2-(4-bromo-2-fluorophenyl)-1Hbenzimidazole-4-carboxamide | 1224157-93-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(4-bromo-2-fluorophenyl)-1Hbenzimidazole-4-carboxamide
• 英文别名: 2-(4-bromo-2-fluorophenyl)-1H-benzimidazole-4-carboxamide
• CAS: 1224157-93-0
• 化学式: C₁₄H₉BrFN₃O
• 分子量: 334.147
• InChiKey: FJNIAUHARXXXOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-bromo-2-fluorophenyl)-1Hbenzimidazole-4-carboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三(邻甲基苯基)磷 4-三正丁基锡基吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-(2-fluoro-4-pyridin-4-ylphenyl)-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  WO2007/41357

  摘要：

  公开号：
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 反应 1.5h， 生成 2-(4-bromo-2-fluorophenyl)-1Hbenzimidazole-4-carboxamide
  参考文献：
  名称：

  Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor

  摘要：

  We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K-i of 1 nM and an EC50 of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.

  DOI：

  10.1021/jm901775y

文献信息

• 1H-BENZIMIDAZOLE-4-CARBOXAMIDES SUBSTITUTED WITH PHENYL AT THE 2-POSITION ARE POTENT PARP INHIBITORS
  申请人：Penning D. Thomas

  公开号：US20070179136A1

  公开（公告）日：2007-08-02

  Compound having formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds having formula (I), methods of treatment comprising compounds having formula (I), and methods of inhibiting the PARP enzyme comprising compounds having formula (I).

  具有公式(I)的化合物可以抑制PARP酶，适用于治疗与PARP相关的疾病或障碍。还公开了包含具有公式(I)的化合物的药物组合物，包括具有公式(I)的化合物的治疗方法，以及包括具有公式(I)的化合物的抑制PARP酶的方法。
• 1H-benzimidazole-4-carboxamides substituted with phenyl at the 2-position are potent PARP inhibitors
  申请人：Penning Thomas D.

  公开号：US08697736B2

  公开（公告）日：2014-04-15

  Compound having formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds having formula (I), methods of treatment comprising compounds having formula (I), and methods of inhibiting the PARP enzyme comprising compounds having formula (I).

  化学式为（I）的化合物可以抑制PARP酶，并且对于用于治疗与PARP相关的疾病或紊乱非常有用。还揭示了包含化学式（I）的化合物的药物组合物、包含化学式（I）的化合物的治疗方法，以及包含化学式（I）的化合物的PARP酶抑制方法。
• US8697736B2
  申请人：——

  公开号：US8697736B2

  公开（公告）日：2014-04-15
• [EN] PROCESS FOR THE PURIFICATION OF AROMATIC DICARBOXYLIC ACID<br/>[FR] PROCÉDÉ ET SYSTÈME
  申请人：DAVY PROCESS TECHN LTD

  公开号：WO2012038751A3

  公开（公告）日：2012-05-10

  [EN] A process for the purification of aromatic dicarboxylic acid comprising the steps of: (a) slurrying crude aromatic dicarboxylic acid solids with water recycled from at least a filtration step in a feed preparation zone; (b) supplying flash steam in vapour phase to the feed preparation zone from at least one of a crystallisation step, a filtration step, and a drier step; (c) preheating the slurried aromatic dicarboxylic acid solids to form a solution; (d) subjecting the heated solution to hydrogenation; (e) pure aromatic dicarboxylic acid to crystallise; (f) filtering out the crystals of pure aromatic dicarboxylic acid and recovering water in a single stage filtration process; (g) supplying at least part of the recovered water to the feed preparation zone; and (h) drying the filtered crystals and recovering same, wherein the flash stream recovered from at least one of a crystallisation step, a filtration step or a drier step is recovered as a vapour phase stream having a pressure of from about atmospheric to 5 barg and is supplied to the feed preparation zone without phase change. Also described is a system for the purification of aromatic dicarboxylic acid and a feed preparation vessel therefor.
  [FR] L'invention concerne un procédé de purification d'acide dicarboxylique aromatique, ce procédé comprenant les étapes consistant à: (a) mettre en suspension des matières solides d'acide dicarboxylique aromatique brut avec de l'eau recyclée, provenant d'au moins une étape de filtration, dans une zone de préparation de charge; (b) acheminer de la vapeur détendue en phase gazeuse dans la zone de préparation de charge, cette vapeur provenant d'une étape de cristallisation, d'une étape de filtration et/ou d'une étape de séchage; (c) préchauffer les matières solides d'acide dicarboxylique aromatique en suspension pour former une solution; (d) soumettre la solution chauffée à une hydrogénation; (e) amener l'acide dicarboxylique aromatique pur à cristalliser; (f) filtrer les cristaux d'acide dicarboxylique aromatique pur et récupérer l'eau au cours d'un processus de filtration en une seule étape; (g) acheminer au moins une partie de l'eau récupérée dans la zone de préparation de charge; et (h) sécher les cristaux filtrés et les récupérer, la vapeur détendue récupérée à l'issue d'une étape de cristallisation, d'une étape de filtration et/ou d'une étape de séchage étant récupérée sous la forme d'un flux en phase gazeuse, dont la pression est comprise approximativement entre la pression atmosphérique et 5 barg, et étant acheminée dans la zone de préparation de charge sans changement de phase. L'invention concerne également un système pour la purification d'acide dicarboxylique aromatique et une cuve de préparation de charge à cet effet.
• WO2007/41357
  申请人：——

  公开号：——

  公开（公告）日：——