Colchicine Models: Synthesis and Binding to Tubulin of Tertamethoxybiphenyls

Abstract
Syntheis of tetramethoxybiphenyl 21 was accomplished from 4‐phenylcylohexane‐1,3‐dione 13 by aromatization to biphenyl 19 and reductive removal of the phenolic OH group as phenyltetrazolyl ether. Tertramethoxybiphenyls 34 and 40 were obtained from 4‐phenylcyclohexenone 26 via ester 27. The tetramethoxybiphenyls 21, 34, and 40, and analogs 28, 29, and 31 were evaluated for antitubulin activity and as antimitotic agents with L1210 murine leukemia cells. Compounds 31 and 34 had significant effects on the invitro polymerization of tubulin. Compound 31 was the most cytotoxic of the six new biphenyls studied (IC50 for cell growth, 0.6M) and caused the accumulation of cells in metaphase arrest.