NH2-VFM-OMe | 158022-24-3

• 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: NH2-VFM-OMe
• 英文别名: H-Val-Phe-Met-OMe；methyl (2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoate
• CAS: 158022-24-3
• 化学式: C₂₀H₃₁N₃O₄S
• 分子量: 409.55
• InChiKey: BWTVZWAUGWKOMN-ULQDDVLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  NH2-VFM-OMe 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-2-[[(2S)-2-[[(2S)-2-[(2-hydroxy-5-nitrobenzoyl)amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid
  参考文献：
  名称：

  Phenol-derived CVFM analog inhibitors of Ras Farnesyltransferase possessing cellular in vitro activity 1

  摘要：

  A study was performed on structure-activity relationships of a series of phenol-derived, CVFM analogs, inhibitors of Pas Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examined, while the VFM moiety of the potent inhibitor CVFM was kept constant. The FTase inhibitory activity, reported as IC50 in table I, was influenced by both the chemical properties and the relative position of the substituents on the phenolic ring. The most active compounds in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently we have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed, While most of the compounds were inactive, two showed a growth inhibitory effect: compound 4 was active against normal as well against transformed cells while derivative 13 was active only against transformed cells. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80031-7
• 作为产物：
  描述：

  benzyl (tert-butoxycarbonyl)-L-valyl-L-phenylalaninate 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 17.25h， 生成 NH2-VFM-OMe
  参考文献：
  名称：

  Phenol-derived CVFM analog inhibitors of Ras Farnesyltransferase possessing cellular in vitro activity 1

  摘要：

  A study was performed on structure-activity relationships of a series of phenol-derived, CVFM analogs, inhibitors of Pas Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examined, while the VFM moiety of the potent inhibitor CVFM was kept constant. The FTase inhibitory activity, reported as IC50 in table I, was influenced by both the chemical properties and the relative position of the substituents on the phenolic ring. The most active compounds in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently we have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed, While most of the compounds were inactive, two showed a growth inhibitory effect: compound 4 was active against normal as well against transformed cells while derivative 13 was active only against transformed cells. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80031-7

文献信息

• New asymmetric synthesis of protein farnesyltransferase inhibitors via palladium-catalyzed cross-coupling reactions of 2-iodo-imidazoles
  作者：Jennifer Kerhervé、Candice Botuha、Joëlle Dubois

  DOI：10.1039/b902601k

  日期：——

  cross-coupling reactions of 2-iodoimidazole have been studied to synthesize imidazole-containing protein farnesyltransferase inhibitors. The Suzuki coupling reaction proved to be very efficient to introduce functionalized alkyl chains at the 2-position of the imidazole ring and a new synthesis of the required alkenylboronates was realised by a reaction of cross metathesis. Asymmetric synthesis of allyl succinic

  钯 的催化交叉偶联反应 2-碘咪唑 已经研究合成 咪唑含蛋白质法呢基转移酶抑制剂。铃木偶联反应被证明非常有效地在咪唑环的2位引入官能化的烷基链，并且通过交叉复分解反应实现了所需烯基硼酸酯的新合成。烯丙基琥珀酸衍生物的不对称合成使我们能够通过Suzuki偶联合成手性蛋白法呢基转移酶抑制剂，并确定我们抑制剂的立体化学对酶活性的影响。
• Synthesis and biological evaluation of potential bisubstrate inhibitors of protein farnesyltransferase. Design and synthesis of functionalized imidazoles
  作者：Renata Marcia de Figueiredo、Laëtitia Coudray、Joëlle Dubois

  DOI：10.1039/b709854e

  日期：——

  A novel series of compounds, derived from 2,5-functionalized imidazoles, have been synthesized as potential bisubstrate inhibitors of protein farnesyltransferase (FTase) using structure-based design. These compounds have a 1,4-diacid chain and a tripeptide connected by an imidazole ring. The synthetic strategy relies on the functionalization at the C-2 position of the heterocycle with the diacid side

  使用基于结构的设计，已经合成了一系列新的化合物，这些化合物衍生自2,5-官能化的咪唑，作为蛋白质法呢基转移酶（FTase）的潜在双底物抑制剂。这些化合物具有1，4-二酸链和通过咪唑环连接的三肽。合成策略依赖于杂环的C-2位具有二酸侧链的功能化和C-5位的肽偶联。以高收率合成了几种新化合物。活性最高的化合物的动力学实验表明，取决于二酸链长，结合方式不同。