Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors

European Journal of Medicinal Chemistry

Volumn 80, Issue , 2014, Pages 364-382

  Reichelt, Andreas ^a   Bailis, Julie M ^b   Bartberger, Michael D ^a   Yao, Guomin ^a   Shu, Hong ^a   Kaller, Matthew R ^a   Allen, John G ^a   Weidner, Margaret F ^b   Keegan, Kathleen S ^b   Dao, Jennifer H ^a  

^a AMGEN INC   (United States)

^b AMGEN INC   (United States)

Author keywords

Cdc7; DNA replication; Kinase inhibitor; MCM2; Thiazole

Indexed keywords

2 (2 AMINOPYRIMIDIN 4 YL) 4 (2 CHLORO 4 METHOXYPHENYL) THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2 CHLORO 4 METHYLPHENYL) THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2 FLUOROPHENYL)THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2 TRIFLUOROMETHYLPHENYL) THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2,4 DICHLOROPHENYL)THIAZOLE 5 CARBOXYLIC ACID; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2,5 DIFLUOROPHENYL)THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (3,5 DICHLOROPHENYL)THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (DIMETHYLAMINO)THIAZOLE 5 CARBOXAMIDE; 2 (2 AMINOPYRIMIDIN 4 YL) 4 (TRIFLUOROMETHYLSULFONYLOXY)THIAZOLE 5 CARBOXYLATE; 2 AMINOPYRIMIDINE 4 CARBONITRILE; 2 AMINOPYRIMIDINE 4 CARBOTHIOAMIDE; CELL CYCLE PROTEIN 7; ETHYL 2 (2 AMINOPYRIDIN 4 YL) 4 PHENYLTHIAZOLE 5 CARBOXYLATE; ETHYL 2 (2 AMINOPYRIMIDIN 4 YL) 4 (2,4 DICHLOROPHENYL) THIAZOLE 5 CARBOXYLATE; ETHYL 2 (2 ETHYL(4 PYRIDYL)) 4 HYDROXYTHIAZOLE 5 CARBOXYLATE; ETHYL 2 (PYRIDIN 4 YL) 4 (TRIFLUOROMETHYLSULFONYLOXY) THIAZOLE 5 CARBOXYLATE; ETHYL 2 TERT BUTYL 4 HYDROXYTHIAZOLE 5 CARBOXYLATE; ETHYL 4 HYDROXY 2 (4 METHOXYPHENYL) 1,3 THIAZOLE 5 ARBOXYLATE; ETHYL 4 HYDROXY 2 (4 PYRIDYL) THIAZOLE 5 CARBOXYLATE; ETHYL 4 HYDROXY 2 (PYRAZIN 2 YL)THIAZOLE 5 CARBOXYLATE; ETHYL 4 HYDROXY 2 (PYRIDIN 2 YL)THIAZOLE 5 CARBOXYLATE; ETHYL 4 HYDROXY 2 (PYRIDIN 3 YL)THIAZOLE 5 CARBOXYLATE 2,2,2 TRIFLUOROACETATE; ETHYL 4 HYDROXY 2 (THIOPHEN 3 YL)THIAZOLE 5 CARBOXYLATE; ETHYL 4 HYDROXY 2 PHENYLTHIAZOLE 5 CARBOXYLATE; ETHYL 4 METHOXY 2 (PYRIDIN 4 YL)THIAZOLE 5 CARBOXYLATE; ETHYL 4 PHENYL 2 (PYRIDIN 4 YL)THIAZOLE 5 CARBOXYLATE; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; CDC7 PROTEIN, HUMAN; CELL CYCLE PROTEIN; MCM2 PROTEIN, HUMAN; MINICHROMOSOME MAINTENANCE PROTEIN 2; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CANCER CELL; CHEMICAL STRUCTURE; DRUG ACTIVITY; DRUG SYNTHESIS; IN VITRO STUDY; MALE; NONHUMAN; PROTEIN PHOSPHORYLATION; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; ENZYME ACTIVE SITE; FEMALE; HCT116 CELL LINE; HUMAN; IC50; METABOLISM; MOLECULAR DOCKING; MOUSE; PHOSPHORYLATION; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; CATALYTIC DOMAIN; CELL CYCLE PROTEINS; CELL LINE, TUMOR; CHEMISTRY TECHNIQUES, SYNTHETIC; FEMALE; HCT116 CELLS; HUMANS; INHIBITORY CONCENTRATION 50; MALE; MICE; MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 2; MOLECULAR DOCKING SIMULATION; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84899845992     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.04.013     Document Type: Article

