Identification of potent and selective TACE inhibitors via the S1 pocket

被引：37

作者：

Condon, Jeffrey S.

Joseph-McCarthy, Diane

Levin, Jeremy I.

Lombart, Henry-Georges

Lovering, Frank E.

Sun, Linhong

Wang, Weiheng

Xu, Weixin

Zhang, Yuhua

机构：

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

[2] Wyeth Ayerst Res, Inflammat, Cambridge, MA 02140 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 01期

关键词：

inflammation; TACE; rheumatoid arthritis;

D O I：

10.1016/j.bmcl.2006.10.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：34 / 39

页数：6

共 24 条

[1]

Aggarwal BB, 1996, EUR CYTOKINE NETW, V7, P93

[2] Synthesis and structure-activity relationships of β- and α-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy [J].

Becker, DP ;

Villamil, CI ;

Barta, TE ;

Bedell, LJ ;

Boehm, TL ;

DeCrescenzo, GA ;

Freskos, JN ;

Getman, DP ;

Hockerman, S ;

Heintz, R ;

Howard, SC ;

Li, MH ;

McDonald, JJ ;

Carron, CP ;

Funckes-Shippy, CL ;

Mehta, PP ;

Munie, GE ;

Swearingen, CA .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (21) :6713-6730

[3]

Bemelmans MHA, 1996, CRIT REV IMMUNOL, V16, P1

[4] 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

[5] A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells [J].

Black, RA ;

Rauch, CT ;

Kozlosky, CJ ;

Peschon, JJ ;

Slack, JL ;

Wolfson, MF ;

Castner, BJ ;

Stocking, KL ;

Reddy, P ;

Srinivasan, S ;

Nelson, N ;

Boiani, N ;

Schooley, KA ;

Gerhart, M ;

Davis, R ;

Fitzner, JN ;

Johnson, RS ;

Paxton, RJ ;

March, CJ ;

Cerretti, DP .

NATURE, 1997, 385 (6618) :729-733

[6] Conversion of potent MMP inhibitors into selective TACE inhibitors [J].

Cherney, RJ ;

King, BW ;

Gilmore, JL ;

Liu, RQ ;

Covington, MB ;

Duan, JJW ;

Decicco, CP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (04) :1028-1031

[7] Discovery of γ-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor α converting enzyme:: Design, synthesis, and structure-activity relationships [J].

Duan, JJW ;

Chen, LH ;

Wasserman, ZR ;

Lu, ZH ;

Liu, RQ ;

Covington, MB ;

Qian, MX ;

Hardman, KD ;

Magolda, RL ;

Newton, RC ;

Christ, DD ;

Wexler, RR ;

Decicco, CP .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (23) :4954-4957

[8] Synthesis and structure-activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors [J].

Gilmore, JL ;

King, BW ;

Harris, C ;

Maduskuie, T ;

Mercer, SE ;

Liu, RQ ;

Covington, MB ;

Qian, MX ;

Ribadeneria, MD ;

Vaddi, K ;

Trzaskos, JM ;

Newton, RC ;

Decicco, CP ;

Duan, JJW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (10) :2699-2704

[9] Reverse hydroxamate-based selective TACE inhibitors [J].

Kamei, N ;

Tanaka, T ;

Kawai, K ;

Miyawaki, K ;

Okuyama, A ;

Murakami, Y ;

Arakawa, Y ;

Haino, M ;

Harada, T ;

Shimano, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (11) :2897-2900

[10] The design and synthesis of aryl hydroxamic acid inhibitors of MMPs and TACE [J].

Levin, JI .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (12) :1289-1310

← 1 2 3 →