A series of N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB1. n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed greater hCB1 receptor affinity than the corresponding unbranched compounds. In particular, the tert-butyl group as a chain terminal moiety strongly improved hCB1 receptor affinity (compound 24: Ki=45.6 nM; 29: Ki=37.5 nM). Acute administration of either compound 12 or 29 resulted in a specific, dose-dependent reduction in food intake in rats. Such results provide an useful basis for the design of new CB1 ligands.
Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands / Silvestri, Romano; Ligresti, A.; LA REGINA, Giuseppe; Piscitelli, Francesco; Gatti, Valerio; Lavecchia, A.; Brizzi, A.; Pasquini, S.; Allarà, M.; Fantini, N.; Carai, M. A. M.; Bigogno, C.; Rozio, M. G.; Sinisi, R.; Novellino, E.; Colombo, E.; DI MARZO, V.; Dondio, G.; Corelli, F.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 45:(2010), pp. 5878-5886. [10.1016/j.ejmech.2010.09.053]
Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands.
SILVESTRI, Romano;LA REGINA, GIUSEPPE;PISCITELLI, FRANCESCO;GATTI, VALERIO;
2010
Abstract
A series of N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB1. n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed greater hCB1 receptor affinity than the corresponding unbranched compounds. In particular, the tert-butyl group as a chain terminal moiety strongly improved hCB1 receptor affinity (compound 24: Ki=45.6 nM; 29: Ki=37.5 nM). Acute administration of either compound 12 or 29 resulted in a specific, dose-dependent reduction in food intake in rats. Such results provide an useful basis for the design of new CB1 ligands.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
