(R)-4-nitrophenyl (1,1,1-trifluoropropan-2-yl)carbamate | 1589602-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-4-nitrophenyl (1,1,1-trifluoropropan-2-yl)carbamate
• 英文别名: (4-nitrophenyl) N-[(2R)-1,1,1-trifluoropropan-2-yl]carbamate
• CAS: 1589602-02-7
• 化学式: C₁₀H₉F₃N₂O₄
• 分子量: 278.188
• InChiKey: ZBUWLRUPSXMMCI-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-(-)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline 、 (R)-4-nitrophenyl (1,1,1-trifluoropropan-2-yl)carbamate 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以45.4%的产率得到(R)-1-(4-(trifluoromethyl)phenyl)-N-((R)-1,1,1-trifluoropropan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide
  参考文献：
  名称：

  Optimization of Potency and Pharmacokinetic Properties of Tetrahydroisoquinoline Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values < 3 mg/kg.

  DOI：

  10.1021/jm401955h