[Synthesis of 2-oxooctahydroimidazo[1,2-alpha]pyridine-3-spiro-4'-piperidine derivatives possessing antiapomorphine activity].
4'-Carbamoyl-1,4'-bipiperidine 1 was dehydrogenated on Pd-C to give 2-oxo-2,3,5,6,7,8-hexahydroimidazo[1,2-alpha]pyridine-3-spiro-4'-p iperidine 2, which was reduced to 2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-alpha]pyridine-3-spiro -4'- piperidine 3 with NaBH4. The iminodibenzyl and similar derivatives of 2 and 3 were synthesized and evaluated by using antiapomorphine test in mice. The derivatives of 3 had more potent antagonistic activity than those of 2 and the order of potency of 3 was: chloriminodibenzyl greater than chlordibenzocycloheptene greater than iminodibenzyl greater than iminostilbene greater than fluorene. Further chemical modification of the most active chloriminodibenzyl derivative 8, such as the substitution of Cl atom to Br atom, N-methylation on amine moiety, the replacement of imidazopyridine ring to imidazopyrrole ring, did not give any positive effect. Therefore, 8 may have potential usefulness as an antipsychotic drug.
Tashiro
C
C
Horii
I
I
Fukuda
T
T
D000818:Animals; D014150:Antipsychotic Agents; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010879:Piperazines; D011725:Pyridines; D001058:Apomorphine