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

• 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: 6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(hydroxymethyl)pyrimidine
• 英文别名: 3-O-ethyl 5-O-methyl 4-(2,3-dichlorophenyl)-2-[[2-(hydroxymethyl)-6-oxo-1H-pyrimidin-4-yl]methoxymethyl]-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₂₄H₂₅Cl₂N₃O₇
• 分子量: 538.384
• InChiKey: CDZMVJCAXCQHEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  9

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 、 溶剂黄146 、 二乙胺 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 108.0h， 生成 6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(hydroxymethyl)pyrimidine
  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 anti-ischaemic and antihypertensive agents
  申请人：Pfizer Limited

  公开号：EP0189254A1

  公开（公告）日：1986-07-30

  1,4-dihydropyridine derivatives of the formula (I): (I) and pharmaceutically acceptable salts; wherein R is aryl or heteroaryl; R1 and R2 are each independently C1-C4 alkyl or 2-methoxyethyl; Y is -(CH2)n-, -CH2CH(CH3)- or -CH2C(CH3)2-; X is a group of the formula: wherein R3 is H, het, -(CH2)n-het, -NH-het, -NH-(CH2)n-het, -O-het, -O-(CH2)n-het, -(CH2)n-OH, -NR6R7, -(CH2)nNR6R7 or -NH--(CH2)pNR6R7; R4 is H, C1-C4 alkyl, -(CH2)pNR6R7, -(CH2)p-OH or -(CH2)n-het; and R5 is H, C1-C4 alkyl or phenyl; wherein R6 and R7 are each independently H or C1-C4 alkyl or the two groups R6 and R7 are taken together with the nitrogen atom to which they are attached to form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-C4 alkyl)piperazinyl group; n is 1-4 and p is 2-4; with the proviso that when R4 is H or C1-C4 alkyl, R3 is not H or -NR6R7. These compounds are useful as anti-ischaemic and antihypertensive agents.

  式 (I) 的 1,4-二氢吡啶衍生物： (I) 及药学上可接受的盐类； 其中 R 是芳基或杂芳基； R1和R2各自独立地是C1-C4烷基或2-甲氧基乙基； Y是-(CH2)n-、-CH2CH(CH3)-或-CH2C(CH3)2-； X是式中的基团： 其中 R3 是 H、het、-(CH2)n-het、-NH-het、-NH-(CH2)n-het、-O-het、-O-(CH2)n-het、-(CH2)n-OH、-NR6R7、-(CH2)nNR6R7 或-NH--(CH2)pNR6R7； R4 是 H、C1-C4 烷基、-(CH2)pNR6R7、-(CH2)p-OH 或 -(CH2)n-het；和 R5 是 H、C1-C4 烷基或苯基；其中 R6 和 R7 各自独立地为 H 或 C1-C4 烷基，或两个基团 R6 和 R7 与它们所连接的氮原子一起形成吡咯烷基、哌啶基、吗啉基、哌嗪基或 N-(C1-C4烷基)哌嗪基； n 为 1-4，p 为 2-4； 但 R4 为 H 或 C1-C4 烷基时，R3 不是 H 或-NR6R7。 这些化合物可用作抗缺血和抗高血压药物。
• 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：——
• 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.