Tricyclic compounds as selective antimuscarinics. 2. Structure-activity relationships of M1-selective antimuscarinics related to pirenzepine
| Autor: | Guenter Trummlitz, Rudolf Hammer, Wolfgang G. Eberlein, Wolfhard W. Engel, Guenther Schmidt |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
chemistry.chemical_classification
medicine.medical_specialty Stereochemistry Molecular Conformation Parasympatholytics Pirenzepine Muscarinic acetylcholine receptor M1 Ring (chemistry) Receptors Muscarinic Rats Structure-Activity Relationship Endocrinology chemistry Internal medicine Drug Discovery medicine Side chain Ic50 values Animals Molecular Medicine Single bond Selectivity Tricyclic medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 31:1169-1174 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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