310
R. J. Chambers et al. / Bioorg. Med. Chem. Lett. 16 (2006) 307–310
yttrium silicate beads (Amersham Biosciencesꢂ) bind
Davies, S. P.; Reddy, H.; Caivano, M.; Cohen, P.
Biochem. J. 2000, 351, 95.
preferentially to the linear nucleotide compared to the
cyclic nucleotide. In the case of PDE2, 3H-cGMP and
unlabeled cGMP are added to the reaction and when the
product, H-GMP, is in close proximity to the beads, the
scintillant within the bead is excited, which is detected
12. For rat liver microsome assay see: (a) Obach, R. S.; Baxter,
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14. Sprague–Dawley rats were dosed with oxindole (2) intra-
venously, 1 mg/kg in EtOH:PEG 400:H2O (1:4:5) and
orally, 30 mg/kg in 0.5% methylcellulose and plasma
samples were drawn at 0.083, 0.25, 0.5, 1, 2, 4, 6, and 8 h
post dose for analysis. Two animals were used for each
dosing route and mean plasma concentrations were used in
subsequent calculations.
3
using
a Packard scintillation counter. The enzyme
concentration used is in the linear range and the KM of
the enzyme was determined (15 lM). The final substrate
concentration is <1/3 of KM (1 lM) so that IC50 values
would approximate the Ki values (a) Bardelle, C.; Smales,
C.; Ito, M.; Nomoto, K.; Wong, E. Y. M.; Kato, H.;
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Kim, S.-H.; Schlessinger, J.; Zhang, K. Y. J. Structure
2004, 12, 2233.
8. Oxindole (2) was evaluated in a broad ligand panel by
Cerep (France) and also for 5-lipoxygenase (5-LO) and
cyclooxygenase (COX-1) inhibition activities.
9. (a) Mylari, B. L.; Carty, T. J.; Moore, P. F.; Zembrow-
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11. Oxindole (2) was evaluated in a panel of kinases by P.
Cohen, University of Dundee, Dundee, Scotland, UK