4-phthalimido-1,3-diphenyl-1H-pyrazole | 216854-29-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-phthalimido-1,3-diphenyl-1H-pyrazole
• 英文别名: 2-(1,3-Diphenyl-1H-pyrazol-4-yl)isoindoline-1,3-dione；2-(1,3-diphenylpyrazol-4-yl)isoindole-1,3-dione
• CAS: 216854-29-4
• 化学式: C₂₃H₁₅N₃O₂
• 分子量: 365.391
• InChiKey: MUOPFEQNOZEERI-UHFFFAOYSA-N

物化性质

• 熔点：
  232-234 °C
• 沸点：
  584.1±52.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-phthalimido-1,3-diphenyl-1H-pyrazole 在 一水合肼 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 4-nitro-N-(1,3-diphenyl-1H-pyrazol-4-yl)benzamide
  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
• 作为产物：
  描述：

  2-(1-苯基乙酮-2-基)异吲哚啉-1,3-二酮 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 4-phthalimido-1,3-diphenyl-1H-pyrazole
  参考文献：
  名称：

  A convenient one-pot synthesis of 4-amino-3-arylpyrazoles from α-phthaloylaminoacetophenones

  摘要：

  Condensation of alpha-phthaloylaminoacetophenones 1a-c with N,N-dimethylformamide dimethyl acetal afforded the novel enamines 3a-c. Cyclization of 3 with hydrazine, alkylhydrazine or phenylhydrazine salts (4a-d) gave 4-phthaloylamino-3-arylpyrazoles 7-9 in high yields. Deprotection of 7-9 was accomplished with hydrazine to provide 4-amino-3-arylpyrazoles 5 in good yields. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01776-6

文献信息

• [EN] HETEROCYCLE SUBSTITUTED AMINO-PYRIDINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS AMINO-PYRIDINE SUBSTITUÉS HÉTÉROCYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：EPIZYME INC

  公开号：WO2016044666A1

  公开（公告）日：2016-03-24

  The present disclosure relates to heterocycle substituted amino-pyridine compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.

  本公开涉及杂环取代的氨基吡啶化合物。本公开还涉及含有这些化合物的药物组合物，以及通过将这些化合物和药物组合物用于需要的受试者来治疗癌症的方法。本公开还涉及将这些化合物用于研究或其他非治疗目的的用途。
• Design and synthesis of novel 3,4-disubstituted pyrazoles for nanomedicine applications against malignant gliomas
  作者：Mauro Comes Franchini、Bianca Flavia Bonini、Carlo Maurizio Camaggi、Denis Gentili、Annalisa Pession、Monica Rani、Elena Strocchi

  DOI：10.1016/j.ejmech.2010.01.014

  日期：2010.5

  A series of novel 3,4-disubstituted pyrazoles were synthesized. The cytotoxicity against U87MG glioma cell line have been investigated in vitro and three of these compounds showed promising inhibitory activity on cell growth with an IC(50) lower than 90 mu M. AutoDock molecular docking into type I TGF-beta receptor (TGF-beta-RI; PDB: 1py5) has been done for lead optimization of the mentioned compounds as potential TGF-beta-RI1 inhibitors. In particular, 3-aryl-4-amido pyrazole containing long omega-amino-aliphatic chain emerged as a good candidate for further optimization. Entrapment into targetable PEG-based micelles improved growth inhibition IC(50) values up to 100 nM and this could lead to a novel drug delivery strategy for treating glioblastoma. (C) 2010 Elsevier Masson SAS. All rights reserved.
• HETEROCYCLE SUBSTITUTED AMINO-PYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Epizyme, Inc.

  公开号：US20170291890A1

  公开（公告）日：2017-10-12

  The present disclosure relates to heterocycle substituted amino-pyridine compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
• 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.
• A convenient one-pot synthesis of 4-amino-3-arylpyrazoles from α-phthaloylaminoacetophenones
  作者：Chen Chen、Keith Wilcoxen、James R. McCarthy

  DOI：10.1016/s0040-4039(98)01776-6

  日期：1998.11

  Condensation of alpha-phthaloylaminoacetophenones 1a-c with N,N-dimethylformamide dimethyl acetal afforded the novel enamines 3a-c. Cyclization of 3 with hydrazine, alkylhydrazine or phenylhydrazine salts (4a-d) gave 4-phthaloylamino-3-arylpyrazoles 7-9 in high yields. Deprotection of 7-9 was accomplished with hydrazine to provide 4-amino-3-arylpyrazoles 5 in good yields. (C) 1998 Elsevier Science Ltd. All rights reserved.