N-(1,3-二苯基-1H-吡唑并-5-基)-4-硝基苯甲酰胺 | 890764-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: N-(1,3-二苯基-1H-吡唑并-5-基)-4-硝基苯甲酰胺
• 中文别名: N-(1,3-二苯基-1H-吡唑-5-基)-4-硝基苯甲酰胺
• 英文名称: 4-nitro-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide
• 英文别名: N-(1,3-diphenyl-1H-pyrazolo-5-yl)-4-nitrobenzamide；N-(1,3-diphenyl-1H-pyrazol-5-yl)-4-nitrobenzamide；N-(2,5-diphenylpyrazol-3-yl)-4-nitrobenzamide
• CAS: 890764-36-0
• 化学式: C₂₂H₁₆N₄O₃
• 分子量: 384.394
• InChiKey: KIALCSMRIHRFPL-UHFFFAOYSA-N

物化性质

• 熔点：
  221-223℃
• 沸点：
  545.0±45.0 °C(Predicted)
• 密度：
  1.30
• 溶解度：
  在 DMSO 中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为产物：
  描述：

  5-氨基-1,3-二苯基哌唑 、 4-硝基苯甲酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以26%的产率得到N-(1,3-二苯基-1H-吡唑并-5-基)-4-硝基苯甲酰胺
  参考文献：
  名称：

  Substituent Effects of N-(1,3-Diphenyl-1H-pyrazol-5-yl)benzamides on Positive Allosteric Modulation of the Metabotropic Glutamate-5 Receptor in Rat Cortical Astrocytes

  摘要：

  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.

  DOI：

  10.1021/jm051252j

文献信息

• BENZAMIDE mGluR5 POSITIVE ALLOSTERIC MODULATORS AND METHODS OF MAKING AND USING SAME
  申请人：Conn P. Jeffrey

  公开号：US20090042855A1

  公开（公告）日：2009-02-12

  In one aspect, the invention relates to compounds, including phenylethynylbenzamide derivatives, cycloalkylethynylbenzamide derivatives, styrylbenzamide derivatives, 4-(3-phenyl-1,2,4-oxadiazol-5-yl)benzamide derivatives, 4-(pyridinylethynyl)benzamide derivatives, and N 1 -phenylterephthalamide derivatives, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及化合物，包括苯乙炔基苯甲酰胺衍生物、环烷基乙炔基苯甲酰胺衍生物、苯乙烯基苯甲酰胺衍生物、4-(3-苯基-1,2,4-噁唑-5-基)苯甲酰胺衍生物、4-(吡啶乙炔基)苯甲酰胺衍生物和N1-苯基对苯二甲酰胺衍生物，它们是代谢型谷氨酸受体亚型5 (mGluR5) 的正向变构调节剂；制备这些化合物的合成方法；含有这些化合物的药物组合物；以及使用这些化合物和组合物治疗与谷氨酸功能失调相关的神经和精神障碍的方法。本摘要旨在作为搜索特定领域的扫描工具，不限制本发明。
• 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.
• METHODS OF TREATING ELEVATIONS IN MTOR SIGNALING
  申请人：Brown University

  公开号：EP2496224A1

  公开（公告）日：2012-09-12
• US8853392B2
  申请人：——

  公开号：US8853392B2

  公开（公告）日：2014-10-07
• [EN] METHODS OF TREATING ELEVATIONS IN MTOR SIGNALING<br/>[FR] MÉTHODES DE TRAITEMENT DES HAUSSES DE LA SIGNALISATION DE MTOR
  申请人：MASSACHUSETTS INST TECHNOLOGY

  公开号：WO2011056849A1

  公开（公告）日：2011-05-12

  Subjects having elevated signaling of a mammalian target of rapamycin (mTOR) are treated with compositions that include at least one compound that activates a Group 1 mGluR. In an embodiment, the subject has tuberous sclerosis complex (TSC). In an embodiment, the compound is a Group 1 mGluR agonist. In another embodiment, the compound is a Group 1 mGluR positive allosteric modulator.