Synthesis and biological evaluation of benzodioxanylpiperazine derivatives as potent serotonin 5-HT1A antagonists:: The discovery of lecozotan

被引：17

作者：

Childers, WE ^{[1
]}

Abou-Gharbia, MA ^{[1
]}

Kelly, MG ^{[1
]}

Andree, TH ^{[1
]}

Harrison, BL ^{[1
]}

Ho, DM ^{[1
]}

Hornby, G ^{[1
]}

Huryn, DM ^{[1
]}

Potestio, L ^{[1
]}

Rosenzweig-Lipson, SJ ^{[1
]}

Schmid, J ^{[1
]}

Smith, DL ^{[1
]}

Sukoff, SJ ^{[1
]}

Zhang, G ^{[1
]}

Schechter, LE ^{[1
]}

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci & Neurosci, Princeton, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 10期

关键词：

D O I：

10.1021/jm049493z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT1A affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT1A receptor and many displayed potent antagonist activity in vitro and varying degrees of intrinsic activity in vivo. Compound 11c (Lecozotan) was selected for further development and is currently in clinical trials.

引用

页码：3467 / 3470

页数：4

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