Derivatives of 4,5,6,7-tetrahydro-7,8,8-trimethyl-3-phenylamino-4,7-methano-2H-indazole with hypoglycemic and hypotensive activities.
By reaction of camphor enamine (I) with phenyl isothiocyanate, the N-phenyl thiocarboxamide (II) was obtained in excellent yield, and in turn gave 4,5,6,7-tetrahydro-7,8,8-trimethyl-3-phenylamino-4,7-methano-2H-indazole (III) in very good yield by reaction with hydrazine hydrate. A series of N-substituted ureas (IV) were synthesized in satisfactory yield by reaction of (III) with alkyl and aryl isocyanates. Ureas (IV) showed in general hypoglycemic and in some cases hypotensive activity in rats, whereas only hypotensive activity was present in the thiocarboxamide (II). Effects on heart rate, antiinflammatory and antipyretic activities in rats, infiltration anesthesia and antiarrhythmic activity in mice, as well as antiacetylcholine activity in vitro, are also reported.
D000771:Anesthesia, Intravenous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis*; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D007191:Indazoles; D011720:Pyrazoles