Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 19, 2006, Pages 5102-5106

  Smith II, Leon ^a   Wong, Wai C ^a   Kiselyov, Alexander S ^a   Burdzovic Wizemann, Sabina ^a   Mao, Yunyu ^a   Xu, Yongjiang ^a   Duncton, Matthew A J ^a   Kim, Ki ^a   Piatnitski, Evgueni L ^a   Doody, Jacqueline F ^a   Wang, Ying ^a   Rosler, Robin L ^a   Milligan, Daniel ^a   Columbus, John ^a   Balagtas, Chris ^a   Lee, Sui Ping ^a   Konovalov, Andrey ^a   Hadari, Yaron R ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Diazepine; Epidermal growth factor receptor; Kinase inhibitor; Oxazepine; Thiazepine

Indexed keywords

BENZODIAZEPINE DERIVATIVE; DIAZEPINE DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; THIAZEPINE DERIVATIVE;

ARTICLE; AUTOPHOSPHORYLATION; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; IC 50; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ANTINEOPLASTIC AGENTS; AZEPINES; CELL LINE, TUMOR; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; INHIBITORY CONCENTRATION 50; NEOPLASM PROTEINS; PHOSPHORYLATION; RECEPTOR, EPIDERMAL GROWTH FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 33747372225     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.07.031     Document Type: Article

References (24)

1. Traxler P. Exp. Opin. Ther. Patents 8 (1998) 1599
2. Bradenber J., Danenberg K.D., Metzger R., Schneider P.M., Park J., Salonga D., Holscher D., and Danenberg P.V. Clin. Cancer Res. 7 (2001) 1850
3. Christensen J.G., Schreck R., Burrows J., Kuruganti P., Chan E., Le P., Chen J., Wang X., Ruslim L., Blake R., Lipson K.E., Ramphal J., Do S., Cui J.J., Cherrington J.M., and Mendel D.B. Cancer Res. 63 (2003) 7345
4. Garcia-Echeverria C., and Fabbro D. Mini-Rev. Med. Chem. 4 (2004) 273
5. Hao D., and Rowinsky E.K. Cancer Invest. 20 (2002) 387
6. Li S., Schmitz K.R., Jeffrey P.D., Wiltzius J.J.W., Kussie P., and Ferguson K.M. Cancer Cell 7 (2005) 301
7. McKillop D., Partridge E.A., Kemp J.V., Spence M.P., Kendrew J., Barnett S., Wood P.G., Giles P.B., Patterson A.B., Bichat F., Guilbaud N., and Stephens T.C. Mol. Cancer Ther. 4 (2005) 641
8. Herbst R.S., Johnson D.H., Mininberg E., Carbone D.P., Henderson T., Kim E.S., Blumenschein Jr. G., Lee J.J., Liu D.D., Truong M.T., Hong W.K., Tran H., Tsao A., Xie D., Ramies D.A., Mass R., Seshagiri S., Eberhard D.A., Kelley S.K., and Sandler A. J. Clin. Oncol. 23 (2005) 2544
9. Smith, L. M., II.; Hadari, Y. PCT. Int. Appl. 20055009384, Chem. Abstr. 2005, 142, 172179.
10. Smith II L., Piatnitski E.L., Kiselyov A.S., Ouyang X., Chen X., Burdzovic-Wizemann S., Xu Y., Wang Y., Rosler R.L., Patel S.N., Chiang H.H., Milligan D.L., Columbus J., Wong W.C., Doody J.F., and Hadari Y.R. Bioorg. Med. Chem. Lett. 16 (2006) 1643
11. Rewcastle G.W., Denny W.A., Bridges A.J., Zhou H., Cody D.R., McMichael A., and Fry D.W. J. Med. Chem. 38 (1995) 3482
12. Rewcastle G.W., Palmer B.D., Bridges A.J., Hollis Showalter H.D., Sun L., Nelson J., McMichael A., Kraker A.J., Fry D.W., and Denny W.A. J. Med. Chem. 39 (1996) 918
13. 1H NMR and LC/MS data.
14. Levkovskaya L.G., Sazonov N.V., Grineva N.A., Mameeva I.E., Serochkina L.A., and Safonova T.S. Chem. Heterocycl. Compd. (English Translation) 21 (1985) 100
15. Duncton M.A.J., Smith II L.M., Burdzovic-Wizeman S., Burns A., Liu H., Mao Y., Wong W.C., and Kiselyov A.S. J. Org. Chem. 70 (2005) 9629
16. Aversa M.C., Bonaccorsi P., and Giannetto P. J. Heterocycl. Chem. 26 (1989) 1383
17. Aversa M.C., and Giannetto P. J. Chem. Res., Synop. (1984) 200
18. Structurally similar diazepines have recently been reported:. Yang J., Che X., Dang W., Wei Z., Gao S., and Bai X. Org. Lett. 7 (2005) 1541
19. 3 (0.2 M, 34 ml) and the pH was adjusted to 9.6. Prior to adding cell lysates to the wells, the plates were washed three times with PBS + 0.1% Tween 20 and blocked by 3% BSA in PBS (200 μl for 1 h incubation). Eighty microliters of cell lysates was transferred to the coated wells and incubated for 1 h at 4 °C. After incubation, the plates were washed three times with PBS + 0.1% Tween 20. To detect autophosphorylated EGFR (tyrosine residues), 100 μl of anti-phosphotyrosine antibodies (RC20:HRP, Transduction Laboratories) was added per well (final concentration 0.5 μg/ml in PBS) and incubated for 1 h. The plates were then washed six times with PBS + 0.1% Tween 20.
20. Barker A.J., Gibson K.H., Grundy W., Godfrey A.A., Barlow J.J., Healy M.P., Woodburn J.R., Ashton S.E., Curry B.J., Scarlett L., Henthorn L., and Richards L. Bioorg. Med. Chem. Lett. 11 (2001) 1911
21. Piatnitski E.L., Duncton M.A.J., Kiselyov A.S., Katoch-Rouse R., Sherman D., Milligan D., Balagtas C., Wong W.C., Kawakami J., and Doody J.F. Bioorg. Med. Chem. Lett. 15 (2005) 4696
22. Duncton M.A.J., Piatnitski E.L., Katoch-Rouse R., Smith II L.M., Kiselyov A.S., Milligan D.L., Balagtas C., Wong W.C., and Doody J.F. Bioorg. Med. Chem. Lett. 16 (2006) 1579
23. 2, 2 mM DTT, and 1 mg/ml BSA) containing 0.5 mmol p-GAT-biotin and 3-4 ng KDR enzyme is added to each well. After 5-10 min preincubation, the kinase reaction is initiated by the addition of 10 μM ATP in the reaction buffer, after which the plate is incubated at room temperature for 45 min. The reaction is stopped by addition of 50 μl KF buffer (50 mM Hepes, pH 7.5, 0.5 M KF, and 1 mg/ml BSA) containing 100 mM EDTA and 0.36 μg/ml PY20K (Eu-cryptate labeled anti-phosphotyrosine antibody, CIS Bio International) in KF buffer is added, and after 2 h incubation at room temperature, the plate is read in a RUBY Star HTRF reader.
24. Caravatti, G.; Bold, G.; Bruggen, J.; Furet, P.; Lane, H.; Mestan, J.; Meyer, T.; Tang, C.; Wartmann, M.; Wood, J.; Zimmerlin, A.; Traxler, P. AACR-NCI-EORTC Meeting, Boston, MA, November 17-21, 2003, Poster #A118.