Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis

被引：94

作者：

Hu, YH

Xiang, JS

DiGrandi, MJ

Du, XM

Ipek, M

Laakso, LM

Li, JC

Li, W

Rush, TS

Schmid, J

Skotnicki, JS

Tam, S

Thomason, JR

Wang, Q

Levin, JI

机构：

[1] Wyeth Ayerst Res, Dept Chem & Screening Sci, Cambridge, MA 02140 USA

[2] Wyeth Res, Dept Chem & Screening Sci, Pearl River, NY 10965 USA

[3] Wyeth Res, Dept Drug Safety & Metab, Andover, MA 01810 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 24期

关键词：

MMP-13; inhibitor; biphenylsulfonamide carboxylate; benzofuran; osteoarthritis;

D O I：

10.1016/j.bmc.2005.07.076

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Modification of alpha-biphenylsulfonamidocarboxylic acids led to potent and selective MMP-13 inhibitors. Compound 16 showed 100% oral bioavailability in rats and demonstrated > 50% inhibition of bovine cartilage degradation at 10 ng/mL. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：6629 / 6644

页数：16

共 26 条

[1] Nucleophilic intramolecular cyclization reactions of alkynechalcogenolates [J].

Abramov, MA ;

Dehaen, W ;

D'hooge, B ;

Petrov, ML ;

Smeets, S ;

Toppet, S ;

Voets, M .

TETRAHEDRON, 2000, 56 (24) :3933-3940

[2] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[3] Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design [J].

Chen, JM ;

Nelson, FC ;

Levin, JI ;

Mobilio, D ;

Moy, FJ ;

Nilakantan, R ;

Zask, A ;

Powers, R .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (40) :9648-9654

[4] Sultam hydroxamates as novel matrix metalloproteinase inhibitors [J].

Cherney, RJ ;

Mo, RW ;

Meyer, DT ;

Hardman, KD ;

Liu, RQ ;

Covington, MB ;

Qian, MX ;

Wasserman, ZR ;

Christ, DD ;

Trzaskos, JM ;

Newton, RC ;

Decicco, CP .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (12) :2981-2983

[5]

Dhanaraj V, 1999, CROAT CHEM ACTA, V72, P575

[6] Identification of MK-944a: A second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors [J].

Dorsey, BD ;

McDonough, C ;

McDaniel, SL ;

Levin, RB ;

Newton, CL ;

Hoffman, JM ;

Darke, PL ;

Zugay-Murphy, JA ;

Emini, EA ;

Schleif, WA ;

Olsen, DB ;

Stahlhut, MW ;

Rutkowski, CA ;

Kuo, LC ;

Lin, JH ;

Chen, IW ;

Michelson, SR ;

Holloway, MK ;

Huff, JR ;

Vacca, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (18) :3386-3399

[7] TOPICALLY ACTIVE CARBONIC-ANHYDRASE INHIBITORS .3. BENZOFURAN-SULFONAMIDE AND INDOLE-2-SULFONAMIDE [J].

GRAHAM, SL ;

HOFFMAN, JM ;

GAUTHERON, P ;

MICHELSON, SR ;

SCHOLZ, TH ;

SCHWAM, H ;

SHEPARD, KL ;

SMITH, AM ;

SMITH, RL ;

SONDEY, JM ;

SUGRUE, MF .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (02) :749-754

[8] Homology modeling of gelatinase catalytic domains and docking simulations of novel sulfonamide inhibitors [J].

Kiyama, R ;

Tamura, Y ;

Watanabe, F ;

Tsuzuki, H ;

Ohtani, M ;

Yodo, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (10) :1723-1738

[9]

LI J, IN PRESS BIOORG MED

[10]

LOVEJOY B, 1999, NAT STRUCT BIOL, P6211

← 1 2 3 →