Insilico ADMET and molecular docking study of novel antihypertensivederivatives designed by bioisosteric replacement of the aminoquinazoline ringin prazosin

Abstract

Considering the global burden of hypertension, this study aims to design and evaluate novel Prazosin analogues with enhanced pharmacokinetic properties and reduced toxicity using a bioisosteric approach. This study will help to find the prominent group for antihypertensive drug development. A bioisosteric approach was employed to generate novel Prazosin analogues using the MolOpt program. The aminoquinazoline moiety of Prazosin was systematically replaced with bioisosteric groups, and the various pharmacoki netics (absorption, distribution, metabolism, excretion, and toxicity) parameters of the newly developed analogs were calculated. Molecular docking studies were performed to assess the binding affinity of the newly designed analogues, and the top
three der ivatives with superior docking scores were identified. The study identified several compounds as promising analogues due to their reduced toxicity (hERG, H HHT, DILI < 0.3), favorable drug likeness QED values (≤ 0.67), and molecular docking score compared to prazosin. Notably, analogues 038, 158, and 190. This study successfully identified novel antihypertensive derivatives with improved ADMET properties, enhanced drug likeness, and favorable molecular docking profiles. The findings provide valuable insight s for the development of next generation antihypertensive agents with optimized pharmacological characteristics.