1- [4-Phenoxy-benzenesulfonyl] -piperazine-2-carboxylic acid, N-hydroxyamide ; 4[4-Phenoxy-benzenesulfonyl]-thiomorpholine-3-carboxylic acid N-hydroxyamide ; 3- [2-Biphenyl-4-yl-ethylsulfanyl] -tetrahydro-pyran--4-carboxylic acid N-hydroxyamide ; 6-Biphenyl-4-yl-3-(carboxylic acid)-hexanoic acid; <BR> <BR> <BR> <BR> 1- [4- (4-Bromo-phenoxy) -benzenesulfonyl] piperdine-2-amidoxime ; <BR> <BR> <BR> <BR> <BR> 2-(3-Biphenylnitrile-4-yl-pyrrol- 1 -yl)-3-carboxy-N-(1 -hydroxy-3-phenyl- <BR> <BR> <BR> <BR> <BR> <BR> prop-2-yl) -propionamide ; {3-[3-(3-Amino-phenyl)-propyl]-2-oxo-tetrahydro-furan-3-yl}- acetic acid; 6-Biphenyl-4-yl-2S-hydroxy-3R-(carboxylic acid)-hexanoic acid; 5-Biphenylvaleric acid ; 1- [4- (Methoxy) -benzenesulfonyl] piperdine-2-amidoxime ; 1-[4-Phenoxy-benzenesulfonyl]-4-methyl-piperazine-2-carboxyl ic acid <BR> <BR> <BR> N-hydroxyamide ; <BR> <BR> <BR> <BR> <BR> {3- (3- (3-Methylamino-phenyl) -propyl) -2-oxo-tetrahydro-furan-3-yl} - acetic acid ; 6-Biphenyl-4-yl-3-(R)-(2-oxo-azepan-3-(S)-ylcarbamoyl)- hexanehydroxamic acid ; 4-(1 H-Indole-2-sulfonyl)-thiomorpholine-3 -carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> 1 R- [4-Bromo-phenoxy) -benzenesulfonyl) -N-amino-piperidine-2- <BR> <BR> <BR> <BR> <BR> carboxamide ; <BR> <BR> <BR> <BR> <BR> <BR> 2-(3-Biphenyl-4-yl-propyl)-3, N-4-dihydroxy-N 1 -(1 (S)-hydroxymethyl-3- <BR> <BR> <BR> <BR> <BR> <BR> methanesulfinyl-propyl) -succinamide ; N- (1-Benzyl-2-hydroxy-ethyl) -3- [3- (4'-carbamoyl-biphenyl-4-yl) -pyrrol- 1-yl] -succinamic acid ; 1- (Methyl-phenylphosphinic) -piperidine-2- (R) -carboxylic acid hydroxamide ;

4- (4- (4-Chlorophenoxy) benzenesulfonyl) -N-hydroxy-morpholine-3R- <BR> <BR> <BR> <BR> <BR> <BR> carboxamide ; 2 S- [1 R-(3 -(4'-Cyano-biphenyl-4-yl)-pyrrol- 1 -yl)-N-(2,2-dimethyl- 1 S- hydroxymethylpropylcarbamoyl) -methyl)] -pentanoic acid ; 2(S,R)- { 1 S-Benzyl-2-hydroxyethylcarbamoyl-[3R-(4'-cyano-biphenyl-4- <BR> <BR> <BR> <BR> yl)-pyrrol-l-yl]-methyl}pentanoic acid; <BR> <BR> <BR> <BR> <BR> <BR> 2S-[3-(Biphenyl-4-yl)-pyrrol-1 R-yl-(1 S-hydroxymethyl-2,2-dimethyl- propylcarbamoyl)-methyl]-5-hydroxypentanoic acid; 1-(1,3-Dihydro-isoindole-2-sulfonyl)-piperidine-2-carboxylic acid hydroxamide ; 3 -[3-(4'-Carbamoyl-biphenyl-4-yl]-pyrrol- 1 -yl)-N-( l -hydroxymethyl-2,2- <BR> <BR> <BR> <BR> dimethyl-propyl) -succinamic acid ; <BR> <BR> <BR> <BR> <BR> 4-M ethyl-1 - (4- (4-chlorophenyl) benzenesulfonyl) -N-hydroxy-2R- piperazinecarboxamide hydrochloride ; 1 - [4-Chlorophenoxybenzenesulfonyl] -N-hydroxy-2R- piperazinecarboxamide ; 2-(3-Phenyl-propylsulfonyl)-cyclohexane carboxylic acid hydroxamide ; I-(Pyrolidine-l-sulfonyl)-piperidine-2-carboxylic acid hydroxyamide ; l-(Piperidine-l-sulfonyl)-piperidine-2-carboxylic acid hydroxyamide ; 4- [4-Bromo-phenoxy-benzenesulfonyl] -oxothiomorpholine-3 -carboxylic acid-N-hydroxyamide ; l- [4- (4-Methoxy-phenylsulfanyl) -benzenesulfonyl] -piperdine-2-carboxylic acid hydroxyamide ; 1 -[4-(4-Nitrile-phenoxy)-benzenesulfonyl]-4-(tert-butoxycarbo nyl)- piperazine-2-carboxylic acid N-hydroxyamide ; <BR> <BR> <BR> <BR> 2S-[3 -(Biphenyl-4-yl)-pyrrol- 1 R-yl-(1 S-hydroxymethyl-2,2-dimethyl- <BR> <BR> <BR> <BR> <BR> <BR> propylcarbamoyl) -methyl] -pent-4-enoic acid ; <BR> <BR> <BR> <BR> <BR> 6-Oxo-3 -(4-phenoxy-benzenesulfonyl)-hexahydro-pyrimidine-4- carboxylic acid hydroxamate ; <BR> <BR> 4-(t-Butoxycabonyl)- 1 -(4-(pyridin-2-yl)oxybenzensulfonyl)-N-hydroxy- <BR> <BR> <BR> <BR> <BR> piperazine-2-carboxamide ;

4- [ (4-Fluorophenoxy) -benzenesulfonyl] -thiomorpholine-3-carboxylic <BR> <BR> <BR> <BR> <BR> acid-N-hydroxyamide ; <BR> <BR> <BR> <BR> <BR> <BR> 4- [4- (Fluoro-phenoxy) -benzenesulfonyl] -oxothiomorpholine-3-carboxylic <BR> <BR> <BR> <BR> <BR> <BR> acid-N-hydroxyamide ; N- (2, 2-Dimethyl-1 S-hydroxymethyl-propyl) -3R- [3- (4-pyridin-4-yl- <BR> <BR> <BR> <BR> phenyl) -pyrrol-1-yl] -succinamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> N-(1 S-Benzyl-2-hydroxy-ethyl)-3 S -(5 -biphenyl-4-yl -furan-2-yl)- succinamic acid ; 4-(4-Butoxy-benzenesulfonyl)-thiomorpholine-3-carboxylic acid hydroxyamide ; 4-(4-Butoxy-benzenesulfonyl)-l-oxothiomorpholine-3-carboxyli c acid hydroxyamide ; 1- [4- (4-Fluorophenyl) benzenesulfonyl] -4- (tert-butoxycarboxyl) -2R- piperazine-2-carboxylic acid hydroxyamide ; l- ( (4- (4-Chlorophenyl) -piperazine) -l-sulfonyl) -piperidine-2-carboxylic acid hydroxamide ; cis-2-Phenethylsulfanyl-cyclohexanecarboxylic acid hydroxyamide ; N-(2-Hydroxy-1S-phenyl-ethyl)-3R-[3-(4-pyridin-4-yl-phenyl)- pyrrol-1- <BR> <BR> <BR> <BR> yl] -succinamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 1- [4- (4-Fluorophenyl) benzenesulfonyl) -N-hydroxy-2R- piperazinecarboxamide hydrochoride ; 1-(Diphenylphosphinic)-pyrolidine-2-(R)-carboxylic acid-hydroxyamide; N, N- { (Diphenylphosphinic) - (acetic acid-sodium salt)} -hydrazide; N-(1-Benzyl-2-hydroxy-ethyl)-3-(1-biphenyl-4-yl-1H-pyrrol-3- yl)- succinamic acid ; trans-2-Phenethylsulfonyl-cyclohexanecarboxylic acid hydroxyamide ; 1 - [4- (4-Fluorophenyl) -piperazine-1 -sulfonylj-piperidme-2-carboxylic acid hydroxamide ; l- [4- (4-Fluorophenylsulfanyl) -benzenesulfonyl] -piperidine-2-carboxylic acid hydroxyamide ; 4-[4-(Bromo-phenoxy)-benzenesulfonyl]-2,2-dimethyl-1-oxo- thiomorpholine-3-carboxylic acid hydroxyamide ;

N-(2,2-Dimethyl-1S-methylcarbamoyl-propyl)-3R-(3-phenyl-pyrr ol-1-yl)- succinamic acid ; 3R-(3-Biphenyl-4-yl)-N-(2-hydroxy-1S-hydroxymethyl-2-methyl- propyl)- succinamic acid ; l-(Pyrrolidine-l-carbonyl)-pyrrolidine-2(R)-carboxylic acid; 1- (Pyrrolidine-1-carbonyl) -pyrrolidine-2 (R) -carboxylic acid hyroxyamide ; l-Phenethylcarbamoyl-pyrrolidine-2(R)-carboxylic acid; R-4-[4-(Bromophenoxy)-benzenesulfonyl]-2,2-dimethyl-1-oxo- thiomorpholine-3-carboxylic acid hydroxyamide ; 4-(Ethoxycarbonyl)methyl- 1 -(4-(4-chlorophenyl)benzenesulfonyl)-N- hydroxy-2R-piperazinecarboxamide hydrochloride ; N-(2R-Hydroxy-indan- 1 R-yl)-3R-[3-(4-pyridin-4-yl-phenyl)-pyrrol- 1 -yl]- succinamic acid ; N-(4,4-Dimethyl-2-oxo-tetrahydro-furan-3S-yl)-3R-[3-(4-pyrid in-4-yl- phenyl) -pyrrol-1-yl] -succinamic acid ; N-(2,2-Dimethyl-1S-methylcarbamoyl-propyl)-3R-[3-(4-pyridin- 4-yl- phenyl-4-yl)-pyrrol-1-yl]-succinamic acid; 1 -Phenethylcarbamoyl-pyrrolidine-2- (R) -carboxylic acid hydroxyamide ; N- (2, 2-Dimethyl-1 S-methyl carbamoyl-propyl) -3R- [3- (4-propyl-phenyl) - pyrrol-1-yl] -succinamic acid ; 1-(4-Benzyl-piperazine-1-sulfonyl)-piperdine-2-carboxylic acid hydroxyamide ; 3 (S) -N-hydroxy-4- (4- (pyridin-4-yl) oxybenzenesulfonyl) -2, 2-dimethyl- tetrahydro-2H-1,4-thiazine-3-carboxamide; 2(R)-4-Methyl-1-(4-(4-fluorophenyl)benzenesulfonyl)-N-hydrox y- piperazine-2-carboxamide ; N-(2,2-Dimethyl-1-methyl carbamoyl-propyl)-3-(5-biphenyl-4-yl-furan-2- yl) -succinamic acid ; N-(2,2-Dimethyl-1S-methylcarbamoyl-propyl)-3R-(3-pyridin-4-y l-pyrrol- 1 -yl) -succinamic acid ; 1 - ( (2-Pyridyl) -4-piperazine-1 -sulfonyl) -piperdine-2-carboxylic acid hydroxyamide ;

