tert-butyl 4-(4-(diethylcarbamoyl)-3-hydroxyphenyl)spiro[chromene-2,4'-piperidine]-1'-carboxylate | 911228-80-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: tert-butyl 4-(4-(diethylcarbamoyl)-3-hydroxyphenyl)spiro[chromene-2,4'-piperidine]-1'-carboxylate
• 英文别名: Tert-butyl 4-[4-(diethylcarbamoyl)-3-hydroxyphenyl]spiro[chromene-2,4'-piperidine]-1'-carboxylate
• CAS: 911228-80-3
• 化学式: C₂₉H₃₆N₂O₅
• 分子量: 492.615
• InChiKey: YJBHYNPSDXHDOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  79.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(diethylcarbamoyl)-3-hydroxyphenyl)spiro[chromene-2,4'-piperidine]-1'-carboxylate 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 32.0h， 以66%的产率得到
  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
• 作为产物：
  描述：

  tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate 、 4-bromo-N,N-diethyl-2-hydroxybenzamide 在 四(三苯基膦)钯 、 sodium carbonate 、 lithium chloride 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 以37%的产率得到tert-butyl 4-(4-(diethylcarbamoyl)-3-hydroxyphenyl)spiro[chromene-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Spirocyclic Delta Opioid Receptor Agonists for the Treatment of Pain: Discovery of N,N-Diethyl-3-hydroxy-4-(spiro[chromene-2,4′-piperidine]-4-yl) Benzamide (ADL5747)

  摘要：

  Selective, nonpeptidic delta opioid receptor agonists have been the subject of great interest as potential novel analgesic agents. The discoveries of BW373U86 (1) and SNC80 (2) contributed to the rapid expansion of research in this field. However, poor drug-like properties and low therapeutic indices have prevented clinical evaluation of these agents. Doses of I and 2 similar to those required for analgesic activity produce convulsions in rodents and nonhuman primates. Recently, we described a novel series of potent, selective. and orally bioavailable delta opioid receptor agonists. The lead derivative, ADL5859 (4), is currently in phase It proof-of-concept studies for the management of pain. Further structure activity relationship exploration has led to the discovery of ADL5747 (36), which is approximately 50-fold more potent than 4 in an animal model of inflammatory pain. On the basis of its favorable efficacy, safety, and pharmacokinetic profile, 36 was selected as a clinical candidate for the treatment of pain.

  DOI：

  10.1021/jm900773n

文献信息

• Spirocyclic Heterocyclic Derivatives And Methods Of Their Use
  申请人：Dolle E. Roland

  公开号：US20080102031A1

  公开（公告）日：2008-05-01

  Spirocyclic heterocyclic derivatives, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the spirocyclic heterocyclic derivatives are ligands of the δ opioid receptor and may be useful, inter alia, for treating and/or preventing pain, anxiety, gastrointestinal disorders, and other δ opioid receptor-mediated conditions.

  本发明公开了螺环异杂环衍生物、含有这些化合物的制药组合物以及它们的制药用途方法。在某些实施例中，螺环异杂环衍生物是δ阿片受体的配体，可能有助于治疗和/或预防疼痛、焦虑、胃肠疾病和其他δ阿片受体介导的疾病等。
• SPIROCYCLIC HETEROCYCLIC DERIVATIVES AND METHODS OF THEIR USE
  申请人：Dolle Roland E.

  公开号：US20100029614A1

  公开（公告）日：2010-02-04

  Spirocyclic heterocyclic derivatives, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the spirocyclic heterocyclic derivatives are ligands of the δ opioid receptor and may be useful, inter alia, for treating and/or preventing pain, anxiety, gastrointestinal disorders, and other δ opioid receptor-mediated conditions.

  本发明公开了螺环杂环衍生物、含有这些化合物的制药组合物以及它们的制药用途的方法。在某些实施例中，螺环杂环衍生物是δ阿片受体的配体，并且可能有用于治疗和/或预防疼痛、焦虑、胃肠障碍和其他δ阿片受体介导的疾病等方面。
• US7338962B2
  申请人：——

  公开号：US7338962B2

  公开（公告）日：2008-03-04
• US7598261B2
  申请人：——

  公开号：US7598261B2

  公开（公告）日：2009-10-06
• US7638527B2
  申请人：——

  公开号：US7638527B2

  公开（公告）日：2009-12-29