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Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs.

Authors :
Xu M
Wang Y
Yang F
Wu C
Wang Z
Ye B
Jiang X
Zhao Q
Li J
Liu Y
Zhang J
Tian G
He Y
Shen J
Jiang H
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Feb 15; Vol. 28 (4), pp. 606-611. Date of Electronic Publication: 2018 Jan 31.
Publication Year :
2018

Abstract

In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D <subscript>2</subscript> , serotonin 5-HT <subscript>1A</subscript> and 5-HT <subscript>2A</subscript> receptors, but also exhibited low potency for α <subscript>1A</subscript> , H <subscript>1</subscript> and 5-HT <subscript>2C</subscript> receptors, indicating a low propensity of side effects like orthostatic hypotension and weight gain. Furthermore, 7h exhibited more potent antipsychotic-like effect than aripiprazole in behavioral studies. The preliminary results were promising enough for further research around this scaffold.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
28
Issue :
4
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
29395980
Full Text :
https://doi.org/10.1016/j.bmcl.2018.01.038