N-substituted dibenzoxazepines as analgesic PGE2 antagonists.
8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide (1, SC-19220) has been previously reported by us and others to be a PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activities. Analogs of SC-19220, in which the acetyl moiety has been replaced with pyridylpropionyl groups and their homologs, have been synthesized as illustrated by compounds 13 and 29. These and other members of this series have been shown to be efficacious analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure activity relationships within this series.
Hallinan
E A
EA
Department of Chemical Research, Searle, Skokie, Illinois 60077.
Hagen
T J
TJ
Husa
R K
RK
Tsymbalov
S
S
Rao
S N
SN
vanHoeck
J P
JP
Rafferty
M F
MF
Stapelfeld
A
A
Savage
M A
MA
Reichman
M
M
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000031:analogs & derivatives*; D003989:Dibenzoxazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water
D000700:Analgesics; D003989:Dibenzoxazepines; D014867:Water; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D015232:Dinoprostone