Preparation of antidotes for anticholinesterase poisoning. IV. Synthesis and protective effectiveness of 2′-(cis- and trans-2″-hydroxycyclohexyl)aminoethyl 1-phenylcyclopentanecarboxylate hydrochlorides

Abstract

The syntheses of cis- and trans-2-aminocyclohexanols and of cis- and trans-2-ethylaminocyclohexanols are described. The cis isomers were prepared by treatment of the corresponding trans-2-acetamidocyclohexanols with thionyl chloride followed by hydrolysis of the resulting intermediate oxazolines. The 2-aminocyclohexanols were converted to 2′-(cis- and trans-2″-hydroxycyclohexyl)aminoethyl 1-phenyl-cyclopentanecarboxylate hydrochlorides (1 and 2, R = H) by treatment with 2′-bromoethyl 1-phenyl-cyclopentanecarboxylate, but attempts to convert the 2-ethylaminocyclohexanols to 1 and 2 (R = C2H5) by a similar reaction were unsuccessful. The anticholinesterase activities of several of the compounds are discussed, as are the potencies of 1 and 2 (R = H) in protecting mice and rats from sarin poisoning.