(S)-3-tert-Butoxycarbonylamino-4-((S)-2-cyano-pyrrolidin-1-yl)-4-oxo-butyric acid benzyl ester | 864921-20-0

• 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)-3-tert-Butoxycarbonylamino-4-((S)-2-cyano-pyrrolidin-1-yl)-4-oxo-butyric acid benzyl ester
• CAS: 864921-20-0
• 化学式: C₂₁H₂₇N₃O₅
• 分子量: 401.462
• InChiKey: DHTLFBWBYRJLKW-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  108.73
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-3-tert-Butoxycarbonylamino-4-((S)-2-cyano-pyrrolidin-1-yl)-4-oxo-butyric acid benzyl ester 在 palladium on activated charcoal 氢气 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (S)-1-[(S)-2-Amino-4-(3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-butyryl]-pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors

  摘要：

  To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine with P2-site 4-substituted glutamic acid derivatives and tested their activities against DPP-IV, DPP8, and DPP-II. Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II. From structure-activity relationship studies, we speculate that the S2 site of DPP8 might be similar to that of DPP-IV, while DPP-IV inhibitor with N-substituted glycine in the P2 site and/or with a moiety involving in hydrophobic interaction with the side chain of Phe357 might provide a better selectivity for DPP-IV over DPP8. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.051
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-苄酯 、 (S)-吡咯烷-2-腈 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (S)-3-tert-Butoxycarbonylamino-4-((S)-2-cyano-pyrrolidin-1-yl)-4-oxo-butyric acid benzyl ester
  参考文献：
  名称：

  Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors

  摘要：

  To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine with P2-site 4-substituted glutamic acid derivatives and tested their activities against DPP-IV, DPP8, and DPP-II. Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II. From structure-activity relationship studies, we speculate that the S2 site of DPP8 might be similar to that of DPP-IV, while DPP-IV inhibitor with N-substituted glycine in the P2 site and/or with a moiety involving in hydrophobic interaction with the side chain of Phe357 might provide a better selectivity for DPP-IV over DPP8. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.051