Bioorg Med Chem Lett. 2007 Mar 1;17(5):1376-80. Epub 2006 Dec 3.

Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.

Neustadt BR, Hao J, Lindo N, Greenlee WJ, Stamford AW, Tulshian D, Ongini E, Hunter J, Monopoli A, Bertorelli R, Foster C, Arik L, Lachowicz J, Ng K, Feng KI.

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Department of Chemical Research, , Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. bernard.neustadt@spcorp.com

Abstract

Antagonism of the adenosine A2A receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A2A antagonist SCH 58261 as a starting point, we identified the potent and selective (vs. A1) antagonist 11h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity.

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Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.

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