Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 24, 2013, Pages 6610-6615

  Anderson, Kevin ^a   Chen, Yi ^a   Chen, Zhi ^a   Dominique, Romyr ^a   Glenn, Kelli ^a   He, Yang ^a   Janson, Cheryl ^a   Luk, Kin Chun ^a   Lukacs, Christine ^a   Polonskaia, Ann ^a   Qiao, Qi ^a   Railkar, Aruna ^a   Rossman, Pamela ^a   Sun, Hongmao ^a   Xiang, Qing ^a   Vilenchik, Masha ^a   Wovkulich, Peter ^a   Zhang, Xiaolei ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

Anti cancer; DYRK1A; DYRK1B; Kinase inhibitor; Pyrido 2,3 d pyrimidine

Indexed keywords

DUAL SPECIFICITY TYROSINE REGULATED KINASE 1A; DUAL SPECIFICITY TYROSINE REGULATED KINASE 1B; PHENYL GROUP; PROTEIN SERINE THREONINE KINASE; PROTEIN SERINE THREONINE KINASE INHIBITOR; PYRIDO[2,3 D]PYRIMIDINE DERIVATIVE; QUINOLONE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CHIRALITY; CRYSTAL STRUCTURE; DATA MINING; DISTRIBUTION VOLUME; DOWN REGULATION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONFORMATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG SYNTHESIS; ENANTIOSELECTIVITY; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; MOLECULAR MODEL; NONHUMAN; POLYMERIZATION; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; SUPERCRITICAL FLUID CHROMATOGRAPHY; X RAY CRYSTALLOGRAPHY;

ANTI-CANCER; DYRK1A; DYRK1B; KINASE-INHIBITOR; PYRIDO[2,3-D]PYRIMIDINE;

ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; ENZYME ACTIVATION; HALF-LIFE; HUMANS; MOLECULAR DYNAMICS SIMULATION; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; PYRIMIDINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84888862217     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.10.055     Document Type: Article

References (21)

1. E. Friedman Cancer 2 2010 1492
2. E. Friedman Int. J. Mol. Sci. 14 2013 5560
3. K. Lee, X. Deng, and E. Friedman Cancer Res. 60 2000 3631
4. X. Deng, D.Z. Ewton, S. Li, A. Naqvi, S.E. Mercer, S. Landas, and E. Friedman Cancer Res. 66 2006 4149
5. K. Jin, S. Park, D.Z. Ewton, and E. Friedman Cancer Res. 6 2007 7247
6. K. Yoshida Biochem. Pharmacol. 76 2008 1389
7. X. Deng, D.Z. Ewton, and E. Friedman Cancer Res. 69 2009 3317
8. C. Yang, D. Ji, E.J. Weinstein, E. Choy, F.J. Hornicek, K.B. Wood, X. Liu, H. Mankin, and Z. Duan Carcinogenesis 31 2010 552
9. J. Gao, Y. Zhao, Y. Lv, Y. Chen, B. Wei, J. Tian, Z. Yang, F. Kong, J. Pang, J. Liu, and H. Shi Cancer Cell Int. 13 2013 2
10. D.Z. Ewton, J. Hu, M. Vilenchik, X. Deng, K.-C. Luk, A. Polonskaia, A.F. Hoffman, K. Zipf, J.F. Boylan, and E.A. Friedman Mol. Cancer Ther. 10 2011 2104
11. J. Hu, H. Deng, and E.A. Friedman Int. J. Cancer 132 2013 2258
12. S. Leder, H. Czajkowska, B. Maenz, K. de Graaf, A. Barthel, H.G. Joost, and W. Becker Biochem. J. 372 2003 881
13. A. Ionescu, F. Dufrasne, M. Gelbcke, I. Jabin, R. Kiss, and D. Lamoral-Theys Mini-Rev. Med. Chem. 12 2012 1315
14. S. Leder, Y. Weber, X. Altafaj, X. Estivill, H.G. Joost, and W. Becker Biochem. Biophys. Res. Commun. 254 1999 474
15. Roos, A. K.; Soundararajan, M.; Elkins, J. M.; Fedorov, O.; Eswaran, J.; Phillips, C.; Pike, A. C. W.; Ugochukwu, E.; Muniz, J. R. C.; Burgess-Brown, N.; Von Delft, F.; Arrowsmith, C. H.; Wikstrom, M.; Edwards, A.; Bountra, C.; Knapp, S. 2009, Protein Data Bank entry 2WO6.
16. Caliper format DYRK1A assay was purchased from ProQinase GmbH, Breisacher Str. 117, D-79106 Freiburg, Germany.
17. F. Perandones, and J.L. Soto J. Heterocycl. Chem. 35 1998 413
18. Experimental procedures for the synthesis, enzymatic inhibition assays and cellular assays of compounds in this article are described in: Anderson, K.; Chen, Y.; Chen, Z.; Luk, K.-C.; Rossman, P. L.; Sun, H.; Wovkulich, P. M. Patent application US 20120184542 A1; Chem. Abstr. 2012, 157, 229681.
19. Y. Lu, T. Shi, Y. Wang, H. Yang, X. Yan, X. Luo, H. Jiang, and W. Zhu J. Med. Chem. 52 2009 2855
20. O. Fedorov, K. Huber, A. Eisenreich, P. Filippakopoulos, O. King, A.N. Bullock, D. Szklarczyk, L.J. Jensen, D. Fabbro, J. Trappe, U. Rauch, F. Bracher, and S. Knapp Chem. Biol. 18 2011 67
21. R. Wilcken, M.O. Zimmermann, A. Lange, A.C. Joerger, and F.M. Boeckler J. Med. Chem. 56 2013 1363