Synthesis and screening of certain aminoguanidine as potential antihypertensive agents

ABSTRACT

The reaction of 3-ethoxycarbonyl-4,6-dimethyl-2-hydroxypyridine [Ia] with NaOC2H5 afforded the respective sodium salt, which was reacted with certain alkyl halides to give the O-alkyl derivatives [Ib-e]. Hydrazinolysis of Ia-e furnished the corresponding hydrazides [II]. Condensation of the latter with S-methylisothiourea sulfate yielded the target aminoguanidines [III]. Structure of the new compounds was based on microanalytical, IR, HNMR and MS spectral data. Pharmacological screening, indicated that some of the newly synthesized compounds exhibited significant antihypertensive activity in both normal and renal hypertensive rats. Compound IIId produced significant increase in heart rate on normal rats, but compound IIIc and IIIe have no significant effect. Compounds IIIc-e have stimulant action on the isolated rabbit intestine. Antihypertensive and adrenergic neurone blocking activities are reported for many guanidine and aminoguanidine derivatives. Aminoguanidines related to guanethidine from a class of compounds with adrenergic neurone blocking properties. Since nicotinic acid has been reported to exhibit vasodilating and hypotensive effects, it was thought to be of interest to prepare new series of aminoguanidines containing the nicotinoyl moiety for screening as antihypertensive agents