Aminoguanidine系化合物の薬理学的研究(第1報)Benzyl-およびBenzylidene-hydrazino-3,4,5,6-tetrahydropyrimidine化合物の降圧作用ならびに一般薬理作用

抄録

The structure-activity relationship between the hypotensive and some general pharmacological effects of aminoguanidine derivatives was investigated and the following results were obtained.1) A moderate length of the intermediate chain between the benzene ring and the aminoguanidino group of the test compounds was required to obtain a much longer hypotension, and the introduction of one methylene group gave the optimum activity.2) Among the test compounds, the benzyl- and benzylidene-hydrazino-3, 4, 5, 6-tetra-hydropyrimidines (BHTP) showed a relatively mild and slowly acting hypotensive effect with a long duration.3) Substitution of 2- and 6-positions in the benzene ring of BHTP with dichloro groups gave a marked hypotensive and some strong general pharmacological actions and, in particular, the anti-form isomer of 2-(2, 6-dichlorobenzylidenehydrazino)-3, 4, 5, 6-tetra-hydropyrimidines (VA) showed the most marked action.4) VA aid not show an α-sympathomimetic action as clonidine, etc., did.5) VA had an inhibitory action as potent as guanethidine on the contractions of the isolated guinea-pig hypogastric nerve-vas deferens induced by electrical stimulations.6) VA inhibited the contractile force of the isolated guinea-pig atria and decreased the heart rate of the isolated rat atria.7) VA had an inhibitory revolution mortor activity in mice, a taming effect in rats, and a sedative and hypnotic action in cats.8) A toxic dose of VA showed clonic convulsion, tremor, and hind leg ataxia, but did not show group toxicity and biting behavior as did clonidine in grouping mice.