2-[(S)-3-(4-Benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-2-methyl-propionic acid methyl ester | 184002-52-6

• 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: 2-[(S)-3-(4-Benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-2-methyl-propionic acid methyl ester
• 英文别名: Boc-Tyr(OBn)-Aib-OMe；methyl 2-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-phenylmethoxyphenyl)propanoyl]amino]propanoate
• CAS: 184002-52-6
• 化学式: C₂₆H₃₄N₂O₆
• 分子量: 470.566
• InChiKey: GFHWSASXBVWLLN-NRFANRHFSA-N

物化性质

• 沸点：
  641.0±55.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(S)-3-(4-Benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-2-methyl-propionic acid methyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide 、 正丁基锂 、 四丁基氟化铵 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 7.67h， 生成 tert-butyl N-[(2S)-1-[[1-[[1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

  摘要：

  N-4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of am-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N-4 prevented nonspecific proteolytic cleavage in biological medium. Aln-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N-4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N-4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00153-8
• 作为产物：
  描述：

  2-氨基异丁酸甲酯盐酸盐 、 symmetric anhydride of Boc-Tyr(Bzl)-OH 在 N-甲基吗啉 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-[(S)-3-(4-Benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-2-methyl-propionic acid methyl ester
  参考文献：
  名称：

  Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

  摘要：

  N-4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of am-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N-4 prevented nonspecific proteolytic cleavage in biological medium. Aln-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N-4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N-4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00153-8

文献信息

• Peptidyl prodrugs and methods of making and using the same
  申请人：University of Pittsburgh of the Commonwealth System of Higher Education

  公开号：US05952294A1

  公开（公告）日：1999-09-14

  Peptidyl prodrugs of therapeutic agents having an activating function are sclosed. These therapeutic agents having activating functions include those having an amino, thiol, or hydroxyl function. Methods of making and using these prodrugs are also disclosed.

  本发明涉及具有激活功能的治疗剂的肽类前药。这些具有激活功能的治疗剂包括具有氨基，巯基或羟基功能的治疗剂。本发明还公开了制备和使用这些前药的方法。