Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5-imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.
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.
Yamanaka
M
M
Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
Suda
S
S
Kabasawa
Y
Y
Kawamura
T
T
Ogawa
T
T
Sawada
K
K
Ohhara
H
H
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
D007093:Imidazoles; D011725:Pyridines