title: Synthesis and gastric antisecretory properties of alpha chain diene derivatives of misoprostol.
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.
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D004285:Dogs; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D016595:Misoprostol; D011453:Prostaglandins / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000897:Anti-Ulcer Agents; D007202:Indicators and Reagents; D011453:Prostaglandins; D016595:Misoprostol; D000527:Alprostadil