Synthesis and structure-activity relationship studies of novel dual inhibitors of soluble epoxide hydrolase and 5-lipoxygenase.
Current research leads to the assumption that drugs affecting more than one target could result in a more efficient treatment of diseases and fewer safety concerns. Administration of drugs inhibiting only one branch of the arachidonic acid cascade is usually accompanied by side effects. We therefore designed and synthesized a library of hybrid molecules incorporating an imidazo[1,2-a]pyridine and an urea moiety as novel soluble epoxide hydrolase (sEH)/5-lipoxygenase (5-LO) dual inhibitors. Evaluation of the compounds was accomplished by in vitro testing using recombinant enzyme assays.
Institute of Pharmaceutical Chemistry, ZAFES/LiFF/OSF, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
Karin
K
Meirer
Carmen B
CB
Rödl
Joanna M
JM
Wisniewska
Sven
S
George
Ann-Kathrin
AK
Häfner
Estel-la
EL
Buscató
Franca-Maria
FM
Klingler
Steffen
S
Hahn
Dirk
D
Berressem
Sandra K
SK
Wittmann
Dieter
D
Steinhilber
Bettina
B
Hofmann
Ewgenij
E
Proschak
D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D007093:Imidazoles; D016859:Lipoxygenase Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; D014508:Urea; D001094:Arachidonate 5-Lipoxygenase; D004851:Epoxide Hydrolases