Bioorganic & Medicinal Chemistry 2004-03-01

Synthesis and pharmacological evaluation of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.

Hideki Kubota, Toshihiro Watanabe, Akio Kakefuda, Noriyuki Masuda, Kouichi Wada, Noe Ishii, Shuichi Sakamoto, Shinichi Tsukamoto

Index: Bioorg. Med. Chem. 12(5) , 871-82, (2004)

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Abstract

A series of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for their bradycardic activities in isolated guinea pig right atria and in urethane-anesthetized rats. These efforts resulted in identification of the compound 8a, which exhibits potent bradycardic activity with minimal influence on mean blood pressure in urethane-anesthetized rats. Oral administration of compound 8a to conscious rats revealed increased potency and prolonged duration of action when compared to Zatebradine.