Synthesis of N-aryl-3-(indol-3-yl)propanamides and their immunosuppressive activities

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 17, 2010, Pages 5203-5206

  Giraud, Francis ^a   Marchand, Pascal ^a   Carbonnelle, Delphine ^a   Sartor, Michael ^a   Lang, François ^a   Duflos, Muriel ^a  

^a UNIVERSITÉ DE NANTES   (France)

Author keywords

Immunosuppressive activity; N Aryl 3 (indol 3 yl)propanamides

Indexed keywords

3 [1 (4 CHLOROBENZYL) 1H INDOL 3 YL] N (4 NITROPHENYL)PROPANAMIDE; IMMUNOSUPPRESSIVE AGENT; ISOQUINOLINE; N ARYL 3 (INDOL 3 YL)PROPANAMIDE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DELAYED HYPERSENSITIVITY; DRUG ACTIVITY; DRUG SYNTHESIS; MOUSE; NONHUMAN; SPLEEN CELL;

AMIDES; ANIMALS; HYPERSENSITIVITY, DELAYED; IMMUNOSUPPRESSIVE AGENTS; INDOLES; INHIBITORY CONCENTRATION 50; MICE;

MURINAE; MUS;

EID: 77955656195     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.07.001     Document Type: Article

References (24)

1. M. Rigol, N. Solanes, M. Sionis, C. Galvez, J. Martorell, I. Rojo, M. Brunet, J. Ramirez, M. Roque, E. Roig, F. Perez-Villa, L. Barquin, J.L. Pomar, G. Sanz, M. Heras, and M.A. Masri J. Heart Lung Transplant. 27 2008 416
2. S.K. Takemoto, P.I. Terasaki, D.W. Gjertson, and J.M. Cecka N. Eng. J. Med. 343 2000 1078
3. X. Yu, P. Carpenter, and C. Anasetti Lancet 357 2001 1959
4. R. Margreiter Lancet 359 2002 741
5. Y. Vanrenterghem, J.P. Van Hoff, M. Klinger, Z. Wlodarczyk, J.P. Squifflet, G. Mourad, P. Neuhaus, A. Jurewicz, L. Rostaing, B. Charpentier, L. Paczek, H. Kreis, R. Chang, L.C. Paul, J.M. Grinyo, and C. Short Transplantation 78 2004 9
6. L.E. Wai, M. Fujiki, S. Takeda, O.M. Martinez, and S.M. Krams Transplantation 85 2008 145
7. A. Gallard, M. Duflos, M.R. Nourrisson, G. Le Baut, N. Grimaud, and J.Y. Petit J. Enzym. Inhib. Med. Chem. 18 2003 201
8. D. Carbonnelle, M. Lardic, A. Dassonville, E. Verron, J.Y. Petit, M. Duflos, and F. Lang Eur. J. Med. Chem. 42 2007 686
9. D. Carbonnelle, M. Duflos, P. Marchand, C. Chauvet, J.Y. Petit, and F. Lang J. Pharmacol. Exp. Ther. 331 2009 710
10. K. Ghoreschi, A. Laurence, and J.J. O'Shea Immunol. Rev. 228 2009 273
11. M. Pesu, A. Laurence, N. Kishore, S.H. Zwillich, G. Chan, and J.J. O'Shea Immunol. Rev. 223 2008 132
12. A.F. Wilks Semin. Cell Dev. Biol. 19 2008 319
13. D.C. Borie, J.J. O'Shea, and P.S. Changelian Trends Mol. Med. 10 2004 532
14. A.C. Papageorgiou, and L.E. Wikman Trends Pharmacol. Sci. 25 2004 558
15. S.T. Wrobleski, and W.J. Pitts Annu. Rep. Med. Chem. 44 2009 247
16. P.S. Changelian, D. Moshinsky, C.F. Kuhn, M.E. Flanagan, M.J. Munchhof, T.M. Harris, J.L. Doty, J. Sun, C.R. Kent, K.S. Magnuson, D.G. Perregaux, P.S. Sawyer, and E.M. Kudlacz Blood 111 2008 2155
17. J.E. Thompson Drug News Perspect. 18 2005 305
18. A.L. Ruchelman, J.E. Kerrigan, T.K. Li, N. Zhou, A. Liu, L.F. Liu, and E.J. LaVoie Bioorg. Med. Chem. 12 2004 3731
19. C. Abeywickrama, S.A. Rotenberg, and A.D. Baker Bioorg. Med. Chem. 14 2006 7796
20. 2 in a final volume of 150 μL of complete RPMI medium supplemented with 50 μM mercaptoethanol. Cell proliferation was assessed in sextuplicate after 72 h of culture, by colorimetric detection. Briefly, cells were incubated with 12.5 μg/well of 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) for 4 h at 37 °C. Formazan products were solubilized by 100 μL of lysis buffer (dimethylformamide (1 V), SDS 20% (2 V), pH 4.7) and overnight incubation at 37 °C. Cell growth was assessed using a MRX microplate reader (Dynex Technologies, Chantilly, USA) with the test wavelength at 570 nm and expressed as optical density (OD) values. The inhibition of splenocytes proliferation was expressed as inhibitory rate [(OD value of control untreated cells - OD value of treated cells)/OD value of control untreated cells group] × 100.
21. R.M. Angell, F.L. Atkinson, M.J. Brown, T.T. Chuang, J.A. Christopher, M. Cichy-Knight, A.K. Dunn, K.E. Hightower, S. Malkakorpi, J.R. Musgrave, M. Neu, P. Rowland, R.L. Shea, J.L. Smith, D.O. Somers, S.A. Thomas, G. Thompson, and R. Wang Bioorg. Med. Chem. Lett. 17 2007 1296
22. J. Weisner, A. Mitsch, H. Jomaa, and M. Schlitzer Bioorg. Med. Chem. Lett. 13 2003 2159
23. 8 SRBC suspended in 40 μL) injected into the right hind footpad. The left footpad was used as a control and injected with PBS alone. The size of both hind footpads was measured with an 'Oditest' (Kroeplin, Germany) 24 h after challenge. DTH reaction was determined by the difference in size between the SRBC- and PBS-injected footpads. Mice were daily treated orally for 5 days with different doses of compound 15, from the time of priming until the SRBC challenge. The DTH inhibition index was calculated as the ratio of DTH reaction in the treated animal versus the DTH reaction in control mice. Results are expressed as mean ± SEM. All results were compared statistically using Dunnett unpaired multiple.
24. 50 values were calculated using Graph Pad Prism software.