Marastoni Mauro, Bazzaro Martina, Bortolotti Fabrizio, Tomatis Roberto
Dipartimento di Scienze Farmaceutiche e Centro di Biotecnologie, via Fossato di Mortara 17-19, Università di Ferrara, I-44100, Ferrara, Italy.
Bioorg Med Chem. 2003 May 29;11(11):2477-83. doi: 10.1016/s0968-0896(02)00563-1.
A series of N-benzyl pseudopeptides was designed, synthesized and tested as HIV-1 protease inhibitors. The ability of the new compounds containing N-benzyl hydroxyalkylamino acid core structure to inhibit HIV replication in cell culture is comparable to their capacity to inhibit the isolated enzyme, a result compatible with good pharmacokinetic properties of these derivatives. The pseudotripeptide Fmoc-Leu-N(Bzl)Hse-Met-NH-tBu was the best inhibitor of the series (IC(50)=170 nM) showing promising inhibition of viral replication (ED(50)=52 nM). All new compounds exhibit high enzymatic resistance and stability against cell cultures and plasma enzymes.
设计、合成了一系列N-苄基假肽，并将其作为HIV-1蛋白酶抑制剂进行测试。含有N-苄基羟烷基氨基酸核心结构的新化合物在细胞培养中抑制HIV复制的能力与其抑制分离酶的能力相当，这一结果与这些衍生物良好的药代动力学性质相符。假三肽Fmoc-Leu-N(Bzl)Hse-Met-NH-tBu是该系列中最佳的抑制剂（IC(50)=170 nM），对病毒复制表现出有前景的抑制作用（ED(50)=52 nM）。所有新化合物对细胞培养和血浆酶均表现出高酶抗性和稳定性。
