MEDI 91

Potent HIV integrase inhibitor with excellent pharmacokinetics

Melissa Egbertson, melissa_egbertson@merck.com¹, Michelle Kuo¹, Debra Perlow¹, Marie Langford¹, Jeffrey Melamed¹, John Wai, john_wai@merck.com¹, Joseph Vacca¹, Audrey Wallace¹, Yvonne Leonard¹, Daria J. Hazuda², Peter J. Felock², Kara Stillmock², William Schleif³, Lori J. Gabryelski³, Gregory Moyer³, Joan Ellis⁴, Lixia Jin⁴, and Steven D. Young¹. (1) Department of Medicinal Chemistry, Merck Research Laboratories, WP14-3, PO Box 4, West Point, PA 19486, (2) Department of Antiviral Research, Merck Research Laboratories, PO Box 4, West Point, PA 19486, (3) Department of Viral Vaccine Research, Merck Research Laboratories, PO Box 4, West Point, PA 19486, (4) Department of Drug Metabolism, Merck Research Laboratories, PO Box 4, West Point, PA 19486

HIV-1 integrase catalyzes the insertion of proviral DNA into the host genome. L-000870810, an 8-hydroxy-1,6-naphthyridine, inhibits HIV-1 replication in cell culture (Hazuda et al. PNAS, 2004, 101, 11233) and significantly decreased viral load and increased CD4 cell count in patients infected with HIV (Little et al. CROI, 2005). Efforts directed at improving compound physical properties in the 1,6-naphthyridine series led to the discovery of the compound A, a equipotent antiviral agent with excellent pharmacokinetic properties.

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007