| PATENT ASSIGNEE'S COUNTRY | USA |
| UPDATE | 05.00 |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 02.05.00 |
| PATENT TITLE |
Lactam metalloprotease inhibitors |
| PATENT ABSTRACT |
The present application describes novel lactams and derivatives thereof of formula I: ##STR1## or pharmaceutically acceptable salt forms thereof, wherein rings ring B is a 4-8 membered cyclic amide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | 02.10.98 |
| PATENT REFERENCES CITED | This data is not available for free |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed as new and desired to be secured by Letter Patent of United States is: 1. A compound of formula I: ##STR168## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein; A is selected from COR.sup.5, --CO.sub.2 H, CH.sub.2 CO.sub.2 H, --CO.sub.2 R.sup.6, --CONHOH, --CONHOR.sup.5, --CONHOR.sup.6, --NHR.sup.a, --N(OH)COR.sup.5, --SH, --CH.sub.2 SH, --SO.sub.2 NHR.sup.a, SN.sub.2 H.sub.2 R.sup.a, PO(OH).sub.2, and PO(OH)NHR.sup.a ; ring B is a 4-8 membered cyclic amide containing 0-1 additional carbonyl groups and 0-1 double bonds; R.sup.1 is U--X--Y--Z--U.sup.a --X.sup.a --Y.sup.a --Z.sup.a ; U is absent or is selected from: O, NR.sup.a, C(O), C(O)O, OC(O), C(O)NR.sup.a, NR.sup.a C(O), OC(O)O, OC(O)NR.sup.a, NR.sup.a C(O)O, NR.sup.a C(O)NR.sup.a, S(O).sub.p, S(O).sub.p NR.sup.a, NR.sup.a S(O).sub.p, and NR.sup.a SO.sub.2 NR.sup.a ; X is absent or selected from C.sub.1-10 alkylene, C.sub.2-10 alkenylene, and C.sub.2-10 alkynylene; Y is absent or selected from O, NR.sup.a, S(O).sub.p, and C(O); Z is absent or selected from a C.sub.3-13 carbocyclic group substituted with 0-5 R.sup.b and a 5-6 membered heterocyclic group containing 1 heteroatom from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; U.sup.a is absent or is selected from: O, NR.sup.a, C(O), C(O)O, OC(O), C(O)NR.sup.a, NR.sup.a C(O), OC(O)O, OC(O)NR.sup.a, NR.sup.a C(O)O, NR.sup.a C(O)NR.sup.a, S(O).sub.p, S(O).sub.p NR.sup.a, NR.sup.a S(O).sub.p, and NR.sup.a SO.sub.2 NR.sup.a ; X.sup.a is absent or selected from C.sub.1-10 alkylene, C.sub.2-10 alkenylene, C.sub.2-10 alkynylene; Y.sup.a is absent or selected from O, NR.sup.a, S(O).sub.p, and C(O); Z.sup.a is quinolinyl substituted with 0-5 R.sup.c ; R.sup.2 is selected from H, Q', C.sub.1-10 alkylene-Q', C.sub.2-10 alkenylene-Q', C.sub.2-10 alkynylene-Q', (CRR').sub.r' O(CRR').sub.r --Q', (CRR').sub.r' NR.sup.a (CRR').sub.r' --Q', (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r --Q', (CRR').sub.r' C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' C(O)(CRR').sub.r --Q', (CRR').sub.r' C(O)O(CRR').sub.r --Q', (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q', (CRR').sub.r'SO.sub.2 NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --Q', and (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --Q'; R, at each occurrence, is independently selected from H, CH.sub.3, CH.sub.2 CH.sub.3, CH.dbd.CH.sub.2, CH.dbd.CHCH.sub.3, and CH.sub.2 CH.dbd.CH.sub.2 ; R', at each occurrence, is independently selected from H, CH.sub.3, CH.sub.2 CH.sub.3, and CH(CH.sub.3).sub.2 ; alternatively, R.sup.1 and R.sup.2 combine to form a C.sub.3-13 carbocyclic group substituted with R.sup.1' and 0-3 R.sup.b or a 5-6 membered heterocyclic group containing 1 heteroatom selected from the group consisting of N, O, and S and substituted with R.sup.1' and 0-3 R.sup.b ; Q' is selected from H, a C.sub.3-13 carbocyclic group substituted with 0-5 R.sup.b and a 5-6 membered heterocyclic group containing 1 heteroatom selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; R.sup.1' is U.sup.a --X.sup.a --Y.sup.a --Z.sup.a ; R.sup.3 is selected from H, Q, C.sub.1-10 alkylene-Q, C.sub.2-10 alkenylene-Q, C.sub.2-10 alkynylene-Q, (CRR').sub.r' (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a (CRR').sub.r --Q, (CRR').sub.r C(O)(CRR').sub.r --Q, (CRR').sub.r C(O)O(CRR').sub.r --Q, (CRR').sub.r' OC(O)(CRR').sub.r --Q, (CRR').sub.r C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r --Q, (CRR').sub.r' OC(O)O(CRR').sub.r --Q, (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q, (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a SO.sub.2 (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a SO.sub.2 NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r" NHQ, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r NHC(O)OR.sup.a, and (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r NHC(O)(CRR').sub.r NHC(O)OR.sup.a, Q is selected from H, a C.sub.3-13 carbocyclic group substituted with 0-5 R.sup.b and a 5-6 membered heterocyclic group containing 1 heteroatom selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; R.sup.4 is selected from H, C.sub.1-10 alkylene-H, C.sub.2-10 alkenylene-H, C.sub.2-10 alkynylene-H, (CRR').sub.r' O(CRR').sub.r --H, (CRR').sub.r' NR.sup.a (CRR').sub.r --H, (CRR').sub.r' C(O)(CRR').sub.r --H, (CRR').sub.r' C(O)O(CRR').sub.r --H, (CRR').sub.r' OC(O)(CRR').sub.r --H, (CRR').sub.r' C(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r --H, (CRR').sub.r' OC(O)O(CRR').sub.r --H, (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' S(O).sub.p (CRR').sub.r --H, (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a SO.sub.2 (CRR').sub.r --H, and (CRR').sub.r' NR.sup.a