N'-acetyl-2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanehydrazide | 885221-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N'-acetyl-2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanehydrazide
• CAS: 885221-10-3
• 化学式: C₂₂H₂₈N₆O₃
• 分子量: 424.503
• InChiKey: PTTFAAHXUXHVBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N'-acetyl-2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanehydrazide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 [3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]-[1-(5-methyl-[1,3,4]oxadiazol-2-yl)propyl]amine
  参考文献：
  名称：

  Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1) receptor antagonist with improved pharmacokinetic properties

  摘要：

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF1 antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a functional CRF1 antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH production assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.095
• 作为产物：
  描述：

  2-[[3-(4-Methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanehydrazide 、 乙酸酐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N'-acetyl-2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanehydrazide
  参考文献：
  名称：

  Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1) receptor antagonist with improved pharmacokinetic properties

  摘要：

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF1 antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a functional CRF1 antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH production assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.095

文献信息

• Pyrazolo[1,5-Alpha]Pyrimidinyl Derivatives Useful as Corticotropin-Releasing Factor (Crf) Receptor Antagonists
  申请人：Lanier Marion

  公开号：US20080194589A1

  公开（公告）日：2008-08-14

  CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R 1 , R 2a , R 2b , Y, Het, n, o, R 6 , Ar and R 7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，可能在治疗多种疾病方面有用，包括治疗哺乳动物CRF过度分泌引起的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药物学上可接受的盐，酯，溶剂合物，立体异构体和前药，其中R1，R2a，R2b，Y，Het，n，o，R6，Ar和R7如本文所定义。还揭示了含有CRF受体拮抗剂与药学可接受载体组合的组合物，以及使用它们的方法。
• US7879862B2
  申请人：——

  公开号：US7879862B2

  公开（公告）日：2011-02-01