Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists.

Abstract

To identify potent and selective 5-HT(2C) receptor agonists, a series of novel benzazepine derivatives were synthesized, and their structure-activity relationships examined. The compounds were evaluated for their 5-HT(2C), 5-HT(2A), and 5-HT(2B) receptor binding affinity and intrinsic activity for the 5-HT(2C) and 5-HT(2A) receptors. Among these compounds, 6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when administered po, which is a symptom of the serotonin syndrome reflecting 5-HT(2C) receptor activation. Moreover, compound 6 was characterized as a partial agonist of 5-HT(2A) receptors; therefore, it had little effect on the cardiovascular system.

• Authors: Itsuro Shimada, Kyoichi Maeno, Yutaka Kondoh, Hidetaka Kaku, Keizo Sugasawa, Yasuharu Kimura, Ken-ichi Hatanaka, Yuki Naitou, Fumikazu Wanibuchi, Shuichi Sakamoto, Shin-ichi Tsukamoto
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 6 Pg. 3309-20 (Mar 15 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18083579 (Publication Type: Journal Article)

Chemical References

• Benzazepines
• Receptor, Serotonin, 5-HT2A
• Receptor, Serotonin, 5-HT2B
• Serotonin 5-HT2 Receptor Agonists

Topics

• Animals
• Benzazepines (chemical synthesis, chemistry, pharmacology)
• Cardiovascular System (drug effects)
• Penile Erection (drug effects)
• Rats
• Receptor, Serotonin, 5-HT2A (drug effects)
• Receptor, Serotonin, 5-HT2B (drug effects)
• Serotonin 5-HT2 Receptor Agonists
• Structure-Activity Relationship