SO.sub.2 NR.sup.a (CRR').sub.r --H; alternatively, R.sup.3 and R.sup.4 combine to form a C.sub.3-13 carbocyclic group substituted with R.sup.1' and 0-3 R.sup.b or a 5-6 membered heterocyclic group containing 1 heteroatom selected from the group consisting of N, O, and S and substituted with R.sup.1' and 0-3 R.sup.b ; R.sup.a, at each occurrence, is independently selected from H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.a', at each occurrence, is independently selected from H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.a", at each occurrence, is independently selected from H, C.sub.1-4 alkyl, benzyl, C.sub.3-7 carbocyclic group, or a 5 to 6 membered heteroaromatic ring containing 1 heteroatom selected from the group consisting of N, O, and S; alternatively, R.sup.a and R.sup.a" taken together with the nitrogen to which they are attached form a 5 or 6 membered ring; R.sup.b, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a", C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, and CF.sub.2 CF.sub.3 ; R.sup.c, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a, C(O)OR.sup.a, C(O) NR.sup.a R.sup.a', NR.sup.a C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, CF.sub.2 CF.sub.3, --CH(.dbd.NOH), --C(.dbd.NOH)CH.sub.3, (CRR').sub.s O(CRR').sub.s' R.sup.d, (CRR').sub.s S(O).sub.p (CRR').sub.s' R.sup.d, (CRR').sub.s NR.sup.a (CRR').sub.s' R.sup.d, phenyl, and a 5-6 membered heterocyclic group containing 1 heteroatom selected from the group consisting of N, O, and S; R.sup.5, at each occurrence, is selected from C.sub.1-10 alkyl substituted with 0-2 R.sup.b, and C.sub.1-8 alkyl substituted with 0-2 R.sup.d ; R.sup.d, at each occurrence, is independently selected from phenyl substituted with 0-3 R.sup.b, biphenyl substituted with 0-2 R.sup.b, naphthyl substituted with 0-3 R.sup.b and a 5-6 membered heteroaryl group containing 1 heteroatom selected from the group consisting of N, O, and S and substituted with 0-3 R.sup.b ; R.sup.6, at each occurrence, is selected from phenyl, naphthyl, C.sub.1-10 alkyl-phenyl-C.sub.1-6 alkyl-, C.sub.3-11 cycloalkyl, C.sub.1-6 alkylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.1-6 alkoxycarbonyloxy-C.sub.1-3 alkyl-, C.sub.2-10 alkoxycarbonyl, C.sub.3-6 cycloalkylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.3-6 cycloalkoxycarbonyloxy-C.sub.1-3 alkyl-, C.sub.3-6 cycloalkoxycarbonyl, phenoxycarbonyl, phenyloxycarbonyloxy-C.sub.1-3 alkyl-, phenylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.1-6 alkoxy-.sub.1-6 alkylcarbonyloxy-C.sub.1-3 alkyl-, --C.sub.1-10 alkyl-NR.sup.7 R.sup.7a, --CH(R.sup.8)OC(.dbd.O)R.sup.9, --CH(R.sup.8)OC(.dbd.O)OR.sup.9 ; R.sup.7 is selected from H and C.sub.1-10 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl-, and phenyl-C.sub.1-6 alkyl-; R.sup.7a is selected from H and C.sub.1-10 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl-, and phenyl-.sub.1-6 alkyl-; R.sup.8 is selected from H and C.sub.1-4 linear alkyl; R.sup.9 is selected from H, C.sub.1-8 alkyl substituted with 1-2 R.sup.e, C.sub.3-8 cycloalkyl substituted with 1-2 R.sup.e, and phenyl substituted with 0-2 R.sup.b ; R.sup.e, at each occurrence, is selected from C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-5 alkoxy, and phenyl substituted with 0-2 R.sup.b ; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; r', at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; r", at each occurrence, is selected from 1, 2, and 3; s, at each occurrence, is selected from 0, 1, 2, and 3; and, s', at each occurrence, is selected from 0, 1, 2, and 3. |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION This invention relates generally to novel lactam metalloprotease inhibitors, pharmaceutical compositions containing the same, and methods of using the same. BACKGROUND OF THE INVENTION There is now a body of evidence that metalloproteinases (MP) are important in the uncontrolled breakdown of connective tissue, including proteoglycan and collagen, leading to resorption of the extracellular matrix. This is a feature of many pathological conditions, such as rheumatoid and osteoarthritis, corneal, epidermal or gastric ulceration; tumor metastasis or invasion; periodontal disease and bone disease. Normally these catabolic enzymes are tightly regulated at the level of their synthesis as well as at their level of extracellular activity through the action of specific inhibitors, such as alpha-2-macroglobulins and TIMP (tissue inhibitor of metalloproteinase), which form inactive complexes with the MP's. Osteo- and Rheumatoid Arthritis (OA and RA respectively) are destructive diseases of articular cartilage characterized by localized erosion of the cartilage surface. Findings have shown that articular cartilage from the femoral heads of patients with OA, for example, had a reduced incorporation of radiolabeled sulfate over controls, suggesting that there must be an enhanced rate of cartilage degradation in OA (Mankin et al. J. Bone Joint Surg. 52A, 1970, 424-434). There are four classes of protein degradative enzymes in mammalian cells: serine, cysteine, aspartic and metalloproteinases. The available evidence supports that it is the metalloproteinases which are responsible for the degradation of the extracellular matrix of articullar cartillage in OA and RA. Increased activities of collagenases and stromelysin have been found in OA cartilage and the activity correlates with severity of the lesion (Mankin et al. Arthritis Rheum. 