| Autor: |
Dunbar PG; Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, Ohio 43606., Durant GJ, Fang Z, Abuh YF, el-Assadi AA, Ngur DO, Periyasamy S, Hoss WP, Messer WS Jr |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1993 Apr 02; Vol. 36 (7), pp. 842-7. |
| DOI: |
10.1021/jm00059a008 |
| Abstrakt: |
A series of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines+ ++ (7a-h) was synthesized for biological evaluation as selective agonists for M1 receptors coupled to phosphoinositide (PI) metabolism in the central nervous system. Each ligand bound with high affinity to muscarinic receptors from rat brain as measured by inhibition of [3H]-(R)-quinuclidinyl benzilate ([3H]-(R)-QNB) binding. 5-(3-Methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine+ ++ trifluoroacetate (CDD-0098-J;7a) displayed high affinity (IC50 = 2.7 +/- 0.69 microM) and efficacy at muscarinic receptors coupled to PI metabolism in the rat cortex and hippocampus. Increasing the length of the alkyl substituent increased affinity for muscarinic receptors yet decreased activity in PI turnover assays. The hippocampal PI response of 7a was blocked by lower concentrations of pirenzepine (8) or by higher concentrations of either AF-DX 116 (9) or p-fluorohexahydrosiladifenidol (10), suggesting that at low concentrations 7a selectively stimulates PI turnover through M1 receptors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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