Guanidine誘導体の構造-活性相関に関する研究 (第1報)

Aminoethylguanidine誘導体の合成および薬理作用

抄録

Aminoethylguanidine derivatives, unknown 1-[2-(N, N-diphenylamino)ethyl]guanidine sulfate (I) and 1-[2-(N-methyl-N-phenylamino)ethyl]guanidine sulfate (II), and known 1-[2-(N, N-diethylamino)ethyl]guanidine sulfate (III), 1-[2-(N, N-dipropylamino)ethyl]guanidine sulfate (IV), 1-[2-(N, N-diisopropylamino)ethyl]guanidine sulfate (V), and 1-(2-piperidinoethyl)guanidine sulfate (VI) were synthesized. Effects of these compounds on blood pressure of albino rats and rabbits, pharmacological actions in general, and acute toxicities were comparatively examined with guanethidine and its derivative, 1-[2-(hexahydro-1-azepinyl)ethyl]guanidine sulfate (VII). III and VI have hypotensive action of fairly long duration on rats and rabbits but their activities were less than that of guanethidine. VII showed long-lasting depression of blood pressure in rabbits but temporary depression in rats. In these compounds, 1-[2-(N, N-diphenylamino)ethyl]guanidine sulfate (I) showed a marked muscle relaxation on N. ischiadicussartorius preparation of Rana nigromaculata. Its activity was almost the same as that of succinylcholine chloride. Antispasmodic and antihistamine activities were tested with isolated small intestine of mice and guinea pigs, respectively. Acute toxicities in mice were also tested. The structure-activity relationship is briefly discussed.