Orally active, nonpeptide oxytocin antagonists.
The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.
Evans
B E
BE
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
Leighton
J L
JL
Rittle
K E
KE
Gilbert
K F
KF
Lundell
G F
GF
Gould
N P
NP
Hobbs
D W
DW
DiPardo
R M
RM
Veber
D F
DF
Pettibone
D J
DJ
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D007752:Obstetric Labor, Premature / Q000188:drug therapy; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin / Q000378:metabolism; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D010880:Piperidines; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; C077566:L 366509; D010121:Oxytocin