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667
13. Snutch, T. P. PCT Int. Appl. WO 01/45709, 2001; Chem.
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ꢀ30, and represent the most selective examples in this
series of thiazolidinone N-type Ca2+ channel blockers.
14. Song, Y.; Bowersox, S. S.; Connor, D. T.; Dooley, D. J.;
Lotarski, S. M.; Malone, T.; Miljanich, G.; Millerman, E.;
Rafferty, M. F.; Rock, D.; Roth, B. D.; Schmidt, J.;
Stoehr, S.; Szoke, B. G.; Taylor, C.; Vartanian, M.; Wang,
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In conclusion, we have identified a series of novel 3-aryl-
thiazolidin-4-ones derived from the initial HTS ‘hits’ 9
and 10. By analysis of SAR, we have identified com-
pound 30 (Table 2) as the most potent, and single enan-
tiomer 61 (Table 5) as the most selective compounds in
this series. These compounds show promise as lead
structures in the quest for clinically effective N-type
blockers in the treatment of pain.
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18. Kato, T.; Ozaki, T.; Tamura, K.; Suzuki, Y.; Akima, M.;
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19. Castle, N. A.; Gross, M.; Mendoza, J. S. PCT Int. Appl.
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23. Reference compound data in the IMR32 assay were
obtained as the following pIC50 values: x-Conotoxin
GVIA: 8.42 0.22 at N-type, no measurable block at L-
type. Nimodipine: 4.97 0.26 at N-type and 7.87 0.27 at
L-type. See Ward, S. D. C.; Hick, C. A.; Thomas, D.
Online Abstract Viewer/Itinerary Planner, Society for
Neuro-science Annual Meeting, New Orleans, Louisiana,
November 8–12, 2003; Society for Neuroscience, Wash-
ington, DC; Program No. 165.7.
24. The HPLC separation method utilised was ChiralpakÒ
50801 (20 lm) as chiral stationary phase. Mobile phase
CH3OH; UV detection at 280 nm. Analysis conditions:
ChiralcelÒ OD-H; mobile phase—95% heptane/5% iso-
propanol; UV detection at 225 nm. Flow rate—1 ml/min,
at 25 °C.