Abstract
A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5-dihydro-2H-thieno[4,3,2-de]quinazo-line-4(3H)-thione were found to be HIV-1 non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively.
MeSH terms
-
Binding Sites
-
Combinatorial Chemistry Techniques
-
Drug Resistance
-
HIV Reverse Transcriptase / antagonists & inhibitors*
-
HIV Reverse Transcriptase / genetics
-
Heterocyclic Compounds, 2-Ring / chemical synthesis
-
Heterocyclic Compounds, 2-Ring / pharmacology
-
Heterocyclic Compounds, 3-Ring / chemical synthesis
-
Heterocyclic Compounds, 3-Ring / pharmacology
-
Humans
-
Inhibitory Concentration 50
-
Models, Molecular
-
Point Mutation
-
Pyrans / chemical synthesis
-
Pyrans / pharmacology*
-
Quinazolines / chemical synthesis
-
Quinazolines / pharmacology*
-
Reverse Transcriptase Inhibitors / chemical synthesis*
-
Reverse Transcriptase Inhibitors / pharmacology
-
Structure-Activity Relationship
Substances
-
Heterocyclic Compounds, 2-Ring
-
Heterocyclic Compounds, 3-Ring
-
Pyrans
-
Quinazolines
-
Reverse Transcriptase Inhibitors
-
HIV Reverse Transcriptase