Synthesis and gastrointestinal pharmacology of the 4-fluoro analogue of enisoprost.
A 4-fluoro analogue of enisoprost was prepared and evaluated for gastric antisecretory and mucosal protective activity in animals. The synthesis centered upon cuprate chemistry but also involved a Wittig reaction to produce a cis fluoro olefinic moiety, a furan rearrangement/isomerization reaction to provide the necessary hydroxycyclopentenone, and a two-carbon-homologation procedure. The fluoro analogue was much less potent as a gastric antisecretory and mucosal protective agent than enisoprost.
Collins
P W
PW
Gastrointestinal Diseases Research Department, G.D. Searle & Co., Skokie, Illinois 60077.
Kramer
S W
SW
Gullikson
G W
GW
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D008297:Male; D011453:Prostaglandins / Q000138:chemical synthesis* / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D011453:Prostaglandins; D011465:Prostaglandins, Synthetic; C054000:4-fluoroenisoprost