(2S,4S)-叔-丁基 2-(3,3-二氟吡咯烷-1-羰基)-4-(4-(嘧啶-2-基)哌嗪-1-基)吡咯烷-1-甲酸基酯 | 869490-24-4

• 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
• 中文名称: (2S,4S)-叔-丁基 2-(3,3-二氟吡咯烷-1-羰基)-4-(4-(嘧啶-2-基)哌嗪-1-基)吡咯烷-1-甲酸基酯
• 英文名称: tert-butyl (2S,4S)-2-(3,3-difluoropyrrolidine-1-carbonyl)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidine-1,2-dicarboxylate
• 英文别名: (2S,4S)-2-(3,3-difluoropyrrolidine-1-carbonyl)-4-(4-pyrimidin-2-ylpiperazin-1-yl)pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2S,4S)-2-(3,3-difluoropyrrolidine-1-carbonyl)-4-(4-pyrimidin-2-ylpiperazin-1-yl)pyrrolidine-1-carboxylate
• CAS: 869490-24-4
• 化学式: C₂₂H₃₂F₂N₆O₃
• 分子量: 466.531
• InChiKey: NGOWROOEDIAESU-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,4S)-叔-丁基 2-(3,3-二氟吡咯烷-1-羰基)-4-(4-(嘧啶-2-基)哌嗪-1-基)吡咯烷-1-甲酸基酯 在 盐酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 4.0h， 以75.9%的产率得到(3,3-二氟吡咯烷-1-基)[(2S,4S)-4-[4-(嘧啶-2-基)哌嗪-1-基]吡咯烷-2-基]甲酮
  参考文献：
  名称：

  Therapeutic compounds

  摘要：

  该发明提供了式（I）的化合物，其前药和立体异构体，以及该化合物、前药和立体异构体的药用可接受盐，其中R1、R2、R3、HET、n、Q、X、Y和Z如本文所述；它们的组合物；以及在治疗糖尿病并发症包括糖尿病神经病变、糖尿病肾病、糖尿病微血管病变等方面的用途。

  公开号：

  US20050256310A1
• 作为产物：
  描述：

  (2S,4R)-BOC-Γ-甲磺酰基氧甲基脯氨酸甲酯 在 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 22.0h， 生成 (2S,4S)-叔-丁基 2-(3,3-二氟吡咯烷-1-羰基)-4-(4-(嘧啶-2-基)哌嗪-1-基)吡咯烷-1-甲酸基酯
  参考文献：
  名称：

  New Synthetic Route to a Dipeptidyl Peptidase-4 Inhibitor

  摘要：

  A new synthetic route to a dipeptidyl peptidase-4 (DPP4) inhibitor was developed and demonstrated on a multigram scale. This approach takes advantage of the cheap and readily available Boc-trans-4-hydroxy-L-proline methyl ester as starting material which was derivatized through an S(N)2 reaction. Several leaving groups were studied, and the nosylate group showed superiority over other derivatives. Formation of an amide using the most costly starting material, 3,3-difluoropyrrolidine, was performed late in the synthesis to minimize its economical impact on the overall cost of the API.

  DOI：

  10.1021/op200309z

文献信息

• THERAPEUTIC COMPOUNDS
  申请人：Hulin Bernard

  公开号：US20070161664A1

  公开（公告）日：2007-07-12

  The invention provides compounds of formula (I), or a pharmaceutically acceptable salt of said compound, or a solvate of said compound or salt, wherein R 1 , R 2 , R 3 , HET, n, Q, X, Y, and Z are as described herein; compositions thereof; and uses thereof including treating Type 2 diabetes.

  本发明提供了式(I)的化合物，或其药学上可接受的盐，或该化合物或盐的溶剂结晶体，其中R1、R2、R3、HET、n、Q、X、Y和Z如本文所述；以及包括治疗2型糖尿病在内的其使用方法和组合物。
• (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: A potent, selective, orally active dipeptidyl peptidase IV inhibitor
  作者：Mark J. Ammirati、Kim M. Andrews、David D. Boyer、Anne M. Brodeur、Dennis E. Danley、Shawn D. Doran、Bernard Hulin、Shenping Liu、R. Kirk McPherson、Stephen J. Orena、Janice C. Parker、Jana Polivkova、Xiayang Qiu、Carolyn B. Soglia、Judith L. Treadway、Maria A. VanVolkenburg、Donald C. Wilder、David W. Piotrowski

  DOI：10.1016/j.bmcl.2009.02.041

  日期：2009.4

  A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC(50) = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes.
• PROLINE DERIVATIVES AND THEIR USE AS DIPEPTIDYL PEPTIDASE IV INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1753748B1

  公开（公告）日：2009-07-29
• Proline derivatives and their use as dipeptidyl peptidase IV inhibitors
  申请人：Pfizer Products Inc.

  公开号：EP2116541B1

  公开（公告）日：2015-02-25
• US7291618B2
  申请人：——

  公开号：US7291618B2

  公开（公告）日：2007-11-06