Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity

被引：11

作者：

Boy, KM ^{[1
]}

Dee, M ^{[1
]}

Yevich, J ^{[1
]}

Torrente, J ^{[1
]}

Gao, Q ^{[1
]}

Iben, L ^{[1
]}

Stark, A ^{[1
]}

Mattson, RJ ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 17期

关键词：

serotonin; SSRI; 5-HT1A; depression;

D O I：

10.1016/j.bmcl.2004.06.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Conformationally constrained aryl cyclohexanes and cyclohexenes based on aryl cyclohexanols 1 were prepared. Locking the aryl ring in plane with the cyclohexane moiety provided potent SSRIs 3. Conversely, fixing the aryl ring perpendicular to the cyclohexane ring via a spiro lactone provided balanced 5-HT1A antagonists with mid-nanomolar range SSRI potency (compounds 2). (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4467 / 4470

页数：4

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