3-[3-(Trifluoromethyl)phenyl]-4-[2-[[(S)-alpha-methylbenzyl]amino]-4-pyrimidinyl]-6-(4-piperidinyl)pyridazine | 271247-18-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-[3-(Trifluoromethyl)phenyl]-4-[2-[[(S)-alpha-methylbenzyl]amino]-4-pyrimidinyl]-6-(4-piperidinyl)pyridazine
• 英文别名: N-[(1S)-1-phenylethyl]-4-[6-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]pyridazin-4-yl]pyrimidin-2-amine
• CAS: 271247-18-8
• 化学式: C₂₈H₂₇F₃N₆
• 分子量: 504.558
• InChiKey: ZXONHXQWZPBOLO-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-2-羟基丙酸 、 3-[3-(Trifluoromethyl)phenyl]-4-[2-[[(S)-alpha-methylbenzyl]amino]-4-pyrimidinyl]-6-(4-piperidinyl)pyridazine 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以93%的产率得到
  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
• 作为产物：
  描述：

  4-甲基-2-甲硫基嘧啶 在 sodium tungstate 、 palladium on activated charcoal 氢气 、 双氧水 、 sodium hydride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 肼 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 甲苯 、 叔丁醇 为溶剂， 反应 73.0h， 生成 3-[3-(Trifluoromethyl)phenyl]-4-[2-[[(S)-alpha-methylbenzyl]amino]-4-pyrimidinyl]-6-(4-piperidinyl)pyridazine
  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

• 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.