Chemoenzymatic synthesis and binding affinity of novel (R)- and (S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics

Yolanda Caro; María Torrado; Christian F Masaguer; Enrique Raviña; Fernando Padín; José Brea; María I Loza

doi:10.1016/j.bmcl.2003.11.064

Chemoenzymatic synthesis and binding affinity of novel (R)- and (S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics

Bioorg Med Chem Lett. 2004 Feb 9;14(3):585-9. doi: 10.1016/j.bmcl.2003.11.064.

Authors

Yolanda Caro¹, María Torrado, Christian F Masaguer, Enrique Raviña, Fernando Padín, José Brea, María I Loza

Affiliation

¹ Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.

PMID: 14741248
DOI: 10.1016/j.bmcl.2003.11.064

Abstract

A series of (R)- and (S)-3-aminomethyl-1-tetralones, conformationally constrained analogues of haloperidol, have been obtained by enzymatic resolution of the corresponding racemic 3-hydroxymethyl-1-tetralones using Pseudomonas fluorescens lipase. Their binding affinities at dopamine D(2) and serotonin 5-HT(2A) and 5-HT(2C) receptors were determined showing in some cases an atypical antipsychotic profile with Meltzer's ratio higher than 1.30.

Publication types

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

MeSH terms

Antipsychotic Agents / chemical synthesis*
Antipsychotic Agents / metabolism*
Binding Sites
Haloperidol / analogs & derivatives
Haloperidol / chemical synthesis*
Haloperidol / metabolism
Lipase / metabolism
Pseudomonas fluorescens / enzymology
Receptors, Dopamine D2 / metabolism*
Receptors, Serotonin / metabolism*
Stereoisomerism
Tetralones / chemical synthesis*
Tetralones / metabolism*

Substances

Antipsychotic Agents
Receptors, Dopamine D2
Receptors, Serotonin
Tetralones
Lipase
Haloperidol