913533-99-0Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)- on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB 2 selective agonists
Manera, Clementina,Benetti, Veronica,Castelli, M. Paola,Cavallini, Tiziana,Lazzarotti, Sara,Pibiri, Fabio,Saccomanni, Giuseppe,Tuccinardi, Tiziano,Vannacci, Alfredo,Martinelli, Adriano,Ferrarini, Pier Luigi
, p. 5947 - 5957 (2006)
On the basis of docking studies carried out using the recently published cannabinoid receptor models, new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB 2 receptors. Compound 10, which presented p-fluorobenzyl and carboxycycloheptylamide substituents bound in the 1 and 3 positions of the 1,8-naphthyiridine-4-one nucleus, showed a high CB2 affinity with a Ki of 1.0 nM. The substitution of the naphthyridine-4-one nucleus with the quinoline-4-one system determined a general increase in CB2 affinity. In particular, the N-cyclohexyl-7-chloro-1-(2-morpholin-4-ylethyl) quinolin-4(1H)-on-3-carboxamide (40) possessed a remarkable affinity, with Ki of 3.3 nM, which was also accompanied by a high selectivity for the CB2 receptor (Ki(CB1/Ki(CB 2) ratio greater than 303). Moreover, the [35S]GTPγ binding assay and functional studies on human basophils indicated that the 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives behaved as CB1 and CB2 receptor agonists.
