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Synthesis and evaluation of new coumarin derivatives as potential atypical antipsychotics.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2014 Mar 03; Vol. 74, pp. 427-39. Date of Electronic Publication: 2014 Jan 15. - Publication Year :
- 2014
-
Abstract
- In this paper, we report the synthesis of novel, potential antipsychotic coumarin derivatives combining potent dopamine D₂, D₃ and serotonin 5-HT(1A), 5-HT(2A) receptors properties. We describe the structure activity relationship that leads us to the promising derivative: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4(1H)-one 27. The unique pharmacological features of compound 27 are a high affinity for dopamine D₂, D₃ and serotonin 5-HT(1A), 5-HT(2A) receptors, together with a low affinity for H₁ receptor (to reduce the risk of obesity under chronic treatment). In animal models, compound 27 inhibited apomorphine-induced climbing and MK-801-induced hyperactivity without observable catalepsy at the highest dose tested. In particular, compound 27 was more potent than clozapine.<br /> (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 74
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24487191
- Full Text :
- https://doi.org/10.1016/j.ejmech.2014.01.012