tert-butyl N-[5-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]-N-propan-2-ylcarbamate | 905300-52-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: tert-butyl N-[5-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]-N-propan-2-ylcarbamate
• CAS: 905300-52-9
• 化学式: C₁₆H₂₁ClN₄O₂S₂
• 分子量: 400.953
• InChiKey: FAGPLYBJMXOHJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[5-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]-N-propan-2-ylcarbamate 、 2-氯苯基硼酸 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 tert-butyl (5-(6-(2-chlorophenyl)-2-(methylthio)pyrimidin-4-yl)thiazol-2-yl)(isopropyl)carbamate
  参考文献：
  名称：

  Utilization of a nitrogen–sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors

  摘要：

  The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.

  DOI：

  10.1016/j.bmcl.2010.07.102
• 作为产物：
  描述：

  4,6-二氯-二甲硫基嘧啶 、 tert-butyl isopropyl(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazol-2-yl)carbamate 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 tert-butyl N-[5-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]-N-propan-2-ylcarbamate
  参考文献：
  名称：

  Utilization of a nitrogen–sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors

  摘要：

  The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.

  DOI：

  10.1016/j.bmcl.2010.07.102

文献信息

• PHENYL-SUBSTITUTED PYRIMIDINE COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Wrobleski Stephen T.

  公开号：US20100029649A1

  公开（公告）日：2010-02-04

  Compounds having the formula (I), and pharmaceutically acceptable salts, and solvates thereof, are useful as kinase inhibitors, wherein: two of X 1 , X 2 , and X 3 are N, and the remaining one of X 1 , X 2 , and X 3 is —CR 1 ; R 1 is hydrogen or —CN; and N, G, Z, R 2 , R 3 , R 4 , R 5 , and R 6 are described in the specification. Also disclosed are pharmaceutical compositions containing compounds of formula (I), and methods of treating conditions associated with the activity of p38 kinase and/or conditions associated with the activity of LIM kinase.

  具有公式（I）的化合物及其药学上可接受的盐和溶剂化物，可用作激酶抑制剂，其中：X1、X2中的两个为N，X1、X2、X3中剩余的一个为—CR1；R1为氢或—CN；N、G、Z、R2、R3、R4、R5和R6在说明书中有所描述。还披露了含有公式（I）化合物的制药组合物，以及治疗与p38激酶活性和/或LIM激酶活性相关的疾病的方法。
• US7923556B2
  申请人：——

  公开号：US7923556B2

  公开（公告）日：2011-04-12
• Utilization of a nitrogen–sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors
  作者：Shuqun Lin、Stephen T. Wrobleski、John Hynes、Sidney Pitt、Rosemary Zhang、Yi Fan、Arthur M. Doweyko、Kevin F. Kish、John S. Sack、Mary F. Malley、Susan E. Kiefer、John A. Newitt、Murray McKinnon、James Trzaskos、Joel C. Barrish、John H. Dodd、Gary L. Schieven、Katerina Leftheris

  DOI：10.1016/j.bmcl.2010.07.102

  日期：2010.10

  The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.