2-<<2-(2-methylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine | 88150-30-5

• 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-<<2-(2-methylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine
• 英文别名: 4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxy-carbonyl-6-methyl-2-(2-N-methylaminoethoxymethyl)-1,4-dihydropyridine；4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-(methylamino)ethoxy methyl]-1,4-dihydropyridine；4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-(2-methylamino-ethoxymethyl)-1,4-dihydropyridine；4-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-(2-methylaminoethoxymethyl)-1,4-dihydropyridine；5-O-ethyl 3-O-methyl 4-(2-chlorophenyl)-2-methyl-6-[2-(methylamino)ethoxymethyl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 88150-30-5
• 化学式: C₂₁H₂₇ClN₂O₅
• 分子量: 422.909
• InChiKey: BHQHUZXFSUAIGH-UHFFFAOYSA-N

物化性质

• 沸点：
  516.8±50.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-<<2-(2-methylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 以 乙醇 为溶剂， 反应 0.5h， 生成 1-<2-<<4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyrid-2-yl>methoxy>ethyl>-2-cyano-1,3-dimethylguanidine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00164a019
• 作为产物：
  描述：

  2-[2-(N-benzyl-N-methylamino)ethoxymethyl]-4-[2-chlorophenyl]-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, oxalate salt 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 2-<<2-(2-methylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine
  参考文献：
  名称：

  长效二氢吡啶类钙拮抗剂。1.结合有碱性取代基的2-烷氧基甲基衍生物。

  摘要：

  描述了一系列在2-位被碱性侧链取代的二氢吡啶，并列出了其作为钙拮抗剂的效力。发现一种化合物2-[（（2-氨基乙氧基）甲基] -4-（2-氯苯基）-3-乙氧基羰基-5-甲氧基羰基-6-甲基-1,4-二氢吡啶（17，氨氯地平）具有可比性。对硝苯地平有效，并具有30 h的消除半衰期。口服生物利用度接近100％，血液动力学反应起效缓慢，效果持久。已经制备了两种对映异构体，并且发现大部分活性与（-）异构体18有关。对17的相似类似物进行的X射线晶体学研究表明，两者之间存在弱氢键侧链氧和质子在环氮上。

  DOI：

  10.1021/jm00159a022

文献信息

• 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。
• 2-(2-quinazolinylaminoalkoxymethyl)-1,4-dihydropyridine derivatives as
  申请人：Pfizer Inc.

  公开号：US04647565A1

  公开（公告）日：1987-03-03

  Dihydropyridines of the formulae ##STR1## wherein R is chlorothienyl or mono- or disubstituted phenyl where said substituent is fluoro, chloro, bromo or trifluoromethyl; R.sup.1 and R.sup.2 are each alykl; R.sup.3 and R.sup.4 when taken separately are each hydrogen or alkyl; R.sup.3 and R.sup.4 when taken together with the nitrogen to which they are attached are piperidine or pyrrolidine; R.sup.5 is alkyl or 2-hydroxyethyl; R.sup.6 is hydrogen or methoxy; X and Z are each hydrogen or methoxy; Y is alkylene; R.sup.7 is chlorophenyl or trifluoromethyl-chlorophenyl; p is 0 or 1; and Q is CH or N are useful in the treatment of hypertension, heart failure and angina.

  上述公式中的二氢吡啶，其中R是氯硫烯基或单取代或双取代苯基，所述取代基为氟、氯、溴或三氟甲基；R.sup.1和R.sup.2分别是烷基；R.sup.3和R.sup.4在单独取时分别是氢或烷基；R.sup.3和R.sup.4与它们连接的氮一起时是哌啶或吡咯啉；R.sup.5是烷基或2-羟乙基；R.sup.6是氢或甲氧基；X和Z分别是氢或甲氧基；Y是烷基；R.sup.7是氯苯基或三氟甲基氯苯基；p为0或1；Q是CH或N，在治疗高血压、心力衰竭和心绞痛方面是有用的。
• Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol
  作者：Shaokun Cai、Hong Tang、Bo Li、Yingbo Shao、Danqi Zhang、Hanliang Zheng、Tianjiao Qiao、Xin Chu、Gang He、Xiao-Song Xue、Gong Chen

  DOI：10.1021/jacs.3c12215

  日期：2024.3.6

  except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular hydride transfer reactions of alkylamines under mild conditions. Besides transformations of small molecules, these reactions enable unique late-stage modification

  烷基胺自发释放氢阴离子的能力通常受到限制，除非在特定的分子内反应设置下。在此，我们证明这种反应活性可以通过在六氟异丙醇（HFIP）溶剂中用甲醛进行简单处理来释放，从而在温和条件下实现烷基胺的各种分子间氢化物转移反应。除了小分子的转化之外，这些反应还可以对复杂肽进行独特的后期修饰。机理研究发现，这些分子间氢化物转移过程的关键在于溶剂介导的大环过渡态的调节构象，其中 HFIP 分子的聚集体充当灵巧的质子穿梭机。重要的是，氮的孤电子对与胺的αC-H键的反键轨道之间的负超共轭在C-H活化中起着关键作用，促进其氢化物释放。
• Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them
  申请人：Pfizer Limited

  公开号：EP0089167A2

  公开（公告）日：1983-09-21

  Dihydropyridines of the formula:- and their pharmaceutically acceptable acid addition salts wherein Y is -(CH2)2-, -(CH2)3-, -CH2CH(CH3)- or -CH2C(CH3)2 -; R is aryl or heteroaryl; R1 and R2 are each independently C,-C4 alkyl or 2-methoxyethyl; and R3 is hydrogen, C1-C4 alkyl, 2-(C1-C4 alkoxy) ethyl, cyclopropylmethyl, benzyl, or- (CH2)m COR4 where m is 1, 2 or 3 and R4 is hydroxy, C1-C4 alkoxy or - NRR56 where R5 and R6 are each independently hydrogen or C1-C4 alkyl, pharmaceutical compositions containing them, and processes for their production. The compounds are particularly useful in the treatment or prevention of a variety of cardiac conditions, e.g. angina pectoris.

  式中的二氢吡啶： - 及其药学上可接受的酸加成盐 其中 Y 是-(CH2)2-、-(CH2)3-、-CH2CH(CH3)-或-CH2C(CH3)2-；R 是芳基或杂芳基；R1 和 R2 各自独立地是 C,-C4烷基或 2-甲氧基乙基； R3是氢、C1-C4烷基、2-(C1-C4烷氧基)乙基、环丙基甲基、苄基或-(CH2)m COR4，其中m是1、2或3，R4是羟基、C1-C4烷氧基或-NRR56，其中R5和R6各自独立地是氢或C1-C4烷基。 这些化合物特别适用于治疗或预防各种心脏疾病，如心绞痛。
• 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。