L-((pyrrolidinyl) hexanoyl)-S-(trans,trans-farnesyl)cysteine methyl ester | 1616271-70-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: L-((pyrrolidinyl) hexanoyl)-S-(trans,trans-farnesyl)cysteine methyl ester
• CAS: 1616271-70-5
• 化学式: C₂₉H₅₀N₂O₃S
• 分子量: 506.794
• InChiKey: RWCJGZUMEYRRKE-YQULFABTSA-N

物化性质

• 沸点：
  636.3±55.0 °C(predicted)
• 密度：
  1.011±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.45
• 重原子数：
  35.0
• 可旋转键数：
  18.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  58.64
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  哌啶 、 L-((pyrrolidinyl) hexanoyl)-S-(trans,trans-farnesyl)cysteine methyl ester 以 neat (no solvent) 为溶剂， 以26%的产率得到N-((R)-1-oxo-1-(piperidin-1-yl)-3-((trans,trans-farnesyl)thio)propan-2-yl)-6-(pyrrolidin-1-yl)hexanamide
  参考文献：
  名称：

  Polyisoprenylated methylated protein methyl esterase: A putative biomarker and therapeutic target for pancreatic cancer

  摘要：

  Pancreatic cancer is the most deadly neo plasm with a 5-year survival rate of less than 6%. Over 90% of cases harbor K-Ras mutations, which are the most challenging to treat due to lack of effective therapies. Here, we reveal that polyisoprenylated methylated protein methyl esterase (PMPMEase) is overexpressed in 93% of pancreatic ductal adenocarcinoma. We further present polyisoprenylated cysteinyl amide inhibitors (PCAIs) as novel compounds designed with structural elements for optimal in vivo activities and selective disruption of polyisoprenylation-mediated protein functions. The PCAIs inhibited PMPMEase with K-i values ranging from 3.7 to 20 mu M. The 48 h E-50 values for pancreatic cancer Mia PaCa-2 and BxPC-3 cell lines were as low as 1.9 mu M while salirasib and farnesylthiosalicylamide were ineffective at 20 mu M. The PCAIs thus have the potential to serve as effective therapies for pancreatic and other cancers with hyperactive growth signaling pathways mediated by Ras and related G-proteins. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.018
• 作为产物：
  描述：

  反式,反式-金合欢醇 在 氨 、 三溴化磷 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 甲苯 为溶剂， 反应 5.0h， 生成 L-((pyrrolidinyl) hexanoyl)-S-(trans,trans-farnesyl)cysteine methyl ester
  参考文献：
  名称：

  Polyisoprenylated methylated protein methyl esterase: A putative biomarker and therapeutic target for pancreatic cancer

  摘要：

  Pancreatic cancer is the most deadly neo plasm with a 5-year survival rate of less than 6%. Over 90% of cases harbor K-Ras mutations, which are the most challenging to treat due to lack of effective therapies. Here, we reveal that polyisoprenylated methylated protein methyl esterase (PMPMEase) is overexpressed in 93% of pancreatic ductal adenocarcinoma. We further present polyisoprenylated cysteinyl amide inhibitors (PCAIs) as novel compounds designed with structural elements for optimal in vivo activities and selective disruption of polyisoprenylation-mediated protein functions. The PCAIs inhibited PMPMEase with K-i values ranging from 3.7 to 20 mu M. The 48 h E-50 values for pancreatic cancer Mia PaCa-2 and BxPC-3 cell lines were as low as 1.9 mu M while salirasib and farnesylthiosalicylamide were ineffective at 20 mu M. The PCAIs thus have the potential to serve as effective therapies for pancreatic and other cancers with hyperactive growth signaling pathways mediated by Ras and related G-proteins. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.018