Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 18, 2013, Pages 5707-5724

  Allen, Charlotte E ^a   Chow, Chiau L ^a   Caldwell, John J ^a   Westwood, Isaac M ^a   M Van Montfort, Rob L ^a   Collins, Ian ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Kinase inhibitor; Protein kinase; Selectivity; Spirocycle

Indexed keywords

1,4,9 TRIBENZYL 1,9 DIAZASPIRO[5.5]UNDECAN 2 ONE; 1,9 DIBENZYL 1,9 DIAZASPIRO[5.5]UNDEC 3 EN 2 ONE; 1,9 DIBENZYL 4 PHENYL 1,9 DIAZASPIRO[5.5]UNDECAN 2 ONE; 4 BENZYL 1 (9H PURIN 6 YL)PIPERIDIN 4 AMINE; 4 BENZYL 1 (ISOQUINOLIN 5 YLSULFONYL)PIPERADIN 4 AMINE; 5 (1,8 DIAZASPIRO[4.5]DECAN 1 YLSULFONYL)ISOQUINOLINE; 5 (1,8 DIAZASPIRO[4.5]DECAN 8 YLSULFONYL)ISOQUINOLINE; 5 (1,9 DIAZASPIRO[5.5]UNDECAN 9 YLSULFONYL)ISOQUINOLINE; 5 (2,8 DIAZASPIRO[4.5]DECAN 8 YLSULFONYL)ISOQUINOLINE; 5 (2,8 DIAZASPIRO[5.5]UNDECAN 2 YLSULFONYL)ISOQUINOLINE; 5 (2,9 DIAZASPIRO[5.5]UNDECAN 2 YLSULFONYL)ISOQUINOLINE; 5 (2,9 DIAZASPIRO[5.5]UNDECAN 9 YLSULFONYL)ISOQUINOLINE; 6 (1,8 DIAZASPIRO[4.5]DECAN 1 YL) 9H PURINE; 6 (1,8 DIAZASPIRO[4.5]DECAN 8 YL) 9H PURINE; 6 (1,9 DIAZASPIRO[5.5]UNDECAN 9 YL) 9H PURINE; 6 (2,8 DIAZASPIRO[4.5]DECAN 8 YL) 9H PURINE; 6 (2,8 DIAZASPIRO[5.5]UNDECAN 2 YL) 9H PURINE; 6 (2,9 DIAZASPIRO[5.5]UNDECAN 2 YL) 9H PURINE; 6 (2,9 DIAZASPIRO[5.5]UNDECAN 9 YL) 9H PURINE; 6 (3 AZASPIRO[5.5]UNDECAN 3 YL) 9H PURINE; 9 (9H PURIN 6 YL) 1 OXA 9 AZASPIRO[5.5]UNDECANE; 9 (9H PURIN 6 YL) 1,9 DIAZASPIRO[5.5]UNDECAN 4 OL; 9 (9H PURIN 6 YL) 2 OXA 9 AZASPIRO[5.5]UNDECANE; 9 (9H PURIN 6YL) 1,9 DIAZASPIRO[5.5]UNDECAN 3 OL; 9 (ISOQUINOLIN 5 YLSULFONYL) 1,9 DIAZASPIRO[5.5]UNDECAN 3 OL; 9 (ISOQUINOLIN 5 YLSULFONYL) 1,9 DIAZASPIRO[5.5]UNDECAN 4 OL; PROTEIN KINASE INHIBITOR; TERT BUTYL 9 BENZYL 3 HYDROXY 1,9 DIAZASPIRO[5.5]UNDECANE 1 CARBOXYLATE; TERT BUTYL 9 BENZYL 4 HYDROXY 1,9 DIAZASPIRO[5.5]UNDECANE 1 CARBOXYLATE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BINDING AFFINITY; BINDING COMPETITION; BINDING SITE; CONFORMATIONAL TRANSITION; CRYSTALLOGRAPHY; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS;

9-BBN; 9-BORABICYCLO[3.1.1.]NONANE BOC TERT-BUTYLOXYCARBONYL; ADENOSINE TRIPHOSPHATE; AGC; ASPARTATE-PHENYLALANINE-GLYCINE SEQUENCE; ATP; BENZYLOXYCARBONYL; CALCIUM/CALMODULIN-DEPENDENT KINASES; CAMK; CBZ; DFG; DIBAL-H; DIISOBUTYLALUMINIUM HYDRIDE; HA; HEAVY ATOM; KINASE INHIBITOR; LE; LIGAND EFFICIENCY; NUCLEOPHILIC AROMATIC SUBSTITUTION; PKA; PKB; PROTEIN KINASE; PROTEIN KINASE A; PROTEIN KINASE B; PROTEIN KINASES A G AND C; RCM; RING-CLOSING METATHESIS; S(N)AR; SELECTIVITY; SPIROCYCLE; TK; TYROSINE KINASE;

ADENOSINE TRIPHOSPHATE; AZA COMPOUNDS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ISOQUINOLINES; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTEIN STRUCTURE, TERTIARY; SPIRO COMPOUNDS;

