Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 4, 2008, Pages 1354-1358

  Cai, Zhen wei ^a   Wei, Donna ^a   Borzilleri, Robert M ^a   Qian, Ligang ^a   Kamath, Amrita ^a   Mortillo, Steven ^a   Wautlet, Barri ^a   Henley, Benjamin J ^a   Jeyaseelan Sr , Robert ^a   Tokarski, John ^a   Hunt, John T ^a   Bhide, Rajeev S ^a   Fargnoli, Joseph ^a   Lombardo, Louis J ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Kinase inhibitors; Pyrrolo 2,1 f 1,2,4 triazine; VEGFR 2

Indexed keywords

1,3,5 OXADIAZOLE; 4 [2,4 DIFLUORO 5 (CYCLOPROPYLCARBAMOYL)PHENYLAMINO]PYRROLO[2,1-F][1,2,4]TRIAZINE; OXADIAZOLE DERIVATIVE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR 2 KINASE INHIBITOR;

ANALYTIC METHOD; ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE, TUMOR; CYCLOPROPANES; CYTOCHROME P-450 ENZYME SYSTEM; ENDOTHELIAL CELLS; HUMANS; LUNG NEOPLASMS; MICE; MICE, NUDE; OXADIAZOLES; PROTEIN KINASE INHIBITORS; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MUS;

EID: 38949108992     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.01.012     Document Type: Article

References (19)

1. Folkman J., and Shing Y. J. Biol. Chem. 267 (1992) 10931
2. Folkman J. J. Semin. Oncol. 28 (2001) 536
3. Carmeliet P., and Jain R.K. Nature 407 (2000) 249
4. Carmeliet P. Nat. Med. 9 (2003) 653
5. Griffioen A.W., and Molema G. Pharmacol. Rev. 52 (2000) 237
6. Folkman J., and Klagsbrun M. Science 235 (1987) 442
7. Thomas K.A. J. Biol. Chem. 271 (1996) 603
8. Gimbrone M. Drug Discov. Today 2 (1997) 50
9. Folkman J. J. Natl. Cancer Inst. 83 (1990) 4
10. Klebl B.M., and Muller G. Expert Opin. Ther. Targets 9 (2005) 975
11. Kumar C.C., and Madison V. Expert Opin. Emerg. Drugs 6 (2001) 303
12. Cohen M.H., Gootenberg J., Keegan P., and Pazdur R. Oncologist 12 (2007) 356
13. Sandler A., Gray R., Perry M.C., Brahmer J., Schiller J.H., Dowlati A., Lilenbaum R., and Johnson D.H. N. Eng. J. Med. 355 (2006) 2542
14. Cardones A.R., and Banez L.L. Current Pharm. Design 12 (2006) 387
15. Sepp-Lorenzino L., and Thomas K. Expert Opin. Investig. Drugs 11 (2002) 1447
16. Borzilleri R.M., Zheng X., Qian L., Ellis C., Cai Z.-W., Wautlet B.S., Mortillo S., Jayaseelan R., Kukral D., Fura A., Kamath A., Vyas V., Tokarski J.S., Barrish J.C., Hunt L.J., Fargnoli J., and Bhide R. J. Med. Chem. 12 (2005) 3991
17. Borzilleri R.M., Bhide R., Barrish J.C., D'Arienzo C.J., Derbin G.M., Fargnoli J., Hunt L.J., Jayaseelan R., Kamath A., Kukral D., Marathe P., Mortillo S., Qian L., Tokarski J.S., Wautlet B.S., Zheng X., and Lombardo L.J. J. Med. Chem. 49 (2006) 3776
18. +.
19. Inhibition of human CYP isozymes by compounds 30, 31, and 37{A table is presented}