Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
Compound 1 (UL-FS 49) has recently been described as the representative of a novel class of antiischemic compounds termed "specific bradycardic agents". In search of specific bradycardic agents with different pharmacokinetic profiles, heteroaromatic analogues of 1 have been synthesized and evaluated for their bradycardic activity, selectivity, and duration of action. The chain length n and the nature of the heteroaromatic system of compounds 2 strongly determine the biological activities. Unsubstituted benzothiophenes and benzofurans in combination with a chain length of n = 2 give the most active bradycardic compounds. Some of the new compounds combine high bradycardic potency and selectivity with a short duration of action and may thus be useful for the development of short-acting specific bradycardic drugs.
Bomhard
A
A
Department of Chemical Research, Dr. Karl Thomae GmbH, Biberach, Germany.
Reiffen
M
M
Heider
J
J
Psiorz
M
M
Lillie
C
C
D000818:Animals; D001552:Benzazepines / Q000737:chemistry* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
D001552:Benzazepines; D002317:Cardiovascular Agents; C043636:zatebradine