(4R)-4-(氨基甲基)吡咯烷酮-2-酮 | 1407997-81-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (4R)-4-(氨基甲基)吡咯烷酮-2-酮
• 英文名称: (4R)-4-(aminomethyl)pyrrolidin-2-one
• CAS: 1407997-81-2
• 化学式: C₅H₁₀N₂O
• 分子量: 114.147
• InChiKey: TXFBWVRKVAEOPA-SCSAIBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4R)-4-(氨基甲基)吡咯烷酮-2-酮 在 potassium acetate 、 sodium hydride 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 (4R)-4-(aminomethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]pyrrolidin-2-one
  参考文献：
  名称：

  US2022/363633

  摘要：

  公开号：

文献信息

• Free-Wilson and Structural Approaches to Co-optimizing Human and Rodent Isoform Potency for 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitors
  作者：Frederick W. Goldberg、Andrew G. Leach、James S. Scott、Wendy L. Snelson、Sam D. Groombridge、Craig S. Donald、Stuart N. L. Bennett、Cristian Bodin、Pablo Morentin Gutierrez、Amy C. Gyte

  DOI：10.1021/jm3013163

  日期：2012.12.13

  11 beta-Hydroxysteroid dehydrogenase 1 (11 beta-HSD1) has been a target of intensive research efforts across the pharmaceutical industry, due to its potential for the treatment of type II diabetes and other elements of the metabolic syndrome. To demonstrate the value of 11 beta-HSD1 in preclinical models, we required inhibitors with good potency against both human and rodent isoforms. Herein, we describe our efforts to understand how to co-optimize human and murine potency within the (5-hydroxy-2-adamantyl)-pyrimidine-5-carboxamide series. Two approaches are described a data-driven (Free-Wilson) analysis and a structure-based design approach. The conclusions from these approaches were used to inform an efficient campaign to design compounds with consistently good human/murine potency within a logD(7.4) range of 1-3. Compounds 20 and 26 demonstrated good rodent PK, which allowed us to demonstrate a PK/PD relationship in rat and mouse. We then evaluated 26 against glycemic and body weight end points in murine disease models, where it demonstrated glucose and body weight efficacy at 300 mg/kg/day but only body weight efficacy at 50 mg/kg/day, despite providing >90% target engagement in the liver.
• Structure‐Activity Studies Reveal Scope for Optimisation of Ebselen‐Type Inhibition of SARS‐CoV‐2 Main Protease
  作者：Siegfried T. D. Thun‐Hohenstein、Timothy F. Suits、Tika R. Malla、Anthony Tumber、Lennart Brewitz、Hani Choudhry、Eidarus Salah、Christopher J. Schofield

  DOI：10.1002/cmdc.202100582

  日期：2022.2.16

  AbstractThe reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID‐19) and other diseases. We report structure‐activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) main protease (Mpro), employing turnover and protein‐observed mass spectrometry‐based assays. The results reveal scope for optimisation of ebselen/ebselen derivative‐ mediated inhibition of Mpro, particularly with respect to improved selectivity.
• US2022/363633
  申请人：——

  公开号：——

  公开（公告）日：——