2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: Modification of target structure to minimize reactive metabolite formation

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 24, 2011, Pages 7325-7330

  Weinberg, Linda R ^a   Albom, Mark S ^a   Angeles, Thelma S ^a   Breslin, Henry J ^a   Gingrich, Diane E ^a   Huang, Zeqi ^a   Lisko, Joseph G ^a   Mason, Jennifer L ^a   Milkiewicz, Karen L ^a   Thieu, Tho V ^a   Underiner, Ted L ^a   Wells, Gregory J ^a   Wells Knecht, Kevin J ^a   Dorsey, Bruce D ^a  

^a CEPHALON INC   (United States)

Author keywords

Glutathione; JAK2; Kinase inhibitors; Pyrrolotriazine

Indexed keywords

2,7 PYRROLO[2,1 F][1,2,4]TRIAZINE; ANILINE; DRUG METABOLITE; GLUTATHIONE; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; HEMATOPOIESIS; HUMAN; MUTATION; MYELOPROLIFERATIVE DISORDER; MYELOPROLIFERATIVE NEOPLASM; STRUCTURE ACTIVITY RELATION;

AMINO ACID SUBSTITUTION; GLUTATHIONE; HUMANS; JANUS KINASE 2; MYELOPROLIFERATIVE DISORDERS; PROTEIN KINASE INHIBITORS; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES;

EID: 81255157474     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.10.032     Document Type: Article

References (17)

1. Y. Hitoshi, N. Lin, D.G. Payan, and V. Markovtsov Int. J. Hematol. 91 2010 189
2. R. Kiss, P.P. Sayeski, and G.M. Keseru Expert Opin. Ther. Pat. 20 2010 471
3. A. Quintas-Cardama, H. Kantarjian, J. Cortes, and S. Verstovsek Nat. Rev. Drug Disc. 10 2011 127
4. M.E. Flanagan, T.A. Blumenkopf, W.H. Brissette, M.F. Brown, J.M. Casavant, C. Shang-Poa, J.L. Doty, E.A. Elliott, M.B. Fisher, M. Hines, C. Kent, E.M. Kudlacz, B.M. Lillie, K.S. Magnuson, S.P. McCurdy, M.J. Munchhof, B.D. Perry, P.S. Sawyer, T.J. Strelevitz, C. Subramanyam, J. Sun, D.A. Whipple, and P.S. Changelian J. Med. Chem. 53 2010 8468
5. C.J. Malemud Pharmaceuticals 3 2010 1446
6. S. Verstovsek Clin. Cancer Res. 16 2010 1988
7. Ahmed, G.; Bohnstedt, A.; Breslin, H. J.; Burke, J.; Curry, M. A.; Diebold, J. L.; Dorsey, B.; Dugan, B. J.; Feng, D.; Gingrich, D. E.; Guo, T.; Ho, K.; Learn, K. S.; Lisko, J. G.; Liu, R.; Mesaros, E. F.; Milkiewicz, K.; Ott, G. R.; Parrish, J.; Theroff, J. P.; Thieu, T. V.; Tripathy, R.; Underiner, T. L.; Wagner, J. C.; Weinberg, L.; Wells, G. J.; You, M.; Zificsak, C. A. International Patent WO 2008051547A1, 2008.
8. T. Thieu, J.A. Sclafani, D.V. Levy, A. McLean, H.J. Breslin, G.R. Ott, R. Bakale, and B.D. Dorsey Org. Lett. 13 2011 4204
9. Ott, G. R.; Wells, G. J.; Thieu, T. V.; Quail, M. R.; Lisko, J. G.; Mesaros, E. F.; Gingrich, D. E.; Ghose, A. K.; Wan, W.; Lu, L.; Cheng, M.; Albom, M. S.; Angeles, T. S.; Huang, Z.; Aimone, L. D.; Ator, M. A.; Ruggeri, B. A.; Dorsey, B. D. J. Med. Chem. 2011, dx.doi.org/10.1021/jm200758k.
10. J. Gan, Q. Ruan, B. He, M. Zhu, W.C. Shyu, and W.G. Humphreys Chem. Res. Toxicol. 22 2009 690
11. C.E.C.A. Hop, A.S. Kalgutkar, and J.R. Soglia Annu. Rep. Med. Chem. 41 2006 369
12. B.K. Park, N.R. Kitteringham, J.L. Maggs, M. Pirmohamed, and D.P. Williams Annu. Rev. Pharmacol. Toxicol. 45 2005 177
13. Wells-Knecht, K. J.; Ott, G. R.; Cheng, M., Wells, G. J.; Breslin, H.; Gingrich, D.; Weinberg, L.; Mesaros, E.; Huang, Z.; Yazdanian, M.; Ator, M. A.; Aimone, L.; Zeigler, K.; Dorsey, B. D. Chem. Res. Toxicol. 2011, submitted for publication.
14. J.L. Walgren, M.D. Mitchell, and D.C. Thompson Crit. Rev. Toxicol. 35 2005 325
15. D.P. Walker, F.C. Bi, A.S. Kalgutkar, J.N. Bauman, S.X. Zhao, J.R. Soglia, G.E. Aspnes, D.W. Kung, J. Klug-McLeod, M.P. Zawistoski, M.A. McGlynn, R. Oliver, M. Dunn, J. Li, D.T. Richter, B.A. Cooper, J.C. Kath, C.A. Hulford, C.L. Autry, M.J. Luzzio, E.J. Ung, W.G. Roberts, P.C. Bonnette, L. Buckbinder, A. Mistry, M.C. Griffor, S. Han, and A. Guzman-Perez Bioorg. Med. Chem. Lett. 18 2008 6071
16. Breslin, H. J.; Chatterjee, S.; Diebold, J. L.; Dorsey, B.; Dunn, D.; Gingrich, D. E.; Hostetler, G. A.; Hudkins, R. L.; Hunter, R.; Josef, K.; Lisko, J. G.; Mesaros, E. F.; Milkiewicz, K.; Ott, G. R.; Sundar, B. G.; Theroff, J. P.; Thieu, T.; Tripathy, R.; Underiner, T. L.; Weinberg, L.; Wells, G. J. International Patent WO 2010071885A1, 2008.
17. Mesaros, E. F.; Thieu, T. V.; Wells, G. J.; Zificsak, C. A.; Wagner, J. C.; Breslin, H. J.; Tripathy, R.; Diebold, J. L.; McHugh, R. J.; Wohler, A. T.; Quail, M. R.; Wan, W.; Lu, L.; Huang, Z.; Albom, M. S.; Angeles, T. S.; Wells-Knecht, K.; Aimone, L. D.; Cheng, M.; Ator, M. A.; Ott, G. R.; Dorsey, B. D. J. Med. Chem. 2011, submitted for publication.