Abstract
Antagonism of the adenosine A(2a) receptor offers great promise in the treatment of Parkinson's disease. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonists, which led to clinical candidate SCH 420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective (vs A(1)) A(2a) antagonist activity, including oral activity in the rat haloperidol-induced catalepsy model. Structure-activity relationships and plasma levels are described for this series.
MeSH terms
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Adenosine A2 Receptor Antagonists*
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Administration, Oral
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Animals
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Area Under Curve
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Catalepsy
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Chemistry, Pharmaceutical / methods
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Drug Design
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Haloperidol / pharmacology
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Models, Chemical
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Parkinson Disease / drug therapy*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Rats
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / pharmacology
Substances
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Adenosine A2 Receptor Antagonists
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Pyrimidines
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Triazoles
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2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine
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Haloperidol