Optimization of a screening lead for factor VIIa/TF.
The structure-based design and progression of a screening lead to a 3nM factor VIIa/TF inhibitor with improved selectivity versus related enzymes is described.
Young
W B
WB
Department of Medicinal Chemistry, Axys Pharmaceuticals, Inc., 385 Oyster Point Blvd., South San Francisco, CA 94080, USA. wendy_young@axyspharm.com
Kolesnikov
A
A
Rai
R
R
Sprengeler
P A
PA
Leahy
E M
EM
Shrader
W D
WD
Sangalang
J
J
Burgess-Henry
J
J
Spencer
J
J
Elrod
K
K
Cregar
L
L
D000578:Amidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010648:Phenylacetates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011517:Prothrombin Time; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C442367:5-(5-amidinoindol-2-yl)-6-hydroxy-3-((3-nitrophenyl)phenyl)acetic acid; D000578:Amidines; D010648:Phenylacetates; D015842:Serine Proteinase Inhibitors; D015942:Factor VIIa