| Abstract
| - Reversal of the A-ring amide link in 1,2-dibenzamidobenzene 1 (fXa Kass = 0.81 × 106 L/mol)led to a series of human factor Xa (hfXa) inhibitors based on N2-aroylanthranilamide 4.Expansion of the SAR around 4 showed that only small planar substituents could beaccommodated in the A-ring for binding to the S1 site of hfXa. Bulky groups such as 4-isopropyl,4-tert-butyl, and 4-dimethylamino were favored in the B-ring to interact with the S4 site ofhfXa. The central (C) ring containing a 5-methanesulfonamido group yielded greater activitythan carbamoyl groups. Combining the beneficial features from the B- and C-ring SAR,compound 55 represents the most potent hfXa inhibitor in the N2-aroylanthranilamide 4 serieswith hfXa Kass = 58 × 106 L/mol (Ki = 11.5 nM).
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