New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by systematic chemical modification of the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB1 receptor antagonists/inverse agonists.1 Several ligands showed potent affinity for the hCB1 receptor at nanomolar concentrations. Docking experiments and molecular dynamics simulations explained the potent hCB1 binding affinity of the new derivatives. The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB1 selective compounds act as antagonists/inverse agonists. References 1. J. Med. Chem. 2008, 51, 1560-1576.
New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as high affinity hCB1 ligands / LA REGINA, Giuseppe; Piscitelli, Francesco; Ligresti, A.; Brizzi, A.; Pasquini, S.; Colombo, G.; Lavecchia, A.; Corelli, F.; DI MARZO, V.; Novellino, R.; Silvestri, Romano. - (2009), pp. 171-171. (Intervento presentato al convegno XXIII Congresso Nazionale della Società Chimica Italiana tenutosi a Sorrento, Italy).
New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as high affinity hCB1 ligands
LA REGINA, GIUSEPPE
;PISCITELLI, FRANCESCO;SILVESTRI, Romano
2009
Abstract
New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by systematic chemical modification of the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB1 receptor antagonists/inverse agonists.1 Several ligands showed potent affinity for the hCB1 receptor at nanomolar concentrations. Docking experiments and molecular dynamics simulations explained the potent hCB1 binding affinity of the new derivatives. The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB1 selective compounds act as antagonists/inverse agonists. References 1. J. Med. Chem. 2008, 51, 1560-1576.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
