Synthesis and anticonvulsant activity of some tetracyclic indole derivatives.
Several related series of cycloalkyl[4,5]pyrrolo[3,2,1-ij]quinolines 7a-g, 8a-c, 10a-3, and 16a-f and indolo[3,2,1-hi]indoles 22a-c and 23a,b were synthesized and tested for anticonvulsant activity. The key preparative step, a Fischer indole reaction between a bicyclic hydrazine and a cyclic ketone, gave the compounds in 34-96% yield. The products were tested in rat maximal electroshock for anticonvulsant activity. Several compounds showed good activity, with 6-[(dimethylamino)methyl]-4,5,6,8,9,10-hexahydrocyclopenta[4,5]pyrrolo[3,2,1-ij]quinoline (7d) and N-methyl-4,5,6,8,9,10,11,12-octahydrocyclohepta[4,5]pyrrolo[3,2,1-ij]quinoline- 6-carboxamide (10c) having ED50's of 12.5 and 12.9 mg/kg po, respectively.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001681:Biological Assay; D004597:Electroshock; D007211:Indoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D007211:Indoles