Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines.

Article Details

Citation

Copy to clipboard

Bardelle C, Coleman T, Cross D, Davenport S, Kettle JG, Ko EJ, Leach AG, Mortlock A, Read J, Roberts NJ, Robins P, Williams EJ

Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines.

Bioorg Med Chem Lett. 2008 Nov 1;18(21):5717-21. doi: 10.1016/j.bmcl.2008.09.087. Epub 2008 Sep 27.

PubMed ID

18851911 [ View in PubMed

]

Abstract

Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE	Ephrin type-B receptor 4	IC 50 (nM)	220	N/A	N/A	Details
3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE	Ephrin type-B receptor 4	IC 50 (nM)	900	N/A	N/A	Details
3-({4-[(5-chloro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl}amino)benzenesulfonamide	Ephrin type-B receptor 4	IC 50 (nM)	40	N/A	N/A	Details
3-({4-[(5-chloro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl}amino)benzenesulfonamide	Ephrin type-B receptor 4	IC 50 (nM)	172	N/A	N/A	Details
N-[3-[[4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL]AMINO]PHENYL]METHANESULFONAMIDE	Ephrin type-B receptor 4	IC 50 (nM)	794	N/A	N/A	Details
N-[3-[[4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL]AMINO]PHENYL]METHANESULFONAMIDE	Ephrin type-B receptor 4	IC 50 (nM)	741	N/A	N/A	Details
N'-(5-chloro-1,3-benzodioxol-4-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine	Ephrin type-B receptor 4	IC 50 (nM)	90	N/A	N/A	Details
N'-(5-chloro-1,3-benzodioxol-4-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine	Ephrin type-B receptor 4	IC 50 (nM)	190	N/A	N/A	Details
N'-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-N-(3-MORPHOLIN-4-YLPHENYL)PYRIMIDINE-2,4-DIAMINE	Ephrin type-B receptor 4	IC 50 (nM)	580	N/A	N/A	Details