Design, synthesis and SAR investigation of thienosultam derivatives as ADAMTS-5 (aggrecanase-2) inhibitors

被引：7

作者：

Atobe, Masakazu ^{[1
]}

Maekawara, Naomi ^{[1
]}

Kawanishi, Masashi ^{[1
]}

Suzuki, Hiroko ^{[1
]}

Tanaka, Eiichi ^{[1
]}

Miyoshi, Shiro ^{[1
]}

机构：

[1] Asahi Kasei Pharma Corp, Pharmaceut Res Ctr, Izunokuni, Shizuoka 4102321, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 07期

关键词：

Osteoarthritis; Aggrecanase-2; ADAMTS-5; Thienosultam; S1 ' pocket; X-RAY-STRUCTURE; BIOLOGICAL EVALUATION; CATALYTIC DOMAIN; CARTILAGE DEGRADATION; POTENT; OSTEOARTHRITIS; DISCOVERY; CATABOLISM; DELETION; CLONING;

D O I：

10.1016/j.bmcl.2013.01.120

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A series of 1,1-dioxothieno[2,3-d]isothiazole (thienosultam) derivatives were designed and synthesized as novel ADAMTS-5 inhibitors for an investigation into a side chain of thienosultam for the S1' pocket. The resulting compounds (19 and 24) show high ADAMTS-5 inhibition and other MMP selectivity, and these compounds show good oral bioavailability. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2111 / 2116

页数：6

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