PMID: 3373484Jun 1, 1988

Tricyclic compounds as selective antimuscarinics. 2. Structure-activity relationships of M1-selective antimuscarinics related to pirenzepine

Journal of Medicinal Chemistry
W G EberleinR Hammer

Abstract

In order to gain some insight into those structural features that control M1 selectivity, a selected set of pirenzepine analogues has been studied in which both the tricyclic ring system and the basic side chain have been varied. Binding studies were conducted in rat tissue homogenates from cerebral cortex (M1) and gastric fundus (M2). The ratio of IC50 values of the test compounds in the two different tissues was taken as a measure of M1 receptor selectivity. Several derivatives, especially those with flexible side chains, i.e. high degree of freedom of rotation around single bonds, proved to be nonselective. Among semirigid compounds only those containing 6-membered ring systems (11, 13, 14, and 15) showed significant M1 selectivity. Principles of structure-activity and structure-selectivity are discussed.

Citations

Oct 8, 1999·European Journal of Pharmacology·F HeitzC Guenet
Feb 12, 2008·Journal of Combinatorial Chemistry·Fuqiang ShiXu Bai
Jul 1, 1991·Journal of Medicinal Chemistry·Y KartonK A Jacobson
Jun 10, 2011·Bioorganic & Medicinal Chemistry Letters·Michael J StocksAlan Young
Apr 12, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Bernard TestaAlessandro Pedretti
Dec 2, 2004·Acta Microbiologica Et Immunologica Hungarica·J MolnárYvette Mándi
May 28, 2019·Molecular Diversity·Gaurangkumar C BrahmbhattMange Ram Yadav
Apr 24, 2014·Angewandte Chemie·Somnath Narayan Karad, Rai-Shung Liu

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