1- [4- (Pyridin-4-ylsulfamyl) -benzenesulfonyl] -piperdine-2-carboxylic acid hydroxyamide ; N- (4-Phenoxy-benzenesulfonyl) -D-tert-leucine ; N-(4-Phenoxy-benzenesulfonyl)-D-tert-leucine, N-hydroxyamide; <BR> <BR> <BR> <BR> N-(8-oxo-4-oxa- 1,7-tricyclo[9.6.1.0 12,17]octadeca-11 (18),12(17),13,15- <BR> <BR> <BR> <BR> <BR> tetraen-9-yl) -3- [4- (4-pyridyl) -3-phenyl-pyrrol-1 -yl) -succinamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 3- [3- (4-Pyridyl) phenyl-4-yl-pyrrol-I -yl] -N- [2, 2-dimethyl-l- (4- pyridyl)carbamoyl-propyl]-succinamic acid; 2, 2-Dimethyl-4- [4- (pyridin-2-yloxy) -benzenesulfonyl] -thio-morpholine-3- carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> N- [4- (4-Fluorophenoxyl) benzenesulfonyl) -D-tert-leucine ; <BR> <BR> <BR> <BR> <BR> <BR> N- [4- (4-Fluorophenoxyl) benzenesulfonyl) -D-tert-leucine, N-hydroxyamide ; 2-[2-(N'-Acetyl-hydrazino)-2-oxo-ethyl]-5-biphenyl-4-yl-pent anoic acid ; 3 (R)-N-Hydroxy-4-(4-(pyridin-4-yl)oxybenzenesulfonyl)-2,2-dim ethyl- tetrahydro-2H-l, 4-thiazine-3-carboxamide hydrochloride ; 2-[4-(4-Chloro-phenoxy)-benzenesulfonylamino]-3,3-dimethyl-b utyric <BR> <BR> <BR> <BR> acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Chloro-phenoxy) -benzenesulfonylamino) -N-hydroxy-3, 3- <BR> <BR> <BR> <BR> <BR> dimethyl-butyramide ; <BR> <BR> <BR> <BR> <BR> <BR> 3 (R) -N-Hydroxy-4- (4- (fur-3-yl) phenoxybenzenesulfonyl) -2, 2-dimethyl- tetrahydro-2H-1,4-thiazine-3-carboxamide; <BR> <BR> <BR> <BR> N- (4-Phenoxy-benzenesulfonyl) -3, 3-dimethyl-S- (benzylthio) -D-cysteine ; <BR> <BR> <BR> <BR> <BR> <BR> N- (4-Phenoxy-benzenesulfonyl) -3, 3-dimethyl-S- (benzylthio) -D-cysteine, <BR> <BR> <BR> <BR> <BR> N-hydroxyamide ; 2- [4- (Pyridin-2-yl-oxy) -benzenesulfonylamino] -3, 3-dimethyl butyric acid ; <BR> <BR> 2- [4- (Pyridin-2-yl-oxy) -benzenesulfonylamino] -N-hydroxy-3, 3-dimethyl <BR> <BR> <BR> <BR> <BR> butyramide ; <BR> <BR> <BR> <BR> <BR> <BR> N- (4-Phenoxy-benzenesulfonyl) -3, 3-dimethyl-S- (methylthio) -D-cysteine ; <BR> <BR> <BR> <BR> <BR> 3-[3-(4'-Carbamoyl-biphenyl-4-yl)-pyrrol- 1 -yl]-N-(2,2-dimethyl- 1 - <BR> <BR> <BR> <BR> <BR> <BR> methylcarbamoyl-propyl) -succinamic acid ;

3- [3- (4'-Cyano-biphenyi-4-yl) -pyrrol- I -y] -N- (2, 2-dimethyl-I - <BR> <BR> <BR> methylcarbamoyl-propyl) -succinamic acid ; 2- (2-Biphenyl-4-yl-ethylsulfonyl) -cyclohex-1 -ene-carboxylic acid hydroxyamide ; 6-(2-Biphenyl-4-yl-ethyl sufonyl)-cyclohex-1-ene-carboxylic acid hydroxyamide ; N- (4-Pyridin-4-yl-oxy-benzenesulfonyl) -3, 3-dimethyl-S- (benzylthio) -D- cysteine ; 3-[3-4'-Carbamoyl-biphenyl-4-yl)-pyrrol- 1 -yl]-N-[2,2-dimethyl- 1 - (pyridin-4-yl-carbamoyl)-propyl]-succinamic acid; <BR> <BR> <BR> N- (4-Phenoxy-benzenesulfonyl) -3, 3-dimethyl-S- (methylthio) -D-cysteine, <BR> <BR> <BR> N-hydroxyamide ; 1- (4-Phenoxy-piperdine-1-sulfonyl) -piperdine-2-carboxylic acid hydroxyamide ; <BR> <BR> <BR> 3 (R) -4- [4- (4-Bromo) phenoxybenzenesulfonyl] -2, 2-dimethyl-tetrahydro- <BR> <BR> <BR> 2H-1,4-thiazine-3-carboxylic acid; N-(4-[4-Chloro-phenoxy]-benzenesulfonyl)-3,3-dimethyl-S-(met hylthio)- D-cysteine ; N-(4-[4-Chlorophenoxy]-benzenesulfonyl)-3,3-dimethyl-S-(meth ylthio) - D-cysteine, N-hydroxyamide ; N- (4- [4-Chlorophenoxy] -benzenesulfonyl)-3,3 -dimethyl-S - (methylsulfoxy)-D-cysteine, N-hydroxyamide; 2(R)-[4-(4-Fluoro-phenoxy)-benzenesulfonylamino]-3-methyl-3- (pyridin- 2-ylsulfanyl) -butyric acid ; 2(R)-[4-(4-Fluoro-phenoxy)-benzenesulfonylamino]-3-methyl-3- (pyridin- 3-ylsulfanyl) -butyric acid ; 2(R)-[4-(4-Fluoro-phenoxy)-benzenesulfonylamino]-3-methyl-3- (pyridin- <BR> <BR> <BR> 4-ylsulfanyl) -butyric acid ; <BR> <BR> <BR> cis-2-(2-Phenyl-ethanesulfonyl)-cycloheaxanecarboxylic acid hydroxyamide ; 3(R)-N-Hydroxy-4-(4-(imidaz- 1 -yl)phenoxybenzenesulfonyl)-2,2- dimethyl-tetrahydro-2H-1,4-thiazine-3-carboxamide;

3 (R) -N-Hydroxy-4- (4- (pyridin-4-yl) oxybenzenesulfonyl) -2, 2-dimethyl- tetrahydro-2H-1,4-thiazine-3-carboxamide; 4-[2-(2-Hydroxycabamoylmethyl-5-phenyl-pentanoylamino)-4-met hyl- pentanoyl-benzoic acid methyl ester ; trans-2- (2-Phenyl-ethanesulfonyl) -cyclohexanecarboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> 3, 3-Dimethyl-2- (4-phenoxy-phenylsulfanylmethyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Chlorophenyl) -piperazine-l-sulfonylamino] -3-methyl-3- (pyridin- 2-ylmethylsulfanyl)-butyric acid; 3R-[3-(4'-Cyano-biphenyl-4-yl)pyrrol-1-yl]-N-[2,2-dimethyl-1 S-(pyridin- 4-ylcarbamoyl)-propyl]-succinamic acid; 3,3-Dimethyl-2-(4-phenoxy-phenylsulfanylmethyl)-butyric acid, <BR> <BR> <BR> <BR> N-hydroxyamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-(2,2-dimethyl- 1 -methylcarbamoyl-propyl)-3 - [1 -(4-fluorophenyl)- 1 H- <BR> <BR> <BR> <BR> <BR> <BR> pyrrol-3-yl]-succinamic acid; 2(R)-[4-(4-Bromo-phenoxy)-benzenesulfonylamino]-3-methyl-3-( pyridi-n- 2-ylsulfanyl) -butyric acid ; 2- (2-Biphenyl-4-yl-ethanesulfonyl) -cyclohexanecarboxylic acid <BR> <BR> <BR> <BR> hydroxamate ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Chlorophenyl) -piperazine-l-sulfonylamino] -3-methyl-3- (pyridin- 2-ylmethylsulfanyl) -butyric acid, N-hydroxyamide ; 3, 3-Dimethyl-2- (4-phenoxy-phenylsulfonylmethyl) -butyric acid ; 3,3-Dimethyl-2-(4-phenoxy-phenylsulfonylmethyl)-butyric acid, N-hydroxyamide ; 3-tert-Butoxycarbonylmethylsulfanyl-2-(4-(4-fluoro- phenoxy) benzenesulfonylamino) -3-methyl-butyric acid ; 1-(4-PhenylSulfanyl-piperidine-l-sulfonyl)-piperidine-2-carb oxylic acid hydroxyamide ; 1- [4- (4-Fluoro-phenoxy) -benzenesulfonyl] -3, 3-dimethyl-5-oxo- piperazine-2-carboxylic acid ; <BR> <BR> N- (4- [4-Fluorophenoxy] -benzenesulfonylamino)-3 -methyl-3 -(1 -benzyl - <BR> <BR> <BR> <BR> <BR> <BR> imidazole-2-yl-sulfanyl) -butyric acid ;