21, 1978, 761-766, Woessner et al. Arthritis Rheum. 26, 1983, 63-68 and Ibid. 27, 1984, 305-312). In addition, aggrecanase (a newly identified metalloproteinase enzymatic activity) has been identified that provides the specific cleavage product of proteoglycan, found in RA and OA patients (Lohmander L. S. et al. Arthritis Rheum. 36, 1993, 1214-22). Therefore metalloproteinases (MP) have been implicated as the key enzymes in the destruction of mammalian cartilage and bone. It can be expected that the pathogenesis of such diseases can be modified in a beneficial manner by the administration of MP inhibitors, and many compounds have been suggested for this purpose (see Wahl et al. Ann. Rep. Med. Chem. 25, 175-184, AP, San Diego, 1990). Tumor necrosis factor (TNF) is a cell associated cytokine that is processed from a 26 kd precursor form to a 17 kd active form. TNF has been shown to be a primary mediator in humans and in animals, of inflammation, fever, and acute phase responses, similar to those observed during acute infection and shock. Excess TNF has been shown to be lethal. There is now considerable evidence that blocking the effects of TNF with specific antibodies can be beneficial in a variety of circumstances including autoimmune diseases such as rheumatoid arthritis (Feldman et al, Lancet, 1994, 344, 1105) and non-insulin dependent diabetes melitus. (Lohmander L. S. et al. Arthritis Rheum. 36, 1993, 1214-22) and Crohn's disease (Macdonald T. et al. Clin. Exp. Immunol. 81, 1990, 301). Compounds which inhibit the production of TNF are therefore of therapeutic importance for the treatment of inflammatory disorders. Recently it has been shown that a matrix metalloproteinase or family of metalloproteinases, hereafter known as TNF-convertases (TNF-C), as well as other MP's are capable of cleaving TNF from its inactive to active form (Gearing et al Nature, 1994, 370, 555). This invention describes molecules that inhibit this conversion and hence the secretion of active TNF-a from cells. These novel molecules provide a means of mechanism based therapeutic intervention for diseases including but not restricted to septic shock, haemodynamic shock, sepsis syndrom, post ischaemic reperfusion injury, malaria, Crohn's disease, inflammatory bowel diseases, mycobacterial infection, meningitis, psoriasis, congestive heart failure, fibrotic diseases, cachexia, graft rejection, cancer, diseases involving angiogenesis, autoimmune diseases, skin inflammatory diseases, osteo and rheumatoid arthritis, multiple sclerosis, radiation damage, hyperoxic alveolar injury, periodontal disease, HIV and non-insulin dependent diabetes melitus. Since excessive TNF production has been noted in several disease conditions also characterized by MMP-mediated tissue degradation, compounds which inhibit both MMPs and TNF production may also have a particular advantage in diseases where both mechansisms are involved. There are several patents which disclose hydroxamate and carboxylate based MMP inhibitors. W095/09841 describes compounds that are hydroxamic acid derivatives and are inhibitors of cytokine production. ##STR2## European Patent Application Publication No. 574,758 A1, discloses hydroxamic acid derivatives as collagenase inhibitors having the general formula: ##STR3## GB 2 268 934 A and WO 94/24140 claim hydroxamate inhibitors of MMPs as inhibitors of TNF production. The compounds of the current invention act as inhibitors of MMPS, in particular aggrecanase and TNF. These novel molecules are provided as anti-inflammatory compounds and cartilage protecting therapeutics. The inhibiton of aggrecanase, TNF-C, and other metalloproteinases by molecules of the present invention indicates they are anti-inflammatory and should prevent the degradation of cartilage by these enzymes, thereby alleviating the pathological conditions of osteo- and rheumatoid arthritis. SUMMARY OF THE INVENTION Accordingly, one object of the present invention is to provide novel lactams which are useful as metalloprotease inhibitors or pharmaceutically acceptable salts or prodrugs thereof. It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof. It is another object of the present invention to provide a method for treating inflammatory disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof. These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that compounds of formula (I): ##STR4## or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are defined below, are effective metalloprotease inhibitors. