ChEMBL logo

ChEMBL

spacer
ChEMBL Statistics
  Loading Statistics...
spacer

Document Report Card

Doc ID CHEMBL2029296
Journal J Med Chem (2012) 55:1490-1499
Title 3-aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one: a novel template for the design of highly selective A2B adenosine receptor antagonists.
Authors Taliani S, Pugliesi I, Barresi E, Simorini F, Salerno S, La Motta C, Marini AM, Cosimelli B, Cosconati S, Di Maro S, Marinelli L, Daniele S, Trincavelli ML, Greco G, Novellino E, Martini C, Da Settimo F.
Abstract In an effort to identify novel ligands possessing high affinity and selectivity for the A(2B) AR subtype, we further investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones V, previously disclosed by us as selective A(1) AR antagonists. Preliminary assays on a number of triazinobenzimidazoles derived from our "in-house" collection revealed that all the derivatives selected showed significant affinity at A(2B) AR, no affinity at A(3) AR, and various degrees of selectivity toward A(1) and A(2A) ARs. Investigation of a new series featuring modified substituents at the 10-position (4'-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position (X) of the triazinobenzimidazole nucleus, yielded highly potent and selective A(2B) AR antagonists. The presence of a pendant 3-phenyl ring appears to hamper the interaction with A(2A) AR, conferring high A(2B)/A(2A) AR selectivity. Derivative 13 (X = Cl, R = C(6)H(5)) is the most potent and selective compound, with an IC(50) of 3.10 nM at A(2B) AR and no affinity at A(1), A(2A), and A(3) ARs.
CiteXplore 22257095
DOI 10.1021/jm201177b

Bioactivity Summary

Assay Summary

Protein Target Summary

Compound Summaries

spacer
spacer