N-(2-fluoro-5-pyridin-3-ylphenyl)-5-methoxy-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide | 181629-98-1

• 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: N-(2-fluoro-5-pyridin-3-ylphenyl)-5-methoxy-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
• CAS: 181629-98-1
• 化学式: C₂₂H₁₇F₄N₃O₂
• 分子量: 431.389
• InChiKey: NTNQMMLNOPGXJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(4-fluoro-3-nitrophenyl)pyridine 在 盐酸 、 tin(ll) chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(2-fluoro-5-pyridin-3-ylphenyl)-5-methoxy-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
  参考文献：
  名称：

  Biarylcarbamoylindolines Are Novel and Selective 5-HT_2C Receptor Inverse Agonists:  Identification of 5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a Potential Antidepressant/Anxiolytic Agent

  摘要：

  The evolution, synthesis, and biological activity of a novel series of 5-HT2C receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT2C affinity and selectivity over 5-HT2A receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT2B receptor. Compounds from this series are inverse agonists at the human cloned 5-HT2C receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

  DOI：

  10.1021/jm990388c

文献信息

• [EN] INDOLE DERIVATIVES AS 5-HT RECEPTOR ANTAGONIST<br/>[FR] DERIVES D'INDOLE UTILISES COMME ANTAGONISTE DU RECEPTEUR DE 5-HT
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1996023783A1

  公开（公告）日：1996-08-08

  (EN) The invention relates to heterocyclic compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders such as anxiety.(FR) L'invention concerne des composés hétérocycliques présentant une activité pharmacologique, leurs procédés de préparation, des compositions les contenant ainsi que leur utilisation dans le traitement de troubles du système nerveux central tels que l'anxiété.

  该发明涉及具有药理活性的杂环化合物，其制备过程，包含它们的组成物以及它们在治疗中枢神经系统障碍，如焦虑症方面的应用。
• Indole derivatives as 5-HT receptor antagonist
  申请人：SmithKline Beecham p.l.c.

  公开号：US20030105139A1

  公开（公告）日：2003-06-05

  The invention relates to heterocyclic compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders such as anxiety.

  本发明涉及具有药理活性的杂环化合物，其制备过程，含有它们的组合物以及它们在治疗中枢神经系统疾病如焦虑症方面的应用。
• INDOLE DERIVATIVES AS 5-HT RECEPTOR ANTAGONIST
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0808312A1

  公开（公告）日：1997-11-26
• US5990133A
  申请人：——

  公开号：US5990133A

  公开（公告）日：1999-11-23
• US6235758B1
  申请人：——

  公开号：US6235758B1

  公开（公告）日：2001-05-22