1-(tert-butoxycarbonyl)-N-[2-(1H-pyrrol-1-yl)phenyl]-L-prolinamide | 916143-41-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(tert-butoxycarbonyl)-N-[2-(1H-pyrrol-1-yl)phenyl]-L-prolinamide
• 英文别名: tert-butyl (2S)-2-[(2-pyrrol-1-ylphenyl)carbamoyl]pyrrolidine-1-carboxylate
• CAS: 916143-41-4
• 化学式: C₂₀H₂₅N₃O₃
• 分子量: 355.437
• InChiKey: OBAWMRUZCUQLJH-KRWDZBQOSA-N

物化性质

• 沸点：
  543.7±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-N-[2-(1H-pyrrol-1-yl)phenyl]-L-prolinamide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.55h， 生成 N-[2-(1H-pyrrol-1-yl)phenyl]-L-prolinamide hydrochloride
  参考文献：
  名称：

  WO2006/127550

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(2-氨基苯基)吡咯 、 BOC-L-脯氨酸 在 吡啶 、 三氯氧磷 作用下， 反应 0.33h， 生成 1-(tert-butoxycarbonyl)-N-[2-(1H-pyrrol-1-yl)phenyl]-L-prolinamide
  参考文献：
  名称：

  WO2006/127550

  摘要：

  公开号：

文献信息

• Proline bis-amide orexin receptor antagonists
  申请人：Bergman Jeffrey M.

  公开号：US20090118200A1

  公开（公告）日：2009-05-07

  The present invention is directed to proline bis-amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及丙氨酸双酰胺化合物，其为促进素受体拮抗剂，可用于治疗或预防涉及促进素受体的神经和精神障碍和疾病。本发明还涉及包含这些化合物的制药组合物以及利用这些化合物和组合物预防或治疗涉及促进素受体的这些疾病的用途。
• WO2006/127550
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PROLINE BIS-AMIDE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS D'OREXINE A BASE DE BIS-AMIDE DE PROLINE
  申请人：MERCK & CO INC

  公开号：WO2006127550A1

  公开（公告）日：2006-11-30

  [EN] The present invention is directed to proline bis-amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
  [FR] La présente invention concerne des composés bis-amide de proline qui sont des antagonistes des récepteurs d'orexine, et qui sont utiles dans le traitement ou la prévention de troubles et de maladies neurologiques et psychiatriques impliquant les récepteurs d'orexine. L'invention concerne également des compositions pharmaceutiques comprenant ces composés, ainsi que l'utilisation de ces composés et compositions dans la prévention ou le traitement de telles maladies impliquant les récepteurs d'orexine.
• Proline bis-amides as potent dual orexin receptor antagonists
  作者：Jeffrey M. Bergman、Anthony J. Roecker、Swati P. Mercer、Rodney A. Bednar、Duane R. Reiss、Richard W. Ransom、C. Meacham Harrell、Douglas J. Pettibone、Wei Lemaire、Kathy L. Murphy、Chunze Li、Thomayant Prueksaritanont、Christopher J. Winrow、John J. Renger、Kenneth S. Koblan、George D. Hartman、Paul J. Coleman

  DOI：10.1016/j.bmcl.2008.01.001

  日期：2008.2

  A series of OX2R/OX1R dual orexin antagonists was prepared based on a proline bis-amide identified as a screening lead. Through a combination of classical and library synthesis, potency enhancing replacements for both amide portions were discovered. N-methylation of the benzimidazole moiety within the lead structure significantly reduced P-gp susceptibility while increasing potency, giving rise to good brain penetration. A compound from this series has demonstrated in vivo central activity when dosed peripherally in a pharmacodynamic model of orexin activity. Published by Elsevier Ltd.