 |
PDBsum entry 2hvx
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Discovery of potent, Selective, Orally active, Nonpeptide inhibitors of human mast cell chymase.
|
|
|
Authors
|
|
M.N.Greco,
M.J.Hawkins,
E.T.Powell,
H.R.Almond,
L.De garavilla,
J.Hall,
L.K.Minor,
Y.Wang,
T.W.Corcoran,
E.Di cera,
A.M.Cantwell,
S.N.Savvides,
B.P.Damiano,
B.E.Maryanoff.
|
|
|
Ref.
|
|
J Med Chem, 2007,
50,
1727-1730.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A series of beta-carboxamido-phosphon(in)ic acids (2) was identified as a new
structural motif for obtaining potent inhibitors of human mast cell chymase. For
example, 1-naphthyl derivative 5f had an IC50 value of 29 nM and (E)-styryl
derivative 6g had an IC50 value of 3.5 nM. An X-ray structure for 5f.chymase
revealed key interactions within the enzyme active site. Compound 5f was
selective for inhibiting chymase versus eight serine proteases. Compound 6h was
orally bioavailable in rats (F=39%), and orally efficacious in a hamster model
of inflammation.
|
|
|
|
|
|
|
