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Abstract：
New dihydropyrimidines bearing various lipophilic pharmacophores and functionalities at position 3 were designed and synthesized. The basic framework of the new compounds was designed to maintain the main structural requirements for calcium channel blocking activity of the known dihydropyridines and dihydropyrimidines calcium channel blockers. The newly synthesized compounds were evaluated as antagonists for CaV1.2 and CaV3.2 using the whole-cell patch clamp technique. Seven compounds (4b, 4c, 6c, 9, 13c, 13e and 17b) showed promising dual calcium channel blocking activity and three compounds (13b, 14b and 17a) were selective against Cav3.2. Their drug-likeness has been assessed using Molinspiration and Molsoft softwares. Their physicochemical properties and pharmacokinetic profiles recommend that they can be considered as drug-like candidates.
摘要：
设计并合成了在3位具有各种亲脂性药效团和官能团的新二氢嘧啶。设计新化合物的基本框架以保持已知的二氢吡啶和二氢嘧啶钙通道阻断剂对钙通道阻断活性的主要结构要求。使用全细胞膜片钳技术评估新合成的化合物作为CaV1.2和CaV3.2的拮抗剂。七个化合物（4b，4c,6c,9、13c、13e和17b）显示出有希望的双钙通道阻断活性，并且三种化合物（13b，14b和17a）对Cav3.2具有选择性。已使用Molimination和Molsoft软件评估了它们的药物相似性。它们的物理化学性质和药代动力学特征表明它们可以被视为药物样候选物。
