[(S)-2-((S)-2-Cyano-pyrrolidin-1-yl)-1-(4-iodo-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester | 680227-80-9

• 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: [(S)-2-((S)-2-Cyano-pyrrolidin-1-yl)-1-(4-iodo-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
• CAS: 680227-80-9
• 化学式: C₁₉H₂₄IN₃O₃
• 分子量: 469.322
• InChiKey: OBWFUIOSKDZPSC-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  82.43
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [(S)-2-((S)-2-Cyano-pyrrolidin-1-yl)-1-(4-iodo-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 copper(ll) sulfate pentahydrate 、 四丁基氟化铵 、 sodium ascorbate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 tert-butyl {(S)-1-[(S)-2-cyanopyrrolidin-1-yl]-3-[4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)phenyl]-1-oxopropan-2-yl}carbamate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors

  摘要：

  A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79-25.52 nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79 nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.034
• 作为产物：
  描述：

  Boc-4-碘-L-苯丙氨酸 、 (S)-吡咯烷-2-腈 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 [(S)-2-((S)-2-Cyano-pyrrolidin-1-yl)-1-(4-iodo-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors

  摘要：

  The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported.

  DOI：

  10.1016/j.bmcl.2005.09.037

文献信息

• Design, Synthesis, Biological Evaluation, and Docking Studies of (<i>S</i>)-Phenylalanine Derivatives with a 2-Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors
  作者：Yang Liu、Yizhe Wu、Haoshu Wu、Li Tang、Peng Wu、Tao Liu、Yongzhou Hu

  DOI：10.1111/cbdd.12139

  日期：2013.8

  A novel series of (S)‐phenylalanine derivatives with a 2‐cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy. Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 (DPP‐4) inhibitors; among them, the cyclopropyl‐substituted phenylalanine derivative 11h displayed the most potent DPP‐4 inhibitory activity with an IC50 value of 0.247 μm. In addition, molecular docking analysis of the representative compounds 11h, 11k, and 15a were performed, which not only revealed the impact of binding modes on DPP‐4 inhibitory activity but also provided additional methodological values for design and optimization.