1-{3-fluoro-4-[2-oxo-2-(1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole | 1057662-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-{3-fluoro-4-[2-oxo-2-(1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole
• 英文别名: 2-[2-fluoro-4-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]phenyl]-1-pyrrolidin-1-ylethanone
• CAS: 1057662-54-0
• 化学式: C₂₀H₂₁F₄N₃O
• 分子量: 395.4
• InChiKey: LDPUPYCJAUQZJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-2-氟苯乙酸 在 copper(l) iodide 、 trans-1,2-Diaminocyclohexane 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.58h， 生成 1-{3-fluoro-4-[2-oxo-2-(1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole
  参考文献：
  名称：

  Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of AMPA Receptor Positive Allosteric Modulators

  摘要：

  A novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and efficacy profiles, leading to identification of a clinical candidate. Unusually for an ion channel target, this optimization was integrated with regular generation of ligand-bound crystal structures and uncovered a novel chemotype with a unique and highly conserved mode of interaction via a trifluoromethyl group.

  DOI：

  10.1021/jm100679e

文献信息

• WO2008/110566
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] COMPOUNDS WHICH POTENTIATE AMPA RECEPTOR AND USES THEREOF IN MEDICINE<br/>[FR] COMPOSÉS QUI POTENTIALISENT LE RÉCEPTEUR AMPA ET SES UTILISATIONS EN MÉDECINE
  申请人：GLAXO GROUP LTD

  公开号：WO2008110566A1

  公开（公告）日：2008-09-18

  [EN] A compound of formula (I) and salts thereof are provided: wherein A is defined in the specification. Processes for preparation, pharmaceutical compositions, and uses thereof as a medicament, for example in the treatment of a disease or condition mediated by a reduction or imbalance in glutamate receptor function, such as schizophrenia or cognition impairment, are also disclosed.
  [FR] L'invention porte sur un composé de formule (I) et ses sels, formule dans laquelle A est défini dans la description. L'invention porte également sur des procédés de préparation, sur des compositions pharmaceutiques et sur des utilisations de ce composé et de ses sels comme médicament, par exemple dans le traitement d'une maladie ou d'un état à médiation par une réduction ou un déséquilibre de la fonction des récepteurs du glutamate, comme la schizophrénie ou une altération de la cognition.
• Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of AMPA Receptor Positive Allosteric Modulators
  作者：Simon E. Ward、Mark Harries、Laura Aldegheri、Nigel E. Austin、Stuart Ballantine、Elisa Ballini、Daniel M. Bradley、Benjamin D. Bax、Brian P. Clarke、Andrew J. Harris、Stephen A. Harrison、Rosemary A. Melarange、Claudette Mookherjee、Julie Mosley、Gianni Dal Negro、Beatrice Oliosi、Kathrine J. Smith、Kevin M. Thewlis、Patrick M. Woollard、Shahnaz P. Yusaf

  DOI：10.1021/jm100679e

  日期：2011.1.13

  A novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and efficacy profiles, leading to identification of a clinical candidate. Unusually for an ion channel target, this optimization was integrated with regular generation of ligand-bound crystal structures and uncovered a novel chemotype with a unique and highly conserved mode of interaction via a trifluoromethyl group.