2feq | pdb_00002feq
orally active thrombin inhibitors
| |||||||||||||
| 2feq, resolution 2.44Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | 34P | ||||||||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
The synthesis and SAR of novel nanomolar thrombin inhibitors with the common backbone HOOC-CH(2)-d-cyclohexylalanyl-3,4-dehydroprolyl-NH-CH(2)-aryl-C(=NH)NH(2) are described together with their ecarin clotting time (ECT) prolongation as measure for thrombin inhibition ex vivo. The aryl P1-moiety mimicking the arginine part of the d-Phe-Pro-Arg derived thrombin inhibitors turned out to be a key component for in vitro potency and in vivo activity. Optimization of this part led to compounds with improved antithrombin activity in rats and dogs after oral administration compared to the recently launched anticoagulant melagatran.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
2FEQ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety., Mack H, Baucke D, Hornberger W, Lange UE, Seitz W, Hoffken HW, Bioorg Med Chem Lett. 2006 May 15;16(10):2641-7. Epub 2006 Mar 6. PMID:16517159
Page seeded by OCA on Thu Mar 20 16:51:33 2008
