Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration

被引：13

作者：

Matsufuji, Tetsuyoshi ^{[1
]}

Shimada, Kousei ^{[1
]}

Kobayashi, Shozo ^{[1
]}

Kawamura, Asuka ^{[1
]}

Fujimoto, Teppei ^{[1
]}

Arita, Tsuyoshi ^{[1
]}

Hara, Takashi ^{[2
]}

Konishi, Masahiro ^{[2
]}

Abe-Ohya, Rie ^{[2
]}

Izumi, Masanori ^{[2
]}

Sogawa, Yoshitaka ^{[2
]}

Nagai, Youko ^{[3
]}

Yoshida, Kazuhiro ^{[3
]}

Takahashi, Hisashi ^{[1
]}

机构：

[1] Daiichi Sankyo Co Ltd, Med Chem Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[2] Daiichi Sankyo Co Ltd, Cardiovasc Metab Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[3] Daiichi Sankyo Co Ltd, Drug Metab & Pharmacokinet Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 03期

关键词：

Bombesin receptor subtype-3 (BRS-3) agonists; Diazepine; Brain penetration; TERT-BUTANESULFINYL IMINES; ASYMMETRIC-SYNTHESIS; AMINES; MK-5046; SYSTEM;

D O I：

10.1016/j.bmcl.2013.12.106

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimization of a novel series of BRS-3 agonists are described. We explored a potent BRS-3 agonist with low brain penetration to avoid an adverse effect derived from central nervous system exposure. Through the derivatization process, chiral diazepines 9f and 9g were identified as possessing low brain penetration as well as potent in vitro activity against human and mouse BRS-3s. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：750 / 755

页数：6

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