title: Identification of non-furan containing A2A antagonists using database mining and molecular similarity approaches.
abstract: Database searching led to the identification of potent A(2A) antagonists which do not contain the privileged furan moiety and which show selectivity over A(1) receptors. Simple substructure searching on a proprietary database identified compounds with activities in the low nM range. A targeted approach to the identification of non-furan containing compounds resulted in the identification of two novel series, with potency, selectivity and directional SAR from screening 113 compounds.
authors.affiliation: Vernalis (R&D) Ltd, Granta Park, Cambridge, CB1 6GB, UK. c.richardson@vernalis.com <c.richardson@vernalis.com>
authors.forename: Christine M
authors.initials: CM
authors.lastname: Richardson
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Gillespie
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Williamson
authors.forename: Allan M
authors.initials: AM
authors.lastname: Jordan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fink
authors.forename: Antony R
authors.initials: AR
authors.lastname: Knight
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sellwood
authors.forename: Anil
authors.initials: A
authors.lastname: Misra
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000586:Amination; D005461:Fluorine / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D005663:Furans; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D005461:Fluorine; C030986:pyrimidine; C039281:furan