Premium
Synthesis and Evaluation of Novel 2,3‐ D ihydrobenzo[ b ][1,4]dioxin‐ and Indolealkylamine Derivatives as Potential Antidepressants
Author(s) -
Wang Songlin,
Chen Yin,
Liu Xinghua,
Xu Xiangqing,
Liu Xin,
Liu BiFeng,
Zhang Guisen
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300238
Subject(s) - serotonin transporter , chemistry , antidepressant , transporter , affinities , pharmacology , fluoxetine , stereochemistry , serotonin , 5 ht receptor , serotonin plasma membrane transport proteins , receptor , pharmacokinetics , 5 ht1a receptor , binding affinities , biochemistry , endocrinology , biology , gene , hippocampus
A series of 2,3‐dihydrobenzo[ b ][1,4]dioxin‐ and indolealkylamine derivatives were synthesized and the target compounds were evaluated for their binding affinities at the 5‐HT 1A receptor and serotonin transporter. Antidepressant‐like activities of the compounds were screened using the tail suspension and forced swim tests in mice. Preliminary results indicated that the target compounds exhibited high binding affinities at the 5‐HT 1A receptor and serotonin transporter, and produced marked antidepressant‐like effects. The best example from this study, compound 5 , exhibited high binding affinities for the 5‐HT 1A receptor ( K i = 96 nM) and serotonin transporter ( K i = 9.8 nM). The intrinsic activity of compound 5 showed agonistic property to the 5‐HT 1A receptor and inhibition of the 5‐HT transporter. Furthermore, compound 5 exhibited greater antidepressant efficacy than fluoxetine and showed acceptable pharmacokinetic properties.