Synthesis and biological evaluation of imidazo[4,5-b]pyridine and 4-heteroaryl-pyrimidine derivatives as anti-cancer agents

European Journal of Medicinal Chemistry

Volumn 57, Issue , 2012, Pages 311-322

  Lukasik, Pawel M ^a   Elabar, Sherifa ^a   Lam, Frankie ^a,b   Shao, Hao ^a   Liu, Xiangrui ^a   Abbas, Abdullah Y ^a   Wang, Shudong ^a,b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

Author keywords

Anti tumour activity; Cancer therapy; Cyclin dependent kinase; Drug discovery; Induction of apoptosis; Mcl 1 anti apoptotic protein; RNA polymerase II

Indexed keywords

3 [4 (1H INDAZOL 1 YL)PYRIMIDIN 2 YLAMINO]BENZENESULFONAMIDE; 4 INDAZOLYL N PHENYLPYRIMIDIN 2 AMINE DERIVATIVE; ANTINEOPLASTIC AGENT; CASPASE 3; CASPASE 7; IMIDAZO[4,5 B]PYRIDINE DERIVATIVE; N PHENYL 4 PYRAZOLO[3,4 B]PYRIDINE PYRIMIDIN 2 AMINE DERIVATIVE; N PHENYLIMIDAZO[4,5 B]PYRIDINE 2 AMINE DERIVATIVE; PROTEIN MCL 1; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVATION; HUMAN; HUMAN CELL; REACTION ANALYSIS; STRUCTURE ANALYSIS;

AMINES; ANTINEOPLASTIC AGENTS; APOPTOSIS; CASPASE 3; CASPASE 7; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 9; DRUG DESIGN; DRUG DISCOVERY; ENZYME ACTIVATION; HUMANS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-BCL-2; PYRIDINES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84867421937     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.09.034     Document Type: Article

References (14)

1. S. Lapenna, and A. Giordano Cell cycle kinases as therapeutic targets for cancer Nat. Rev. Drug Discov. 8 2009 547 566
2. S. Wang, and P.M. Fischer Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology Trends Pharmacol. Sci. 6 2008 302 313
3. C. Barriere, D. Santamaria, A. Cerqueira, J. Galan, A. Martin, S. Ortega, M. Malumbres, P. Dubus, and M. Barbacid Mice thrive without Cdk4 and Cdk2 Mol. Oncol. 1 2007 72 83
4. J.C. Byrd, T.S. Lin, J.T. Dalton, D. Wu, M.A. Phelps, B. Fischer, M. Moran, K.A. Blum, B. Rovin, M. Brooker-McEldowney, S. Broering, L.J. Schaaf, A.J. Johnson, D.M. Lucas, N.A. Heerema, G. Lozanski, D.C. Young, J.R. Suarez, A.D. Colevas, and M.R. Grever Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia Blood 109 2007 399 404
5. R. Chen, M.J. Keating, V. Gandhi, and W. Plunkett Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death Blood 106 2005 2513 2519
6. R. Chen, W.G. Wierda, S. Chubb, R.E. Hawtin, J.A. Fox, M.J. Keating, V. Gandhi, and W. Plunkett Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia Blood 113 2009 4637 4645
7. S. Wang, C. Meades, G. Wood, A. Osnowski, S. Anderson, R. Yuill, M. Thomas, M. Mezna, W. Jackson, C. Midgley, G. Griffiths, I. Fleming, S. Green, I. McNae, S.Y. Wu, C. McInnes, D. Zheleva, M.D. Walkinshaw, and P.M. Fischer 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity J. Med. Chem. 47 2004 1662 1675
8. S. Wang, G. Wood, C. Meades, G. Griffiths, C. Midgley, I. McNae, C. McInnes, S. Anderson, W. Jackson, M. Mezna, R. Yuill, M. Walkinshaw, and P.M. Fischer Synthesis and biological activity of 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine CDK inhibitors Bioorg. Med. Chem. Lett. 14 2004 4237 4240
9. S. Wang, G. Griffiths, C.A. Midgley, A.L. Barnett, M. Cooper, J. Grabarek, L. Ingram, W. Jackson, G. Kontopidis, S.J. McClue, C. McInnes, J. McLachlan, C. Meades, M. Mezna, I. Stuart, M.P. Thomas, D.I. Zheleva, D.P. Lane, R.C. Jackson, D.M. Glover, D.G. Blake, and P.M. Fischer Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents Chem. Biol. 17 2010 1111 1121
10. S. Wang, C.A. Midgley, F. Scaerou, J.B. Grabarek, G. Griffiths, W. Jackson, G. Kontopidis, S.J. McClue, C. McInnes, C. Meades, M. Mezna, A. Plater, I. Stuart, M.P. Thomas, G. Wood, R.G. Clarke, D.G. Blake, D.I. Zheleva, D.P. Lane, R.C. Jackson, D.M. Glover, and P.M. Fischer Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors J. Med. Chem. 53 2010 4367 4378
11. X. Liu, S. Shi, F. Lam, C. Pepper, P.M. Fischer, and S. Wang CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol Int. J. Cancer 130 2012 1216 1226
12. X. Liu, F. Lam, S. Shi, P.M. Fischer, and S. Wang In vitro antitumor mechanism of a novel cyclin-dependent kinase inhibitor CDKI-83 Invest. New Drugs 30 2012 889 897
13. F. Crestey, S. Stiebing, R. Legay, V. Collot, and S. Rault Design and synthesis of a new indazole library: direct conversion of N-methoxy-N- methylamides (Weinreb amides) to 3-keto and 3-formylindazoles Tetrahedron 63 2007 419 428
14. I.K. Khanna, R.M. Weier, K.T. Lentz, L. Swenton, and D.C. Lankin Facile, regioselective syntheses of N-alkylated 2,3-diaminopyridines and imidazo[4,5-b]pyridines J. Org. Chem. 60 1995 960 965