4-[3-Bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazolin-1-ium chloride methanol solvate and 4-[(3-hydroxyphenyl)amino]-6,7-dimethoxy-1-quinazolinium chloride.
The title compounds, C16H15BrN3(O3)(+).Cl(-).CH4O (WHI-P154) and C16H16N3(O3)(+).Cl(-) (WHI-P180), are potent inhibitors [WHI-P154 with IC50 = 5.6 microM and WHI-P180 with IC50 = 4.0 microM for epidermal growth factor receptor (EGFR) kinase inhibition] of the EGFR tyrosine kinase as well as Janus Kinase 3. The molecular structures of these compounds are very similar except for the dihedral angle between the anilino and quinazoline moieties which is 1.10 (5) degrees for WHI-P154, and 45.66 (6) and 25.29 (7) degrees for the two molecules of WHI-P180 in the asymmetric unit. The nitrogen at the N3 position is protonated in both structures and participates in hydrogen bonding with the chlorine anions.
Ghosh
S
S
Department of Structural Biology, Parker Hughes Institute, 2665 Long Lake Road, Ste 330, St Paul, MN 55113, USA. sghosh@ih.org
Jennissen
J D
JD
Liu
X P
XP
Uckun
F M
FM
D000818:Animals; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006860:Hydrogen Bonding; D053616:Janus Kinase 3; D008407:Mast Cells / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000737:chemistry*
D004791:Enzyme Inhibitors; D011799:Quinazolines; C404933:WHI P164; C118361:WHI P180; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D053616:Janus Kinase 3