SAR-study on a new class of imidazo[1,2-a]pyridine-based inhibitors of 5-lipoxygenase.
A novel class of 5-lipoxygenase (5-LO) inhibitors characterized by a central imidazo[1,2-a]pyridine scaffold, a cyclohexyl moiety and an aromatic system, is presented. This scaffold was identified in a virtual screening study and exhibits promising inhibitory potential on the 5-LO. Here, we investigate the structure-activity relationships of this compound class. With N-cyclohexyl-6-methyl-2-(4-morpholinophenyl)imidazo[1,2-a]pyridine-3-amine (14), we identified a potent 5-LO inhibitor (IC(50)=0.16μM (intact cells) and 0.1μM (cell-free)), which may possess potential as an effective lead compound intervening with inflammatory diseases and certain types of cancer.
Institute of Pharmaceutical Chemistry, ZAFES/LiFF/OSF Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
Martina
M
Hieke
Carmen B
CB
Rödl
Joanna M
JM
Wisniewska
Estel
E
la Buscató
Holger
H
Stark
Manfred
M
Schubert-Zsilavecz
Dieter
D
Steinhilber
Bettina
B
Hofmann
Ewgenij
E
Proschak
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D016859:Lipoxygenase Inhibitors; D011725:Pyridines; D001094:Arachidonate 5-Lipoxygenase; C001439:imidazo(1,2-a)pyridine