Tert-butyl 4-[4-(dimethylcarbamoyl)phenyl]spiro[chromene-2,4'-piperidine]-1'-carboxylate | 1013334-46-7

• 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-(dimethylcarbamoyl)phenyl]spiro[chromene-2,4'-piperidine]-1'-carboxylate
• CAS: 1013334-46-7
• 化学式: C₂₇H₃₂N₂O₄
• 分子量: 448.562
• InChiKey: MXUZTDHZZXVCSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[4-(dimethylcarbamoyl)phenyl]spiro[chromene-2,4'-piperidine]-1'-carboxylate 在 盐酸 、 水 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 N,N-dimethyl-4-(spiro[chromene-2,4'-piperidine]-4-yl)benzamide
  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
• 作为产物：
  描述：

  4-(1'-(tert-butoxycarbonyl)spiro[chromene-2,4'-piperidine]-4-yl)benzoic acid 、 二甲胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 Tert-butyl 4-[4-(dimethylcarbamoyl)phenyl]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 Delta Opioid Receptor Agonists for the Treatment of Pain: Discovery of <i>N</i>,<i>N</i>-Diethyl-3-hydroxy-4-(spiro[chromene-2,4′-piperidine]-4-yl) Benzamide (ADL5747)
  作者：Bertrand Le Bourdonnec、Rolf T. Windh、Lara K. Leister、Q. Jean Zhou、Christopher W. Ajello、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、Michael J. Derelanko、Steve Kutz、Patrick J. Little、Robert N. DeHaven、Diane L. DeHaven-Hudkins、Roland E. Dolle

  DOI：10.1021/jm900773n

  日期：2009.9.24

  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.