References (38)

1. H. Masai, and K. Arai Cdc7 kinase complex: a key regulator in the initiation of DNA replication Journal of Cellular Physiology 190 2002 287 296 (Pubitemid 34111969)
2. K. Labib How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells? Genes & Development 24 2010 1208 1219
3. J.M. Kim, N. Kakusho, M. Yamada, Y. Kanoh, N. Takemoto, and H. Masai Cdc7 kinase mediates claspin phosphorylation in DNA replication checkpoint Oncogene 27 2008 3475 3482 (Pubitemid 351769309)
4. V. Costanzo, D. Shechter, P.J. Lupardus, K.A. Cimprich, M. Gottesman, and J. Gautier An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication Molecular Cell 11 2003 203 213 (Pubitemid 36126601)
5. T. Tsuji, E. Lau, G.G. Chiang, and W. Jiang The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control Molecular Cell 32 2008 862 869
6. S. Ito, C. Taniyami, N. Arai, and H. Masai Cdc7 as a potential new target for cancer therapy Drug News & Perspectives 21 2008 481 488
7. A. Montagnoli, J. Moll, and F. Colotta Targeting cell division cycle 7 kinase: a new approach for cancer therapy Clinical Cancer Research 16 2010 4503 4508
8. R. Swords, D. Mahalingam, M. O'Dwyer, C. Santocanale, K. Kelly, J. Carew, and F. Giles Cdc7 kinase - a new target for drug development European Journal of Cancer 46 2010 33 40
9. A. Montagnoli, P. Tenca, F. Sola, D. Carpani, D. Brotherton, C. Albanese, and C. Santocanale Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells Cancer Research 64 2004 7110 7116 (Pubitemid 39331024)
10. A. Montagnoli, B. Valsasina, V. Croci, M. Menichincheri, S. Rainoldi, V. Marchesi, M. Tibolla, P. Tenca, D. Brotherton, C. Albanese, V. Patton, R. Alzani, A. Ciavolella, F. Sola, A. Molinari, D. Volpi, N. Avanzi, F. Fiorentini, M. Cattoni, S. Healy, D. Ballinari, E. Pesenti, A. Isacchi, J. Moll, A. Bensimon, E. Vanotti, and C. Santocanale A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity Nature Chemical Biology 4 2008 357 365 (Pubitemid 351693995)
11. E. Lau, G.G. Chiang, R.T. Abraham, and W. Jiang Divergent S phase checkpoint activation arising from prereplicative complex deficiency controls cell survival Molecular Biology of the Cell 20 2009 3953 3964
12. S. Tudzarova, M.W. Trotter, A. Wollenschlaeger, C. Mulvey, J. Godovac-Zimmermann, G.H. Williams, and K. Stoeber Molecular architecture of the DNA replication origin activation checkpoint EMBO Journal 29 2010 3381 3394
13. P.R. Dohrmann, G. Oshiro, M. Tecklenburg, and R.A. Sclafani RAD53 regulates DBF4 independently of checkpoint function in Saccharomyces cerevisiae Genetics 151 1999 965 977 (Pubitemid 29118108)
14. G.F. Hess, R.F. Drong, K.L. Weiland, J.L. Slightom, R.A. Sclafani, and R.E. Hollingsworth A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines Gene 211 1998 133 140 (Pubitemid 28200934)
15. D. Bonte, C. Lindvall, H. Liu, K. Dykema, K. Furge, and M. Weinreich Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation Neoplasia 10 2008 920 931
16. M. Choschzick, A. Lebeau, A.H. Marx, L. Tharun, L. Terracciano, U. Heilenkotter, F. Jaenicke, C. Bokemeyer, R. Simon, G. Sauter, and J. Schwarz Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer Human Pathology 41 2010 358 365