2(R)-[4-(4-Fluoro-phenoxy)benzenesulfonylamino] -3 -methyl-3 -(pyridi-n- 2-yl-sulfanyl) -butyric acid, hydroxyamide ; 3 (R)-N-Hydroxy-4-(4-((pyridin-4 -yl)methyl)oxybenzenesulfonyl)-2,2 - dimethyl-tetrahydro-2H-1,4-thiazine-3-carboxamide; 1-[4-(4-Chloro-phenoxy)-benzenesulfonyl]-4-(1 -methyl-1H-imidazole-4- sulfonyl) -piperazine-2-carboxylic acid hydroxamide ; N- (2, 2-Dirnethyl-1 S-methylcarbamoyl-propyl) -3 R- [1- (4'-cyanobiphenyl- 4-yl)-1H-pyrrol-3-yl]-succinamic acid; 3-Carboxymethylsulfanyl-2-(4-(4-fluoro-phenoxy)- benzenesulfonylamino) -3-methyl-butyric acid ; 2,2-Dimethyl-1-oxo-4-[4-(pyridin-4yloxy)-benzenesulfonyl]-1S 14- thiomorpholine-3-carboxylic acid hydroamide ; l- [4- (Pyridin-2-ylsulfanyl) -piperidme-l-sulfonyl] -piperidine-2-carboxylic acid hydroxyamide ; 2(R)-[4-(4-(fur-3-yl)-phenoxy)-benzenesulfonylamino]-3-methy l-3- (pyridi-n-yl-sulfanyl) -butyric acid ; 2,2-Dimethyl-1-oxo-4-[4-(pyridin-4yloxy)-benzenesulfonyl]-1S 14- thiomorpholine-3-carboxylic acid hydroamide ; {2- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -2-hydroxycarbamoyl- 1, 1-dimethyl-ethylsulfanyl} -acetic acid tert-butyl ester ; 1- [4- (Pyridin-4-ylsulfanyl) -piperidine-1-sulfonyl] -piperidine-2-carboxylic acid hydroxyamide ; 2(R)-[4-(4-Bromo-phenoxy)benzenesulfonylamino]-3-methyl-3-(p yridi-n- yl-sulfanyl) -butyric acid, hydroxyamide ; trans-2- (2-Biphenyl-4-yl-ethylsulfanyl) -cyclohexanecarboxylic acid hydroxyamide ; N-[1S-(1H-Imidazol-2-yl)-3-methyl-butyl]-3R-[3-(4-pyridin-4- yl-phenyl) - pyrrol- 1 -yl]-succinamic acid formate ; <BR> <BR> <BR> <BR> N-Methyl-3-[3-(4-pyridin-4-yl-phenyl)-pyrrol-1-yl]-succinami c acid; <BR> <BR> <BR> <BR> <BR> <BR> N(4)-(2,2-Dimethyl - 1 S-hydroxymethyl-propyl)-N( I )-hydroxy-3 R- [3 -(4- pyridin-4-yl-phenyl)-pyrrol-1-yl]-succindiamide;

{2-[4-(4-Fluoro-phenoxy)-benzenesulfonylamino] -2-hydroxycarbamoyl- <BR> <BR> <BR> <BR> <BR> <BR> l,l-dimethyl-ethylsulfanyl}-acetic acid; 1- [4 [ (4-Fluoro-phenoxy) -benzenesulfonyl)] -3, 3-dimethyl -5-oxo- piperazine-2-carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> N- (4- [4-Bromophenoxy] -benzenesulfonylamino)-3 -methyl-3 -(1 -benzyl- <BR> <BR> <BR> <BR> <BR> <BR> imidazole-2-yl-sulfanyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3R-[3-(4'-Cyanobiphenyl-4-yl)-pyrrol- 1 -yl]-N-(2,2-dimethyl- 1 S- hydroxymethyl-propyl)-succinamic acid; 2-(R)-[4-(4-Iodophenoxy)benzenesulfonylamino]-3-methyl-3-(py ridi-n-2- yl-sulfanyl) -butyric acid ; 0 3R-[3-(4-Cyano-phenyl)-pyrrol-1-yl]-N-(2,2-dimethyl-1S-hydro xymethyl- propyl) -succinamic acid ; 2(R)-[4-(4-Iodo-phenoxy)benzenesulfonylamino]-3-methyl-3-(py ridi-n-yl- sulfonyl) butyric acid, hydroxyamide ; 2(R)-[4-(4-Nitrile-phenoxy)benzenesulfonylamino]-3-methyl-3- (pyridi-n- <BR> <BR> <BR> <BR> yl-sulfonyl) butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Fluoro-phenoxy) -benzene sulfonylamino] -3, 3-dimethyl-pent-4- enoic acid ; <BR> <BR> <BR> <BR> 2- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -3-methyl-3- (5-methyl- <BR> <BR> <BR> <BR> <BR> <BR> isoxazole-3-ylmethylsulfanyl) -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Bromo-phenoxy) -benzenesulfonylamino] -3-methyl-3- (5-methyl- <BR> <BR> <BR> <BR> <BR> <BR> isoazole-3-ylmethylsulfanyl) -butyric acid ; 2- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -N-hydroxy-3-methyl-3- (5-methyl-isoxazole-3-ylmethylsulfanyl) -butyramide ; 2-[4-(4-Bromo-phenoxy)-benzenesulfonylamino]-N-hydroxy-3-met hyl-3- <BR> <BR> <BR> <BR> (5-methyl-isoxazole-3-ylmethylsulfanyl) -butyramide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Fluorophenoxy) -benzenesulfonylamino] -3-methyl-3- (carbomethoxyethylsulfanyl)-butyric acid; 1- [2- (Benzothiazol-2-ylsulfanyl) -piperidine-1-sulfonyl] -piperidine-2- carboxylic acid hydroxyamide ;

3R-[3-(4-Cyano-phenyl)-pyrrol-1-yl]-N-(2,2-dimethyl-1S- <BR> <BR> <BR> <BR> methylcarbamoyl-propyl) -succinamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 2- [4- (4-Fluorophenoxy) -benzenesulfonylamino] -3-methyl-3- (hydroxyethylsulfanyl)-butyric acid; [4-Methoxy-benzenesulfonylamino] -3 -methyl-3 -(pyridin-2-yl-sulfanyl)- butyric acid ; N-(4,4-Dimethyl-2-oxo-tetrahydro-furan-3S-yl)-3R-[1-(4'-cyan obiphenyl- 4-yl)-1H-pyrrol-3-yl]-succinamic acid; 2-[4-(4-Fluorophenoxy)-benzenesulfonylamino] -3 -methyl-3 - (amidoethylsulfanyl)-butyric acid; [4-Methoxy-benzenesulfonylamino] -3-methyl-3-(pyridin-2-ylsulfanyl)- butyric acid ; 2- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -3, 3-dimethyl-5-phenyl- pent-4-enoic acid ; 5- [4- (4-Fluoro-phenoxy) -benzenesulfonyl] -4, 5, 6, 7-tetrahydro-3H- imidazole [4,5,-c]pyridine-6-carboxylic acid hydroxyamide 2(R)-[4-(4-Methylphenoxy)benzenesulfonylamino]-3-methyl-3-(p yridi-n- <BR> <BR> <BR> <BR> yl-sulfonyl) butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> 3 (S) -4- (4- ( (Pyrid-4-yl) oxy) benzenesulfonyl) -2, 2-dimethyl-tetrahydro-2H- <BR> <BR> <BR> <BR> <BR> <BR> 1,4-thiazine-3-carboxylic acid; 1- [4- (Pyridin-4-ylsulfanyl) -piperidine-1-sulfanyl] -piperidine-2-carboxylic acid hydroxyamide ; N- [ I -(1 H-imidazol-2-yl)-3 -methyl-butyl] -3 - [1 -(4'-cyanobiphenyl -4-yl)- 1H-pyrrol-3-yl]-succinamic acid; 3R-{3-[(4-Cyano-phenyl)-acetyl]-pyrrol-1-yl}-N-(2,2-dimethyl -1S- <BR> <BR> <BR> <BR> methylcarbamoyl-propyl) -succinamic acid ; <BR> <BR> <BR> <BR> <BR> <BR> 1 -[4-(4-Methoxy-phenylsulfamyl)-piperidine- 1 -sulfonyl]-piperidine-2- carboxylic acid hydroxamide ; 3R-[3-(4-Cyano-phenyl)-pyrrol-1-yl]-N-(2,2-dimethyl-1S- methylcarbamoyl-propyl) -succinamic acid methyl ester ; 2(R)- [4-(4-Methylphenoxy)benzenesulfonylamino]-3-methyl-3-(pyridi -n- yl-sulfonyl) butyric acid, hydroxyamide ;

