4-溴-3-[4-(氯甲基)-3-氟苯甲酰基]-N,N-二甲基-1H-吲哚-1-羧酰胺 | 200418-19-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 4-溴-3-[4-(氯甲基)-3-氟苯甲酰基]-N,N-二甲基-1H-吲哚-1-羧酰胺
• 英文名称: 4-bromo-3-[4-(chloromethyl)-3-fluorobenzoyl]-N,N-dimethyl-1H-Indole-1-carboxamide
• 英文别名: 4-bromo-3-[4-(chloromethyl)-3-fluorobenzoyl]-N,N-dimethylindole-1-carboxamide
• CAS: 200418-19-5
• 化学式: C₁₉H₁₅BrClFN₂O₂
• 分子量: 437.696
• InChiKey: GUAPPXJGCWOWAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  42.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-溴-3-[4-(氯甲基)-3-氟苯甲酰基]-N,N-二甲基-1H-吲哚-1-羧酰胺 在 platinum on activated charcoal potassium fluoride 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 sodium azide 、 水 、 氢气 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 120.0 ℃ 、405.3 kPa 条件下， 反应 49.0h， 生成 1H-Indole-1-carboxamide, 4-ethynyl-3-((3-fluoro-4-((2-methyl-1H-imidazo(4,5-c)pyridin-1-yl)methyl)phenyl)hydroxymethyl)-N,N-dimethyl-
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+
• 作为产物：
  描述：

  4-溴吲哚 在 氢氧化钾 、 三氯化铝 作用下， 反应 6.92h， 生成 4-溴-3-[4-(氯甲基)-3-氟苯甲酰基]-N,N-二甲基-1H-吲哚-1-羧酰胺
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+

文献信息

• J. Med. Chem. 1998, 41, 74-95
  作者：

  DOI：——

  日期：——
• Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists
  作者：Michael L. Curtin、Steven K. Davidsen、H. Robin Heyman、Robert B. Garland、George S. Sheppard、Alan S. Florjancic、Lianhong Xu、George M. Carrera、Douglas H. Steinman、Jeff A. Trautmann、Daniel H. Albert、Terrance J. Magoc、Paul Tapang、David A. Rhein、Richard G. Conway、Gongjin Luo、Jon F. Denissen、Kennan C. Marsh、Douglas W. Morgan、James B. Summers

  DOI：10.1021/jm970389+

  日期：1998.1.1

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.