Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates

被引：49

作者：

Levin, JI

Chen, JM

Cheung, K

Cole, D

Crago, C

Santos, ED

Du, X

Khafizova, G

MacEwan, G

Niu, C

Salaski, EJ

Zask, A

Cummons, T

Sung, A

Xu, J

Zhang, Y

Xu, W

Ayral-Kaloustian, S

Jin, G

Cowling, R

Barone, D

Mohler, KM

Black, RA

Skotnicki, JS

机构：

[1] Wyeth Ayerst Res, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Princeton, NJ 08543 USA

[3] Wyeth Ayerst Res, Cambridge, MA 02140 USA

[4] Immunex Corp, Seattle, WA 98101 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(03)00514-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1' group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. (C) 2003 Elsevier Ltd. All rights reserved.

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页码：2799 / 2803

页数：5

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