QSAR: Conceptions and Misconceptions
Ariëns Ej · Quantitative Structure-Activity Relationships · 1992
Abstract The basis for QSAR‐studies on drugs, pesticides and other xenobiotics is the maxim: “Exposure of nature (including man) and its environment to xenobiotics (including drugs) is only justified if the desirable actions adequately compensate for the undesirable actions and the never fully excluded risks”. QSAR requires a clearcut congenerity which implies: a 3‐dimensional homology of the various molecular fragments in the chemical framework in the series of compounds “compared”. QSAR in drug etc. development has to comprise activity as well as selectivity. QSAR in relation to drug‐receptor interaction requires restriction to isoregional and isochiral structural variation in the group of congeneric agents compared. In QSAR based on the integral approach, e.g. fractional constants related to lipophilicity or molecular connectivity, overall qualities such as passive membrane penetration and tissue accumulation play a predominant role. QSMR – Quantitative Structure‐Metabolism Relationship – is an essential factor in in vivo QSAR. Eudismic analysis is a prerequisite for QSAR dealing with CCD's, CCP's – Composite Chiral Drugs or Pesticides. Disregard of isomeric ballast invalidates QSAR on chiral agents.