2(S)-[2-(o-methoxyphenyl)-4-(2(R)-1,4-benzodioxan-2-ylmethylaminocarbonyl)benzamido]-4-methylthiobutyric acid methyl ester | 1191885-90-1

• 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(S)-[2-(o-methoxyphenyl)-4-(2(R)-1,4-benzodioxan-2-ylmethylaminocarbonyl)benzamido]-4-methylthiobutyric acid methyl ester
• 英文别名: methyl (2S)-2-[[4-[[(3R)-2,3-dihydro-1,4-benzodioxin-3-yl]methylcarbamoyl]-2-(2-methoxyphenyl)benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 1191885-90-1
• 化学式: C₃₀H₃₂N₂O₇S
• 分子量: 564.659
• InChiKey: LOLPBMSXYFJANG-YKSBVNFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-5-(((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)carbamoyl)-2'-methoxy-[1,1'-biphenyl]-2-carboxylic acid 、 L-蛋氨酸甲酯盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.25h， 生成 2(S)-[2-(o-methoxyphenyl)-4-(2(R)-1,4-benzodioxan-2-ylmethylaminocarbonyl)benzamido]-4-methylthiobutyric acid methyl ester
  参考文献：
  名称：

  New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2'-methyl or 2'-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester Of L-methionine, glycine or L-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for anti proliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2'-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.065

文献信息

• New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition
  作者：Cristiano Bolchi、Marco Pallavicini、Laura Fumagalli、Nicola Ferri、Alberto Corsini、Chiara Rusconi、Ermanno Valoti

  DOI：10.1016/j.bmcl.2009.07.065

  日期：2009.9

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2'-methyl or 2'-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester Of L-methionine, glycine or L-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for anti proliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2'-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.