[2-(4-methoxybenzoyl)-1,3-dioxo-indan-4-yl]carbamic acid phenyl ester | 478162-09-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-methoxybenzoyl)-1,3-dioxo-indan-4-yl]carbamic acid phenyl ester
• 英文别名: [2-(4-Methoxybenzoyl)-1,3-dioxo-indan-4-yl]-carbamic acid phenyl ester；phenyl N-[2-(4-methoxybenzoyl)-1,3-dioxoinden-4-yl]carbamate
• CAS: 478162-09-3
• 化学式: C₂₄H₁₇NO₆
• 分子量: 415.402
• InChiKey: YVRFKBZKAHPHDR-UHFFFAOYSA-N

物化性质

• 熔点：
  256-258 °C
• 沸点：
  627.7±55.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  4-乙酰氨基-2-(4-甲氧基苯甲酰基)-1,3-二酮	4-(Acetylamino)-2-(4-methoxybenzoyl)indane-1,3-dione	247149-95-7	C19H15NO5	337.332
  ——	4-amino-2-(4-methoxy-benzoyl)indan-1,3-dione	247149-97-9	C17H13NO4	295.295

反应信息

• 作为反应物：
  描述：

  [2-(4-methoxybenzoyl)-1,3-dioxo-indan-4-yl]carbamic acid phenyl ester 在 4-二甲氨基吡啶 、 氨 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 [2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-urea
  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：

  4-乙酰氨基-2-(4-甲氧基苯甲酰基)-1,3-二酮 在 sodium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 生成 [2-(4-methoxybenzoyl)-1,3-dioxo-indan-4-yl]carbamic acid phenyl ester
  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

• Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents
  申请人：——

  公开号：US20030073686A1

  公开（公告）日：2003-04-17

  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吲哚并［1，2-c］吡唑-4-酮类化合物（I），它们是强效的细胞周期蛋白依赖性激酶抑制剂，与催化亚基cdk1-7及其调节亚基cyclin A-G有关。本发明还提供了一种新的治疗癌症或其他增殖性疾病的方法，即通过给患者投与这些化合物之一或其药学上可接受的盐形式的治疗有效量。或者，可以通过给患者投与本发明化合物之一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。
• 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。
• Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening
  作者：Taikou Usui、Hyun Seung Ban、Junpei Kawada、Takatsugu Hirokawa、Hiroyuki Nakamura

  DOI：10.1016/j.bmcl.2007.10.084

  日期：2008.1

  A series of indenopyrazoles 8 and 9 were designed and synthesized as EGFR tyrosine kinase inhibitors by in silico high-throughput screening. Compounds 8b and 8d showed significant inhibition of A431 cell growth (GI(50) = 0.062 and 0.057 mu M, respectively). Compounds 8b and 9a showed inhibitory activity toward both EGFR and VEGFR-2 (KDR) tyrosine kinases, whereas 8d inhibited VEGFR-2 tyrosine kinase, exclusively. (C) 2007 Elsevier Ltd. All rights reserved.
• SEMICARBAZIDES AND THEIR USES
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1404670A1

  公开（公告）日：2004-04-07
• EP1404670A4
  申请人：——

  公开号：EP1404670A4

  公开（公告）日：2004-11-24