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5. Sch 420814 has recently received the designation of preladanant.
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7. This work was presented in part at the symposium ‘Targeting Adenosine A2A
Receptors in Parkinson’s Disease and Other CNS Disorders’, Boston (May 2006).
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Compounds 16 and 18 of that report correspond to 16e and 16g of this report.
Utilization of our intermediate 19 is described.
11. This synthetic methodology differs significantly from that reported in Refs. 8
and 9.
12. A detailed description of the adenosine receptor binding assays is provided in
Bioorg. Med Chem. Lett. 2005, 15, 1333, Refs. 11. For Ki values cited here, SEM
was <15% of the derived Ki.
13. The antagonist nature of the receptor binding is concluded from functional
assay of 16g, Kb = 0.5 nM, the similarity to the series of antagonist 1a, and the
anti-cataleptic activity shown by these compounds.
14. Plasma levels were determined in the rat over a 6h period employing cassette
dosing as described in Korfmacher, W. A.; Cox, K. A.; Ng, K. J.; Veals, J.; Hsieh,
Y.; Wainhaus, S.; Broske, L.; Prelusky, D.; Nomeir, A.; White, R. E. Rapid
Commun. Mass Spectrom. 2001, 15, 335.
15. Assay methodology described in Ongini, E.; Dionosotti, S.; Gessi, S.; Irenius, E.;
Fredholm, B. B. Naunyn Schmiederbergs Arch. Pharmacol. 1999, 359, 7.