 |
PDBsum entry 3b8q
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Naphthamides as novel and potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: design, Synthesis, And evaluation.
|
|
|
Authors
|
|
J.C.Harmange,
M.M.Weiss,
J.Germain,
A.J.Polverino,
G.Borg,
J.Bready,
D.Chen,
D.Choquette,
A.Coxon,
T.Demelfi,
L.Dipietro,
N.Doerr,
J.Estrada,
J.Flynn,
R.F.Graceffa,
S.P.Harriman,
S.Kaufman,
D.S.La,
A.Long,
M.W.Martin,
S.Neervannan,
V.F.Patel,
M.Potashman,
K.Regal,
P.M.Roveto,
M.L.Schrag,
C.Starnes,
A.Tasker,
Y.Teffera,
L.Wang,
R.D.White,
D.A.Whittington,
R.Zanon.
|
|
|
Ref.
|
|
J Med Chem, 2008,
51,
1649-1667.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A series of naphthyl-based compounds were synthesized as potential inhibitors of
vascular endothelial growth factor (VEGF) receptors. Investigations of
structure-activity relationships led to the identification of a series of
naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase
family. Numerous analogues demonstrated low nanomolar inhibition of
VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and
of these several compounds possessed favorable pharmacokinetic (PK) profiles. In
particular, compound 48 demonstrated significant antitumor efficacy against
established HT29 human colon adenocarcinoma xenografts implanted in athymic
mice. A full account of the preparation, structure-activity relationships,
pharmacokinetic properties, and pharmacology of analogues within this series is
presented.
|
|
|
|
|
|
|
