Syn-dfci-00114

• 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: Syn-dfci-00114
• 英文别名: 2-[4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-methoxyanilino]-9-methyl-5,7-dihydropyrimido[5,4-d][1,3]benzodiazepin-6-one
• 化学式: C₂₅H₂₉N₇O₂
• 分子量: 459.551
• InChiKey: YEUMCRKFUPOKOM-IYBDPMFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  103.44
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2,6-dimethylpiperazine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 Syn-dfci-00114
  参考文献：
  名称：

  Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

  摘要：

  The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.

  DOI：

  10.1016/j.bmcl.2020.127456

文献信息

• Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing
  作者：Zhengnian Li、Chelsea E. Powell、Brian J. Groendyke、Thomas W. Gero、Frederic Feru、John Feutrill、Bailing Chen、Bin Li、Hilary Szabo、Nathanael S. Gray、David A. Scott

  DOI：10.1016/j.bmcl.2020.127456

  日期：2020.10

  The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.