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Document Report Card

Doc ID CHEMBL1143166
Journal J Med Chem (2008) 51:1764-1770
Title Derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine as novel, potent, and selective A3 adenosine receptor antagonists.
Authors Cosimelli B, Greco G, Ehlardo M, Novellino E, Da Settimo F, Taliani S, La Motta C, Bellandi M, Tuccinardi T, Martinelli A, Ciampi O, Trincavelli ML, Martini C.
Abstract A number of derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine ( 5) were synthesized and biologically evaluated as A 3 adenosine receptor (A 3 AR) antagonists. The new compounds were designed as open chain analogues of a triazolopyrimidinone derivative displaying submicromolar affinity for the A 3 AR, which had been previously identified using a 3D database search. Substituents R, R', and R'' attached to the parent compound 5 were chosen according to factorial design and stepwise lead optimization approaches, taking into account the essentially hydrophobic nature of the A 3 AR binding site. As a result, 5m (R = n-C 3H 7, R' = 4-ClC 6H 4CH 2, R'' = CH 3) was identified among the pyrimidine derivatives as the ligand featuring the best combination of potency and selectivity for the target receptor. This compound binds to the A 3 AR with a K i of 3.5 nM and is devoid of appreciable affinity for the A 1, A 2A, and A 2B ARs.
CiteXplore 18269230
DOI 10.1021/jm701159t

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