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS [1] Thus, in a first embodiment, the present invention provides a novel compound of formula I: ##STR5## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein; A is selected from COR.sup.5, --CO.sub.2 H, CH.sub.2 CO.sub.2 H, --CO.sub.2 R.sup.6, --CONHOH, --CONHOR.sup.5, --CONHOR.sup.6, --NHR.sup.a, --N(OH)COR.sup.5, --SH, --CH.sub.2 SH, --SO.sub.2 NHR.sup.a, SN.sub.2 H.sub.2 R.sup.a, PO(OH).sub.2, and PO(OH)NHR.sup.a ; ring B is a 4-8 membered cyclic amide containing from 0-3 additional heteroatoms selected from O, NR.sup.a, and S(O).sub.p, 0-1 additional carbonyl groups and 0-1 double bonds; R.sup.1 is U--X--Y--Z--U.sup.a --X.sup.a --Y.sup.a --Z.sup.a ; U is absent or is selected from: O, NR.sup.a, C(O), C(O)O, OC(O), C(O)NR.sup.a, NR.sup.a C(O), OC(O)O, OC(O)NR.sup.a, NR.sup.a C(O)O, NR.sup.a C(O)NR.sup.a, S(O).sub.p, S(O).sub.p NR.sup.a, NR.sup.a S(O).sub.p, and NR.sup.a SO.sub.2 NR.sup.a ; X is absent or selected from C.sub.1-10 alkylene, C.sub.2-10 alkenylene, and C.sub.2-10 alkynylene; Y is absent or selected from O, NR.sup.a, S(O).sub.p, and C(O); Z is absent or selected from a C.sub.3-13 carbocyclic residue substituted with 0-5 R.sup.b and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; U.sup.a is absent or is selected from: O, NR.sup.a, C(O), C(O)O, OC(O), C(O)NR.sup.a, NR.sup.a C(O), OC(O)O, OC(O)NR.sup.a, NR.sup.a C(O)O, NR.sup.a C(O)NR.sup.a, S(O).sub.p, S(O).sub.p NR.sup.a, NR.sup.a S(O).sub.p, and NR.sup.a SO.sub.2 NR.sup.a ; X.sup.a is absent or selected from C.sub.1-10 alkylene, C.sub.2-10 alkenylene, C.sub.2-10 alkynylene; Y.sup.a is absent or selected from O, NR.sup.a, S(O).sub.p, and C(O); Z.sup.a is selected from H, a C.sub.3-13 carbocyclic residue substituted with 0-5 R.sup.c and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.c ; R.sup.2 is selected from H, Q', C.sub.1-10 alkylene-Q', C.sub.2-10 alkenylene-Q', C.sub.2-10 alkynylene-Q', (CRR').sub.r' O(CRR').sub.r --Q', (CRR').sub.r' NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r --Q', (CRR').sub.r' C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' C(O) (CRR').sub.r --Q', (CRR').sub.r' C(O)O(CRR').sub.r --Q', (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q', (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --Q', and (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --Q'; R, at each occurrence, is independently selected from H, CH.sub.3, CH.sub.2 CH.sub.3, CH.dbd.CH.sub.2, CH.dbd.CHCH.sub.3, and CH.sub.2 CH.dbd.CH.sub.2 ; R', at each occurrence, is independently selected from H, CH.sub.3, CH.sub.2 CH.sub.3, and CH(CH.sub.3).sub.2 ; alternatively, R.sup.1 and R.sup.2 combine to form a C.sub.3-13 carbocyclic residue substituted with R.sup.1' and 0-3 R.sup.b or a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with R.sup.1' and 0-3 R.sup.b ; Q' is selected from H, a C.sub.3-13 carbocyclic residue substituted with 0-5 R.sup.b and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; R.sup.1' is U.sup.a --X.sup.a --Y.sup.a --Z.sup.a ; R.sup.3 is selected from H, Q, C.sub.1-10 alkylene-Q, C.sub.2-10 alkenylene-Q, C.sub.2-10 alkynylene-Q, (CRR').sub.r' O(CRR').sub.r --Q, (CRR').sub.r' NR.sup.a (CRR').sub.r --Q, (CRR').sub.r C(O) (CRR').sub.r --Q, (CRR').sub.r C(O)O(CRR').sub.r --Q, (CRR').sub.r' OC(O)(CRR').sub.r --Q, (CRR').sub.r C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r --Q, (CRR').sub.r' OC(O)O(CRR').sub.r --Q, (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q, (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a SO.sub.2 (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a SO.sub.2 NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r" NHQ, (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r NHC(O)OR.sup.a, and (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r NHC(O) (CRR').sub.r NHC(O)OR.sup.a, Q is selected from H, a C.sub.3-13 carbocyclic residue substituted with 0-5 R.sup.b and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; R.sup.4 is selected from H, C.sub.1-10 alkylene-H, C.sub.2-10 alkenylene-H, C.sub.2-10 alkynylene-H, (CRR').sub.r' O(CRR').sub.r --H, (CRR').sub.r' NR.sup.a (CRR').sub.r --H, (CRR').sub.r' C(O)(CRR').sub.r --H, (CRR').sub.r' C(O)O(CRR').sub.r --H, (CRR').sub.r' OC(O)(CRR').sub.r --H, (CRR').sub.r' C(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r --H, (CRR').sub.r' OC(O)O(CRR').sub.r --H, (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --H, (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --H, (CRR').sub.r' S(O).sub.p (CRR').sub.r --H, (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --H, (CRR').sub.r' NR.sup.a SO.sub.2 (CRR').sub.r --H, and (CRR').sub.r' NR.sup.a SO.sub.2 NR.sup.a (CRR').sub.r --H; alternatively, R.sup.3 and R.sup.4 combine to form a C.sub.3-13 carbocyclic residue substituted with R.sup.1' and 0-3 R.sup.b or a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with R.sup.1' and 0-3 R.sup.b ; R.sup.a, at each occurrence, is independently selected from H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.a', at each occurrence, is independently selected from H, C.sub.1-4 alkyl, phenyl and benzyl; R.sup.a", at each occurrence, is independently selected from H, C.sub.1-4 alkyl, benzyl, C.sub.3-7 carbocyclic residue, or a 5 to 6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group consisting of N, O, and S; alternatively, R.sup.a and R.sup.a' taken together with the nitrogen to which they are attached form a 5 or 6 membered ring containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R.sup.b, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a", C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, and CF.sub.2 CF.sub.3 ; R.sup.c, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', NR.sup.a