 |
PDBsum entry 6acb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
6acb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Optimization of chromeno[2,3- C]pyrrol-9(2 h)-Ones as highly potent, Selective, And orally bioavailable pde5 inhibitors: structure-Activity relationship, X-Ray crystal structure, And pharmacodynamic effect on pulmonary arterial hypertension.
|
|
|
Authors
|
|
D.Wu,
Y.Huang,
Y.Chen,
Y.Y.Huang,
H.Geng,
T.Zhang,
C.Zhang,
Z.Li,
L.Guo,
J.Chen,
H.B.Luo.
|
|
|
Ref.
|
|
J Med Chem, 2018,
61,
8468-8473.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
To further explore the structure-activity relationship around the chromeno[2,3-
c]pyrrol-9(2 H)-one scaffold, 19 derivatives as inhibitors against PDE5 were
discovered. The most potent inhibitor 3 has an IC50 of 0.32 nM with
remarkable selectivity and druglike profile. Oral administration of 3 (1.25
mg/kg) caused comparable therapeutic effects to sildenafil (10.0 mg/kg) against
pulmonary arterial hypertension. Further, different binding patterns from
sildenafil were revealed in cocrystal structures, which provide structural
templates for discovery of highly potent PDE5 inhibitors.
|
|
|
|
|
|
|
