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Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Nov 15; Vol. 25 (22), pp. 5299-305. Date of Electronic Publication: 2015 Sep 21. - Publication Year :
- 2015
-
Abstract
- The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antipsychotic Agents pharmacology
Antipsychotic Agents toxicity
Ether-A-Go-Go Potassium Channels antagonists & inhibitors
Humans
Mice
Oxazoles pharmacology
Oxazoles toxicity
Patch-Clamp Techniques
Piperazines pharmacology
Piperazines toxicity
Piperidines pharmacology
Piperidines toxicity
Potassium Channel Blockers chemical synthesis
Potassium Channel Blockers pharmacology
Potassium Channel Blockers toxicity
Rats
Receptors, Dopamine D2 agonists
Serotonin 5-HT1 Receptor Agonists chemical synthesis
Serotonin 5-HT1 Receptor Agonists pharmacology
Serotonin 5-HT1 Receptor Agonists toxicity
Serotonin 5-HT2 Receptor Agonists chemical synthesis
Serotonin 5-HT2 Receptor Agonists pharmacology
Serotonin 5-HT2 Receptor Agonists toxicity
Structure-Activity Relationship
Swine
Antipsychotic Agents chemical synthesis
Oxazoles chemical synthesis
Piperazines chemical synthesis
Piperidines chemical synthesis
Schizophrenia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 25
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 26483200
- Full Text :
- https://doi.org/10.1016/j.bmcl.2015.09.045