Synthesis and orexigenic activity of some 1-methyl-4-piperidylidene-Substituted pyrrolo[2,1-g][3] benzazepine and dibenzocycloheptene derivatives.
The synthesis and orexigenic activity of some unsubstituted and Bz-carboxylic acid substituted 1-methyl-4-piperidylidenepyrrolo[2,1-b][3]benzazepine and dibenzocycloheptene derivatives are described. 10,11-Dihydro-3-carboxycyproheptadine (7c) has been selected for clinical evaluation as a orexigenic agent based on its low threshold dose for increasing food consumption in cats (0.031 mg/kg po) and its lack of undesirable central nervous system activity. The levorotatory enantiomer of 3-carboxycyproheptadine (1d) and the 9-carboxypyrrolobenzazepine derivative 4f also possess orexigenic activity, but with these compounds such activity diminishes sharply below 0.25 mg/kg po. The unsubstituted 1-methyl-4-(5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidine (4d) and its 6,11-dihydroanalogue (4a) are comparable to cyproheptadine (1a) in promoting hyperphagia in cats.
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D003533:Cyproheptadine / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000138:chemical synthesis* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D013268:Stimulation, Chemical
D001552:Benzazepines; D003986:Dibenzocycloheptenes; D003533:Cyproheptadine