EID: 84882901491     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.07.021     Document Type: Article

References (51)

1. G. Manning, D.B. Whyte, R. Martinez, T. Hunter, and S. Sudarsanam Science 298 2002 1912
2. P. Blume-Jensen, and T. Hunter Nature 411 2001 355
3. D. Hanahan, and R.A. Weinberg Cell 144 2011 646
4. I. Collins, and P. Workman Curr. Sig. Transduc. Ther. 1 2006 13
5. L. Zhang, and R.J. Daly Crit. Rev. Oncog. 17 2012 233
6. S. Faivre, S. Djelloul, and E. Raymond Semin. Oncol. 33 2006 407
7. L. Gossage, and T. Eisen Clin. Cancer Res. 16 2010 1973
8. Z. Knight, H. Lin, and K.M. Shokat Nat. Rev. Cancer 10 2010 130
9. R. Morphy J. Med. Chem. 53 2010 1413
10. P. Traxler, and P. Furet Pharmacol. Ther. 82 1999 195
11. A.K. Ghose, T. Herbertz, D.A. Pippin, J.M. Salvino, and J.P. Mallamo J. Med. Chem. 51 2008 5149
12. R.Y. Patel, and R.J. Doerksen J. Proteome Res. 9 2010 4433
13. J.J. Caldwell, T.G. Davies, A. Donald, T. McHardy, M.G. Rowlands, G.W. Aherne, L.K. Hunter, K. Taylor, R. Ruddle, F.I. Raynaud, M. Verdonk, P. Workman, M.D. Garrett, and I. Collins J. Med. Chem. 51 2008 2147
14. T. McHardy, J.J. Caldwell, K.-M. Cheung, L.J. Hunter, K. Taylor, M. Rowlands, R. Ruddle, A. Henley, A. Brandon, M. Valenti, T.G. Davies, L. Fazal, L. Seavers, F.I. Raynaud, S. Eccles, G.W. Aherne, M.D. Garrett, and I. Collins J. Med. Chem. 53 2010 2239
15. K.D. Freeman-Cook, C. Autry, G. Borzillo, D. Gordon, E. Barbacci-Tobin, V. Bernardo, D. Briere, T. Clark, M. Corbett, J. Jakubczak, S. Kakar, E. Knauth, B. Lippa, M.J. Luzzio, M. Mansour, G. Martinelli, M. Marx, K. Nelson, J. Pandit, F. Rajamohan, S. Robinson, C. Subramanyam, L. Wei, M. Wythes, and J. Morris J. Med. Chem. 53 2010 4615 Erratum in J. Med. Chem. 2010, 53, 5895
16. C.R.W. Guimaraes, B.K. Rai, M.J. Munchhof, S. Liu, J. Wang, S.K. Bhattacharya, and L. Buckbinder J. Chem. Inf. Mod. 51 2011 1199
17. I.D. Jenkins, F. Lacrampe, J. Ripper, L. Alcaraz, P. Van Le, G. Nikolakopoulos, P. De Almeida Leone, R.H. White, and R.J. Quinn J. Org. Chem. 74 2008 1304
18. N.A. Meanwell Chem. Res. Toxicol. 24 2011 1420
19. Y. Yang, O. Engkvist, A. Llinàs, and H. Chen J. Med. Chem. 55 2012 3667
20. M. Ishikawa, and Y. Hashimoto J. Med. Chem. 55 2011 1534
21. Plettenburg, O.; Schoenau, C.; Loehn, M.; Hachtel, S.; Pfeiffer-Marek, S.; Mendez-Perez, M.; Kannt, A.; Dedio, J.; Kohlmann, M.; Schiffer, A.; Begis, G.; Duclos, O.; Jeannot, F. Intl. Pat. Appl. WO2013045413, 2013; Chem. Abstr. 2013, 158, 534920.
22. Hodges, A. J.; Matteucci, M.; Sharpe, A.; Sun, M.; Wang, X.; Tsui, V. H. US Pat. Appl. US20130079321, 2013; Chem. Abstr. 2013, 158, 504146.
23. Fernandez, J. P.; Gonzalez, S. M.; Hernando, J. I. M.; Herguea, A. R; Ferreira, M. R. R.; Aparico, C. A. Intl. Pat. Appl. WO2013004984, 2013; Chem. Abstr. 2013, 158, 187521.
24. J. Pastor, J. Oyarzabal, G. Saluste, R.M. Alvarez, V. Rivero, F. Ramo, E. Cendon, C. Blanco-Aparicio, N. Ajenjo, A. Cebria, M.I. Albarran, D. Cebrian, A. Corrionero, J. Fominaya, G. Montoya, and M. Mazzorana Bioorg. Med. Chem. Lett. 22 2012 1591
25. B. Lippa, G. Pan, M. Corbett, C. Li, G.S. Kauffman, J. Pandit, S. Robinson, L. Wei, E. Kozina, E.S. Marr, G. Borzillo, E. Knauth, E.G. Barbacci-Tobin, P. Vincent, M. Troutman, D. Baker, F. Rajamohan, S. Kakar, T. Tracey Clark, and J. Morris Bioorg. Med. Chem. Lett. 18 2008 3359
