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ID: ALA3997825

Journal: Bioorg Med Chem Lett

Title: Discovery of 2-oxopiperazine dengue inhibitors by scaffold morphing of a phenotypic high-throughput screening hit.

Authors: Kounde CS, Yeo HQ, Wang QY, Wan KF, Dong H, Karuna R, Dix I, Wagner T, Zou B, Simon O, Bonamy GMC, Yeung BKS, Yokokawa F.

Abstract: A series of 2-oxopiperazine derivatives were designed from the pyrrolopiperazinone cell-based screening hit 4 as a dengue virus inhibitor. Systematic investigation of the structure-activity relationship (SAR) around the piperazinone ring led to the identification of compound (S)-29, which exhibited potent anti-dengue activity in the cell-based assay across all four dengue serotypes with EC50<0.1μM. Cross-resistant analysis confirmed that the virus NS4B protein remained the target of the new oxopiperazine analogs obtained via scaffold morphing from the HTS hit 4.

CiteXplore: 28216045

DOI: 10.1016/j.bmcl.2017.02.005