74879-13-3Relevant academic research and scientific papers
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%).
HIV INTEGRASE INHIBITORS
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Page/Page column 79, (2008/06/13)
Hydroxy-substituted pyrazinopyrrolopyridazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I) wherein R1, R2, R3, R4, R5, R6 and R7 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
Absolute Configuration of 6-Methyl-5,6,7,8-tetrahydropterin produced by Enzymic Reduction (Dihydrofolate Reductase and NADPH) of 6-Methyl-7,8-dihydropterin
Armarego, Wilfred L. F.,Waring, Paul,Williams, Jeffrey W.
, p. 334 - 336 (2007/10/02)
Dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP oxidoreductase, E.C.1.5.1.3.) and NADPH, which catalyse the reduction of 7,8-dihydrofolic acid (1) stereospecifically to give one diastereoisomer of 5,6,7,8-tetrahydrofolic acid (3), also catalyse the reduction of 6-methyl-7,8-dihydropterin (2) stereospecifically to (-)-6-methyl-5,6,7,8-tetrahydropterin (4); the absolute configuration at C-6 of the pterin (4) is shown to be S by correlation with S-alanine using a series of methylations, degradations, and syntheses, and if the most probable assumption is made that the stereospecificities of these two reactions are the same, then the absolute configuration at C-6 of enzymically produced 5,6,7,8-tetrahydrofolic acid should be S.
