1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylic acid | 960299-43-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylic acid
• CAS: 960299-43-8
• 化学式: C₁₂H₁₂FNO₃
• 分子量: 237.231
• InChiKey: JCNHPLIJZGORQU-UHFFFAOYSA-N

物化性质

• 沸点：
  515.3±45.0 °C(Predicted)
• 密度：
  1.358±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylic acid 在 溴 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以91%的产率得到3-bromo-1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

  摘要：

  一系列包含新型3-羧基哌啶-2-酮骨架的化合物基于引导结构BMS-777607进行设计、合成并评估其对c-Met激酶的抑制作用及对MKN45癌细胞系的细胞毒性。结果表明，五种化合物对c-Met展现出显著的抑制效果，IC50值为8.6−81 nM，而四种化合物对MKN45细胞增殖表现出强劲的抑制活性，IC50在0.57−16 μM之间。

  DOI：

  10.3390/molecules19022655
• 作为产物：
  描述：

  isobutyl 1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.0h， 以87%的产率得到1-(4-fluorophenyl)-2-oxopiperidine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

  摘要：

  一系列包含新型3-羧基哌啶-2-酮骨架的化合物基于引导结构BMS-777607进行设计、合成并评估其对c-Met激酶的抑制作用及对MKN45癌细胞系的细胞毒性。结果表明，五种化合物对c-Met展现出显著的抑制效果，IC50值为8.6−81 nM，而四种化合物对MKN45细胞增殖表现出强劲的抑制活性，IC50在0.57−16 μM之间。

  DOI：

  10.3390/molecules19022655

文献信息

• [EN] PYRAZOLO[3,4-b]PYRIDINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES<br/>[FR] COMPOSÉS PYRAZOLO[3,4-B]PYRIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASES TAM ET MET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2020047184A1

  公开（公告）日：2020-03-05

  Provided herein are compounds of the Formula (I): and stereoisomers, tautomers and pharmaceutically acceptable salts thereof, wherein R1, R2, R9, X1 and G are as defined herein, which are inhibitors of one or more TAM kinases and/or c-Met kinase, and are useful in the treatment and prevention of diseases which can be treated with a TAM kinase inhibitor and/or a c-Met kinase inhibitor.

  本文提供了Formula (I)的化合物及其立体异构体、互变异构体和药学上可接受的盐，其中R1、R2、R9、X1和G如本文所定义，它们是一种或多种TAM激酶和/或c-Met激酶的抑制剂，并且在治疗和预防可以用TAM激酶抑制剂和/或c-Met激酶抑制剂治疗的疾病中非常有用。
• QUINOLINE COMPOUNDS AND METHODS OF USE
  申请人：Gaudino John

  公开号：US20110053931A1

  公开（公告）日：2011-03-03

  Compounds of Formula (I), and stereoisomers, geometric isomers, tautomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof, are useful for inhibiting receptor tyrosine kinases and for treating hyperproliferative disorders mediated thereby. Methods of using compounds of Formula (I), and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  式（I）的化合物及其立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、盐和药学上可接受的前药，用于抑制受体酪氨酸激酶并治疗由此介导的过度增殖性疾病。本文揭示了使用式（I）的化合物及其立体异构体、几何异构体、互变异构体、溶剂化物和药学上可接受的盐，在哺乳动物细胞中进行体外、体内和原位诊断、预防或治疗此类疾病或相关病理条件的方法。
• Discovery of novel type II c-Met inhibitors based on BMS-777607
  作者：Wei Zhang、Jing Ai、Dakuo Shi、Xia Peng、Yinchun Ji、Jian Liu、Meiyu Geng、Yingxia Li

  DOI：10.1016/j.ejmech.2014.04.056

  日期：2014.6

  Twenty-two new analogs based on the structure of BMS-777607 were designed, synthesized, and evaluated to determine their biological activities. Compounds bearing a cyclic sulfonamide or α-chloropiperidone scaffold exhibited good activity, which may provide a new basis for further structural optimization. Quinoline-containing analogs exhibited better results than did their counterparts with an aminopyrimidine, aminopyridine, or pyrrolopyridine unit. Two analogs, 22d and 22e, stood out as the most potent c-Met inhibitors with IC50s of 0.9 and 1.7 nM, respectively. These two compounds were more potent than BMS-777607 in enzymatic inhibition and cell proliferation studies.
• PYRAZOLO[3,4-b]PYRIDINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES
  申请人：Array BioPharma Inc.

  公开号：US20200079770A1

  公开（公告）日：2020-03-12

  Provided herein are compounds of the Formula I: and stereoisomers, tautomers and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 9 , X 1 and G are as defined herein, which are inhibitors of one or more TAM kinases and/or c-Met kinase, and are useful in the treatment and prevention of diseases which can be treated with a TAM kinase inhibitor and/or a c-Met kinase inhibitor.
• [EN] QUINOLINE COMPOUNDS AND METHODS OF USE<br/>[FR] QUINOLINES ET MÉTHODES D'UTILISATION
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2007146824A2

  公开（公告）日：2007-12-21

  [EN] Compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof, are useful for inhibiting receptor tyrosine kinases and for treating hyperproliferative disorders mediated thereby. Methods of using compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed. [ Formula I]
  [FR] La présente invention a pour objet des composés de Formule I, ainsi que les stéréoisomères, isomères géométriques, tautomères, solvates, métabolites, sels et promédicaments de qualité pharmaceutique desdits composés, qui peuvent être employés dans l'inhibition des récepteurs tyrosine kinases et dans le traitement de troubles hyperproliférants les faisant intervenir. La présente invention a également pour objet des méthodes d'utilisation des composés de Formule I, ainsi que des stéréoisomères, isomères géométriques, tautomères, solvates et sels de qualité pharmaceutique desdits composés, dans des diagnostics in vitro, in situ et in vivo, ainsi que pour le traitement prophylactique ou thérapeutique de tels troubles dans les cellules de mammifères, ou d'états pathologiques associés. [Formule I]