Synthesis and contractile activity of new acetylenic and allenic analogues of leukotrienes C4 and D4: importance of the Z-11,12 double bond.
The (5S,6R) isomers of new acetylenic and allenic analogues of leukotrienes C4 and D4 were synthesized for comparative pharmacological studies on intestinal smooth muscle preparations. These new analogues are poor spasmogenic agonists, the replacement of the 11,12-ene with a relatively more stable triple bond causing an important reduction in intrinsic activity. They did not show any significant antagonist activity. Unexpectedly, these results prove that the 11,12 portion in the triene structure of the lipophilic chain is critical for an agonist activity.
Lellouche
J P
JP
Service des Molecules Marquées, Centre d'Etudes Nucleaires de Saclay, C.E.A., Gif sur Yvette, France.
Aubert
F
F
Beaucourt
J P
JP
Rechencq
E
E
Niel
G
G
Girard
J P
JP
Rossi
J C
JC
Boucard
M
M
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D008168:Lung / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D013189:SRS-A