The discovery of glycine and related amino acid-based factor Xa inhibitors
Journal Article
·
· Bioorgan. Med. Chem.
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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007765
- Journal Information:
- Bioorgan. Med. Chem., Journal Name: Bioorgan. Med. Chem. Journal Issue: (13) ; 2006 Vol. 14; ISSN 0968-0896; ISSN BMECEP
- Country of Publication:
- United States
- Language:
- ENGLISH
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