(R)-ethyl 2-((R)-2-aMino-3-(benzylthio)propanaMido)-2-phenylacetate | 874096-43-2

• 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: (R)-ethyl 2-((R)-2-aMino-3-(benzylthio)propanaMido)-2-phenylacetate
• 英文别名: ethyl (2R)-2-[[(2R)-2-amino-3-benzylsulfanylpropanoyl]amino]-2-phenylacetate
• CAS: 874096-43-2
• 化学式: C₂₀H₂₄N₂O₃S
• 分子量: 372.488
• InChiKey: YGKYCIPBLRIHEF-ZWKOTPCHSA-N

物化性质

• 沸点：
  563.6±50.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-ethyl 2-((R)-2-aMino-3-(benzylthio)propanaMido)-2-phenylacetate 在 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Peptide-bond modified glutathione conjugate analogs modulate GSTπ function in GSH-conjugation, drug sensitivity and JNK signaling

  摘要：

  Glutathione S-transferase pi (CST, E.C.2.5.1.18) overexpression contributes to resistance of cancer cells towards cytostatic drugs. Furthermore, GST pi is involved in the cellular stress response through inhibition of Jun N-terminal-kinase (JNK), a process that can be modulated by CST inhibitors. GSH conjugates are potent CST inhibitors, but are sensitive towards gamma-glutamyltranspeptidase (gamma GT)-mediated breakdown. In search for new peptidase stable CST inhibitors we employed the following strategy: (1) selection of a suitable (GST inhibiting) peptide-bond isostere from a series of previously synthesized gamma GT stabilized GSH-analogs. (2) The use of this peptidomimetic strategy to prepare a GSTT, selective inhibitor. Two gamma GT stable GSH conjugate analogs inhibited human GSTs, although non-selectively. One of these, a urethane-type peptide-bond is well accepted by GSTs and we selected this modification for the development of a gamma GT stable, GST pi selective inhibitor, UrPhg-Et-2. This compound displayed selectivity for GST pi compared to alpha and mu class enzymes. Furthermore, the inhibitor reversed GST pi-mediated drug resistance (MDR) in breast tumor cells. In addition, short-term exposure of cells to UrPhg-Et-2 led to GST pi oligornerization and JNK activation, suggesting that it activates the JNK-cJun signaling module through GST pi dissociation. Altogether, we show the successful use of peptidomimetic glutathione conjugate analogs as CST inhibitors and MDR-modifiers. As many MDR related enzymes, such as MRP1, glyoxalase 1 and DNA-pk are also inhibited by GSH conjugates, these peptidomimetic compounds can be used as scaffolds for the development of multi-target MDR drugs. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.11.003
• 作为产物：
  描述：

  Boc-S-苄基-L-半光氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-ethyl 2-((R)-2-aMino-3-(benzylthio)propanaMido)-2-phenylacetate
  参考文献：
  名称：

  Peptide-bond modified glutathione conjugate analogs modulate GSTπ function in GSH-conjugation, drug sensitivity and JNK signaling

  摘要：

  Glutathione S-transferase pi (CST, E.C.2.5.1.18) overexpression contributes to resistance of cancer cells towards cytostatic drugs. Furthermore, GST pi is involved in the cellular stress response through inhibition of Jun N-terminal-kinase (JNK), a process that can be modulated by CST inhibitors. GSH conjugates are potent CST inhibitors, but are sensitive towards gamma-glutamyltranspeptidase (gamma GT)-mediated breakdown. In search for new peptidase stable CST inhibitors we employed the following strategy: (1) selection of a suitable (GST inhibiting) peptide-bond isostere from a series of previously synthesized gamma GT stabilized GSH-analogs. (2) The use of this peptidomimetic strategy to prepare a GSTT, selective inhibitor. Two gamma GT stable GSH conjugate analogs inhibited human GSTs, although non-selectively. One of these, a urethane-type peptide-bond is well accepted by GSTs and we selected this modification for the development of a gamma GT stable, GST pi selective inhibitor, UrPhg-Et-2. This compound displayed selectivity for GST pi compared to alpha and mu class enzymes. Furthermore, the inhibitor reversed GST pi-mediated drug resistance (MDR) in breast tumor cells. In addition, short-term exposure of cells to UrPhg-Et-2 led to GST pi oligornerization and JNK activation, suggesting that it activates the JNK-cJun signaling module through GST pi dissociation. Altogether, we show the successful use of peptidomimetic glutathione conjugate analogs as CST inhibitors and MDR-modifiers. As many MDR related enzymes, such as MRP1, glyoxalase 1 and DNA-pk are also inhibited by GSH conjugates, these peptidomimetic compounds can be used as scaffolds for the development of multi-target MDR drugs. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.11.003

文献信息

• Glutathione analogs and paralog panels comprising glutathione mimics
  申请人：Terrapin Technologies, Inc.

