2-amino-6-cyclohexylpyrimidin-4-ol | 501681-00-1

• 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: 2-amino-6-cyclohexylpyrimidin-4-ol
• 英文别名: 2-Amino-6-cyclohexylpyrimidin-4-OL；2-amino-4-cyclohexyl-1H-pyrimidin-6-one
• CAS: 501681-00-1
• 化学式: C₁₀H₁₅N₃O
• mdl: MFCD11047075
• 分子量: 193.249
• InChiKey: LMFRKQOMSHKODC-UHFFFAOYSA-N

物化性质

• 沸点：
  343.7±25.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-6-cyclohexylpyrimidin-4-ol 在 盐酸 、 甲酸 、 四乙基氯化铵 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 18.33h， 生成 4-cyclohexyl-6-(R)-(3-methylaminopyrrolidin-1-yl)pyrimidin-2-ylamine
  参考文献：
  名称：

  Discovery and SAR of 6-Alkyl-2,4-diaminopyrimidines as Histamine H₄ Receptor Antagonists

  摘要：

  This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.

  DOI：

  10.1021/jm401727m
• 作为产物：
  描述：

  Guanidine hydrochloride 、 3-环己基-3-氧代丙酸乙酯 生成 2-amino-6-cyclohexylpyrimidin-4-ol
  参考文献：
  名称：

  摘要：

  DOI：

文献信息

• [EN] MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR<br/>[FR] MODULATEURS DU RÉGULATEUR DE LA CONDUCTANCE TRANSMEMBRANAIRE DE LA MUCOVISCIDOSE
  申请人：VERTEX PHARMA

  公开号：WO2022076627A1

  公开（公告）日：2022-04-14

  This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) having the core structure:, pharmaceutical compositions containing at least one such modulator, methods of treating CFTR mediated diseases, including cystic fibrosis using such modulators and pharmaceutical compositions, combination therapies and combination pharmaceuticals employing those modulators, and processes and intermediates for making such modulators.

  本公开提供囊性纤维化跨膜传导调节因子（CFTR）的调节剂，其具有以下核心结构：，包含至少一种这样的调节剂的药物组合物，使用这样的调节剂和药物组合物治疗CFTR介导的疾病，包括囊性纤维化的方法，使用这些调节剂的组合疗法和组合药物，以及制造这些调节剂的过程和中间体。
• Discovery and SAR of 6-Alkyl-2,4-diaminopyrimidines as Histamine H₄ Receptor Antagonists
  作者：Brad M. Savall、Frank Chavez、Kevin Tays、Paul J. Dunford、Jeffery M. Cowden、Michael D. Hack、Ronald L. Wolin、Robin L. Thurmond、James P. Edwards

  DOI：10.1021/jm401727m

  日期：2014.3.27

  This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.