1.
Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors.
Bioorg Med Chem Lett
; 18(4): 1346-9, 2008 Feb 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18207394
RESUMEN
Derivatives of milnacipran were synthesized and studied as monoamine transporter inhibitors. Potent analogs were discovered at NET (9k) and at both NET and SERT (9s and 9u). A pharmacophore model was established based on the conformational analysis of milnacipran in aqueous solution using NMR techniques and was consistent with the SAR results.
Asunto(s)
Ciclopropanos/química , Ciclopropanos/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Acetamidas/química , Acetamidas/farmacología , Alquilación , Amidas/química , Amidas/farmacología , Indoles/química , Indoles/farmacología , Milnaciprán , Modelos Moleculares , Conformación Molecular , Resonancia Magnética Nuclear Biomolecular , Estereoisomerismo , Relación Estructura-Actividad , Proteínas de Transporte Vesicular de Monoaminas/química
2.
Bioorg Med Chem Lett
; 18(11): 3328-32, 2008 Jun 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18445525
RESUMEN
A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC(50) values of 1.7nM at NET and 25nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1-II.