title: Synthesis and pharmacological evaluation of some 3-substituted octahydropyrido(2,1-c)(1,4)oxazines.
abstract: 3-Phenyloctahydropyrido[2,1-c][1,4]oxazine hydrochloride and the 10R and 10S diastereomers have been synthesized from (+/-)-, (+)-, and (-)-2-piperidinemethanol. Treatment of 2-piperidinemethanol with alpha-bromoacetophenone gave 3-hydroxy-3-phenyloctahydropyrido[2,1-c][1,4]oxazine which was readily converted to the 3-phenyl derivative by catalytic hydrogenolysis. These compounds were shown to possess a depressant action on the CNS which was quantitated in terms of reduction of locomotor activity in mice. Qualitative differences were noted in the central effects of the 3-phenyl compound and its hemiketal derivative. Further, qualitative differences in the effects of the diastereomers of the 3-phenyl compound on locomotor activity of mice were also noted. The results of this study suggest that the octahydropyrido[2,1-c]1,4]oxazine system may provide a useful molecular framework for the construction of agents exhibiting pharmacologically useful actions in the CNS.
mesh_terms: D000818:Animals; D003864:Depression, Chemical; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D013237:Stereoisomerism
chemical_list: D010078:Oxazines; D010880:Piperidines