ethyl 4<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-butynoate | 121590-52-1

• 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: ethyl 4<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-butynoate
• 英文别名: ethyl 4-{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-yl]methoxy}-2-butynoate；3-O-ethyl 5-O-methyl 4-(2,3-dichlorophenyl)-2-[(4-ethoxy-4-oxobut-2-ynoxy)methyl]-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 121590-52-1
• 化学式: C₂₄H₂₅Cl₂NO₇
• 分子量: 510.371
• InChiKey: NOCYHGVKFFRUSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 4<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-butynoate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 以64%的产率得到4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-2-(4-hydroxy-2-butynyloxy)-methyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 7. Compounds containing unsaturation in the 2-substituent on the 1,4-dihydropyridine ring

  摘要：

  To evaluate the effect of introducing unsaturation into the 2-substituent of 1,4-dihydropyridines related to amlodipine (1), a number of alkene and alkyne analogues were prepared and their calcium antagonist activity was assessed. For several series of compounds, in vitro potency increased in the order alkane < alkene < alkyne. This trend may either reflect decreasing entropy loss on binding to the DHP receptor or be a consequence of a favourable pi-interaction with the DHP receptor.

  DOI：

  10.1016/0223-5234(91)90197-u
• 作为产物：
  描述：

  β-氨基巴豆酸甲酯 在 哌啶 、 正丁基锂 、 苄基三甲基氢氧化铵 作用下， 以 二甲基亚砜 为溶剂， 反应 28.5h， 生成 ethyl 4<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-butynoate
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 3. Synthesis and structure-activity relationships for a series of 2-[(heterocyclylmethoxy)methyl] derivatives

  摘要：

  The preparation of 1,4-dihydropyridines containing (heterocyclylmethoxy)methyl groups in the 2-position is described and the structural identification of certain of the compounds using 1H NMR spectroscopic methods is reported. The calcium antagonist activity of the compounds on rat aorta is listed and is compared with the negative inotropic potency as determined by using a Langendorff-perfused guinea pig heart model. Several compounds are more potent than nifedipine and show greater selectivity for the vasculature over the heart. One compound, 2-[(2-amino-4-hydroxypyrimidin-6-yl)methoxy]-4- (2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl- 1,4-dihydropyridine (27, UK-56,593), was identified as a potent (IC50 = 1.6 x 10(-9) M), tissue-selective calcium antagonist which proved to have a markedly longer duration of action (greater than 4.5 h) than nifedipine in the anesthetized dog on intravenous administration.

  DOI：

  10.1021/jm00130a026

文献信息

• Dihydropyridine derivatives
  申请人：Pfizer Inc.

  公开号：US04957930A1

  公开（公告）日：1990-09-18

  Dihydropyridines having unsaturated side chains are disclosed. The compounds are useful anti-ischemic and antihypertensive agents.

  揭示了具有不饱和侧链的二氢吡啶类化合物。这些化合物是有用的抗缺血和降压药物。
• 1,4 Dihydropyridine derivatives, process for their preparation and their uses in pharmaceutical compositions
  申请人：Pfizer Limited

  公开号：EP0295769A2

  公开（公告）日：1988-12-21

  Dihydropyridine derivatives of the formula: where R is aryl or heteroaryl, R¹ and R² are each alkyl or methoxyethyl, X is O or S, Y is -CH=CH- or -C≡C-, and Z is -CHR⁵OH, -CONH₂, -CO₂R⁶ or -CH₂NR³R⁴, where R³ and R⁴ are H or alkyl or together form a 5- or 6-membered ring, R⁵ is H, alkyl or aryl, and R⁶ is H or alkyl, are anti-ischaemic and antihypertensive agents. All except compounds in which Y is -C≡C- ­and Z is -CO₂alkyl are novel.

  式中的二氢吡啶衍生物： 其中 R 是芳基或杂芳基，R¹ 和 R² 各自是烷基或甲氧基乙基，X 是 O 或 S，Y 是 -CH=CH- 或 -C≡C-，Z 是 -CHR⁵OH、-CONH₂、-CO₂R⁶ 或 -CH₂NR³R⁴、其中 R³ 和 R⁴ 是 H 或烷基或共同形成 5 或 6 元环，R⁵ 是 H、烷基或芳基，R⁶ 是 H 或烷基，这些化合物都是抗缺血和抗高血压药物。除 Y 为-C≡C-和 Z 为-CO₂烷基的化合物外，其他化合物均为新型化合物。
• ALKER, DAVID;CAMPBELL, SIMON F.;CROSS, PETER E.;BURGES, ROGER A.;CARTER, +, J. MED. CHEM., 32,(1989) N0, C. 2381-2388
  作者：ALKER, DAVID、CAMPBELL, SIMON F.、CROSS, PETER E.、BURGES, ROGER A.、CARTER, +

  DOI：——

  日期：——
• US4957930A
  申请人：——

  公开号：US4957930A

  公开（公告）日：1990-09-18
• Long-acting dihydropyridine calcium antagonists. 3. Synthesis and structure-activity relationships for a series of 2-[(heterocyclylmethoxy)methyl] derivatives
  作者：David Alker、Simon F. Campbell、Peter E. Cross、Roger A. Burges、Anthony J. Carter、Donald G. Gardiner

  DOI：10.1021/jm00130a026

  日期：1989.10

  The preparation of 1,4-dihydropyridines containing (heterocyclylmethoxy)methyl groups in the 2-position is described and the structural identification of certain of the compounds using 1H NMR spectroscopic methods is reported. The calcium antagonist activity of the compounds on rat aorta is listed and is compared with the negative inotropic potency as determined by using a Langendorff-perfused guinea pig heart model. Several compounds are more potent than nifedipine and show greater selectivity for the vasculature over the heart. One compound, 2-[(2-amino-4-hydroxypyrimidin-6-yl)methoxy]-4- (2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl- 1,4-dihydropyridine (27, UK-56,593), was identified as a potent (IC50 = 1.6 x 10(-9) M), tissue-selective calcium antagonist which proved to have a markedly longer duration of action (greater than 4.5 h) than nifedipine in the anesthetized dog on intravenous administration.