Discovery and structure-activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors

Journal of Medicinal Chemistry

Volumn 54, Issue 7, 2011, Pages 2341-2350

  Charrier, Jean Damien ^a   Miller, Andrew ^a   Kay, David P ^a   Brenchley, Guy ^a   Twin, Heather C ^a   Collier, Philip N ^a   Ramaya, Sharn ^a   Keily, Shazia B ^a   Durrant, Steven J ^a   Knegtel, Ronald M A ^a   Tanner, Adam J ^a   Brown, Kieron ^a   Curnock, Adam P ^a   Jimenez, Juan Miguel ^a  

^a VERTEX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

[4 [2 (PYRROLIDIN 1 YLMETHYL)PYRROLIDIN 1 YL]BENZOYLAMINO] 5 [6 (METHYLAMINO)PYRAZIN 2 YL]PYRIDIN 2 ONE; AMRINONE; INTERLEUKIN 2; PROTEIN KINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION;

ADENOSINE TRIPHOSPHATE; CATALYTIC DOMAIN; DRUG DESIGN; HYDROGEN BONDING; MALEIMIDES; MODELS, MOLECULAR; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRIDONES; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 79953771938     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101499u     Document Type: Article

References (32)

1. Berg, L. J.; Finkelstein, L. D.; Lucas, J. A.; Schwartzberg, P. L. Tec family kinases in T lymphocyte development and function Annu. Rev. Immunol. 2005, 23, 549-600 (Pubitemid 40563180)
2. Liao, X. C.; Littman, D. R. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk Immunity 1995, 3, 757-769 (Pubitemid 26091149)
3. Fowell, D. J.; Shinkai, K.; Liao, X. C.; Beebe, A. M.; Coffman, R. L.; Littman, D. R.; Locksley, R. M. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells Immunity 1999, 11, 399-409 (Pubitemid 29504195)
4. Schaeffer, E. M.; Debnath, J.; Yap, G.; McVicar, D.; Liao, X. C.; Littman, D. R.; Sher, A.; Varmus, H. E.; Lenardo, M. J.; Schwartzberg, P. L. Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity Science 1999, 284, 638-641 (Pubitemid 29289587)
5. Schaeffer, E. M.; Yap, G. S.; Lewis, C. M.; Czar, M. J.; McVicar, D. W.; Cheever, A. W.; Sher, A.; Schwartzberg, P. L. Mutation of Tec family kinases alters T helper cell differentiation Nat. Immunol. 2001, 2, 1183-1188 (Pubitemid 33130154)
6. Mueller, C.; August, A. Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK J. Immunol. 2003, 170, 5056-5063 (Pubitemid 36559524)
7. Matsumoto, Y.; Oshida, T.; Obayashi, I.; Imai, Y.; Matsui, K.; Yoshida, N. L.; Nagata, N.; Ogawa, K.; Obayashi, M.; Kashiwabara, T.; Gunji, S.; Nagasu, T.; Sugita, Y.; Tanaka, T.; Tsujimoto, G.; Katsunuma, T.; Akasawa, A.; Saito, H. Identification of highly expressed genes in peripheral blood T cells from patients with atopic dermatitis Int. Arch. Allergy Immunol. 2002, 129, 327-340
8. Sahu, N.; August, A. ITK inhibitors in inflammation and immune-mediated disorders Curr. Top. Med. Chem. 2009, 9, 690-703
9. Lo, H.-Y. Itk inhibitors: a patent review Expert Opin. Ther. Pat. 2010, 20, 459-469
10. Das, J.; Chunjian, L.; Moquin, R. V.; Lin, J.; Furch, J. A.; Spergel, S. H.; McIntyre, K. W.; Shuster, D. J.; O'Day, K. D.; Penhallow, B.; Hung, C.-Y.; Kanner, S. B.; Lin, T.-A.; Dodd, J. H.; Barrish, J. C.; Wityak, J. Discovery and SAR of 2-amino-5-[(thiomethyl)aryl]thiazoles as potent and selective Itk inhibitors Bioorg. Med. Chem. Lett. 2006, 16, 2411-2415
