Discovery and optimisation of a potent and selective tertiary sulfonamide oxytocin antagonist.
The optimisation of a tertiary sulfonamide high-throughput screening hit is described. A combination of high-throughput chemistry, pharmacophore analysis and in silico PK profiling resulted in the discovery of potent sulfonamide oxytocin receptor antagonists with oral exposure and good selectivity over vasopressin receptors.
Barton
Nicholas P
NP
GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Coldharbour Road, Harlow, Essex CM19 5AD, England, UK.
Bellenie
Benjamin R
BR
Doran
Andrew T
AT
Emmons
Amanda J
AJ
Heer
Jag P
JP
Salvagno
Cristian M
CM
D000284:Administration, Oral; D055808:Drug Discovery; D008958:Models, Molecular; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D013449:Sulfonamides; D010121:Oxytocin