2phb
From Proteopedia
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | , | ||||||
| Gene: | F10 (Homo sapiens) | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Domains: | Tryp_SPc, vWA_Matrilin | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
An Orally Efficacious Factor Xa Inhibitor
Contents |
Overview
Herein, we report the discovery of novel, proline-based factor Xa inhibitors containing a neutral P1 chlorophenyl pharmacophore. Through the additional incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4 pharmacophore, we discovered compound 7 (PD 0348292). This compound is a selective, orally bioavailable, efficacious FXa inhibitor that is currently in phase II clinical trials for the treatment and prevention of thrombotic disorders.
Disease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this Structure
2PHB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarb oxamide (PD 0348292), an orally efficacious factor Xa inhibitor., Kohrt JT, Bigge CF, Bryant JW, Casimiro-Garcia A, Chi L, Cody WL, Dahring T, Dudley DA, Filipski KJ, Haarer S, Heemstra R, Janiczek N, Narasimhan L, McClanahan T, Peterson JT, Sahasrabudhe V, Schaum R, Van Huis CA, Welch KM, Zhang E, Leadley RJ, Edmunds JJ, Chem Biol Drug Des. 2007 Aug;70(2):100-12. PMID:17683371
Page seeded by OCA on Wed Mar 26 09:52:22 2008
