| Literature DB >> 10715154 |
Y K Yee1, A L Tebbe, J H Linebarger, D W Beight, T J Craft, D Gifford-Moore, T Goodson, D K Herron, V J Klimkowski, J A Kyle, J S Sawyer, G F Smith, J M Tinsley, R D Towner, L Weir, M R Wiley.
Abstract
Reversal of the A-ring amide link in 1,2-dibenzamidobenzene 1 (fXa K(ass) = 0.81 x 10(6) L/mol) led to a series of human factor Xa (hfXa) inhibitors based on N(2)-aroylanthranilamide 4. Expansion of the SAR around 4 showed that only small planar substituents could be accommodated 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 of hfXa. The central (C) ring containing a 5-methanesulfonamido group yielded greater activity than carbamoyl groups. Combining the beneficial features from the B- and C-ring SAR, compound 55 represents the most potent hfXa inhibitor in the N(2)-aroylanthranilamide 4 series with hfXa K(ass) = 58 x 10(6) L/mol (K(i) = 11.5 nM).Entities:
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Year: 2000 PMID： 10715154 DOI： 10.1021/jm990327e
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446