Synthesis and in vitro characterization of novel amino terminally modified oxotremorine derivatives for brain muscarinic receptors
| Autor: | D S, Garvey, J T, Wasicak, J Y, Chung, Y K, Shue, G M, Carrera, P D, May, M M, McKinney, D, Anderson, E, Cadman, L, Vella-Rountree |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Intrinsic activity Tertiary amine Stereochemistry Azetidine Partial agonist chemistry.chemical_compound Drug Discovery Muscarinic acetylcholine receptor Oxotremorine medicine Animals Cerebral Cortex Rats Inbred Strains Muscarinic acetylcholine receptor M2 Pirenzepine Muscarinic acetylcholine receptor M1 Receptors Muscarinic Corpus Striatum Rats chemistry Biochemistry Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 35:1550-1557 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00087a008 |
| Popis: | A series of novel 2-substituted acetylenic pyrrolidines and piperidines related to oxotremorine (1) were prepared and evaluated in vitro as muscarinic cholinergic agents at brain M1 and M2 receptors. One analogue, 3-(2-oxo-1-pyrrolidinyl)-1-[2(R)-pyrrolidinyl]-1-propyne hydrogen oxalate (6a), was found to be a partial agonist producing a PI hydrolysis response at cortical M1 receptors approximately 3-fold larger than that produced by 1. The intrinsic activity profile of 6a at brain muscarinic receptors is similar to those of azetidine oxo analogue 2 and dimethylamino oxo analogue. All three compounds are partial M1 agonists and full M2 agonists; however, the profile of 6a in binding studies is significantly different. While 2 and 3 exhibit large M2 selectivities ranging between 8-fold to several hundred-fold, the binding profile of 6a shows almost no subtype selectivity. |
| Databáze: | OpenAIRE |
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