8-{4-bromo-5-[4-(trifluoromethyl)phenyl]oxazol-2-ylamino}-1,2,3,4-tetrahydronaphthalen-2-ol | 1238894-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 8-{4-bromo-5-[4-(trifluoromethyl)phenyl]oxazol-2-ylamino}-1,2,3,4-tetrahydronaphthalen-2-ol
• 英文别名: 8-[[4-bromo-5-[4-(trifluoromethyl)phenyl]-1,3-oxazol-2-yl]amino]-1,2,3,4-tetrahydronaphthalen-2-ol
• CAS: 1238894-27-3
• 化学式: C₂₀H₁₆BrF₃N₂O₂
• 分子量: 453.258
• InChiKey: UNUKLCQFLQMDAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-{4-bromo-5-[4-(trifluoromethyl)phenyl]oxazol-2-ylamino}-1,2,3,4-tetrahydronaphthalen-2-ol 在 Chiralcel-OD 作用下， 以 正己烷 、 异丙醇 为溶剂， 以38%的产率得到(R)-8-{4-bromo-5-[4-(trifluoromethyl)phenyl]oxazol-2-ylamino}-1,2,3,4-tetrahydronaphthalen-2-ol
  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
• 作为产物：
  描述：

  4-bromo-N-[7-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydronaphthalen-1-yl]-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine 在 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 为溶剂， 以59%的产率得到8-{4-bromo-5-[4-(trifluoromethyl)phenyl]oxazol-2-ylamino}-1,2,3,4-tetrahydronaphthalen-2-ol
  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

文献信息

• Synthesis and biological evaluation of 5-substituted and 4,5-disubstituted-2-arylamino oxazole TRPV1 antagonists
  作者：Richard J. Perner、John R. Koenig、Stanley DiDomenico、Arthur Gomtsyan、Robert G. Schmidt、Chih-Hung Lee、Margaret C. Hsu、Heath A. McDonald、Donna M. Gauvin、Shailen Joshi、Teresa M. Turner、Regina M. Reilly、Philip R. Kym、Michael E. Kort

  DOI：10.1016/j.bmc.2010.04.099

  日期：2010.7

  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.