STUDIES ON QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP OF THE STEREOISOMERS OF 3 METHYLFENTANYL DERIVATIVES
SB Rong · Yaoxue xuebao · 1997
Comparative molecular field analysis (CoMFA) method was used to study the three dimensional structure activity relationship (3D QSAR) of the stereoisomers of 3 methylfentanyl and ohmefentanyl. The CoMFA QSAR model has very good predictive ability (γ 2 cross validated =0 716, n optimal component =5, γ 2 conventional =0 999, s=0 052, F=1305 1), in which the conformations of the studied compounds could be their possibly bioactive conformations. By quantum chemical calculation (AM1), the structural and stereo parameters of the above possibly bioactive conformations were obtained. On the basis of these parameters, the QSAR equations of the studied compounds were derived by partial least squares (PLS) method. The PLS QSAR model with better predictive ability showed that, the analgesic activity is closely dependent on the net charge of nitrogen atom in piperidine (N PA ) as well as the geometric parameters of N PA , O PA , 1 β phenyl ring, 4 N phenyl ring, 3 methyl and 2′ hydroxyl.