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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2010-11-22
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pubmed:abstractText |
The 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 model.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BeauchampDerek ADA,
pubmed-author:BouletJamieJ,
pubmed-author:BranumShawnS,
pubmed-author:BullingtonJames LJL,
pubmed-author:ChakravartyDevrajD,
pubmed-author:DamonSandraS,
pubmed-author:DavisScottS,
pubmed-author:DemarestKeithK,
pubmed-author:HallDanielD,
pubmed-author:HansenKristinK,
pubmed-author:HeintzelmanGeoffrey RGR,
pubmed-author:JacksonPaul FPF,
pubmed-author:LiXunX,
pubmed-author:OsborneMelville CMC,
pubmed-author:PalmerDavidD,
pubmed-author:RassnickStefanieS,
pubmed-author:ReyesMayraM,
pubmed-author:RhodesKennethK,
pubmed-author:RupertKenneth CKC,
pubmed-author:RussellRonaldR,
pubmed-author:ShookBrian CBC,
pubmed-author:TangYutingY,
pubmed-author:WellsKenneth MKM,
pubmed-author:WestoverLoriL,
pubmed-author:YouellsScottS
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8104-15
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pubmed:meshHeading |
pubmed-meshheading:20973483-Adenosine A1 Receptor Antagonists,
pubmed-meshheading:20973483-Adenosine A2 Receptor Antagonists,
pubmed-meshheading:20973483-Administration, Oral,
pubmed-meshheading:20973483-Animals,
pubmed-meshheading:20973483-Antiparkinson Agents,
pubmed-meshheading:20973483-Callithrix,
pubmed-meshheading:20973483-Disease Models, Animal,
pubmed-meshheading:20973483-Female,
pubmed-meshheading:20973483-Indenes,
pubmed-meshheading:20973483-Macaca fascicularis,
pubmed-meshheading:20973483-Male,
pubmed-meshheading:20973483-Mice,
pubmed-meshheading:20973483-Mice, Inbred BALB C,
pubmed-meshheading:20973483-Parkinson Disease,
pubmed-meshheading:20973483-Pyrimidines,
pubmed-meshheading:20973483-Rats,
pubmed-meshheading:20973483-Rats, Sprague-Dawley,
pubmed-meshheading:20973483-Receptor, Adenosine A2A
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pubmed:year |
2010
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pubmed:articleTitle |
In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.
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pubmed:affiliation |
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, P.O. Box 776, Spring House, Pennsylvania 19477, USA. bshook@its.jnj.com
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pubmed:publicationType |
Journal Article
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