[(7R)-4-(4-Amino-5-methylthieno[2,3-d]pyrimidin-2-yl)hexahydro-7-methyl-1H-1,4-diazepin-1-yl][2-(2H-1,2,3-triazol-2-yl)phenyl]-methanone | 1030377-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [(7R)-4-(4-Amino-5-methylthieno[2,3-d]pyrimidin-2-yl)hexahydro-7-methyl-1H-1,4-diazepin-1-yl][2-(2H-1,2,3-triazol-2-yl)phenyl]-methanone
• 英文别名: [(7R)-4-(4-amino-5-methylthieno[2,3-d]pyrimidin-2-yl)-7-methyl-1,4-diazepan-1-yl]-[2-(triazol-2-yl)phenyl]methanone
• CAS: 1030377-48-0
• 化学式: C₂₂H₂₄N₈OS
• 分子量: 448.552
• InChiKey: LSRYXWRLTUFERQ-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二氯-5-甲基噻吩并[2,3-D]嘧啶 在 ammonium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 生成 [(7R)-4-(4-Amino-5-methylthieno[2,3-d]pyrimidin-2-yl)hexahydro-7-methyl-1H-1,4-diazepin-1-yl][2-(2H-1,2,3-triazol-2-yl)phenyl]-methanone
  参考文献：
  名称：

  Discovery of dual orexin receptor antagonists with rat sleep efficacy enabled by expansion of the acetonitrile-assisted/diphosgene-mediated 2,4-dichloropyrimidine synthesis

  摘要：

  Recent clinical studies have demonstrated that dual orexin receptor antagonists (OX1R and OX2R antagonists or DORAs) represent a novel treatment option for insomnia patients. Previously we have disclosed several compounds in the diazepane amide DORA series with excellent potency and both preclinical and clinical sleep efficacy. Additional SAR studies in this series were enabled by the expansion of the acetonitrile-assisted, diphosgene-mediated 2,4-dichloropyrimidine synthesis to novel substrates providing an array of Western heterocycles. These heterocycles were utilized to synthesize analogs in short order with high levels of potency on orexin 1 and orexin 2 receptors as well as in vivo sleep efficacy in the rat. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.052

文献信息

• Substituted diazepan orexin receptor antagonists
  申请人：Bergman Jeffrey M.

  公开号：US20080132490A1

  公开（公告）日：2008-06-05

  The present invention is directed to substituted diazepan 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.

  本发明涉及替代二氮杂环丙烷化合物，其为促进睡眠蛋白受体的拮抗剂，可用于治疗或预防神经和精神疾病，以及涉及促进睡眠蛋白受体的疾病。该发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在预防或治疗涉及促进睡眠蛋白受体的疾病中的用途。
• Substituted diazepan compounds as orexin receptor antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2392572A1

  公开（公告）日：2011-12-07

  The present invention is directed to substituted diazepan 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.

  本发明涉及取代的二氮杂环庚烷化合物，它们是奥曲肽受体的拮抗剂，可用于治疗或预防涉及奥曲肽受体的神经和精神紊乱及疾病。本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗涉及奥曲肽受体的此类疾病中的用途。
• SUBSTITUTED DIAZEPAN OREXIN RECEPTOR ANTAGONISTS
  申请人：Bergman Jeffrey M.

  公开号：US20110195957A1

  公开（公告）日：2011-08-11

  The present invention is directed to substituted diazepan 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.
• US7951797B2
  申请人：——

  公开号：US7951797B2

  公开（公告）日：2011-05-31
• [EN] SUBSTITUTED DIAZEPAN COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE SOUS FORME DE COMPOSÉS DE DIAZÉPANE SUBSTITUÉS
  申请人：MERCK & CO INC

  公开号：WO2008069997A1

  公开（公告）日：2008-06-12

  [EN] The present invention is directed to substituted diazepan 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 de diazépane substitués qui sont des antagonistes des récepteurs de l'orexine et se révèlent utiles pour le traitement ou la prévention de troubles et de maladies neurologiques et psychiatriques dans lesquels les récepteurs de l'orexine sont impliqués. L'invention concerne également des compositions pharmaceutiques renfermant ces composés ainsi que l'utilisation de ces composés et de ces compositions dans la prévention ou le traitement de maladies dans lesquelles les récepteurs de l'orexine sont impliqués.