Bulletin of the Korean Chemical Society

  • 제27권9호
  • /
  • Pages.1353-1358
  • /
  • 2006
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Development of Novel Small Chemical Inhibitors for Lck SH Domain with in vitro T-cell Inhibitory Activity

  • 발행 : 2006.09.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

We investigated in vitro T-cell inhibitory activity and bioavailability of small chemical inhibitors for Lck SH2 domain, which had a different scaffold such as an amide bond, reduced amide bond, N-methyl amide bond, thioamide bond, and urethane bond. Each of these compounds, with its particular scaffold, showed a different logP value, stability against serum enzyme, stability in buffer solution, and in vitro T-cell inhibitory activity. Overall results indicated that the SH2 inhibitor containing urethane bond can be a new lead compound because of its superior bioavailability, potent in vitro T-cell inhibitory activity, and facile synthesis.

키워드

참고문헌

  1. Cantley, L. C.; Auger, K. R.; Carpenter, C.; Duckworth, B.; Graziani, A.; Kappeller, R.; Soltoff, S. Cell 1991, 64, 241
  2. Botfield, M. C.; Green, J. Ann. Rep. Med. Chem. 1995, 30, 227 https://doi.org/10.1016/S0065-7743(08)60937-9
  3. Pawson, T.; Gish, G. D.; Nash, P. Trends Cell Biol. 2001, 11, 504 https://doi.org/10.1016/S0962-8924(01)02154-7
  4. Broadbridge, R. J.; Sharma, R. P. Current Drug Targets 2000, 1, 365 https://doi.org/10.2174/1389450003349074
  5. Beaulieu, P. L; Cameron, D. R.; Ferland, J. M.; Gauthier, J.; Ghiro, E.; Gillard, J.; Gorys, V.; Poirier, M.; Rancourt, J.; Wernic, D.; Llinas-Brunet, M.; Betageri, R.; Cardozo, M.; Hickey, E. R.; Ingraham, R.; Jakes, S.; Kabcenell, A.; Kirrane, T.; Lukas, S.; Patel, U.; Proudfoot, J.; Sharma, R.; Tong, L.; Moss, N. J. Med. Chem. 1999, 42, 1757 https://doi.org/10.1021/jm980676t
  6. Rye, C. S.; Baell, J. B. Curr. Med. Chem. 2005, 26, 3127
  7. Costantio, L.; Barlocoo, D. Curr. Med. Chem. 2004, 20, 2725
  8. Vu C. B. Curr. Med. Chem. 2000, 10, 1081
  9. Garcia-Echeverria, C. Curr. Med. Chem. 2001, 13, 1589
  10. Sawyer, T. K. Biopolymers 1998, 47, 243 https://doi.org/10.1002/(SICI)1097-0282(1998)47:3<243::AID-BIP4>3.0.CO;2-P
  11. Sony, Y. L.; Peach, M. L.; Roller, P. P.; Qiu, S.; Wang, S.; Long, Y. Q. J. Med. Chem. 2006, 49, 1585 https://doi.org/10.1021/jm050910x
  12. Shakespeare, W.; Yang, M.; Bohacek, R.; Cerasoli, F.; Stebbins, K.; Sundaramoorthi, R.; Azimioara, M.; Vu, C.; Pradeepan, S.; Metcalf III, C.; Haraldson, C.; Merry, T.; Dalgarno, D.; Narula, S.; Hatada, M.; Lu, X.; Schravendijk, M.; Adams, S.; Violette, S.; Smith, J.; Guan, W.; Bartlett, C.; Herson, L.; Iuliucci, J.; Weigele, M.; Sawyer, T. K. Proc. Natl. Acad. Sci. USA 2000, 17, 9373
  13. Lee, T. R.; Lawrence, D. S. J. Med. Chem. 2000, 43, 1173 https://doi.org/10.1021/jm990462r
  14. Park, S.; Won, J.; Lee, K. H. Bioorg. Med. Chem. Lett. 2002, 12, 2711 https://doi.org/10.1016/S0960-894X(02)00523-1
  15. Kang, S.; Park, S.; Shim, H.; Lee, K. H. Bull. Korean Chem. Soc. 2003, 24, 664 https://doi.org/10.5012/bkcs.2003.24.5.664
  16. Won, J.; Hur, E. M.; Hur, Y.; Park, S.; Kang, M.; Choi, Y.; Park, C.; Lee, K. H.; Yun, Y. Eur. J. Immunology 2003, 33, 870 https://doi.org/10.1002/eji.200323010
  17. Hur, Y.; Yun, Y.; Won, J. J. Immunol. 2004, 172, 79 https://doi.org/10.4049/jimmunol.172.1.79
  18. Kang, M. A.; Yun, S. Y.; Won, J. Blood 2003, 101, 3534 https://doi.org/10.1182/blood-2002-07-1992
  19. Petersen, M.; Simmonds, M. S. Phytochemistry 2003, 62, 121 https://doi.org/10.1016/S0031-9422(02)00513-7
  20. Bogucki, D. E.; Charlton, J. L. Can. J. Chem. 1997, 75, 1783 https://doi.org/10.1139/v97-612
  21. Eicher, T.; Ott, M.; Speicher, A. Synthesis 1996, 755
  22. Nakazawa, T.; Ohsawa, K. J. Nat. Prod. 1998, 61, 993 https://doi.org/10.1021/np980072s
  23. Park, S. H.; Kang, S. H.; Lim, S. H.; Oh, H. S.; Lee, K. H. Bioorg. Med. Chem. Lett. 2003, 13, 3455 https://doi.org/10.1016/S0960-894X(03)00735-2
  24. Lee, T. R.; Lawrence, D. S. J. Med. Chem. 1999, 42, 784 https://doi.org/10.1021/jm980663f
  25. Choi, Y. B.; Kim, C. K.; Yun, Y. J. Immunol. 1999, 163, 5242
  26. Nasal, A.; Siluk, D.; Kaliszan, R. Curr. Med. Chem. 2003, 10, 381 https://doi.org/10.2174/0929867033368268
  27. Valko, K.; My Du, D.; Bevan, D.; Reynolds, D. P.; Abraham, M. H. Curr. Med. Chem. 2001, 8, 1137 https://doi.org/10.2174/0929867013372643
  28. Powell, M. F.; Stewart, T., Jr.; Otvos, L.; Urge, L.; Gaeta, F. C. A.; Sette, A.; Arrhenius T. Pharm. Res. 1993, 10, 1268 https://doi.org/10.1023/A:1018953309913
  29. Hong, S. Y.; Oh, J. E.; Lee, K. H. Biochem. Pharmacol. 1999, 58, 1775 https://doi.org/10.1016/S0006-2952(99)00259-2
  30. Zacharie, B.; Lagraoui, M.; Dimarco, M.; Penney, C. L.; Gagnon, L. J. Med. Chem. 1999, 42, 2046 https://doi.org/10.1021/jm9900467

피인용 문헌

  1. Development of Novel Small Chemical Inhibitors for Lck SH Domain with in vitro T-Cell Inhibitory Activity. vol.38, pp.7, 2007, https://doi.org/10.1002/chin.200707217