Identification of non-furan containing A2A antagonists using database mining and molecular similarity approaches.
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.
Richardson
Christine M
CM
Vernalis (R&D) Ltd, Granta Park, Cambridge, CB1 6GB, UK. c.richardson@vernalis.com <c.richardson@vernalis.com>
Gillespie
Roger J
RJ
Williamson
Douglas S
DS
Jordan
Allan M
AM
Fink
Alexandra
A
Knight
Antony R
AR
Sellwood
Daniel M
DM
Misra
Anil
A
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
D058917:Adenosine A2 Receptor Antagonists; D005663:Furans; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D005461:Fluorine; C030986:pyrimidine; C039281:furan