PubMed:20973483 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/20973483","sourcedb":"PubMed","sourceid":"20973483","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/20973483","text":"In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.\nThe in vivo characterization of a dual adenosine A(2A)/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% to 30.5%. Compound 1 is a potent A(2A)/A(1) receptor antagonist in vitro (A(2A) K(i) = 4.1 nM; A(1) K(i) = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate 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