N-cyclopropyl-4-(6-morpholinopyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine | 551920-33-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-cyclopropyl-4-(6-morpholinopyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine
• 英文别名: N-cyclopropyl-4-[6-(4-morpholinyl)pyrazolo[1,5-b]pyridazin-3-yl]-2-pyrimidinamine；N-cyclopropyl-4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine
• CAS: 551920-33-3
• 化学式: C₁₇H₁₉N₇O
• 分子量: 337.384
• InChiKey: RLKIXFRFDGFKOP-UHFFFAOYSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (9CI)-2-氯-4-乙炔嘧啶 在 碳酸氢钠 、 hydroxylamine-O-sulfonic acid 作用下， 以 水 、 正丁醇 为溶剂， 反应 19.0h， 生成 N-cyclopropyl-4-(6-morpholinopyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine
  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

• [EN] PYRADAZINE COMPOUNDS AS GSK-3 INHIBITORS<br/>[FR] COMPOSES DE PYRADAZINE UTILES COMME INHIBITEURS DE GSK-3
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004035588A1

  公开（公告）日：2004-04-29

  The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds according to formula (I) and methods of their use.

  本发明通常涉及激酶抑制剂，如GSK3，更具体地涉及根据式(I)的融合吡啶并嘧啶化合物及其使用方法。
• Pyradazine compounds as gsk-3 inhibitors
  申请人：Dickerson Howard Scott

  公开号：US20060069097A1

  公开（公告）日：2006-03-30

  The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds and methods of their use.

  本发明通常涉及抑制激酶的抑制剂，例如GSK3，更具体地涉及融合嘧啶二氮杂环化合物及其使用方法。
• Pyrazolopyridazine derivatves
  申请人：Badiang G Jennifer

  公开号：US20050090507A1

  公开（公告）日：2005-04-28

  Fused pyradazine derivatives, which are useful as CDK inhibitors are described herein. The described invention also includes methods of making such fused pyradazines derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了可用作 CDK 抑制剂的融合哒嗪衍生物。所描述的发明还包括制造这种融合哒嗪衍生物的方法，以及将其用于治疗过度增殖性疾病的方法。
• Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors
  作者：Kirk L. Stevens、Michael J. Reno、Jennifer B. Alberti、Daniel J. Price、Laurie S. Kane-Carson、Victoria B. Knick、Lisa M. Shewchuk、Anne M. Hassell、James M. Veal、Stephen T. Davis、Robert J. Griffin、Michael R. Peel

  DOI：10.1016/j.bmcl.2008.09.069

  日期：2008.11

  A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3beta.
• PYRAZOLOPYRIDAZINE DERIVATIVES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1463730B1

  公开（公告）日：2006-04-19