title: Synthesis and potential anti-inflammatory activity of some tetrahydrophthalazinones.
abstract: A solid-phase route for the preparation of 4a,5,8,8a-tetrahydrophthalazinon-1-ones employing the Diels-Alder reaction has been developed. Some of the new compounds have been tested for inhibition of LPS-stimulated TNF-alpha production in human whole blood from patients with chronic obstructive pulmonary disease (COPD). This evaluation revealed two compounds 17 and 18 of interest, incorporating an arylpiperazine moiety, which were found to inhibit LPS-induced TNF-alpha release like the well known anti-inflammatory PDE4 inhibitors, rolipram and roflumilast.
authors.affiliation: Faculté de Pharmacie, 35043 Rennes-cédex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gouault
authors.forename: Benoit
authors.initials: B
authors.lastname: Pinel
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Cupif
authors.forename: Alexandra
authors.initials: A
authors.lastname: Depince
authors.forename: Corinne A E
authors.initials: CA
authors.lastname: Martin-Chouly
authors.forename: Chantal
authors.initials: C
authors.lastname: Belleguic
authors.forename: Michele
authors.initials: M
authors.lastname: David
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000631:Aminopyridines / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003521:Cyclopropanes / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D020889:Rolipram / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D003521:Cyclopropanes; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D014409:Tumor Necrosis Factor-alpha; C424423:Roflumilast; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; C020976:azelastine