Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency.
Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; Ki = 1.4 nM).
Williams
P D
PD
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Bock
M G
MG
Evans
B E
BE
Freidinger
R M
RM
Gallicchio
S N
SN
Guidotti
M T
MT
Jacobson
M A
MA
Kuo
M S
MS
Levy
M R
MR
Lis
E V
EV
Michelson
S R
SR
Pawluczyk
J M
JM
Perlow
D S
DS
Pettibone
D J
DJ
Quigley
A G
AG
Reiss
D R
DR
Salvatore
C
C
Stauffer
K J
KJ
Woyden
C J
CJ
D000818:Animals; D048588:Benzoxazines; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010078:Oxazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D013329:Structure-Activity Relationship
D048588:Benzoxazines; C096766:L 371257; D010078:Oxazines; D010880:Piperidines; D010121:Oxytocin