Synthesis and binding affinity of new pyrazole and isoxazole derivatives as potential atypical antipsychotics

María Barceló; Enrique Raviña; Christian F Masaguer; Eduardo Domínguez; Filipe Miguel Areias; José Brea; María I Loza

doi:10.1016/j.bmcl.2007.06.045

Synthesis and binding affinity of new pyrazole and isoxazole derivatives as potential atypical antipsychotics

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4873-7. doi: 10.1016/j.bmcl.2007.06.045. Epub 2007 Jun 14.

Authors

María Barceló¹, Enrique Raviña, Christian F Masaguer, Eduardo Domínguez, Filipe Miguel Areias, José Brea, María I Loza

Affiliation

¹ Departamento de Química Orgánica, Laboratorio de Química Farmacéutica, Universidad de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.

PMID: 17588750
DOI: 10.1016/j.bmcl.2007.06.045

Abstract

We describe the synthesis and binding affinities on D(2), 5-HT(2A) and 5-HT(2C) receptors of 6-aminomethyl-6,7-dihydro-1H-indazol-4(5H)-ones and 6-aminomethyl-6,7-dihydro-3-methyl-benzo[d]isoxazol-4(5H)-ones, as conformationally constrained butyrophenone analogues. One of the new compounds showed good in vitro binding features, and a Meltzer's ratio characteristic of an atypical antipsychotic profile.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents / chemical synthesis
Antipsychotic Agents / chemistry
Antipsychotic Agents / pharmacology*
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Hydrogen Bonding
Isoxazoles / chemical synthesis
Isoxazoles / chemistry*
Kinetics
Models, Chemical
Molecular Conformation
Protein Binding
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Receptor, Serotonin, 5-HT2A / chemistry
Receptor, Serotonin, 5-HT2C / chemistry
Receptors, Dopamine D2 / chemistry
Software

Substances

Antipsychotic Agents
Isoxazoles
Pyrazoles
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT2C
Receptors, Dopamine D2