Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors

A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone®, in 62–76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC50=0.014 μM) and selective COX-2 (Selectivity Index >7142) inhibitory activity.