Identification of small molecule agonists of the motilin receptor.
High-throughput screening resulted in the identification of a series of novel motilin receptor agonists with relatively low molecular weights. The series originated from an array of biphenyl derivatives designed to target 7-transmembrane (7-TM) receptors. Further investigation of the structure-activity relationship within the series resulted in the identification of compound (22) as a potent and selective agonist at the motilin receptor.
Heightman
Tom D
TD
Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. tom.heightman@sgc.ox.ac.uk
Conway
Elizabeth
E
Corbett
David F
DF
Macdonald
Gregor J
GJ
Stemp
Geoffrey
G
Westaway
Susan M
SM
Celestini
Paolo
P
Gagliardi
Stefania
S
Riccaboni
Mauro
M
Ronzoni
Silvano
S
Vaidya
Kalindi
K
Butler
Sharon
S
McKay
Fiona
F
Muir
Alison
A
Powney
Ben
B
Winborn
Kim
K
Wise
Alan
A
Jarvie
Emma M
EM
Sanger
Gareth J
GJ
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000737:chemistry*; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; D011994:Recombinant Proteins; C050802:motilin receptor