4-(3-trifluoromethylphenyl)-4-oxo-3-(2-methylthiopyrimidin-4-yl)-1-oxo-1-(N-carbobenzoxypiperidin-4-yl)butane | 271247-33-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-trifluoromethylphenyl)-4-oxo-3-(2-methylthiopyrimidin-4-yl)-1-oxo-1-(N-carbobenzoxypiperidin-4-yl)butane
• 英文别名: Benzyl 4-[3-(2-methylsulfanylpyrimidin-4-yl)-4-oxo-4-[3-(trifluoromethyl)phenyl]butanoyl]piperidine-1-carboxylate；benzyl 4-[3-(2-methylsulfanylpyrimidin-4-yl)-4-oxo-4-[3-(trifluoromethyl)phenyl]butanoyl]piperidine-1-carboxylate
• CAS: 271247-33-7
• 化学式: C₂₉H₂₈F₃N₃O₄S
• 分子量: 571.62
• InChiKey: PXPMLEOHCXMIFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-(3-trifluoromethylphenyl)-4-oxo-3-(2-methylthiopyrimidin-4-yl)-1-oxo-1-(N-carbobenzoxypiperidin-4-yl)butane 在 sodium tungstate 、 双氧水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醇 、 乙酸乙酯 、 甲苯 为溶剂， 反应 76.0h， 生成 3-(3-trifluoromethylphenyl)-4-(2-methylsulfonylpyrimidin-4-yl)-6-(N-carbobenzoxypiperidin-4-yl)pyridazine
  参考文献：
  名称：

  Pyridazine based inhibitors of p38 MAPK

  摘要：

  Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38 MAPK. The most active isomers were those possessing an aryl group alpha and a heteroaryl group beta relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC50 1-20 nM) in vitro activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00834-4
• 作为产物：
  描述：

  4-甲基-2-甲硫基嘧啶 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 18.5h， 生成 4-(3-trifluoromethylphenyl)-4-oxo-3-(2-methylthiopyrimidin-4-yl)-1-oxo-1-(N-carbobenzoxypiperidin-4-yl)butane
  参考文献：
  名称：

  Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase

  摘要：

  Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.

  DOI：

  10.1016/j.bmcl.2005.02.010

文献信息

• Compounds having cytokine inhibitory activity
  申请人：Merck & Co., Inc.

  公开号：US06350744B1

  公开（公告）日：2002-02-26

  There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which exhibit utility for the treatment of cytokine mediated diseases such as arthritis.

  公开了化合物的结构式（I）及其药学上可接受的盐，其对治疗细胞因子介导的疾病如关节炎具有实用性。
• Pyridazine based inhibitors of p38 MAPK
  作者：Charles J McIntyre、Gerald S Ponticello、Nigel J Liverton、Stephen J O’Keefe、Edward A O’Neill、Margaret Pang、Cheryl D Schwartz、David A Claremon

  DOI：10.1016/s0960-894x(01)00834-4

  日期：2002.2

  Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38 MAPK. The most active isomers were those possessing an aryl group alpha and a heteroaryl group beta relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC50 1-20 nM) in vitro activity. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase
  作者：Nuria Tamayo、Lillian Liao、Martin Goldberg、David Powers、Yan-Yan Tudor、Violeta Yu、Lu Min Wong、Bradley Henkle、Scot Middleton、Rashid Syed、Timothy Harvey、Graham Jang、Randall Hungate、Celia Dominguez

  DOI：10.1016/j.bmcl.2005.02.010

  日期：2005.5

  Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.