Tricyclic compounds as selective antimuscarinics. 2. Structure-activity relationships of M1-selective antimuscarinics related to pirenzepine
- 1 June 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (6) , 1169-1174
- https://doi.org/10.1021/jm00401a016
Abstract
In order to gain some insight into these 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 selectively. Principles of structure-activity and structure-selectivity are discussed.This publication has 2 references indexed in Scilit:
- Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity towards the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogsJournal of Medicinal Chemistry, 1987
- Geometric structure and pseudorotational potential of pyrrolidine. An ab initio and electron diffraction studyJournal of the American Chemical Society, 1985