INSIGHT INTO THE STRUCTURAL REQUIREMENTS OF SULFONYL DERIVATIVES BASED ON TWO AND THREE-DIMENSIONAL DESCRIPTORS: QSAR STUDIES

摘要

The present work provides the rationale to the changes in the structure to have more potent analogs sulfonyl derivatives were reported to possess potent activity for the angiotensin AT, receptor. We report here 2D QSAR and k-nearest neighbor molecular field analysis based model for sulfonylureas compounds as AT1 receptor. The here k-nearest neighbor contour plots provided further understanding of the relationship between structural features of substituted sulfonyl derivatives and their activities which should be applicable to design newer potential AT1 receptor. The renin-angiotensin system (RAS) plays a key role in regulating cardiovascular homeostasis and electrolyte fluid balance in normotensive and hypertensive subjects1. Activation of the renin-angiotensin cascade begins with renin secretion from the juxtaglomerular apparatus of the kidney and culminates in the formation of the octapeptide angiotensin 11, which then interacts with specific receptors present in different tissues2. Two basic types of receptors: the AT1 receptor, responsible for the majority of effects attributed to this peptide, and the AT2 receptor, with a functional role yet uncertain3. Angiotensins II are the regulation of blood pressure through vasoconstriction, the regulation of volemia through the stimulated release of vasopressin and aldosterone, which induces saline retention, and the regulation of the adrenocorticotropic hormone.