التفاصيل البيبلوغرافية
| العنوان: |
N2-Aroylanthranilamide Inhibitors of Human Factor Xa |
| المؤلفون: |
Yee, Y. K., Tebbe, A. L., Linebarger, J. H., Beight, D. W., Craft, T. J., Gifford-Moore, D., Goodson, T., Jr., Herron, D. K., Klimkowski, V. J., Kyle, J. A., Sawyer, J. S., Smith, G. F., Tinsley, J. M., Towner, R. D., Weir, L., Wiley, M. R. |
| المصدر: |
Journal of Medicinal Chemistry; March 9, 2000, Vol. 43 Issue: 5 p873-882, 10p |
| مستخلص: |
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 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 N2-aroylanthranilamide 4 series with hfXa Kass = 58 × 106 L/mol (Ki = 11.5 nM). |
| قاعدة البيانات: |
Supplemental Index |