N-isobutyryl-L-cysteine methyl ester

• 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: N-isobutyryl-L-cysteine methyl ester
• 英文别名: methyl (2R)-2-(2-methylpropanoylamino)-3-sulfanylpropanoate
• 化学式: C₈H₁₅NO₃S
• 分子量: 205.278
• InChiKey: JULKWKBSOSTPCV-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  56.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-半胱氨酸甲酯盐酸盐 、 异丁酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-isobutyryl-L-cysteine methyl ester
  参考文献：
  名称：

  Preclinical Characterization of 3β-(N-Acetyl l-cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer

  摘要：

  The transcription factor STAT3 is a potential target for the treatment of castration-resistant prostate cancer. Galiellalactone (1), a direct inhibitor of STAT3, prevents the transcription of STAT3 regulated genes. In this study we characterized 6 (GPAS12, Johansson, M.; Sterner, O. Patent WO 2015/132396 A1, 2015), a prodrug of 1. In vitro studies showed that 6 is rapidly converted to 1 in plasma and is stable in a buffer solution. The pharmacokinetics of 6 following a single oral dose indicated that the prodrug was rapidly absorbed and converted to 1 with a t(max) of 15 min. Oral administration of 6 in mice increased the plasma exposure of the active parent compound 20-fold compared to when 1 was dosed orally. 6 treated mice bearing DU145 xenograft tumors had significantly reduced tumor growth compared to untreated mice. The favorable druglike properties and safety profile of 6 warrant further studies of 6 for the treatment of castration-resistant prostate cancer.

  DOI：

  10.1021/acs.jmedchem.5b01814

文献信息

• Development of a Cysteine-Catalyzed Enantioselective Rauhut−Currier Reaction
  作者：Carrie E. Aroyan、Alpay Dermenci、Scott J. Miller

  DOI：10.1021/jo101018t

  日期：2010.9.3

  Herein, we report a full account of the development of an enantioselective Rauhut-Currier process that affords products in high yields and enantioselectivities using a cysteine-based catalyst. While traditional Morita-Baylis-Hillman catalysts were found to be essentially ineffective, various derivatives of protected cysteine were found to exhibit extraordinary reactivity and enantiotopic control. Extensive screening of reaction conditions led us to discover the enhanced effects of water as an additive and the chelating power of potassium in achieving higher enantiomer ratios. Mechanistic experiments also provided insight on the potential mechanism of the reaction in addition to possible transition states that provide the absolute stereochemistry formed in the observed products. Also included is a brief survey of the reaction scope involving different ring sizes as well as functionalized substrates.
• Enantioselective Rauhut−Currier Reactions Promoted by Protected Cysteine
  作者：Carrie E. Aroyan、Scott J. Miller

  DOI：10.1021/ja067139f

  日期：2007.1.1

  We report highly enantioselective examples of the Rauhut-Currier cycloisomerization reaction (the "vinylogous Morita-Baylis-Hillman reaction"). The reaction is highly practical and is catalyzed by a commercially available derivative of the proteinogenic amino acid cysteine. Reactions are conducted in the presence of potassium tert-butoxide and a critical concentration of water in bulk acetonitrile. A mechanistic model is advanced that may account for reaction selectivity that is predicated on organizational chelation of K ion in the product-determining step in which the Cys derivative undergoes limination.
• Preclinical Characterization of 3β-(<i>N</i>-Acetyl <scp>l</scp>-cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer
  作者：Zilma Escobar、Anders Bjartell、Giacomo Canesin、Susan Evans-Axelsson、Olov Sterner、Rebecka Hellsten、Martin H Johansson

  DOI：10.1021/acs.jmedchem.5b01814

  日期：2016.5.26

  The transcription factor STAT3 is a potential target for the treatment of castration-resistant prostate cancer. Galiellalactone (1), a direct inhibitor of STAT3, prevents the transcription of STAT3 regulated genes. In this study we characterized 6 (GPAS12, Johansson, M.; Sterner, O. Patent WO 2015/132396 A1, 2015), a prodrug of 1. In vitro studies showed that 6 is rapidly converted to 1 in plasma and is stable in a buffer solution. The pharmacokinetics of 6 following a single oral dose indicated that the prodrug was rapidly absorbed and converted to 1 with a t(max) of 15 min. Oral administration of 6 in mice increased the plasma exposure of the active parent compound 20-fold compared to when 1 was dosed orally. 6 treated mice bearing DU145 xenograft tumors had significantly reduced tumor growth compared to untreated mice. The favorable druglike properties and safety profile of 6 warrant further studies of 6 for the treatment of castration-resistant prostate cancer.