Structure-activity relationship investigations of a potent and selective benzodiazepine oxytocin antagonist.
We have investigated the structure-activity relationships of the 1- and 3-substituents and replacements of the 5-phenyl group of GW405212X 1, a potent selective oxytocin antagonist. The effect of these modifications on oxytocin binding antagonism and on pharmacokinetic parameters is reported.
Wyatt
P G
PG
Department of Medicinal Chemistry, GlaxoSmithKline, Medicines Research Centre, Stevenage, Herts, UK. pw29967@gsk.com
Allen
M J
MJ
Chilcott
J
J
Hickin
G
G
Miller
N D
ND
Woollard
P M
PM
D000284:Administration, Oral; D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D004285:Dogs; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019151:Peptide Library; D011485:Protein Binding; D018045:Receptors, Oxytocin / Q000378:metabolism; D013329:Structure-Activity Relationship; D015149:Tocolytic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
D019151:Peptide Library; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; D001569:Benzodiazepines; D010121:Oxytocin