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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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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container_end_page 613
container_issue 2
container_start_page 609
container_title Journal of medicinal chemistry
container_volume 39
creator Hallinan, E. Ann
Hagen, Timothy J
Tsymbalov, Sofya
Husa, Robert K
Lee, Albert C
Stapelfeld, Awilda
Savage, Michael A
description 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 Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype.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.
doi_str_mv 10.1021/jm950454k
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
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
title Aminoacetyl Moiety as a Potential Surrogate for Diacylhydrazine Group of SC-51089, a Potent PGE2 Antagonist, and Its Analogs
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