合成一些新型 C2 取代的二氢嘧啶并对其作为 L-/T 型钙通道阻滞剂的电生理活性进行评价。
Synthesis of some new C2 substituted dihydropyrimidines and their electrophysiological evaluation as L-/T-type calcium channel blockers.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria 21311, Egypt.
出版信息
Bioorg Chem. 2019 Jul;88:102915. doi: 10.1016/j.bioorg.2019.04.009. Epub 2019 Apr 11.
Drugs targeting different calcium channel subtypes have strong therapeutic potential for future drug development for cardiovascular disorders, neuropsychiatric diseases and cancer. This study aims to design and synthesize a new series of C2 substituted dihydropyrimidines to mimic the structure features of third generation long acting dihydropyridine calcium channel blockers and dihydropyrimidines analogues. The target compounds have been evaluated as blockers for Ca1.2 and Ca3.2 utilizing the whole-cell patch clamp technique. Among the tested compounds, compound 7a showed moderate calcium channel blockade activity against Ca3.2. Moreover, the predicted physicochemical properties and pharmacokinetic profiles of the target compounds recommend that they can be considered as drug-like candidates. The results highlight some significant information for the future design of lead compounds as calcium channel blockers.
针对不同钙通道亚型的药物在未来心血管疾病、神经精神疾病和癌症的药物开发方面具有强大的治疗潜力。本研究旨在设计和合成一系列新的 C2 取代的二氢嘧啶，以模拟第三代长效二氢吡啶钙通道阻滞剂和二氢嘧啶类似物的结构特征。利用全细胞膜片钳技术，评估目标化合物作为 Ca1.2 和 Ca3.2 的阻断剂的活性。在所测试的化合物中，化合物 7a 对 Ca3.2 显示出中等的钙通道阻断活性。此外，目标化合物的预测物理化学性质和药代动力学特征表明，它们可以被认为是类药性候选物。研究结果为钙通道阻滞剂的先导化合物的未来设计提供了一些重要信息。
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