SYNTHESIS AND LOCAL-ANESTHETIC ACTIVITY OF 2 HOMOLOGICAL SERIES OF DIASTEREOMERIC PHENYLCARBAMATES

By using stereospecific reactions we prepared two homological series o f diastereomeric + cis- and + trans-N, alkoxyphenylcarbamoyloxy)cycloh exylmethyl-ammonium chlorides with number of carbons in the alkoxy gro up varying from one to eight. Structure of the prepared compounds was proved by NMR and IR spectroscopy. The principal physico-chemical char acteristics, including partition coefficients, were obtained and relat ive local anesthetic activity was measured using a surface in vivo mod el. It was found that (1) for both cis- and trans-isomers there is a p arabolic relationship between log activity and molecular lipophilicity (as measured by TLC R(M) and log P values), (2) all drugs prepared fo r this study use hydrophobic pathway to block inactivated channels, an d (3) there is no strict requirement for precise disposition of the fu nctional groups responsible for receptor binding, probably due to conf ormational flexibility of the sodium channel protein.