title: Synthesis, biological evaluation and molecular modelling studies on benzothiadiazine derivatives as PDE4 selective inhibitors.
abstract: A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoforms PDE3, PDE4 and PDE7. The compounds characterized by the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N1 position of 2,1,3-benzothiadiazine core (8, 13, 18), were found active and selective at micromolar level versus PDE4 and could be studied as new leads for the treatment of asthma and COPD (Chronic Obstructive Pulmonary Disease). The antioxidant activity evaluation on the same compounds highlighted 13 as the most significative. Molecular modelling studies gave further support to biological results and suggested targeted modifications so as to improve their potency.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. tait.annalisa@unimore.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Tait
authors.forename: Amedeo
authors.initials: A
authors.lastname: Luppi
authors.forename: Armin
authors.initials: A
authors.lastname: Hatzelmann
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
authors.forename: Luisa
authors.initials: L
authors.lastname: Mosti
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D001249:Asthma / Q000188:drug therapy; D001483:Base Sequence; D001581:Benzothiadiazines / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D017931:DNA Primers; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D013055:Spectrophotometry, Infrared
chemical_list: D001581:Benzothiadiazines; D017931:DNA Primers; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4