´
M.-O. Contour-Galcera et al. / Bioorg. Med. Chem. Lett. 15 (2005) 3555–3559
3559
Table 5. EC50 values (nM) for inhibition of forskolin-induced cAMP
accumulation, by selected 3-thio-1,2,4-triazoles
12. Warhurst, G.; Higgs, N. B.; Fakhoury, H.; Warhurst, A.
C.; Garde, J.; Coy, D. H. Gastroenterology 1996, 111, 325.
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2001, 58, 91.
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Compound
EC50 (nM)a
sst2
22 14
sst5
34 9.0
5o
5p
14 3.7
6.3 2.1
4.0 1.5
44 9.4
52 13
5r
5s
SRIF-14
2.3 0.15
0.19 0.065
0.10 0.028
a Results are expressed as means SEM of three experiments per-
formed in triplicate (compound concentration ranging from 0.1 nM
to 10 lM).
18. Poitout, L.; Roubert, P.; Contour-Galcera, M.-O.; Moi-
net, C.; Lannoy, J.; Pommier, J.; Plas, P.; Bigg, D.;
Thurieau, C. J. Med. Chem. 2001, 44, 2990.
19. Hiroshi, M.; Suzuki, N.; Miki, T. WO Pat. Appl. 98-
JP1797, 1998.
Lys9 residue of the b-turn. These novel non-peptidic sst2
and sst5 preferential ligands were shown to be agonists.
20. Kane, J. M.; Miller, F. P. EP Patent 276793, 1988.
21. Starck, D.; Treiber, H.; Unger, L.; Neumann-Schultz, B.;
Blumbach, K.; Schobel, D. Patent WO 0042037, 2000.
22. Temple, C.; Montgomery, J. A.. In Weissberger, A.,
Taylor, E. C., Eds.; The Chemistry of Heterocyclic
Compounds; Wiley-Interscience: New York, 1981; Vol.
37, p 251.
Studies are in progress with BN82945 (5o) and BN83010
(5s), to evaluate the therapeutic potential of this new
class of non-peptidic somatostatin receptor ligands.
Acknowledgment
23. Theoclitou, M.-E.; Delaet, N. G. J.; Robinson, L. A.
J. Comb. Chem. 2002, 4, 315.
24. Wilson, M. W.; Hernandez, A. S.; Calvet, A. P.; Hodges,
J. C. Mol. Divers. 1998, 3, 95.
´
We thank Jose Camara and his team for analytical
support.
25. Bailey, N.; Cooper, A. W. J.; Deal, M. J.; Dean, A. W.;
Gore, A. L.; Hawes, M. C.; Judd, D. B.; Merritt, A. T.;
Storer, R.; Travers, S.; Watson, S. P. Chimia 1997, 51, 832.
26. Galcera Contour, M. -O.; Thurieau, C.; Sidhu, A.;
Roubert, P. WO 03045926, 2003.
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incubated for 5 min at 37 °C with 1 lM forskolin and
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