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Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs.
- 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.)
- Subjects :
- Animals
Antipsychotic Agents chemical synthesis
Antipsychotic Agents chemistry
Antipsychotic Agents metabolism
Aripiprazole pharmacology
Dopamine D2 Receptor Antagonists chemical synthesis
Dopamine D2 Receptor Antagonists chemistry
Dopamine D2 Receptor Antagonists metabolism
Dopamine D2 Receptor Antagonists pharmacology
Humans
Male
Mice, Inbred ICR
Microsomes, Liver metabolism
Molecular Structure
Picolinic Acids chemical synthesis
Picolinic Acids chemistry
Picolinic Acids metabolism
Risperidone pharmacology
Serotonin 5-HT1 Receptor Antagonists chemical synthesis
Serotonin 5-HT1 Receptor Antagonists chemistry
Serotonin 5-HT1 Receptor Antagonists metabolism
Serotonin 5-HT1 Receptor Antagonists pharmacology
Serotonin 5-HT2 Receptor Antagonists chemical synthesis
Serotonin 5-HT2 Receptor Antagonists chemistry
Serotonin 5-HT2 Receptor Antagonists metabolism
Serotonin 5-HT2 Receptor Antagonists pharmacology
Structure-Activity Relationship
Antipsychotic Agents pharmacology
Picolinic Acids pharmacology
Subjects
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