5-{[3-(1H-benzimidazole-2-yl)propyl]methylamino}-2-(4-bromophenyl)-2-isopropylpentanoic acid methyl ester | 1061457-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-{[3-(1H-benzimidazole-2-yl)propyl]methylamino}-2-(4-bromophenyl)-2-isopropylpentanoic acid methyl ester
• 英文别名: methyl 5-((3-(1H-benzo[d]imidazol-2-yl)propyl)(methyl)amino)-2-(4-bromophenyl)-2-isopropylpentanoate；methyl 5-[3-(1H-benzimidazol-2-yl)propyl-methylamino]-2-(4-bromophenyl)-2-propan-2-ylpentanoate
• CAS: 1061457-72-4
• 化学式: C₂₆H₃₄BrN₃O₂
• 分子量: 500.479
• InChiKey: DUAKQKCVTZFHSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-{[3-(1H-benzimidazole-2-yl)propyl]methylamino}-2-(4-bromophenyl)-2-isopropylpentanoic acid methyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以88%的产率得到5-[3-(1H-benzimidazol-2-yl)propyl-methylamino]-2-(4-bromophenyl)-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：

  [3-(1H-苯并咪唑-2-基)-丙基]-甲胺 、 methyl isopropyl(3-bromopropyl)-4-bromophenylacetate 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以36%的产率得到5-{[3-(1H-benzimidazole-2-yl)propyl]methylamino}-2-(4-bromophenyl)-2-isopropylpentanoic acid methyl ester
  参考文献：
  名称：

  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

  摘要：

  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。

  公开号：

  US20100056545A1

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。
• 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：Korea Institute of Science and Technology

  公开号：US07939672B2

  公开（公告）日：2011-05-10

  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, R1, and R3 are as defined herein.

  本文披露了一种新的苯乙酸衍生物，其化学式为1，或其药学上可接受的盐，以及其制备方法和包含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。本发明所述的含有苯乙酸衍生物的组合物有效地抑制了T型钙离子通道的激活，可能有助于预防或治疗高血压、癌症、癫痫和由T型钙离子通道激活引起的神经性疼痛等疾病。其中，X、R1和R3如本文所定义。
• USES, COMPOSITIONS AND METHODS
  申请人：Fisahn Andre

  公开号：US20210038589A1

  公开（公告）日：2021-02-11

  The present invention relates generally to calcium channel inhibitors for use in treating and/or preventing an amyloid disease of the nervous system. The invention also relates to related pharmaceutical compositions, kits and screening methods.
• T-TYPE CALCIUM CHANNEL MODULATORS AND METHODS OF USE THEREOF
  申请人：Praxis Precision Medicines, inc.

  公开号：US20210128537A1

  公开（公告）日：2021-05-06

  Described herein are compounds useful for preventing and/or treating a disease or condition relating to aberrant function of a T-type calcium channel, such as epilepsy and epilepsy syndromes (e.g., absence seizures, juvenile myoclonic epilepsy, or a genetic epilepsy) and mood disorders. The present invention further comprises methods for modulating the function of a T-type calcium channel.
• US7939672B2
  申请人：——

  公开号：US7939672B2

  公开（公告）日：2011-05-10