A new class of serotonin 5-HT1A receptor ligands related to NAN-190, buspirone and aripiprazole has been designed using our potent 5-HT3 receptor ligands as templates. The designed pyrrolidone derivatives 10a-n were prepared by means of the straightforward chemistry consisting in the reaction of the appropriate gamma-haloester derivatives with the suitable mylpiperazinylalkylamines. The nanomolar 5-HT1A receptor affinity and the agonist-like profile shown by fused pyrrolidone derivatives 10k,m stimulated the rationalization of the interaction with an homology model of the 5-HT1A receptor and the evaluation of their selectivity profiles and the pharmacokinetic properties. Interestingly, the results of the profiling assays suggested for close congeners 10k,m a significantly divergent binding pattern with compound 10m showing an appreciable selectivity for 5-HT1AR. (c) 2013 Elsevier Masson SAS. All rights reserved.
Cappelli, A., Manini, M., Valenti, S., Castriconi, F., Giuliani, G., Anzini, M., et al. (2013). Synthesis and structure–activity relationship studies in serotonin 5-HT1A receptor agonists based on fused pyrrolidone scaffolds. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 63, 85-94 [10.1016/j.ejmech.2013.01.044].
Synthesis and structure–activity relationship studies in serotonin 5-HT1A receptor agonists based on fused pyrrolidone scaffolds
Cappelli, Andrea;Manini, Monica;Valenti, Salvatore;Castriconi, Federica;Giuliani, Germano;Anzini, Maurizio;Butini, Stefania;Gemma, Sandra;Campiani, Giuseppe;Giorgi, Gianluca;
2013-01-01
Abstract
A new class of serotonin 5-HT1A receptor ligands related to NAN-190, buspirone and aripiprazole has been designed using our potent 5-HT3 receptor ligands as templates. The designed pyrrolidone derivatives 10a-n were prepared by means of the straightforward chemistry consisting in the reaction of the appropriate gamma-haloester derivatives with the suitable mylpiperazinylalkylamines. The nanomolar 5-HT1A receptor affinity and the agonist-like profile shown by fused pyrrolidone derivatives 10k,m stimulated the rationalization of the interaction with an homology model of the 5-HT1A receptor and the evaluation of their selectivity profiles and the pharmacokinetic properties. Interestingly, the results of the profiling assays suggested for close congeners 10k,m a significantly divergent binding pattern with compound 10m showing an appreciable selectivity for 5-HT1AR. (c) 2013 Elsevier Masson SAS. All rights reserved.
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https://hdl.handle.net/11365/43025
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