Imidazole moiety replacements in the 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor receptor-1 (IGF-1R) to improve cytochrome P450 profile

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 11, 2007, Pages 3072-3076

  Velaparthi, Upender ^a   Liu, Peiying ^a   Balasubramanian, Balu ^a   Carboni, Joan ^a   Attar, Ricardo ^a   Gottardis, Marco ^a   Li, Aixin ^a   Greer, Ann ^a   Zoeckler, Mary ^a   Wittman, Mark D ^a   Vyas, Dolatrai ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Benzimidazole; CYP450 inhibition; IGF 1R; Imidazole; Imidazoline; Insulin like growth factor 1 receptor; Pyridone; Tyrosine kinase

Indexed keywords

3 (1H BENZI[D]IMIDAZOL 2 YL)PYRIDIN 2(1H) ONE; BENZIMIDAZOLE DERIVATIVE; CYTOCHROME P450; IMIDAZOLE; PYRIDINE DERIVATIVE; SOMATOMEDIN C RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; IMIDAZOLES; INHIBITORY CONCENTRATION 50; RECEPTOR, IGF TYPE 1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34247844537     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.03.048     Document Type: Article

References (34)

1. Baserga R. Expert Opin. Ther. Targets 9 (2005) 753
2. Garcia-Echeverria C. IDrugs 9 (2006) 415
3. Baserga R. Oncogene 183 (2000) 1
4. Valentinis B., and Baserga R. J. Clin. Pathol. Mol. Pathol. 54 (2001) 133
5. Pollak M.N., Schernhammer E.S., and Hankinson S.E. Nat. Rev. Cancer 4 (2004) 505
6. Yee D. Br. J. Cancer 94 (2006) 465
7. Hofmann F., and Garcia-Echeverria C. Drug Discov. Today 10 (2005) 1041
8. Bahr C., and Groner B. Growth Horm. IGF Res. 14 (2004) 287
9. Zhang H., and Yee D. Expert Opin. Investig. Drugs 13 (2004) 1569
10. Reiss K., Wang J.Y., Romano G., Furnari F.B., Cavenee W.K., Morrione A., Tu X., and Baserga R. Oncogene 19 (2000) 2687
11. Reiss K., Wang J.Y., Romano G., Tu X., Peruzzi F., and Baserga R. Oncogene 20 (2001) 490
12. Yu H., and Rohan T. J. Natl. Cancer Inst. 92 (2000) 1472
13. Baserga R. Cancer Res. 55 (1995) 249
14. Garcia-Echeverria C., Pearson M.A., Marti A., Meyer T., Mestan J., Zimmermann J., Gao J., Brueggen J., Capraro H.G., Cozens R., Evans D.B., Fabbro D., Furet P., Porta D.G., Liebetanz J., Martiny-Baron G., Ruetz S., and Hoffman F. Cancer Cell 5 (2004) 231
15. Mitsiades C.S., Mitsiades N.S., McMullan C.J., Poulaki V., Shringarpure R., Akiyama M., Hideshima T., Chauhan D., Joseph M., Libermann T.A., Garcia-Echeverria C., Pearson M.A., Hoffmann F., Anderson K.C., and Kung A.L. Cancer Cell 5 (2004) 221
16. Bell I.M., Stirdivant S.M., Ahern J., Cullberson C., Darke P.L., Dinsmore C.J., Drakas R.A., Gallicchio S.N., Graham S.L., Heimbrook D.C., Hall D.L., Hua J., Kett N.R., Kim A.S., Kornienko M., Kuo L.C., Munshi S.K., Quigley A.G., Reid J.C., Trotter W., Waxman L.H., Williams T.M., and Zartman C.B. Biochemistry 44 (2005) 9430
17. Girnita A., Girnita L., del Prete F., Bartolazzi A., Larsson O., and Axelson M. Cancer Res. 64 (2004) 236
18. Vasilcanu D., Girnita A., Girnita L., Vasilcanu R., Axelson M., and Larsson O. Oncogene 23 (2005) 7854
19. Blum G., Gazit A., and Levitzki A. J. Biol. Chem. 273 (2003) 40442
20. Girnita A., Girnita L., del Prete F., Bartolazzi A., Larsson O., and Axelson M. Cancer Res. 64 (2004) 236
21. Sarma P.K.S., Tandon R., Gupta P., Dastidar S.G., Ray A., Das B., and Cliffe I.A. Expert Opin. Ther. Patents 17 (2007) 25
