Download MendeleyThe discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor
Kohrt, J.T., Bigge, C.F., Bryant, J.W., Casimiro-Garcia, A., Chi, L., Cody, W.L., Dahring, T., Dudley, D.A., Filipski, K.J., Haarer, S., Heemstra, R., Janiczek, N., Narasimhan, L., McClanahan, T., Peterson, J.T., Sahasrabudhe, V., Schaum, R., Van Huis, C.A., Welch, K.M., Zhang, E., Leadley, R.J., Edmunds, J.J.(2007) Chem Biol Drug Des 70: 100-112
- PubMed: 17683371
- DOI: https://doi.org/10.1111/j.1747-0285.2007.00539.x
- Primary Citation of Related Structures:
2PHB - PubMed Abstract:
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.
Organizational Affiliation:
Michigan Laboratories, Ann Arbor Campus, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.kohrt@pfizer.com