1 - [4- (4-Methyl-phenylsulfamyl) -piperidine-1 -sulfonyl] -piperidine-2- carboxylic acid hydroxamide ; 4- (4-Methoxy-benzenesulfonyl) -2, 2-dimethyl-thiomorpholine-3- carboxylic acid ; 4-4 (-Methoxy-benzenesulfonyl) -2, 2-dimethyl-thiomorpholine-3- carboxylic acid hydroxyamide ; 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -2, 2-dimethyl-thiomorpholine- 3-carboxylic acid ; 4-[4-(4-Chloro-phenoxy)-benzenesulfonyl]-2,2-dimethyl-thiomo rpholine- 3-carboxylic acid hydroxyamide ; 2(R)- [4-(4-bromo-phenoxy)benzenesulfoxylamino]-3-methyl-3-(pyridi -n- yl-sulfuroxide) butyric acid, hydroxyamide ; 4-(4-Methoxy-bezensulfonyl)-2,2-dimethyl- 1 -oxo-thiomorpholine-3- carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> 2, 2-Dimethyl-4- [4- (pyridin-4-yloxy) -benzenesulfonyl] thiomorpholin-3-ol ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 4- [4- (4-Chloro-phenoxy) -benzenesulfonyl] -2, 2-dimethoxy-1 -oxo- thiomorpholine-3-carboxylic acid hydroxyamide ; 2-(R)-3-Methyl-3-(pyridin-2-yl-sulfanyl)-[4-(4-trifluorometh ylphenoxy) - <BR> <BR> <BR> <BR> benzenesulfonylamino] -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3 (R) -4- (4- (Pyridin-4-yl) oxybenzenesulfonyl) -2, 2-dimethyl-tetrahydro-2H- 1,4-thiazine-3-carboxamide; <BR> <BR> <BR> <BR> <BR> 2R-3-Methyl-3-[(5-methyl-isoxazol-3-yl)methylsulfanyl] - [4- (pyridin-4-yl- <BR> <BR> <BR> <BR> <BR> <BR> <BR> oxy) -benzenesulfonylamino] -butyric acid ; 2R-N-Hydroxy-3-methyl-3-[(5-methyl-isoxazol-3-yl)methylsulfa nyl]- [4- (pyridin-4-yl-oxy)-benzenesulfonylamino]-butyramide; 2R-[4-(4-Bromophenoxy)-benzenesulfonylamino]-3-hydroxy-3-met hyl- butyric acid ; 3(S)-2,2-Dimethyl-4-[4-(pyridin-4-ylsulfanyl)-benzenesulfony l]- thiomorpholine-3-carboxylic acid hydroxyamide ; 2R-3-Methyl-3- [ (5-methyl-isoxazol-3-yl) methylsulfanyl] - [4- (pyridin-4-yl- sulfanyl)-benzenesulfonylamino]-butyric acid; 2R-N-Hydroxy-3-methyl-3- [ (5-methyl-isoxazol-3-yl) methylsulfanyl] - [4- (pyridin-4-yl-sulfanyl)-benzenesulfonylamino]-butyramide;

3, 3-Dimethyl-2R- [4- (pyridin-4-ylsulfanyl) -piperidine-l-sulfonylamino] - butyric acid ; <BR> <BR> <BR> <BR> 3,3 -Dimethyl -N-hydroxy-2R- [4-(pyridin-4-ylsulfanyl)-piperidine- 1 - <BR> <BR> <BR> <BR> <BR> <BR> sulfonylamino] -butyramide ; <BR> <BR> <BR> <BR> <BR> 2R- [4- (4-Bromophenoxy) -benzenesulfonylamino] -N-hydroxy-3-methyl-3- <BR> <BR> <BR> <BR> <BR> [(1 -methyl-imidazol-2-yl)methylsulfanyl]-butyramide; <BR> <BR> <BR> <BR> <BR> <BR> 2R-[4-(4-Bromophenoxy)-benzenesulfonylamino]-3-methyl-3-[(1 -methyl- <BR> <BR> <BR> <BR> <BR> imidazol-2-yl) methylsulfanyl] -butyric acid ; <BR> <BR> <BR> <BR> <BR> <BR> N-Hydroxy-2- [ (4-methylbenzenesulfonyl) amino] acetamide ; <BR> <BR> <BR> <BR> <BR> 1- [4- (4-Imidazol-1-yl-phenoxy) -piperidine-1-sulfonyl] -piperidine-2- carboxylic acid hydroxyamide ; 1 - [4- (4-Imidazol-l -yl-phenylsulfanyl) -piperidine-l -sulfonylj-piperidine-2- carboxylic acid hydroxyamide ; 2 (R) - [4- (4-Chloro-benzoyl) -cyclohexanesulfonyl] -piperidine-l-carboxylic acid hydroxyamide ; 1 (R)-[4-(4-Chloro-benzoyl)-piperidine- 1 -sulfonyl]-piperidine-2-carboxylic acid amide ; I (R)-(4-Pyridin-2-yl-piperazine- 1 -sulfonyl)-piperidine-2-carboxylic acid hydroxyamide ; 1 (R)- [4-(4-Imidazol- 1 -yl-phenoxy)-piperidine- 1 -sulfonyl] -piperidine-2- carboxylic acid ; 1 (R) - [4- (4-Imidazol-l -yl-phenoxy) -piperidine-l -sulfonyl] - piperidine-2- carboxylic acid hydroxyamide ; <BR> <BR> <BR> <BR> N-Hydroxy-3, 3 -dimethyl-2R- [4- (morpholine-4-carbonyl) piperidine-1 - <BR> <BR> <BR> <BR> <BR> <BR> sulfonylamino] butyramide ; N-Hydroxy-3-methyl-3-(5-methyl-isoxazol-3-yl-methylsulfanyl) -2R-[4- (pyridin-4-ylsulfanyl)-piperidine-sulfonylamino]-butyramide; 4-(4'-Chloro-biphenyl-4-yl)-2RS-[2-(1,3-dioxo- 1,3-dihydro-isoindol-2-yl)- ethyl]-4-oxo-butyric acid; 4-(4'-Chloro-biphenyl-4-yl)-2R-[2-(1,3 -dioxo- 1,3 -dihydro-isoindol-2-yl)- ethyl]-4-oxo-butyric acid;

N-Hydroxy-2R- [4-(4-imidazol- 1 -yl-phenoxy)-piperidine- 1 - sulfonylamino]-3,3-dimethyl-butyramide; 2R-[4-(4-Chloro-benzoyl)-piperazine-1-sulfonylamino]-N-hydro xy-3- methyl-3-methylsulfanyl-butyramide ; N-Hydroxy-3-methyl-3-methylsulfanyl-2R-[4-(pyridin-4-ylsulfa nyl)- piperidine-1-sulfonylamino] -butyramide ; 4-(Pyridin-4-yloxy)benzenesulfonic acid; 4-(Pyridin-4-yloxy)benzenesulfonyl chloride hydrochloride ; (3S)-2,2-Dimethyl-3-thiomorpholine carboxylic acid ; 3 (R) -N-Hydroxy-4- (4- (pyridin-4-yl) oxybenzenesulfonyl) -2, 2-dimethyl- 1,1-dioxo-tetrahydro-2H-1,4-thiazine-3-carboxamide; 1 R-3 S-2,2-Dimethyl- 1 -oxo-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]- 1 - thiomorpholine-3-carboxylic acid amide ; 1S-3S-2,2-Dimethyl-1-oxo-4-[4-(pyridin-4-yloxy)-benzenesulfo nyl]-1- thiomorpholine-3-carboxylic acid amide ; and 4-[4-(1-Hydroxy-pyridin-4-yloxy)-benzenesulfonyl]-2,2-dimeth yl- thiomorpholine-3-carboxylic acid amide.

Especially preferred are the MMP inhibitors currently in clinical development, for example batimastat (2).

MMP compounds in clinical development include batimastat (2) for the treatment of malignant pleural effusion, and marimastat (1) for the treatment of pancreatic cancer. Galardin (3) is for the treatment of corneal ulcers, and a specific MMP-1 inhibitor is RO 31-9790 (4).

Compounds in Clinical Development All that is required to practice the present invention is to administer to a mammal suffering from atherosclerosis, an effective amount of a matrix metalloproteinase inhibitor and an ACAT inhibitor. Compounds which can inhibit the actions of matrix metalloproteinase enzymes can be identified utilizing routine in vitro and in vivo assays. Several compounds from within the foregoing classes have been evaluated in such standard assays and determined to be potent matrix metalloproteinase inhibitors. The assays measure the amount by which a test compound reduces the hydrolysis of a thiopeptolide substrate caused by a matrix metalloproteinase enzyme. Such assays are described in detail by Ye, et al., in Biochemis, Vol. 31, No 45,1992, (11231-11235), which is incorporated herein by reference.

Thiopeptolide substrates show virtually no decomposition or hydrolysis in the absence of a matrix metalloproteinase enzyme. A typical thiopeptolide substrate commonly utilized for assays is Ac-Pro-Leu-Gly-thioester-Leu-Leu- Gly-O Et. A 100 ,uL assay mixture will contain 50 mM of 2-morpholinoethane sulfonic acid monohydrate (MES, pH 6. 0) 10 mM CaC12, 100,uM thiopeptolide

substrate, and 1 mM 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB). The thiopeptolide substrate concentration is varied from 10 to 800 go to obtain Km and Kcat values. The change in absorbance at 405 nm is monitored on a Thermo Max microplate reader (molecular Devices, Menlo Park, CA) at room temperature (22°C). The calculation of the amount of hydrolysis of the thiopeptolide substrate is based on E412 = 13600 m~l cm~l for the DTNB-derived product 3-carboxy- 4-nitrothiophenoxide. Assays are carried out with and without matrix metalloproteinase inhibitor compounds, and the amount of hydrolysis is compared for a determination of inhibitory activity of the test compounds.

Several representative compounds have been evaluated for their ability to inhibit various matrix metalloproteinase enzymes. Table I below presents inhibitory activity for compounds from various classes. In the table, MMP-1 refers to interstitial collagenase ; MMP-2 refers to Gelatinase A ; MMP-3 refers to stromelysin ; MMP-7 refers to matrilysin ; and MMP-9 refers to Gelatinase B. Test compounds were evaluated at various concentrations in order to determine their respective 1050 values, the micromolar concentration of compound required to cause a 50% inhibition of the hydrolytic activity of the respective enzyme.

As noted above, any matrix metalloproteinase inhibitor can be used to treat or prevent atherosclerotic lesions according to this invention.

