Structural modification of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinoline platelet activating factor receptor antagonists

• Published in: Journal of medicinal chemistry 1993-10, Vol.36 (21), p.3098-3102
• Main Authors: Houlihan, William J, Cheon, Seung H, Parrino, Vincent A, Handley, Dean A, Larson, Douglas A
• Format: Article
• Language: English
• Subjects: Animals; Binding, Competitive; Bronchoconstriction - drug effects; Chemistry; Exact sciences and technology; Guinea Pigs; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Humans; Isoquinolines - chemical synthesis; Isoquinolines - pharmacology; Organic chemistry; Platelet Activating Factor - antagonists & inhibitors; Platelet Membrane Glycoproteins - antagonists & inhibitors; Platelet Membrane Glycoproteins - metabolism; Preparations and properties; Pyridines - chemical synthesis; Pyridines - pharmacology; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Structure-Activity Relationship; Thienopyridines; Thiophenes - chemical synthesis; Thiophenes - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00073a008

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.