17. E. Vanotti, R. Amici, A. Bargiotti, J. Berthelsen, R. Bosotti, A. Ciavolella, A. Cirla, C. Cristiani, R. D'Alessio, B. Forte, A. Isacchi, K. Martina, M. Menichincheri, A. Molinari, A. Montagnoli, P. Orsini, A. Pillan, F. Roletto, A. Scolaro, M. Tibolla, B. Valsasina, M. Varasi, D. Volpi, and C. Santocanale Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships Journal of Medicinal Chemistry 51 2008 487 501 (Pubitemid 351252277)
18. M. Menichincheri, A. Bargiotti, J. Berthelsen, J.A. Bertrand, R. Bossi, A. Ciavolella, A. Cirla, C. Cristiani, V. Croci, R. D'Alessio, M. Fasolini, F. Fiorentini, B. Forte, A. Isacchi, K. Martina, A. Molinari, A. Montagnoli, P. Orsini, F. Orzi, E. Pesenti, D. Pezzetta, A. Pillan, I. Poggesi, F. Roletto, A. Scolaro, M. Tato, M. Tibolla, B. Valsasina, M. Varasi, D. Volpi, C. Santocanale, and E. Vanotti First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery Journal of Medicinal Chemistry 52 2009 293 307
19. M. Menichincheri, C. Albanese, C. Alli, D. Ballinari, A. Bargiotti, M. Caldarelli, A. Ciavolella, A. Cirla, M. Colombo, F. Colotta, V. Croci, R. D'Alessio, M. D'Anello, A. Ermoli, F. Fiorentini, B. Forte, A. Galvani, P. Giordano, A. Isacchi, K. Martina, A. Molinari, J.K. Moll, A. Montagnoli, P. Orsini, F. Orzi, E. Pesenti, A. Pillan, F. Roletto, A. Scolaro, M. Tato, M. Tibolla, B. Valsasina, M. Varasi, P. Vianello, D. Volpi, C. Santocanale, and E. Vanotti Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding Journal of Medicinal Chemistry 53 2010 7296 7315
20. A. Ermoli, A. Bargiotti, M.G. Brasca, A. Ciavolella, N. Colombo, G. Fachin, A. Isacchi, M. Menichincheri, A. Molinari, A. Montagnoli, A. Pillan, S. Rainoldi, F.R. Sirtori, F. Sola, S. Thieffine, M. Tibolla, B. Valsasina, D. Volpi, C. Santocanale, and E. Vanotti Cell division cycle 7 kinase inhibitors: 1H-pyrrolo[2,3-b]pyridines, synthesis and structure-activity relationships Journal of Medicinal Chemistry 52 2009 4380 4390
21. C.M. Shafer, M. Lindvall, C. Bellamacina, T.G. Gesner, A. Yabannavar, W. Jia, S. Lin, and A. Walter 4-(1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors Bioorganic & Medicinal Chemistry Letters 18 2008 4482 4485
22. C. Zhao, C. Tovar, X. Yin, Q. Xu, I.T. Todorov, L.T. Vassilev, and L. Chen Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors Bioorganic & Medicinal Chemistry Letters 19 2009 319 323
23. K.W. Woods, C. Lai, Y.T. Miyashiro, A.S. Florjancic, E.K. Han, N. Soni, Y. Shi, L. Lasko, J.D. Leverson, E.F. Johnson, A.R. Shoemaker, and T.D. Penning Aminopyrimidinone cdc7 kinase inhibitors Bioorganic & Medicinal Chemistry Letters 22 2012 1940 1943
24. E.S. Koltun, A.L. Tsuhako, D.S. Brown, N. Aay, A. Arcalas, V. Chan, H. Du, S. Engst, K. Ferguson, M. Franzini, A. Galan, C.R. Holst, P. Huang, B. Kane, M.H. Kim, J. Li, D. Markby, M. Mohan, K. Noson, A. Plonowski, S.J. Richards, S. Robertson, K. Shaw, G. Stott, T.J. Stout, J. Young, P. Yu, C.A. Zaharia, W. Zhang, P. Zhou, J.M. Nuss, W. Xu, and P.C. Kearney Discovery of XL413, a potent and selective CDC7 inhibitor Bioorganic & Medicinal Chemistry Letters 22 2012 3727 3731
25. N. Nakajima, and M. Ubukata Preparation of nitriles from primary amides under Swern oxidation conditions Tetrahedron Letters 38 1997 2099 2102 (Pubitemid 27117757)
