10-Hydroxy-7, 8-dihydropyrazino [1′, 2′: 1, 5] pyrrolo [2, 3-d] pyridazine-1, 9 (2H, 6H)-diones: Potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors …

…, TE Fisher, V Sherman, CF Homnick, DD Staas…

Index: Wiscount, Catherine M.; Williams, Peter D.; Tran, Lekhanh O.; Embrey, Mark W.; Fisher, Thorsten E.; Sherman, Vanessa; Homnick, Carl F.; Donnette Staas; Lyle, Terry A.; Wai, John S.; Vacca, Joseph P.; Wang, ZiQiang; Felock, Peter J.; Stillmock, Kara A.; Witmer, Marc V.; Miller, Michael D.; Hazuda, Daria J.; Day, Alysha M.; Gabryelski, Lori J.; Ecto, Linda T.; Schleif, William A.; DiStefano, Daniel J.; Kochansky, Christopher J.; Reza Anari Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 16 p. 4581 - 4583

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Citation Number: 18

Abstract

A series of 10-hydroxy-7, 8-dihydropyrazino [1′, 2′: 1, 5] pyrrolo [2, 3-d] pyridazine-1, 9 (2H, 6H)-diones was synthesized and tested for their inhibition of HIV-1 replication in cell culture. Structure–activity studies indicated that high antiviral potency against wild-type virus as well as viruses containing integrase mutations that confer resistance to three different structural classes of integrase inhibitors could be achieved by incorporation of small ...