title: Synthesis of heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors: effects on the inhibitory activity of the replacement of the cyclopentene central core with pyrazole, thiophene or isoxazole ring.
abstract: Several heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors, in which the cyclopentene moiety was replaced by pyrazole, thiophene or isoxazole ring, were synthesized, in order to verify the influence of the different nature of the central core on the COX inhibitory properties of these kinds of molecules. Among the compounds tested, only the 3-(p-methylsulfonylphenyl) substituted thiophene derivatives 17 and 22, showed a certain COX-2 inhibitory activity, accompanied by an appreciable COX-2 versus COX-1 selectivity. Only one of the 1-(p-methylsulfonylphenyl)pyrazole compounds (16) displayed a modest inhibitory activity towards both type of isoenzymes, while the pyrazole 1-(p-aminosulfonylphenyl) substituted 12 proved to be significantly active only towards COX-1. All the isoxazole derivatives were inactive on both COX isoforms.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126, Pisa, Italy. balsamo@farm.unipi.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Balsamo
authors.forename: Isabella
authors.initials: I
authors.lastname: Coletta
authors.forename: Angelo
authors.initials: A
authors.lastname: Guglielmotti
authors.forename: Carla
authors.initials: C
authors.lastname: Landolfi
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Milanese
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Mario
authors.initials: M
authors.lastname: Pinza
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000588:Amines; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D003517:Cyclopentanes; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D011720:Pyrazoles; D013876:Thiophenes; C031280:pyrazole; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone