N-(2-aminoethyl)-5-[2-({4-[4-(methylsulfonyl)piperazin-1-yl]pyridin-2-yl}amino)-1,3-thiazol-5-yl]nicotinamide

• 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: N-(2-aminoethyl)-5-[2-({4-[4-(methylsulfonyl)piperazin-1-yl]pyridin-2-yl}amino)-1,3-thiazol-5-yl]nicotinamide
• 英文别名: N-(2-aminoethyl)-5-[2-[[4-(4-methylsulfonylpiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]pyridine-3-carboxamide
• 化学式: C₂₁H₂₆N₈O₃S₂
• 分子量: 502.621
• InChiKey: ACQFRIFMXKIEAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  183
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-溴烟酰胺 在 盐酸 、 四(三苯基膦)钯 、 亚硝酸特丁酯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 potassium acetate 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 、 copper dichloride 作用下， 以 N,N-二甲基乙酰胺 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-aminoethyl)-5-[2-({4-[4-(methylsulfonyl)piperazin-1-yl]pyridin-2-yl}amino)-1,3-thiazol-5-yl]nicotinamide
  参考文献：
  名称：

  Pyridyl aminothiazoles as potent Chk1 inhibitors: Optimization of cellular activity

  摘要：

  Translation of significant biochemical activity of pyridyl aminothiazole class of Chk1 inhibitors into functional CEA potency required analysis and adjustment of both physical properties and kinase selectivity profile of the series. The steps toward optimization of cellular potency included elimination of CDK7 activity, reduction of molecular weight and polar surface area and increase in lipophilicity of the molecules in the series. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.120

文献信息

• Inhibitors of checkpoint kinases
  申请人：Arrington Kenneth L.

  公开号：US20090233896A1

  公开（公告）日：2009-09-17

  The instant invention provides for compounds which comprise substituted pyridyl aminothiazoles that inhibit CHK1 activity. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.

  本发明提供了一种包括取代的吡啶基氨基噻唑的化合物，该化合物抑制CHK1活性。本发明还提供了包括这种抑制剂化合物的组合物和通过将该化合物用于需要治疗癌症的患者中来抑制CHK1活性的方法。
• INHIBITORS OF CHECKPOINT KINASES
  申请人：Merck & Co., Inc.

  公开号：EP1893607A2

  公开（公告）日：2008-03-05
• [EN] INHIBITORS OF CHECKPOINT KINASES<br/>[FR] INHIBITEURS DE KINASES CHECKPOINT
  申请人：MERCK & CO INC

  公开号：WO2006135604A2

  公开（公告）日：2006-12-21

  [EN] The instant invention provides for compounds which comprise substituted pyridyl aminothiazoles that inhibit CHK1 activity. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.
  [FR] L'invention concerne des composés comprenant des pyridyl aminothiazoles substitués qui inhibent l'activité de CHK1. Elle concerne aussi des compositions comprenant de tels composés inhibiteurs, et des procédés visant à inhiber l'activité de CHK1 par l'administration du composé à un patient nécessitant un traitement anticancéreux.
• Pyridyl aminothiazoles as potent Chk1 inhibitors: Optimization of cellular activity
  作者：Vadim Y. Dudkin、Cheng Wang、Kenneth L. Arrington、Mark E. Fraley、George D. Hartman、Steven M. Stirdivant、Robert A. Drakas、Keith Rickert、Eileen S. Walsh、Kelly Hamilton、Carolyn A. Buser、James Hardwick、Weikang Tao、Stephen C. Beck、Xianzhi Mao、Robert B. Lobell、Laura Sepp-Lorenzino

  DOI：10.1016/j.bmcl.2012.01.120

  日期：2012.4

  Translation of significant biochemical activity of pyridyl aminothiazole class of Chk1 inhibitors into functional CEA potency required analysis and adjustment of both physical properties and kinase selectivity profile of the series. The steps toward optimization of cellular potency included elimination of CDK7 activity, reduction of molecular weight and polar surface area and increase in lipophilicity of the molecules in the series. (C) 2012 Elsevier Ltd. All rights reserved.