Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of diarylsulfones

Chad E. Stephens, Takita M. Felder, J. Walter Sowell, Graciela Andrei, Jan Balzarini, Robert Snoeck, Erik De Clercq

Research output: Contribution to journalArticle

55 Scopus citations


Based on general SARs previously described for anti-HIV-1 diarylsulfone derivatives, a series of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes has been prepared and evaluated as potential antiviral and antitumor agents. In cell culture, some of the 2-aminothiophenes exhibited moderate and selective activity against HIV-1, with 2-amino-3-(2-nitrophenylsulfonyl)thiophene (7e) being most attractive (EC50= 3.8 μg/mL, CC50= > 100 μg/mL). In broad-spectrum antiviral assays, the 3-arylsulfonyl-2-(trifluoroacetamido)thiophenes (8c-g) and 2-acetamido-3-arylsulfonyl-5-nitrothiophenes (9f-g) proved considerably active (IC50= 0.1-10 μg/mL) against human cytomegalovirus (CMV) and/or varicella zoster virus (VZV). Based on the activity of the trifluoroacetamides, ring-modified furan, N-(substituted)pyrrole, phenyl, and 3,4-thiophene analogues were prepared, and these compounds were also active against CMV and/or VZV, with the notable exception of the 3,4-thiophene derivative. In contrast to other amines, the 2-aminopyrrole precursors (13a-d) also exhibited potent activity against CMV. Unfortunately, most of these compounds displayed significant cytotoxicity against human fibroblasts, the cells supporting CMV and VZV replication, and thus selectivity indices were low. The most notable exception to this was the naphthyl-substituted aminopyrrole 13d, which exhibited both potent (IC50= 0.3 μg/mL) and selective (CC50= > 50 μg/mL) activity against CMV. Finally, thiophene aryl amides 8i-k displayed moderate in vitro activity against certain leukemia, breast, and colon cancer cell lines.

Original languageEnglish (US)
Pages (from-to)1123-1132
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number5
StatePublished - May 1 2001
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this