C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, CF.sub.2 CF.sub.3, --CH(.dbd.NOH), --C(.dbd.NOH)CH.sub.3, (CRR').sub.s O(CRR').sub.s' R.sup.d, (CRR').sub.s S(O).sub.p (CRR').sub.s' R.sup.d, (CRR').sub.s NR.sup.a (CRR').sub.s' R.sup.d, phenyl, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; R.sup.5, at each occurrence, is selected from C.sub.1-10 alkyl substituted with 0-2 R.sup.b, and C.sub.1-8 alkyl substituted with 0-2 R.sup.d ; R.sup.d, at each occurrence, is independently selected from phenyl substituted with 0-3 R.sup.b, biphenyl substituted with 0-2 R.sup.b, naphthyl substituted with 0-3 R.sup.b and a 5-10 membered heteroaryl system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-3 R.sup.b ; R.sup.6, at each occurrence, is selected from phenyl, naphthyl, C.sub.1-10 alkyl-phenyl-C.sub.1-6 alkyl-, C.sub.3-11 cycloalkyl, C.sub.1-6 alkylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.1-6 alkoxycarbonyloxy-C.sub.1-3 alkyl-, C.sub.2-10 alkoxycarbonyl, C.sub.3-6 cycloalkylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.3-6 cycloalkoxycarbonyloxy-C.sub.1-3 alkyl-, C.sub.3-6 cycloalkoxycarbonyl, phenoxycarbonyl, phenyloxycarbonyloxy-C.sub.1-3 alkyl-, phenylcarbonyloxy-C.sub.1-3 alkyl-, C.sub.1-6 alkoxy-C.sub.1-6 alkylcarbonyloxy-C.sub.1-3 alkyl-, [5-(C.sub.1-5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl]methyl, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyl, --C.sub.1-10 alkyl-NR.sup.7 R.sup.7a, --CH(R.sup.8)OC(.dbd.O)R.sup.9, --CH(R.sup.8)OC(.dbd.O)OR.sup.9, and ##STR6## R.sup.7 is selected from H and C.sub.1-10 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl-, and phenyl-C.sub.1-6 alkyl-; R.sup.7a is selected from H and C.sub.1-10 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl-, and phenyl-C.sub.1-6 alkyl-; R.sup.8 is selected from H and C.sub.1-4 linear alkyl; R.sup.9 is selected from H, C.sub.1-8 alkyl substituted with 1-2 R.sup.e, C.sub.3-8 cycloalkyl substituted with 1-2 R.sup.e, and phenyl substituted with 0-2 R.sup.b ; R.sup.e, at each occurrence, is selected from C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-5 alkoxy, phenyl substituted with 0-2 R.sup.b ; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; r', at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; r", at each occurrence, is selected from 1, 2, and 3; s, at each occurrence, is selected from 0, 1, 2, and 3; and, s', at each occurrence, is selected from 0, 1, 2, and 3. [2] In a preferred embodiment, the present invention provides a novel compound of formula I, wherein; A is selected from COR.sup.5, --CO.sub.2 H, CH.sub.2 CO.sub.2 H, --CONHOH, --CONHOR.sup.5, --CONHOR.sup.6, --N(OH)COR.sup.5, --SH, and --CH.sub.2 SH; ring B is a 4-7 membered cyclic amide containing from 0-2 additional heteroatoms selected from O, NR.sup.a, and S(O).sub.p, and 0-1 additional carbonyl groups and 0-1 double bonds; U is absent; Y is absent; Z is absent or selected from a C.sub.5-10 carbocyclic residue substituted with 0-5 R.sup.b and a 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; U.sup.a is absent or is selected from: O, NR.sup.a, C(O), C(O)NR.sup.a, NR.sup.a C(O), OC(O)NR.sup.a, NR.sup.a C(O)O, NR.sup.a C(O)NR.sup.a, S(O).sub.p NR.sup.a, and NR.sup.a S(O).sub.p ; R.sup.2 is selected from H, Q', C.sub.1-5 alkylene-Q', C.sub.2-5 alkenylene-Q', C.sub.2-5 alkynylene-Q', (CRR').sub.r' O(CRR').sub.r --Q', (CRR').sub.r' NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r --Q', (CRR').sub.r' C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q', (CRR').sub.r' C(O)(CRR').sub.r --Q', (CRR').sub.r' C(O)O(CRR').sub.r --Q', (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q', and (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --Q'; Q' is selected from H, phenyl substituted with 0-3 R.sup.b and a 5-6 membered heteroaryl system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-3 R.sup.b ; R.sup.3 is selected from H, Q, C.sub.1-10 alkylene-Q, C.sub.2-10 alkenylene-Q, C.sub.2-10 alkynylene-Q, (CRR').sub.r' O(CRR').sub.r --Q, (CRR').sub.r NR.sup.a (CRR').sub.r --Q, (CRR').sub.r C(O)(CRR').sub.r --Q, (CRR').sub.r C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)(CRR').sub.r --Q, (CRR').sub.r' OC(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)O(CRR').sub.r --Q, (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' S(O).sub.p (CRR').sub.r --Q, (CRR').sub.r' SO.sub.2 NR.sup.a (CRR').sub.r --Q, (CRR').sub.r' NR.sup.a SO.sub.2 (CRR').sub.r --Q, and (CRR').sub.r' NR.sup.a SO.sub.2 NR.sup.a (CRR').sub.r --Q; R, at each occurrence, is independently selected from H, CH.sub.3, and CH.sub.2 CH.sub.3 ; R', at each occurrence, is independently selected from H and CH.sub.3 ; Q is selected from H, a C.sub.3-10 carbocyclic residue substituted with 0-5 R.sup.b and a 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; and, R.sup.c, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, CF.sub.2 CF.sub.3, and a 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S. [3] In a more preferred embodiment, the present invention provides a novel compound of formula I, wherein; A is selected from --CO.sub.2 H, CH.sub.2 CO.sub.2 H, --CONHOH, --CONHOR.sup.5, and --N(OH)COR.sup.5 ; ring B is a 4-6 membered cyclic amide containing from 0-2 additional