Cholinergic activity of acetylenic imidazoles and related compounds
| Autor: | C. G. Chidester, Richard F. Heier, Roland R. Russell, Jeanette Kay Morris, Sage Gp, Jonathan W. Francis, Vimala H. Sethy, Malcolm W. Moon, Collins Rj |
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| Rok vydání: | 1991 |
| Předmět: |
Stereochemistry
Substituent Muscarinic Antagonists Partial agonist Pyrrolidine Mice Structure-Activity Relationship chemistry.chemical_compound X-Ray Diffraction Amide Tremor Drug Discovery Oxotremorine medicine Animals Imidazole Molecular Structure Acetylene Imidazoles Brain Biological activity Receptors Muscarinic Rats chemistry Tears Lactam Molecular Medicine Salivation medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 34:2314-2327 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00112a002 |
| Popis: | A series of acetylenic imidazoles related to oxotremorine (1a) were prepared and evaluated as cholinergic agents with in vitro binding assays and in vivo pharmacological tests in mice. 1-[4-(1H-Imidazol-1-yl)-2-butynyl]-2-pyrrolidinone (1b) was a cholinergic agonist with one-half the potency of oxotremorine. Analogues of 1b with a 5- or 2-methyl substituent in the imidazole ring (compounds 1c and 1g) were cholinergic partial agonists. Analogues of 1b with a methyl substituent at the 5-position in the pyrrolidinone ring (7b) or at the alpha-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine analogues. Agonist and antagonist conformations for these compounds at muscarinic receptors are proposed. |
| Databáze: | OpenAIRE |
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