[(3S,4S)-1-Benzyl-4-(5,5-difluoro-2-oxo-piperidin-1-yl)-pyrrolidin-3-yl]-carbamic acid methyl ester | 1000303-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(3S,4S)-1-Benzyl-4-(5,5-difluoro-2-oxo-piperidin-1-yl)-pyrrolidin-3-yl]-carbamic acid methyl ester
• 英文别名: methyl N-[(3S,4S)-1-benzyl-4-(5,5-difluoro-2-oxopiperidin-1-yl)pyrrolidin-3-yl]carbamate
• CAS: 1000303-24-1
• 化学式: C₁₈H₂₃F₂N₃O₃
• 分子量: 367.396
• InChiKey: YENJLVCFSYASCX-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(3S,4S)-1-Benzyl-4-(5,5-difluoro-2-oxo-piperidin-1-yl)-pyrrolidin-3-yl]-carbamic acid methyl ester 在 磷酰基乙酸 、 20 % Pd(OH)2/C 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 叔丁醇 为溶剂， 50.0 ℃ 、517.12 kPa 条件下， 生成 1-((3S,4S)-4-amino-1-(6-(3,3-difluoropyrrolidin-1-yl)-2-methylpyrimidin-4-yl)pyrrolidin-3-yl)-5,5-difluoropiperidin-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
• 作为产物：
  描述：

  ethyl 5-chloro-4-oxopentanoate 在 二乙胺基三氟化硫 、 水 、 sodium hydride 、 1-丙基磷酸酐 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 [(3S,4S)-1-Benzyl-4-(5,5-difluoro-2-oxo-piperidin-1-yl)-pyrrolidin-3-yl]-carbamic acid methyl ester
  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

• Substituted 3-Amino-Pyrrolidino-4-Lactams
  申请人：Piotrowski David W.

  公开号：US20070299076A1

  公开（公告）日：2007-12-27

  The invention provides compounds of formula (1), and the pharmaceutically acceptable salt thereof, wherein R 1 , n and R 2 are as described herein; compositions thereof; and uses thereof.

  这项发明提供了式（1）的化合物，以及其药用可接受的盐，其中R1、n和R2如本文所述；以及它们的组合物；以及它们的用途。
• Substituted 3-amino-pyrrolidino-4-lactams
  申请人：Pfizer, Inc.

  公开号：US07485641B2

  公开（公告）日：2009-02-03

  The invention provides compounds of formula (1), and the pharmaceutically acceptable salt thereof, wherein R1, n and R2 are as described herein; compositions thereof; and uses thereof.

  本发明提供了式(1)的化合物及其药学上可接受的盐，其中R1、n和R2如本文所述；它们的组成；以及它们的用途。
• US7485641B2
  申请人：——

  公开号：US7485641B2

  公开（公告）日：2009-02-03