2-Aminobenzimidazoles as potent ITK antagonists: de novo design of a pyrrole system targeting additional hydrogen bonding interaction

Tetrahedron Letters

Volumn 49, Issue 51, 2008, Pages 7337-7340

  Lo, Ho Yin ^a   Bentzien, Jörg ^a   White, Andre ^a   Man, Chuk C ^a   Fleck, Roman W ^a   Pullen, Steven S ^a   Khine, Hnin Hnin ^a   King, Josephine ^a   Woska Jr , Joseph R ^a   Wolak, John P ^a   Kashem, Mohammed A ^a   Roth, Gregory P ^b   Takahashi, Hidenori ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^b Burnham Institute for Medical Research at Lake Nona   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINOBENZIMIDAZOLE DERIVATIVE; INTERLEUKIN 2 INDUCIBLE T CELL KINASE INHIBITOR; PHOSPHOTRANSFERASE INHIBITOR; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; HYDROGEN BOND; MOLECULAR MODEL; X RAY CRYSTALLOGRAPHY;

EID: 55049135319     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.10.057     Document Type: Article

References (13)

1. Smith C.I., Islam T.C., Mattsson P.T., Mohamed A.J., Nore B.F., and Vihinen M. Bioessays 23 (2001) 436-446
2. Forssel J., Sideras P., Eriksson C., Malm-Erjefält M., Rydell-Törmänen K., Ericsson P., and Erjefält J.S. Am. J. Respir. Cell. Mol. Biol. 32 (2005) 511-520
3. Schaeffer E.M., Yap G.S., Lewis C.M., Czar M.J., McVicar D.W., Cheever A.W., Sher A., and Schwartzberg P.L. Nature Immune. 2 (2001) 1183-1188
4. Kanner S.B., and Perez-Villar J.J. Trends Immunol. 24 (2003) 249-253
5. Snow R.J., Abeywardane A., Cywin C.L., Lord J., Kashem M.A., Khine H.H., Kowalski J.A., Pullen S.S., Roth G.P., Sarko C.R., Wilson N.S., Winters M., and Wolak J.P. Bioorg. Med. Chem. Lett. 17 (2007) 3660-3665
6. Winters, M. P.; Robinson, D. J.; Khine, H. H.; Pullen, S. S.; Woska, Jr., J. R.; 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.; Moriaty, K. J. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2008.09.016, in press.
7. Moriarty, K. J.; Takahashi, H.; Pullen, S. S.; Khine, H. H.; Sallati, R. H.; Raymond, E. L.; Woska, Jr., J. R.; Jeanfavre, D. D.; Roth, G. P.; Winters, M. P.; Qiao, L.; Ryan, D.; DesJarlais, R.; Robinson, D.; Wilson, M.; Bobko, M.; Cook, B. N.; Lo, H. Y.; Nemoto, P. A.; Kashem, M. A. et al. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2008.09.015, in press.
8. 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. Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2008.09.017, in press.
9. Kashem M.A., Nelson R.M., Yingling J.D., Pullen S.S., Prokopowicz III A.S., Jones J.W., Wolak J.P., Rogers G.R., Morelock M.M., Snow R.J., Homon C.A., and Jakes S. J. Biomol. Screening 12 (2007) 70-83
10. Takata R., and Kurosaki T. J. Exp. Med. 184 (1996) 31
11. White, A.; Abeywardane, A.; Cook, B. N.; Fuschetto, N.; Gautschi, E.; John, A.; Kroe, R. R.; Kronkaitis, A.; Li, Xiang; Pullen, S. S.; Roma, T.; Moriarty, K. J.; Roth, G. P.; Snow, R. J.; Studts, J. M.; Takahashi, H.; Farmer, B. T, II. J. Biol. Chem, submitted for publication.
12. 2O (10 mL/2 mL). 1 N NaOH (2 mL) was added, and the solution was stirred at room temperature for 12 h. The pH of the solution was adjusted to 6 by the addition of 0.1 N HCl. The solution was then concentrated, and the residue was purified by column chromatography to afford benzoyl pyrrole 6 (230 mg, 76%) as a white solid.
13. 50's are calculated by SAS.