Ac-Ala(D)-BoroPro

• 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: Ac-Ala(D)-BoroPro
• 英文别名: (R)-1-((R)-2-acetamidopropanoyl)pyrrolidin-2-ylboronic acid；[(2R)-1-[(2R)-2-acetamidopropanoyl]pyrrolidin-2-yl]boronic acid
• 化学式: C₉H₁₇BN₂O₄
• 分子量: 228.056
• InChiKey: METFGSCNIQTFJC-SVRRBLITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.49
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-乙酰-D-丙氨酸 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 、 苯硼酸 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 Ac-Ala(D)-BoroPro
  参考文献：
  名称：

  Synthesis and structure–activity relationship of N-acyl-Gly-, N-acyl-Sar- and N-blocked-boroPro inhibitors of FAP, DPP4, and POP

  摘要：

  The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N-Acyl-Sar-boroPro analogs retained selectivity against DPP4 and potent POP inhibitory activity but displayed decreased FAP inhibitory activity.

  DOI：

  10.1016/j.bmcl.2006.11.072

文献信息

• Identification of Selective and Potent Inhibitors of Fibroblast Activation Protein and Prolyl Oligopeptidase
  作者：Sarah E. Poplawski、Jack H. Lai、Youhua Li、Zhiping Jin、Yuxin Liu、Wengen Wu、Yong Wu、Yuhong Zhou、James L. Sudmeier、David G. Sanford、William W. Bachovchin

  DOI：10.1021/jm400351a

  日期：2013.5.9

  Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for PAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-D-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets.
• Synthesis and structure–activity relationship of N-acyl-Gly-, N-acyl-Sar- and N-blocked-boroPro inhibitors of FAP, DPP4, and POP
  作者：Thuy Tran、Clifford Quan、Conrad Yap Edosada、Mark Mayeda、Christian Wiesmann、Dan Sutherlin、Beni B. Wolf

  DOI：10.1016/j.bmcl.2006.11.072

  日期：2007.3

  The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N-Acyl-Sar-boroPro analogs retained selectivity against DPP4 and potent POP inhibitory activity but displayed decreased FAP inhibitory activity.