1-phenylsulfonyl-3-[(4-bromomethyl)phenylsulfonyl]indole | 170499-49-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-phenylsulfonyl-3-[(4-bromomethyl)phenylsulfonyl]indole
• 英文别名: 1-(Benzenesulfonyl)-3-[4-(bromomethyl)phenyl]sulfonylindole
• CAS: 170499-49-7
• 化学式: C₂₁H₁₆BrNO₄S₂
• 分子量: 490.398
• InChiKey: VAJDOHLFGGYJFZ-UHFFFAOYSA-N

物化性质

• 沸点：
  692.1±65.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-phenylsulfonyl-3-[(4-bromomethyl)phenylsulfonyl]indole 在 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 生成 1H-吲哚,3-[[4-(氨基甲基)苯基]磺酰]-1-(苯磺酰)-
  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：

  1-phenylsulfonyl-3-(4-methylphenylsulfonyl)indole 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 生成 1-phenylsulfonyl-3-[(4-bromomethyl)phenylsulfonyl]indole
  参考文献：
  名称：

  Platelet activating factor antagonists: imidazopyridine indoles

  摘要：

  本发明涉及具有公式##STR1##的化合物及其药用可接受的盐，这些化合物是PAF的强效拮抗剂，可用于治疗与PAF相关的疾病，包括哮喘、休克、呼吸窘迫综合征、急性炎症、移植器官排斥、胃肠道溃疡、过敏性皮肤病、迟发性细胞免疫、分娩、胎儿肺成熟和细胞分化。

  公开号：

  US05486525A1

文献信息

• Platelet activating factor antagonists: imidazopyridine indoles
  申请人：Abbott Laboratories

  公开号：US05486525A1

  公开（公告）日：1996-01-23

  The present invention relates to 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.

  本发明涉及具有公式##STR1##的化合物及其药用可接受的盐，这些化合物是PAF的强效拮抗剂，可用于治疗与PAF相关的疾病，包括哮喘、休克、呼吸窘迫综合征、急性炎症、移植器官排斥、胃肠道溃疡、过敏性皮肤病、迟发性细胞免疫、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
• 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.