Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 13, 2009, Pages 3536-3540

  Kemnitzer, William ^a   Sirisoma, Nilantha ^a   May, Chris ^a   Tseng, Ben ^a   Drewe, John ^a   Cai, Sui Xiong ^a  

^a EpiCept Corporation   (United States)

Author keywords

Anticancer agents; Apoptosis inducers; HTS; In vivo activity; SAR

Indexed keywords

4 (4 METHOXYANILINO) N,2,5 TRIMETHYLTHIENO[2,3 D]PYRIMIDINE; 4 ANILINO N METHYLTHIENO[2,3 D]PYRIMIDINE; 4 ANILINO N METHYLTHIENO[3,2 D]PYRIMIDINE DERIVATIVE; CASPASE; N [(BENZO[D][1,3]DIOXOL 5 YL)METHYL] 6 PHENYLTHIENO[3,2 D]PYRIMIDIN 4 AMINE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG DOSE COMPARISON; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT;

ANILINE COMPOUNDS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CASPASES; CELL LINE, TUMOR; DRUG DISCOVERY; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 66349125267     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.04.145     Document Type: Article

References (30)

1. Fischer U., and Schulze-Osthoff K. Pharmacol. Rev. 57 (2005) 187
2. O'Driscoll L., Linehan R., and Clynes M. Curr. Cancer Drug Targets 3 (2003) 131
3. Grivicich I., Regner A., da Rocha A.B., Grass L.B., Alves P.A., Kayser G.B., Schwartsmann G., and Henriques J.A. Oncol. Res. 15 (2005) 385
4. Kolomeichuk S.N., Bene A., Upreti M., Dennis R.A., Lyle C.S., Rajasekaran M., and Chambers T.C. Mol. Pharmacol. 73 (2008) 128
5. Kolenko V.M., Uzzo R.G., Bukowski R., and Finke J.H. Apoptosis 5 (2000) 17
6. Fesik S.W. Nat. Rev. Cancer 5 (2005) 876
7. Zobel K., Wang L., Varfolomeev E., Franklin M.C., Elliott L.O., Wallweber H.J., Okawa D.C., Flygare J.A., Vucic D., Fairbrother W.J., and Deshayes K. ACS Chem. Biol. 1 (2006) 525
8. Shangary S., Qin D., McEachern D., Liu M., Miller R.S., Qiu S., Nikolovska-Coleska Z., Ding K., Wang G., Chen J., Bernard D., Zhang J., Lu Y., Gu Q., Shah B.R., Pienta K.J., Ling X., Kang S., Guo M., Sun Y., Yang D., and Wang S. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 3933
9. Cai S.X., Zhang H.-Z., Guastella J., Drewe J., Yang W., and Weber E. Bioorg. Med. Chem. Lett. 11 (2001) 39
10. Zhang H.-Z., Kasibhatla S., Guastella J., Drewe J., Tseng B., and Cai S.X. Bioconjugate Chem. 14 (2003) 458
11. Thornberry N.A. Chem. Biol. 5 (1998) R97
12. Cai S.X., Drewe J., and Kasibhatla S. Curr. Med. Chem. 13 (2006) 2627
13. Zhang H.-Z., Kasibhatla S., Wang Y., Herich J., Guastella J., Tseng B., Drewe J., and Cai S.X. Bioorg. Med. Chem. 12 (2004) 309
14. Kasibhatla S., Jessen K., Maliartchouk S., Wang J., English N., Drewe J., Qui L., Archer S., Ponce A., Sirisoma N., Jiang S., Zhang H.-Z., Gehlsen K., Cai S.X., Green D.R., and Tseng B. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 12095
15. Kemnitzer W., Kasibhatla S., Jiang S., Zhang H., Wang Y., Zhao J., Jia S., Herich J., Labreque D., Storer R., Meerovitch K., Bouffard D., Rej R., Denis R., Blais C., Lamothe S., Attardo G., Gourdeau H., Tseng B., Drewe J., and Cai S.X. J. Med. Chem. 47 (2004) 6299
