6-benzenesulfonyl-8-cyclopentyl-2-methylsulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one | 1312471-76-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 6-benzenesulfonyl-8-cyclopentyl-2-methylsulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 8-cyclopentyl-2-(methylsulfinyl)-6-(phenylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one；6-(Benzenesulfonyl)-8-cyclopentyl-2-methylsulfinylpyrido[2,3-d]pyrimidin-7-one
• CAS: 1312471-76-3
• 化学式: C₁₉H₁₉N₃O₄S₂
• 分子量: 417.51
• InChiKey: PRGAKDXBMLRXQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-甲基哌嗪)苯胺 、 6-benzenesulfonyl-8-cyclopentyl-2-methylsulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one 以 甲苯 为溶剂， 以51%的产率得到6-benzenesulfonyl-8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)phenylamino]-8H-pyrido[2,3-d]pyrimidine-7-one
  参考文献：
  名称：

  Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

  摘要：

  The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure-activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2[-4-(4-methyl-piperazin-l-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARKS kinases. Here, we report the synthesis, structure-activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound.

  DOI：

  10.1021/jm401073p
• 作为产物：
  描述：

  6-benzenesulfonyl-8-cyclopentyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以90%的产率得到6-benzenesulfonyl-8-cyclopentyl-2-methylsulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

  摘要：

  The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure-activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2[-4-(4-methyl-piperazin-l-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARKS kinases. Here, we report the synthesis, structure-activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound.

  DOI：

  10.1021/jm401073p

文献信息

• SUBSTITUTED PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES AND THERAPEUTIC USES THEREOF
  申请人：Reddy E. Premkumar

  公开号：US20120269831A1

  公开（公告）日：2012-10-25

  Compounds useful as antiproliferative agents according to Formula (I), wherein n, A, R 1 , R 2 , and Ar 1 are as defined herein, and salts thereof; antibody conjugates, pharmaceutical compositions, methods of treatment, and synthetic methods are provided.

  提供了按照公式（I）定义的可用作抗增殖剂的化合物，其中n，A，R1，R2和Ar1如本文中所定义的，以及其盐; 还提供了抗体偶联物，制药组合物，治疗方法和合成方法。
• US8889696B2
  申请人：——

  公开号：US8889696B2

  公开（公告）日：2014-11-18