2FES
Orally active thrombin inhibitors
Summary for 2FES
| Entry DOI | 10.2210/pdb2fes/pdb |
| Related | 1O0D |
| Related PRD ID | PRD_000480 PRD_000613 |
| Descriptor | Thrombin light chain, Thrombin heavy chain, Decapeptide Hirudin Analogue, ... (5 entities in total) |
| Functional Keywords | thrombin inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) More |
| Cellular location | Secreted, extracellular space: P00734 P00734 |
| Total number of polymer chains | 3 |
| Total formula weight | 35854.95 |
| Authors | Hoeffken, H.W. (deposition date: 2005-12-16, release date: 2006-05-09, Last modification date: 2023-08-30) |
| Primary citation | Mack, H.,Baucke, D.,Hornberger, W.,Lange, U.E.W.,Seitz, W.,Hoeffken, H.W. Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Bioorg.Med.Chem.Lett., 16:2641-2647, 2006 Cited by PubMed Abstract: 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. PubMed: 16517159DOI: 10.1016/j.bmcl.2006.02.040 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.42 Å) |
Structure validation
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