tert-butyl 6-(tert-butyldimethylsilyloxy)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate | 911227-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: tert-butyl 6-(tert-butyldimethylsilyloxy)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 6-[tert-butyl(dimethyl)silyl]oxy-4-oxospiro[3H-chromene-2,4'-piperidine]-1'-carboxylate
• CAS: 911227-49-1
• 化学式: C₂₄H₃₇NO₅Si
• 分子量: 447.647
• InChiKey: AHEDSXUITRNAPR-UHFFFAOYSA-N

物化性质

• 沸点：
  516.6±50.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.81
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 tert-butyl 6-(tert-butyldimethylsilyloxy)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以90.5%的产率得到tert-butyl 6-(tert-butyldimethylsilyloxy)-4-(trifluoromethylsulfonyloxy)spiro[chromene-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Potent, Orally Bioavailable Delta Opioid Receptor Agonists for the Treatment of Pain: Discovery of N,N-Diethyl-4-(5-hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859)

  摘要：

  Selective 6 opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable 6 agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.

  DOI：

  10.1021/jm8008986
• 作为产物：
  描述：

  1′-tert-butoxycarbonyl-6-hydroxy-4-oxospiro[chromane-2,4′-piperidine] 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 以76%的产率得到tert-butyl 6-(tert-butyldimethylsilyloxy)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  [EN] SPIROCYCLIC HETEROCYCLIC DERIVATIVES AND METHODS OF THEIR USE
  [FR] DERIVES HETEROCYCLIQUES SPIROCYCLIQUES ET LEURS METHODES D'UTILISATION

  摘要：

  公开号：

  WO2005033073A3

文献信息

• WO2006/105442
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] SPIROCYCLIC HETEROCYCLIC DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DERIVES HETEROCYCLIQUES SPIROCYCLIQUES ET LEURS METHODES D'UTILISATION
  申请人：ADOLOR CORP

  公开号：WO2005033073A3

  公开（公告）日：2005-07-28
• Potent, Orally Bioavailable Delta Opioid Receptor Agonists for the Treatment of Pain: Discovery of <i>N</i>,<i>N</i>-Diethyl-4-(5-hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859)
  作者：Bertrand Le Bourdonnec、Rolf T. Windh、Christopher W. Ajello、Lara K. Leister、Minghua Gu、Guo-Hua Chu、Paul A. Tuthill、William M. Barker、Michael Koblish、Daniel D. Wiant、Thomas M. Graczyk、Serge Belanger、Joel A. Cassel、Marina S. Feschenko、Bernice L. Brogdon、Steven A. Smith、David D. Christ、Michael J. Derelanko、Steve Kutz、Patrick J. Little、Robert N. DeHaven、Diane L. DeHaven-Hudkins、Roland E. Dolle

  DOI：10.1021/jm8008986

  日期：2008.10.9

  Selective 6 opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable 6 agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.