H-Pro-Ile-Val-OMe | 127255-01-0

• 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: H-Pro-Ile-Val-OMe
• 英文别名: methyl (2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-[[(2S)-pyrrolidine-2-carbonyl]amino]pentanoyl]amino]butanoate
• CAS: 127255-01-0
• 化学式: C₁₇H₃₁N₃O₄
• 分子量: 341.451
• InChiKey: GVAHGOJFXKWIGP-XUXIUFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diazidomalonyl 、 H-Pro-Ile-Val-OMe 以 乙醚 、 二氯甲烷 为溶剂， 以15%的产率得到(S)-2-((2S,3S)-2-{[(S)-1-(3-{(S)-2-[(1S,2S)-1-((S)-1-Methoxycarbonyl-2-methyl-propylcarbamoyl)-2-methyl-butylcarbamoyl]-pyrrolidin-1-yl}-3-oxo-propionyl)-pyrrolidine-2-carbonyl]-amino}-3-methyl-pentanoylamino)-3-methyl-butyric acid methyl ester
  参考文献：
  名称：

  Synthesis of symmetrical pseudopeptides as potential inhibitors of the human immunodeficiency virus-1 protease

  摘要：

  It is demonstrated that HIV-1 protease is essential for the assembly and infectivity of the acquired immunodeficiency syndrome (AIDS) virus. This protease is an aspartyl protease with a 2-fold symmetry axis. Potential inhibitors were synthesized and consisted of a spacer linking 2 peptidic chains. They had to satisfy the following constraints: a C-2 symmetry axis, a backbone similar to the peptidic substrates, and side-chains filling the subsites S-n...S'(n). The compounds were synthesized via peptidic synthetic methods and evaluated in an enzymatic test with HIV-1 protease. Several compounds displayed an inhibitory activity at 10 mu M. They possessed the spacers CO, CO-CO, CO-CH2-CHOH-CO and the terminal chain Phe-O-iC(4)H(9). However, the structural-variation-based optimization of these different compounds failed and no potent inhibitors were prepared.

  DOI：

  10.1016/0223-5234(94)90025-6
• 作为产物：
  描述：

  (S)-2-[(1S,2S)-1-((S)-1-Methoxycarbonyl-2-methyl-propylcarbamoyl)-2-methyl-butylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 H-Pro-Ile-Val-OMe
  参考文献：
  名称：

  New hydroxyethylamine HIV protease inhibitors that suppress viral replication

  摘要：

  The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with K(i) values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEMX174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cell (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 mug/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.

  DOI：

  10.1021/jm00099a008

文献信息

• Ikeda, Shoji; Ashley, Jon A.; Wirsching, Peter, Journal of the American Chemical Society, 1992, vol. 114, # 19, p. 7604 - 7606
  作者：Ikeda, Shoji、Ashley, Jon A.、Wirsching, Peter、Janda, Kim D.

  DOI：——

  日期：——