ACAT inhibitors useful in the practice of the instant invention are those of Formula I or a pharmaceutically acceptable salt thereof wherein : X and Y are selected from oxygen, sulfur and (CR'R") n wherein n is an integer of from 1 to 4 and R'and R'are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R"together form a spirocycloalkyl or a carbonyl ; R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl ; RI and R2 are each independently selected from

(a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected from phenyl, an alkyl group having from 1 to 6 carbon atoms and which is straight or branched, an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched ; phenoxy, hydroxy, fluorine, chlorine, bromine, nitro, trifluoromethyl, - COOH, -COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched, - (CH2) pNR3R4 wherein p is zero or one, and each of R3 and R4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms ; (b) 1 - or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected from phenyl, an alkyl group having from 1 to 6 carbon atoms and which is straight or branched, an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched ; hydroxy, phenoxy, fluorine, chlorine,

bromine, nitro, trifluoromethyl, - COOH, -COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched, - (CH2) pNR3R4 wherein p, R3 and R4 have the meanings defined above ; (c) arylalkyl ; (d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from I to 3 double bonds ; or (e) adamantyl or a cycloalkyl group wherein the cycloalkyl moiety has from 3 to 6 carbon atoms.

Preferred compounds of the instant invention are those of Formula I : wherein R1 is phenyl or is phenyl disubstituted in the 2, 6-positions, wherein R2 is phenyl or is phenyl disubstituted in the 2, 6-positions, wherein each of Rl and R2 is phenyl, wherein each phenyl is disubstituted in the 2, 6-position, wherein R1 is phenyl disubstituted in the 2, 6-positions and R2 is phenyl trisubstituted in the 2, 4, 6-positions, wherein R1 is 2, 6-bis (l-methylethyl) phenyl and R2 is 2, 6-bis (l- methylethyl) phenyl or 2,4,6-tris( l -methylethyl)phenyl, wherein one of R1 and R2 is the group wherein t is zero or 1 to 4 ; w is zero or 1 to 4 with the proviso that the sum of t and w is not greater than 5 ;

R5 and R6 are each independently selected from hydrogen or alkyl having from 1 to 6 carbon atoms, or when RS is hydrogen, R6 can be selected from the groups defined for R7; and R7 is phenyl or phenyl substituted with from 1 to 3 substituents selected from a straight or branched alkyl group having from 1 to 6 carbon atoms, straight or branched alkoxy group having from 1 to 6 carbon atoms, phenoxy, hydroxy, fluorine, chlorine, bromine, nitro, trifluoromethyl, -COOH, COOalkyl wherein alkyl has from 1 to 4 carbon atoms, or - (CH2) pNR3R4 wherein P, R3 and R4 have the meanings defined above.

Also preferred compounds of the instant invention are those of Formula I wherein X is oxygen, sulfur or (CR'R") n ; Y is oxygen, sulfur or (CR'R")n, with the proviso that at least one of X or Y is (CR'R") n wherein n is an integer of from 1 to 4 and R'and R"are each independently hydrogen, straight or branched alkyl of from 1 to 6 carbons, optionally substituted phenyl, halogen, hydroxy, alkoxy, acyloxy, cycloalkyl, or R'and R"taken together form a carbonyl or a spirocycloalkyl group of from 3 to 10 carbons ; R is hydrogen ; RI is phenyl optionally substituted, straight or branched alkyl of from 1 to 10 carbon atoms, cycloalkyl of from 3 to 10 carbon atoms ; R is phenyl optionally substituted, straight or branched alkyl of from 1 to 10 carbon atoms, cycloalkyl of from 3 to 8 carbon atoms, phenoxy optionally substituted with the proviso that only if X is (CR'R")n can RI be optionally substituted phenoxy and only if Y is (CR'R")n can R2 be optionally substituted phenoxy, and with the further proviso that at least one of R1 and R2 is optionally substituted phenyl or phenoxy.

More preferred compounds of the instant invention are those of Formula I wherein X is oxygen ;

Y is (CR'R")n wherein n is an integer of from 1 to 2 ; R is hydrogen ; RI is optionally substituted phenyl ; R2 is optionally substituted phenyl or phenoxy, straight or branched alkyl of from 1 to 10 carbons, or cycloalkyl of from 3 to 10 carbons ; and R'and R"are each independently hydrogen, straight or branched alkyl of from 1 to 6 carbons, optionally substituted phenyl, halogen, hydroxy, alkoxy, acyloxy, cycloalkyl, or R'and R"taken together form a carbonyl or a spirocycloalkyl.

Preferred compounds of Formula I include, but are not limited to the following : Sulfamic acid (phenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [ [2, 4, 6-tris (l -methylethyl) phenyl] acetyl-2, 6-bis (l -methyl- ethyl) phenyl ester, Sulfamic acid[[2,6-bisf l -methylethyl)phenyl]acetyl]-2,6-bisf l -methyl- ethyl) phenyl ester, Sulfamic acid [ [2, 4, 6-tris (l-methylethyl) phenyl] acetyl-2, 4, 6-tris (l-methyl- ethyl) phenyl ester, Sulfamic acid [ [2, 6-bis ( 1 -methylethyl) phenyl] acetyl] -2, 4, 6-tris ( 1 -methyl- ethyl) phenyl ester, Sulfamic acid [adamantaneacetylJ-2, 6-bis [1-methylethyl) phenyl ester, Sulfamic acid [ [2, 6-bis (l-methylethyl) phenyl] acetyl] -2, 6-bis (l-methyl- ethyl) phenyl ester-sodium salt, Sulfamic acid [ [2, 4, 6-tris (l-methylethyl) phenyl] acetyl] -2, 6-bis (l-methyl- ethyl) phenyl ester-sodium salt, Sulfamic acid (decanoyl)-2,6-bis-(1-methylethyl)phenyl ester, Sulfamic acid (dodecanoyl)-2,6-bis-(1-methylethyl)phenyl ester, 2, 6-Bis (l-methylethyl) -N- [ [ [2, 4, 6-tris (l-methylethyl) phenyl] methyl] - sulfonyl] benzeneacetamide, 2,6-Bis( l -methylethyl)-N-[[[2,4,6-trisf l -methylethyl)phenyl]methyl]- sulfonyl] benzeneacetamide-sodium salt,

2, 6-Bis ( 1-methylethyl) phenyl [ [ [2, 4, 6-tris ( 1-methylethyl) phenyl] methyl] - <BR> <BR> <BR> <BR> <BR> <BR> <BR> sulfonyl] carbamate, <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2,6-Bisf l -methylethyl)phenyl[[[2,4,6-trisf l -methylethyl)phenyl]methyl]- sulfonyl] carbamate-sodium salt, Sulfamic acid (1-oXo-3,3-diphenylpropyl)-2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid [2, 6-dichlorophenyl (acetyl)] -2, 6-bis (1-methylethyl) phenyl ester, Sulfamic acid [2, 6-dichlorophenyl (acetyl)] -2, 6-bis (I-methylethyl) phenyl ester, Sulfamic acid trans- [ (2-phenylcyclopropyl) carbonyl] -2, 6-bis (l- methylethyl) phenyl ester, Sulfamic acid [2, 5-dimethoxyphenyl (acetyl)] -2, 6-bis (l- methylethyl) phenyl ester, Sulfamic acid [2, 4, 6-trimethoxyphenyl (acetyl)] -2, 6-bis (l- methylethyl) phenyl ester, Sulfamic acid [2, 4, 6-trimethylphenyl (acetyl)] -2, 6-bis (l- methylethyl) phenyl ester, Sulfamic acid [2-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [3-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-methoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (oxophenylacetyl)-2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid [2-trifluoromethylphenyl(acetyl)]-2,6-bis(1- methylethyl) phenyl ester, Sulfamic acid (l-oXo-2-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclopentylphenylacetyl)-2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid (cyclohexylacetyl)-2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid (diphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (triphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(l-phenylcyclopentyl)carbonyl]-2,6-bis(l- methylethyl) phenyl ester,

Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1- methylethyl) phenyl ester, Sulfamic acid (l-oXo-2-phenylbutyl)-2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid (cyclohexylphenylacetyl) -2, 6-bis ( 1-methylethyl) phenyl ester, Sulfamic acid (l-oXo-2,2-diphenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [ (9H-fluoren-9-yl) carbonyl] -2, 6-bis (I-methylethyl) phenyl ester, Sulfamic acid (l-oXo-3-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [1-oxo-3- [2, 4, 6-tris (I-methylethyl) phenyl] -2-propenyl] - 2, 6-bis ( 1 -methylethyl) phenyl ester, Sulfamic acid [1-oxo--'5- [2, 4, 6-tris (I-methylethyl) phenyl] propyl] - 2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(acetyloxy) [2,4,6-trisf l -methylethyl)phenyl] acetyl] - 2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [hydroxy[2,4,6-tris(1-methylethyl)phenyl]acetyl]- 2,6-bis(l-methylethyl)phenyl ester, Sulfamic acid [fluoro[2,4,6-tris(1-methylethyl)phenyl]acetyl]- 2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1- methylethyl) phenyl ester sodium salt, Sulfamic acid [[2,4,6-tris(1 -methylethyl)phenoxy]acetyl]-2,6-bis(1 - methylethyl) phenyl ester, Sulfamic acid [[2,6-bis(1 -methylethyl)phenoxy]acetyl]-2,6-bis(1 - methylethyl) phenyl ester, and Sulfamic acid [[2,4,6-tris(l-methylethyl)phenyl]acetyl]- 2, 6-bis (phenyl) phenyl ester.

