Figure 2 . Elimination score (SE) for the most promising rasagiline derivatives, according to SS. Columns are divided to show the influence of the new contributions included in each score, with respect to the previous one.
Figure 2 shows that the new properties included in SE,ADME8, and the toxicity indexes have the largest contribution to SE,ADMETSA. Thus, the proposed index emphasizes the importance of toxicity in the choice of candidates drugs. Figure 3 shows a more meticulous analysis of the individual contributions of the different parameters to the SE,ADMETSA elimination score.
The largest deviations arise mainly from LD50, M, PSA, MW, HBA, and HBD.
Regarding LD50, the rasagiline derivatives deviating the most from the average value (R-8, RI-36 and RII-2) are less toxic to rats than the reference compounds (LD50 = 960.8)140-142. Their LD50 were estimated to be 1970.2, 1613.9, 1882.0, and 2644.1, respectively. Thus, these important deviations imply a more desirable behaviour, compared to the reference set. Therefore, these derivatives were included in the subset selected as the most promising, based on ADMETSA properties. A similar trend was found for the Ames mutagenicity, i.e., the compounds predicted as the least mutagenic are just those that deviate the most from the reference set (M = 0.41)140-142. They are RI, RI-4, RI-36, RI-49, RI-97, RII-2, and RII-10 all with M ≤ 0.03. Consequently, it is essential not only to detect the designed molecules with the largest deviation from the reference set, but also to examine what causes such deviations. Otherwise, promising candidates could be excluded for no good reason.