1-<2-<<4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyrid-2-yl>methoxy>ethyl>-3-methylurea | 93849-23-1

• 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: 1-<2-<<4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyrid-2-yl>methoxy>ethyl>-3-methylurea
• 英文别名: 1-<2-{[4-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridin-2-yl]methoxy}ethyl>-3-methylurea；5-O-ethyl 3-O-methyl 4-(2-chlorophenyl)-2-methyl-6-[2-(methylcarbamoylamino)ethoxymethyl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 93849-23-1
• 化学式: C₂₂H₂₈ClN₃O₆
• 分子量: 465.934
• InChiKey: RRLUUJCGNWEBAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氨氯地平 、 异氰酸甲酯 以 二氯甲烷 为溶剂， 生成 1-<2-<<4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyrid-2-yl>methoxy>ethyl>-3-methylurea
  参考文献：
  名称：

  4-aryl-3,5-bis(alkoxycarbonyl)-6-methyl

  摘要：

  1,4-二氢吡啶衍生物的化学式为：##STR1## 其中 R 是芳基或杂环芳基；R.sup.1 和 R.sup.2 分别是 C.sub.1 -C.sub.4 烷基或 2-甲氧基乙基；n 为 2、3 或 4；R.sup.3 是 H、C.sub.1 -C.sub.4 烷基、CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 烷基) 或 CH.sub.2 CN；R.sup.4 是 COR.sup.5、CSR.sup.5、C(.dbd.NR.sup.6)R.sup.7 或 SO.sub.2 R.sup.5 的基团，其中 R.sup.5 是 C.sub.1 -C.sub.4 烷基、NH.sub.2、NH(C.sub.1 -C.sub.4 烷基)、NH(C.sub.3 -C.sub.6 环烷基)、N(C.sub.1 -C.sub.4 烷基).sub.2、NHCH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 烷基)、NHCH.sub.2 CONH.sub.2、NHCH.sub.2 CO.sub.2 H、NH(CH.sub.2).sub.2 NH.sub.2、NHNH.sub.2、NHNRCO.sub.2 (C.sub.1 -C.sub.4 烷基)、NH-芳基、NHCO-芳基或杂环芳基、NH-杂环芳基或 NHCO-杂环芳基，或当 R.sup.4 是 C(.dbd.O)R.sup.5 时，R.sup.5 可以是 H 或 CF.sub.3；R.sup.6 是 H、CN、CO.sub.2 (C.sub.1 -C.sub.4 烷基)、CO(C.sub.1 -C.sub.4 烷基)、SO.sub.2 (C.sub.1 -C.sub.4 烷基)、SO.sub.2 -芳基、SO.sub.2 NH.sub.2、SO.sub.2 N(C.sub.1 -C.sub.4 烷基).sub.2、NO.sub.2 或芳基；R.sup.7 是 NH.sub.2、NH(C.sub.1 -C.sub.4 烷基)、NHCO(C.sub.1 -C.sub.4 烷基)、NH(CH.sub.2).sub.m N(C.sub.1 -C.sub.4 烷基).sub.2，其中 m 为 2 到 4，或 NH-杂环芳基；以及它们的药学上可接受的酸盐，以及含有这类化合物的药物制剂，具有作为抗缺血和降压药物的用途。

  公开号：

  US04590195A1

文献信息

• Dihydropyridine anti-ischaemic and antihypertensive agents
  申请人：Pfizer Limited

