1-((3S,4S)-4-amino-1-(6-(2,4,5-trifluorophenyl)pyrimidin-4-yl)pyrrolidin-3-yl)piperidin-2-one | 1293389-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-((3S,4S)-4-amino-1-(6-(2,4,5-trifluorophenyl)pyrimidin-4-yl)pyrrolidin-3-yl)piperidin-2-one
• 英文别名: 1-[(3S,4S)-4-amino-1-[6-(2,4,5-trifluorophenyl)pyrimidin-4-yl]pyrrolidin-3-yl]piperidin-2-one
• CAS: 1293389-06-6
• 化学式: C₁₉H₂₀F₃N₅O
• 分子量: 391.396
• InChiKey: ZSJZHAJFTNGTOQ-RDJZCZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl (3S,4S)-4-(2-oxopiperidin-1-yl)pyrrolidin-3-ylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 生成 1-((3S,4S)-4-amino-1-(6-(2,4,5-trifluorophenyl)pyrimidin-4-yl)pyrrolidin-3-yl)piperidin-2-one
  参考文献：
  名称：

  1-((3S,4S)-4-Amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes

  摘要：

  A 3-amino-4-substituted pyrrolidine series of dipeptidyl peptidase IV (DPP-4) inhibitors was rapidly developed into a candidate series by identification of a polar valerolactam replacement for the lipophilic 2,4,5-trifluorophenyl pharmacophore. The addition of a gem-difluoro substituent to the lactam improved overall DPP-4 inhibition and an efficient asymmetric route to 3,4-diaminopyrrolidines was developed. Advanced profiling of a subset of analogs identified 5o with an acceptable human DPP-4 inhibition profile based on a rat PK/PD model and a projected human dose that was suitable for clinical development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.055

文献信息

• 1-((3S,4S)-4-Amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes
  作者：Kim M. Andrews、David A. Beebe、John W. Benbow、David A. Boyer、Shawn D. Doran、Yu Hui、Shenping Liu、R. Kirk McPherson、Constantin Neagu、Janice C. Parker、David W. Piotrowski、Steven R. Schneider、Judith L. Treadway、Maria A. VanVolkenberg、William J. Zembrowski

  DOI：10.1016/j.bmcl.2011.01.055

  日期：2011.3

  A 3-amino-4-substituted pyrrolidine series of dipeptidyl peptidase IV (DPP-4) inhibitors was rapidly developed into a candidate series by identification of a polar valerolactam replacement for the lipophilic 2,4,5-trifluorophenyl pharmacophore. The addition of a gem-difluoro substituent to the lactam improved overall DPP-4 inhibition and an efficient asymmetric route to 3,4-diaminopyrrolidines was developed. Advanced profiling of a subset of analogs identified 5o with an acceptable human DPP-4 inhibition profile based on a rat PK/PD model and a projected human dose that was suitable for clinical development. (C) 2011 Elsevier Ltd. All rights reserved.