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Synthesis and gastric antisecretory properties of alpha chain diene derivatives of misoprostol.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1986 Jul; Vol. 29 (7), pp. 1195-201. - Publication Year :
- 1986
-
Abstract
- The synthesis and gastric antisecretory activity in dogs of seven alpha chain diene derivatives of misoprostol are described. The key intermediates in the preparation of these compounds were C-9 tert-butyldimethylsilyl enol ethers that were obtained by in situ silylation of cuprate enolates derived from alpha chain unsaturated cyclopentenones. Selenylation chemistry on these intermediates provided the C2-C3 trans dienes that, where possible, were also deconjugated to produce the corresponding C3-C4 dienes. The most interesting structure in this series is the C5-C6 cis, C3-C4 cis/trans (1:1) diene that could not be readily separated chromatographically into its individual geometric isomers. The gastric antisecretory activity of the mixture of isomers was approximately 3 times greater than that of misoprostol by intragastric administration. The separation of undesired diarrheogenic effects from antisecretory activity was significantly improved relative to misoprostol.
- Subjects :
- Alprostadil chemical synthesis
Alprostadil pharmacology
Animals
Dogs
Female
Gastric Juice drug effects
Indicators and Reagents
Magnetic Resonance Spectroscopy
Misoprostol
Prostaglandins pharmacology
Structure-Activity Relationship
Alprostadil analogs & derivatives
Anti-Ulcer Agents chemical synthesis
Gastric Juice metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 29
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 3100795
- Full Text :
- https://doi.org/10.1021/jm00157a013