3-chloroacetyl-6-(4-fluorophenyl)indole | 170499-33-9

• 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
• 英文名称: 3-chloroacetyl-6-(4-fluorophenyl)indole
• 英文别名: 6-(4-fluorophenyl)-3-chloroacetylindole；2-chloro-1-[6-(4-fluorophenyl)-1H-indol-3-yl]ethanone
• CAS: 170499-33-9
• 化学式: C₁₆H₁₁ClFNO
• 分子量: 287.721
• InChiKey: HOQBAMABCMDWGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  32.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloroacetyl-6-(4-fluorophenyl)indole 在 N,N-二甲基丙烯基脲 、 氢氧化钾 、 sodium bromide 作用下， 反应 22.25h， 生成 1-N,N-dimethylcarbamoyl-6-(4-fluorophenyl)-3-[(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methylcarbonyl]indole
  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：

  氯乙酰氯 、 6-(4-氟苯基)吲哚 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以2.8 g的产率得到3-chloroacetyl-6-(4-fluorophenyl)indole
  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

• Indole-3-carbonyl and indole-3-sulfonyl derivatives as platelet
  申请人：Abbott Laboratories

  公开号：US05567711A1

  公开（公告）日：1996-10-22

  The present invention provides compounds of formula ##STR1## and the pharmaceutically acceptable salts thereof which are potent antagonists of PAF and are useful in the treatment of PAF-related disorders including asthma, shock, respiratory distress syndrome, acute inflammation, transplanted organ rejection, gastrointestinal ulceration, allergic skin diseases, delayed cellular immunity, parturition, fetal lung maturation, and cellular differentiation.

  本发明提供了公式##STR1##的化合物及其药学上可接受的盐，它们是PAF的强效拮抗剂，并可用于治疗与PAF相关的疾病，包括哮喘，休克，呼吸窘迫综合症，急性炎症，移植器官排斥，胃肠溃疡，过敏性皮肤病，延迟细胞免疫，分娩，胎儿肺成熟和细胞分化。
• PLATELET ACTIVATING FACTOR ANTAGONISTS: IMIDAZOPYRIDINE INDOLES
  申请人：Abbott Laboratories

  公开号：EP0734386B1

  公开（公告）日：2002-02-06
• INDOLE-3-CARBONYL AND INDOLE-3-SULFONYL DERIVATIVES AS PLATELET ACTIVATING FACTOR ANTAGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：EP0821685B1

  公开（公告）日：2001-10-04
• US5486525A
  申请人：——

  公开号：US5486525A

  公开（公告）日：1996-01-23
• US5567711A
  申请人：——

  公开号：US5567711A

  公开（公告）日：1996-10-22