1-N,N-dimethylcarbamoyl-5-(4-fluorophenyl)-3-{4-[(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methyl]benzoyl}indole

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 1-N,N-dimethylcarbamoyl-5-(4-fluorophenyl)-3-{4-[(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methyl]benzoyl}indole
• 英文别名: 5-(4-fluorophenyl)-N,N-dimethyl-3-[4-[(2-methylimidazo[4,5-c]pyridin-1-yl)methyl]benzoyl]indole-1-carboxamide
• 化学式: C₃₂H₂₆FN₅O₂
• 分子量: 531.589
• InChiKey: YVKILYGWHWHBGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯甲基苯甲酰氯 在 N,N-二甲基丙烯基脲 、 三氯化铝 、 sodium bromide 作用下， 反应 6.75h， 生成 1-N,N-dimethylcarbamoyl-5-(4-fluorophenyl)-3-{4-[(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methyl]benzoyl}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

• PLATELET ACTIVATING FACTOR ANTAGONISTS: IMIDAZOPYRIDINE INDOLES
  申请人：Abbott Laboratories

  公开号：EP0734386B1

  公开（公告）日：2002-02-06
• US5486525A
  申请人：——

  公开号：US5486525A

  公开（公告）日：1996-01-23
• [EN] PLATELET ACTIVATING FACTOR ANTAGONISTS: IMIDAZOPYRIDINE INDOLES<br/>[FR] ANTAGONISTES DU FACTEUR D'ACTIVATION PLAQUETTAIRE: INDOLES D'IMIDAZOPYRIDINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1995016687A1

  公开（公告）日：1995-06-22

  (EN) The present invention relates to compounds of formula (I) 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.(FR) L'invention concerne des composés de formule (I) et des sels pharmaceutiquement acceptables de ces derniers constituant des antagonistes puissants du facteur d'activation plaquettaire et convenant au traitement de troubles relatifs audit facteur, dont l'asthme, l'état de choc, le syndrome de détresse respiratoire, l'inflammation aigüe, le rejet d'organe transplanté, l'ulcération gastro-intestinale, les affections allergiques cutanées, l'immunité cellulaire retardée, la parturition, la maturation pulmonaire f÷tale, et la différentiation cellulaire.
• 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.