STRUCTURES OF N-BENZYL-(4-DIPHENYLACETOXY)PIPERDINES AND N-CYCLOHEXYLMETHYL-(4-DIPHENYLACETOXY)PIPERIDINES

The crystal structures of N-benzyl-4-(diphenylacetoxy)piperidine metho bromide (I) and hydrobromide (II) and N-(cyclohexylmethyl)-4-(diphenyl acetoxy)piperidine hydrochloride (III) were determined. Cations of (I) -benzyl-4-(diphenyl-acetoxy)-N-methylpiperidinium] and (II) [N-benzyl -4-(diphenylacetoxy)piperidinium] adopt similar U-shaped conformations with the benzene ring of the benzyl moiety approaching the diphenylac etate group, while the cation of (III) -cyclohexylmethyl-4-(diphenylac etoxy)piperidinium] adopts a completely different (stretched) conforma tion. Compounds (I)-(III) are much less active at muscarinic M2 recept ors than at M3 receptors but there is no simple correlation between bi ological selectivity and crystal structure. This may be because select ivity depends on steric hindrance: the molecules do not fit the recept ors, particularly M2 receptors, as well as might be expected, and the energy differences represented by different conformations are small co mpared with other factors which determine, and limit, binding.