N-[4-[N-[2(R)-(tert-butoxycarbonyl)amino-3-(triphenylmethyl)thio]propyl]amino-2-phenylbenzoyl]-methionine methyl ester | 180977-20-2

• 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: N-[4-[N-[2(R)-(tert-butoxycarbonyl)amino-3-(triphenylmethyl)thio]propyl]amino-2-phenylbenzoyl]-methionine methyl ester
• 英文别名: 4-[2(R)-tert-butoxycarbonylamino-3-triphenylmethylthiopropyl]amino-2-phenylbenzoyl-(S)-methionine methyl ester；methyl (2S)-2-[[4-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]-2-phenylbenzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 180977-20-2
• 化学式: C₄₆H₅₁N₃O₅S₂
• 分子量: 790.06
• InChiKey: CZJVMLLLUVKMMU-UMBAWLCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  56
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[4-[N-[2(R)-(tert-butoxycarbonyl)amino-3-(triphenylmethyl)thio]propyl]amino-2-phenylbenzoyl]-methionine methyl ester 在 mercury dichloride 、 硫化氢 、 盐酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 0.33h， 以81%的产率得到N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]-methionine methyl ester hydrochloride
  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：

  N-[4-nitro-2-phenylbenzoyl]-methionine methyl ester 在 盐酸 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 16.17h， 生成 N-[4-[N-[2(R)-(tert-butoxycarbonyl)amino-3-(triphenylmethyl)thio]propyl]amino-2-phenylbenzoyl]-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。
• US5965539A
  申请人：——

  公开号：US5965539A

  公开（公告）日：1999-10-12
• Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors
  作者：Yimin Qian、Juan Jose Marugan、Renae D. Fossum、Andreas Vogt、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1016/s0968-0896(99)00252-7

  日期：1999.12

  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.