propan-2-yl (2S)-2-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-2-thiophen-2-ylbenzoyl]amino]-4-methylsulfanylbutanoate | 1613316-35-0

• 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: propan-2-yl (2S)-2-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-2-thiophen-2-ylbenzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 1613316-35-0
• 化学式: C₂₈H₃₁NO₆S₂
• 分子量: 541.689
• InChiKey: SKLWCFDYUHSUIT-AKRCKQFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  propan-2-yl (2S)-2-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-2-thiophen-2-ylbenzoyl]amino]-4-methylsulfanylbutanoate 在 甲醇 、 sodium hydroxide 作用下， 反应 18.0h， 以100%的产率得到(2S)-2-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-2-thiophen-2-ylbenzoyl]amino]-4-methylsulfanylbutanoic acid
  参考文献：
  名称：

  Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4-thiazoly-lacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.078
• 作为产物：
  描述：

  2-溴-4-羟基苯甲酸甲酯 在 甲醇 、 sodium phosphate dodecahydrate 、 四(三苯基膦)钯 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.5h， 生成 propan-2-yl (2S)-2-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)-2-thiophen-2-ylbenzoyl]amino]-4-methylsulfanylbutanoate
  参考文献：
  名称：

  Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4-thiazoly-lacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.078

文献信息

• Farnesyltransferase inhibitors: CAAX mimetics based on different biaryl scaffolds
  作者：Valentina Straniero、Marco Pallavicini、Giuseppe Chiodini、Paola Ruggeri、Laura Fumagalli、Cristiano Bolchi、Alberto Corsini、Nicola Ferri、Chiara Ricci、Ermanno Valoti

  DOI：10.1016/j.bmcl.2014.04.078

  日期：2014.7

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed as farnesyltransferase (FTase) inhibitors (FTIs) by replacing AA with o-aryl or o-heteroaryl substituted p-hydroxy- or p-aminobenzoic acid, while maintaining the replacement of C with 1,4-benzodioxan-2-ylmethyl or 2-amino-4-thiazoly-lacetyl residue as in previous CAAX mimetics. Both FTase inhibition and antiproliferative effect were showed by two thiazole derivatives, namely those with 1-naphthyl (10 and 10a) or 3-furanyl (15 and 15a) in the central spacer, and by the benzodioxane derivative with 2-thienyl (6 and 6a) in the same position. Accumulation of unprenylated RAS was demonstrated in cells incubated with 15a. Consistently with FTIs literature, such results delineate the biaryl scaffold not only as a spacer but also as a sensible area of these mimetic molecules, where modifications at the branching aromatic ring are not indifferent and should be matter of further investigation. (C) 2014 Elsevier Ltd. All rights reserved.