Design and synthesis of factor Xa inhibitors and their prodrugs

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 2, 2003, Pages 297-300

  Song, Yonghong ^a   Clizbe, Lane ^a   Bhakta, Chhaya ^a   Teng, Willy ^a   Wong, Paul ^a   Huang, Brian ^a   Tran, Katherine ^a   Sinha, Uma ^a   Park, Gary ^a   Reed, Andrea ^a   Scarborough, Robert M ^a   Zhu, Bing Yan ^a  

^a MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 10A INHIBITOR; AMIDINE; BLOOD CLOTTING FACTOR 10A; PRODRUG; SERINE PROTEINASE INHIBITOR;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; IC 50; NONHUMAN; RAT; ANIMAL; BIOAVAILABILITY; DRUG ANTAGONISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

AMIDINES; ANIMALS; BIOLOGICAL AVAILABILITY; DOGS; DRUG DESIGN; FACTOR XA; PRODRUGS; RATS; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037212871     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00921-6     Document Type: Article

References (12)

1. Song, Y.; Clizbe, L.; Bhakta, C.; Teng, W.; Wong, P.; Huang, B.; Tran, K.; Sinha, U.; Park, G.; Reed, A.; Scarborough, R. M.; Zhu, B.-Y. Books of Abstracts, 223th National Meeting of the American Chemical Society, Orlando, FL, April 7-11, 2002; American Chemical Society: Washington, DC, 2002; MEDI 26.
2. (a) Zhu B.-Y., Scarborough R.M. Annu. Rep. Med. Chem. 35:2000;83.
3. (b) Zhu B.-Y., Scarborough R.M. Curr. Opin. Cardiovasc., Pulm. Renal Invest. Drugs. 1:1999;63.
4. (c) Sanderson P.E.J. Annu. Rep. Med. Chem. 36:2001;79.
5. Song, Y.; Clizbe, L.; Bhakta, C.; Teng, W.; Li, W.; Wu, Y.; Jia, Z. J.; Zhang, P.; Wang, L.; Doughan, B.; Su, T.; Kanter, J.; Woolfrey, J.; Wong, P.; Huang, B.; Tran, K.; Sinha, U.; Park, G.; Reed, A.; Malinowski, J.; Hollenbach, S.; Scarborough, R. M.; Zhu, B.-Y. Books of Abstracts, Part 2, 221st National Meeting of the American Chemical Society, San Diego, CA, April 1-5, 2001; American Chemical Society: Washington, DC, 2001; MEDI 063.
6. Song Y., Clizbe L., Bhakta C., Teng W., Li W., Wu Y., Jia Z.J., Zhang P., Wang L., Doughan B., Su T., Kanter J., Woolfrey J., Wong P., Huang B., Tran K., Sinha U., Park G., Reed A., Malinowski J., Hollenbach S., Scarborough R.M., Zhu B.-Y. Bioorg. Med. Chem. Lett. 12:2002;1511.
7. Weller T., Alig L., Beresini M., Blackburn B., Bunting S., Hadvary P., Muller M.H., Knopp D., Levet-Trafit B., Lipari M.T., Modi N.B., Muller M., Refino C.J., Schmitt M., Schonholzer P., Weiss S., Steiner B. J. Med. Chem. 39:1996;3139.
8. Oh Y.S., Yun M., Hwang S.Y., Hong S., Shin Y., Lee K., Yoon K.H., Yoo Y.J., Kim D.S., Lee S.H., Lee Y.H., Park H.D., Lee C.H., Lee S.K., Kim S. Bioorg. Med. Chem. Lett. 8:1998;631.
9. 8.
10. Song Y., Clizbe L., Bhakta C., Teng W., Li W., Wong P., Huang B., Sinha U., Park G., Reed A., Scarborough R.M., Zhu B.-Y. Bioorg. Med. Chem. Lett. 12:2002;2043.
11. The prodrugs were administered orally whereas the active forms were administered intravenously. Bioavailability was calculated based on the AUC for the active form of the drug.
12. Strehlke, P.; Bohlmann, R.; Schneider, M.; Nishino, Y.; Muhn-Seipoldy, H.-P. US Patent 5,344,834, 1994.