N-[(2-chloro-4-fluorophenyl)methyl]-2-[3,5-dimethyl-1-(phenylmethyl)-1H-pyrazol-4-yl]acetamide | 1082825-07-7

• 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: N-[(2-chloro-4-fluorophenyl)methyl]-2-[3,5-dimethyl-1-(phenylmethyl)-1H-pyrazol-4-yl]acetamide
• 英文别名: 2-(1-benzyl-3,5-dimethylpyrazol-4-yl)-N-[(2-chloro-4-fluorophenyl)methyl]acetamide
• CAS: 1082825-07-7
• 化学式: C₂₁H₂₁ClFN₃O
• 分子量: 385.869
• InChiKey: XOUOKRMHXOPQDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,5-dimethyl-1-benzyl-pyrazol-4-acetic acid-ethyl ester 、 2-氯-4-氟苄胺 在 水 、 lithium hydroxide 、 N-乙基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-[(2-chloro-4-fluorophenyl)methyl]-2-[3,5-dimethyl-1-(phenylmethyl)-1H-pyrazol-4-yl]acetamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

  摘要：

  High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.096

文献信息

• Pyrazole Derivatives as P2X7 Modulators
  申请人：Beswick Paul John

  公开号：US20110046137A1

  公开（公告）日：2011-02-24

  The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: The pyrazole derivatives of formula (I) or salts thereof modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor (P2X7 receptor antagonists). The invention also relates to the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment or prevention of disorders/diseases mediated by the P2X7 receptor, for example pain, inflammation or a neurodegenerative disease.

  本发明涉及公式(I)的化合物或其药学上可接受的盐：公式(I)的吡唑衍生物或其盐调节P2X7受体功能，能够拮抗ATP在P2X7受体上的作用（P2X7受体拮抗剂）。本发明还涉及使用这些化合物或盐，或其制剂在治疗或预防由P2X7受体介导的疾病/紊乱，例如疼痛，炎症或神经退行性疾病。
• PYRAZOLE DERIVATIVES AS P2X7 MODULATORS
  申请人：Glaxo Group Limited

  公开号：EP2155685A1

  公开（公告）日：2010-02-24
• [EN] PYRAZOLE DERIVATIVES AS P2X7 MODULATORS<br/>[FR] DÉRIVÉS DU PYRAZOLE UTILISÉS COMME MODULATEURS DE P2X7
  申请人：GLAXO GROUP LTD

  公开号：WO2008138876A1

  公开（公告）日：2008-11-20

  [EN] The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: The pyrazole derivatives of formula (I) or salts thereof modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor (P2X7 receptor antagonists). The invention also relates to the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment or prevention of disorders / diseases mediated by the P2X7 receptor, for example pain, inflammation or a neurodegenerative disease.
  [FR] L'invention concerne un composé de la formule (I) ou un sel pharmaceutiquement acceptable de ce dernier. Les dérivés pyrazole de la formule (I) ou leurs sels modulent la fonction du récepteur P2X7 et sont capables d'exercer une action antagoniste sur les effets de l'ATP sur le récepteur P2X7 (antagonistes du récepteur P2X7). L'invention se rapporte également à l'utilisation desdits composés ou de leurs sels, ou de compositions pharmaceutiques les renfermant, dans le traitement ou la prévention de troubles et maladies médiés par le récepteur P2X7, par exemple la douleur, l'inflammation ou une maladie neurodégénérative.
• Synthesis and structure–activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor
  作者：Laura J. Chambers、Alexander J. Stevens、Andrew P. Moses、Anton D. Michel、Daryl S. Walter、David J. Davies、David G. Livermore、Elena Fonfria、Emmanuel H. Demont、Mythily Vimal、Pam J. Theobald、Paul J. Beswick、Robert J. Gleave、Shilina A. Roman、Stefan Senger

  DOI：10.1016/j.bmcl.2010.03.096

  日期：2010.5

  High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties. (C) 2010 Elsevier Ltd. All rights reserved.