Collect. Czech. Chem. Commun. 2005, 70, 1357-1371

The Antileukotrienic Derivatives and Homologues of [(Quinolin-2-ylmethoxy)sulfanyl]benzoic Acids with Reduced Lipophilicity

Miroslav Kuchařa,b,*, Bohumila Brunováa, Richard Junekb, Robert Rodlinga, Josef Hájíčeka, Vladimíra Panajotovác and Antonín Janderac

a Zentiva VUFB, Research Institute for Pharmacy and Biochemistry, 102 01 Prague 10, Czech Republic
b Research Centre LN00B125, Zentiva, a.s., 102 01 Prague 10, Czech Republic
c REaD-VUFB, Ltd., 180 66 Prague 9, Czech Republic


A series of ({[(quinolin-2-ylmethoxy)phenyl]sulfanyl}phenyl)acetic acids 2 and S-oxidized derivatives of {[(quinolin-2-ylmethoxy)phenyl]sulfanyl}benzoic acids 3 were prepared and their antileukotrienic and antiasthmatic activities evaluated. Regression analysis led to the conclusion that the antileukotrienic activities of compounds 2 correspond to the relationships between these activities and lipophilicity, derived for the previously synthesized series of substituted (arylsulfanyl)benzoic acids 1A, 1B and 1C. Acids 3 are outliers from these relationships, probably due to a somewhat different mechanism of action. A higher antiasthmatic activity was observed in some [(arylsulfanyl)phenyl]acetic acids 2 in comparison with the corresponding analogs bearing the (arylsulfanyl)benzoic acid moiety. The inhibition of 5-lipoxygenase activated protein (FLAP) was determined for these compounds, and the influence of the direct inhibition of LTB4 biosynthesis is discussed to explain the differences in the antiasthmatic effect of the compounds under study.

Keywords: [(Phenylsulfanyl)phenyl]acetic acids; Arylacetic acids; Quinolines; Antileukotrienic activities; FLAP inhibition; Lipophilicity; Regression analysis; Antiasthmatic effect.

References: 33 live references.