Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Eur J Med Chem. 2011 Nov;46(11):5641-53. doi: 10.1016/j.ejmech.2011.09.037. Epub 2011 Sep 29.
New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB(1)K(i) = 2.3 nM, CB(1) SI = 163.6) showed CB(1) receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB(2)K(i) = 0.51 nM, CB(2) SI = 30.0) showed significant affinity and selectivity for the CB(2) 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 CB(1) or CB(2) receptor ligands.
新型 1-芳基-5-(1H-吡咯-1-基)-1H-吡唑-3-甲酰胺被合成作为大麻素（CB）受体配体。化合物 11（CB1K(i) = 2.3 nM，CB1SI = 163.6）表现出优于利莫那班和 AM251 的 CB1 受体亲和力和选择性。11 的急性给药 2mg/kg 可减少大鼠蔗糖，但不减少常规食物的摄入。另一方面，化合物 23（CB2K(i) = 0.51 nM，CB2SI = 30.0）对 CB2 受体表现出显著的亲和力和选择性。本文结果表明，1-芳基-5-(1H-吡咯-1-基)-1H-吡唑-3-甲酰胺可作为设计 CB1 或 CB2 受体配体的有效支架。
