5-甲基-6-三氟甲基吲哚啉 | 200711-22-4

• 物质功能分类: 有机原料 - 有机氟化合物
• 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: 5-甲基-6-三氟甲基吲哚啉
• 英文名称: 5-methyl-6-trifluoromethylindoline
• 英文别名: 5-Methyl-6-(trifluoromethyl)indoline；5-methyl-6-(trifluoromethyl)-2,3-dihydro-1H-indole
• CAS: 200711-22-4
• 化学式: C₁₀H₁₀F₃N
• 分子量: 201.191
• InChiKey: SJDNGKSDFPRJQU-UHFFFAOYSA-N

物化性质

• 沸点：
  233.9±40.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P273
• 危险性描述：
  H302,H412

反应信息

• 作为反应物：
  描述：

  phenyl N-[[2-(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamate 、 5-甲基-6-三氟甲基吲哚啉 在 phenyl N-[[2-(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamate 作用下， 以76的产率得到5-methyl-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid [6-(2-methyl-pyridin-3-yloxy)-pyridin-3-yl]-amide
  参考文献：
  名称：

  Indoline derivatives useful as 5-HT-2C receptor antagonists

  摘要：

  本发明涉及公式（I）的化合物或其盐，其中X为CH或N；R1为氢或C1-6烷基；R2和R3基团独立地为C1-6烷基或三氟甲基，具有药理活性，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中的应用。

  公开号：

  US06369060B1
• 作为产物：
  描述：

  5-甲氧基-6-(三氟甲基)吲哚啉 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 碘代三甲硅烷 、 lithium chloride 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 71.5h， 生成 5-甲基-6-三氟甲基吲哚啉
  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] INDOLINE DERIVATIVES USEFUL AS 5-HT-2C RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE L'INDOLINE UTILES COMME ANTAGONISTES DES RECEPTEURS 5HT-2C
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1997048699A1

  公开（公告）日：1997-12-24

  (EN) The invention relates to heterocyclic compounds of formula (I) or a salt thereof wherein X is CH or N; R1 is hydrogen or C1-6 alkyl; R2 and R3 groups are independently halogen, C1-6 alkyl, or trifluoromethyl, 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 de formule (I), dans laquelle X est CH ou N; R1 est hydrogène ou alkyle C1-C6; et les groupes R2 et R3 sont indépendamment halogène, alkyle C1-C6 ou trifluorométhyle; et leurs sels; ces composés ayant une activité pharmacologique. L'invention concerne également des procédés permettant de les préparer et des compositions les contenant, ainsi que leur utilisation dans le traitement des troubles du système nerveux central tels que l'angoisse.

  该发明涉及公式（I）的杂环化合物或其盐，其中X为CH或N; R1为氢或C1-6烷基; R2和R3基团独立地为卤素，C1-6烷基或三氟甲基，具有药理活性，其制备过程，含有它们的组合物以及它们在治疗如焦虑症等中枢神经系统疾病中的用途。
• Accelerated Synthesis of Bicyclo[1.1.1]pentylamines: A High-Throughput Approach
  作者：Maialen Alonso、Santiago Cañellas、Francisca Delgado、Marta Serrano、Alejandro Diéguez-Vázquez、José Enrique Gómez

  DOI：10.1021/acs.orglett.2c04226

  日期：2023.2.10

  high-throughput automated synthesis to rapidly develop library-amenable reaction conditions and maximize design space to expand access to BCPAs. This new protocol relies on a copper-mediated C–N coupling approach and uses accessible and bench-stable iodo-BCP building blocks. Its applicability has been exemplified by incorporating BCPs in drug-like compounds, providing straightforward access to a library of valuable

  双环 [1.1.1] 戊胺 (BCPA) 等应变双环子结构越来越多地作为芳胺生物电子等排物在药物化学中成为目标。在这里，我们利用高通量自动化合成来快速开发适合库的反应条件并最大化设计空间以扩大对 BCPA 的访问。这个新协议依赖于铜介导的 C-N 耦合方法，并使用可访问且稳定的碘-BCP 构建块。它的适用性已通过将 BCP 掺入类药物化合物中得到例证，从而可以直接访问有价值的类苯胺电子等排物库。
• 1-[2-[(Heteroaryloxy)heteroaryl]carbamoyl]indolines: novel and selective 5-HT2C receptor inverse agonists with potential as antidepressant/Anxiolytic agents
  作者：Steven M. Bromidge、Steven Dabbs、Susannah Davies、D.Malcolm Duckworth、Ian T. Forbes、Graham E. Jones、Jerome Jones、Frank D. King、Damian V. Saunders、Thomas P. Blackburn、Vicky Holland、Guy A. Kennett、Sean Lightowler、Derek N. Middlemiss、Graham J. Riley、Brenda Trail、Martyn D. Wood

  DOI：10.1016/s0960-894x(00)00364-4

  日期：2000.8

  Bisaryl ethers have been identified with excellent 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 11, 27 and 38 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their potential as novel non-sedating anxiolytic and antidepressants is under investigation. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134)
  作者：Steven M Bromidge、Stephen E Clarke、Tracey Gager、Kerry Griffith、Phillip Jeffrey、Andrew J Jennings、Graham F Joiner、Frank D King、Peter J Lovell、Stephen F Moss、Helen Newman、Graham Riley、Derek Rogers、Carol Routledge、Halina Serafinowska、Douglas R Smith

  DOI：10.1016/s0960-894x(00)00597-7

  日期：2001.1

  Substituted N-phenyl-4-methoxy-3-piperazin-1-ylbenzenesulfonamides and conformationally restricted analogues have been identified as high affinity and selective 5-HT6 antagonists. Compounds from this series had a range of pharmacokinetic profiles in rat and in general there was a correlation between clearance and CNS penetration. Based on its overall biological profile 2 (SB-357134) was selected for further pre-clinical evaluation. (C) 2000 Elsevier Science Ltd. All rights reserved.
• 1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists
  作者：Steven M. Bromidge、Susannah Davies、D.Malcolm Duckworth、Ian T. Forbes、Graham E. Jones、Jerome Jones、Frank D. King、Thomas P. Blackburn、Vicky Holland、Guy A. Kennett、Sean Lightowler、Derek N. Middlemiss、Graham J. Riley、Brenda Trail、Martyn D. Wood

  DOI：10.1016/s0960-894x(00)00365-6

  日期：2000.8

  Bisarylmethoxyethers have been identified with nanomolar 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 1, 2, 8, 12, 14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their therapeutic potential is currently under further investigation. (C) 2000 Elsevier Science Ltd. All rights reserved.