Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286.
The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described.
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada. lianhai_li@merck.com
Lianhai
L
Li
Carl
C
Berthelette
Anne
A
Chateauneuf
Marc
M
Ouellet
Claudio F
CF
Sturino
Zhaoyin
Z
Wang
D000284:Administration, Oral; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D006845:Hydrocarbons, Fluorinated; D016859:Lipoxygenase Inhibitors; C556360:MK-5286; D013876:Thiophenes; D014230:Triazoles; C088015:benzothiophene; D001094:Arachidonate 5-Lipoxygenase