Z-Pro-Pro-Gly-OEt | 6735-68-8

• 英文名称: Z-Pro-Pro-Gly-OEt
• 英文别名: N-benzyloxycarbonyl-(2S)-prolyl-(2S)-prolylglycine ethyl ester；Cbz-Pro-Pro-Gly-OEt；benzyl (2S)-2-[(2S)-2-[(2-ethoxy-2-oxoethyl)carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carboxylate
• CAS: 6735-68-8
• 化学式: C₂₂H₂₉N₃O₆
• 分子量: 431.489
• InChiKey: CUSVVXCMSVNUGK-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Z-Pro-Pro-Gly-OEt 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以553 g的产率得到H-Pro-Pro-Gly-OEt
  参考文献：
  名称：

  Selective inhibition of prolyl 4-hydroxylases by bipyridinedicarboxylates

  摘要：

  Collagen is the most abundant protein in animals. A variety of indications are associated with the overproduction of collagen, including fibrotic diseases and cancer metastasis. The stability of collagen relies on the posttranslational modification of proline residues to form (2S,4R)-4-hydroxyproline. This modification is catalyzed by collagen prolyl 4-hydroxylases (CP4Hs), which are Fe(II)- and alpha-ketoglutarate (AKG)-dependent dioxygenases located in the lumen of the endoplasmic reticulum. Human CP4Hs are validated targets for treatment of both fibrotic diseases and metastatic breast cancer. Herein, we report on 2,2'-bipyridinedicarboxylates as inhibitors of a human CP4H. Although most 2,2'-bipyridinedicarboxylates are capable of inhibition via iron sequestration, the 4,5'-and 5,5'-dicarboxylates were found to be potent competitive inhibitors of CP4H, and the 5,5'-dicarboxylate was selective in its inhibitory activity. Our findings clarify a strategy for developing CP4H inhibitors of clinical utility. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.003
• 作为产物：
  描述：

  甘氨酸乙酯盐酸盐 、 Cbz-Pro-Pro-OH 在 ethylene dichloride hydrochloride 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以63%的产率得到Z-Pro-Pro-Gly-OEt
  参考文献：
  名称：

  INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE

  摘要：

  Biheteroaryl二羧酸酯和酯，以及它们的盐，可用作CP4H活性的调节剂，更具体地作为CP4H的抑制剂。化合物的结构式:及其盐，其中:X为S、O、NH或NR，其中R为具有1-3个碳原子的烷基基团；R1和R2独立地为—OR7，或—NHSO2R8，其中R7选自：氢、烷基、烯基、烷氧基烷基、—R′—CO—R″、—R′—CO—O—R″、—CO—R″、—R′—O—CO—R″、—R′—CO—NR″、—CO—NR″或—R′—O—CO—NR″，而R8选自氢、烷基、芳基、芳基烷基；R3、R4和R6独立地为氢、烷基、烷氧基、烯基、烯氧基、卤代烷基、卤代烯基、卤素、羟基、羟基烷基、羟基烯基、芳基、芳氧基、芳基烷基或芳基烷氧基；R5为氢、卤素、具有1-3个碳原子的烷基，或具有1-3个碳原子的烷氧基；—R′—为二价的直链或支链烷基，而—R″为烷基、烯基、芳基烷基或芳基。用于体内和体外抑制CP4H的方法。

  公开号：

  US20160280701A1

文献信息

• Biondi, Laura; Cavaggion, Franco; Filira, Fernando, Gazzetta Chimica Italiana, 1988, vol. 118, # 6, p. 427 - 434
  作者：Biondi, Laura、Cavaggion, Franco、Filira, Fernando、Rocchi, Raniero

  DOI：——

  日期：——
• ROCCHI, R.;BIONDI, L.;FILIRA, F.;SCOLARO, B., INT. J. PEPTIDE AND PROTEIN RES., 30,(1987) N 2, 240-256
  作者：ROCCHI, R.、BIONDI, L.、FILIRA, F.、SCOLARO, B.

  DOI：——

  日期：——
• BIONDI, LAURA;CAVAGGION, FRANCO;FILIRA, FERNANDO;ROCCHI, RANIERO, GAZZ. CHIM. ITAL., 118,(1988) N 6, C. 427-433
  作者：BIONDI, LAURA、CAVAGGION, FRANCO、FILIRA, FERNANDO、ROCCHI, RANIERO

  DOI：——

  日期：——
• US9809586B2
  申请人：——

  公开号：US9809586B2

  公开（公告）日：2017-11-07
• [EN] INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE<br/>[FR] INHIBITEURS DE LA COLLAGÈNE PROLYL-4-HYDROXYLASE
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2016160706A1

  公开（公告）日：2016-10-06

  Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula (I) and salts thereof where: X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms; R1 and R2 independently are -OR7, or -NHSO2R8, where R7 is selected from: hydrogen, alkyl, alkenyl, alkoxyalkyl, -R'-CO-R", -R'-CO-O-R", -CO-R", -R'-O-CO-R", -R'-CO-NR", -CO-NR", or -R'-O-CO-NR", and R8 is selected from hydrogen, alkyl, aryl, arylalkyl; R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, haloalkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; -R'- is a divalent straight chain or branched alkylene, and-R" is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.