propan-2-yl (2S)-2-[[2-(2-methylphenyl)-4-[[2-(2-sulfanylidene-3H-1,3-thiazol-4-yl)acetyl]amino]benzoyl]amino]-4-methylsulfanylbutanoate | 1334402-18-4

• 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-[[2-(2-methylphenyl)-4-[[2-(2-sulfanylidene-3H-1,3-thiazol-4-yl)acetyl]amino]benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 1334402-18-4
• 化学式: C₂₇H₃₁N₃O₄S₃
• 分子量: 557.759
• InChiKey: HZGXVNDKXMRECA-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  propan-2-yl (2S)-2-[[2-(2-methylphenyl)-4-[[2-(2-sulfanylidene-3H-1,3-thiazol-4-yl)acetyl]amino]benzoyl]amino]-4-methylsulfanylbutanoate 在 甲醇 、 potassium hydroxide 作用下， 反应 15.0h， 生成 (2S)-2-[[2-(2-methylphenyl)-4-[[2-(2-sulfanylidene-3H-1,3-thiazol-4-yl)acetyl]amino]benzoyl]amino]-4-methylsulfanylbutanoic acid
  参考文献：
  名称：

  Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.003
• 作为产物：
  描述：

  在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 propan-2-yl (2S)-2-[[2-(2-methylphenyl)-4-[[2-(2-sulfanylidene-3H-1,3-thiazol-4-yl)acetyl]amino]benzoyl]amino]-4-methylsulfanylbutanoate
  参考文献：
  名称：

  Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.003

文献信息

• Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase
  作者：Cristiano Bolchi、Marco Pallavicini、Sergio K. Bernini、Giuseppe Chiodini、Alberto Corsini、Nicola Ferri、Laura Fumagalli、Valentina Straniero、Ermanno Valoti

  DOI：10.1016/j.bmcl.2011.07.003

  日期：2011.9

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics. (C) 2011 Elsevier Ltd. All rights reserved.