N-Substituted dibenzoxazepines as analgesic PGE2 antagonists

• Published in: Journal of medicinal chemistry Vol. 36; no. 22; pp. 3293 - 3299
• Main Authors: Hallinan, E. Ann, Hagen, Timothy J, Husa, Robert K, Tsymbalov, Sofya, Rao, Shashidhar N, vanHoeck, Jean Pierre, Rafferty, Michael F, Stapelfeld, Awilda, Savage, Michael A, Reichman, Melvin
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.10.1993
• Subjects: Analgesics - chemical synthesis; Analgesics - pharmacology; Animals; Chemical Phenomena; Chemistry; Chemistry, Physical; Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide - analogs & derivatives; Dibenzoxazepines - chemical synthesis; Dibenzoxazepines - pharmacology; Dinoprostone - antagonists & inhibitors; Exact sciences and technology; Guinea Pigs; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; In Vitro Techniques; Male; Mice; Mice, Inbred Strains; Nociceptors - drug effects; Organic chemistry; Preparations and properties; Solubility; Structure-Activity Relationship; Water; Rodentia; Prostaglandin E2; Semicarbazides; Tricyclic compound; In vivo; Vertebrata; Mammalia; Analgesic; Structure activity relation; Mouse; Animal; Aromatic compound; Antagonist; Oxygen nitrogen heterocycle
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00074a010

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.