Preparation Of Some New Heterocyclic Compounds Which Possess Potent Hypotensive Activity

Abstract

Hypertension remains a critical global health challenge, driving the continuous search for novel therapeutic agents with improved efficacy and safety profiles. Heterocyclic compounds are pivotal scaffolds in cardiovascular drug discovery. This study describes the design, synthesis, and pharmacological evaluation of a new series of thiazolidinone-based heterocyclic derivatives as potential antihypertensive agents. The target compounds were efficiently synthesized via a cyclocondensation reaction between 4-substituted thiosemicarbazides and chloroacetic acid, yielding twelve novel analogues. All structures were unequivocally characterized using spectroscopic techniques (IR, ¹H NMR, ¹³C NMR, and Mass Spectrometry). The hypotensive activity was assessed in vivo using an Nω-Nitro-L-arginine methyl ester (L-NAME) induced hypertensive rat model. Several compounds elicited a significant dose-dependent reduction in systolic and diastolic blood pressure. Notably, compound 7c, bearing a 4-chlorophenyl moiety, emerged as the most potent, producing a maximum reduction in systolic blood pressure of 38.5 ± 2.1 mmHg, an effect comparable to the standard drug Captopril. Preliminary structure-activity relationship (SAR) analysis indicated that electron-withdrawing substituents on the phenyl ring enhance hypotensive potency. The findings suggest that this novel thiazolidinone series represents a promising lead for the development of new antihypertensive drugs.