Convulsant Activities of Aminocyclanol Derivatives as Influenced by Stereochemical Configurations. ∗

Abstract

Summary and conclusions

Generally, it has been found that cis and trans isomers of 1,2-tertiary aminocyclanols and their esters, studied largely in the cyclohexane series, are capable of exhibiting convulsant activity in the mouse and the cat. From graded activities in the mouse it is observed that with few exceptions each cis isomer of a given cis-trans pair is more potent than its corresponding trans isomer. Within the tertiary amino compounds as a class, it appears that convulsant activity in the mouse, which is roughly paralleled in the cat, runs in the increasing sequence alcohols < phenylacetate esters < di-phenylacetate esters ≤ benzilate esters. The cis quaternary alcohols 3 and 7 are active in cats and mice, whereas the trans isomers 4 and 8 are strikingly inactive in cats. Further, the probability that active and inactive members of a quaternary cis-trans pair (e.g. 7 and 8, and 4 and 3) reach the same receptor centers in the cat is indicated by the observations that 8 protects against the action of 7, and 4 against 3. Finally, the quaternary cis and trans benzilates 18 and 19 appear to show strong species specificity, with high activity in mice (cis better than trans) and low activity in cats.