Synthesis and biological activity of new leukotriene antagonists (racemates and enantiomerically pure compounds).
Two series of structural analogues of leukotrienes C4, D4 and E4 (LTC4, LTD4, LTE4) were prepared. The compounds were evaluated for their ability to antagonize leukotriene-induced contractions of guinea pig lung strips. In comparison to FPL-55712, compounds 1a and 2h were more potent antagonists against LTC4 (2- and 3fold, respectively) and LTD4 (6- and 60fold respectively). Moreover, in vivo compounds 1a and 2h exhibited antagonism against leukotrienes (C4, D4, E4) and PAF, the most potent mediators in bronchial asthma. 2h also showed antagonistic activity when tested by inhalation.
Anagnostopulos
C
C
Hoechst AG, Frankfurt (Main), FRG.
Bartmann
W
W
Beck
G
G
Below
P
P
Bergmann
A
A
Linz
W
W
Schacht
U
U
Schölkens
B A
BA
Wess
G
G
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D013189:SRS-A / Q000494:pharmacology; D013329:Structure-Activity Relationship
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D013189:SRS-A