Antipyrinsaeuremethylester | 66379-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Antipyrinsaeuremethylester
• 英文别名: methyl 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate；1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid methyl ester；1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-carbonsaeure-methylester；methyl 2,3-dimethyl-1-phenyl-3-pyrazolin-5-one-4-carboxylate；methyl 1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxylate
• CAS: 66379-70-2
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: ZZZJXOKUXIXGIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Antipyrinsaeuremethylester 在 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.33h， 生成 methyl 5-((tert-butoxycarbonyl)methyl)-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate
  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
• 作为产物：
  描述：

  甲醇 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.67h， 以77%的产率得到Antipyrinsaeuremethylester
  参考文献：
  名称：

  WO2006/116713

  摘要：

  公开号：

文献信息

• Preparation of organic acids and/or esters
  申请人：Shell Oil Company

  公开号：US04249015A1

  公开（公告）日：1981-02-03

  Carboxylic acids and/or esters are prepared by converting the ##STR1## moiety in a 1-substituted 2,2-trihaloethanol, or derivative wherein X represents halogen and R is hydrogen or an acyl group to an organic acid and/or ester grouping of the formula ##STR2## wherein R' is hydrogen or alkyl of 1 to 6 carbon atoms, in the process which comprises reacting the 1-substituted 2,2,2-trihaloethanol or acylated derivative with molecular oxygen in the presence of a catalyst comprising a complex of a transition metal having an atomic number from 21-30, 39-48 or 57-80 and at least one molecule of a ligand containing trivalent nitrogen, phosphorus, arsenic or antimony. This reaction is carried out in a reaction medium comprising an alcohol or aqueous alcohol having 1 to 6 carbon atoms optionally containing an alkali metal, said alcoholic solvent also serving as a reactant source when carboxylic acid esters are formed.

  羧酸和/或酯可以通过将1-取代的2,2-三卤乙醇或其衍生物中的## STR1##基团转化为式## STR2##中R'为氢或1至6个碳原子的烷基的有机酸和/或酯基团来制备，其中X代表卤素，R为氢或酰基。该过程包括在过渡金属的复合物催化下，将1-取代的2,2,2-三卤乙醇或酰化衍生物与分子氧反应。所述过渡金属的原子序数为21-30、39-48或57-80，所述配体至少包含三价氮、磷、砷或锑的分子。该反应在反应介质中进行，所述反应介质包括含有1至6个碳原子的醇或水醇，可选地含有碱金属。当形成羧酸酯时，所述醇溶剂也作为反应物源。
• Substituted amide derivatives and methods of use
  申请人：Kim Tae-Seong

  公开号：US20080312232A1

  公开（公告）日：2008-12-18

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF 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，如HGF介导的疾病具有有效性。本发明涵盖了新型化合物、类似物、前药及其药学上可接受的盐、药物组合物和用于预防和治疗涉及癌症等疾病和其他疾病或状况的方法。本发明还涉及制备这些化合物的过程，以及在这些过程中有用的中间体。
• METHOD OF TREATING CANCER WITH SUBSTITUTED AMIDE DERIVATIVES
  申请人：KIM Tae-Seong

  公开号：US20120070413A1

  公开（公告）日：2012-03-22

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF 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.

  选定的化合物对于预防和治疗疾病，如HGF介导的疾病非常有效。本发明包括新颖的化合物、类似物、前药和其药学上可接受的盐、制药组合物以及用于预防和治疗涉及癌症等疾病和其他疾病或情况的方法。本发明还涉及制备这些化合物的过程以及在这些过程中有用的中间体。
• SUBSTITUTED AMIDE DERIVATIVES AND METHODS OF USE
  申请人：Kim Tae-Seong

  公开号：US20110118252A1

  公开（公告）日：2011-05-19

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF 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.

  选定的化合物对于预防和治疗疾病，如HGF介导的疾病具有有效性。该发明包括新型化合物、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癌症等疾病和其他疾病或状况的方法。本发明还涉及制备这些化合物的过程以及在这些过程中有用的中间体。
• Method of treating cancer with substituted amide derivatives
  申请人：Kim Tae-Seong

  公开号：US08685983B2

  公开（公告）日：2014-04-01

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF 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，如HGF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、药物组合物以及用于预防和治疗包括癌症等疾病和其他疾病或病症的方法。该发明还涉及制备这些化合物的过程以及在这些过程中有用的中间体。