16. Kemnitzer W., Drewe J., Jiang S., Zhang H., Zhao J., Crogan-Grundy C., Xu L., Lamothe S., Gourdeau H., Denis R., Tseng B., Kasibhatla S., and Cai S.X. J. Med. Chem. 50 (2007) 2858
17. Kemnitzer W., Drewe J., Jiang S., Zhang H., Crogan-Grundy C., Labreque D., Bubenick M., Attardo G., Denis R., Lamothe S., Gourdeau H., Tseng B., Kasibhatla S., and Cai S.X. J. Med. Chem. 51 (2008) 417
18. Kasibhatla S., Gourdeau H., Meerovitch K., Drewe J., Reddy S., Qiu L., Zhang H., Bergeron F., Bouffard D., Yang Q., Herich J., Lamothe S., Cai S.X., and Tseng B. Mol. Cancer Ther. 3 (2004) 1365
19. Gourdeau H., Leblond L., Hamelin B., Desputeau C., Dong K., Kianicka I., Custeau D., Bourdeau C., Geerts L., Cai S.X., Drewe J., Labrecque D., Kasibhatla S., and Tseng B. Mol. Cancer Ther. 3 (2004) 1375
20. Zhang H.-Z., Kasibhatla S., Kuemmerle J., Kemnitzer W., Oliis-Mason K., Qui L., Crogran-Grundy C., Tseng B., Drewe J., and Cai S.X. J. Med. Chem. 48 (2005) 5215
21. Jessen K., English N., Wang J., Qui L., Brand R., Maliartchouk S., Drewe J., Kuemmerle J., Zhang H.-Z., Gehlsen K., Tseng B., Cai S.X., and Kasibhatla S. Mol. Cancer Ther. 4 (2005) 761
22. Sirisoma N., Kasibhatla S., Pervin A., Zhang H., Jiang S., Willardsen J.A., Anderson M., Baichwal V., Mather G.G., Jessing K., Hussain R., Hoang K., Pleiman C.M., Tseng B., Drewe J., and Cai S.X. J. Med. Chem. 51 (2008) 4771
23. Sirisoma N., Pervin A., Zhang H., Jiang S., Willardsen A.J., Anderson M., Mather G.G., Pleiman C.M., Kasibhatla S., Tseng B., Drewe J., and Cai S.X. J. Med. Chem. 52 (2009) 2341
24. Kasibhatla S., Baichwal V., Cai S.X., Roth B., Skvortsova I., Skvortsov S., Lukas P., English N.M., Sirisoma N., Drewe J., Pervin A., Tseng B., Carlson R.O., and Pleiman C.M. Cancer Res. 67 (2007) 5865
25. Showalter H.D., Bridges A.J., Zhou H., Sercel A.D., McMichael A., and Fry D.W. J. Med. Chem. 42 (1999) 5464
26. Munchhof M.J., Beebe J.S., Casavant J.M., Cooper B.A., Doty J.L., Higdon R.C., Hillerman S.M., Soderstrom C.I., Knauth E.A., Marx M.A., Rossi A.M., Sobolov S.B., and Sun J. Bioorg. Med. Chem. Lett. 14 (2004) 21
27. Rheault T.R., Caferro T.R., Dickerson S.H., Donaldson K.H., Gaul M.D., Goetz A.S., Mullin R.J., McDonald O.B., Petrov K.G., Rusnak D.W., Shewchuk L.M., Spehar G.M., Truesdale A.T., Vanderwall D.E., Wood E.R., and Uehling D.E. Bioorg. Med. Chem. Lett. 19 (2009) 817
28. 3): 7.20-7.17 (m, 2H), 6.97-6.94 (m, 2H), 6.73 (dd, J = 6.0 and 0.5 Hz, 1H), 5.55 (dd, J = 6.0 and 0.8 Hz, 1H), 3.86 (s, 3H), 3.55 (s, 3H), 2.65 (s, 3H).
29. Cai S.X., Nguyen B., Jia S., Guastella J., Reddy S., Tseng B., Drewe J., and Kasibhatla S. J. Med. Chem. 46 (2003) 2474
30. Barron D.M., Chatterjee S.K., Ravindra R., Roof R., Baloglu E., Kingston D.G.I., and Bane S. Anal. Biochem. 315 (2003) 49