26. Z.P. Demko, and K.B. Sharpless Preparation of 5-substituted 1H-tetrazoles from nitriles in water Journal of Organic Chemistry 66 2001 7945 7950 (Pubitemid 34182824)
27. R.M. Rzasa, M.R. Kaller, G. Liu, E. Magal, T.T. Nguyen, T.D. Osslund, D. Powers, V.J. Santora, V.N. Viswanadhan, H.-L. Wang, X. Xiong, W. Zhong, and M.H. Norman Structure-activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors Bioorganic & Medicinal Chemistry 15 2007 6574 6595 (Pubitemid 47302311)
28. S. Hughes, F. Elustondo, A. Di Fonzo, F.G. Leroux, A.C. Wong, A.P. Snijders, S.J. Matthews, and P. Cherepanov Crystal structure of human CDC7 kinase in complex with its activator DBF4 Nature Structural & Molecular Biology 19 2012 1101 1109
29. Gaussian 09, Revision D.01, M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, and D.J. Fox, Gaussian, Inc., Wallingford CT, 2013.
30. D.A. Case, D.A. Pearlman, J.W. Caldwell, T.E. Cheatham III, J. Wang, W.S. Ross, C.L. Simmerling, T.A. Darden, K.M. Merz, R.V. Stanton, A.L. Cheng, J.J. Vincent, M. Crowley, V. Tsui, H. Gohlke, R.J. Radmer, Y. Duan, J. Pitera, I. Massova, G.L. Seibel, U.C. Singh, P.K. Weiner, and P.A. Kollman AMBER 7 2002 University of California San Francisco
31. A. Montagnoli, B. Valsasina, D. Brotherton, S. Troiani, S. Rainoldi, P. Tenca, A. Molinari, and C. Santocanale Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases Journal of Biological Chemistry 281 2006 10281 10290 (Pubitemid 43864566)
32. W.H. Cho, Y.J. Lee, S.I. Kong, J. Hurwitz, and J.K. Lee CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein Proceedings of the National Academy of Sciences 103 2006 11521 11526 (Pubitemid 44182484)
33. S. Wang, and P.M. Fischer Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology Trends in Pharmacological Sciences 29 2008 302 313
34. A. Natoni, L.S. Murillo, A.E. Kliszczak, M.A. Catherwood, A. Montagnoli, A. Samali, M. O'Dwyer, and C. Santocanale Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells Molecular Cancer Therapeutics 10 2011 1624 1634
35. F. Pierre, P.C. Chua, S.E. O'Brien, A. Siddiqui-Jain, P. Bourbon, M. Haddach, J. Michaux, J. Nagasawa, M.K. Schwaebe, E. Stefan, A. Vialettes, J.P. Whitten, T.K. Chen, L. Darjania, R. Stansfield, K. Anderes, J. Bliesath, D. Drygin, C. Ho, M. Omori, C. Proffitt, N. Streiner, K. Trent, W.G. Rice, and D.M. Ryckman Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine- 8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer Journal of Medicinal Chemistry 54 2011 635 654
36. C.A. Thorne, A.J. Hanson, J. Schneider, E. Tahinci, D. Orton, C.S. Cselenyi, K.K. Jernigan, K.C. Meyers, B.I. Hang, A.G. Waterson, K. Kim, B. Melancon, V.P. Ghidu, G.A. Sulikowski, B. LaFleur, A. Salic, L.A. Lee, D.M. Miller 3rd, and E. Lee Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α Nature Chemical Biology 6 2010 829 836
37. G.J. Yu, C.L. Yoo, B. Yang, M.W. Lodewyk, L. Meng, T.T. El-Idressy, J.C. Fettinger, D.J. Tantillo, A.S. Verkman, and M.J. Kurth Potent s-cis-locked bithiazole correctors of DF508 cystic fibrosis transmembrane conductance regulator cellular processing for cystic fibrosis therapy Journal of Medicinal Chemistry 51 2008 6044 6054
38. H. Gökce, and S. Bahçeli Analysis of molecular structure and vibrational spectra of 2-(2'-thienyl)pyridine Journal of Molecular Structure 1005 2011 100 106