 |
PDBsum entry 2qu6
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Design, Synthesis, And evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors.
|
|
|
Authors
|
|
M.H.Potashman,
J.Bready,
A.Coxon,
T.M.Demelfi,
L.Dipietro,
N.Doerr,
D.Elbaum,
J.Estrada,
P.Gallant,
J.Germain,
Y.Gu,
J.C.Harmange,
S.A.Kaufman,
R.Kendall,
J.L.Kim,
G.N.Kumar,
A.M.Long,
S.Neervannan,
V.F.Patel,
A.Polverino,
P.Rose,
S.V.Plas,
D.Whittington,
R.Zanon,
H.Zhao.
|
|
|
Ref.
|
|
J Med Chem, 2007,
50,
4351-4373.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Inhibition of the VEGF signaling pathway has become a valuable approach in the
treatment of cancers. Guided by X-ray crystallography and molecular modeling, a
series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as
potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular
proliferation assays. In this report we describe the synthesis and
structure-activity relationship of a series of 2-aminobenzimidazoles and
benzoxazoles, culminating in the identification of benzoxazole 22 as a potent
and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile.
Compound 22 demonstrated efficacy in both the murine matrigel model for vascular
permeability (79% inhibition observed at 100 mg/kg) and the rat corneal
angiogenesis model (ED(50) = 16.3 mg/kg).
|
|
|
|
|
|
|
