Chemoenzymatic synthesis and binding affinity of novel (R)- and (S)-3-aminomethyl-1-tetralones, potential atypical antipsychotics.
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.
Caro
Yolanda
Y
Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
Torrado
María
M
Masaguer
Christian F
CF
Raviña
Enrique
E
Padín
Fernando
F
Brea
José
J
Loza
María I
MI
D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism*; D001665:Binding Sites; D006220:Haloperidol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D011551:Pseudomonas fluorescens / Q000201:enzymology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013237:Stereoisomerism; D044024:Tetralones / Q000138:chemical synthesis* / Q000378:metabolism*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044024:Tetralones; D008049:Lipase; D006220:Haloperidol