TY - JOUR
T1 - Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of diarylsulfones
AU - Stephens, Chad E.
AU - Felder, Takita M.
AU - Sowell, J. Walter
AU - Andrei, Graciela
AU - Balzarini, Jan
AU - Snoeck, Robert
AU - De Clercq, Erik
N1 - Funding Information:
The authors are grateful to the Developmental Therapeutics Program of the National Cancer Institute, USA, for evaluating compounds for antitumor activity, and to Mrs. A. Absillis, A. Camps, F. De Meyer, L. Vandenheurck and A. Van Lierde for excellent technical assistance. The research was supported, in part, by the College of Pharmacy, University of South Carolina, and by grants from the Fonds voor Geneeskunde Wetenschappelijk Onderzoek — Vlaanderen (G.0104.98), the Belgian Geconceteerde Onderzoeksacties (GOA 00/12) and the Biomedical Health Programme of the European Commission.
PY - 2001/5
Y1 - 2001/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S0968-0896(00)00333-3
DO - 10.1016/S0968-0896(00)00333-3
M3 - Article
C2 - 11377170
AN - SCOPUS:0035018516
SN - 0968-0896
VL - 9
SP - 1123
EP - 1132
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 5
ER -