Antiimplantation agents: Part IV. 4-Benzhydrylidenepiperidines & tetrahydropyran analogues of F 6066

Abstract

Several α-(4-pyridyl)benzhydrols (8) have been synthesised by Grignard reaction on 4-aroylpyridines (6) or ethyl isonicotinate (7). The quaternary salts,9 of 8 are reduced catalytically to α-(4-piperidyi)benzhydrols (10) which undergo dehydration to benzhydrylidenepiperidines (11). Demethylation of 11c with HBr affords 11d which is further acelylated to provide 11e, an azaisoster of F 6066. Reduction of 9 with sodium borohydride furnishes the tetrahydropyridyl derivatives (12) which undergo acid-catalysed rearrangement to the benzhydrylidenepiperidin-3-ols 13 (14). Treatment of ethyl tetrahydropyran-4-earboxylate with p-anisylmagnesium bromide affords the benzhydrol (19), which is dehydrated to 20. Among the compounds tested, 8b-8d show moderate antiimplantation activity in rats.