N-[7-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydronaphthalen-1-yl]-N-methyl-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine | 914091-33-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[7-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydronaphthalen-1-yl]-N-methyl-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine
• 英文别名: N-(7-{[tert-butyl(dimethyl)silyl]oxy}-5,6,7,8-tetrahydronaphthalen-1-yl)-N-methyl-5-[4-(trifluoromethyl)phenyl]-1,3-oxazol-2-amine；N-[7-[tert-butyl(dimethyl)silyl]oxy-5,6,7,8-tetrahydronaphthalen-1-yl]-N-methyl-5-[4-(trifluoromethyl)phenyl]-1,3-oxazol-2-amine
• CAS: 914091-33-1
• 化学式: C₂₇H₃₃F₃N₂O₂Si
• 分子量: 502.652
• InChiKey: ZVJGCAGQLFMMPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.01
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[7-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydronaphthalen-1-yl]-N-methyl-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以62%的产率得到8-[methyl{5-[4-(trifluoromethyl)phenyl]oxazol-2-yl}amino]-1,2,3,4-tetrahydronaphthalen-2-ol
  参考文献：
  名称：

  WO2006/122250

  摘要：

  公开号：
• 作为产物：
  描述：

  碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.08h， 以18%的产率得到N-[7-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydronaphthalen-1-yl]-N-methyl-5-[4-(trifluoromethyl)phenyl]oxazol-2-amine
  参考文献：
  名称：

  WO2006/122250

  摘要：

  公开号：

文献信息

• Antagonists of the vanilloid receptor subtype 1 (VR1) and use thereof
  申请人：Gomtsyan Arthur

  公开号：US20060281799A1

  公开（公告）日：2006-12-14

  The present invention is directed to compounds of formula (I) wherein variables W, X, Y, D, A, n, R 1 , R 2 and R 9 are as defined in the description.

  本发明涉及式(I)的化合物，其中变量W、X、Y、D、A、n、R1、R2和R9如描述中所定义。
• ANTAGONISTS OF THE VANILLOID RECEPTOR SUBTYPE 1 (VR1) AND USE THEREOF
  申请人：Gomtsyan Arthur

  公开号：US20100010055A1

  公开（公告）日：2010-01-14

  The present invention is directed to compounds of formula (I) wherein variables W, X, Y, D, A, n, R 1 , R 2 and R 9 are as defined in the description.

  本发明涉及式（I）的化合物，其中变量W，X，Y，D，A，n，R1，R2和R9如描述中所定义。
• 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.