Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 16, 2004, Pages 4165-4168

  Gomtsyan, Arthur ^a   Didomenico, Stanley ^a   Lee, Chih Hung ^a   Stewart, Andrew O ^a   Bhagwat, Shripad S ^a,b   Kowaluk, Elizabeth A ^a   Jarvis, Michael F ^a  

^a ABBOTT LABORATORIES   (United States)

^b CELGENE CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE KINASE INHIBITOR; PTERIDINE DERIVATIVE; PYRAZOLOPYRIMIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ARTICLE; CHEMICAL MODIFICATION; DRUG SCREENING; DRUG SYNTHESIS; SUBSTITUTION REACTION;

ADENOSINE KINASE; ENZYME INHIBITORS; PTERIDINES; PYRAZOLES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 3142771943     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.06.029     Document Type: Article

References (22)

1. Ralevic V., Burnstock G. Pharmacol. Rev. 50:1998;413
2. Williams M., Jarvis M. Biochem. Pharmacol. 59:2000;1173
3. Arch J.R.S., Newsholme E.A. Essays Biochem. 14:1978;82
4. Moser G.H., Schrader J., Duessen A. Am. J. Physiol. 25:1989;C799
5. Davies L.P., Jamieson D.D., Baird-Lambert J.A., Kazlauskas R. Biochem. Pharmacol. 33:1984;347
6. For more nucleoside-type AK inhibitors, see: Cowart M.C., Bennett M.J., Kerwin J.F. Jr. J. Org. Chem. 64:1999;2240
7. Erion M.D., Ugarkar B.G., DaRe J., Castellino A.J., Fujitaki J.M., Dixon R., Appleman J.R., Wiesner J.B. Nucleos. Nucleot. 16:1997;1013
8. Ugarkar B.G., Castellino A.J., DaRe J.S., Ramirez-Weinhouse M., Kopcho J.J., Rosengren S., Erion M.D. J. Med. Chem. 46:2003;4750. and references cited therein
9. Lee C.-H., Jiang M., Cowart M., Gfesser G., Perner R., Kim K., Gu Y.G., Williams M., Jarvis M., Kowaluk E., Stewart A., Bhagwat S. J. Med. Chem. 44:2001;2133
10. Cowart M., Lee C.-H., Gfesser G.A., Bayburt E.K., Bhagwat S.S., Stewart A.O., Yu H., Kohlhaas K.L., McGaraughty S., Wismer C.T., Mikusa J., Zhu C., Alexander K.M., Jarvis M.F., Kowaluk E.A. Bioorg. Med. Chem. Lett. 11:2001;83-86
11. Gfesser G.A., Bayburt E.K., Cowart M., Didomenico S., Gomtsyan A., Lee C.-H., Stewart A.O., Jarvis M.F., Kowaluk E.A., Bhagwat S.S. Eur. J. Med. Chem. 38:2003;245
12. Perner R.J., Gu Y.-G., Lee C.-H., Bayburt E.K., McKie J., Alexander K.M., Kohlhaas K.L., Wismer C.T., Mikusa J., Jarvis M.F., Kowaluk E.A., Bhagwat S.S. J. Med. Chem. 46:2003;5249
13. Gomtsyan A., Didomenico S., Lee C.-H., Matulenko M.A., Kim K., Kowaluk E.A., Wismer C.T., Mikusa J., Yu H., Kohlhaas K., Jarvis M.F., Bhagwat S.S. J. Med. Chem. 45:2002;3639
14. For a review on nonnucleoside AK inhibitors, see: Gomtsyan A., Lee C.-H. Curr. Pharmaceut. Des. 10:2004;1093
15. Hajduk P.J., Gomtsyan A., Didomenico S., Cowart M., Bayburt E.K., Solomon L., Severin J., Smith R., Walter K., Holzman T.F., Stewart A., McGaraughty S., Jarvis M.F., Kowaluk E.A., Fesik S.W. J. Med. Chem. 43:2000;4781
16. Kuo D.L. Tetrahedron. 48:1992;9233
17. Temple C., Laseter A.G., Rose J.D., Montgomery J.A. J. Heterocycl. Chem. 7:1970;1195
18. Larock R.C., Yum E.K. J. Am. Chem. Soc. 113:1991;6689
19. Larock R.C., Yum E.K., Refvik M.D. J. Org. Chem. 63:1998;7652
20. One of the reviewers offered to explain that discrepancy by a limited overall size of the binding pocket, that is, the morpholino and methyl groups make 13e larger and consequently less fit to the binding pocket than morpholino and hydrogen in 13d. Although this could be a reasonable argument, there are many pyridopyrimidine AK inhibitors with the 7-substituent much larger than morpholino group, but still showing single or low double digit potency, see: Zheng G.Z., Mao Y., Lee Ch.-H., Pratt J.R., Koenig R.J., Perner R., Cowart M., Gfesser G., McGaraughty S., Chu K., Zhu C., Yu H., Kohlhaas K., Alexander K., Wismer C., Mikusa J., Jarvis M.F., Kowaluk E.A., Stewart A.O. Bioorg. Med. Chem. Lett. 13:2003;3041
21. For the description of AK inhibition assay, see: Jarvis M.F., Yu H., Kohlhaas K., Alexander K., Lee C.-H., Jiang M., Bhagwat S.S., Williams M., Kowaluk E.A. J. Pharmacol. Exp. Ther. 295:2000;1165
22. Unpublished data