Leukotriene B4 receptor antagonists: the LY255283 series of hydroxyacetophenones.
Basic Information
ID: ALA1126041
Journal: J Med Chem
Title: Leukotriene B4 receptor antagonists: the LY255283 series of hydroxyacetophenones.
Authors: Herron DK, Goodson T, Bollinger NG, Swanson-Bean D, Wright IG, Staten GS, Thompson AR, Froelich LL, Jackson WT.
Abstract: A series of hydroxyacetophenones was prepared for evaluation as leukotriene B4 (LTB4) receptor antagonists, culminating in 1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5- yl)heptyl]oxy]phenyl]ethanone (compound 35, LY255283). Using an assay for inhibition of specific [3H]LTB4 binding to human PMN, we found that substitution of a nonpolar substituent in the 5-position was required for activity. Best activity was realized with hydrogen in the 3-position, hydroxyl in the 2-position, short chain alkyl ketone in the 1-position, and a six- or eight-carbon chain linking the oxygen in the 4-position with an unsaturated terminal function. Compound 35, having an IC50 of 87 nM in the binding assay, was chosen for further preclinical evaluation.
CiteXplore: 1316967
DOI: 10.1021/jm00088a018
Patent ID: ┄