tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate | 911228-63-2

• 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 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxylate；4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-spiro[2H-1-benzopyran-2,4'-piperidine]-1'-carboxylic acid 1,1-dimethylethyl ester
• CAS: 911228-63-2
• 化学式: C₂₄H₃₄BNO₅
• 分子量: 427.349
• InChiKey: HGFULWJJTHSPRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.86
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate 、 5-溴-N,N-二乙基-2-糠酰胺 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， 生成 Tert-butyl 4-[5-(diethylcarbamoyl)furan-2-yl]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
• 作为产物：
  描述：

  4-氧代-2-螺(N-叔丁基哌啶-4-基)-吡喃 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 potassium acetate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chromene-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  [EN] NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  [FR] NOUVEAUX COMPOSÉS SPIRO UTILES EN TANT QU'INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE

  摘要：

  结构式（I）的杂环芳香化合物相对于其他已知的硬脂酰辅酶A去饱和酶（SCD1）具有选择性抑制作用。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病（如动脉粥样硬化）、肥胖、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗和肝脂肪变性。

  公开号：

  WO2011011872A1

文献信息

• 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.
• 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.
• [EN] NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] NOUVEAUX COMPOSÉS SPIRO UTILES EN TANT QU'INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2011011872A1

  公开（公告）日：2011-02-03

  Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式（I）的杂环芳香化合物相对于其他已知的硬脂酰辅酶A去饱和酶（SCD1）具有选择性抑制作用。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病（如动脉粥样硬化）、肥胖、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗和肝脂肪变性。