Potent carboxylate inhibitors of stromelysin containing P2' piperazic acids and P1' biaryl moeities

被引：13

作者：

Cherney, RJ

Decicco, CP

Nelson, DJ

Wang, L

Meyer, DT

Hardman, KD

Copeland, RA

Arner, EC

机构：

[1] DuPont Merck Pharmaceutical Co., Experimental Station, Wilmington

[2] Chem. Phys. Sci. Inflammatory D., Experimental Station, Wilmington

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(97)00308-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several carboxylate derivatives with variation at the P1' residue were synthesized and evaluated as stromelysin (MMP-3) inhibitors. Compounds containing a biphenyl moiety at P1' were found to be potent inhibitors of MMP-3. An X-ray crystal structure of the most potent compound, carboxylate 19, revealed an important interaction between the inhibitor's biphenyl and histidine 224 in the S1' pocket of MMP-3. (C) 1997 Elsevier Science Ltd.

引用

页码：1757 / 1762

页数：6

共 18 条

[11] HARDMAN KD, UNPUB
[12] A REGIOCONTROLLED AND STEREOCONTROLLED TOTAL SYNTHESIS OF (-)-INDOLACTAM-V
KOGAN, TP
SOMERS, TC
VENUTI, MC
[J]. TETRAHEDRON, 1990, 46 (19) : 6623 - 6632
[13] Probing the P3' pocket of stromelysin with piperazic acid analogs
Nugiel, DA
Jacobs, K
Decicco, CP
Nelson, DJ
Copeland, RA
Hardman, KD
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (24) : 3053 - 3056
[14] Schwartz M A, 1992, Prog Med Chem, V29, P271, DOI 10.1016/S0079-6468(08)70011-0
[15] SINGH J, 1992, ATLAS PROTEIN SIDE C, P374
[16] CLONING OF THE GENES FOR HUMAN STROMELYSIN AND STROMELYSIN .2. DIFFERENTIAL EXPRESSION IN RHEUMATOID SYNOVIAL FIBROBLASTS
SIRUM, KL
BRINCKERHOFF, CE
[J]. BIOCHEMISTRY, 1989, 28 (22) : 8691 - 8698
[17] DETECTION OF STROMELYSIN AND COLLAGENASE IN SYNOVIAL-FLUID FROM PATIENTS WITH RHEUMATOID-ARTHRITIS AND POSTTRAUMATIC KNEE INJURY
WALAKOVITS, LA
MOORE, VL
BHARDWAJ, N
GALLICK, GS
LARK, MW
[J]. ARTHRITIS AND RHEUMATISM, 1992, 35 (01): : 35 - 42
[18] [No title captured]

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