Gogliotti RD, Ellsworth EL, Holler TP, Hupe D, Foltin SK, Kennedy RM, Sanchez JP, Domagala JM; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 5th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 5th 1998 Chic Ill. 1998 Feb 1-5; 5th: 200 (abstract no. 641).
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI.
HIV integrase is an enzyme which incorporates the double-stranded DNA product which results from reverse transcription of viral RNA into the host genome and is thus essential for replication. Since this enzyme is not indigenous to the host, it represents an attractive target for new anti-HIV agents. We now report that appropriately substituted quinolones represented generically by 1, are potent inhibitors of HIV-1 integrase, binding to the core domain. They inhibit HIV-1 integrase processing and disintegration reactions. (Figure: see text) To develop an SAR in this series, combinatorial methods were utilized in conjunction with single compound synthesis to provide compounds possessing excellent in vitro activities. The SAR developed by changing R, R' and R" will be noted. For example, PD176931 (2) has an IC(50) of 297 nM in the integrase processing assay.
Publication Types:
Keywords:
- Anti-HIV Agents
- HIV Integrase
- HIV Integrase Inhibitors
- In Vitro
- Integrases
- Quinolones
Other ID:
UI: 102236225
From Meeting Abstracts