(2-{benzyl[2-(toluene-4-sulfonyloxymethyl)acryloyl]amino}-4-methylpentanoylamino)acetic acid benzyl ester | 1353048-80-2

• 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: (2-{benzyl[2-(toluene-4-sulfonyloxymethyl)acryloyl]amino}-4-methylpentanoylamino)acetic acid benzyl ester
• 英文别名: Benzyl 2-[[2-[benzyl-[2-[(4-methylphenyl)sulfonyloxymethyl]prop-2-enoyl]amino]-4-methylpentanoyl]amino]acetate
• CAS: 1353048-80-2
• 化学式: C₃₃H₃₈N₂O₇S
• 分子量: 606.74
• InChiKey: WRFCRJKZHCBQIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  43
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-{benzyl[2-(toluene-4-sulfonyloxymethyl)acryloyl]amino}-4-methylpentanoylamino)acetic acid benzyl ester 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 13.0h， 以93%的产率得到{2-[benzyl(2-iodomethylacryloyl)amino]-4-methylpentanoylamino}acetic acid benzyl ester
  参考文献：
  名称：

  Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System

  摘要：

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.

  DOI：

  10.1021/jm201359d
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 在 4-二甲氨基吡啶 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 63.0h， 生成 (2-{benzyl[2-(toluene-4-sulfonyloxymethyl)acryloyl]amino}-4-methylpentanoylamino)acetic acid benzyl ester
  参考文献：
  名称：

  Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System

  摘要：

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.

  DOI：

  10.1021/jm201359d

文献信息

• Studies toward Novel Peptidomimetic Inhibitors of Thioredoxin–Thioredoxin Reductase System
  作者：Szymon Kłossowski、Angelika Muchowicz、Małgorzata Firczuk、Marta Świech、Adam Redzej、Jakub Golab、Ryszard Ostaszewski

  DOI：10.1021/jm201359d

  日期：2012.1.12

  Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-kappa B and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.