Details

Autor(en) / Beteiligte

• Embrey, Mark W.
• Wai, John S.
• Funk, Timothy W.
• Homnick, Carl F.
• Perlow, Debbie S.
• Young, Steven D.
• Vacca, Joseph P.
• Hazuda, Daria J.
• Felock, Peter J.
• Stillmock, Kara A.
• Witmer, Marc V.
• Moyer, Gregory
• Schleif, William A.
• Gabryelski, Lori J.
• Jin, Lixia
• Chen, I-Wu
• Ellis, Joan D.
• Wong, Bradley K.
• Lin, Jiunn H.
• Leonard, Yvonne M.
• Tsou, Nancy N.
• Zhuang, Linghang

Titel

A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2005-10, Vol.15 (20), p.4550-4554

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2005

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide 1 led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC 95 of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs.