Synthesis of some potential antihypertensive phthalazinyl- and quinoxalinylguanidines.
A series of phthalazinyl- and quinoxalinylguanidines has been synthesized and evaluated for potential antihypertensive activity. Unsubstituted guanidines were prepared by treating the appropriate intermediate chloro compounds with guanidine free base. Substituted guanidines were prepared by treating the cyanamides 9 and 16 with the appropriate amine; with hydrazines, cyanamide 9 gave the triazoles 14 and 15. Moderate falls in blood pressure were observed with compounds 10, 11, 14, and 15. The triazole 15 caused a 25% fall in heart rate. Some of the compounds (10, 11, 13, and 18) displayed weak alpha-adrenoceptor antagonist properties in vitro, and this activity was confirmed in the pithed rat (in vivo).
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003900:Desoxycorticosterone; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010793:Phthalazines / Q000138:chemical synthesis / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D006146:Guanidines; D010793:Phthalazines; D011810:Quinoxalines; D003900:Desoxycorticosterone