Aminoacetyl Moiety as a Potential Surrogate for Diacylhydrazine Group of SC-51089, a Potent PGE2 Antagonist, and Its Analogs

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which co...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1996-01, Vol.39 (2), p.609-613
Main Authors: Hallinan, E. Ann, Hagen, Timothy J, Tsymbalov, Sofya, Husa, Robert K, Lee, Albert C, Stapelfeld, Awilda, Savage, Michael A
Format: Article
Language:English
Subjects:
Analgesics
Analgesics - chemistry
Analgesics - pharmacology
Animals
Biological and medical sciences
Cells, Cultured
Dinoprostone - antagonists & inhibitors
Guinea Pigs
Hydrazines - chemistry
Hydrazines - pharmacology
Ileum - drug effects
Ileum - metabolism
In Vitro Techniques
Liver - cytology
Liver - drug effects
Magnetic Resonance Spectroscopy
Medical sciences
Neuropharmacology
Oxazepines - chemistry
Oxazepines - pharmacology
Pharmacology. Drug treatments
Prostaglandin Antagonists - chemistry
Prostaglandin Antagonists - pharmacology
Rats
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Summary:8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure−activity relationships within these series.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm950454k