Quantitative Structure‐Activity Relationships in the Displacement of the Dihydrosafrole Metabolite‐Cytochrome P‐450 Complex
Michael T. Murray, Craig B. Marcus, C.F. Wilkinson · Quantitative Structure-Activity Relationships · 1985
Abstract Twenty‐one 2‐substituted benzimidazoles and two naphtho‐[2,3‐d]‐imidazoles were evaluated for their in vitro ability to displace the dihydrosafrole metabolite from its complex with microsomal cytochrome P‐450. Several proved to be extremely effective displacers, the most active being 2‐(2′,3′‐dichloro‐phenoxy)methylbenzimidazole. Quantitative structure‐activity analyses (QSAR) using the descriptors log P (partition coefficient) and MR2 (molar refractivity) established that up to eighty‐eight percent of the variance in the displacement data could be accounted for in terms of the MR2 of the 2‐substituent of the benzimidazole ring. Other QSAR analyses involving molecular connectivity indices (χ) supported the assertion that steric parameters are of primary importance in the displacement process.