3351-57-3Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of N-acyl-1,2,3,4- tetrahydroisoquinoline derivatives as novel specific bradycardic agents
Kubota, Hideki,Watanabe, Toshihiro,Kakefuda, Akio,Masuda, Noriyuki,Wada, Kouichi,Ishii, Noe,Sakamoto, Shuichi,Tsukamoto, Shinichi
, p. 871 - 882 (2007/10/03)
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
(±)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific bradycardic agents
Kubota, Hideki,Kakefuda, Akio,Watanabe, Toshihiro,Taguchi, Yasuko,Ishii, Noe,Masuda, Noriyuki,Sakamoto, Shuichi,Tsukamoto, Shin-Ichi
, p. 2155 - 2158 (2007/10/03)
A series of (±)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines were prepared and their bradycardic activities were examined in isolated guinea-pigs' right atria and in anesthetized rats. Modifications on the benzyl moiety of the parent compound, 1, led to the identification of compound 11e as a potent and specific bradycardic agent.
Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing If Channel Inhibitory Activity
Kubota, Hideki,Kakefuda, Akio,Watanabe, Toshihiro,Ishii, Noe,Wada, Koichi,Masuda, Noriyuki,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
, p. 4728 - 4740 (2007/10/03)
A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (± )-6,7-Dimethoxy-2-{1- [3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3, 4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against If currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of If currents (IC50 = 0.32 μM) in guinea pig pacemaker cells.
