L-alanyl-2-(5-fluorouracil-1-yl)-L-glycine | 89625-90-1

• 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: L-alanyl-2-(5-fluorouracil-1-yl)-L-glycine
• 英文别名: 2-[[(2S)-2-aminopropanoyl]amino]-2-(5-fluoro-2,4-dioxo-pyrimidin-1-yl)acetic acid；2-[[(2S)-2-aminopropanoyl]amino]-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetic acid
• CAS: 89625-90-1
• 化学式: C₉H₁₁FN₄O₅
• 分子量: 274.209
• InChiKey: KIKHXLDDKLVSNQ-WWLRPLJCSA-N

物化性质

• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  142
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  Cbz-(S)-alanyl-(2R,S)-acetoxyglycine benzyl ester 在 palladium on activated charcoal 三乙胺 、 环己烯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.33h， 生成 L-alanyl-2-(5-fluorouracil-1-yl)-L-glycine
  参考文献：
  名称：

  A novel peptide delivery system involving peptidase activated prodrugs as antimicrobial agents. Synthesis and biological activity of peptidyl derivatives of 5-fluorouracil

  摘要：

  As an approach to the development of antimicrobial agents, a novel peptide carrier system was designed, based on the chemical instability of alpha-substituted glycine analogues, with the explicit intent of actively transporting therapeutically useful compounds into microbial cells. Peptides containing 5-fluorouracil (5-FU) linked to the peptide backbone were selected to test the feasibility of this new delivery system. These peptide conjugates were designed such that they would be substrates for both the microbial peptide permeases and peptidases. After entry into cells, enzymatic hydrolysis of the peptide generates an unstable alpha-(5-FU)-glycine that spontaneously decomposes to release 5-FU. The 5-FU-peptide conjugates were tested for antifungal (Candida albicans) and antibacterial (Escherichia coli) activity and were found to have antimicrobial activities comparable to free 5-FU. Noninhibitory peptides antagonized the antimicrobial activities of the 5-FU-peptide conjugates but not of free 5-FU, a result consistent with peptide transport mediated entry of the peptide conjugates into cells. Further support for this conclusion was provided by the finding that biological activities were dependent upon peptide stereochemistry.

  DOI：

  10.1021/jm00377a012

文献信息

• Oligopeptide prodrugs
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0094815A2

  公开（公告）日：1983-11-23

  Prodrugs are described whose structures have a oligopeptide chain which is substituted by a nucleophilic chemotherapeutic residue at the a-position. The products have increased cell membrane permeability and beneficial physico-chemical properties.

  所述原药的结构是在 a 位被亲核化疗残基取代的低聚肽链。这些产品具有更高的细胞膜渗透性和有益的物理化学特性。
• MEDICINAL PREPARATIONS
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP1142589A1

  公开（公告）日：2001-10-10

  The present invention provides a pharmaceutical preparation comprising a compound which can be obtained by reacting a compound having a free amino group with a sugar having the reducing power. The preparation is capable of improving the in vivo durability of various compounds and releasing the compounds in response to changes in pH, and thus is useful for causing the compounds to act specifically on target parts.

  本发明提供了一种药物制剂，其中包含一种化合物，该化合物可通过使具有游离氨基的化合物与具有还原力的糖反应而获得。该制剂能够提高各种化合物在体内的耐久性，并能根据 pH 值的变化释放化合物，因此有助于使化合物专门作用于目标部位。
• US4454065A
  申请人：——

  公开号：US4454065A

  公开（公告）日：1984-06-12
• US4479898A
  申请人：——

  公开号：US4479898A

  公开（公告）日：1984-10-30
• US7067618B1
  申请人：——

  公开号：US7067618B1

  公开（公告）日：2006-06-27