heteroatoms selected from O, NR.sup.a, and S(O).sub.p, and 0-1 additional carbonyl groups and 0-1 double bonds; Z is absent or selected from a C.sub.5-6 carbocyclic residue substituted with 0-3 R.sup.b and a 5-9 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b ; U.sup.a is absent or is selected from: O, NR.sup.a, C(O), C(O)NR.sup.a, NR.sup.a C(O), and S(O).sub.p NR.sup.a ; X.sup.a is absent or C.sub.1-10 alkylene; R.sup.2 is selected from H, C.sub.1-5 alkylene-Q', (CH.sub.2).sub.r' O(CH.sub.2).sub.r --Q', (CH.sub.2).sub.r' NR.sup.a (CH.sub.2).sub.r --Q', (CRR').sub.r' NR.sup.a C(O) (CRR').sub.r --Q', (CH.sub.2).sub.r' C(O)NR.sup.a (CH.sub.2).sub.r --Q', (CRR').sub.r' NR.sup.a C(O)NR.sup.a (CRR').sub.r --Q', and (CH.sub.2).sub.r C(O)(CH.sub.2).sub.r --Q'; R.sup.c, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, CF.sub.2 CF.sub.3, and a 5-9 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; and, Q is selected from H, a C.sub.5-6 carbocyclic residue substituted with 0-5 R.sup.b and a 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.b. [4] In a further preferred embodiment, the present invention provides a novel compound of formula I, wherein; A is selected from --CO.sub.2 H, CH.sub.2 CO.sub.2 H, --CONHOH, and --CONHOR.sup.5 ; ring B is a 4-5 membered cyclic amide containing from 0-2 additional heteroatoms selected from O, NR.sup.a, and S(O).sub.p, and 0-1 additional carbonyl groups and 0-1 double bonds; X is absent or selected from C.sub.1-4 alkylene, C.sub.2-4 alkenylene, and C.sub.2-4 alkynylene; Z is absent or selected from phenyl substituted with 0-3 R.sup.b and a 5-9 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-3 R.sup.b ; X.sup.a is absent or C.sub.1-4 alkylene; Y.sup.a is absent or selected from O and NR.sup.a ; Z.sup.a is selected from H, a C.sub.5-10 carbocyclic residue substituted with 0-5 R.sup.c and a 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 R.sup.c ; R.sup.4 is selected from H, C.sub.1-4 alkylene-H, (CH.sub.2).sub.r' O(CH.sub.2).sub.r --H, and (CH.sub.2).sub.r' NR.sup.a (CH.sub.2).sub.r --H; and, R.sup.c, at each occurrence, is independently selected from C.sub.1-6 alkyl, OR.sup.a, Cl, F, Br, I, .dbd.O, CN, NO.sub.2, NR.sup.a R.sup.a', C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.a R.sup.a', S(O).sub.2 NR.sup.a R.sup.a', S(O).sub.p R.sup.a, CF.sub.3, CF.sub.2 CF.sub.3, and a 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S. [5] In another preferred embodiment, the present invention provides novel compounds selected from: [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(phenylmethoxy)phenyl]-1-pyr rolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-(4-methoxyphenyl)-1-pyrrolidine acetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(1-methylethoxy)phenyl]-2-oxo-1-py rrolidineacetamide; [1(R)]-3-[4-(1,1-dimethylethoxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-oxo- 1-pyrrolidineacetamide; [1(R)]-3-(4-(cyclohexyloxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-1-pyr rolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[4-(1,1-dimethylethyl)phenyl methoxy]phenyl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(trans-3-phenyl-2-propenylox y)phenyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3-methylphenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimethyl-2 -oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3,5-dimethylphenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimeth yl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(2-propenyloxy)phenyl]-1-pyr rolidineacetamide; [1(R)]-3-[4-[(3-cyanophenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimethyl-2- oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.-3-dimethyl-3-[4-[(2-nitrophenyl)methoxy]phenyl]-2- oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.-3-dimethyl-3-[4-[(3-nitrophenyl)methoxy]phenyl]-2- oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[(4-nitrophenyl)methoxy]phenyl]-2- oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[(1-naphthalenyl)methoxy]phenyl]-2 -oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-(4-hydroxyphenyl)-.alpha.,3-dimethyl-2-oxo-1-pyrrolidine acetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(2-pyridinyl)methoxy]phenyl ]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(3-pyridinyl)methoxy]phenyl ]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(4-pyridinyl)methoxy]phenyl ]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(2-methylpropyl)phenyl]-2-oxo-1-py rrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-phenyl-1-pyrrolidineacetamide; N-hydroxy-2-oxo-3-phenyl-1-pyrrolidineacetamide; (+/-)-N-hydroxy-3-methyl-2-oxo-3-phenyl-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.-methyl-2-oxo-3-phenyl-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-(4-methoxyphenyl)-.alpha.-methyl-2-oxo-1-pyrrolidineacet amide; [1(R)]-3-cyclohexyl-N-hydroxy-.alpha.,3-dimethyl-2-oxo-1-pyrrolidineacetami de; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-(2-phenylethyl)-1-pyrrolidineac etamide; [1(R)]-3-(2-cyclohexylethyl)-N-hydroxy-.alpha.,3-dimethyl-2-oxo-1-pyrrolidi neacetamide; [1(R)]-N-hydroxy-.alpha.-methyl-2-oxo-3-phenyl-3-(phenylmethyl)-2-oxo-1-pyr rolidineacetamide; [1(R)]-3,4,4',5'-tetrahydro-N-hydroxy-.alpha.