6-(4-氟苯基)吲哚-1,3-二羧酸二甲基酰胺 | 170499-71-5

• 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: 6-(4-氟苯基)吲哚-1,3-二羧酸二甲基酰胺
• 英文名称: 6-(4-fluorophenyl)indole-1,3-dicarboxylic acid dimethyl amide
• 英文别名: 1-(Dimethylcarbamoyl)-6-(4-fluorophenyl)indole-3-carboxylic acid
• CAS: 170499-71-5
• 化学式: C₁₈H₁₅FN₂O₃
• 分子量: 326.327
• InChiKey: RCMOVTVQEWJTSK-UHFFFAOYSA-N

物化性质

• 沸点：
  535.4±58.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine 、 6-(4-氟苯基)吲哚-1,3-二羧酸二甲基酰胺 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 生成 6-(4-fluorophenyl)-3-{[4-(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methylpiperidin-1-yl]carbonyl}indole-1-carboxylic acid dimethyl amide
  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：

  6-(4-氟苯基)吲哚 在 氢氧化钾 、 sodium chlorite 、 sodium dihydrogenphosphate 、 氯化亚砜 、 2-甲基-2-丁烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 4.25h， 生成 6-(4-氟苯基)吲哚-1,3-二羧酸二甲基酰胺
  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

• 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
• US5567711A
  申请人：——

  公开号：US5567711A

  公开（公告）日：1996-10-22
• [EN] INDOLE-3-CARBONYL AND INDOLE-3-SULFONYL DERIVATIVES AS PLATELET ACTIVATING FACTOR ANTAGONISTS<br/>[FR] DERIVES D'INDOLE-3-CARBONYLE ET D'INDOLE-3-SULFONYLE UTILISES EN TANT QU'ANTAGONISTES DU FACTEUR D'ACTIVATION DES PLAQUETTES
  申请人：ABBOTT LABORATORIES

  公开号：WO1996033196A1

  公开（公告）日：1996-10-24

  (EN) The present invention provides 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) La présente invention décrit des composés de formule (I) et leurs sels pharmaceutiquement acceptables qui sont des antagonistes puissants du facteur d'activation des plaquettes (PAF) et qui sont utilisés dans le traitement de troubles relatifs au PAF, tels que l'asthme, l'état de choc, le syndrome de détresse respiratoire, l'inflammation aiguë, le rejet d'organes transplantés, l'ulcération gastro-intestinale, les maladies allergiques de la peau, l'immunité retardée des cellules, la parturition, la maturation pulmonaire du f÷tus et la différenciation 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.