1068150-83-3Relevant articles and documents
10-Hydroxy-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyrid azine-1,9(2H,6H)-diones: Potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors with activity against integrase mutants
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
scheme or table, p. 4581 - 4583 (2009/04/08)
A series of 10-hydroxy-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyrid azine-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 aliphatic groups at certain positions on the core template. An optimal compound from this study, 16, inhibits integrase strand-transfer activity with an IC50 value of ≤10 nM, inhibits HIV-1 replication in cell culture with an IC95 value of 35 nM in the presence of 50% normal human serum, and displays modest pharmacokinetic properties in rats (iv t1/2 = 5.3 h, F = 17%).
