3-(2-chloro-6-fluorophenyl)-7-(methylthio)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione | 1395028-17-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-(2-chloro-6-fluorophenyl)-7-(methylthio)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-(2-chloro-6-fluorophenyl)-2-methylsulfanyl-8H-pyrimido[4,5-d]pyrimidine-5,7-dione
• CAS: 1395028-17-7
• 化学式: C₁₃H₈ClFN₄O₂S
• 分子量: 338.75
• InChiKey: RJXBXTCJLXRPPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 4.42h， 生成 4-(2-chloro-6-fluorophenyl)-8-methanesulfinyl-4H-3,4,7,9,9b-pentaazacyclopenta[a]naphthalene 5-one
  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
• 作为产物：
  描述：

  2-甲基巯基-4-氨基嘧啶-5-甲酸乙酯 、 1-chloro-3-fluoro-2-isocyanatobenzene 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.17h， 生成 3-(2-chloro-6-fluorophenyl)-7-(methylthio)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione
  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。
• Tricyclic inhibitors of kinases
  申请人：Tong Yunsong

  公开号：US08710065B2

  公开（公告）日：2014-04-29

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein X, Y, Z, R3 and R4 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.

  本发明涉及公式（I）的化合物或药物可接受的盐，其中X，Y，Z，R3和R4在描述中定义。本发明还涉及含有所述化合物的组合物，该组合物对于抑制kinase（例如wee-1）和治疗癌症等疾病的方法是有用的。
• US8710065B2
  申请人：——

  公开号：US8710065B2

  公开（公告）日：2014-04-29
• [EN] TRICYCLIC INHIBITORS OF KINASES<br/>[FR] INHIBITEURS TRICYCLIQUES DE KINASES
  申请人：ABBOTT LAB

  公开号：WO2012161812A1

  公开（公告）日：2012-11-29

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, ( l ) wherein X, Y, Z, R3 and R4 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.