Bicyclic pyridones as potent, efficacious and orally bioavailable thrombin inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 10, 2000, Pages 1069-1072

  Coburn, Craig A ^a   Rush, Diane M ^a   Williams, Peter D ^a   Homnick, Carl ^a   Lyle, Elizabeth A ^a   Lewis, S Dale ^a   Lucas Jr , Bobby J ^a   Di Muzio Mower, Jillian M ^a   Juliano, Marylou ^a   Krueger, Julie A ^a   Vastag, Kari ^a   Chen, I Wu ^a   Vacca, Joseph P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PYRIDONE DERIVATIVE; THROMBIN; THROMBIN INHIBITOR; TRYPSIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTERY THROMBOSIS; ARTICLE; DOG; DRUG ABSORPTION; DRUG DESIGN; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; DRUG SYNTHESIS; EXPERIMENTAL MODEL; MOLECULAR MIMICRY; NONHUMAN; PROTEIN MODIFICATION; RAT; THROMBOSIS PREVENTION;

ACETAMIDES; AMINOPYRIDINES; ANIMALS; ANTICOAGULANTS; BIOLOGICAL AVAILABILITY; DIPEPTIDES; DOGS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; MOLECULAR MIMICRY; PYRIDONES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN; THROMBOSIS;

ANIMALIA; CANIS FAMILIARIS;

EID: 18344409157     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00170-0     Document Type: Article

References (10)

1. Goldsack N.R., Chambers R.C., Dabbag K., Laurent J. Int. J. Biochem. Cell Biol. 30:1998;641.
2. Fevig J.M., Wexler R.R. Ann. Rep. Med. Chem. 34:1999;81.
3. Sanderson P.E.J., Dyer D.L., Naylor-Olsen A.M., Vacca J.P., Gardell S.J., Lewis S.D., Lucas B.J., Lyle E.A., Lynch J.J., Mulichak A.M. Bioorg. Med. Chem. Lett. 7:1997;1497.
4. Tamura S.T., Semple J.E., Reiner J.E., Goldman E.A., Brunck T.K., Lim-Wilby M.S., Carpenter S.H., Rote W.E., Oldeshulte G.L., Richard B.M., Nutt R.F., Ripka W.C. Bioorg. Med. Chem. Lett. 7:1997;1543.
5. Sanderson P.E.J., Cutrona K.J., Dorsey B.D., Dyer D.L., McDonough C.J., Naylor-Olsen A.M., Chen I.-W., Chen Z., Cook J.J., Gardell S.J., Krueger J.A., Lewis S.D., Lin J.H., Lucas B.J., Lyle E.A., Lynch J.J., Stranieri M.T., Vastag K., Shafer J.A., Vacca J.P. Bioorg. Med. Chem. Lett. 8:1998;817.
6. Sanderson P.E.J., Lyle T.A., Cutrona K.J., Dyer D.L., Dorsey B.D., McDonough C.J., 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., Lyle E.A., Lynch J.J., Stranieri M.T., Vastag K., Yan Y., Shafer J.A., Vacca J.P. J. Med. Chem. 41:1998;4466.
7. Clive D.L.J., Sedgeworth J. J. Heterocycl. Chem. 24:1987;509.
8. Hoffman J.M., Wai J.S., Thomas C.M., Levin R.B., O'Brien J.A., Goldman M.E. J. Med. Chem. 35:1992;3784.
9. Separation of the enantiomers of these bicyclic compounds was performed on a Chiracel OD column (9:1 hexane:EtOH containing 0.1% diethylamine).
10. Kurz K.D., Main B.W., Sandusky G.E. Thromb. Res. 60:1990;269.