6-(2-chloro-6-fluorophenyl)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}imidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one trifluoroacetic acid | 1395028-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(2-chloro-6-fluorophenyl)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}imidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one trifluoroacetic acid
• 英文别名: 6-(2-chloro-6-fluorophenyl)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}imidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one trifluoroacetate
• CAS: 1395028-16-6
• 化学式: C₂HF₃O₂*C₂₅H₂₂ClFN₈O
• 分子量: 618.978
• InChiKey: XRMMGQMHQJZUPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  43.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  120.89
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  3-(2-chloro-6-fluorophenyl)-7-(methylthio)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione 在 盐酸 、 水 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.59h， 生成 6-(2-chloro-6-fluorophenyl)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}imidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one trifluoroacetic acid
  参考文献：
  名称：

  Pyrimidine-Based Tricyclic Molecules as Potent and Orally Efficacious Inhibitors of Wee1 Kinase

  摘要：

  Aided by molecular modeling, compounds with a pyrimidine-based tricyclic scaffold were designed and confirmed to inhibit Wee1 kinase. Structure-activity studies identified key pharmacophores at the aminoaryl and halo-benzene regions responsible for binding affinity with sub-nM Ki values. The potent inhibitors demonstrated sub-mu M activities in both functional and mechanism-based cellular assays and also possessed desirable pharmacokinetic profiles. The lead molecule, 31, showed oral efficacy in potentiating the antiproliferative activity of irinotecan, a cytotoxic agent, in a NCI-H1299 mouse xenograft model.

  DOI：

  10.1021/ml5002745

文献信息

• TRICYCLIC INHIBITORS OF KINASES
  申请人：Tong Yunsong

  公开号：US20120220572A1

  公开（公告）日：2012-08-30

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein X, Y, Z, R 3 and R 4 are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.

  本发明涉及式(I)的化合物或药用可接受的盐，其中X、Y、Z、R3和R4在描述中有定义。本发明还涉及含有上述化合物的组合物，用于抑制wee-1等激酶，并治疗癌症等疾病的方法。