5-bromo-2-chloro-N-(4-methylcyclohexyl)pyrimidin-4-amine | 477593-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-bromo-2-chloro-N-(4-methylcyclohexyl)pyrimidin-4-amine
• CAS: 477593-30-9
• 化学式: C₁₁H₁₅BrClN₃
• 分子量: 304.617
• InChiKey: CTMAYZVFYFZDDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-2-chloro-N-(4-methylcyclohexyl)pyrimidin-4-amine 在 bis-triphenylphosphine-palladium(II) chloride 、 ammonium hydroxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 异丙醇 为溶剂， 反应 1.5h， 生成 9-(4-methylcyclohexyl)-N-(5-(1-piperazinyl)-2-pyridinyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3

  摘要：

  We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays, led to the discovery of 28 (AMG 925), a potent and orally bioavailable dual inhibitor of CDK4 and FLT3, including many FLT3 mutants reported to date. Compound 28 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb+) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, compound 28 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation.

  DOI：

  10.1021/jm500118j
• 作为产物：
  描述：

  5-溴-2,4-二氯嘧啶 、 1-氨基-4-甲基环己烷 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-bromo-2-chloro-N-(4-methylcyclohexyl)pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3

  摘要：

  We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays, led to the discovery of 28 (AMG 925), a potent and orally bioavailable dual inhibitor of CDK4 and FLT3, including many FLT3 mutants reported to date. Compound 28 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb+) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, compound 28 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation.

  DOI：

  10.1021/jm500118j

文献信息

• CDK-Inhibitory pyrimidines, their production and use as pharmaceutical agents
  申请人：Brumby Thomas

  公开号：US20080039447A1

  公开（公告）日：2008-02-14

  This invention relates to pyrimidine derivatives of general formula I in which R 1 , R 2 , X, A and B have the meanings that are contained in the description, as inhibitors of the cyclin-dependent kinases, their production as well as their use as medications for treating various diseases.

  本发明涉及通式I的嘧啶衍生物，其中R1、R2、X、A和B的含义如描述中所含，作为细胞周期蛋白依赖性激酶的抑制剂，它们的生产以及它们作为治疗各种疾病的药物的使用。
• US7291624B2
  申请人：——

  公开号：US7291624B2

  公开（公告）日：2007-11-06
• US7235561B2
  申请人：——

  公开号：US7235561B2

  公开（公告）日：2007-06-26
• US7598260B2
  申请人：——

  公开号：US7598260B2

  公开（公告）日：2009-10-06