Synthesis and pharmacological evaluation of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.
A series of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized, and their bradycardic activities were investigated in the isolated right atria of guinea pigs and in conscious rats. These efforts identified the achiral compound 2f, which exhibited potent and long-lasting bradycardic activity with minimal effects on mean blood pressure in conscious rats.
Kubota
Hideki
H
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. kubota.hideki @yamanouchi.co.jp
Watanabe
Toshihiro
T
Kakefuda
Akio
A
Masuda
Noriyuki
N
Wada
Kouichi
K
Ishii
Noe
N
Sakamoto
Shuichi
S
Tsukamoto
Shin-ichi
S
D000818:Animals; D001919:Bradycardia / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology
D002316:Cardiotonic Agents; D010881:Piperidones; D044005:Tetrahydroisoquinolines