481
14 Quantitative Structure-Property Relationship Analysis …
compound is characterized by a low solubility if the molecule has more than 6
fragments. Compound is characterized by a high solubility if a molecule has six or
fewer
fragments and at the same time no more than 18 & &
+
+
fragments.
Statistical models 3 and 4 that quite fairly describe both studied properties
(Table 14.4) were obtained using PLS method [10].
It is important to note that these models are characterized by lesser prediction
errors for the training and test sets than models 1 and 2. Ouite low Q
2
values can be
explained by the fact that the PLS method is more suited to the analysis of continuous (but not binary) data. As a result of the interpretation of models obtained by PLS
method, molecular fragments that promote or prevent penetration and solubility of
drugs were identified (Table 14.5).
The following rules were established: (1) The degree of penetration of drugs
remains practically unchanged, and the solubility decreases with an increase in the
length of alkyl chains (-С 4 Н 8 - and above); (2) Amides of carboxylic acids are dissolved better than esters of acids; (3) The degree of penetration increases in the
acid-amide-ester row; (4) To a large extent, the penetration is prevented due to the
Fig. 14.4 Classification trees describing a the solubility, b the degree of penetration of compounds
14 Quantitative Structure-Property Relationship Analysis …
compound is characterized by a low solubility if the molecule has more than 6
fragments. Compound is characterized by a high solubility if a molecule has six or
fewer
fragments and at the same time no more than 18 & &
+
+
fragments.
Statistical models 3 and 4 that quite fairly describe both studied properties
(Table 14.4) were obtained using PLS method [10].
It is important to note that these models are characterized by lesser prediction
errors for the training and test sets than models 1 and 2. Ouite low Q
2
values can be
explained by the fact that the PLS method is more suited to the analysis of continuous (but not binary) data. As a result of the interpretation of models obtained by PLS
method, molecular fragments that promote or prevent penetration and solubility of
drugs were identified (Table 14.5).
The following rules were established: (1) The degree of penetration of drugs
remains practically unchanged, and the solubility decreases with an increase in the
length of alkyl chains (-С 4 Н 8 - and above); (2) Amides of carboxylic acids are dissolved better than esters of acids; (3) The degree of penetration increases in the
acid-amide-ester row; (4) To a large extent, the penetration is prevented due to the
Fig. 14.4 Classification trees describing a the solubility, b the degree of penetration of compounds