2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid methyl ester 2-chloroethyl ester | 100427-00-7

• 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: 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid methyl ester 2-chloroethyl ester
• 英文别名: 2-Chloroethyl methyl 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；5-O-(2-chloroethyl) 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 100427-00-7
• 化学式: C₁₈H₁₈Cl₃NO₄
• 分子量: 418.704
• InChiKey: IHRRYMKGBMJTKQ-UHFFFAOYSA-N

物化性质

• 沸点：
  512.4±50.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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 、 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid methyl ester 2-chloroethyl ester 生成 5-O-[2-[3,3-diphenylpropyl(methyl)amino]ethyl] 3-O-methyl 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：

  β-氨基巴豆酸甲酯 、 2-[1-(2,3-Dichloro-phenyl)-meth-(E)-ylidene]-3-oxo-butyric acid 2-chloro-ethyl ester 以 异丙醇 为溶剂， 反应 8.0h， 以44%的产率得到2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid methyl ester 2-chloroethyl ester
  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

• 3,5-Diacyl-4-aryl-1,4 dihydropyridine derivatives, their uses and
  申请人：Ciba-Geigy Corporation

  公开号：US04853393A1

  公开（公告）日：1989-08-01

  Compounds of the formula ##STR1## in which R represents a carbocyclic or heterocyclic aryl radical, R.sub.1 represents lower alkyl, one of the groups R.sub.2 and R.sub.3 represents lower alkyl and the other represents lower alkyl, cyano or amino, X represents oxygen or the group --NH--, and Alk represents lower alkylene which separates the group X from the ring nitrogen atom by at least two carbon atoms, Y represents the group --CHOH-- or --(C.dbd.O)--, and Ar.sub.1 represents a monocyclic aryl or heteroaryl radical, Ar.sub.1 being other than unsubstituted phenyl if R.sub.1, R.sub.2 and R.sub.3 each represents lower alkyl, X represents oxygen, Alk represents straight-chain alkylene having from 2 to 4 carbon atoms, Y represents the group --(C.dbd.O)-- and R has the meaning given, and salts thereof have cardiovascular, especially coronary-dilatory and antihypertensive properties.

  式为##STR1##的化合物，其中R代表碳环或杂环芳基基团，R.sub.1代表较低的烷基，R.sub.2和R.sub.3中的一个代表较低的烷基，另一个代表较低的烷基、氰基或氨基，X代表氧或--NH--基团，Alk代表较低的烷基，将基团X与环氮原子隔开至少两个碳原子，Y代表--CHOH--或--(C.dbd.O)--基团，Ar.sub.1代表单环芳基或杂环芳基基团，如果R.sub.1、R.sub.2和R.sub.3每个代表较低的烷基，X代表氧，Alk代表具有2至4个碳原子的直链烷基，Y代表--(C.dbd.O)--基团，R具有所给的含义，以及其盐具有心血管、特别是冠脉扩张和降压作用。
• 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。
• Process for the preparation of 1,4-dihydropyridine derivatives
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0371492B1

  公开（公告）日：1995-06-21
• 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