  公开号：EP0119050A2

  公开（公告）日：1984-09-19

  1,4-Dihydropyridine derivatives of the formula:- wherein R is aryl or heteroaryl; R1 and R2 are each C1-C4 alkyl or 2-methoxyethyl; n is 2, 3 or 4; R3 is H, C1-C4 alkyl, CH2CO2(C1-C4 alkyl) or CH2CN; and R4 is a group of the formula COR5, CSR5, C(=NR6)R7 or SO2R5, wherein R5 is C,-C4 alkyl, NHz, NH(C1-C4 alkyl), NH(C3-C6 cycloalkyl), N(C1-C4 alkyl)2, NHCH2CO2(C1-C4 alkyl), NHCH2CONH2, NHCH2CO2H, NH(CH2)2NH2, NHNH2, NHNHCO2(C1-C4 alkyl), NH-aryl, NHCO-aryl or a heterocyclic, NH-heterocyclic or NHCO-heterocyclic group, or when R4 is C(=O)R5, R5 may be H or CF3; R6 is H, CN, CO2(C1-C4 alkyl), CO(C1-C4 alkyl), SO2(C1-C4 alkyl), SO2-aryl, SO2NH2, SO2N(C1-C4 alkyl)2, NO2 or aryl; and R7 is NHz, NH(C1-C4 alkyl), NHCO(C1-C4 alkyl), NH(CH2)mN(C1-C4 alkyl)2 wherein m is 2 to 4 or a NH-heterocyclic group; and their pharmaceutically acceptable acid addition 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：- 1，4-二氢吡啶衍生物 其中 R 是芳基或杂芳基；R1 和 R2 分别是 C1-C4 烷基或 2-甲氧基乙基；n 是 2、3 或 4；R3 是 H、C1-C4 烷基、CH2CO2(C1-C4 烷基)或 CH2CN；和 R4 是式 COR5、CSR5、C(＝NR6)R7 或 SO2R5 的基团，其中 R5 是 C,-C4烷基、NHz、NH(C1-C4 烷基)、NH(C3-C6 环烷基)、N(C1-C4 烷基)2、NHCH2CO2(C1-C4 烷基)、NHCH2CONH2、NHCH2CO2H、NH(CH2)2NH2、NHNH2、NHNHCO2(C1-C4 烷基)、NH-芳基、NHCO-芳基或杂环、NH-杂环或 NHCO-杂环基团，或者当 R4 是 C(=O)R5 时，R5 可以是 H 或 CF3；R6 是 H、CN、CO2(C1-C4 烷基)、CO(C1-C4 烷基)、SO2(C1-C4 烷基)、SO2-芳基、SO2NH2、SO2N(C1-C4 烷基)2、NO2 或芳基；以及 R7 是 NHz、NH(C1-C4 烷基)、NHCO(C1-C4 烷基)、NH(CH2)mN(C1-C4 烷基)2（其中 m 为 2 至 4）或 NH-杂环基团；及其药学上可接受的酸加成盐，以及含有此类化合物的药物制剂，具有抗缺血和降压作用。
• Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and nonbasic derivatives of 2[(2-aminoethoxy)methyl]-1,4-dihydropyridine calcium antagonists
  作者：David Alker、Simon F. Campbell、Peter E. Cross、Roger A. Burges、Anthony J. Carter、Donald G. Gardiner

  DOI：10.1021/jm00164a019

  日期：1990.2

  The preparation of a series of 1,4-dihydropyridines (DHPs) which have polar, acyclic, nonbasic substituents on an ethoxymethyl chain at the 2-position is described. In addition, in order to assess the effects of incorporating a basic center into DHPs of this type, a series of glycinamides were also prepared. The calcium antagonist activity on rat aorta of both these classes of DHP is compared with their negative inotropic activity as determined by using a Langendorff perfused guinea pig heart model. A number of the compounds evaluated have activity of the same order as nifedipine although those with more extended substituents have lower potency, particularly when a basic substituent is present. The compounds examined displayed a wide variation in selectivity for vascular over cardiac tissue. A number of structure-activity relationship trends were identified and possible explanations to account for the differences in selectivity observed are advanced. One of the compounds, 2-[[2-[[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6- methyl-1,4-dihydropyrid-2-yl]methoxy]ethyl]amino]acetamide (26, UK-51,656), was identified as a potent (IC50 = 4 x 10(-9) M) calcium antagonist which is 20-fold selective for vascular over cardiac tissue and which has a markedly longer duration of action (greater than 5 h) than nifedipine in the anesthetized dog on intravenous administration. The pharmacokinetic half-life of 26 was established as 4.7 h and possible explanations are advanced to account for 26 having a shorter plasma half-life than amlodipine and a longer plasma half-life than felodipine.
• ALKER, DAVID;CAMPBELL, SIMON F.;CROSS, PETER E.;BURGES, ROGER A.;CARTER, +, J. MED. CHEM., 33,(1990) N, C. 585-591
  作者：ALKER, DAVID、CAMPBELL, SIMON F.、CROSS, PETER E.、BURGES, ROGER A.、CARTER, +

  DOI：——

  日期：——
• 4-aryl-3,5-bis(alkoxycarbonyl)-6-methyl
  申请人：Pfizer Inc.

