Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationships

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 23, 2005, Pages 5288-5292

  Gavrin, Lori Krim ^a   Green, Neal ^a   Hu, Yonghan ^a   Janz, Kristin ^a   Kaila, Neelu ^a   Li, Huan Qiu ^a   Tam, Steve Y ^a   Thomason, Jennifer R ^a   Gopalsamy, Ariamala ^b   Ciszewski, Greg ^b   Cuozzo, John W ^a   Hall, J Perry ^a   Hsu, Sang ^a   Telliez, Jean Baptiste ^a   Lin, Lih Ling ^a  

^a PFIZER INC   (United States)

^b WYETH RESEARCH   (United States)

Author keywords

1,7 Naphthyridine 3 carbonitriles; Tpl2 kinase

Indexed keywords

CYANIDE; MITOGEN ACTIVATED PROTEIN KINASE 3; NAPHTHYRIDINE DERIVATIVE; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; CYTOKINE PRODUCTION; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME SYNTHESIS; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; INHIBITION KINETICS; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION;

ARTHRITIS, RHEUMATOID; HUMANS; MAP KINASE KINASE KINASES; NAPHTHYRIDINES; NITRILES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

EID: 26844453571     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.029     Document Type: Article

References (34)

1. M. Feldmann, and R. Mani Annu. Rev. Immunol. 19 2001 163
2. B. Jarvis, and D. Faulds Drugs 57 1999 945
3. R. Maini, E.W. St. Clair, F. Breedveld, D. Furst, J. Kalden, M. Weisman, J. Smolen, P. Emery, G. Harriman, M. Feldmann, and P. Lipsky Lancet 354 1999 1932
4. H. Sasai, T. Higashi, S. Nakamori, J. Miyoshi, F. Suzuki, T. Nomura, and T. Kakunaga Br. J. Cancer 67 1993 262
5. J. Miyoshi, T. Higashi, H. Mukai, T. Ohuchi, and T. Kakunaga Mol. Cell. Biol. 11 1991 4008
6. T.K. Schlesinger, G.R. Franger, T. Yujiri, and G.L. Johnson Front. Biosci. 3 1998 D1181
7. C.D. Dumitru, J.D. Ceci, C. Tsatsanis, D. Konoyiannis, K. Stamatakis, J.H. Lin, C. Patriotis, N.A. Jenkins, N.G. Copeland, G. Kollias, and P.N. Tsichlis Cell 103 2000 1071
8. A.G. Eliopoulos, C.D. Dumitru, C.C. Wang, J. Cho, and P.N. Tsichlis EMBO J. 21 2002 4831
9. X. Lin, E.T. Cunningham Jr., Y. Mu, R. Gelziunas, and W.C. Greene Immunity 10 1999 271
10. M. Chiarello, M.J. Marinissen, and J.S. Gutkind Mol. Cell. Biol. 20 2000 1747
11. A. Salmeron, T.B. Ahmad, G.W. Carlile, D. Pappin, R.P. Narsimhan, and S.C. Ley EMBO J. 15 1996 817
12. B. Luciano, S. Hsu, P.B. Channavajhala, L.-L. Lin, and J.W. Cuozzo J. Biol. Chem. 279 2004 52117
13. A. Wissner, P.R. Hamann, R. Nilakantan, L.M. Greenberger, F. Ye, T.A. Rapuano, and F. Loganzo Bioorg. Med. Chem. Lett. 14 2004 1411
14. 6O (MH+) 409.1538, found 409.1542.
15. 3, and 1% BSA. The detection plate was washed again and incubated for 30 min with DELFIA Europium (Eu) labeled goat anti-rabbit IgG (Perkin-Elmer), 1:4000 in the same buffer used for the primary incubation. After a final wash, Eu detection solution was added to each well and the Eu signal was measured in a Wallac Victor Multilabel Counter. Data were imported into Excel and IC50 calculations were performed using the Xlfit (IDBS) software package.
16. A. Wissner, D.M. Berger, D.H. Boschelli, B.M. Floyd, L.M. Greenberger, B.C. Gruber, B.D. Johnson, N. Mamuya, R. Nilakantan, F.M. Reich, R. Shen, H. Tsou, E. Upeslacis, Y.F. Wang, B. Wu, and N. Zhang J. Med. Chem. 43 2000 3244
17. Y.D. Wang, K. Miller, D.H. Boschelli, F. Ye, B. Wu, B.M. Floyd, D.W. Powell, A. Wissner, J.M. Weber, and F. Boschelli Bioorg. Med. Chem. Lett. 10 2000 2477
18. D.H. Boschelli, Y.D. Wang, F. Ye, B. Wu, N. Zhang, M. Dutia, D.W. Powell, A. Wissner, K. Arndt, J.M. Weber, and F. Boschelli J. Med. Chem. 44 2001 822
