2-(2-甲基苯基)-2-异丙基-5-(N-2-(3,4-二甲氧基苯基)乙基-N-甲基氨基)戊腈 | 117721-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(2-甲基苯基)-2-异丙基-5-(N-2-(3,4-二甲氧基苯基)乙基-N-甲基氨基)戊腈
• 英文名称: 2-isopropyl-2-(2-methylphenyl)-5-(N-methyl-N-homoveratrylamino)-valeronitrile
• 英文别名: Mepamil；5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-(2-methylphenyl)-2-propan-2-ylpentanenitrile
• CAS: 117721-47-8
• 化学式: C₂₆H₃₆N₂O₂
• 分子量: 408.584
• InChiKey: WSTHECAEFYKCPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-isopropyl-2-(2-methylphenyl)-5-oxo valeronitrile 、 N-甲基-2-(3,4-二甲氧基苯基)乙胺 生成 2-(2-甲基苯基)-2-异丙基-5-(N-2-(3,4-二甲氧基苯基)乙基-N-甲基氨基)戊腈
  参考文献：
  名称：

  BLAHA, LUDVIK;RAJSNER, MIROSLAV;HELFERT, IVAN;TRCKA, VACLAV

  摘要：

  DOI：

文献信息

• 2-Isopropyl-2-(2-methylphenyl)-5-(N-methyl-N-homoveratr
  申请人：Spofa, spojene podniky pro zdravotnickou

  公开号：US04847403A1

  公开（公告）日：1989-07-11

  2-Isopropyl-2-(2-methylphenyl)-5-(N-methylhomoveratrylamino)-valeronitrile ("mepamil") of the Formula I: ##STR1## preferably administered in the form of water-soluble acid addition salts such as e.g. hydrochloride. The claimed compound is advantageously prepared by alkylation of 2-(2-methylphenyl)-3-methylbutyronitrile with 3,3-diethoxypropylchloride. Subsequently, the obtained 5,5-diethoxy-2-isopropyl-2-(2-Methylphenyl)-valeronitrile is mildly, acidically hydrolisized to yield the appropriate aldehye, i.e. 2-isopropyl-2-(2-methylphenyl)-5-oxovaleronitrile. This aldehyde is then reacted with N-methylhomoveratrylamine under conditions of reductive alkylation, suitably by catalytic hydrogenation over a platinum or palladium catalyst or by chemical reduction with the use of formic acid as a reducing agent. The resulting base is optionally converted by neutralization with a pharmaceutically acceptable organic or inorganic acid, i.e. hydrochloric or fumaric acid, into the corresponding acid addition salt.

  2-异丙基-2-(2-甲基苯基)-5-(N-甲基同香豆素基)戊腈（“mepamil”）的化学式为I：##STR1## 最好以水溶性酸盐的形式（例如盐酸）进行给药。所述化合物的制备方法是通过将2-(2-甲基苯基)-3-甲基丁腈烷基化与3,3-二乙氧基丙基氯化物。随后，所得的5,5-二乙氧基-2-异丙基-2-(2-甲基苯基)-戊腈在酸性条件下轻度水解，得到适当的醛，即2-异丙基-2-(2-甲基苯基)-5-氧代戊腈。然后，将该醛与N-甲基同香豆酰胺在还原性烷基化条件下反应，适宜地使用铂或钯催化剂的氢化或使用甲酸作为还原剂的化学还原。所得到的碱可以通过与药用可接受的有机或无机酸（例如盐酸或富马酸）中和转化为相应的酸盐。
• SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKERS AND USES THEREOF
  申请人：Milestone Pharmaceuticals Inc.

  公开号：US20170312243A1

  公开（公告）日：2017-11-02

  The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

  本发明涉及使用药效学有效量的短效钙通道阻滞剂来治疗缺血性心脏病、心脏心律失常、急诊室高血压危机、手术前、手术中或手术后的高血压、再灌注后无反流现象以及与骨骼肌血流减少相关的疾病。本发明还涉及制备用于这些方法的制药组合物以及用于这些方法的工具箱。
• 2-Isopropyl-2-phenyl-5-(N-methyl-2-phenylethylamino)-valeronitrile derivatives and processes for their preparation
  申请人：SPOFA Spojené Podniky Pro Zdravotnickou Vyrobu

  公开号：EP0257768A1

  公开（公告）日：1988-03-02

  2-Isopropyl-2-phenyl-5-1N-methyl-2-phenylethylaminol- valeronitrile derivatives of the general formula I wherein R is a methyl, chlorine, bromine, C1 to C4 alkoxyl or methylthio group, preferably administered in the form of soluble acid addition salts, notablythe 2-methylphenyl analog as its hydrochloride, possess significant calcium-antagonistic and cardiac antiarrythmic activity. Preparation is by alkylation of the corresponding butyroni- triie derivative (obtained from the respective substituted benzyicyanide by alkylation with isopropylbromide) by 3,3-diethoxypropylchloride, subsequent acidic hydrolysis of the 5,5-diethoxy-2-isopropyl-2-phenylvaleronitrile derivative obtained to the appropriate aldehyde, and reductive alkylation of this aldehyde with N-methylhomoveratrylamine by catalytic hydrogenation over a platinum or palladium catalyst or chemical reduction using formic acid. The resulting base is optionally neutralized with a pharmaceutically acceptable organic or inorganic acid, e.g. hydrochloric or fumaric acid, into the corresponding acid addition salt.

  通式 I 的 2-异丙基-2-苯基-5-1N-甲基-2-苯乙基氨基戊腈衍生物，其中 R 是甲基、氯、溴、C1 至 C4 烷氧基或甲硫基。 其中 R 是甲基、氯、溴、C1 至 C4 烷氧基或甲硫基，最好以可溶性酸加成盐的形式给药，特别是 2-甲基苯基类似物盐酸盐，具有显著的钙拮抗剂和抗心律失常活性。 制备方法是用 3,3-二乙氧基丙基盐酸盐烷基化相应的丁腈三酸衍生物（从各自取代的苄基氰化物中用异丙基溴烷基化得到），然后酸性水解 5、5-二乙氧基-2-异丙基-2-苯基戊腈衍生物的酸性水解，得到相应的醛，然后通过铂或钯催化剂上的催化氢化作用或甲酸的化学还原作用，将该醛与 N-甲基高藜芦胺还原烷基化。得到的碱可选择与药学上可接受的有机酸或无机酸（如盐酸或富马酸）中和，生成相应的酸加成盐。
• Short acting phenylalkylamine calcium channel blockers and uses thereof
  申请人：Milestone Pharmaceuticals Inc.

  公开号：US10010523B2

  公开（公告）日：2018-07-03

  The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

  本发明涉及使用药学有效量的短效钙通道阻滞化合物治疗缺血性心脏疾病、心律失常、急诊室环境中的高血压危象、手术前、手术中或手术后的高血压、再灌注后的无回流现象以及与骨骼肌血流量减少有关的疾病。本发明还涉及配制成用于此类方法的药物组合物以及用于此类方法的试剂盒。
• US4847403A
  申请人：——

  公开号：US4847403A

  公开（公告）日：1989-07-11