3-Amino-4-sulfonylpyridinone acetamide and related pyridothiadiazine thrombin inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 8, 2003, Pages 1441-1444

  Sanderson, Philip E J ^a   Cutrona, Kellie J ^a   Savage, Kelly L ^a   Naylor Olsen, Adel M ^a   Bickel, Denise J ^a   Bohn, Dennis L ^a   Clayton, Franklin C ^a   Krueger, Julie A ^a   Lewis, S Dale ^a   Lucas, Bobby J ^a   Lyle, Elizabeth A ^a   Wallace, Audrey A ^a   Welsh, Denice C ^a   Yan, Youwei ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; AMINOPYRIDINE DERIVATIVE; BICYCLO COMPOUND; CYCLOPROPANE DERIVATIVE; FERRIC CHLORIDE; HYDROGEN; PLASMA KALLIKREIN; PLASMIN; PYRIDONE DERIVATIVE; SULFONE DERIVATIVE; THIADIAZINE DERIVATIVE; THROMBIN; THROMBIN INHIBITOR; TYROSINE;

ANIMAL EXPERIMENT; ARTERY THROMBOSIS; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DOG; DRUG BINDING SITE; DRUG CONFORMATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HYDROGEN BOND; MOLECULAR MODEL; NONHUMAN; RAT; X RAY CRYSTALLOGRAPHY;

CANIS FAMILIARIS; INSERTION SEQUENCES;

EID: 0037451873     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00154-9     Document Type: Article

References (19)

1. Coburn C.A. Exp. Opin. Ther. Pat. 11:2001;1.
2. 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., 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.
3. Sanderson P.E.J., Cutrona K.J., Dyer D.L., Krueger J.A., Kuo L.C., Lewis S.D., Lucas B.J., Yan Y. Bioorg. Med. Chem. Lett. 13:2003;161.
4. Sanderson, P. E. J., Lyle, T. A., Coburn, C. A. WO199831670, 1998; US Patent 6,017,934, 2000.
5. For covalent, boronate thrombin inhibitors containing 4-sulfonylpyridinone acetamide groups, see: Lassalle, G.; Bellevergue, P.; Mallart, S.; Bourbier, J. C.; Galtier, D.; Martin, V. FR 2758329, 1998.
6. Sanderson, P. E. J.; Cutrona, K. J. US Patent 6,117,888, 2000.
7. Coburn C.A., Rush D.M., Williams P.D., Homnick C., Lyle E.A., Lewis S.D., Lucas B.J., Di Muzio-Mower J.M., Juliano M., Krueger J.A., Vastag K., Chen I.-W., Vacca J.P. Bioorg. Med. Chem. Lett. 10:2000;1069. See also ref 1.
8. For covalent, arginine aldehyde derivatives with 4-alkylpyridinone acetamide groups see: Reiner J.E., Lim-Wilby S., Brunck T.K., Ha-Uong T., Goldman E.A., Abelman M.A., Nutt R.F., Semple J.E., Tamura S.Y. Bioorg. Med. Chem. Lett. 9:1999;895.
9. Coburn, C. A., Kolatac, C., Rush, D. M., Vacca, J. P. US Patent 5,869,487, 1999.
10. For the synthesis of a related 4-(trifluoromethylsulfonyloxy)pyridinone, see: Lassalle, G.; Bellevergue, P.; Bourbier, J. C.; Galtier, D.; Martin, V. WO9831671, 1998; US Patent 6,252,082, 2001. See also ref 5.
11. Ueno Y., Kojima A., Okawara M. Chem. Lett. 1984;2125.
12. Conditions developed for the reductive cleavage of benzothiazole-2-sulfonamides: Vedejs E., Lin S., Klapars A., Wang J. J. Am. Chem. Soc. 118:1996;9796.
13. For the reaction of lithium sulfinates with NCS, see: Graham S.L., Hoffman J.M., Gautheron P., Michelson S.R., Scholz T.H., Schwam H., Shepard K.L., Smith A.M., Smith R.L., Sondey J.M., Sugrue M.F. J. Med. Chem. 33:1990;749.
14. Cragoe E.J., Nicholson J.A., Sprague J.M. J. Med. Pharm. Chem. 4:1961;369.
15. i data quoted in this report are for the human enzymes.
16. Kurz K.D., Main B.W., Sandusky G.E. Thromb. Res. 60:1990;269 Lewis S.D., Ng A.S., Lyle E.A., Mellot M.J., Appleby S.D., Brady S.F., Stauffer K.J., Sisko J.T., Mao S.-S., Veber D.F., Nutt R.F., Lynch J.J., Cook J.J., Gardell S.J., Shafer J.A. Thromb. Haemost. 74:1995;1107.
17. Kurz K.D., Main B.W., Sandusky G.E. Thromb. Res. 60:1990;269 Lewis S.D., Ng A.S., Lyle E.A., Mellot M.J., Appleby S.D., Brady S.F., Stauffer K.J., Sisko J.T., Mao S.-S., Veber D.F., Nutt R.F., Lynch J.J., Cook J.J., Gardell S.J., Shafer J.A. Thromb. Haemost. 74:1995;1107.
18. sym of 0.057 and completeness of 98%. The structure was determined using the difference Fourier method and was refined to an R factor of 0.199.
19. sym of 0.057 and completeness of 98%. The structure was determined using the difference Fourier method and was refined to an R factor of 0.199.