Novel benzoxazin-3-one derivatives: Design, synthesis, molecular modeling, anti-HIV-1 and integrase inhibitory assay.

INTRODUCTION Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3'-end nucleotide as a streamlined metal chelating pharmacophore. METHOD In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisoster replacement strategy of 2-benzoxazolinone. RESULT Molecular modeling studies revealed that amide functionality alongside oxadiazole heteroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupy hydrophobic site created by the cytidylate nucleotide (DC-16). CONCLUSION The most potent and selective compound displayed 110 µM IC50 with selectivity index of more than 2.

• Publication year

  2019

• Venue

  Medicinal chemistry

• Publication date

  Unknown publication date

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.2174/1573406415666190826161123PMID 31448713
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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