2q1j

From Proteopedia

Revision as of 21:22, 12 November 2007

The discovery of glycine and related amino acid-based factor xa inhibitors

Overview

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.

Disease

Known disease associated with this structure: Factor X deficiency OMIM:[227600]

About this Structure

2Q1J is a Protein complex structure of sequences from Homo sapiens with CA and FXI as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.

Reference

The discovery of glycine and related amino acid-based factor Xa inhibitors., Kohrt JT, Filipski KJ, Cody WL, Bigge CF, La F, Welch K, Dahring T, Bryant JW, Leonard D, Bolton G, Narasimhan L, Zhang E, Peterson JT, Haarer S, Sahasrabudhe V, Janiczek N, Desiraju S, Hena M, Fiakpui C, Saraswat N, Sharma R, Sun S, Maiti SN, Leadley R, Edmunds JJ, Bioorg Med Chem. 2006 Jul 1;14(13):4379-92. Epub 2006 Mar 10. PMID:16529937

Page seeded by OCA on Mon Nov 12 23:28:51 2007