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Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase.

Authors :
Costi R
Métifiot M
Chung S
Cuzzucoli Crucitti G
Maddali K
Pescatori L
Messore A
Madia VN
Pupo G
Scipione L
Tortorella S
Di Leva FS
Cosconati S
Marinelli L
Novellino E
Le Grice SF
Corona A
Pommier Y
Marchand C
Di Santo R
Source :
Journal of medicinal chemistry [J Med Chem] 2014 Apr 24; Vol. 57 (8), pp. 3223-34. Date of Electronic Publication: 2014 Apr 11.
Publication Year :
2014

Abstract

A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies. Molecular modeling studies based on both the HIV-1 IN and RNase H catalytic core domains provided new structural insights for the future development of these compounds as dual HIV-1 IN and RNase H inhibitors.

Details

Language :
English
ISSN :
1520-4804
Volume :
57
Issue :
8
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
24684270
Full Text :
https://doi.org/10.1021/jm5001503