Scala Angela, Piperno Anna, Micale Nicola, Christ Frauke, Debyser Zeger
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno D'Alcontres 31, Messina I-98166, Italy.
Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, UZ St. Rafael, Kapucijnenvoer 33, BE-3000 Leuven, Belgium.
ACS Med Chem Lett. 2018 Dec 15;10(4):398-401. doi: 10.1021/acsmedchemlett.8b00511. eCollection 2019 Apr 11.
A new tetrahydroindazolylbenzamide derivative has been synthesized, characterized, and evaluated as HIV-inhibitor. The biological data revealed the ability to inhibit HIV proliferation with low cytotoxicity allowing for significant selectivity (EC 2.77 μM; CC 118.7 μM; SI = 68). The compound did not inhibit the viral integrase as demonstrated by studies. QPCR experiments showed that the block of viral replication occurred at early replication steps, prior to integration, profiling it as a late reverse transcription inhibitor. An efficient multistep strategy was adopted for the synthesis of the scaffold, consisting of a sequential ring-opening reaction of oxazol-5-(4)-one with 1,3-diketone, followed by cyclocondensation with hydrazine and hydrolysis of the nitrile to the desired carboxamide.
一种新的四氢吲唑基苯甲酰胺衍生物已被合成、表征并作为HIV抑制剂进行评估。生物学数据显示该化合物具有抑制HIV增殖的能力，且细胞毒性低，具有显著的选择性（EC 2.77 μM；CC 118.7 μM；SI = 68）。研究表明该化合物不抑制病毒整合酶。QPCR实验表明，病毒复制的阻断发生在整合之前的早期复制步骤，将其定性为晚期逆转录抑制剂。采用了一种高效的多步策略来合成该骨架，包括恶唑-5-(4)-酮与1,3-二酮的顺序开环反应，随后与肼进行环缩合反应以及腈水解为所需的羧酰胺。