19. D.H. Boschelli, F. Ye, Y.D. Wang, M. Dutia, S.L. Johnson, B. Wu, K. Miller, D.W. Powell, D. Yaczko, M. Young, M. Tischler, K. Arndt, C. Discafani, C. Etienne, J. Gibbons, J. Grod, J. Lucas, J.M. Weber, and F. Boschelli J. Med. Chem. 44 2001 3965
20. N. Zhang, B. Wu, A. Wissner, D.W. Powell, S.K. Rabindran, C. Kohler, and F. Boschelli Bioorg. Med. Chem. Lett. 12 2002 423
21. D. Berger, M. Dutia, D. Powell, B. Wu, A. Wissner, F. Demorin, J. Weber, and F. Boschelli Bioorg. Med. Chem. Lett. 12 2002 2761
22. A. Wissner, B.M. Floyd, S.K. Rabindran, R. Nilakantan, L.M. Greenberger, R. Shen, Y.F. Wang, and H. Tsou Bioorg. Med. Chem. Lett. 12 2002 2893
23. D. Berger, M. Dutia, D. Powell, A. Wissner, F. Demorin, Y. Raifeld, J. Weber, and F. Boschelli Bioorg. Med. Chem. Lett. 12 2002 2989
24. D. Berger, M. Dutia, D. Powell, B. Wu, A. Wissner, D.H. Boschelli, B.M. Floyd, N. Zhang, N. Torres, J. Levin, X. Du, D. Wojciechowicz, C. Discafani, C. Kohler, S.C. Kim, L.R. Feldberg, K. Collins, and R. Mallon Bioorg. Med. Chem. Lett. 13 2003 3031
25. A. Wissner, E. Overbeek, M.F. Reich, B. Floyd, B.D. Johnson, N. Mamuya, E.C. Rosfjord, C. Discafani, R. Davis, X. Shi, S.K. Rabindran, B.C. Gruber, F. Ye, W.A. Hallett, R. Nilakantan, R. Shen, Y.F. Wang, L.M. Greenberger, and H. Tsou J. Med. Chem. 46 2003 49
26. H. Tsou, N. Mamuya, B.D. Johnson, M.F. Reich, B.C. Gruber, F. Ye, R. Nilakantan, R. Shen, C. Discafani, R. DeBlanc, R. Davis, F.E. Koehn, L.M. Greenberger, Y.F. Wang, and A. Wissner J. Med. Chem. 44 2001 2719
27. J.B. Smaill, H.D.H. Showalter, H. Zhou, A.J. Bridges, D.J. McNamara, D.W. Fry, J.M. Nelson, V. Sherwood, P.W. Vincent, B.J. Roberts, W.L. Elliott, and W.A. Denny J. Med. Chem. 44 2001 429
28. L.F. Hennequin, E.S.E. Stokes, A.P. Thomas, C. Johnstone, P.A. Plé, D.J. Ogilvie, M. Dukes, S.R. Wedge, J. Kendrew, and J.O. Curwen J. Med. Chem. 45 2002 1300
29. R. Banerjee, Z. Rachid, J. McNamee, and B.J. Jean-Claude J. Med. Chem. 46 2003 5546
30. P.A. Plé, T.P. Green, L.F. Hennequin, J. Curwen, M. Fennell, J. Allen, C. Lambert-van der Brempt, and G. Costello J. Med. Chem. 47 2004 871
31. The amino unit of this tailpiece: G.A.M. Giardina, L.F. Raveglia, M. Grugni, H.M. Sarau, C. Farina, A.D. Medhurst, D. Graziani, D.B. Schmidt, R. Rigolio, M. Luttmann, S. Cavagners, J.J. Foley, V. Vecchietti, and D.W.P. Hay J. Med. Chem. 42 1999 1053
32. 2. Thirty minutes prior to LPS stimulation, compounds (in 100% DMSO) are added. LPS is then added to 10 ng/mL and the cultures are allowed to incubate for an additional ∼3 h. Media supernatants are then harvested and analyzed for TNF-α by standard ELISA or electrochemiluminescence on a Sector6000 reader (Meso Scale Discovery).
33. Inhibition of TNF-α in human blood: blood is drawn from healthy male volunteers into heparin tubes. At 37°C, the blood is diluted 1-to-5 with pre-warmed RPMI/3% FCS, and then dispensed into 96-well-formatted 200 μL tube strips and capped. Thirty minutes prior to LPS stimulation compounds (in 100% DMSO) are added. Final DMSO concentrations equal 1.0%. LPS is then added to 10 ng/mL and the cultures are allowed to incubate for an additional ∼3 h. Samples are centrifuged in a strip rotor at 6500 rpm, and the plasma supernatants are analyzed by standard ELISA or electrochemiluminescence on a Sector6000 reader (Meso Scale Discovery).
34. For an example see: R.J. Cherney, J.J.W. Duan, M.E. Voss, L. Chen, L. Wang, D.T. Meyer, Z.R. Wasserman, K.D. Hardman, R.Q. Liu, M.B. Covington, M. Qian, S. Mandlekar, D.D. Christ, J.M. Trzaskos, R.C. Newton, R.L. Magolda, R.R. Wexler, and C. Decicco J. Med. Chem. 46 2003 1811