title: Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists.
abstract: Movement disorders such as Parkinson's disease and Huntington's disease are serious life-limiting and debilitating movement disorders. Their onset typically occurs from mid-life to late in life, and effective diagnostic techniques for detecting and following the disease course are lacking. Our goal is to develop receptor imaging agents for positron emission tomography (PET) that selectively target the most relevant subtype of adenosine receptors (AR) that are highly expressed in the striatum, that is, the A(2A) AR. To further this goal, we have synthesized and characterized pharmacologically a family of high affinity A(2A) AR ligands, based on the known antagonist, SCH 442416 (R=-Me), which have structural variability on the terminus (R=-Et, -i-Pr, -allyl, and others). A O-fluoroethyl analogue suitable for use as a PET tracer had a K(i) value of 12.4 nM and was highly selective for the A(2A) AR in comparison to the A(1) and A(3) ARs.
authors.affiliation: Chemical Biology Unit, Laboratory of Cell Biology and Biochemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 8, Rm 121, NIH, NIDDK, LCBB, Bethesda, MD 20892-0810, United States.
authors.forename: Bidhan A
authors.initials: BA
authors.lastname: Shinkre
authors.forename: T Santhosh
authors.initials: TS
authors.lastname: Kumar
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Francesca
authors.initials: F
authors.lastname: Deflorian
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: William C
authors.initials: WC
authors.lastname: Trenkle
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D049268:Positron-Emission Tomography; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry*; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism; D014230:Triazoles / Q000737:chemistry*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D011720:Pyrazoles; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C045575:1,2,4-triazole; C030986:pyrimidine; C416650:SCH 442416
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