(2S,4E,7S)-2,7-bis(benzyloxycarbonylamino)oct-4-en-1,8-dioic acid | 314728-13-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,4E,7S)-2,7-bis(benzyloxycarbonylamino)oct-4-en-1,8-dioic acid
• 英文别名: (E,2S,7S)-2,7-bis(phenylmethoxycarbonylamino)oct-4-enedioic acid
• CAS: 314728-13-7
• 化学式: C₂₄H₂₆N₂O₈
• 分子量: 470.479
• InChiKey: SLCVTPKXSONMGL-RLFQVEEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4E,7S)-2,7-bis(benzyloxycarbonylamino)oct-4-en-1,8-dioic acid 在 RhCl(PPh₃)3 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 20.0 ℃ 、2.76 MPa 条件下， 反应 132.0h， 生成 benzyl N-[(2S,7S)-1,8-dioxo-1,8-bis[[2-oxo-2-[3-(propylamino)propylamino]ethyl]amino]-7-(phenylmethoxycarbonylamino)octan-2-yl]carbamate
  参考文献：
  名称：

  Inhibition of Trypanothione Reductase by Substrate Analogues

  摘要：

  [GRAPHICS]Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K-i values ranging from 30 to 91 muM.

  DOI：

  10.1021/ol0065423
• 作为产物：
  描述：

  N-Cbz-L-天冬氨酸 1-甲酯 在 碳酸氢钠 盐酸 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 lithium hydroxide 、 sodium hypochlorite 、 9-borabicyclo[3.3.1]nonane dimer 、 正丁基锂 、 四溴化碳 、 硼烷 、 三乙胺 、 三苯基膦 、 sodium bromide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 57.67h， 生成 (2S,4E,7S)-2,7-bis(benzyloxycarbonylamino)oct-4-en-1,8-dioic acid
  参考文献：
  名称：

  Inhibition of Trypanothione Reductase by Substrate Analogues

  摘要：

  [GRAPHICS]Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K-i values ranging from 30 to 91 muM.

  DOI：

  10.1021/ol0065423

文献信息

• Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase
  作者：Michael H. Duyzend、Christopher T. Clark、Shayna L. Simmons、Wade B. Johnson、Anna M. Larson、Aaron M. Leconte、Andrew W. Wills、Matthew Ginder-Vogel、April K. Wilhelm、Josephine A. Czechowicz、David G. Alberg

  DOI：10.3109/14756366.2011.604319

  日期：2012.12.1

  Trypanothione reductase (TR) is found in the trypanosomatid parasites, where it catalyses the NADPH-dependent reduction of the glutathione analogue, trypanothione, and is a key player in the parasite's defenses against oxidative stress. TR is a promising target for the development of antitrypanosomal drugs; here, we report our synthesis and evaluation of compounds 3-5 as low micromolar Trypanosoma

  在锥虫的寄生虫中发现了锥虫硫磷还原酶（TR），它催化NADPH依赖性的谷胱甘肽类似物锥虫硫磷还原，并且是寄生虫防御氧化应激的关键因素。TR是开发抗锥虫药物的有希望的目标；在这里，我们报告了作为低微摩尔克氏锥虫TR抑制剂的化合物3-5的合成和评估。尽管将4和5设计为潜在的不可逆抑制剂，但这些化合物以及3均显示出可逆的竞争抑制作用。化合物3被证明是最有效的抑制剂，K（i）= 2 µM。
• Inhibition of Trypanothione Reductase by Substrate Analogues
  作者：Elizabeth A. Garrard、Emily C. Borman、Brian N. Cook、Emily J. Pike、David G. Alberg

  DOI：10.1021/ol0065423

  日期：2000.11.1

  [GRAPHICS]Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K-i values ranging from 30 to 91 muM.