Synthesis of (2E)-2-methyl-3-(4-([4-(quinolin-2-ylmethoxy)phenyl]sulfanyl)phenyl)prop-2-enoic acid (VUFB 20609) and 2-methyl-3-(4-([4-(quinolin-2-ylmethoxy)phenyl]sulfanyl)phenyl)propanoic acid (VUFB 20584) as potential antileukotrienic agents.
The syntheses of (2E)-2-methyl-3-(4-([4-(quinolin-2-ylmethoxy)phenyl]sulfanyl)phenyl) prop-2-enoic acid (VUFB 20609) and racemic 2-methyl-3-(4-([4-(quinolin-2-ylmethoxy) phenyl]sulfanyl)phenyl)propanoic acid (VUFB 20584) as new potential antileukotrienic drugs are described. Due to a low reactivity of the 4-substituted aryl bromides (coupling of the 4-substituted aryl bromides do not provide an activating functional group with 4-methoxybenzene-1-thiol), special conditions, in particular specific heterogeneous copper catalysts, were used. Catalytic hydrogenation of the conjugated double bond on Pd/C in the presence of the sulfanyl group is discussed. In-vitro cytotoxicity testing was performed using a microplate colorimetric acid phosphatase assay. Antiplatelet activity was evaluated using an in-vitro test in human platelet-rich plasma. Some substances inhibited arachidonic acid-induced platelet aggregation.
Jampílek
J
J
Research Centre LN00B125, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Dolezal
M
M
Kunes
J
J
Víchová
P
P
Jun
D
D
Hanika
Jirí
J
O'Connor
R
R
Clynes
M
M
D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D006865:Hydrogenation; D020024:Leukotriene Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C492996:2-methyl-3-(4-((4-(quinolin-2-ylmethoxy) phenyl)sulfanyl)phenyl)propanoic acid; C492997:2-methyl-3-(4-((4-(quinolin-2-ylmethoxy)phenyl)sulfanyl)phenyl) prop-2-enoic acid; D020024:Leukotriene Antagonists; D010975:Platelet Aggregation Inhibitors; D011804:Quinolines; D013440:Sulfides; D016718:Arachidonic Acid