Figure 1.

Structures of the 27 propofol analogues used in the 4D-QSAR training set. Each type of activity measure is expressed as −log(EC₅₀) in the construction of the QSAR models where EC₅₀ is in molar units. The same compounds are inactive in all three screens, with the minor exception of phenol not showing activity for direct activation. It should be pointed out here that about half of the 27 analogues were tested as far as aqueous solubility allowed but did not show activity, even when applied for very long periods of time. The inactive compounds were monitored down to −log(EC₅₀) = 2 (which corresponds to a ligand concentration of 10 mM). However, the lower limit in activity for each of the three measures was varied from 2 to 0 in the construction of the 4D-QSAR models. The optimum 4D-QSAR model for each activity class was obtained by setting the activity of each inactive analogue to −log(EC₅₀) = 1.0. The −log(EC₅₀) values for each of the analogues and each of the three activity types are given in Table 1. This manner of including class measures, as opposed to actual activity measures, in QSAR model building must be carefully monitored and kept in mind in interpreting the resultant model.