2002 pharmacology, medicinal chemistry, vaccines, serums

pharmacology, medicinal chemistry, vaccines, serumsV 1100

32 - 241Non-Covalent Thrombin Inhibitors Featuring P3-Heterocycles withP1-Monocyclic Arginine Surrogates. — A structure-based designstrategy, which hybridizes the prototypical P3-pyridone-P1-argininals alongwith reference inhibitors, leads to a novel family of non-covalent thrombininhibitors such as (I) and (II). The S2 specificity pocket is investigated witheight P4-residues and the S1 pocket with fifteen rigid arginine surrogates byretention of the potent P3-pyridine and pyrazinone pharmacophores at the S2

pocket. Inhibitors of greatest interest in terms of activity, selectivity, and/orPK profiles include targets (I) and (II). — (SEMPLE, J. EDWARD; ET AL.;Bioorg. Med. Chem. Lett. 12 (2002) 8, 1203-1208; Dep. Med. Chem., CorvasInt., Inc., San Diego, CA 92121, USA; EN)

1