(R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid | 1038867-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-((R)-2-hydroxy-propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid；1-[(2R)-2-hydroxypropyl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxylic acid
• CAS: 1038867-85-4
• 化学式: C₁₄H₁₆N₂O₄
• 分子量: 276.292
• InChiKey: ZMNYLNHGWLZHCE-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid 、 4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluoroaniline 在 三乙醇胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以85.2%的产率得到(R)-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  AMINO ESTER DERIVATIVES, SAILTS THEREOF AND METHODS OF USE

  摘要：

  本发明提供了氨基酯化合物、盐及其药物配方，用于调节蛋白酪氨酸激酶活性，以及调节细胞间和/或细胞内信号传导。该发明还提供了包含这些化合物的药用合适组合物，以及使用这些组合物治疗哺乳动物，特别是人类的增生性疾病的方法。

  公开号：

  US20100239576A1
• 作为产物：
  描述：

  benzyl 5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate 在 magnesium(II) perchlorate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.51h， 生成 (R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of Novel Class II c-Met Inhibitors: 2. SAR and Kinase Selectivity Profiles of the Pyrazolone Series

  摘要：

  As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with detailed SAR information, we demonstrate that the low kinase selectivity associated with class II c-Met inhibitors can be improved significantly. This work resulted in the discovery of potent c-Met inhibitors with improved selectivity profiles over VEGFR-2 and IGF-1R that could serve as useful tools to probe the relationship between kinase selectivity and in vivo efficacy in tumor xenograft models. Compound 59e (AMG 458) was ultimately advanced into preclinical safety studies.

  DOI：

  10.1021/jm201331s

文献信息

• AMINO ESTER DERIVATIVES, SAILTS THEREOF AND METHODS OF USE
  申请人：Xi Ning

  公开号：US20100239576A1

  公开（公告）日：2010-09-23

  The present invention provides amino ester compounds, salts, and pharmaceutical formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明提供了氨基酯化合物、盐及其药物配方，用于调节蛋白酪氨酸激酶活性，以及调节细胞间和/或细胞内信号传导。该发明还提供了包含这些化合物的药用合适组合物，以及使用这些组合物治疗哺乳动物，特别是人类的增生性疾病的方法。
• Bis-aryl amide derivatives and methods of use
  申请人：Booker Shon

  公开号：US20080234268A1

  公开（公告）日：2008-09-25

  Selected compounds are effective for prophylaxis and treatment of diseases, such as c-Met mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗疾病，例如c-Met介导的疾病具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐、药物组合物以及预防和治疗涉及癌症等疾病和其他疾病或病情的方法。该发明还涉及用于制备此类化合物的过程以及在此类过程中有用的中间体。
• Amino ester derivatives, sailts thereof and methods of use
  申请人：——

  公开号：US08232294B2

  公开（公告）日：2012-07-31

  The present invention provides amino ester compounds, salts, and pharmaceutical formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明提供了氨基酯化合物、盐和药物配制物，用于调节蛋白酪氨酸激酶活性，以及调节细胞内和/或细胞间信号传导。本发明还提供了包含这种化合物的药学上可接受的组合物，并使用这些组合物治疗哺乳动物，特别是人类的增殖过度性疾病的方法。
• BIS-ARYL AMIDE DERIVATIVES USEFUL FOR THE TREATMENT OF CANCER
  申请人：Amgen Inc.

  公开号：EP2118069A2

  公开（公告）日：2009-11-18
• US7759344B2
  申请人：——

  公开号：US7759344B2

  公开（公告）日：2010-07-20