Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates

التفاصيل البيبلوغرافية
العنوان:	Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates
المؤلفون:	Sanderson, P. E. J., Lyle, T. A., Cutrona, K. J., Dyer, D. L., Dorsey, B. D., McDonough, C. M., Naylor-Olsen, A. M., Chen, I-W., Chen, Z., Cook, J. J., Cooper, C. M., Gardell, S. J., Hare, T. R., Krueger, J. A., Lewis, S. D., Lin, J. H., Lucas, B. J., Jr., Lyle, E. A., Lynch, J. J., Jr., Stranieri, M. T., Vastag, K., Yan, Y., Shafer, J. A., Vacca, J. P.
المصدر:	Journal of Medicinal Chemistry; November 5, 1998, Vol. 41 Issue: 23 p4466-4474, 9p
مستخلص:	We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804