title: A class of 5-benzylidene-2-phenylthiazolinones with high potency as direct 5-lipoxygenase inhibitors.
abstract: A novel class of potent direct 5-lipoxygenase (5-LO) inhibitors bearing a thiazolinone-scaffold identified by virtual screening is presented. A range of substitutions and the importance of the 2-phenyl moiety were evaluated. This series is characterized by high potency in intact polymorphonuclear leukocytes and a cell-free system, exemplified by (Z)-2-(4-chlorophenyl)-5-(4-methoxybenzylidene)-5H-thiazol-4-one (18, IC(50) = 0.28 and 0.09 μM). These disubstituted thiazolinones may possess potential for intervention with inflammatory and allergic diseases and certain cancer types.
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt, Germany. hofmann@pharmchem.uni-frankfurt.de
authors.forename: Bettina
authors.initials: B
authors.lastname: Hofmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Barzen
authors.forename: Carmen B
authors.initials: CB
authors.lastname: Rödl
authors.forename: Andreas
authors.initials: A
authors.lastname: Kiehl
authors.forename: Julia
authors.initials: J
authors.lastname: Borig
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Zivković
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry*; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C558746:2-(4-chlorophenyl)-5-(4-methoxybenzylidene)-5H-thiazol-4-one; D001597:Benzylidene Compounds; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; D001094:Arachidonate 5-Lipoxygenase