11. Das, J.; Furch, J. A.; Liu, C.; Moquin, R. V.; Lin, J.; Spergel, S. H.; McIntyre, K. W.; Shuster, D. J.; O'Day, K. D.; Penhallow, B.; Hung, C.-Y.; Doweyko, A. M.; Kamath, A.; Zhang, H.; Marathe, P.; Kanner, S. B.; Lin, T.-A.; Dodd, J. H.; Barrish, J. C.; Wityak, J. Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors Biorg. Med. Chem. Lett. 2006, 16, 3706-3712 (Pubitemid 44137221)
12. Snow, R. J.; Abeywardane, A.; Campbell, S.; Lord, J.; Kashem, M. A.; Khine, H. H.; King, J.; Kowalski, J. A.; Pullen, S. S.; Roma, T.; Roth, G. P.; Sarko, C. R.; Wilson, N. S.; Winters, M. P.; Wolak, J. P.; Cywin, C. L. Hit-to-lead studies on benzimidazole inhibitors of ITK: discovery of a novel class of kinase inhibitors Biorg. Med. Chem. Lett. 2007, 17, 3660-3665 (Pubitemid 46898812)
13. Moriarty, K. J.; Winters, M.; Qiao, L.; Ryan, D.; DesJarlis, R.; Robinson, D.; Cook, B. N.; Kashem, M. A.; Kaplita, P. V.; Liu, L. H.; Farrell, T. M.; Khine, H. H.; King, J.; Pullen, S. S.; Roth, G. P.; Magolda, R.; Takahashi, H. Itk kinase inhibitors: initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead Bioorg. Med. Chem. Lett. 2008, 18, 5537-5540
14. Moriarty, K. J.; Takahashi, H.; Pullen, S. S.; Khine, H. H.; Sallati, R. H.; Raymond, E. L.; Woska, J. R., Jr.; Jeanfavre, D. D.; Roth, G. P.; Winters, M. P.; Qiao, L.; Ryan, D.; DesJarlais, R.; Robinson, D.; Wilson, M.; Bobko, M.; Cook, B. N.; Yin, Lo, H.; Nemoto, P. A.; Kashem, M. A.; Wolak, J. P.; White, A.; Magolda, R. L.; Tomczuk, B. Discovery, SAR and X-ray structure of 1 H -benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk) Bioorg. Med. Chem. Lett. 2008, 18, 5545-5549
15. Cook, B. N.; Bentzien, J.; White, A.; Nemoto, P. A.; Wang, J.; Man, C. C.; Soleymanzadeh, F.; Khine, H. H.; Kashem, M. A.; Kugler, S. Z., Jr.; Wolak, J. P.; Roth, G. P.; De Lombaert, S.; Pullen, S. S.; Takahashi, H. Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design Bioorg. Med. Chem. Lett. 2009, 19, 773-777
16. Winters, M. P.; Robinson, D. J.; Khine, H. H.; Pullen, S. S.; Woska, J. R., Jr.; Raymond, E. L.; Sellati, R.; Cywin, C. L.; Snow, R. J.; Kashem, M. A.; Wolak, J. P.; King, J.; Kaplita, P. V.; Liu, L. H.; Farrell, T. M.; DesJarlais, R.; Roth, G. P.; Takahashi, H.; Moriarty, K. J. 5-Aminomethyl- 1H -benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk) Bioorg. Med. Chem. Lett. 2008, 18, 5541-5544
17. Riether, D.; Zindell, R.; Kowalski, J. A.; Cook, B. N.; Bentzien, J.; De Lombaert, S.; Thomson, D.; Kugler, S. Z., Jr.; Skow, D.; Martin, L. S.; Raymond, E. L.; Khine, H. H.; O'Shea, K.; Woska, J. R., Jr.; Jeanfavre, D.; Sellati, R.; Ralph, K. L. M.; Ahlberg, J.; Labissiere, G.; Kashem, M. A.; Pullen, S. S.; Takahashi, H. 5-Aminomethylbenzimidazoles as potent ITK antagonists Bioorg. Med. Chem. Lett. 2009, 19, 1588-1591
18. Lin, T. A.; McIntyre, K. W.; Das, J.; Liu, C.; O'Day, K. D.; Penhallow, B.; Hung, C. Y.; Whitney, G. S.; Shuster, D. J.; Yang, X.; Townsend, R.; Postelnek, J.; Spergel, S. H.; Lin, J.; Moquin, R. V.; Furch, J. A.; Kamath, A. V.; Zhang, H.; Marathe, P. H.; Perez-Villar, J. J.; Doweyko, A.; Killar, L.; Dodd, J. H.; Barrish, J. C.; Wityak, J.; Kanner, S. B. Selective Itk inhibitors block T-cell activation and murine lung inflammation Biochemistry 2004, 43, 11056-11062 (Pubitemid 39433694)
