6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-2-(ethylamino)-8-(piperidin-4-ylmethyl)pyrido[2,3-d]pyrimidin-7(8H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-2-(ethylamino)-8-(piperidin-4-ylmethyl)pyrido[2,3-d]pyrimidin-7(8H)-one
• 英文别名: 6-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]-2-(ethylamino)-8-(piperidin-4-ylmethyl)pyrido[2,3-d]pyrimidin-7-one
• 化学式: C₂₆H₂₈ClN₇O
• 分子量: 490.008
• InChiKey: GMQHFTHVKUIAEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-2-(ethylamino)-8-(piperidin-4-ylmethyl)pyrido[2,3-d]pyrimidin-7(8H)-one 、 2-溴乙醇 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 以37%的产率得到6-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]-2-(ethylamino)-8-[[1-(2-hydroxyethyl)-4-piperidyl]methyl]pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  SERINE/THREONINE KINASE INHIBITORS

  摘要：

  具有公式I的化合物，其中R1、R2、R3、R4、R5、Ra、Rb、Rc、Rd、Re、n、r、s和t的定义如本文所述，并且这些化合物是PAK1的抑制剂。还公开了用于治疗癌症和过度增殖性疾病的组合物和方法。

  公开号：

  US20150031674A1
• 作为产物：
  描述：

  2-氯-6-甲基吡嗪 在 盐酸 、 四(三苯基膦)钯 、 正丁基锂 、 sodium carbonate 、 caesium carbonate 、 三氟乙酸 、 sodium hydroxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 2.67h， 生成 6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-2-(ethylamino)-8-(piperidin-4-ylmethyl)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  SERINE/THREONINE KINASE INHIBITORS

  摘要：

  具有公式I的化合物，其中R1、R2、R3、R4、R5、Ra、Rb、Rc、Rd、Re、n、r、s和t的定义如本文所述，并且这些化合物是PAK1的抑制剂。还公开了用于治疗癌症和过度增殖性疾病的组合物和方法。

  公开号：

  US20150031674A1

文献信息

• Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-p<i>K</i>_a Polar Moiety
  作者：Chudi O. Ndubaku、James J. Crawford、Joy Drobnick、Ignacio Aliagas、David Campbell、Ping Dong、Laura M. Dornan、Sergio Duron、Jennifer Epler、Lewis Gazzard、Christopher E. Heise、Klaus P. Hoeflich、Diana Jakubiak、Hank La、Wendy Lee、Baiwei Lin、Joseph P. Lyssikatos、Jasna Maksimoska、Ronen Marmorstein、Lesley J. Murray、Thomas O’Brien、Angela Oh、Sreemathy Ramaswamy、Weiru Wang、Xianrui Zhao、Yu Zhong、Elizabeth Blackwood、Joachim Rudolph

  DOI：10.1021/acsmedchemlett.5b00398

  日期：2015.12.10

  Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (1) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing pK(a) and logP simultaneously. When positioned properly within the scaffold, this group conferred several benefits including potency, pharmacokinetics, and selectivity. Mouse xenograft PK/PD studies were carried out using an advanced compound, G-5555 (12), derived from this approach. These studies concluded that dose-dependent pathway modulation was achievable and paves the way for further in vivo investigations of PAK1 function in cancer and other diseases.
• [EN] PYRIMIDINE-PYRIDINONE SERINE/THREONINE KINASE INHIBITORS<br/>[FR] INHIBITEURS PYRIMIDINE-PYRIDINONE DE SÉRINE/THRÉONINE KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015011252A1

  公开（公告）日：2015-01-29

  Compounds having the formula (I) wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAKl. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
• SERINE/THREONINE KINASE INHIBITORS
  申请人：GENENTECH, INC.

  公开号：US20150031674A1

  公开（公告）日：2015-01-29

  Compounds having the formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R a , R b , R c , R d , R e , n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

  具有公式I的化合物，其中R1、R2、R3、R4、R5、Ra、Rb、Rc、Rd、Re、n、r、s和t的定义如本文所述，并且这些化合物是PAK1的抑制剂。还公开了用于治疗癌症和过度增殖性疾病的组合物和方法。