Other ACAT inhibitors useful in the practice of this invention are selected from : 4-Hexadecylamino-benzoic acid monosodium salt ; 3,5-Dimethyl-1-[5-(1,4,5-triphenyl-2H-imidazol-2-ylsulfanyl) -pentyl]-1H- pyrazole monosodium salt ;

8-(1,4,5-Triphenyl-2H-imidazol-2-yloxy)-octanoic acid; 9-Bromo-6,11-dihydro-dibenzo[b,e]oxepine-11-carboxylic acid (2, 6- <BR> <BR> <BR> <BR> diisopropyl-phenyl) -amide ; <BR> <BR> <BR> <BR> <BR> <BR> 5- ( (3, 5-Di-tert-butyl-4-hydroxy-phenylamino) - { [4- (2, 2-dimethyl-propyl) - <BR> <BR> <BR> <BR> <BR> <BR> benzyl]-hexyl-amino} -methylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione; <BR> <BR> <BR> <BR> <BR> 3- (2, 4-Difluoro-phenyl) -l- [4- (2, 2-dimethyl-propyl) -benzyl] -l-heptyl-urea ; <BR> <BR> <BR> <BR> <BR> <BR> 1 -Heptyl- 1 -[4-(3 -methyl-butyl)-benzyl] -3 -(2,4,6-trifluoro-phenyl)-urea; 3-(2,4-Difluoro-phenyl)-1-[5-(4,5-diphenyl-1H-imidazol-2-yls ulfanyl)- <BR> <BR> <BR> <BR> pentyl]- 1 -heptyl-urea; <BR> <BR> <BR> <BR> <BR> 1 -Butyl-3- {2-[3-(5-ethyl-4-phenyl-imidazol- 1 -yl)-propoxy] -6-methyl-<BR> <BR> <BR> <BR> <BR> <BR> phenyl} -urea; l- (2- {2- [4- (2, 2-Dimethyl-propyl) -phenyl] -ethyl} -4, 6-difluoro-phenyl) - 3-heptyl-urea ; Octadeca-9, 12-dienoic acid (l-phenyl-ethyl)-amide; 3-(1H-Indol-3-yl)-2-octadec-9-enoylamino-propionic acid ethyl ester ; 3-(Dimethyl-nonyl-silanyl)-N-(1-phenyl-2-p-tolyl-ethyl)-prop ionamide; (R) 2-Hexyl-decanoic acid (6-methyl-2,4-bis-methylsulfanyl-pyridin-3-yl)- amide ; N-[2-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-ethyl]-4-fluoro- <BR> <BR> <BR> <BR> benzenesulfonamide ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (2-Ethoxy-ethylsulfanyl) -4, 5-diphenyl-1 H-imidazole ; 4-Cyano-N-[2-(4-cyano-phenyl)-3-methyl-5,5-bis-trifluorometh yl- 4,5-dihydro-3H-imidazol-4-yl]-N-methyl-benzamide; l- {3- [3- (l-Methyl-lH-imidazol-2-yl) -2-phenethyl-2H-chromen-6-yloxyj- propyl} -cyclopentanecarboxylic acid ethyl ester ; <BR> <BR> <BR> <BR> 1 -[4-(2-Chloro-phenyl)-2-ethyl-thieno[2,3-b]pyridin-5-yl] -3-(2,4-difluoro- <BR> <BR> <BR> <BR> <BR> <BR> phenyl) -urea ; <BR> <BR> <BR> <BR> <BR> <BR> 1- (2-Cyclohexyl- [ 1, 3] dithiolan-2-ylmethyl) -3- (2, 6-diisopropyl-phenyl) - urea ; 1-Cycloheptyl-1-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)- 3- (2, 4, 6-trimethyl-phenyl) -urea ; 1-{2-[4-(1,2-Dimethoxy-ethoxy)-phenyl]-ethyl}-3-(2,4-dimetho xy- phenyl) -1 -heptyl-urea ;

2-(4- {2-[3-(2,4-Dimethoxy-phenyl)- 1 -heptyl-ureido]-ethyl} -phenoxy)- 2-methyl-propionic acid ; <BR> <BR> <BR> <BR> 3 -(2,4-Difluoro-phenyl)- 1 -octyl- 1 -(2,3,4,5 -tetrahydro-benzo[b]oxepin- <BR> <BR> <BR> <BR> <BR> <BR> <BR> 5-yl) -urea ; <BR> <BR> <BR> <BR> <BR> <BR> N- (2, 6-Diisopropyl-phenyl) -2-octadecylsulfanyl-acetamide ; 2-Bromo-6,11-dihydro-dibenzo[b,e]oxepine-11-carboxylic acid <BR> <BR> <BR> <BR> (2, 6-diisopropyl-phenyl) -amide ; <BR> <BR> <BR> <BR> <BR> <BR> () N- (1, 2-Diphenyl-ethyl) -3- (2-heptyloxy-phenyl) -propionamide ; 2, 2-Dimethyl-dodecanoic acid (7-methoxy-4-oxo-chroman-8-yl) -amide ; (Z) 1-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-octadec-9- en- 1-one ; (Z)2,2,5,5-Tetramethyl-[1,3]dioxane-4-carboxylic acid [2- (2-octadec- 9-enoylamino-ethylcarbamoyl)-ethyl]-amide; 1-Benzyl-1-(5-methyl-3-phenyl-benzofuran-2-ylmethyl)-3-(2,4, 6-trifluoro- phenyl) -urea ; 5-Chloro-3-o-tolyl-benzofuran-2-carboxylic acid (2, 6-diisopropyl-phenyl) - amide ; <BR> <BR> <BR> <BR> 2-(2,4a-Dimethyl-4a,5-dihydro-naphthalen- 1 -ylsulfanyl)-N- {2-[(6,6- <BR> <BR> <BR> <BR> <BR> <BR> <BR> dimethyl-hepta-2,4-diynyl)-pentyl-amino]-ethyl } -acetamide; (Z)Octadec-9-enoic acid [2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-1-phenyl- <BR> <BR> <BR> <BR> ethyl]-amide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- (4-Dihexylamino-6-mercapto-2-methyl-pyrimidin-5-yl) -4- (phenyl- <BR> <BR> <BR> <BR> <BR> <BR> propyl-amino) -butyramide ; (Z) 1 -(6,7-Dimethoxy-3 -phenyl-3,4-dihydro- 1 H-isoquinolin-2-yl)-octadec- 9-en-l-one ; (trans) 1,4-Bis-(4-methoxy-phenyl)-3-(3-phenyl-propyl)-azetidin-2-on e; 1-Butyl-3-{2-dimethylamino-6-[3-(4-phenyl-imidazol-1-yl)-pro poxy]- <BR> <BR> phenyl} -urea; <BR> <BR> <BR> <BR> <BR> <BR> 1 - { 2-Dimethylamino-6- [3 -(4-phenyl-imidazol- 1 -yl)-propoxy] -phenyl } - <BR> <BR> <BR> <BR> <BR> <BR> <BR> 3-pentyl-urea ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 1- {2-Dimethylamino-6- [3- (5-methyl-4-phenyl-imidazol-1-yl) -propoxy] - <BR> <BR> <BR> <BR> <BR> <BR> phenyl } -3 -pentyl -urea;

1 -(2- {2-[4-(2,2-Dimethyl-propyl)-phenyl]-ethyl} -4,6-difluoro-phenyl)- <BR> <BR> <BR> <BR> <BR> 3-heptyl-urea ; <BR> <BR> <BR> <BR> <BR> <BR> (4S-trans)6-(4,5-Diphenyl- 1 H-imidazol-2-ylsulfanylmethyl)-4-hydroxy- <BR> <BR> <BR> <BR> <BR> <BR> 4-methyl-tetrahydro-pyran-2-one ; 2-(3-[1,3]Dioxan-2-yl-propylsulfanyl)-4,5-diphenyl-1H-imidaz ole; Hydroxy-phenyl-acetic acid 3,3,5-trimethyl-cyclohexyl ester; Acetic acid 1-(11-hydroxy-4-methoxy-9-methyl-5-oxo-5H,7H-6,12-dioxa- dibenzo[a,d]cycloocten-3-yl)-3-methyl-butyl ester; <BR> <BR> <BR> <BR> 10-Hydroxy-2, 4a, 6a, 6b, 9, 10, 12a-heptamethyl-4-octadecanoyloxy- <BR> <BR> <BR> <BR> <BR> 1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10, 11,12,12a,12b,13,14b-eicosahydro-picene- 2-carboxylic acid ; 3- [ (2, 2, 5, 5-Tetramethyl- [l, 3] dioxane-4-carbonyl) -amino] -propionicacid 2- [3- (2, 2-dimethyl-propyl) -3-nonyl-ureido] -cyclohexyl ester ; l- (2, 6-Diisopropyl-phenyl) -3- (2-p-tolyl-heptyl) -urea ; 1 - [4-(2-Chloro-phenyl)-6,8-dimethyl-quinolin-3 -yl] -3 -(2,4-difluoro- <BR> <BR> <BR> <BR> phenyl) -urea ; <BR> <BR> <BR> <BR> <BR> <BR> 1 - [4-(2-Chloro-phenyl)- 1,6,7-trimethyl-2-oxo- 1,2-dihydro-quinolin-3 -yl] -<BR> <BR> <BR> <BR> <BR> 3- (2, 4-difluoro-phenyl) -urea ; 1 -[4-(2-Chloro-phenyl)-6,7-dimethyl-2-oxo-2H-chromen-3-yl] - 3- (2, 4-difluoro-phenyl) -urea ; (S) l- [6-Bromo-5- (2-chloro-phenyl) -l, 3-dimethyl-2-oxo-2, 3-dihydro-lH- <BR> <BR> <BR> <BR> benzo [e] [l, 4] diazepin-7-yl] -3- (2-hydroxy-l -hydroxymethyl-1 -methyl-ethyl) -urea ; 3-(4,5-Diphenyl-1H-imidazol-2-ylsulfanylmethyl)-1-methyl-pip eridine; <BR> <BR> <BR> <BR> 2-(5,5-Dimethyl-[1,3]dioxan-2-yl)-4,5-diphenyl- lH-imidazole; <BR> <BR> <BR> <BR> <BR> <BR> 2,2-Dimethyl-5 - [3 -(1 -methyl- I H-imidazol-2-yl)-2-propyl-chroman- 6-yloxy] -pentanoic acid ethyl ester ; <BR> <BR> <BR> <BR> N- (4-Hexadecylamino-benzoyl) -4-methyl-benzenesulfonamide ; <BR> <BR> <BR> <BR> <BR> <BR> 2- (4-Chloro-phenyl) -6-cyclohexyl-4- (2-oxo-2-phenyl-ethyl) -6, 7-dihydro- 4H- 1,4,6,8a-tetraaza-s-indacene-5,8-dione; [2-(3-tert-Butyl-4-hydroxy-naphthalen-1-yl)-1-(diethoxy-phos phoryl)- vinyl] -phosphonic acid diethyl ester ;

5-[1 -(acetyloxy)-3-methylbutyl]-2'-(hydroxymethyl)-4-methoxy-4'- <BR> <BR> <BR> <BR> <BR> methylspiro[benzofuran-2(3H),1 '-cyclohexa-2',4'-diene]-3,6'-dione; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 5-[1 -(acetyloxy)-3-methylbutyl]-4-methoxy-4'-methyl- 3,6-dioxospiro[benzofuran-2(3H), 1'-cyclohexa-2',4'-diene]-2'-carboxaldehyde; (3α,4α,22α,24α)-3-hydroxy-22-[(1-oxooctadecyl)oxy]-24-no rolean-12-en- 29-oic acid ; 1- [5- (4, 5-Diphenyl-IH-imidazole-2-sulfinyl) -pentyl] -3, 5-dimethyl-IH- pyrazole ; and <BR> <BR> N-butyl-3 - [ [ (4-decyloxyphenyl) carbonyl] amino] -4- (methylthio) - <BR> <BR> <BR> <BR> <BR> <BR> <BR> benzamide ; The compounds, both ACAT and MMP inhibitors, include all possible stereoisomers.