-methyl-2-oxospiro[naphthalene -2(1H),3'-[3H]pyrrole]-1'(2'H)-acetamide; [1(R)]-3-[4-[(3,5-dibromophenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimethy l-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[[3,5-bis(trifluoromethyl)phenyl]methoxy]phenyl]-N-hydroxy-.alp ha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3,5-dichlorophenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimeth yl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[(2-methyl-1-naphthalenyl)methoxy] phenyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3,5-dimethoxyphenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-dimet hyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[[4-chloro-2-(trifluoromethyl)-6-quinolinyl]methoxy]phenyl]-N-h ydroxy-.alpha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[[4-(1,2,3-thiadiazol-4-yl)p henyl]methoxy]phenyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-([1,1'-biphenyl]-2-ylmethoxy)phenyl]-N-hydroxy-.alpha.,3-dimeth yl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-.alpha.,3- dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-(1H-benzotriazol-1-ylmethoxy)phenyl]-N-hydroxy-.alpha.,3-dimeth yl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(4,6-dimethyl-2-pyrimidinyl)methoxy]phenyl]-N-hydroxy-.alpha., 3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-(1,3-benzodioxol-5-ylmethoxy)phenyl]-N-hydroxy-.alpha.,3-dimeth yl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2-chloro-6-ethoxy-4-pyridinyl)methoxy]phenyl]-N-hydroxy-.alph a.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(4-quinolinylmethoxy)phenyl] -1-pyrrolidineacetamide; [1(R)]-3-[4-[(4,5-dimethyl-2-thiazolyl)methoxy]phenyl]-N-hydroxy-.alpha.,3- dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-N-hydroxy-.alpha.,3- dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[(3-methyl-5-nitrophenyl)methoxy]p henyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3-amino-5-methylphenyl)methoxy]phenyl]-N-hydroxy-.alpha.,3-di methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[[3-(acetylamino)-5-methylphenyl]methoxy]phenyl]-N-hydroxy-.alp ha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-1,1-dimethylethyl [2-[[3-[[4-[1-[2-(hydroxyamino)-1-methyl-2-oxoethyl]-3-methyl-2-oxo-3-pyrr olidinyl]phenoxy]methyl]-5-methylphenyl]amino]-2-oxoethyl]carbamate; [1(R)]-3-[4-[[3-[(aminoacetyl)amino]-5-methylphenyl]methoxy]phenyl]-N-hydro xy-.alpha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-1,1-dimethylethyl [2-[[2-[[3-[[4-[1-[2-(hydroxyamino)-1-methyl-2-oxoethyl]-3-methyl-2-oxo-3- pyrrolidinyl]phenoxy]methyl]-5-methylphenyl]amino]-2-oxoethyl]amino]-2-oxoe thyl]carbamate; [1(R)]-3-[4-[[3-[[[(aminoacetyl)amino]acetyl]amino]-5-methylphenyl]methoxy] phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-[3-[[4-[1-[2-(hydroxyamino)-1-methyl-2-oxoethyl]-3-methyl-2-oxo-3- pyrrolidinyl]phenoxy]methyl]-5-methylphenyl]-4-morpholinecarboxamide; 3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-.alpha.,.alpha.,3 -trimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[1,1'-biphenyl]-4-yl-N-hydroxy-.alpha.,3-dimethyl-2-oxo-1-pyrrolid ineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-(2'-methyl[1,1'-biphenyl]-4-yl)-2-oxo -1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-(4'-methyl[1,1'-biphenyl]-4-yl)-2-oxo -1-pyrrolidineacetamide; [1(R)-3-(3',4'-dimethoxy[1,1'-biphenyl]-4-yl)-N-hydroxy-.alpha.,3-dimethyl- 2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[2'-(trifluoromethyl)[1,1'-biph enyl]-4-yl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(4-methylphenoxy)phenyl]-2-oxo-1-p yrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-(4-phenoxyphenyl)-1-pyrrolidine acetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(2-methylphenoxy)phenyl]-2-oxo-1-p yrrolidineacetamide; [1(R)]-3-[4-(3,5-dichlorophenoxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-oxo -1-pyrrolidineacetamide; [1(R)]-3-[4-(3,4-dimethoxyphenoxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-ox o-1-pyrrolidineacetamide; [1(R)]-3-[4-(1,3-benzodioxol-5-yloxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2 -oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[3-(1-methylethyl)phenoxy]phenyl]- 2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-[4-(3-methoxyphenoxy)phenyl]-.alpha.,3-dimethyl-2-oxo-1- pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(3-thienyloxy)phenyl]-1-pyrr olidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-(3,4,5-trimethoxyphenoxy)phe nyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-[3,5-bis(trifluoromethyl)phenoxy]phenyl]-N-hydroxy-.alpha.,3-di methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(1-naphthalenyloxy)phenyl]-2-oxo-1 -pyrrolidineacetamide; [1(R)]-N-hydroxy-3-[4-[3-[(hydroxyimino)methyl]phenoxy]phenyl]-.alpha.,3-di methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-[4-[4-[1-(hydroxyimino) ethyl]phenoxy]phenyl]-.alpha.,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-([1,1'-biphenyl]-4-yloxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2 -oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-(3,5-dibromophenoxy)phenyl]-N-hydroxy-.alpha.,3-dimethyl-2-oxo- 1-pyrrolidineacetamide; [1(R)]-3-[4-[3-(acetylamino)phenoxy]phenyl]--hydroxy-.alpha.,3-dimethyl-2-o