New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB1Ki = 2.3 nanoM, CB1 SI = 163.6) showed CB1 receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2 mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB2Ki = 0.51 nanoM, CB2 SI = 30.0) showed significant affinity and selectivity for the CB2 receptor. The results presented here show that the 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB1 or CB2 receptor ligands.
1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: an effective scaffold for the design of either CB1 or CB2 receptor ligands / Piscitelli, Francesco; Ligresti, A.; LA REGINA, Giuseppe; Gatti, Valerio; Brizzi, A.; Pasquini, S.; Allarà, M.; Carai, M. A. M.; Novellino, E.; Colombo, G.; Di Marzo, V.; Corelli, F.; Silvestri, Romano. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 46:(2011), pp. 5641-5653. [10.1016/j.ejmech.2011.09.037]
1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: an effective scaffold for the design of either CB1 or CB2 receptor ligands.
PISCITELLI, FRANCESCO;LA REGINA, GIUSEPPE;GATTI, VALERIO;SILVESTRI, Romano
2011
Abstract
New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB1Ki = 2.3 nanoM, CB1 SI = 163.6) showed CB1 receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2 mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB2Ki = 0.51 nanoM, CB2 SI = 30.0) showed significant affinity and selectivity for the CB2 receptor. The results presented here show that the 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB1 or CB2 receptor ligands.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