METHODS The direct antiatherosclerotic potential of ACAT and MMP inhibitors is evaluated in a model of atherosclerotic lesion regression. Male New Zealand White rabbits (Kuiper Farms, Gary, Indiana) weighing 1. 2 to 1. 5 kg are meal-fed a chow diet (Purina 5321) supplemented with 0. 5% cholesterol (C), 3% peanut (PNO) oil, and 3% coconut (CNO) oil diet for a total of 9 weeks followed by a 0% C, 3% PNO, and 3% CNO diet (chow/fat diet) for 6 weeks prior to an 8-week administration of the ACAT inhibitor, for example, sulfamic acid [ [2, 4, 6-tris- (I-methylethyl)phenyl]acetyl-2,6-bis(l-methylethyl)phenyl ester, the HMG-CoA reductase inhibitor, for example, simvastatin, either alone or together. The dietary regimen consists of feeding 30 g for the first week, 40 g for 2 weeks, 50 g for 2 weeks, 60 g for 4 weeks, 70 g for the next 6 weeks, and 80 g for the final 8 weeks. After 1 week of diet initiation, a chronic endothelial injury is induced in the abdominal aorta and femoral artery by surgically inserting a sterile, indwelling, 18-cm nylon monofilament with a diameter of 200 1M into the lumen of the right femoral artery. After the initial 15-week lesion induction phase, which consists of both a hypercholesterolemic and plasma cholesterol normalization stage, the animals are randomized on the basis of their 24-hour postmeal plasma total cholesterol values into groups which are not statistically different. A group of animals, termed the time zero control (n = 16), is necropsied prior to drug administration while a second group, termed the progression control (n = 16), is maintained on the chow/fat diet for the remaining 8 weeks of the study. Additional groups of animals are administered either ACAT inhibitors, MMP inhibitors, or coadministered both compounds.

Other ACAT inhibitors useful in the practice of the instant invention are those of Formula 1 below wherein n is zero, one or two ; wherein R1 is selected from

(a) phenyl which is unsubstituted or is substituted with from one to three substituents selected from : alkyl having from 1 to 4 carbon atoms and which is straight or branched, alkoxy having from 1 to 3 carbon atoms and which is straight or branched, alkylthio having from 1 to 3 carbon atoms and which is straight or branched, hydroxy, phenyl, fluorine, chlorine, bromine, nitro, cyano, trifluoromethyl, - COOH, -COOalkyl wherein alkyl has from 1 to 4 carbon atoms and which is straight or branched, - (CH2) mNR5R6 wherein m is zero or one, and each of Rs and R6 is hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms ; (b) I - or 2-naphthyl which is unsubstituted or substituted with 1 to 3 substituents selected from : alkyl having from 1 to 4 carbon atoms and which is straight or branched, alkoxy having from 1 to 3 carbon atoms and which is straight or branched, hydroxy, fluorine, chlorine, bromine, nitro, cyano, trifluoromethyl, - COOH, -COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched, - (CH2) mNR5R6 wherein m, R5, and R6 have the meanings defined above ; (c) the group wherein R7 is a lower alkyl group having from 1 to 3 carbon atoms and is straight or branched ; (d) the group wherein Rg and R9 are straight or branched alkyl having from 1 to 4 carbon atoms or phenyl, and R l g is a straight or branched hydrocarbon group having from I to 18 carbon atoms which is saturated or is unsaturated containing one double bond or two nonadjacent double bonds ; phenyl ; phenyl substituted with from one to three substituents selected from straight or branched alkyl having 1 to 4 carbon atoms, straight or branched alkoxy having from 1 to 3 carbon atoms, hydroxy, fluorine, chlorine, bromine, nitro, cyano, trifluoromethyl, -COOH, -COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched or - (CH2) mNR5R6 wherein m, ruz and R6 are as defined above ; or a heterocyclic group selected from 2-, 3-, or 4-pyridyl, 2-, 4-, or 5-pyrimidinyl, 2- or 3-pyrazinyl, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolinyl, or 3- or 4-pyridazinyl and the N-oxides thereof ; (e) the group

(f) the group

(g) a straight or branched hydrocarbon group having from 1 to 18 carbon atoms which is saturated or is unsaturated containing one double bond or two nonadjacent double bonds ; (h) a cycloalkyl group having from 3 to 8 carbon atoms ; (i) a heteroaromatic group selected from 2-, 3-, or 4-pyridyl which is unsubstituted or substituted with an alkyl group having from 1 to 4 carbon atoms or 2-, 4-, or 5-pyrimidinyl, and the N-oxides thereof ; (j) the group wherein --- denotes a single or double bond ; Y and Z are each independently hydrogen, a straight or branched alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 3 carbon atoms or halo ; X is oxygen or two hydrogen atoms ; Rl 1 is hydrogen or a straight or branched alkyl group of 1 to 4 carbon atoms, and n'is zero or one ; or (k) is selected from the group wherein R12, R13, R14, and R 15 are each independently hydrogen, halo, a straight or branched alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 3 carbon atoms, and alkylthio group of 1 to 3 carbon atoms, cycloaklylthio of five to seven carbon atoms, phenylalkylthio in which alkyl is 1 to 4 carbon atoms, substituted phenylthio, heteroarylthio, or heteroaryloxy ; and B, D, E, and G are nitrogen or carbon where one or more of B, D, and E is nitrogen ; with the proviso that when G = nitrogen the group is attached to the nitrogen atom of Formula I at the 4- or 5-position of the pyrimidine ring (a and b) ; wherein R2 and R3 are the same or different and are selected from : (a) hydrogen, halo or one of R2 or R3 is hydroxy ; (b) a straight or branched alkyl group having from 1 to 12 carbon atoms, or a cycloalkyl group having from 3 to 8 carbon atoms ; (c) a phenyl or phenylalkyl group where alkyl is from 1 to 4 carbon atoms and which the phenyl ring unsubstituted or substituted with from 1 to 3 substituents selected from straight or branched alkyl having from 1 to 4 carbon atoms, straight or branched alkoxy having from 1 to 4 carbon atoms, alkythio, straight or branched having 1 to 4 carbon atoms, hydroxy, fluorine, chlorine, bromine, trifluoromethyl, cyano, nitro, phenyl, or (CH2) mNR5R6 wherein m, R5, and R6 have the meanings defined above ; (d) a straight or branched alkenyl group having from 2 to 6 carbon atoms ; or

(e) R2 and R3 taken together with the carbon atom to which they are attached form an alkylidene group of 1 to 4 carbon atoms, a benzylidene or a spiroalkyl group having from 3 to 7 carbon atoms ; or when R2 is hydrogen, F, alkyl of C 1 _ 12 atoms, R3 is a heteroaryl selected from a 5- or 6-membered monocyclic or fused bicyclic heterocyclic group containing at least 1 to 4 heteroatoms in at least one ring, said heteroatoms being nitrogen, oxygen, or sulfur and combinations thereof, said heterocyclic group being unsubstituted or substituted with an alkyl group having from 1 to 4 carbon atoms and the N-oxides thereof ; (g) 1 - or 2-naphthyl which is unsubstituted or substituted with 1 to 3 substituents selected from : alkyl having from 1 to 4 carbon atoms and which is straight or branched, alkoxy having from 1 to 3 carbon atoms and which is straight or branched, wherein R4 is a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and is saturated or is unsaturated and has 1 double bond or has 2 nonadjacent double bonds or is alkylthio having 1 to 20 carbon atoms and is saturated ; or a pharmaceutically acceptable salt or individual enantiomeric isomer thereof.

Specifically, the following compounds are useful in the instant invention : <BR> <BR> <BR> <BR> N- [2, 6-Bis (l-methylethyl) phenyl] -2-dodecyl-2H-tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-Dodecyl-N- (2, 4, 6-trimethoxyphenyl) -2H-tetrazole-5-acetamide ; N-(2,4-Difluorophenyl)-2-dodecyl-2H-tetrazole-5-acetamide; <BR> <BR> <BR> <BR> 2-Tetradecyl-N- (2, 4, 6-tri-methoxyphenyl) -2H-tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N- (4, 6-Dimethoxy-5-pyrimidinyl) -2-dodecyl-2H-tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> N-(4,6-Dimethoxy-5-pyrimidinyl)-2-dodecyl- 1 H-tetrazole-5-acetamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-Dodecyl-N- (3-methyl-2-pyridinyl) -2H-tetrazole-5-acetamide ; 2-Dodecyl-N- (1, 3, 5-trimethyl-1 H-pyrazol-4-yl) -2H-tetrazole-5-acetamide ; 1 -Dodecyl-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-tetrazole-5- acetamide; (#)2-Dodecyl-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazo le- 5-acetamide ; () 2-Dodecyl-N, a-diphenyl-2H-tetrazole-5-acetamide ;

