Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286

Lianhai Li; Carl Berthelette; Anne Chateauneuf; Marc Ouellet; Claudio F Sturino; Zhaoyin Wang

doi:10.1016/j.bmcl.2010.10.024

Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7440-3. doi: 10.1016/j.bmcl.2010.10.024. Epub 2010 Oct 15.

Authors

Lianhai Li¹, Carl Berthelette, Anne Chateauneuf, Marc Ouellet, Claudio F Sturino, Zhaoyin Wang

Affiliation

¹ Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada. [email protected]

PMID: 21044840
DOI: 10.1016/j.bmcl.2010.10.024

Abstract

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.

MeSH terms

Administration, Oral
Animals
Arachidonate 5-Lipoxygenase / chemistry*
Arachidonate 5-Lipoxygenase / metabolism
Dogs
Drug Evaluation, Preclinical
Humans
Hydrocarbons, Fluorinated / chemical synthesis
Hydrocarbons, Fluorinated / chemistry*
Hydrocarbons, Fluorinated / pharmacology
Lipoxygenase Inhibitors / chemical synthesis
Lipoxygenase Inhibitors / chemistry*
Lipoxygenase Inhibitors / pharmacokinetics
Rats
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacology

Substances

Hydrocarbons, Fluorinated
Lipoxygenase Inhibitors
MK-5286
Thiophenes
Triazoles
benzothiophene
Arachidonate 5-Lipoxygenase