Z-Nle-ONp | 24181-97-3

• 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: Z-Nle-ONp
• 英文别名: Z-L-Nle-ONp；(4-nitrophenyl) (2S)-2-(phenylmethoxycarbonylamino)hexanoate
• CAS: 24181-97-3
• 化学式: C₂₀H₂₂N₂O₆
• 分子量: 386.404
• InChiKey: UFQPOFZGPUCSGU-SFHVURJKSA-N

物化性质

• 沸点：
  566.7±45.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Z-Nle-ONp 在 N-甲基吗啉 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 1-<5'-(N-norleucylamino)-5'-deoxy-β-D-allofuranosyluronamide>uracil
  参考文献：
  名称：

  Synthesis and biological properties of chitin synthetase inhibitors resistant to cellular peptidases

  摘要：

  The synthesis and biological properties of seven polyoxins (4-10) designed to avoid peptidase hydrolysis in Candida albicans are presented. Five dipeptidyl and two tripeptidyl polyoxin analogues were synthesized by coupling an amino acid active ester or azlactone to uracil polyoxin C (2) or polyoxin D (1), subsequent removal of the protecting group, and purification by preparative HPLC. A new and novel route for introducing an n-propyl group onto the alpha-amino group of peptides is reported. With the exception of a carboxamide derivative, 8, all analogues were resistant to hydrolysis by a cell extract or permeabilized cells of Candida. Chitin synthetase inhibition constants were determined for 4-10 and the KI values ranged from 7.15 X 10(-6) M for octanoyl-phenylalanyl-polyoxin D (10) to 1.06 X 10(-3) M for D-tryptophanyl-uracil polyoxin C (6). These novel polyoxins do not compete with the transport of either peptides or uridine into the cell. Millimolar concentrations of compounds 4-10 are required to inhibit growth, cause morphological alterations, or reduce the viability of C. albicans.

  DOI：

  10.1021/jm00155a034

文献信息

• Design of anticandidal agents: synthesis and biological properties of analogs of polyoxin L
  作者：Ponniah Shenbagamurthi、Herb A. Smith、Jeffrey M. Becker、Alvin Steinfeld、Fred Naider

  DOI：10.1021/jm00364a030

  日期：1983.10

  Six analogues of polyoxin L were synthesized from uridine. All of these analogues inhibited chitin synthetase from Candida albicans. Derivatization of the amine terminus of the polyoxin analogues resulted in loss of activity, and analogues containing aromatic amino acid residues were the most efficient inhibitors of chitin synthetase. The concentration of tryptophanyl uracil polyoxin C, 8, which caused 50% inhibition of chitin synthetase activity, was 1.6 X 10(-6) M. This was virtually identical with the activity found for polyoxin D. None of the inhibitors effectively competed with the entry of (Met)3 into C. albicans. All of the analogues caused severe morphological distortions of the yeast in culture, and a number of analogues killed C. albicans at millimolar concentrations. The results suggest that chitin synthetase inhibitors may have potential as anticandidal drugs.