6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one | 1452230-82-8

• 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: 6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one
• 英文别名: 6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-methylsulfanylpyrido[4,3-d]pyrimidin-5-one
• CAS: 1452230-82-8
• 化学式: C₁₅H₁₁Cl₂N₃O₂S
• 分子量: 368.243
• InChiKey: NHTKZKOJFGHOTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  91.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one 在 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 17.5h， 生成 6-(2,6-dichlorophenyl)-2-(2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-isoquinolin]-7'-ylamino)-8-(hydroxymethyl)pyrido[4,3-d]pyrimidin-5(6H)-one TFA salt
  参考文献：
  名称：

  PYRIDOPYRIMIDINONE INHIBITORS OF KINASES

  摘要：

  本发明涉及式(I)化合物或药理可接受的盐，其中R1、R2、R3、R4和B在描述中定义。本发明还涉及包含所述化合物的组合物，这些化合物可用于抑制诸如wee-1的激酶，以及治疗诸如癌症疾病的方法。

  公开号：

  US20130225589A1
• 作为产物：
  描述：

  5-嘧啶羧酸,4-乙基-2-(甲硫基)- 在 sodium tetrahydroborate 、 氯化亚砜 、 cerium(III) chloride heptahydrate 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 为溶剂， 反应 40.5h， 生成 6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one
  参考文献：
  名称：

  Investigation of biaryl heterocycles as inhibitors of Wee1 kinase

  摘要：

  In continuation of our previous research towards the discovery of potent, selective and drug-like Wee1 inhibitors, 2 novel series of biaryl heterocycles were designed, synthesized and evaluated. The new biaryl cores were designed to enable structure - activity exploration of substituents at C-8 or N-8 which were used for tuning compound properties and to improve compound profiles. The lead molecule 33 demonstrated a desirable pharmacokinetic profile and potentiated the anti-proliferative activity of irinotecan in vivo when dosed orally in the human breast MX-1 xenograft model.

  DOI：

  10.1016/j.bmcl.2019.04.017

文献信息

• US9718821B2
  申请人：——

  公开号：US9718821B2

  公开（公告）日：2017-08-01
• [EN] PYRIDOPYRIMIDINONE INHIBITORS OF KINASES<br/>[FR] DÉRIVÉS DE PYRIDOPYRIMIDINONE INHIBITEURS DE KINASES
  申请人：ABBVIE INC

  公开号：WO2013126656A1

  公开（公告）日：2013-08-29

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R1, R2, R3, R4, and B 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.
• PYRIDOPYRIMIDINONE INHIBITORS OF KINASES
  申请人：AbbVie Inc.

  公开号：US20130225589A1

  公开（公告）日：2013-08-29

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R 1 , R 2 , R 3 , R 4 , and B 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)化合物或药理可接受的盐，其中R1、R2、R3、R4和B在描述中定义。本发明还涉及包含所述化合物的组合物，这些化合物可用于抑制诸如wee-1的激酶，以及治疗诸如癌症疾病的方法。
• Investigation of biaryl heterocycles as inhibitors of Wee1 kinase
  作者：Anthony Mastracchio、Chunqiu Lai、Maricel Torrent、Kenneth Bromberg、Fritz G. Buchanan、Debra Ferguson、Velitchka Bontcheva、Eric F. Johnson、Loren Lasko、David Maag、Alexander R. Shoemaker、Thomas D. Penning

  DOI：10.1016/j.bmcl.2019.04.017

  日期：2019.6

  In continuation of our previous research towards the discovery of potent, selective and drug-like Wee1 inhibitors, 2 novel series of biaryl heterocycles were designed, synthesized and evaluated. The new biaryl cores were designed to enable structure - activity exploration of substituents at C-8 or N-8 which were used for tuning compound properties and to improve compound profiles. The lead molecule 33 demonstrated a desirable pharmacokinetic profile and potentiated the anti-proliferative activity of irinotecan in vivo when dosed orally in the human breast MX-1 xenograft model.