26. Baldino, C. M.; Caserta, J. L.; Dumas, S. A.; Lee, C.; Flanders, Y. L. US Pat. Appl. US20120270892, 2012; Chem. Abstr. 2012, 157, 663061.
27. Zhang, J.; Jin, H.; Tian, Y.; Zhu, Z.; Li, Z.; Wang, G.; Wan, S.; Ye, L.; You, W.; Wu, S. Chin. Pat. Appl. CN102516263, 2012; Chem. Abstr. 2012, 157, 165620.
28. I. Collins, J. Caldwell, T. Fonseca, A. Donald, V. Bavetsias, L.-J.K. Hunter, M.D. Garrett, M.G. Rowlands, G.W. Aherne, T.G. Davies, V. Berdini, S.J. Woodhead, D. Davis, L.C.A. Seavers, P.G. Wyatt, P. Workman, and E. McDonald Bioorg. Med. Chem. 14 2006 1255
29. J.J. Caldwell, and I. Collins Synlett 2006 2565
30. S. Rodriguez, E. Castillo, M. Carda, and J.A. Marco Tetrahedron 58 2002 1185
31. S. Hanessian, W.A.L. van Otterlo, I. Nilsson, and U. Bauer Tetrahedron Lett. 43 2002 1995
32. E. Prusov, and M.E. Maier Tetrahedron 63 2007 10469
33. A. Padwa, and J.T. Kuethe J. Org. Chem. 63 1998 4256
34. K. McEleney, D.P. Allen, A.E. Holliday, and C.M. Crudden Org. Lett. 8 2006 2663
35. M. Bujard, A. Briot, V. Gouverneur, and C. Mioskowski Tetrahedron Lett. 40 1999 8785
36. I.C. Stewart, T. Ung, A.A. Pletnev, J.M. Berlin, R.H. Grubbs, and Y. Schrodi Org. Lett. 9 2007 1589
37. D.L. Schmidt, C.B. Roberts, P.F. Reigler, M.F. Lemanski, and E.P. Schram A. Wold, J.K. Ruff, Inorganic Syntheses 2007 John Wiley & Sons Inc. 47 52
38. A. Card, C. Caldwell, H. Min, B. Lokchander, X. Hualin, S. Sciabola, A.V. Kamath, S.L. Clugston, W.R. Tschantz, W. Leyu, and D.J. Moshinsky J. Biomol. Screen. 14 2009 31
39. D. Perrin, C. Fremaux, and A. Scheer J. Biomol. Screen. 11 2006 359
40. A.L. Hopkins, C.R. Groom, and A. Alex Drug Discovery Today 9 2004 430
41. L.A. Smyth, and I. Collins J. Chem. Biol. 2 2009 131
42. H. Hidaka, M. Watanabe, and R. Kobayashi Methods Enzymol. 201 1991 328
43. S.L. Posy, M.A. Hermsmeier, W. Vaccaro, K. Ott, G. Todderud, J.S. Lippy, G.L. Trainor, D.A. Loughney, and S.R. Johnson J. Med. Chem. 54 2011 54
44. P. Bamborough, M.J. Brown, J.A. Christopher, C. Chung, and G.W. Mellor J. Med. Chem. 54 2011 5131
45. L.A. Smyth, T.P. Matthews, and I. Collins Bioorg. Med. Chem. 19 2011 3569
46. T.P. Matthews, T. McHardy, S. Klair, K. Boxall, M. Fisher, M. Cherry, C.E. Allen, G.J. Addison, J. Ellard, G.W. Aherne, I.M. Westwood, R. van Montfort, M.D. Garrett, J.C. Reader, and I. Collins Bioorg. Med. Chem. Lett. 20 2010 4045
47. G. Saxty, S.J. Woodhead, V. Berdini, T.G. Davies, M.L. Verdonk, P.G. Wyatt, R.G. Boyle, D. Barford, R. Downham, M.D. Garrett, and R.A. Carr J. Med. Chem. 50 2007 2293
48. T.G. Davies, M.L. Verdonk, B. Graham, S. Saalau-Bethell, C.C.F. Hamlett, T. McHardy, I. Collins, M.D. Garrett, P. Workman, S.J. Woodhead, H. Jhoti, and D. Barford J. Mol. Biol. 367 2007 882
49. P. Akamine, Madhusudan, J. Wu, N. Xuong, L.F. Ten Eyck, and S.S. Taylor J. Mol. Biol. 327 2003 159
50. http://www.chemcomp.com/MOE-Molecular-Operating-Environment.htm (Chemical Computing Group); accessed 15.05.2013.
51. L. Potterton, S. McNicholas, E. Krissinel, J. Gruber, K. Cowtan, P. Emsley, G.N. Murshudov, S. Cohen, A. Perrakis, and M. Noble Acta Cryst. D60 2004 2288