Synthesis and biological evaluation of 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives as new ligands of cannabinoid receptors

Design, Synthesis, and Biological Evaluation of New 1,8-Naphthyridin-4(1H)-on-3-carboxamide and Quinolin-4(1H)-on-3-carboxamide Derivatives as CB2Selective Agonists

“…34 Furthermore, the substitution of the methyl group in position 7 of the 1,8-naphthyridine nucleus with an atom of chlorine (12-14 and 33), or the lack of any substituent in the same position (18)(19)(20), generally determines the maintenance or an increase in the affinity (except for compounds 13 and 19, which showed a 4-fold and 5-fold decrease in affinity compared with the methyl analogues 34 ).…”

“…As reported in Scheme 3, the diazotization of compound 27 34 with NaNO 2 in aqueous 96% sulfuric acid gave the 7-hydroxy derivative The 7-acetamido-1,8-naphthyridin-4(1H)-on-3-carboxylic acid ethyl ester 30 37 was heated at 120°C in a sealed tube with 4-methylcyclohexylamine (Scheme 4). Under these conditions, the hydrolysis of the acetamido group also takes place, and thus, the 7-amino-3-carboxamide derivative 31 was obtained.…”

“…33 We have previously reported the synthesis and the binding activity at mouse cannabinoid receptors of a series of 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives whose general structure is A (Figure 1). 34 The binding results showed that the naphthyridine derivatives generally exhibit a higher affinity for the CB 2 than for the CB 1 receptor, and for some of these compounds the K i (CB 1 )/K i (CB 2 ) ratio was higher than 20. Furthermore, some of these compounds exhibit a CB 2 affinity value in the nanomolar range.…”

Recent developments in cannabinoid ligands

“…A series of CB 2 selective 1,8-naphthyridines was synthesized after the development of 277 (Ferrarini et al, 2004). These compounds also have the 3-carboxyamide of the arylpyrazoles, but contain an alkyl or arylalkyl substituent on the N1 position similar to that of the AAIs.…”

“…,8-Naphthyridine derivatives(Ferrarini et al, 2004) Affinity of compounds for CB 1 receptor was evaluated using mouse cerebellum membranes and [ 3 H]-CP 55,940. Affinity for CB 2 receptor was assayed using mouse spleen homogenate and [ 3 H]-CP 55,940.…”