Synthesis and structure-activity relationships of acyclic omega chain conjugated diene analogues of enisoprost.
A series of acyclic omega chain conjugated diene analogues of enisoprost were synthesized and evaluated for gastric antisecretory and diarrheagenic activities in comparison to enisoprost and a previously identified cyclic dienyl analogue. Several novel approaches to the cuprate reagents involved in the synthesis of the series are described. From this SAR study, it appears that both the conjugated diene and the overall space filling characteristics of the omega chain are important components to the pharmacological profiles and selectivity of these compounds and that a cyclic structure is not required.
Collins
P W
PW
Gastrointestinal Diseases Research, G.D. Searle & Co., Skokie, Illinois 60077.
Shone
R L
RL
Perkins
W E
WE
Gasiecki
A F
AF
Kalish
V J
VJ
Kramer
S W
SW
Bianchi
R G
RG
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D000527:Alprostadil; C054594:enisoprost