Literature summary for 2.7.7.49 extracted from

Kennedy-Smith, J.; Arora, N.; Billedeau, J.; Fretland, J.; Hang, J.; Heilek, G.; Harris, S.; Hirschfeld, D.; Javanbakht, H.; Li, Y.; Liang, W.; Roetz, R.; Smith, M.; Su, G.; Suh, J.; Villasenor, A.; Wu, J.; Yasuda, D.; Klumpp, K.; Sweeney, Z.
Synthesis and biological activity of new pyridone diaryl ether non-nucleoside inhibitors of HIV-1 reverse transcriptase (2010), MedChemComm, 1, 79-83.

No PubMed abstract available

Protein Variants

Protein Variants	Comment	Organism
K103N	site-directed mutagenesis	Human immunodeficiency virus 1
Y181C	site-directed mutagenesis	Human immunodeficiency virus 1

Inhibitors

Inhibitors	Comment	Organism
3-([3-bromo-2-oxo-5-[(pyridin-3-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-([3-bromo-2-oxo-5-[(pyridin-4-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-([3-bromo-5-fluoro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-([3-bromo-6-[2-(3-chlorophenyl)ethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-([6-[2-(1,3-benzoxazol-2-yl)ethyl]-3-chloro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-2-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-6-methyl-2-oxo-5-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-6-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([3-chloro-6-[2-(3-chlorophenyl)ethyl]-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-([6-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(dimethylamino)-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-[[3-chloro-2-oxo-6-(2-phenylethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-[[3-chloro-5-fluoro-2-oxo-6-(2-phenylethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile	-	Human immunodeficiency virus 1
3-chloro-5-[[3-chloro-6-methyl-2-oxo-5-(phenoxymethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile	-	Human immunodeficiency virus 1
3-[(5-benzyl-3-bromo-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-[(5-benzyl-3-bromo-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-[6-bromo-3-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-2-fluorophenoxy]-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
3-[[3-bromo-2-oxo-5-(pyridin-4-ylmethoxy)-1,2-dihydropyridin-4-yl]oxy]-5-chlorobenzonitrile	-	Human immunodeficiency virus 1
efavirenz	-	Human immunodeficiency virus 1
additional information	synthesis and inhibitory potencies of pyridone diaryl ether non-nucleoside inhibitors of HIV-1 reverse transcriptase, structure-based drug design, overview	Human immunodeficiency virus 1

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Human immunodeficiency virus 1

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
deoxynucleoside triphosphate + DNAn	Human immunodeficiency virus 1	-	diphosphate + DNAn+1	-	?

Organism

Organism	UniProt	Comment	Textmining
Human immunodeficiency virus 1	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
deoxynucleoside triphosphate + DNAn	-	Human immunodeficiency virus 1	diphosphate + DNAn+1	-	?

Synonyms

Synonyms	Comment	Organism
HIV-1 reverse transcriptase	-	Human immunodeficiency virus 1

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000001	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-5-fluoro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000001	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-5-fluoro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000002	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-methyl-2-oxo-5-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000002	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	efavirenz
0.000002	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-5-fluoro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000003	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	efavirenz
0.000003	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-methyl-2-oxo-5-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000004	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([6-[2-(1,3-benzoxazol-2-yl)ethyl]-3-chloro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000004	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-methyl-2-oxo-5-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000005	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-[[3-chloro-6-methyl-2-oxo-5-(phenoxymethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile
0.000006	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-[2-(3-chlorophenyl)ethyl]-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000006	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-[[3-chloro-6-methyl-2-oxo-5-(phenoxymethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile
0.000006	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([6-[2-(1,3-benzoxazol-2-yl)ethyl]-3-chloro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000006	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-[[3-chloro-6-methyl-2-oxo-5-(phenoxymethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile
0.000007	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000007	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-[2-(3-chlorophenyl)ethyl]-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000007	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-[[3-chloro-5-fluoro-2-oxo-6-(2-phenylethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile
0.000008	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-6-[2-(3-chlorophenyl)ethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000008	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-3-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000008	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-6-[2-(3-chlorophenyl)ethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000008	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-4-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000008	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000008	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-[[3-chloro-2-oxo-6-(2-phenylethyl)-1,2-dihydropyridin-4-yl]oxy]benzonitrile
0.00001	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-4-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.00001	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000011	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[[3-bromo-2-oxo-5-(pyridin-4-ylmethoxy)-1,2-dihydropyridin-4-yl]oxy]-5-chlorobenzonitrile
0.000011	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-3-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000012	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-[2-(3-chlorophenyl)ethyl]-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000012	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[6-bromo-3-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-2-fluorophenoxy]-5-chlorobenzonitrile
0.000013	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[[3-bromo-2-oxo-5-(pyridin-4-ylmethoxy)-1,2-dihydropyridin-4-yl]oxy]-5-chlorobenzonitrile
0.000014	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000014	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-4-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000016	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-2-oxo-5-[(pyridin-3-yloxy)methyl]-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000016	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([6-[2-(1,3-benzoxazol-2-yl)ethyl]-3-chloro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000016	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000017	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-([3-bromo-6-[2-(3-chlorophenyl)ethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)-5-chlorobenzonitrile
0.000019	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000021	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-4-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000021	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-2-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000021	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[[3-bromo-2-oxo-5-(pyridin-4-ylmethoxy)-1,2-dihydropyridin-4-yl]oxy]-5-chlorobenzonitrile
0.000022	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000022	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.00003	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-6-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000033	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-2-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.000034	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000041	-	mutant Y181C, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000065	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	efavirenz
0.000071	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-[(5-benzyl-3-bromo-2-oxo-1,2-dihydropyridin-4-yl)oxy]-5-chlorobenzonitrile
0.000078	-	mutant K103N, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([3-chloro-2-oxo-6-[2-(pyridin-2-yl)ethyl]-1,2-dihydropyridin-4-yl]oxy)benzonitrile
0.00022	-	wild-type enzyme, pH and temperature not specified in the publication	Human immunodeficiency virus 1	3-chloro-5-([6-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(dimethylamino)-5-fluoro-2-oxo-1,2-dihydropyridin-4-yl]oxy)benzonitrile