trans-4-(4-pyrazolo[1,5-b]pyridazin-3-yl-pyrimidin-2-ylamino)-cyclohexanol | 1032451-95-8

• 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: trans-4-(4-pyrazolo[1,5-b]pyridazin-3-yl-pyrimidin-2-ylamino)-cyclohexanol
• 英文别名: 4-((4-(pyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-yl)amino)-cyclohexan-1-ol
• CAS: 1032451-95-8
• 化学式: C₁₆H₁₈N₆O
• 分子量: 310.359
• InChiKey: YDMIWBCFXWPNFP-HAQNSBGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  88.23
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2-氯-4-((三甲基甲硅烷基)乙炔基)嘧啶 在 碳酸氢钠 、 potassium hydroxide 、 hydroxylamine-O-sulfonic acid 作用下， 以 甲醇 、 水 、 正丁醇 为溶剂， 反应 4.0h， 生成 trans-4-(4-pyrazolo[1,5-b]pyridazin-3-yl-pyrimidin-2-ylamino)-cyclohexanol
  参考文献：
  名称：

  Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis

  摘要：

  From a high-throughput screen of 42 444 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against human kinases GSK-3 beta, CDK-2, and CDK-4 were leveraged to try to improve the selectivity of the series, resulting in 23a which showed selectivity for T. b. brucei over these three human enzymes. In parallel, properties known to influence the absorption, distribution, metabolism, and excretion (ADME) profile of the series were optimized resulting in 20g being progressed into an efficacy study in mice. Though 20g showed toxicity in mice, it also demonstrated CNS penetration in a PK study and significant reduction of parasitemia in four out of the six mice.

  DOI：

  10.1021/acs.jmedchem.9b01741

文献信息

• JNK modulators
  申请人：Dunn James Patrick

  公开号：US20080146565A1

  公开（公告）日：2008-06-19

  Compounds of formula I modulate JNK: wherein the variables are as defined herein.

  式I的化合物调节JNK： 其中变量的定义如本文所述。
• US8399462B2
  申请人：——

  公开号：US8399462B2

  公开（公告）日：2013-03-19
• [EN] SUBSTITUTED PYRIMIDINES AND THEIR USE AS JNK MODULATORS<br/>[FR] PYRIMIDINES SUBSTITUÉES ET LEUR UTILISATION EN TANT QUE MODULATEURS DE JNK
  申请人：HOFFMANN LA ROCHE

  公开号：WO2008068171A1

  公开（公告）日：2008-06-12

  [EN] The invention is concerned with novel JNK modulator of formula (I) wherein X¹, X², X³, X⁴, X⁵, X⁶, R, R¹, Z and n are as defined in the description and the claims, as well as physiologically acceptable salts thereof.
  [FR] L'invention porte sur un nouveau modulateur de JNK représenté par la formule (I) dans laquelle X¹, X², X³, X⁴, X⁵, X⁶, R, R¹, Z et n sont tels que définis dans la description et les revendications, ainsi que sur des sels physiologiquement acceptables de celui-ci.