Download MendeleyThe Discovery of Glycine and Related Amino Acid-Based Factor Xa Inhibitors
Kohrt, J.T., Filipski, K.J., Cody, W.L., Bigge, C.F., La, F., Welch, K., Dahring, T., Bryant, J.W., Leonard, D., Bolton, G., Narasimhan, L., Zhang, E., Peterson, J.T., Haarer, S., Sahasrabudhe, V., Janiczek, N., Desiraju, S., Hena, M., Fiakpui, C., Saraswat, N., Sharma, R., Sun, S., Maiti, S.N., Leadley, R., Edmunds, J.J.(2006) Bioorg Med Chem 14: 4379-4392
- PubMed: 16529937
- DOI: https://doi.org/10.1016/j.bmc.2006.02.040
- Primary Citation of Related Structures:
2Q1J - PubMed Abstract:
Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability.
Organizational Affiliation:
Pfizer Global Research and Development, Michigan Labs, Ann Arbor, 48105, USA. jeffrey.kohrt@pfizer.com
