2-chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]acetamide | 247148-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]acetamide
• 英文别名: 3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one；2-Chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide；2-chloro-N-[3-(4-methoxyphenyl)-4-oxo-1H-indeno[1,2-c]pyrazol-5-yl]acetamide
• CAS: 247148-41-0
• 化学式: C₁₉H₁₄ClN₃O₃
• 分子量: 367.791
• InChiKey: MOMRUZSXOGRRPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  84.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]acetamide 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以62%的产率得到3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one
  参考文献：
  名称：

  Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 2. Probing the Indeno Ring Substituent Pattern

  摘要：

  We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmacophores led us to a series of semicarbazide-based. inhibitors that are highly potent against CDK2 and CDK4 while maintaining selectivity against other relevant serine/threonine kinases. These compounds were active against a transformed human colon cancer cell line (HCT116) while maintaining an acceptable margin of activity against a normal fibroblast cell line. The compounds were found to be highly protein bound in our cell-based assay with the exception of 11k, which maintained a reasonable level of activity in the presence of human plasma proteins.

  DOI：

  10.1021/jm020171+
• 作为产物：
  描述：

  3-(4-methoxyphenyl)-5-(ethylamido)indeno[1,2-c]pyrazol-4-one 在 盐酸 、 碳酸氢钠 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 4.0h， 生成 2-chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]acetamide
  参考文献：
  名称：

  Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 2. Probing the Indeno Ring Substituent Pattern

  摘要：

  We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmacophores led us to a series of semicarbazide-based. inhibitors that are highly potent against CDK2 and CDK4 while maintaining selectivity against other relevant serine/threonine kinases. These compounds were active against a transformed human colon cancer cell line (HCT116) while maintaining an acceptable margin of activity against a normal fibroblast cell line. The compounds were found to be highly protein bound in our cell-based assay with the exception of 11k, which maintained a reasonable level of activity in the presence of human plasma proteins.

  DOI：

  10.1021/jm020171+

文献信息

• Indeno [1,2-c]pyrazol-4-ones and their uses
  申请人：——

  公开号：US20010027195A1

  公开（公告）日：2001-10-04

  The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I): 1 that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-9 and their regulatory subunits know as cyclins A-H. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及合成一种新类别的indeno[1,2-c]pyrazol-4-ones化合物，其化学式为(I):1，这些化合物是一类名为细胞周期依赖性激酶的酶的强效抑制剂，与催化亚基cdk1-9及其调节亚基cyclins A-H有关。本发明还提供了一种新颖的治疗癌症或其他增生性疾病的方法，即通过给予这些化合物中的一种或其药用可接受的盐形式的治疗有效剂量。另外，可以通过给予本发明化合物之一与一种或多种其他已知的抗癌或抗增生剂的治疗有效组合来治疗癌症或其他增生性疾病。
• Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US20040048844A1

  公开（公告）日：2004-03-11

  The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I): 1 that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-7 and their regulatory subunits know as cyclins A-G. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及合成一类新的indeno[1,2-c]pyrazol-4-ones化合物，其化学式为(I):1，它们是强效的cyclin dependent kinases酶抑制剂，这些酶与催化亚单位cdk1-7及其调节亚单位cyclin A-G有关。本发明还提供了一种新的治疗癌症或其他增生性疾病的方法，即通过给患者服用这些化合物或其药学上可接受的盐形式的治疗有效剂量来治疗。另外，可以通过给患者同时服用本发明化合物和一种或多种其他已知的抗癌或抗增生剂来治疗癌症或其他增生性疾病。
• Semicarbazides and their uses
  申请人：——

  公开号：US20040242869A1

  公开（公告）日：2004-12-02

  The present invention relates to the synthesis of a new class of 5-substituted-3-(4-OR 1 -phenyl)-2H-indeno[1,2-c]pyrazol-4-ones of formula (I): 1 that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-7 and their regulatory subunits know as cyclins A-G. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及一种新型5-取代-3-(4-OR1-苯基)-2H-吲哚[1,2-c]吡唑-4-酮的合成，其化合物式为(I):1，该化合物是一种有效的细胞周期蛋白依赖性激酶抑制剂，可以抑制cdk1-7催化亚基及其调节亚基cyclin A-G。本发明还提供了一种治疗癌症或其他增殖性疾病的新方法，通过给患者施用这些化合物或其药学上可接受的盐形式的治疗有效剂量。另外，也可以通过给患者施用本发明化合物和一种或多种其他已知的抗癌或抗增殖剂的治疗有效组合来治疗癌症或其他增殖性疾病。
• 5-AMINOINDENO[1,2-C]PYRAZOL-4-ONES AS ANTI-CANCER AND ANTI-PROLIFERATIVE AGENTS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1071668B1

  公开（公告）日：2009-06-03
• ACYLSEMICARBAZIDES AS CYCLIN DEPENDENT KINASE INHIBITORS USEFUL AS ANTI-CANCER AND ANTI-PROLIFERATIVE AGENTS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1417177A2

  公开（公告）日：2004-05-12