  公开号：US05599903A1

  公开（公告）日：1997-02-04

  Compounds of the formula ##STR1## or the alkyl (1-6 C), alkenyl (1-6 C), or arylalkyl (7-12 C) amides or salts including the cycloamido forms thereof; wherein n is 1 or 2; wherein when n is 1, X is a mono- or disubstituted or unsubstituted hydrocarbyl (1-20 C) moiety optionally containing 1 or 2 nonadjacent heteroatoms (O, S or N), and wherein said substitution is selected from the group consisting of halo, OR, and SR, wherein R is H or lower alkyl (1-4 C); when n is 2, one X is as above defined and the other X is lower alkyl (1-4 C); Y is selected from the group consisting of ##STR2## wherein m is 1 or 2; and AA.sub.C is an amino acid coupled through a peptide bond to the remainder of the compound of formula 1, are useful as affinity ligands, elution reagents, solution inhibitors, diagnostic reagents and therapeutics. These compounds and analogous tripeptide glutathione analogs can be used as members of panels to obtain specific characteristic profiles for various glutathione-S-transferases.

  公式为##STR1##的化合物或烷基（1-6 C），烯基（1-6 C）或芳基烷基（7-12 C）酰胺或盐，包括其环形酰胺形式; 其中n为1或2; 当n为1时，X是单取代，双取代或未取代的碳氢化合物（1-20 C）基团，可选地含有1或2个非相邻杂原子（O，S或N），其中所述取代基被选自卤素，OR和SR的群，其中R为H或较低的烷基（1-4 C）; 当n为2时，一个X如上所述定义，另一个X是较低的烷基（1-4 C）; Y被选自##STR2##其中m为1或2; AA.sub.C是通过肽键与公式1的余下部分耦合的氨基酸，可用作亲和配体，洗脱试剂，溶液抑制剂，诊断试剂和治疗剂。这些化合物和类似的三肽谷胱甘肽类似物可用作面板的成员，以获得各种谷胱甘肽S-转移酶的特定特征剖面。
• PREPARATION OF CRYSTALLINE EZATIOSTAT HYDROCHLORIDE ANSOLVATE FORM D
  申请人：LECLERC Guyselaine

  公开号：US20110301376A1

  公开（公告）日：2011-12-08

  Provided herein are processes of preparing ezatiostat hydrochloride, and crystalline ezatiostat hydrochloride ansolvate form D.
• US8841476B2
  申请人：——

  公开号：US8841476B2

  公开（公告）日：2014-09-23
• [EN] PREPARATION OF CRYSTALLINE EZATIOSTAT HYDROCHLORIDE ANSOLVATE FORM D<br/>[FR] PRÉPARATION DE LA FORME D ANSOLVATE DU CHLORHYDRATE D'EZATIOSTAT CRISTALLIN
  申请人：TELIK INC

  公开号：WO2011156061A1

  公开（公告）日：2011-12-15

  Provided herein are processes of preparing ezatiostat hydrochloride, and crystalline ezatiostat hydrochloride ansolvate form D.
• Peptide-bond modified glutathione conjugate analogs modulate GSTπ function in GSH-conjugation, drug sensitivity and JNK signaling
  作者：Danny Burg、Joey Riepsaame、Chantal Pont、Gerard Mulder、Bob van de Water

  DOI：10.1016/j.bcp.2005.11.003

  日期：2006.1

  Glutathione S-transferase pi (CST, E.C.2.5.1.18) overexpression contributes to resistance of cancer cells towards cytostatic drugs. Furthermore, GST pi is involved in the cellular stress response through inhibition of Jun N-terminal-kinase (JNK), a process that can be modulated by CST inhibitors. GSH conjugates are potent CST inhibitors, but are sensitive towards gamma-glutamyltranspeptidase (gamma GT)-mediated breakdown. In search for new peptidase stable CST inhibitors we employed the following strategy: (1) selection of a suitable (GST inhibiting) peptide-bond isostere from a series of previously synthesized gamma GT stabilized GSH-analogs. (2) The use of this peptidomimetic strategy to prepare a GSTT, selective inhibitor. Two gamma GT stable GSH conjugate analogs inhibited human GSTs, although non-selectively. One of these, a urethane-type peptide-bond is well accepted by GSTs and we selected this modification for the development of a gamma GT stable, GST pi selective inhibitor, UrPhg-Et-2. This compound displayed selectivity for GST pi compared to alpha and mu class enzymes. Furthermore, the inhibitor reversed GST pi-mediated drug resistance (MDR) in breast tumor cells. In addition, short-term exposure of cells to UrPhg-Et-2 led to GST pi oligornerization and JNK activation, suggesting that it activates the JNK-cJun signaling module through GST pi dissociation. Altogether, we show the successful use of peptidomimetic glutathione conjugate analogs as CST inhibitors and MDR-modifiers. As many MDR related enzymes, such as MRP1, glyoxalase 1 and DNA-pk are also inhibited by GSH conjugates, these peptidomimetic compounds can be used as scaffolds for the development of multi-target MDR drugs. (c) 2005 Elsevier Inc. All rights reserved.