(R)-3-methyl-1,4-diazepan-2-one | 790207-81-7

• 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: (R)-3-methyl-1,4-diazepan-2-one
• 英文别名: (3R)-3-methyl-1,4-diazepan-2-one
• CAS: 790207-81-7
• 化学式: C₆H₁₂N₂O
• 分子量: 128.174
• InChiKey: PPFMWEFKLWLFKX-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-3-methyl-1,4-diazepan-2-one 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-4-[(3S)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-methyl-1,4-diazepan-2-one
  参考文献：
  名称：

  (3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

  摘要：

  Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

  DOI：

  10.1016/j.bmcl.2006.09.099
• 作为产物：
  描述：

  (R)-methyl 2-[(tert-butoxycarbonyl)(2-cyanoethyl)amino]propanoate 在 platinum(IV) oxide 、 氢气 、 三甲基铝 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 甲苯 为溶剂， 反应 112.0h， 生成 (R)-3-methyl-1,4-diazepan-2-one
  参考文献：
  名称：

  [EN] BET INHIBITORS FOR MODULATING DUX4 EXPRESSION IN FSHD
  [FR] INHIBITEURS DE BET POUR MODULER L'EXPRESSION DE DUX4 DANS LA FSHD

  摘要：

  本公开提供了以下式的BET抑制剂：其中变量在此处定义，以及其药物组合物。本公开还提供了治疗患者的方法，包括给予溴和额外端（BET）结构域抑制剂治疗FSHD以调节DUX4表达。在某些实施例中，本方法包括使用一个或多个BET抑制剂作为FSHD患者的治疗剂，包括正在接受一种或多种缓解治疗（如治疗和/或导致肌肉增加的药物）的患者。

  公开号：

  WO2020132004A1

文献信息

• [EN] AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] AMINOCYCLOHEXANES EN TANT QU'INHIBITEURS DE DIPEPTIDYL PEPTIDASE-IV POUR LE TRAITEMENT OU LA PRÉVENTION DE DIABÈTES
  申请人：MERCK & CO INC

  公开号：WO2006009886A1

  公开（公告）日：2006-01-26

  The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme ('DPP-IV inhibitors') and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. 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 the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及一种新型的取代氨基环己烷，它们是二肽基肽酶-IV酶（'DPP-IV抑制剂'）的抑制剂，并且在治疗或预防涉及二肽基肽酶-IV酶的疾病中具有用处，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及二肽基肽酶-IV酶的这类疾病中使用这些化合物和组合物。
• Optimization of 1,4-diazepan-2-one containing dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes
  作者：Gui-Bai Liang、Xiaoxia Qian、Dennis Feng、Tesfaye Biftu、George Eiermann、Huaibing He、Barbara Leiting、Kathy Lyons、Aleksandr Petrov、Ranabir Sinha-Roy、Bei Zhang、Joseph Wu、Xiaoping Zhang、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2007.01.039

  日期：2007.4

  Following the discovery of N-acyl-1,4-diazepan-2-one as a novel pharmacophore for potent and selective DPP-4 inhibitors, optimization of this new lead with different substitution on the seven-membered ring resulted in several highly potent and selective, orally bioavailable, and efficacious DPP-4 inhibitors, such as 3R-methyl-1-cyclopropyl-1,4-diazepan-2-one derivative 9i (DPP-4 IC(50)=8.0 nM) and 3R,6R-dimethyl-1

  在发现N-酰基-1,4-二氮杂-2-酮作为有效和选择性DPP-4抑制剂的新型药效团后，对这种新的先导物进行了优化，在七元环上进行了不同的取代，从而产生了数个高效且高效的DPP-4抑制剂。选择性，口服可生物利用且有效的DPP-4抑制剂，例如3R-甲基-1-环丙基-1,4-二氮杂-2-酮衍生物9i（DPP-4 IC（50）= 8.0 nM）和3R，6R-二甲基-1,4-二氮杂-2-酮衍生物14a（DPP-4 IC（50）= 9.7 nM）。
• Aminocyclohexanes as Dipeptidyl Peptidase-Iv Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Biftu Tesfaye

  公开号：US20070254865A1

  公开（公告）日：2007-11-01

  The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. 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 the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型的取代氨基环己烷，其为二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂，并且对于二肽基肽酶-IV酶参与的疾病，例如糖尿病和特别是2型糖尿病的治疗或预防有用。该发明还涉及包含这些化合物的制药组合物以及在预防或治疗二肽基肽酶-IV酶参与的这些疾病中使用这些化合物和组合物。
• Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design
  作者：Gui-Bai Liang、Xiaoxia Qian、Tesfaye Biftu、Suresh Singh、Ying-Duo Gao、Giovanna Scapin、Sangita Patel、Barbara Leiting、Reshma Patel、Joseph Wu、Xiaoping Zhang、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2008.05.061

  日期：2008.7

  Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.
• AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1761532B1

  公开（公告）日：2013-04-10