Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part II: Exploration of 6-6 fused rings as alternative S1 moieties

被引：32

作者：

Yoshikawa, Kenji ^{[1
]}

Kobayashi, Shozo ^{[2
]}

Nakamoto, Yumi ^{[2
]}

Haginoya, Noriyasu ^{[1
]}

Komoriya, Satoshi ^{[2
]}

Yoshino, Toshiharu ^{[1
]}

Nagata, Tsutomu ^{[2
]}

Mochizuki, Akiyoshi ^{[2
]}

Watanabe, Kengo ^{[2
]}

Suzuki, Makoto ^{[1
]}

Kanno, Hideyuki ^{[3
]}

Ohta, Toshiharu ^{[1
]}

机构：

[1] Daiichi Sankyo Co Ltd, R&D Div, Edogawa Ku, Tokyo 1348630, Japan

[2] Daiichi Sankyo Co Ltd, R&D Div, Shinagawa Ku, Tokyo 1408710, Japan

[3] Daiichi Sankyo RD Associe Co Ltd, Edogawa Ku, Tokyo 1348630, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 24期

关键词：

Anticoagulant; Factor Xa inhibitor; Solubility; Food effect; DISCOVERY; CHEMISTRY; ESTERS;

D O I：

10.1016/j.bmc.2009.10.024

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：

A series of cis-1,2-diaminocyclohexane derivatives possessing a 6-6 fused ring for the S1 moiety were synthesized as novel factor Xa (fXa) inhibitors. The synthesis, structure-activity relationship (SAR), and physicochemical properties are reported herein, together with the discovery of compound 45c, which has potent anti-fXa activity, good physicochemical properties and pharmacokinetic (PK) profiles, including a reduced negative food effect. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：8221 / 8233

页数：13

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