Structural modification of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinoline platelet activating factor receptor antagonists.
In an effort to determine the effect of modification of the imidazo[2,1-a]isoquinoline portion of the PAF-receptor antagonist SDZ 64-412 (1), several new analogs were prepared and evaluated in vitro and in vivo. One of these, 5-[4-[2-(3,4,5-trimethoxyphenyl)ethyl]phenyl]-2,3-dihydroimidazo [1,2-a]thieno[2,3-c]pyridine (6) was 4-5 times more potent than 1 in inhibiting PAF-induced bronchoconstriction and hemoconcentration when administered po to the guinea pig.
Houlihan
W J
WJ
Sandoz Research Institute, East Hanover, New Jersey 07936.
Cheon
S H
SH
Parrino
V A
VA
Handley
D A
DA
Larson
D A
DA
D000818:Animals; D001667:Binding, Competitive; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship; D058924:Thienopyridines; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
C083826:5-(4-(2-(3,4,5-trimethoxyphenyl)ethyl)phenyl)-2,3-dihydroimidazo(1,2a)thieno(2,3-c)pyridine; D007546:Isoquinolines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011725:Pyridines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D013876:Thiophenes; C039351:platelet activating factor receptor; C057722:SDZ 64-412