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Literature summary for 2.7.10.1 extracted from

  • Hu, E.; Tasker, A.; White, R.D.; Kunz, R.K.; Human, J.; Chen, N.; Buerli, R.; Hungate, R.; Novak, P.; Itano, A.; Zhang, X.; Yu, V.; Nguyen, Y.; Tudor, Y.; Plant, M.; Flynn, S.; Xu, Y.; Meagher, K.L.; Whittington, D.A.; Ng, G.Y.
    Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit (2008), J. Med. Chem., 51, 3065-3068.
    View publication on PubMed
Search for more literature for 2.7.10.1

Application

Application Comment Organism
drug development aminoquinazoline pyridones are potent, selective, and orally efficacious c-Kit inhibitors for the treatment of fibrotic diseases. Compounds show greater than 200fold selectivity against KDR, p38, Lck, and Src Mus musculus
drug development aminoquinazoline pyridones are potent, selective, and orally efficacious c-Kit inhibitors for the treatment of fibrotic diseases. Compounds show greater than 200fold selectivity against KDR, p38, Lck, and Src Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
co-crystallization of pyridone, bisamide or 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one with the V916T mutant KDR protein Homo sapiens

Protein Variants

Protein Variants Comment Organism
V916T KDR mutant, which shares the majority of residues with c-Kit in the ATP binding pocket. Inhibitor 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one binds in the DFG-out conformation. Two nitrogens from the aminoquinazoline portion of the molecule form hydrogen bonding interactions with linker region of the enzyme at Cys673. The pyridone scaffold is further anchored by the hydrogen bond contacts between its carbonyl group and Asp810 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one cyclopentylethyl Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one pyridone, nonselective inhibitor of c-Kit Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one exhibits poor selectivity Homo sapiens
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one
-
 Mus musculus
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one exhibits potent inhibition of c-Kit, greater than 200fold selectivity against KDR, p38, Lck, and Src, and desirable pharmacokinetic properties Homo sapiens
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one
-
 Homo sapiens
3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one
-
 Homo sapiens
ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate
-
 Homo sapiens
imatinib
-
 Homo sapiens
N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide bisamide Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P35968
-
-
Mus musculus P05532 C57BL/6 mice
-
Mus musculus C57BL/6 P05532 C57BL/6 mice
-

Source Tissue

Source Tissue Comment Organism Textmining
mast cell
-
 Mus musculus
-
UT-7 cell
-
 Homo sapiens
-

Synonyms

Synonyms Comment Organism
c-kit
-
 Mus musculus
KDR
-
 Homo sapiens
receptor tyrosine kinase c-Kit
-
 Mus musculus
receptor tyrosine kinase c-Kit
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000001
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one
0.0000021
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one
0.0000061
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one
0.0000079
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one
0.00001
-
 c-Kit Homo sapiens 1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
0.000011
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one
0.000013
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one
0.000014
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one
0.000014
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one
0.000017
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one
0.000017
-
 c-Kit Homo sapiens ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate
0.00002
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one
0.00002
-
 c-Kit Homo sapiens 1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
0.000022
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one
0.00004
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one
0.000048
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one
0.000052
-
 c-Kit Homo sapiens imatinib
0.00006
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one
0.000065
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one
0.000077
-
 c-Kit Homo sapiens N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide
0.00021
-
 c-Kit Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one
0.001
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one
0.0014
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one
0.0018
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one
0.0034
-
 KDR Homo sapiens 1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
0.0043
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one
0.0044
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens 1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one
0.005
-
 KDR Homo sapiens ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate
0.005
-
 KDR Homo sapiens 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one
0.025
-
 KDR Homo sapiens imatinib
0.025
-
 KDR Homo sapiens N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide