Collect. Czech. Chem. Commun.
2004, 69, 2098-2120
https://doi.org/10.1135/cccc20042098
Derivatives of (Phenylsulfanyl)benzoic Acids with Multiple Antileukotrienic Activity
Miroslav Kuchařa,b,*, Vojtěch Kmoníčekc, Vladimíra Panajotovác, Antonín Janderac, Bohumila Brunováa, Richard Junekb, Věra Bucharovác, Jan Čejkad and Dalibor Šatinskýe
a VUFB, Research Institute for Pharmacy and Biochemistry, 102 01 Prague 10, Czech Republic
b Research Centre LN00B125, Léčiva, Ltd., 102 01 Prague 10, Czech Republic
c REaD-VUFB, Ltd.,180 66 Prague 9, Czech Republic
d Department of Chemistry of Solid State, Institute of Chemical Technology, Prague, 166 28 Prague 6, Czech Republic
e School of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic
Abstract
A series of derivatives of (phenylsulfanyl)benzoic acids bearing quinoline, 2,4-dihydroxy-3-propylacetophenone and 2,4-difluorobiphenyl moieties were prepared and their antileukotrienic activities evaluated. Some of the compounds were found to display multiple antileukotrienic effect in the inhibition of LTB4 biosynthesis, binding to LTD4 and LTB4 receptors, superior to the standards (zileuton and zafirlukast) used. The compounds had an antiinflammatory effect, manifested with quinoline derivatives by a significant inhibition of bronchospasm induced by LTD4 and/or albumin. The results of regression analysis correspond to the observation that the most active compounds belong to quinoline derivatives with the lowest lipophilicity. X-ray analysis of the quinoline compounds revealed that an intramolecular hydrophobic interaction of their aromatic rings does not occur in the solid state.
Keywords: (Phenylsulfanyl)benzoic acids; Antileukotrienic activity; Regression analysis; Lipophilicity; Antiinflammatory and antiasthmatic effects; QSAR.
References: 42 live references.