19. Li, R.; Xue, L.; Zhu, T.; Jiang, Q.; Cui, X.; Yan, Z.; McGee, D.; Wang, J.; Gantla, V. R.; Pickens, J. C.; McGrath, D.; Chucholowski, A.; Morris, S. W.; Webb, T. R. Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic lymphoma kinase J. Med. Chem. 2006, 49, 1006-1015 (Pubitemid 43221648)
20. Kuethe, J.; Wong, A.; Davis, I. W. Rapid and efficient synthesis of 1 H -indol-2-yl-1 H -quinolin-2-ones Org. Lett. 2003, 5, 3975-3978 (Pubitemid 37412180)
21. Kiethe, J. Y.; Wong, A.; Qu, C.; Smitrovitch, J.; Davies, I. W.; Hughes, D. L. Synthesis of 5-substituted-1 H -indol-2-yl-1 H -quinolin-2-ones: a novel class of KDR kinase inhibitors J. Org. Chem. 2005, 70, 2555-2567
22. Durrant, S. J.; Pinder, J. L.; Charrier, J.- D.; Jimenez, J.- M.; Brenchey, G.; Collier, P. N.; Kay, D.; Miller, A.; Pierard, F.; Ramaya, S.; Sadiq, S.; Twin, H. Synthesis of a stable pyridyl boronate and its reaction with aryl and heteroaryl halides Heterocycles 2006, 70, 509-517
23. Zhu, L.; Duquette, J.; Zhang, M. An improved preparation of arylboronates: application in one-pot Suzuki biaryl synthesis J. Org. Chem. 2003, 68, 3729-3732 (Pubitemid 36520407)
24. Brown, K.; Long, J. M.; Vial, S. C.; Dedi, N.; Dunster, N. J.; Renwick, S. B.; Tanner, A. J.; Frantz, J. D.; Fleming, M. A.; Cheetham, G. M. Crystal structures of interleukin-2 tyrosine kinase and their implications for the design of selective inhibitors J. Biol. Chem. 2004, 279, 18727-32 (Pubitemid 38623297)
25. Gajiwala, K. S.; Wu, J. C.; Christensen, J.; Deshmukh, G. D.; Diehl, W.; DiNitto, J. P.; English, J. M.; Greig, M. J.; He, Y. A.; Jacques, S. L.; Lunney, E. A.; McTigue, M.; Molina, D.; Quenzer, T.; Wells, P. A.; Yu, X.; Zhang, Y.; Zou, A.; Emmett, M. R.; Marshall, A. G.; Zhang, H. M.; Demetri, G. D. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 1542-1547
26. Mol, C. D.; Dougan, D. R.; Schneider, T. R.; Skene, R. J.; Kraus, M. L.; Scheibe, D. N.; Snell, G. P.; Zou, H.; Sang, B. C.; Wilson, K. P. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase J. Biol. Chem. 2004, 279, 31655-31663 (Pubitemid 39037836)
27. Mol, C. D.; Lim, K. B.; Sridhar, V.; Zou, H.; Chien, E. Y.; Sang, B. C.; Nowakowski, J.; Kassel, D. B.; Cronin, C. N.; McRee, D. E. Structure of a c-kit product complex reveals the basis for kinase transactivation J. Biol. Chem. 2003, 278, 31461-31464 (Pubitemid 37048320)
28. Griffith, J.; Black, J.; Faerman, C.; Swenson, L.; Wynn, M.; Lu, F.; Lippke, J.; Saxena, K. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain Mol. Cell 2004, 13, 169-178 (Pubitemid 38183264)
29. Abel, R.; Young, T.; Farid, R.; Berne, B. J.; Friesner, R. A. Role of the active-site solvent in the thermodynamics of factor Xa ligand binding J. Am. Chem. Soc. 2008, 130, 2817-2831 (Pubitemid 351416242)
30. Knegtel, R. M. A.; Robinson, D. Unpublished results.
31. Howard, J. A. K.; Hoy, V. J.; O'Hagan, D.; Smith, G. T. How good is fluorine as a hydrogen bond acceptor Tetrahedron 1996, 52, 12613-12622 (Pubitemid 26295489)
32. Manning, G.; Whyte, D. B.; Martinez, R; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome Science 2002, 298, 1912-1934 (Pubitemid 35425239)