5-O-(1-chloropropan-2-yl) 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 100427-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-O-(1-chloropropan-2-yl) 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 100427-02-9
• 化学式: C₂₂H₂₆Cl₃NO₄
• 分子量: 474.812
• InChiKey: MGHIWTJBRDLINI-UHFFFAOYSA-N

物化性质

• 沸点：
  545.8±50.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-甲基-3,3-二苯基丙胺 、 5-O-(1-chloropropan-2-yl) 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 以5%的产率得到5-O-[1-[3,3-diphenylpropyl(methyl)amino]propan-2-yl] 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9
• 作为产物：
  描述：

  乙酰乙酸异丁酯 在 氨 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 生成 5-O-(1-chloropropan-2-yl) 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9

文献信息

• Asymmetrical diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid
  申请人：RECORDATI S.A. CHEMICAL and PHARMACEUTICAL COMPANY

  公开号：EP0153016A2

  公开（公告）日：1985-08-28

  Compounds I (Ph = phenyl; Ar = 2 - nitrophenyl, 3-nitrophenyl, 2,3-dichlorphenyl or benzofurazan-4-yl; A = C2 - C6 alkylene; R = C1 - C6 alkyl optionally C1 - C6 alkoxy monosubstituted; R1 = H, OH or C1- C4 alkyl; R2 = H or CH3) have antihypertensive activity and are effective against coronary heart diseases. They are prepared starting from the aldehyde ArCHO and esters of acetoacetic acid and 3-amino-crotonic acid. Pharmaceutical preparations containing them are also described.

  化合物 I（Ph =苯基；Ar = 2-硝基苯基、3-硝基苯基、2,3-二氯苯基或苯并呋咱-4-基；A = C2 - C6 亚烷基；R = C1 - C6 烷基，可选 C1 - C6 烷氧基单取代；R1 = H、OH 或 C1 - C4 烷基；R2 = H 或 CH3）具有抗高血压活性，对冠心病有效。 它们是由醛 ArCHO 以及乙酰乙酸酯和 3-氨基巴豆酸酯制备而成。 此外，还介绍了含有这些化合物的药物制剂。
• US4772621A
  申请人：——

  公开号：US4772621A

  公开（公告）日：1988-09-20
• US4705797A
  申请人：——

  公开号：US4705797A

  公开（公告）日：1987-11-10
• Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity
  作者：Amedeo Leonardi、Gianni Motta、Renzo Pennini、Rodolfo Testa、Giorgio Sironi、Alberto Catto、Alberto Cerri、Marco Zappa、Giorgio Bianchi、Dante Nardi

  DOI：10.1016/s0223-5234(98)80015-9

  日期：1998.6

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.