(_)-N-[2,6-bisf l-Methylethyl)phenyl]-2-dodecyl-ot-phenyl-2H-tetrazole- 5-acetamide ; (#)-N-(2,4-Difluorophenyl)-2-dodecyl-α-phenyl-2H-tetrazole- 5-acetamide ; (#)-2-Octyl-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazol e- 5-acetamide ; (#)-2-Hexadecyl-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetr azole- 5-acetamide ; () -N- (4, 6-Dimethoxy-5-pyrimidinyl) -2-dodecyl-a-phenyl-2H-tetrazole- 5-acetamide ; <BR> <BR> <BR> <BR> (#)-N-(5,7-Dimethyl-1,8-naphthyridine-2-yl)-2 -dodecyl-α-phenyl-2H- <BR> <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-phenyl-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)- 2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (#)-N-Cyclopropyl-2-dodecyl-α-phenyl-2H-tetrazole-5-acetami de; <BR> <BR> <BR> <BR> <BR> <BR> () -2-Dodecyl-a-phenyl-N-2-pyridinyl-2H-tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> () -2-Dodecyl-N- (3-methyl-2-pyridinyl) -a-phenyl-2H-tetrazole- 5-acetamide ; () -2-Dodecyl-N- (3-methyl-2-pyridinyl) -2-phenyl-2H-tetrazole- 5-acetamide, N-oxide ; <BR> <BR> <BR> <BR> (#)-N-(1,1-Dimethylethyl)-2-dodecyl-α-phenyl-2H-tetrazole-5 -acetamide; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-(2-pyridyl)-N-(2,4,6-trimethoxyphenyl)-2H-t etrazole- 5-acetamide ; <BR> <BR> <BR> <BR> (_)-N-[2,6-Bisf l -methylethyl)phenyl]-2-dodecyl-a-2-pyridinyl-2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; 2-Dodecyl-a, a-dimethyl-N- (2, 4, 6-trimethoxyphenyl) -2H-tetrazole- 5-acetamide ; 2-Dodecyl-a, a'- (2-propenyl) -N- (2, 4, 6-trimethoxyphenyl) -2H-tetrazole- 5-acetamide ; 1-(2-Dodecyl-2H-tetrazol-5-yl)-N-(2,4,6-trimethoxyphenyl) - yclopentanecarboxamide ;

2-Tridecyl-a, a-dimethyl-N- (2, 4, 6-trimethoxyphenyl) -2H-tetrazole- 5-acetamide ; 2-Dodecyl-N- (2, 4, 6-trimethoxyphenyl) -2H-tetrazole-5-propanamide ; N-(2,6-bis(1-Methylethyl)phenyl)-2-dodecyl-2H-tetrazole-5-pr opanamide; N-(2,4-Difluorophenyl)-2-dodecyl-2H-tetrazole-5-propanamide; <BR> <BR> <BR> <BR> 1 -Dodecyl-N-(2,4,6-trimethoxyphenyl)- 1 H-tetrazole-5 -propanamide; <BR> <BR> <BR> <BR> <BR> () -n- (2, 4-Difluorophenyl) -1 -dodecyl-a-phenyl-1 H-tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> <BR> (#)-N-[2,6-bis(1-Methylethyl)phenyl]-1-dodecyl-α-phenyl-1H- tetrazole- 5-acetamide ; <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-methyl-α-phenyl-N-(2,4,6-trimethoxyphenyl) -2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-(4-fluorophenyl)-N-(2,4,6-trimethoxyphenyl) -2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-2-naphthalenyl-N-(2,4,6-trimethoxyphenyl)-2 H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-α-([1,1'-Biphenyl]-4-yl)-2-dodecyl-N-(2,4,6-trimethoxy- phenyl)-2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-methyl-N-(2,4,6-trimethoxy-phenyl)-2H-tetra zole- 5-acetamide ; (#)-2-Dodecyl-α-phenylmethyl-N-(2,4,6-trimethoxyphenyl)-2H- tetrazole- 5-acetamide ; (#)-2-Dodecyl-α-cyclohexyl-N-(2,4,6-trimethoxy-phenyl)-2H-t etrazole- 5-acetamide ; (-) -2-Dodecyl-a-phenyl-N- (2, 4, 6-trimethoxy-phenyl) -2H-tetrazole- 5-acetamide [a] D =-58° (1% in CH30H); (+)-2-Dodecyl-α-phenyl-N-(2,4,6-trimethoxy-phenyl)-2H-tetra zole- 5-acetamide [α]D= +55.1°(1% in CH3OH); (#)-N-[2,6-Bis(1-Methylethyl)phenyl]-2-dodecyl-α-fluoro-α- phenyl-2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> (#)-2-Dodecyl-α-fluoro-α-phenyl-N-(2,4,6-trimethoxy phenyl)-2H- <BR> <BR> <BR> <BR> <BR> <BR> tetrazole-5-acetamide ;

N- [2, 6-bis (l-Methylethyl) phenyl] -5-decyl-2H-tetrazole-2-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> N- [2, 6-bis (l-Methylethyl) phenyl-5-dodecyl-2H-tetrazole-2-acetamide ; <BR> <BR> <BR> <BR> <BR> () -N- [2, 6-bis (l-Methylethyl) phenyl] -5-dodecyl-a-phenyl-2H-tetrazole- 2-acetamide ; (#)-N-[2,6-bis(1-Methylethyl)phenyl]-5-dodecyl-α-pentyl-2H- tetrazole- 2-acetamide ; <BR> <BR> <BR> <BR> (_)-N-[2,6-bisf l -Methylethyl)phenyl-5-(dodecylthio)-(x-phenyl-2H- <BR> <BR> <BR> <BR> <BR> tetrazole-2-acetamide ; <BR> <BR> <BR> <BR> <BR> <BR> () -5-Decyl-a-phenyl-N- (2, 4, 6-trimethoxyphenyl-2H-tetrazole- 2-acetamide ; 5-Dodecyl-N-(2,4,6-trimethoxy-phenyl) -2H-tetrazole-2-acetamide ; (#)-5-Dodecyl-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetraz ole- 2-acetamide ; (#)-5-Dodecyl-α-pentyl-N-(2,4,6-trimethoxyphenyl)-2H-tetraz ole- 2-acetamide ; <BR> <BR> <BR> <BR> (_)-N-(2,4 -Difluorophenyl -5 -dodecyl -a-phenyl -2 H-tetrazole-2-acetamide; <BR> <BR> <BR> <BR> <BR> <BR> 5-Dodecyl-α,α-dimethyl-N-(2,4,6-trimethoxyphenyl)-2H-tetra zole- 2-acetamide ; (#)-5-(Dodecylthio)-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H- tetrazole- 2-acetamide ; or (#)-5-(Dodecylsulfinyl)-α-phenyl-N-(2,4,6)-trimethoxyphenyl )-2H- tetrazole-2-acetamide.

The compounds to be employed in the present invention can be prepared and administered in a wide variety of oral and parenteral dosage forms for treating and preventing atherosclerosis. The compounds can be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compounds can be administered by inhalation, for example, intranasally. Additionally, the compounds can be administered transdermally. It will be obvious to those skilled in the art that the following dosage forms may comprise as the active component, either a compound as a free base, acid, or a corresponding pharmaceutically acceptable

salt of such compound. The active compound generally is present in a concentration of about 5% to about 95% by weight of the formulation.

For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.

In powders, the carrier is a finely divided solid which is in a mixture with the finely divided active component.

In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.

The powders and tablets preferably contain from 5% or 10% to about 70% of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term"preparation"is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component, with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogenous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify.

Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution.

Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing, and thickening agents as desired.

Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.

Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration.

Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

The pharmaceutical preparation is preferably in unit dosage form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.

The quantity of active component in a unit-dose preparation may be varied or adjusted from 1 to 1000 mg, preferably 10 to 100 mg according to the particular application and the potency of the active component. The composition can, if desired, also contain other compatible therapeutic agents.

The compounds utilized in the pharmaceutical method of this invention are administered at a dose that is effective to inhibit the hydrolytic activity of one or more matrix metalloproteinase enzymes. Such effective amounts are thus those which prevent or treat CHF and ventricular dilatation. The compounds can also be used prophalactically at the same dose levels. The initial dosage of about 1 mg to about 100 mg per kilogram daily will be effective to prevent and treat heart failure. A daily dose range of about 5 to about 75 mg is preferred. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed.

Determination of the proper dosage for a particular situation is within the skill of the art. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstance is reached. For convenience, the total daily dosage may be divided and administered in portions during the day if desired. Typical dosages will be from about 0. 1 to about 500 mg/kg, and ideally about 25 to about 250 mg/kg.

The following examples illustrate typical formulations that can be utilized in the invention.

Tablet Formulation Ingredient Amount (mg) 2-(4'-bromobiphenyl-4-sulfonylamino)-3-methyl- 25 butyric acid ACAT Compound Lactose 50 Corn starch (for mix) 10 Corn starch (paste) 10 Magnesium stearate (1%) 5 Total 100 The biphenylsulfonamide, lactose, and corn starch (for mix) are blended to uniformity. The corn starch (for paste) is suspended in 200 mL of water and heated with stirring to form a paste. The paste is used to granulate the mixed powders. The wet granules are passed through a No. 8 hand screen and dried at 80°C. The dry granules are lubricated with the 1% magnesium stearate and pressed into a tablet. Such tablets can be administered to a human from one to four times a day for treatment of atherosclerosis and arthritis.

Preparation for Oral Solution Ingredient Amount (R)-2-(4'-Cyanobiphenyl-4-sulfonylamino)-3-phenyl- 400 mg propionic acid sodium salt ACAT Compound Sorbitol solution (70% N. F.) 40 mL Sodium benzoate 20 mg Saccharin 5 mg Red dye 10 mg Cherry flavor 20 mg Distilled water q. s. 100 mL The sorbitol solution is added to 40 mL of distilled water, and the biphenylsulfonamide is dissolved therein. The saccharin, sodium benzoate, flavor, and dye are added and dissolved. The volume is adjusted to 100 mL with distilled water. Each milliliter of syrup contains 4 mg of invention compound.

Parenteral Solution In a solution of 700 mL of propylene glycol and 200 mL of water for injection is suspended 20 g of (S) -2- (4'-amino-biphenyl-4-sulfonylamino) - 3- (3-ethoxyphenyl) -propionic acid. After suspension is complete, the pH is adjusted to 6. 5 with 1N sodium hydroxide, and the volume is made up to 1000 mL with water for injection. The formulation is sterilized, filled into 5. 0 mL ampoules each containing 2. 0 mL, and sealed under nitrogen.