1-<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-propyne | 101411-65-8

• 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: 1-<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-propyne
• 英文别名: 1-{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-yl]methoxy}-2-propyne；1-{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-yl]methoxy}prop-2-yne；5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2-methyl-6-(prop-2-ynoxymethyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 101411-65-8
• 化学式: C₂₁H₂₁Cl₂NO₅
• 分子量: 438.307
• InChiKey: YAZNVEYZLISSMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  537.1±50.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-propyne 在 Lindlar's catalyst 正丁基锂 、 氢气 作用下， 以 吡啶 为溶剂， 反应 0.75h， 生成 4-(2,3-dichlorophenyl)-2-(4-dimethylamino-(2Z)-butenyloxy)methyl-3-ethoxycarbonyl-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：

  4-氯乙酰乙酸乙酯 在 哌啶 、 sodium hydride 作用下， 反应 40.0h， 生成 1-<<4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl>methoxy>-2-propyne
  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。
• Antihypertensive 2-hydroxyalkoxyalkyl dihydropyridines
  申请人：Pfizer Inc.

  公开号：US04654353A1

  公开（公告）日：1987-03-31

  Compounds of the formula: ##STR1## where R is an optionally substituted aryl or heteroaryl group; R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl; and Y is --(CH.sub.2).sub.n -- where n is 2, 3 or 4, --CH.sub.2 CH(CH.sub.3)-- or --Ch.sub.2 C(CH.sub.3).sub.2 --; and their pharmaceutically acceptable salts. The compounds have utility as anti-ischaemic and antihypertensive agents and as synthetic intermediates to other dihydropyridine calcium antagonists.

  式为：##STR1## 其中 R 是可选择取代的芳基或杂环芳基；R.sup.1 和 R.sup.2 分别独立地为 C.sub.1 -C.sub.4 烷基或 2-甲氧乙基；Y 为 --(CH.sub.2).sub.n --，其中 n 为 2、3 或 4，--CH.sub.2 CH(CH.sub.3)-- 或 --Ch.sub.2 C(CH.sub.3).sub.2 --；以及它们的药用可接受盐。这些化合物可用作抗缺血和降压药物，以及作为其他二氢吡啶钙拮抗剂的合成中间体。
• 2-oxygen containing heteroalkoxyalkyl dihydropyridine intermediates
  申请人：Pfizer Inc.

  公开号：US04732985A1

  公开（公告）日：1988-03-22

  1,4-Dihydropyridine anti-ischaemic and antihypertensive agent of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is 2-chlorophenyl, 2,3-dichlorophenyl or 2-chloro-3-trifluoromethylphenyl; R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl; X is O or S; R.sup.3 is H or C.sub.1 -C.sub.4 alkyl; and R.sup.4 is 1,2,4-triazol-1-ylmethyl, imidazol-1-ylmethyl, azidomethyl, 2,4,5-trimethylimidazol-1-ylmethyl, 3,4-dihydro-4-oxopyrimidin-2-ylthiomethyl, pyrimidin-2-ylthiomethyl; pyrimidin-2-ylaminomethyl, 3,4-dihydro-4-oxopyrimidin-2-ylaminomethyl, 2-aminopyrimidin-4-yloxymethyl, methoxymethyl, 2-furyl, 2-pyridylmethyl, imidazol-2-yl, hydroxymethyl, aminomethyl, 1,2,4-triazol-4-ylmethyl or 2-hydroxyethyl, and intermediates leading thereto.

  1,4-二氢吡啶抗缺血和降压剂的化学式为：##STR1## 或其药用盐，其中R为2-氯苯基、2,3-二氯苯基或2-氯-3-三氟甲基苯基；R.sup.1和R.sup.2分别独立为C.sub.1-C.sub.4烷基；X为O或S；R.sup.3为H或C.sub.1-C.sub.4烷基；R.sup.4为1,2,4-三唑-1-基甲基、咪唑-1-基甲基、叠氮基甲基、2,4,5-三甲基咪唑-1-基甲基、3,4-二氢-4-氧代嘧啶-2-基硫甲基、嘧啶-2-基硫甲基、嘧啶-2-基氨基甲基、3,4-二氢-4-氧代嘧啶-2-基氨基甲基、2-氨基嘧啶-4-氧甲基、甲氧基甲基、2-呋喃基、2-吡啶基甲基、咪唑-2-基、羟甲基、氨基甲基、1,2,4-三唑-4-基甲基或2-羟乙基，以及导致这些中间体的化合物。
• Long-acting dihydropyridine calcium antagonists. 6. Structure-activity relationships around 4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-2-[(2-hydroxyethoxy)methyl]-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine
  作者：David Alker、Simon F. Campbell、Peter E. Cross

