N-t-butoxycarbonyl-1-[2-amino-4-(3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-butyryl]-pyrrolidine-2-carbonitrile | 861429-59-6

• 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: N-t-butoxycarbonyl-1-[2-amino-4-(3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-butyryl]-pyrrolidine-2-carbonitrile
• CAS: 861429-59-6
• 化学式: C₂₃H₃₀N₄O₄
• 分子量: 426.516
• InChiKey: DHDZAKIUGSRZHL-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.37
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  102.74
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-t-butoxycarbonyl-1-[2-amino-4-(3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-butyryl]-pyrrolidine-2-carbonitrile 在 三氟乙酸 作用下， 以 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：

  (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 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-t-butoxycarbonyl-1-[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

文献信息

• [EN] PYRROLIDINE COMPOUNDS<br/>[FR] COMPOSES DE PYRROLIDINE
  申请人：NAT HEALTH RESEARCH INSTITUTES

  公开号：WO2005087235A1

  公开（公告）日：2005-09-22

  A compound of the following formula (I) wherein R1, R2, R3, R4, R5, R6, W, X, Y, Z, m, n, and p are as defined herein. This invention also covers methods for inhibiting dipeptidyl peptidase IV or VIII, or treating Type II diabetes with such a compound.

  一种具有以下化学式（I）的化合物，其中R1、R2、R3、R4、R5、R6、W、X、Y、Z、m、n和p的定义如本文所述。本发明还涵盖了使用这种化合物抑制二肽基肽酶IV或VIII，或者治疗II型糖尿病的方法。