Pyridinone diketo acids: inhibitors of HIV replication
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorsVasu Nair, Byung I. Seo, Vinod R. Uchil
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Abstract
A new class of diketo acids constructed on pyridinone scaffolds, designed as inhibitors of HIV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other integrase-based anti-HIV agents). Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.
Claims48
A compound according to the structure of formula I:
- wherein the scaffold is independently the 2- and 4-pyridinones identified herein and their regioisomers;
- R1 and R2 are each independently H, C1-6 alkyl, C1-6 fluoroalkyl, unsubstituted or substituted C5-6 cycloalkyl, C1-6 alkenyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, C2-6 alkyl phenyl which phenyl moiety may be optionally substituted, unsubstituted or substituted heteroaryl, C1-6 alkyl substituted with a heteroaryl group which heteroaryl group is optionally substituted, C1-6 alkyl S(O)R or alkyl (SO2)R where R is alkyl, phenyl or substituted phenyl, C1-6 alkyl CO2Ra where Ra is C1-6 alkyl or H, C1-6 alkyl CORa′ where Ra− is C1-6 alkyl;
- R3 and R4 are independently selected from H, C1-6 alkyl, halogen, hydroxyl, unsubstituted or substituted benzyl, or unsubstituted or substituted phenylthio;
- R5 is CO2Rc or P(O)(ORc)(ORc), where each Rc is independently from H and C1-6 alkyl,
- Or a pharmaceutically acceptable salt thereof.
A compound selected from the group consisting of
- 4-(1,5-dibenzyl-1,2-dihydro-2-oxopyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid;
- 4-(1,5-dibenzyl-1,4-dihydro-4-oxopyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid;
- 3-Acetyl-1,5-dibenzyl-3-pyridin-2(1H)-one;
- 3-Acetyl-1,5-dibenzyl-1H-pyridin-4-one;
- Methyl-4-(1,5-dibenzyl-1,2-dihydro-2-oxopyridin-3-yl)-2-hydroxy-4-oxobut-2-enoate;
- and
- Methyl 4-(1,5-dibenzyl-4-oxo-1,4-dihydro-pyridin-3-yl)-2-hydroxy-4-oxo-but-2-enoate, or a pharmaceutically acceptable salt thereof.
The compound
- 4(1,5-dibenzyl-1,2-dihydro-2-oxopyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid;
- 4-(1,5-dibenzyl-1,4-dihydro-4-oxopyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid, or
- a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.