1-(3-chloro-4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one

• 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: 1-(3-chloro-4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one
• 英文别名: 2-(3-Chloro-4-fluoro-phenyl)-5-methyl-2,4-dihydro-pyrazol-3-one；2-(3-chloro-4-fluorophenyl)-5-methyl-4H-pyrazol-3-one
• 化学式: C₁₀H₈ClFN₂O
• 分子量: 226.638
• InChiKey: PXGIGJZFZKVCHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one 在 溶剂黄146 作用下， 反应 2.0h， 生成 (4Z)-1-(3-chloro-4-fluorophenyl)-4-(((3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-3-methyl-1H-pyrazol-5(4H)-one
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents

  摘要：

  Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50 = 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14 mu M, 0.18 mu M, 0.09 mu M, 0.03 mu M, and 1.06 mu M against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.07.011
• 作为产物：
  描述：

  3-氯-4-氟苯胺 在 盐酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 3.5h， 生成 1-(3-chloro-4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents

  摘要：

  Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50 = 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14 mu M, 0.18 mu M, 0.09 mu M, 0.03 mu M, and 1.06 mu M against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.07.011

文献信息

• Pyrazolone Compounds As Metabotropic Glutamate Receptor Agonists For The Treatment Of Neurological And Psychiatric Disorders
  申请人：Balestra Michael

  公开号：US20090069340A1

  公开（公告）日：2009-03-12

  Compounds of Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, and n are as defined for Formula (I) in the description, processes for the preparation of the compounds and new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and the use of the compounds in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.

  公式（I）的化合物，其中R1，R2，R3，R4，R5，R6，X和n的定义如描述中的公式（I），制备该化合物的过程以及用于制备的新中间体，含有该化合物的制药组合物以及在治疗或预防与谷氨酸功能障碍有关的神经系统和精神障碍中使用该化合物。
• PYRAZOLONE COMPOUNDS AS METABOTROPIC GLUTAMATE RECEPTOR AGONISTS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  申请人：AstraZeneca AB

  公开号：EP1833800A1

  公开（公告）日：2007-09-19
• [EN] PYRAZOLONE COMPOUNDS AS METABOTROPIC GLUTAMATE RECEPTOR AGONISTS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS<br/>[FR] COMPOSES DE PYRAZOLONE UTILISES COMME AGONISTES DU RECEPTEUR DE GLUTAMATE METABOTROPIQUE POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES ET PSYCHIATRIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2006071730A1

  公开（公告）日：2006-07-06

  [EN] Compounds of Formula (I), wherein R¹, R², R³, R⁴, R⁵, R⁶, X, and n are as defined for Formula (I) in the description, processes for the preparation of the compounds and new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and the use of the compounds in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.
  [FR] La présente invention concerne des composés ayant la formule (I), dans laquelle R¹, R², R³, R⁴, R⁵, R⁶, X et n sont tels que définis pour la formule (I) dans la description, des procédés de préparation desdits composés et de nouveaux produits intermédiaires utilisés pour ladite préparation, des compositions pharmaceutiques contenant lesdits composés et l'utilisation desdits composés pour le traitement ou la prévention de troubles neurologiques et psychiatriques associés au dysfonctionnement glutamatergique.
• Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents
  作者：Shunguang Zhou、Jianguo Ren、Mingmei Liu、Lixiang Ren、Yajing Liu、Ping Gong

  DOI：10.1016/j.bioorg.2014.07.011

  日期：2014.12

  Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50 = 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14 mu M, 0.18 mu M, 0.09 mu M, 0.03 mu M, and 1.06 mu M against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively. (C) 2014 Elsevier Inc. All rights reserved.