Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.

被引：9

作者：

Sauerberg, P ^{[1
]}

Jeppesen, L

Olesen, PH

Sheardown, MJ

Fink-Jensen, A

Rasmussen, T

Rimvall, K

Shannon, HE

Bymaster, FP

DeLapp, NW

Calligaro, DO

Ward, JS

Whitesitt, CA

Thomsen, C

机构：

[1] Novo Nordisk AS, Hlth Care Discovery, Malov 2760, Denmark

[2] Eli Lilly & Co, Lilly Res Labs, Lilly Corp Ctr, Indianapolis, IN 46285 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(98)00509-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Series of analogs to the functional mi selective agonist, xanomeline (hexyloxy-TZTP), were evaluated for their in vitro ml efficacy in cell lines transfected with the human ml receptor. Systematic variation of the side chain and the azacyclic ring led to the discovery of potent muscarinic agonists with robust ml efficacy, ail having the phenylpropargyloxy/thio as the side chain. The most selective compound was the phenylpropargylthio-[3.2.1] endo analog 28, which is a potent and efficacious mi agonist with no m2 activity. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：2897 / 2902

页数：6

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