Medicinal chemical studies on antiplasmin drugs. VIII. 4-Aminomethylcyclohexanecarboxylic acid derivatives having a carboxyl or carboxymethyl group at C2.

Abstract

Four isomers of 4-aminomethyl-1, 2-cyclohexanedicarboxylic acid (4) were synthesized from dimethyl 4-cyanophthalate (2) via 4-aminomethylphthalic acid (3), and the isomers of 4-aminomethyl-2-carboxymethylcyclohexanecarboxylic acid (14) were also synthesized from 5-aminophthalide (10). The configurations and preferred conformations in aqueous solution of the former isomers were determined on the basis of the nuclear magnetic resonance spectra and by converting the compounds to trimethyl 1, 2, 4-cyclohexanetricarboxylates (5), which were compared with 5 obtained from methyl bicyclo [2. 2. 2]-5-octene-2-carboxylate (8), trimethyl trimellitate (6), and trimellitic acid (9). Those of the latter isomers were deduced from the nuclear magnetic resonance spectra snd the relationships of the isomerization products of 14. The compound t-4-aminomethyl-r-1, c-2-cyclohexanedicarboxylic acid (4C), which is thought to exist in the 1-e, 2-a, 4-e form in aqueous solution, showed more potent antiplasmin activity than trans-4-aminomethyl-cyclohexanecarboxylic acid (1A).