Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists |
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Authors: | Shimada Itsuro Maeno Kyoichi Kondoh Yutaka Kaku Hidetaka Sugasawa Keizo Kimura Yasuharu Hatanaka Ken-ichi Naitou Yuki Wanibuchi Fumikazu Sakamoto Shuichi Tsukamoto Shin-ichi |
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Affiliation: | Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. itsuro.shimada@jp.astellas.com |
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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. |
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