N-(isoquinolin-5-yl)-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine | 1238894-04-6

• 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-(isoquinolin-5-yl)-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine
• 英文别名: N-isoquinolin-5-yl-5-[4-(trifluoromethyl)phenyl]-1,3-oxazol-2-amine
• CAS: 1238894-04-6
• 化学式: C₁₉H₁₂F₃N₃O
• 分子量: 355.319
• InChiKey: HNEULCHPLQURLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (9ci)-5-异硫代氰酰基异喹啉 、 2-azido-1-(4-(trifluoromethyl)phenyl)ethanone 在 三苯基膦 作用下， 以 1,4-二氧六环 为溶剂， 以28%的产率得到N-(isoquinolin-5-yl)-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-substituted and 4,5-disubstituted-2-arylamino oxazole TRPV1 antagonists

  摘要：

  The synthesis and structure-activity relationships of a series of 5-monosubstituted and 4,5-disubstituted 2-arylaminooxazoles as novel antagonists of the transient receptor potential vanilloid 1 (TRPV1) receptor are described. The 7-hydroxy group of the tetrahydronaphthyl moiety on the 2-amino substituent of the oxazole ring was important for obtaining excellent in vitro potency at the human TRPV1 receptor, while a variety of alkyl and phenyl substituents at the 4- and 5-positions of the oxazole ring were well tolerated and yielded potent TRPV1 antagonists. Despite excellent in vitro potency, the 5-monosubstituted compounds suffered from poor pharmacokinetics. It was found that 4,5-disubstitution on the oxazole ring was critical to the improvement of the overall pharmacokinetic profile of these analogues, which led to the discovery of compound (R)-27, a novel TRPV1 antagonist with good oral activity in preclinical animal models of pain. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.099