Physical Sciences and Mathematics Commons^™

Modeling Of Flexible Drug-Like Molecules : Qsar Of Gbr 12909 Analog Dat/Sert Selectivity, Kathleen Mary Gilbert

Dissertations

The dopamine reuptake inhibitor GBR 12909 and related dialkyl piperazine and piperidine analogs have been studied as agonist substitution therapies acting on the dopamine transporter (DAT) to treat cocaine addiction. Undesirable binding to the serotonin transporter (SERT) can vary greatly depending on the specific substituents on the molecule. This study uses Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices (CoMSIA) techniques to determine a stable and predictive model for DAT/SERT selectivity for a set of flexible GBR 12909 analogs.

Families of analogs were constructed from six pairs of naphthyl-substituted piperazine and piperidine templates identified by hierarchical clustering as …