(S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propionylamino)-3-methoxy-benzoylamino]-4-methylsulfanyl-butyric acid methyl ester | 180977-01-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propionylamino)-3-methoxy-benzoylamino]-4-methylsulfanyl-butyric acid methyl ester
• 英文别名: methyl (2S)-2-[[3-methoxy-4-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropanoyl]amino]benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 180977-01-9
• 化学式: C₄₁H₄₇N₃O₇S₂
• 分子量: 757.972
• InChiKey: ODEJDRCXHIUJQN-HEVIKAOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.28
• 重原子数：
  53.0
• 可旋转键数：
  16.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  132.06
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propionylamino)-3-methoxy-benzoylamino]-4-methylsulfanyl-butyric acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propionylamino)-3-methoxy-benzoylamino]-4-methylsulfanyl-butyric acid
  参考文献：
  名称：

  Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors

  摘要：

  Cysteine farnesylation at the carboxylate terminal tetrapeptide CAAX of Ras protein is catalyzed by farnesyltransferase. This lipid modification is necessary for regulatory function of both normal and oncogenic Ras. The high frequency of Ras mutation in human cancers has prompted an intensive study on finding ways of controlling oncogenic Ras function. Inhibition of farnesyltransferase is among the most sought after targets for cancer chemotherapy. We report here the design, synthesis and biological characterization of a series of peptidomimetics as farnesyltransferase inhibitors. These compounds are extremely potent towards farnesyltransferase with IC50 values ranging from subnanomolar to low nanomolar concentrations. They have a high selectivity for farnesyltransferase over the closely related geranylgeranyltransferase-I. Structure-activity relationship studies demonstrated that a properly positioned hydrophobic group significantly enhanced inhibition potency, reflecting an improved complementarity to the large hydrophobic pocket in the CAAX binding site. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00252-7
• 作为产物：
  描述：

  4-氨基-3-甲氧基苯甲酸 在 盐酸 、 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 13.5h， 生成 (S)-2-[4-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propionylamino)-3-methoxy-benzoylamino]-4-methylsulfanyl-butyric acid methyl ester
  参考文献：
  名称：

  Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors

  摘要：

  Cysteine farnesylation at the carboxylate terminal tetrapeptide CAAX of Ras protein is catalyzed by farnesyltransferase. This lipid modification is necessary for regulatory function of both normal and oncogenic Ras. The high frequency of Ras mutation in human cancers has prompted an intensive study on finding ways of controlling oncogenic Ras function. Inhibition of farnesyltransferase is among the most sought after targets for cancer chemotherapy. We report here the design, synthesis and biological characterization of a series of peptidomimetics as farnesyltransferase inhibitors. These compounds are extremely potent towards farnesyltransferase with IC50 values ranging from subnanomolar to low nanomolar concentrations. They have a high selectivity for farnesyltransferase over the closely related geranylgeranyltransferase-I. Structure-activity relationship studies demonstrated that a properly positioned hydrophobic group significantly enhanced inhibition potency, reflecting an improved complementarity to the large hydrophobic pocket in the CAAX binding site. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00252-7