SYNTHESIS AND SCREENING OF CERTAIN ARYLOXYACETYLAMINOGUANIDINES AS POTENTIAL ANTIHYPERTENSIVE AGENTS

Ethyl aryloxyacetates (2a-k) have been synthesized either by the ester ification of aryloxyacetic acids (1a-j) with ethanol in the presence o f concentrated sulphuric acid or by reacting potassium naphthoxides wi th ethyl chloroacetate in dimethylformamide. Hydrazinolysis of either 1a, b, d, f, j or 2a-k furnishes the corresponding hydrazides (3). On the other hand, the acid chlorides (4f-h) have been prepared via the r eaction of 1a-f with thionyl chloride in dry benzene, which on refluxi ng with aminoguanidine bicarbonate in dry benzene give the target amin oguanidine hydrochlorides (5a-h). Meanwhile, the desired aminoguanidin e sulphates (5a-e) have been obtained by condensing 2a-e with S-methyl isothiourea sulphate in aqueous ethanol. Additionally, the new aminotr iazole sulphates (6a-h) are obtained either by refluxing 2a-h with S-m ethylisothiourea sulphate or by fusion of 1a,b, h, j with aminoguanidi ne sulphate. Structures of the new compounds are based on elemental an alyses and IR, (1)HNMR and mass spectral data. Pharmacological screeni ng, indicates that some of the newly synthesized compounds exhibit sig nificant antihypertensive activity in both normal and renal hypertensi ve rats. Compound 5b produces significant decrease in the heart rate o f normal rats. Compounds 5f and 5g have no significant effect. Compoun ds 5f,g, h have inhibition effect on the isolated rabbit intestine.