Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 4, 2011, Pages 1270-1274

  Liu, Kevin K C ^a   Huang, Xiaojun ^a,c   Bagrodia, Shubha ^a   Chen, Jeffrey H ^a   Greasley, Samantha ^a   Cheng, Hengmiao ^a   Sun, Shaoxian ^a   Knighton, Dan ^a   Rodgers, Caroline ^a   Rafidi, Kristina ^a   Zou, Aihua ^a   Xiao, Jiezhan ^b   Yan, Shengyong ^b  

^a PFIZER INC   (United States)

^b WUXI APPTEC   (China)

^c NONE   (United States)

Author keywords

iMHBS; Kinase inhibitor; mTOR; PI3K

Indexed keywords

KETONE DERIVATIVE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MOLECULAR SCAFFOLD; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; PTERIDINONE DERIVATIVE; PYRIDO[2,3 D]PYRIMIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CELL LINE; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME PHOSPHORYLATION; HYDROGEN BOND;

BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; HUMANS; HYDROGEN BONDING; MODELS, CHEMICAL; MODELS, MOLECULAR; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; TOR SERINE-THREONINE KINASES;

EID: 79851512182     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.12.026     Document Type: Article

References (20)

1. J.A. Engelman, J. Luo, and L.C. Cantley Nat. Rev. Genet. 7 2006 606
2. S. Huang, and P.J. Houghton Curr. Opin. Pharmacol. 3 2003 371
3. D.D. Sarbassov, S.M. Ali, and D.M. Sabatini Curr. Opin. Cell Biol. 17 2005 596
4. D.A. Guertin, and D.M. Sabatini Sci. Signal. 2 2009 24
5. S.-Y. Sun, L.M. Rosenberg, X. Wang, Z. Zhou, P. Yue, H. Fu, and F.R. Khuri Cancer Res. 65 2005 7052
6. A. Carracedo, and P.P. Pandolfi Oncogene 27 2008 5527
7. K.E. O'Reilly, F. Rojo, Q.-B. She, D. Solit, G.B. Mills, D. Smith, H. Lane, F. Hoffmann, D.J. Hicklin, D.L. Ludwig, J. Baselga, and N. Rosen Cancer Res. 66 2006 1500
8. Cheng, H.; Bhumralkar, D.; Dress, K. R.; Hoffman, J. E.; Johnson, M. C.; Kania, R. S.; Le, P. T. Q.; Nambu, M. D.; Pairish, M. A.; Plewe, M. B.; Tran, K. T. WO 2008032162, 2008.
9. Bruendl, M. M.; Gogliotti, R. D.; Goodman, A. P.; Reichard, G. WO 2005105801, 2005.
10. H. Cheng, S. Bagrodia, S. Bailey, M. Edwards, J. Hoffman, Q. Hu, R. Kania, D.R. Knighton, M.A. Marx, S. Ninkovic, S. Sun, and E. Zhang MedChemComm 1 2010 139
11. K.K.-C. Liu, S. Bagrodia, S. Bailey, H. Cheng, J. Chen, L. Guo, M. Hemkens, J.E. Hoffman, J. Hu, T.O. Johnson, D. Knighton, Z. Liu, M.A. Marx, A.D. McHarg, M.D. Nambu, S. Ninkovic, B. Pascual, K. Rafidi, M-L. Rodgers C., G.L. Smith, S. Sun, H. Wang, A. Yang, J. Yuan, E. Zhang, and A. Zou Bioorg. Med. Chem. Lett. 20 2010 6096
12. P. Furet, G. Bold, F. Hofmann, P. Manley, T. Meyer, and K.-H. Altmann Bioorg. Med. Chem. Lett. 13 2003 2967 2971
13. T. Honma, K. Hayashi, T. Aoyama, N. Hashimoto, T. Machida, K. Fukasawa, T. Iwama, C. Ikeura, M. Ikuta, I. Suzuki-Takahashi, Y. Iwasawa, T. Hayama, S. Nishimura, and H. Morishima J. Med. Chem. 44 2001 4615
14. J. Dumas, R.A. Smith, and T.B. Lowinger Curr. Opin. Drug Discov. Devel. 7 2004 600
15. Z. Wan, J.C. Boehm, M.J. Bower, S. Kassis, J.C. Lee, B. Zhao, and J.L. Adams Bioorg. Med. Chem. Lett. 13 2003 1191
16. P. Furet, G. Caravatti, V. Guagnano, M. Lang, T. Meyer, and J. Schoepfer Bioorg. Med. Chem. Lett. 18 2008 897
17. A. Patgiri, A.L. Jochim, and P.S. Arora Acc. Chem. Res. 41 2008 1289
18. A.L. Hopkins, C.R. Groom, and A. Alex Drug Discovery Today 9 2004 430
19. T. Steiner Angew. Chem., Int. Ed. 41 2002 48
20. A. Beauchard, H. Laborie, H. Rouillard, O. Lozach, Y. Ferandin, R. Le Guevel, C. Guguen-Guillouzo, L. Meijer, T. Besson, and V. Thiery Bioorg. Med. Chem. 17 2009 6257