title: Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5-imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.
abstract: Structural modification of the cardiotonic agent, loprinone (E-1020, 1), suggested by data that it has a less positive chronotropic effect than milrinone (15), led us to find novel bradycardic agents that were structurally different from homoveratryl amine derivatives. Alkyl-oxy, -thio, and -amino derivatives at the 2-position of the pyridine ring of 1 produced bradycardic activity without a significant effect on blood pressure and myocardial contractility. Aryloxy analogues also decreased heart rate, and members with an electron-withdrawing group at the ortho position of the phenyl ring showed higher activity. Replacement of the imidazo[1,2-alpha]pyridine with pyridine resulted in diminished activity. The mechanism of bradycardic activity of these compounds seems to be direct action on the sinus node.
authors.affiliation: Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamanaka
authors.forename: S
authors.initials: S
authors.lastname: Suda
authors.forename: Y
authors.initials: Y
authors.lastname: Kabasawa
authors.forename: T
authors.initials: T
authors.lastname: Kawamura
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Ohhara
mesh_terms: D000818:Animals; D004285:Dogs; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D011725:Pyridines