  公开号：US04590195A1

  公开（公告）日：1986-05-20

  1,4-Dihydropyridine derivatives of the formula: ##STR1## wherein R is aryl or heteroaryl; R.sup.1 and R.sup.2 are each C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl; n is 2, 3 or 4; R.sup.3 is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 alkyl) or CH.sub.2 CN; and R.sup.4 is a group of the formula COR.sup.5, CSR.sup.5, C(.dbd.NR.sup.6)R.sup.7 or SO.sub.2 R.sup.5, wherein R.sup.5 is C.sub.1 -C.sub.4 alkyl, NH.sub.2, NH(C.sub.1 -C.sub.4 alkyl), NH(C.sub.3 -C.sub.6 cycloalkyl), N(C.sub.1 -C.sub.4 alkyl).sub.2, NHCH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 alkyl), NHCH.sub.2 CONH.sub.2, NHCH.sub.2 CO.sub.2 H, NH(CH.sub.2).sub.2 NH.sub.2, NHNH.sub.2, NHNRCO.sub.2 (C.sub.1 -C.sub.4 alkyl), NH-aryl, NHCO-aryl or a heterocyclic, NH-heterocyclic or NHCO-heterocyclic group, or when R.sup.4 is C(.dbd.O)R.sup.5, R.sup.5 may be H or CF.sub.3 ; R.sup.6 is H, CN, CO.sub.2 (C.sub.1 -C.sub.4 alkyl), CO(C.sub.1 -C.sub.4 alkyl), SO.sub.2 (C.sub.1 -C.sub.4 alkyl), SO.sub.2 -aryl, SO.sub.2 NH.sub.2, SO.sub.2 N(C.sub.1 -C.sub.4 alkyl).sub.2, NO.sub.2 or aryl; and R.sup.7 is NH.sub.2, NH(C.sub.1 -C.sub.4 alkyl), NHCO(C.sub.1 -C.sub.4 alkyl), NH(CH.sub.2).sub.m N(C.sub.1 -C.sub.4 alkyl).sub.2 wherein m is 2 to 4 or a NH-heterocyclic group; and their pharmaceutically acceptable acid addition salts, and pharmaceutical preparation containing such compounds, have utility as anti-ischaemic and antihypertensive agents.

  1,4-二氢吡啶衍生物的化学式为：##STR1## 其中 R 是芳基或杂环芳基；R.sup.1 和 R.sup.2 分别是 C.sub.1 -C.sub.4 烷基或 2-甲氧基乙基；n 为 2、3 或 4；R.sup.3 是 H、C.sub.1 -C.sub.4 烷基、CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 烷基) 或 CH.sub.2 CN；R.sup.4 是 COR.sup.5、CSR.sup.5、C(.dbd.NR.sup.6)R.sup.7 或 SO.sub.2 R.sup.5 的基团，其中 R.sup.5 是 C.sub.1 -C.sub.4 烷基、NH.sub.2、NH(C.sub.1 -C.sub.4 烷基)、NH(C.sub.3 -C.sub.6 环烷基)、N(C.sub.1 -C.sub.4 烷基).sub.2、NHCH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 烷基)、NHCH.sub.2 CONH.sub.2、NHCH.sub.2 CO.sub.2 H、NH(CH.sub.2).sub.2 NH.sub.2、NHNH.sub.2、NHNRCO.sub.2 (C.sub.1 -C.sub.4 烷基)、NH-芳基、NHCO-芳基或杂环芳基、NH-杂环芳基或 NHCO-杂环芳基，或当 R.sup.4 是 C(.dbd.O)R.sup.5 时，R.sup.5 可以是 H 或 CF.sub.3；R.sup.6 是 H、CN、CO.sub.2 (C.sub.1 -C.sub.4 烷基)、CO(C.sub.1 -C.sub.4 烷基)、SO.sub.2 (C.sub.1 -C.sub.4 烷基)、SO.sub.2 -芳基、SO.sub.2 NH.sub.2、SO.sub.2 N(C.sub.1 -C.sub.4 烷基).sub.2、NO.sub.2 或芳基；R.sup.7 是 NH.sub.2、NH(C.sub.1 -C.sub.4 烷基)、NHCO(C.sub.1 -C.sub.4 烷基)、NH(CH.sub.2).sub.m N(C.sub.1 -C.sub.4 烷基).sub.2，其中 m 为 2 到 4，或 NH-杂环芳基；以及它们的药学上可接受的酸盐，以及含有这类化合物的药物制剂，具有作为抗缺血和降压药物的用途。