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Document Report Card

Doc ID CHEMBL1155896
Journal J Med Chem (2008) 51:4449-4455
Title 2-Amino-6-furan-2-yl-4-substituted nicotinonitriles as A2A adenosine receptor antagonists.
Authors Mantri M, de Graaf O, van Veldhoven J, Goblyos A, von Frijtag Drabbe Kunzel JK, Mulder-Krieger T, Link R, de Vries H, Beukers MW, Brussee J, Ijzerman AP.
Abstract A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds having a 2-amino nicotinonitrile core moiety. From our data, we conclude that the presence of at least one furan group rather than phenyl is beneficial for high affinity on the A 2A adenosine receptor. Compounds 39 (LUF6050) and 44 (LUF6080) of the series had K i values of 1.4 and 1.0 nM, respectively, with reasonable selectivity toward the other adenosine receptor subtypes, A 1, A 2B, and A 3. The high affinity of 44 was corroborated in a cAMP second messenger assay, yielding subnanomolar potency for this compound.
CiteXplore 18637670
DOI 10.1021/jm701594y

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