22. Mulvihill M.J., Ji Q.-S., Werner D., Beck P., Cesario C., Cooke A., Cox M., Crew A., Dong H., Feng L., Foreman K.W., Mak G., Nigro A., O'Connor M., Saroglou L., Stolz K.M., Sujka I., Volk B., Weng Q., and Wilkes R. Bioorg. Med. Chem. Lett. 17 (2007) 1091
23. Wittman M., Carboni J., Attar R., Balasubramanian B., Balimane P., Brassil P., Beaulieu F., Chang C., Clarke W., Dell J., Eummer J., Frennesson D., Gottardis M., Greer A., Hansel S., Hurlburt W., Jacobson B., Krishnanathan S., Lee F.Y., Li A., Lin T.-A., Liu P., Ouellet C., Sang X., Saulnier M., Stoffan K., Sun Y., Velaparthi U., Wong H., Yang Z., Zimmermann K., Zoeckler M., and Vyas D. J. Med. Chem. 48 (2005) 5639
24. Carboni J.M., Lee A.V., Hadsell D.L., Rowley B.R., Lee F.Y., Bol D.K., Camuso A.E., Gottardis M., Greer A.F., Ho C.P., Hurlburt W., Li A., Saulnier M., Velaparthi U., Wang C., Wen M.-L., Westhouse R.A., Wittman M., Zimmermann K., Rupnow B.A., and Wong T.W. Cancer Res. 65 (2005) 3781
25. Haluska P., Carboni J.M., Loegering D.A., Lee F.Y., Wittman M., Saulnier M.G., Frennesson D.B., Kalli K.R., Conover C.A., Attar R.M., Kaufmann S.H., Gottardis M., and Erlichman C. Cancer Res. 66 (2006) 362
26. Velaparthi U., Wittman M., Liu P., Stoffan K., Zimmermann K., Sang X., Carboni J., Li A., Greer A., Chiehying C., Jacobsen B., Sun Y., Jacobson B., Langley D., Balasubramanian B., and Vyas D. Bioorg. Med. Chem. Lett. 17 (2007) 2317
27. Wittman D.M., Balasubramanian B., Stoffan K., Velaparthi U., Krishnanathan S., Carboni J., Li A., Greer A., Chieying C., Jacobsen B., Sun Y., Hansel S., Zoeckler M., and Vyas D. Bioorg. Med. Chem. Lett. 17 (2007) 974
28. Dresser G.K., Spence D., and Bailey D. Clin. Pharmacokinet. 28 (2000) 41
29. Tang C., Chiba M., Nishime J., Hochman J.H., Chen I.-W., Williams T.M., and Lin J.H. Drug Metab. Dispos. 28 (2000) 680
30. Yamaguchi H.N. Yakuzaishikai Zasshi 49 (1997) 1829
31. 2, 0.5 mM dithiothreitol, and bovine serum albumin at 0.1 mg/ml. The reaction mixtures were incubated at 27 °C for 1 h and kinase activity was determined by quantitation of the amount of radioactive phosphate transferred to the poly(Glu/Tyr) substrate. Incorporation was measured by acid precipitation of the proteins and scintillation counting. Compounds were dissolved in dimethylsulfoxide to a concentration of 10 mM and were added to the kinase assays such that the final concentration of dimethylsulfoxide was no more than 1%, which has been shown to have no effect on kinase activity.
32. CYP Enzyme Assay. The ability of test compounds to inhibit CYP microsomes (supersomes) was measured using 3-cyano-7-ethoxycoumarin (CYP1A2 and CYP2C19), 7-benzyloxy-4-trifluoromethyl coumarin (CYP3A4), 7-methoxy-4-trifluoromethyl coumarin (CYP2C9), and 3-[2-(N,N-diethyl-N-thylamino)ethyl]-7-methoxy-4-methyl coumarin (CYP2D6) as substrates. Assays were performed in 384-well microplates in a total volume of 30 μl. Incubations were performed with microsomes derived from baculovirus-infected cells, which were obtained from BD Gentest (Woburn, MA).
33. Fang F.G., Xie S., and Lowery M.W. J. Org. Chem. 59 (1994) 6142
34. The imidate ester was heated with aminoacetaldehyde diethyl acetal and the resultant amidine was subjected to acid mediated cyclization. For example, see:. Walsh J.S., Wang R., Bagan E., Wang C.C., Wislocki P., and Miwa G.T. J. Med. Chem. 30 (1987) 150