Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry.
High-throughput screening of an array of biphenylmethylamines synthesised by high-throughput solid-phase chemistry resulted in the identification of compounds with high-affinity for the 5-ht5A receptor. The structure-activity relationship within this series and further array synthesis led to the identification of the biphenylmethylamine derivative 11, a potent and selective 5-ht5A receptor antagonist.
Corbett
David F
DF
High-Throughput Chemistry, Discovery Research, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow Essex CM19 5AW, UK. david.f.corbett@gsk.com
Heightman
Tom D
TD
Moss
Stephen F
SF
Bromidge
Steven M
SM
Coggon
Sara A
SA
Longley
Mark J
MJ
Roa
Ana Maria
AM
Williams
Jennifer A
JA
Thomas
David R
DR
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D015394:Molecular Structure; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C078730:serotonin 5 receptor; D016244:Guanosine 5'-O-(3-Thiotriphosphate)