1-Aryl-4,6-dihydropyrazolo[4,3-d][1]benzazepin-5(1H)-ones: A new class of antiproliferative agents with selectivity for human leukemia and breast cancer cell lines

European Journal of Medicinal Chemistry

Volumn 42, Issue 11-12, 2007, Pages 1317-1324

  Kohfeld, Simone ^a   Jones, Peter G ^a   Totzke, Frank ^b   Schächtele, Christoph ^b   Kubbutat, Michael H G ^b   Kunick, Conrad ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^b PROQINASE GMBH   (Germany)

Author keywords

Antiproliferative activity; COMPARE; Cyclization; Kinase

Indexed keywords

1 (2 BROMOPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (2 CHLOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (2 FLUOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5(1H)ONE; 1 (2 METHYLPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (2,4 DIFLUOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (3 CHLOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (3,5 DICHLOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 BROMOPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 CHLOROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 METHOXYPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 METHYLPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 NITROPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 TERT BUTYLPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 (4 TRIFLUOROMETHYLPHENYL) 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5 (1H)ONE; 1 PHENYL 4,6 DIHYDROPYRAZOLO[4,3 D][1]BENZAZEPIN 5(1H)ONE; 4 [(DIMETHYLAMINO)METHYLIDENE] 3,4 DIHYDRO 1H [1]BENZAZEPINE 2,5 DIONE; 4 [[2 (2 BROMOPHENYL)HYDRAZINO]METHYLENE] 3,4 DIHYDRO 1H [1]BENZAZEPINE 2,5 DIONE; 4 [[2 (3,5 DICHLOROPHENYL)HYDRAZINO]METHYLENE] 3,4 DIHYDRO 1H [1]BENZAZEPINE 2,5 DIONE; ANTINEOPLASTIC AGENT; HYDRAZINE DERIVATIVE; PHOSPHOTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; CYCLIZATION; DRUG MECHANISM; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LEUKEMIA;

BENZAZEPINES; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; COMPUTATIONAL BIOLOGY; HUMANS; INDOLES; INHIBITORY CONCENTRATION 50; LEUKEMIA; PROTEIN KINASE INHIBITORS;

EID: 36248983261     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2007.02.007     Document Type: Article

References (24)

1. Kunick C., Lauenroth K., Wieking K., Xie X., Schultz C., Gussio R., Zaharevitz D., Leost M., Meijer L., Weber A., Jørgensen F.S., and Lemcke T. J. Med. Chem. 47 (2004) 22-36
2. Leost M., Schultz C., Link A., Wu Y.-Z., Biernat J., Mandelkow E.-M., Bibb J.A., Snyder G.L., Greengard P., Zaharevitz D.W., Gussio R., Senderowicz A.M., Sausville E.A., Kunick C., and Meijer L. Eur. J. Biochem. 267 (2000) 5983-5994
3. Kunick C., Lauenroth K., Leost M., Meijer L., and Lemcke T. Bioorg. Med. Chem. Lett. 14 (2004) 413-416
4. Knockaert M., Wieking K., Schmitt S., Leost M., Grant K.M., Mottram J.C., Kunick C., and Meijer L. J. Biol. Chem. 277 (2002) 25493-25501
5. Xie X., Lemcke T., Gussio R., Zaharevitz D.W., Leost M., Meijer L., and Kunick C. Eur. J. Med. Chem. 40 (2005) 655-661
6. Pies T., Schaper K.-J., Leost M., Zaharevitz D.W., Gussio R., Meijer L., and Kunick C. Arch. Pharm. Pharm. Med. Chem. 337 (2004) 486-492
7. Kunick C., Schultz C., Lemcke T., Zaharevitz D.W., Gussio R., Jalluri R.K., Sausville E.A., Leost M., and Meijer L. Bioorg. Med. Chem. Lett. 10 (2000) 567-569
8. Bertrand J.A., Thieffine S., Vulpetti A., Cristiani C., Valsasina B., Knapp S., Kalisz H.M., and Flocco M. J. Mol. Biol. 333 (2003) 393-407
9. Melani F., Cecchi L., Palazzino G., and Filacchioni G. J. Heterocycl. Chem. 23 (1986) 173-176
10. Chen W.-Y., and Gilman N.W. J. Heterocycl. Chem. 20 (1983) 663-666
11. Schenone P., Mosti L., and Menozzi G. J. Heterocycl. Chem. 19 (1982) 1355-1361
12. Olivera R., SanMartin R., and Domínguez E. J. Org. Chem. 65 (2000) 7010-7019
13. Olivera R., Churruca F., SanMartin R., and Domínguez E. J. Org. Chem. 67 (2002) 7215-7225
14. Dawood K.M. J. Heterocycl. Chem. 42 (2005) 221-225
15. Molteni V., Hamilton M.M., Mao L., Crane C.M., Termin A.P., and Wilson D.M. Synthesis (2002) 1669-1674
16. Tonkikh N.N., Ryzhanova K.V., Petrova M.V., and Strakovs A. Chem. Heterocycl. Compd. 39 (2003) 651-653
17. Reidlinger C., Dworczak R., and Junek H. Monatsh. Chem. 129 (1998) 1207-1211
18. Paull K.D., Shoemaker R.H., Hodes L., Monks A., Scudiero D.A., Rubinstein L., Plowman J., and Boyd M.R. J. Natl. Cancer Inst. 81 (1989) 1088-1092
19. Boyd M.R., and Paull K.D. Drug Dev. Res. 34 (1995) 91-109
20. Zaharevitz D.W., Gussio R., Leost M., Senderowicz A., Lahusen T., Kunick C., Meijer L., and Sausville E.A. Cancer Res. 59 (1999) 2566-2569
21. Gray G.D., and Wickstrom E. BioTechniques 21 (1996) 780-782
22. Monks A., Scudiero D., Skehan P., Shoemaker R., Paull K., Vistica D., Hose C., Langley J., Cronise P., Vaigro-Wolff A., Gray-Goodrich M., Campbell H., Mayo J., and Boyd M. J. Natl. Cancer Inst. 83 (1991) 757-766
23. Monks A., Scudiero D.A., Johnson G.S., Paull K.D., and Sausville E.A. Anti-Cancer Drug Des. 12 (1997) 533-541
24. Kunick C., Bleeker C., Prühs C., Totzke F., Schächtele C., Kubbutat M.H.G., and Link A. Bioorg. Med. Chem. Lett. 16 (2006) 2148-2153