6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(methylthio)pyrimidine | 101988-81-2

• 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-(methylthio)pyrimidine
• 英文别名: 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2-methyl-6-[(2-methylsulfanyl-6-oxo-1H-pyrimidin-4-yl)methoxymethyl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 101988-81-2
• 化学式: C₂₄H₂₅Cl₂N₃O₆S
• 分子量: 554.451
• InChiKey: LMQYRKQKRZMUAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 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：
  141
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-氨甲基吡啶 、 6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(methylthio)pyrimidine 反应 7.0h， 以28%的产率得到6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(2-pyridylmethyl)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
• 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 156.0h， 生成 6-({[4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl]methoxy}methyl)-4-hydroxy-2-(methylthio)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：EP0165032A2

  公开（公告）日：1985-12-18

  1, 4-Dihydropyridines of the formula:- wherein R is aryl or heteroaryl; R, and R2 are each C1-C4 alkyl or 2-methoxyethyl; X is a 5 or 6 memebred nitrogen-containing aromatic heterocyclic ring which is substituted with one or more C1-C4 alkoxy groups and which may optionally be additionally substituted with one or more C1-C4 alkyl, aryl, hydroxy, oxo. CN, N(R4)2, (CH2)mCON(R4)2 or (CH2)mCO2R5 groups, wherein m is 0 or 1, each R4 is independently H or Cl-C4 alkyl or the two groups R4 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 and R5 is H or C1-C4 alkyl; and Y is -(CH2)n-, -CH2CH(CH3)- or -CH2C/CH3)2- wherein n is 1 to 3; are calcium channel blockers useful as anti-ischaemic and antihypertensive agents.

  式中的 1，4-二氢吡啶 其中 R 为芳基或杂芳基；R 和 R2 各为 C1-C4 烷基或 2-甲氧基乙基；X 为 5 或 6 目含氮芳香杂环，该环被一个或多个 C1-C4 烷氧基基团取代，还可任选被一个或多个 C1-C4 烷基、芳基、羟基、氧代、CN、N(R4)2、(CH2)mCON(R4)2 或 (CH2)mCO2R5 基团取代。CN、N(R4)2、(CH2)mCON(R4)2 或 (CH2)mCO2R5 基团，其中 m 为 0 或 1，每个 R4 独立地为 H 或 Cl-C4 烷基，或两个基团 R4 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，R5 为 H 或 C1-C4 烷基；和 Y 是-(CH2)n-、-CH2CH(CH3)- 或-CH2C/CH3)2-，其中 n 是 1 至 3；是可用作抗缺血和抗高血压药物的钙通道阻滞剂。
• 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.