title: Synthesis and cycloxygenase inhibitory properties of new naphthalene-methylsulfonamido, naphthalene-methylsulfonyl and tetrahydronaphthalen-methylsulfonamido compounds.
abstract: We synthesized a series of new naphthalene derivatives: naproxen- and 6-methoxy naphthalene acetic acid-like 1-5. In these compounds the carboxylic function, typical of the classical NSAIDs, was replaced by a methylsulfonamido (1, 2 and 6a-c) or methylsulfonyl (3-5) group present in some selective COX-2 inhibitors. We also synthesized compounds 7 and 8 in which the naphthalene portion was substituted by tetrahydronaphthalene ring. Some of the new compounds were assayed for their enzymatic inhibitory activity towards cycloxygenase enzymes. Compounds 4 and 6b, at a concentration of 10 µM exhibit percentage inhibition values of 65%, 50% and 29%, 87% towards COX-2 and COX-1, respectively. The substitution of carboxylic group with a mehylsulfonamido or a methylsulfonyl groups does not allow to direct the selectivity versus to cycloxygenase enzymes.
authors.affiliation: Dipartimento di Farmacia, Università Pisa Via Bonanno , Pisa , Italy and.
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Lidia
authors.initials: L
authors.lastname: Ciccone
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Claudio
authors.initials: C
authors.lastname: Milanese
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D009281:Naphthalenes; D013449:Sulfonamides; C031721:naphthalene; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Cycloxygenase inhibitors; naphthalene derivatives; naphthalene-methylsulfonamido compounds; naphthalene-methylsulfonyl compounds; tetrahydronaphthalenmethylsulfonamido compounds