2-amino-6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-3-methylpyrimidine

• 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-amino-6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-3-methylpyrimidine
• 英文别名: 2-Amino-6-{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridin-2-yl]methoxymethyl}-3-methyl-4-pyrimidone；3-O-ethyl 5-O-methyl 2-[(2-amino-1-methyl-6-oxopyrimidin-4-yl)methoxymethyl]-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₂₄H₂₆Cl₂N₄O₆
• 分子量: 537.4
• InChiKey: FXUYWQOCUSZYJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  β-氨基巴豆酸甲酯 在 哌啶 、 正丁基锂 、 敌草腈 、 水 、 苄基三甲基氢氧化铵 、 potassium carbonate 、 溶剂黄146 、 二乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 137.5h， 生成 2-amino-6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-3-methylpyrimidine
  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

• 2-(4-Pyrimidone alkoxyalkyl) dihydropyridine anti-ischaemic and
  申请人：Pfizer Inc.

  公开号：US04568677A1

  公开（公告）日：1986-02-04

  1,4-Dihydropyridine derivatives of the formula: ##STR1## wherein R is aryl or heteroaryl; R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl; X is a 5 or 6 membered nitrogen-containing heterocyclic ring which is substituted with one or more hydroxyl or oxo groups and which may optionally be fused to a further 5 or 6 membered nitrogen-containing heterocyclic ring, and which may optionally be further substituted in the heterocyclic ring or further fused heterocyclic ring; Y is --(CH.sub.2).sub.n --, --CH.sub.2 CH(CH.sub.3)-- or --CH.sub.2 C(CH.sub.3).sub.2 --; and n is 1 to 3 when X is linked to Y by a ring carbon atom, or 2 or 3 when X is linked to Y by a ring nitrogen atom; and their pharmaceutically acceptable salts, and pharmacuetical preparation containing such compounds, have utility as anti-ischaemic and antihypertensive agents.

  公式为：##STR1##，其中R为芳基或杂芳基；R.sup.1和R.sup.2各自独立地为C.sub.1-C.sub.4烷基或2-甲氧基乙基；X是一个含氮杂环，其为5或6成员的，被一个或多个羟基或羰基基团取代，且可以选择性地与另一个5或6成员的含氮杂环融合，可以在杂环环或进一步融合的杂环环中进一步取代；Y为--（CH.sub.2）.sub.n --，--CH.sub.2 CH（CH.sub.3）--或--CH.sub.2 C（CH.sub.3）.sub.2 --；当X通过一个环碳原子与Y连接时，n为1到3，或当X通过一个环氮原子与Y连接时，n为2或3；它们的药学上可接受的盐和含有这种化合物的药物制剂，具有作为抗缺血和降压剂的用途。
• Dihydropyridine anti-ischaemic and antihypertensive agents
  申请人：Pfizer Limited

  公开号：EP0132375A2

  公开（公告）日：1985-01-30

  1,4-Dihydropyridine derivatives of the formula: wherein R is aryl or heteroaryl; R1 and R are each independently C1-C4 alkyl or 2-methoxyethyl; X is a 5 or 6 membered nitrogen-containing heterocyclic ring which is substituted with one or more hydroxyl or oxo groups and which may optionally be fused to a further 5 or 6 membered nitrogen-containing heterocyclic ring, and which may optionally be further substituted in the heterocyclic ring or further fused heterocyclic ring; Y is -(CH2)n-, -CH2CH(CH3)- or-CH2C(CH3)2-; and n is 1 to 3 when X is linked to Y by a ring carbon atom, or 2 or 3 when X is linked to Y by a ring nitrogen atom; and their pharmaceutically acceptable salts, and pharmaceutical preparation containing such compounds, have utility as anti-ischaemic and antihypertensive agents.

  式中的 1,4-二氢吡啶衍生物： 其中 R 是芳基或杂芳基；R1 和 R 各自独立地是 C1-C4 烷基或 2-甲氧基乙基；X 是 5 或 6 位含氮杂环，该杂环被一个或多个羟基或氧代基团取代，并可任选与另一个 5 或 6 位含氮杂环融合，且可任选在杂环或进一步融合的杂环中被进一步取代；Y是-(CH2)n-、-CH2CH(CH3)-或-CH2C(CH3)2-；当X通过环碳原子与Y相连时，n是1至3，当X通过环氮原子与Y相连时，n是2或3；它们的药学上可接受的盐和含有这些化合物的药物制剂可用作抗缺血性和抗高血压药物。
• 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：——
• US4568677A
  申请人：——

  公开号：US4568677A

  公开（公告）日：1986-02-04
• 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.