1-Alkyl-3-amino-5-aryl-1H-1,2,4]triazoles:: Novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF1) receptor antagonist activities

被引：56

作者：

Chen, C ^{[1
]}

Dagnino, R ^{[1
]}

Huang, CQ ^{[1
]}

McCarthy, JR ^{[1
]}

Grigoriadis, DE ^{[1
]}

机构：

[1] Neurocrine Biosci Inc, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(01)00657-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cyclizations of alkythydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate. dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a,N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF1 receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF1 receptor (K-i = 9 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：3165 / 3168

页数：4

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[2]

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[3]

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