Pyridazine Derivatives: Molecular Docking, ADMET Prediction, and Synthesis for Antihypertensive Activity.

Gagandeep Kaur, Ankur Thakur, Lovish Sharma, Nidhi Rani
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Abstract

Introduction: The drug discovery and development domain has witnessed remarkable advancements due to the integration of computational methods, particularly Computer-Aided Drug Design (CADD). Discovering and creating new drugs involves structural modifications to enhance their effectiveness and physical attributes. This frequently includes employing semisynthetic techniques to investigate structure-activity relationships thoroughly. Noticeable progress in molecular biology, computational chemistry, combinatorial chemistry, and highthroughput screening is steering transformative changes in the pharmaceutical industry.

Background: High blood pressure or hypertension, a significant health issue, elevates the chances of heart, kidney, and brain complications, among other health concerns. It's a leading cause of untimely mortality globally. Therefore, it is important to search for new antihypertensive compounds that have fewer side effects and higher therapeutic activity.

Methods: Following molecular docking of the pyridazine derivatives, compounds were subjected to In-silico ADMET analysis. Subsequently, a low molecular weight compound was synthesized. Among the synthesized compounds characterization procedures include TLC, FT-IR, 1HNMR, and LC-MS techniques.

Result: Compound 8 exhibited the most favorable molecular docking results with alpha A1 and beta 1 adrenergic receptors. Compounds 3, 5, and 6 fulfilled the essential ADMET criteria. Subsequently, Compounds 3, 4, and 5 underwent additional synthesis and characterization procedures, including TLC, FT-IR, 1H-NMR, and LC-MS techniques.

Conclusion: Similar behavior was observed in compounds 6, 8, 10, and 11, all violating Pfizer's 3/75 rules in terms of TPAS. Hydrazinolysis of these b-benzoyl propionic acids produced pyridazine, which was utilized in synthesizing pyridazine derivatives. TLC, FT-IR, 1HNMR, and LCMS have characterized the compounds.

哒嗪衍生物:分子对接、ADMET 预测和抗高血压活性合成。
导言:由于整合了计算方法,特别是计算机辅助药物设计(CADD),药物发现和开发领域取得了显著进步。发现和创造新药涉及结构改造,以提高其有效性和物理属性。这通常包括采用半合成技术来彻底研究结构-活性关系。分子生物学、计算化学、组合化学和高通量筛选等领域取得的显著进展正在推动制药业发生变革:背景:高血压是一个重要的健康问题,会增加心脏、肾脏和大脑并发症以及其他健康问题的几率。它是导致全球过早死亡的主要原因。因此,寻找副作用小、治疗活性高的新型降压化合物非常重要:方法:在对哒嗪衍生物进行分子对接后,对化合物进行了 In-silico ADMET 分析。随后,合成了低分子量化合物。在合成的化合物中,表征程序包括 TLC、傅立叶变换红外光谱、1HNMR 和 LC-MS 技术:结果:化合物 8 与 alpha A1 和 beta 1 肾上腺素能受体的分子对接结果最理想。化合物 3、5 和 6 符合基本的 ADMET 标准。随后,化合物 3、4 和 5 又进行了额外的合成和表征程序,包括 TLC、傅立叶变换红外光谱、1H-NMR 和 LC-MS 技术:在化合物 6、8、10 和 11 中也观察到了类似的行为,所有这些化合物都违反了辉瑞公司关于 TPAS 的 3/75 规则。这些 b-苯甲酰基丙酸的肼解作用产生了哒嗪,可用于合成哒嗪衍生物。TLC、FT-IR、1HNMR 和 LCMS 对这些化合物进行了表征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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