Medicinal Chemical Studies on Antiplasmin Drugs. III. 4-Aminomethylcyclohexanecarboxylic Acid and Its Derivatives having a Methyl Group

抄録

To investigate the structure-activity relationship between two isomers of 4-aminomethylcyclohexanecarboxylic acid (AMCHA) in connection with their antiplasmin activity, their conformations in H₂O were simply estimated on the basis of conformational free energy (-⊿G°). The nuclear magnetic resonance spectra of both isomers of 4-tertbutylcyclohexylmethylamine hydrochloride and of cyclohexylmethylamine hydrochloride gave a value of -⊿G°=1.4 kcal/mol for the N^⁺H₃CH₂-group. The biologically active trans AMCHA in H₂O exists, as in its crystal structure, largely in the equatorial N^⁺H₃CH₂-equatorial COO-form, while about 79% of cis AMCHA exists as the axial N^⁺H₃CH₂-equatorial COO-form, in contrast to the crystal structures of its hydrohalides. Further, 1-Me AMCHA, 4-Me AMCHA and 4-(1-aminoethyl) cyclohexanecarboxylic acid were synthesized. The stereoisomers of these compounds were separated and the configurations of the isomers were determined. No compound showed a more potent antiplasmin activity than trans AMCHA.