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.
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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Catalepsy / chemically induced
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Catalepsy / drug therapy
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Disease Models, Animal
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Parkinson Disease / drug therapy
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Piperazine
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Piperazines / administration & dosage
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Piperazines / chemical synthesis*
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Piperazines / pharmacokinetics
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Pyrimidines / administration & dosage
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacokinetics
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Rats
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Structure-Activity Relationship
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Substrate Specificity
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Treatment Outcome
Substances
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Adenosine A2 Receptor Antagonists
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Piperazines
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Pyrimidines
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Piperazine