N-(1,3-diphenyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(1,3-diphenyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)benzamide
• 英文别名: N-(2,5-diphenylpyrazol-3-yl)-4-(trifluoromethyl)benzamide
• 化学式: C₂₃H₁₆F₃N₃O
• 分子量: 407.395
• InChiKey: KFZBTHNKNHZQIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氨基-1,3-二苯基哌唑 、 4-三氟甲基苯甲酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到N-(1,3-diphenyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)benzamide
  参考文献：
  名称：

  从一系列可增强体内受体功能的N-（1,3-二苯基-1H-吡唑-5-基）苯甲酰胺中发现了代谢型谷氨酸受体亚型5的正变构调节剂。

  摘要：

  该报告描述了代谢型谷氨酸受体亚型5（mGluR5）的第一个中央活性的变构调节剂的发现。适当取代的N-（1,3-二苯基-1H-吡唑-5-基）苯甲酰胺（例如8种）已被鉴定为mGluR5的新型强力正构构变构剂，可增强对谷氨酸的反应。迭代的类似物文库合成方法为增效剂提供了对mGluR5（相对于mGluRs 1-4、7、8）具有出色的效能和选择性。化合物8q在已知抗精神病药活跃的动物行为模型中证明了其概念的体内证据，支持基于精神分裂症NMDA功能减退模型的新型抗精神病药的开发。

  DOI：

  10.1021/jm049400d

文献信息

• Pyrazole modulators of metabotropic glutamate receptors
  申请人：Lindsley W. Craig

  公开号：US20060281803A1

  公开（公告）日：2006-12-14

  The present invention is directed to compounds which are allosteric modulators of metabotropic glutamate receptors, including the mGluR5 receptor, and which are useful in the treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及化合物，它们是代谢性谷氨酸受体的别构调节剂，包括mGluR5受体，并且在治疗与谷氨酸功能障碍和代谢性谷氨酸受体相关的神经和精神障碍以及相关疾病方面有用。该发明还涉及包含这些化合物的制药组合物以及在预防或治疗代谢性谷氨酸受体相关疾病方面使用这些化合物和组合物。
• Substituent Effects of <i>N</i>-(1,3-Diphenyl-1<i>H</i>-pyrazol-5-yl)benzamides on Positive Allosteric Modulation of the Metabotropic Glutamate-5 Receptor in Rat Cortical Astrocytes
  作者：Tomas de Paulis、Kamondanai Hemstapat、Yelin Chen、Yongqin Zhang、Samir Saleh、David Alagille、Ronald M. Baldwin、Gilles D. Tamagnan、P. Jeffrey Conn

  DOI：10.1021/jm051252j

  日期：2006.6.1

  CDPPB [3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide] was recently described as the first centrally active, positive allosteric modulator of rat and human metabotropic glutamate receptor (mGluR) mGluR(5) subtype. We explored the structural requirements for potentiation of glutamate-induced calcium release in naturally expressed mGluR5 in cultured rat astrocytes and increasing affinity for the allosteric antagonist binding site by evaluating 50 analogues of CDPPB. In the fluorometric calcium assay, CDPPB exhibited an EC50 value of 77 +/- 15 nM in potentiating mGluR(5)-mediated responses in cortical astrocytes and a K-i value of 3760 ( 430 nM in displacing [H-3] methoxyPEPy binding in membranes of cultured HEK-293 cells expressing rat mGluR5. The structure-activity relationships showed that electronegative aromatic substituents in the para-position of the benzamide moiety of CDPPB increase potency. Both binding and functional activities were further increased with a halogen atom in the ortho-position of the 1-phenyl ring. These effects of substitution do not match those of either aromatic ring of MPEP [2-methyl-6-(phenylethynyl)-pyridine] for the antagonist allosteric binding site. Combination of the optimal substituents and aromatic positions resulted in 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl) benzamide (VU-1545) showing K-i) 156 (29 nM and EC50) 9.6 (1.9 nM in the binding and functional assays, respectively.
• An efficient one-pot synthesis of N-(1,3-diphenyl-1H-pyrazol- 5-yl)amides
  作者：Wei-Nien Su、Tsung-Ping Lin、Kaung-Min Cheng、Kuan-Chin Sung、Shao-Kai Lin、Fung Fuh Wong

  DOI：10.1002/jhet.343

  日期：——

  Abstractmagnified image A “one‐pot” method for the synthesis of N‐(1,3‐diphenyl‐1H‐pyrazol‐5‐yl)amides was developed by cyclization of benzoylacetonitrile (1) and phenylhydrazine in neat condition followed by acylation. The corresponding N‐(1,3‐diphenyl‐1H‐pyrazol‐5‐yl)amides were provided in good to excellent yields (70–90%). The significant advantages of the new synthetic method are excellent yields and simple work‐up procedure without isolation and purification of intermediary 5‐amino‐1,3‐diphenyl pyrazol (2). J. Heterocyclic Chem., (2010).
• [EN] PYRAZOLE MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] MODULATEURS PYRAZOLE DE RECEPTEURS DE GLUTAMATE METABOTROPIQUES
  申请人：MERCK & CO INC

  公开号：WO2005030128A2

  公开（公告）日：2005-04-07

  The present invention is directed to compounds which are allosteric modulators of metabotropic glutamate receptors, including the mGluR5 receptor, and which are useful in the treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.