xo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-(4-nitrophenoxy)phenyl]-2-oxo-1-py rrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-(4-methylphenyl)-2-oxo-1-pyrrolidinea cetamide; [1(R)]-3-[4-[[(2,6-dimethyl-4-pyridinyl)oxy]methyl]phenyl]-N-hydroxy-.alpha .,3-dimethyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(4-quinolinyloxy)methyl]phe nyl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-(4-nitrophenyl)-2-oxo-1-pyrrolidineac etamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(phenylcarbonyl)amino]pheny l]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(phenylsulfonyl)amino]pheny l]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[[(phenylamino)carbonyl]amin o]phenyl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-3-[4-[(1-naphthalenylmethyl)amino]pheny l]-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-.alpha.,3-dimethyl-2-oxo-3-[4-[(4-quinolinylmethyl)amino]p henyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-[[(3,5-dimethoxyphenyl)methyl]amino]phenyl]-N-hydroxy-.alpha.,3 -dimethyl-2-oxo-1-pyrrolidineacetamide; 3-[4-[(3,5-dimethylphenyl)methoxy]phenyl]-N-hydroxy-3-methyl-2-oxo-1-pyrrol idineacetamide; 3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-2-oxo-1- pyrrolidineacetamide; 3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-2-oxo-1- pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-.alpha.-(1-methylethyl)-2-oxo-3-[4-(4-quinolinylm ethoxy)phenyl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-.alpha.-(1-methylethyl)-2-oxo-3-[4-(phenylmethoxy )phenyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-(1-methylethyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[[3,5-bis(trifluoromethyl)phenyl]methoxy]phenyl]-N-hydroxy-3-me thyl-.alpha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(3,5-dichlorophenyl)methoxy]phenyl]-N-hydroxy-3-methyl-.alpha. -(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-.alpha.-(2-methylpropyl)-2-oxo-3-[3-(phenylmethox y)propyl]-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-3-[2-methyl-4-(phenylmethoxy)phenyl]-.alpha.-(2-m ethylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]-2-methylphenyl]-N-hydroxy-3 -methyl-.alpha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-3-[2-methyl-4-(2-naphthalenylmethoxy)phenyl]-.alp ha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-.alpha.-(2-methylpropyl)-3-[2-methyl-4-(4-pyridin ylmethoxy)phenyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]-2-methylphenyl]-N-hydroxy-3 -methyl-.alpha.-(2-methylpropyl)-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-hydroxy-3-methyl-.alpha.-[2-(methylthio)ethyl]-2-oxo-3-[4-(phenylm ethoxy)phenyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-(3,5-dibromophenoxy)phenyl]-3-methyl-.alpha.-[2-(methylsulfonyl )ethyl]-2-oxo-1-pyrrolidineacetic acid; [1(R)]-3-[4-[3,5-bis(trifluoromethyl)phenoxy]phenyl]-N-hydroxy-3-methyl-.al pha.-[2-(methylsulfonyl)ethyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-(3,5-dibromophenoxy)phenyl]-N-hydroxy-3-methyl-.alpha.-[2-(meth ylsulfonyl)ethyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-[2-(methylsulfonyl)ethyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-[2-(methylsulfonyl)ethyl]-2-oxo-1-pyrrolidineacetamide [1(R)]-N-hydroxy-3-methyl-.alpha.-[2-(methylsulfonyl)ethyl]-2-oxo-3-[4-(4-q uinolinylmethoxy)phenyl]-1-pyrrolidineacetamide; N-hydroxy-1-[3-methyl-2-oxo-3-[4-(phenylmethoxy)phenyl]-1-pyrrolidinyl]cycl opropanecarboxamide; [1(R)]-N-hydroxy-.alpha.-[(4-hydroxyphenyl)methyl]-3-methyl-2-oxo-3-[4-(phe nylmethoxy)phenyl]-1-pyrrolidineacetamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-.alpha.-(2 -hydroxyethyl)-3-methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-1,1-dimethylethyl [5-[3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-3-methyl-2-oxo-1-pyrro lidinyl]-6-(hydroxyamino)-6-oxohexyl]carbamate; [1(R)]-.alpha.-(4-aminobutyl)-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]pheny l]-N-hydroxy-3-methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-.alpha.-[4-(acetylamino)butyl]-3-[4-[(2,6-dichloro-4-pyridinyl)metho xy]phenyl]-N-hydroxy-3-methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-N-[5-[3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-3-methyl-2-oxo -1-pyrrolidinyl]-6-(hydroxyamino)-6-oxohexyl]-3-pyridineacetamide; [1(R)]-N-[5-[3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-3-methyl-2-oxo -1-pyrrolidinyl]-6-(hydroxyamino)-6-oxohexyl]-4-morpholinecarboxamide; [1(R)]-3-[4-[(2,6-dichloro-4-pyridinyl)methoxy]phenyl]-N-hydroxy-3-methyl-. alpha.-[4-[(methylsulfonyl)amino]butyl]-2-oxo-1-pyrrolidineacetamide; [1(R)]-.alpha.-[4-(acetylamino)butyl]-3-[4-[(2,6-dimethyl-4-pyridinyl)metho xy]phenyl]-N-hydroxy-3-methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-1,1-dimethylethyl [5-[3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-3-methyl-2-oxo-1-pyrro lidinyl]-6-(hydroxyamino)-6-oxohexyl]carbamate; [1(R)]-.alpha.-(4-aminobutyl)-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]pheny l]-N-hydroxy-3-methyl-2-oxo-1-pyrrolidineacetamide; [1(R)]-.alpha.-[4-[(aminoacetyl)amino]butyl]-3-[4-[(2,6-dimethyl-4-pyridiny l)methoxy]phenyl]-N-hydroxy-3-methyl-2-oxo-1-pyrrolidineacetamide; |
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