8-cyclopentyl-2-(3,4,5-trimethoxyphenylamino)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile | 1357470-34-8

• 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: 8-cyclopentyl-2-(3,4,5-trimethoxyphenylamino)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile
• 英文别名: 8-cyclopentyl-7-oxo-2-((3,4,5-trimethoxyphenyl)amino)-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile；8-Cyclopentyl-7-oxo-2-(3,4,5-trimethoxyanilino)pyrido[2,3-d]pyrimidine-6-carbonitrile
• CAS: 1357470-34-8
• 化学式: C₂₂H₂₃N₅O₄
• 分子量: 421.456
• InChiKey: YNDJCUZGIVBCGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氨基-2-甲巯基嘧啶-5-甲醛 在 sodium hydride 、 溶剂黄146 、 间氯过氧苯甲酸 、 苄胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.08h， 生成 8-cyclopentyl-2-(3,4,5-trimethoxyphenylamino)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile
  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

• 2-SUBSTITUTED-8-ALKYL-7-OXO-7,8-DIHYDROPYRIDO[2,3-D] PYRIMIDINE-6-CARBONITRILES AND USES THEREOF
  申请人：Reddy E. Premkumar

  公开号：US20130131058A1

  公开（公告）日：2013-05-23

  Compounds according to Formula (I), as well salts thereof: wherein R 1 and R 2 are as defined herein, are useful as antiproliferative agents and kinase inhibitors. Synthetic methods for preparing the compounds of Formula (I) are also provided.

  根据化学式（I）及其盐，其中R1和R2的定义如下，这些化合物可用作抗增殖剂和激酶抑制剂。本发明还提供了制备化学式（I）化合物的合成方法。
• 2-SUBSTITUTED-8-ALKYL-7-OXO-7,8-DIHYDROPYRIDO[2,3-D]PYRIMIDINE-6-CARBONITRILES AND USES THEREOF
  申请人：Temple University - Of The Commonwealth System of Higher Education

  公开号：EP2600719B1

  公开（公告）日：2014-10-08
• EP3125920B1
  申请人：——

  公开号：EP3125920B1

  公开（公告）日：2020-12-23
• COMBINATION OF ANALOGS OR DERIVATIVES OF DIANHYDROGALACTITOL WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT CANCER
  申请人：Delmar Pharmaceuticals, Inc.

  公开号：EP3294284A1

  公开（公告）日：2018-03-21
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF IN COMBINATION WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND BRAIN METASTASES
  申请人：Del Mar Pharmaceuticals

  公开号：US20160008316A1

  公开（公告）日：2016-01-14

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.