Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 15, 2007, Pages 4382-4386

  Lagu, Bharat ^a   Gerchak, Chrissy ^a   Pan, Meng ^a   Hou, Cuifen ^a   Singer, Monica ^a   Malaviya, Ravi ^a   Matheis, Michele ^a   Olini, Gil ^a   Cavender, Druie ^a   Wachter, Michael ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Asthma; CCR2 antagonist; Chemokine receptor 2; Chemotaxis; MCP 1; Monocytes; Quaternary ammonium salt

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CHEMOKINE RECEPTOR ANTAGONIST; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; PIPERIDINE; PYRROLIDINE DERIVATIVE; QUATERNARY AMMONIUM DERIVATIVE;

ARTICLE; ASTHMA; BINDING AFFINITY; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; LIPOPHILICITY; LUNG LAVAGE; STRUCTURE ACTIVITY RELATION;

ANTI-ASTHMATIC AGENTS; ASTHMA; HUMANS; RECEPTORS, CHEMOKINE;

EID: 34347373032     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.01.115     Document Type: Article

References (24)

1. Bachman M.F., Kopf M., and Marsland B.J. Nat. Rev. Immunol. 103 (2006) 3733
2. Rollins B. J. Mol. Med. Today 2 (1996) 198
3. Dawson J., Miltz W., Mir A.K., and Weissner C. Expert Opin. Ther. Targets 7 (2003) 35
4. Feria M., and Diaz-Gonzalez F. Expert Opin. Ther. Pat. 16 (2006) 49
5. Saunders J., and Tarby C.M. Drug Discovery Today 4 (1999) 80
6. Boring L., Gosling J., Chensue S.W., Kunkel S.L., Farsee R.V., Broxmeyer H.E., and Charo I.F. J. Clin. Invest. 100 (1997) 2552
7. Kuziel W.A., Morgan S.J., Dawson T.C., Griffin S., Smithies O., Ley K., and Maeda N. Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 12053
8. Gao Z., and Metz W.A. Chem. Rev. 103 (2003) 3733
9. Forbes I.T., Cooper D.G., Dodds E.K., Hickey D.M.B., Ife R.J., Messon M., Stockley M., Berkhout T.A., Gohil J., Groot P.H.E., and Moores K. Bioorg. Med. Chem. Lett. (2000) 1803
10. Witherington J., Bordas V., Cooper D.G., Forbes I.T., Gribble A.D., Ife R.J., Berkhout T.A., Gohil J., Groot P.H.E., and Moores K. Bioorg. Med. Chem. Lett. (2000) 1803
11. Pasternak A., Marino D., Vicario P.P., Ayala J.M., Casceierri M., Parsons W., Mills S.G., MacCoss M., and Yang L. J. Med. Chem. 49 (2006) 4801
12. Mirazadegan T., Diehl F., Ebi B., Bhakta S., Polsky I., McCarley D., Mulkins M., Weatherhead G.S., Lapierre J.M., Dankwardt J., Morgans Jr. D., Wilhelm R., and Jarnagin K. J. Biol. Chem. 275 (2000) 25562
13. Moree W.J., Kataoka K., Ramirez-Weinhouse M.M., Shiota T., Imai M., Sudo M., Tsutsumi T., Endo N., Muroga Y., hada T., Tanaka H., Morita T., Greene J., Barnum D., Saunders J., Kato Y., Meyers P.L., and Tarby C.M. Bioorg. Med. Chem. Lett. 14 (2004) 5413
14. Warner-Lambert Co. US6,184235B1.
15. Shirashi M., Aramaki Y., Seto H., Nishikawa Y., Kanzaki N., Okamoto M., Sawda H., Nishimura O., Baba M., and Fujino M. J. Med. Chem. 43 (2000) 2049
16. Hashimoto H., Ikemoto T., Itoh T., Maruyama H., Hanaoka T., Wakimasu M., Mitsudera H., and Tomimatsu K. Org. Process Res. Dev. 6 (2002) 70
17. THP-1 cells were incubated with 0.5 nM 125-I labeled MCP-1 (Perkin-Elmer Life Sciences, Inc., Boston, MA) in the presence of varying concentrations of either unlabeled MCP-1 (R&D systems, Minneapolis, MN)or the test compound for 2 h at 30 °C in a 96-well plate. Cells were then harvested onto a filter plate, dried, and 20 μL of Microscint-20 was added to each well. Plates were counted in a TopCount NXT microplate scintillation and luminescence counter (Perkin-Elmer Life Sciences, Inc., Boston, MA). Blank values (buffer only) were subtracted from all the values and drug treated values were compared to vehicle treated values. One micromolar cold MCP-1 was used for non-specific binding.
18. In this model, mice are injected ip with zymosan, a polysaccharide derived from the cell walls of yeast (Saccharomyces cerevisiae). A rapid influx of neutrophils into the peritoneal cavity occurs, peaking at ∼4 h, which is followed by a wave of monocyte infiltration which is maximal at 16-24 h. MCP-1 concentration in peritoneal lavage fluid peaks at ∼4 h, and an antibody to MCP-1 significantly inhibits monocyte infiltration.
19. Ajuebor M.N., Flower R.J., Hannon R., Christie M., Bowers K., Verity A., and Perretti M. J. Leukocyte Biol. 63 (1998) 108
20. Alam R., York J., Boyars M., Stafford S., Grant J.A., Lee J., Forsythe P., Sim T., and Ida N. Am. J. Respir. Crit. Care Med. 153 (1996) 1398
21. Hsieh K.H., Chou C.C., and Chiang B.L. J. Allergy Clin. Immunol. 98 (1996) 580
22. Gonzalo J.A., Lloyd C.M., Wen D., Albar J.P., Wells T.N.C., Proudfoot A., Martinez A.C., Dorf M., Bjerke T., Coyle A.J., and Gutierrez-Ramos J. J. Exp. Med. 188 (1998) 157
23. Barnes P.J. Nat. Rev. Drug Disc. 10 (2004) 831
24. Williams C.J., and Galli S.J. J. Exp. Med. 192 (2000) 455