Antihypertensive thiadiazoles. 2. Vasodilator activity of some 2-aryl-5-guanidino-1,3,4-thiadiazoles
| Autor: | Brian Gadie, Anthony J. Nelson, Stephen Turner, Robin Pape, Malcolm Myers, Stafford A. Hale, John F. Saville, John C. Doxey, Timothy L. Berridge, Alan Horsley |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Male
Vascular smooth muscle Chemical Phenomena Stereochemistry Blood Pressure Vasodilation Guanidines Medicinal chemistry Muscle Smooth Vascular Structure-Activity Relationship chemistry.chemical_compound Thiadiazoles Drug Discovery Animals Structure–activity relationship Guanidine Antihypertensive Agents Decerebrate State Chemistry Aryl Biological activity Rats Blood pressure Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 31:906-913 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11. The iminoimidazolidine 93 showed a somewhat longer duration of action than the guanidine derivatives. Preliminary studies in a pithed rat preparation indicated that these thiadiazole derivatives (11, 63, and 93) lowered blood pressure by a direct relaxant effect on vascular smooth muscle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|