6-chloro-9-(4-(difluoromethoxy)-2-methoxyphenyl)-2,8-dimethyl-9H-purine | 1198109-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-chloro-9-(4-(difluoromethoxy)-2-methoxyphenyl)-2,8-dimethyl-9H-purine
• 英文别名: 6-Chloro-9-[4-(difluoromethoxy)-2-methoxyphenyl]-2,8-dimethylpurine；6-chloro-9-[4-(difluoromethoxy)-2-methoxyphenyl]-2,8-dimethylpurine
• CAS: 1198109-92-0
• 化学式: C₁₅H₁₃ClF₂N₄O₂
• 分子量: 354.744
• InChiKey: VOUVNXKXNAXNHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  62.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(4-(difluoromethoxy)-2-methoxyphenyl)-2,8-dimethyl-9H-purine 、 双环丙基甲胺 以 乙腈 为溶剂， 反应 0.5h， 生成 N-(dicyclopropylmethyl)-9-(4-(difluoromethoxy)-2-methoxyphenyl)-2,8-dimethyl-9H-purine-6-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 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 45.0h， 生成 6-chloro-9-(4-(difluoromethoxy)-2-methoxyphenyl)-2,8-dimethyl-9H-purine
  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.