The design and preparation of metabolically protected new arylpiperazine 5-HT1A ligands.

Article Details

Citation

Tandon M, O'Donnell MM, Porte A, Vensel D, Yang D, Palma R, Beresford A, Ashwell MA

The design and preparation of metabolically protected new arylpiperazine 5-HT1A ligands.

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1709-12.

PubMed ID
15026055 [ View in PubMed
]
Abstract

New arylpiperazines related to buspirone, gepirone and NAN-190 were designed and screened in silico for their 5-HT(1A) affinity and potential sites of metabolism by human cytochrome p450 (CYP3A4). Modifications to these structures were assessed in silico for their influence on both 5HT(1A) affinity and metabolism. Selected new molecules were synthesized and purified in a parallel chemistry approach to determine structure activity relationships (SARs). The resulting molecules were assessed in vitro for their 5HT(1A) affinity and half-life in a heterologously expressed human CYP3A4 assay. Molecular features responsible for 5-HT(1A) affinity and CYP3A4 stability are described.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Buspirone5-hydroxytryptamine receptor 1AIC 50 (nM)25N/AN/ADetails