  DOI：10.1021/jm00105a004

  日期：1991.1

  4-dihydropyridine (2) is described, and its potent calcium antagonist activity on rat aorta (IC50 = 4 x 10(-9) M) and marked tissue selectivity in vitro for vascular smooth muscle over cardiac smooth muscle are established. In order to exploit the excellent in vitro profile of compound 2, a range of analogues were prepared but none were found to have superior calcium antagonist potency and tissue selectivity. Compound

  描述了4-（2,3-二氯苯基）-3-（乙氧基羰基）-2-[（2-羟基乙氧基）甲基] -5-（甲氧基羰基）-6-甲基-1,4-二氢吡啶的制备（2） ，并建立了其对大鼠主动脉的强钙拮抗剂活性（IC50 = 4 x 10（-9）M）和体外对血管平滑肌优于心脏平滑肌的明显组织选择性。为了利用化合物2的出色的体外特性，制备了一系列类似物，但没有一个具有出色的钙拮抗剂效价和组织选择性。化合物2在麻醉的狗中具有出色的体内活性（ED50 = 12微克/ kg，可降低CVR），在清醒的狗中血浆半衰期为7.2小时。将2的药代动力学参数与对结构相关化合物氨氯地平和非洛地平测定的参数进行比较。
• Dihydropyridine anti-ischaemic and antihypertensive agents
  申请人：Pfizer Inc.

  公开号：US04892881A1

  公开（公告）日：1990-01-09

  1,4-Dihydropyridine anti-ischaemic and antihypertensive agent of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is 2-chlorophenyl, 2,3-dichlorophenyl or 2-chloro-3-trifluoromethylphenyl; R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl; X is O or S; R.sup.3 is H or C.sub.1 -C.sub.4 alkyl; and R.sup.4 is 1,2,4-triazol-1-ylmethyl, imidazol-1-ylmethyl, azidomethyl, 2,4,5-trimethylimidazol-1-ylmethyl, 3,4-dihydro-4-oxopyrimidin-2-ylthiomethyl, pyrimidin-2-ylthiomethyl; pyrimidin-2-ylaminomethyl, 3,4-dihydro-4-oxopyrimidin-2-ylaminomethyl, 2-aminopyrimidin-4-yloxymethyl, methoxymethyl, 2-furyl, 2-pyridylmethyl, imidazol-2-yl, hydroxymethyl, aminomethyl, 1,2,4-triazol-4-ylmethyl or 2-hydroxyethyl, and intermediates leading thereto.

  1,4-二氢吡啶抗缺血和降压剂的化学式为：##STR1##或其药学上可接受的盐，其中R为2-氯苯基，2,3-二氯苯基或2-氯-3-三氟甲基苯基；R.sup.1和R.sup.2各自独立地为C.sub.1-C.sub.4烷基；X为O或S；R.sup.3为H或C.sub.1-C.sub.4烷基；R.sup.4为1,2,4-三唑-1-基甲基，咪唑-1-基甲基，偶氮基甲基，2,4,5-三甲基咪唑-1-基甲基，3,4-二氢-4-氧代嘧啶-2-基硫甲基，嘧啶-2-基硫甲基；嘧啶-2-基氨甲基，3,4-二氢-4-氧代嘧啶-2-基氨甲基，2-氨基嘧啶-4-氧甲基，甲氧甲基，2-呋喃基，2-吡啶基甲基，咪唑-2-基，羟甲基，氨基甲基，1,2,4-三唑-4-基甲基或2-羟乙基，以及导致这些中间体的。