methyl 2-(4-bromophenyl)-2-isopropyl-5-(4-(2-methoxyphenyl)piperazine-1-yl)pentanoate | 1061285-01-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: methyl 2-(4-bromophenyl)-2-isopropyl-5-(4-(2-methoxyphenyl)piperazine-1-yl)pentanoate
• 英文别名: Methyl 2-(4-bromophenyl)-2-isopropyl-5-(4-(2-methoxyphenyl)piperazin-1-yl)pentanoate；methyl 2-(4-bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-2-propan-2-ylpentanoate
• CAS: 1061285-01-5
• 化学式: C₂₆H₃₅BrN₂O₃
• 分子量: 503.479
• InChiKey: LJRBNBCTAYVKFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-bromophenyl)-2-isopropyl-5-(4-(2-methoxyphenyl)piperazine-1-yl)pentanoate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以82%的产率得到2-(4-Bromophenyl)-5-[4-(2-methoxyphenyl)piperazin-1-yl]-2-propan-2-ylpentanoic acid
  参考文献：
  名称：

  Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker

  摘要：

  To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound's amines, most appreciably alleviated hERG toxicity while maintaining T-type calcium channel blocking activity. Notably, the benzimidazole amide 5 selectively blocked T-type calcium channels without inhibiting hERG (hERG/T-type >= 220) and L-type channels (L-type/T-type = 96), and exhibited an excellent pharmacokinetic profile in rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.078
• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 、 methyl isopropyl(3-bromopropyl)-4-bromophenylacetate 在 三乙胺 、 sodium iodide 作用下， 以 乙腈 为溶剂， 生成 methyl 2-(4-bromophenyl)-2-isopropyl-5-(4-(2-methoxyphenyl)piperazine-1-yl)pentanoate
  参考文献：
  名称：

  Synthesis and evaluation of α,α′-disubstituted phenylacetate derivatives for T-type calcium channel blockers

  摘要：

  We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC50 = 8.17 +/- 0.48 nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC50 = 1.34 +/- 0.49 mu M). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.037

文献信息

• NOVEL PHENYLACETATE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF AND COMPOSITION FOR PREVENTION OR TREATMENT OF DISEASES INDUCED BY ACTIVATION OF T-TYPE CALCIUM ION CHANNEL CONTAINING THE SAME AS AN ACTIVE INGREDIENT
  申请人：SHIN Kye Jung

  公开号：US20100056545A1

  公开（公告）日：2010-03-04

  Disclosed herein are a new phenylacetate derivative represented by Chemical Formula 1 or pharmaceutically acceptable salt thereof, a preparation method thereof, and a composition for prevention or treatment of diseases induced by the activation of T-type calcium ion channels containing the same. The composition containing the phenylacetate derivative according to the present invention effectively inhibits the activation of T-type calcium ion channels and may be useful in the prevention or treatment of diseases such as hypertension, cancer, epilepsy, and neurogenic pains induced by the activation of T-type calcium ion channels. wherein, X, R 1 , and R 3 are as defined herein.

  本公开揭示了一种由化学式1表示的新苯乙酸盐衍生物或其药用可接受的盐，其制备方法以及含有该衍生物的预防或治疗由T型钙离子通道激活引起的疾病的组合物。根据本发明的含有苯乙酸盐衍生物的组合物有效抑制T型钙离子通道的激活，并可能在预防或治疗高血压、癌症、癫痫和由T型钙离子通道激活引起的神经痛等疾病中发挥作用。其中，X，R1和R3如本文所定义。
• US7939672B2
  申请人：——

  公开号：US7939672B2

  公开（公告）日：2011-05-10
• Synthesis and evaluation of α,α′-disubstituted phenylacetate derivatives for T-type calcium channel blockers
  作者：Hyung Kook Lee、Yun Suk Lee、Eun Joo Roh、Hyewhon Rhim、Jae Yeol Lee、Kye Jung Shin

  DOI：10.1016/j.bmcl.2008.06.037

  日期：2008.8

  We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC50 = 8.17 +/- 0.48 nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC50 = 1.34 +/- 0.49 mu M). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model. (c) 2008 Elsevier Ltd. All rights reserved.
• Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker
  作者：Yeon Jae Choi、Jae Hong Seo、Kye Jung Shin

  DOI：10.1016/j.bmcl.2013.12.078

  日期：2014.2

  To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound's amines, most appreciably alleviated hERG toxicity while maintaining T-type calcium channel blocking activity. Notably, the benzimidazole amide 5 selectively blocked T-type calcium channels without inhibiting hERG (hERG/T-type >= 220) and L-type channels (L-type/T-type = 96), and exhibited an excellent pharmacokinetic profile in rats. (C) 2013 Elsevier Ltd. All rights reserved.