Multivariate Free‐Wilson Analysis of Some N‐Alkylmorphinan‐6‐one Opioids Using PLS
Ulf Norinder · Quantitative Structure-Activity Relationships · 1993
Abstract The PLS method is used to derive an improved, unified and statistically significant Free‐Wilson QSAR model for the analgesic potency of some N‐alkylmorphinan‐6‐one opioids by the inclusion of a large number of first order cross‐terms between the substituents. To obtain high potency the R1/R2 substituent‐pair should be a cyclo‐butyl and a hydrogen (fenol), respectively, while the R3 substituent can be either an oxygen or a methylene bridge. The R4− and R5 substituents can both be a hydrogen or a methyl group to retain high potency of the opioids. Contrary to this, the R1/R2 pairs cyclo‐propyl/hydrogen and cyclo‐butyl/methyl as well as a n‐propyl substituent in the R5 position are quite unfavorable in this respect.