6-chloro-4-N-[4-(difluoromethoxy)phenyl]-2-methylpyrimidine-4,5-diamine | 1198115-49-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-chloro-4-N-[4-(difluoromethoxy)phenyl]-2-methylpyrimidine-4,5-diamine
• CAS: 1198115-49-9
• 化学式: C₁₂H₁₁ClF₂N₄O
• 分子量: 300.695
• InChiKey: HNEAZQSGLILPSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-chloro-4-N-[4-(difluoromethoxy)phenyl]-2-methylpyrimidine-4,5-diamine 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 21.5h， 生成 dicyclopropylmethyl-[9-(4-difluoromethoxyphenyl)-2,8-dimethyl-9H-purin-6-yl]-amine
  参考文献：
  名称：

  Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles

  摘要：

  Optimisation of the potency of a bicyclic CRF antagonist whilst retaining metabolic stability is described. A core change and incorporation of metabolically stable lipophilic groups resulted in a further potency gain without increasing metabolic liability. Pharmacological investigation of binding kinetics led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with slow dissociation kinetics and an encouraging pharmacokinetic profile. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.040
• 作为产物：
  描述：

  2-甲基-4,6-二氯-5-氨基嘧啶 、 4-二氟甲氧基苯胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 6-chloro-4-N-[4-(difluoromethoxy)phenyl]-2-methylpyrimidine-4,5-diamine
  参考文献：
  名称：

  Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles

  摘要：

  Optimisation of the potency of a bicyclic CRF antagonist whilst retaining metabolic stability is described. A core change and incorporation of metabolically stable lipophilic groups resulted in a further potency gain without increasing metabolic liability. Pharmacological investigation of binding kinetics led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with slow dissociation kinetics and an encouraging pharmacokinetic profile. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.040

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：PFIZER LTD

  公开号：WO2009144632A1

  公开（公告）日：2009-12-03

  The present invention relates to a class of substituted purine compounds of formula (I), uses thereof, processes for the preparation thereof and compositions containing said compounds. These compounds have utility in a variety of therapeutic areas including sexual dysfunction.(I).

  本发明涉及一类取代嘌呤化合物的公式（I），其用途、制备过程以及包含所述化合物的组合物。这些化合物在包括性功能障碍在内的多种治疗领域具有用途。
• Discovery of potent, metabolically stable purine CRF-1 antagonists with differentiated binding kinetic profiles
  作者：Duncan C. Miller、Wolfgang Klute、Alan D. Brown

  DOI：10.1016/j.bmcl.2011.08.040

  日期：2011.10

  Optimisation of the potency of a bicyclic CRF antagonist whilst retaining metabolic stability is described. A core change and incorporation of metabolically stable lipophilic groups resulted in a further potency gain without increasing metabolic liability. Pharmacological investigation of binding kinetics led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with slow dissociation kinetics and an encouraging pharmacokinetic profile. (C) 2011 Elsevier Ltd. All rights reserved.