title: Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaline and quinazoline derivatives as CB2 receptor agonists.
abstract: Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [³⁵S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC₅₀ = 7.8; E(max) = 75%). The isoquinolin-1-yl(3-trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC₅₀ = 5.8; E(max) = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC₅₀ = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist.
authors.affiliation: University of Eastern Finland, Kuopio, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Saari
authors.forename: Jonna-Carita
authors.initials: JC
authors.lastname: Törmä
authors.forename: Tapio
authors.initials: T
authors.lastname: Nevalainen
mesh_terms: D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008872:Microwaves; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007546:Isoquinolines; D009025:Morpholines; C557924:N-(morpholinyl)-1-(3-(trifluoromethyl)phenylamino)isoquinoline-4-carboxamide; D011799:Quinazolines; D011804:Quinolines; D011810:Quinoxalines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C037219:quinoline; C039109:isoquinoline