Pharmacophore Mapping of Tricyclic Isoxazoles for Their Affinity Towards Alpha-2 Adrenoreceptors #
BioChem Press, Soma Samanta, Parthasarathi Panda, Tarun Jha · 2006
Motivation. Blockage of alpha–2 adrenoreceptors in brain enhances noradrenergic neurotransmission and increases extracellular dopamine as well as serotonin (5–HT) levels, which is beneficial for depressant patients. To identify pharmacophoric requirements, a quantitative structure activity relationship (QSAR) study was performed using electrotopological state atom (ETSA) indices and refractotopological state atom (RTSA) indices on tricyclic isoxazole derivatives for their affinity towards the alpha–2 adrenoreceptors. Method. Correlation analysis and multiple linear regression analysis were employed to model the experimental activity. Results. The QSAR models were obtained separately for alpha–2A and 2C adrenoreceptor binding affinity. It was found that some atoms played important roles to both the activities and some other atoms played different roles in selectivity of compound towards alpha–2A and 2C adrenoreceptor binding affinity. Conclusions. Electrotopological state atom (ETSA) and refractotopological state atom (RTSA) indices have potentiality to determine or recognize the pharmacophoric atoms and combination of these two helps to map pharmacophore of trycyclic isoxazoles.