4-nitro-2-(3,5-dimethylphenyl)benzoyl methionine methyl ester | 180977-07-5

• 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: 4-nitro-2-(3,5-dimethylphenyl)benzoyl methionine methyl ester
• 英文别名: methyl (2S)-2-[[2-(3,5-dimethylphenyl)-4-nitrobenzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 180977-07-5
• 化学式: C₂₁H₂₄N₂O₅S
• 分子量: 416.498
• InChiKey: WLAUQJGYBWOFHM-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-nitro-2-(3,5-dimethylphenyl)benzoyl methionine methyl ester 在 三乙基硅烷 、 lithium hydroxide 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 14.0h， 生成 cysteinyl-4-amino-2-(3,5-dimethylphenyl)benzoyl methionine trifluoroacetate
  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：

  (2S)-2-氨基-4-甲硫基丁酸甲酯 、 4-Nitro-2-(3,5-dimethylphenyl)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 4-nitro-2-(3,5-dimethylphenyl)benzoyl methionine 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

文献信息

• Inhibitors of prenyl transferases
  申请人：Univeristy of Pittsburgh

  公开号：US05965539A1

  公开（公告）日：1999-10-12

  Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.

  抑制戊二烯基转移酶，特别是戊二烯基转移酶和戊二烯基转移酶I的化合物，制备这些化合物的方法，含有这些化合物的药物组合物，以及使用方法。
• Inhibitors of farnesyltransferase
  申请人：University of Pittsburgh

  公开号：US05834434A1

  公开（公告）日：1998-11-10

  Peptidomimetics of the formula C.beta.X where C is cysteine, X is any naturally occuring amino acid, and .beta. is a hydrophobic spacer, most notably 2-phenyl-4-aminobenzoic acid. These compounds are effective inhibitors of p2lras farnesyltrasferase, block Ras-dependent oncogenic signalling and inhibit human tumor growth in vivo in animal models. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also disclosed.

  公式为C.beta.X的肽类模拟物，其中C代表半胱氨酸，X代表任何自然存在的氨基酸，.beta.代表疏水间隔物，尤其是2-苯基-4-氨基苯甲酸。这些化合物是p2lras法尼基转移酶的有效抑制剂，可以阻断Ras依赖的致癌信号传导，并在动物模型中有效抑制人类肿瘤生长。还披露了通过功能化肽和肽类模拟物的末端氨基和羧基团制备的前药。这些功能化衍生物表现出增加的细胞摄取。还披露了其他结构修饰。
• INHIBITORS OF PRENYL TRANSFERASES
  申请人：UNIVERSITY OF PITTSBURGH

  公开号：EP0794789A1

  公开（公告）日：1997-09-17
• EP0794789A4
  申请人：——

  公开号：EP0794789A4

  公开（公告）日：1999-05-26
• US5834434A
  申请人：——

  公开号：US5834434A

  公开（公告）日：1998-11-10