# Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin
## 4 Discussion
The correlation equation shows that the ALOGPs and XLOGP3 programs best reproduce the experimental lipophilicity, and the correlation cofactor is equal to 0.928 and 0.937, respectively (Table 5). The lipophilicity values obtained by the correlation equation are presented in Table S1. The obtained values show that the experimental lipophilicity could be predicted using the milogP and XLOGP3 programs. The relationship between the lipophilicity and structure of the tested compounds **3-18** was analysed using the similarity analysis (Figure 4). The cluster analysis shows that the compounds are localized in two main clusters. The derivatives localized in the first cluster have one or more hydroxyl groups as the substituent connected with the triazole ring. The second cluster is divided into three subclusters. In the first and third subcluster, mono- (**3-6**) and bistriazoles (**11-14**) are localized which contain a substituent with a phenyl ring. The second subcluster contains derivatives **10** and **18** which contain an ethylacetyle substituent at the triazole ring. The measure of similarity of two compounds is the Euclidean distance (ED). If the ED distance is similar, it means that the compounds exhibit similar features [63; 64; 65; 66]. As seen in Table S2, the derivatives in different subclusters have the same ED distance, which means that the compounds show high similarity. The analysis of Euclidean distance shows that lipophilicity strongly depends on the type of substituent connected with the triazole ring. Moreover, the replacement of a hydroxyl group at the C3 position of betulin by a triazole substituent slightly affects the logP parameter. Figure 3: The profile of changes in theoretical lipophilicity for derivatives **3–18**. \begin{table}
\begin{tabular}{c c c c} \hline
**Program** & **Correlation Equation** & **r** & **SD** \\ \hline ALOGPs & logP\({}_{\mathrm{TLC}}\) = 0.928 LogP\({}_{\mathrm{calc}}\) + 0.580 & 0.928 & 0.670 \\ ALCOGP & logP\({}_{\mathrm{TLC}}\) = 0.841 LogP\({}_{\mathrm{calc}}\) + 3.907 & 0.840 & 0.827 \\ milogP & logP\({}_{\mathrm{TLC}}\) = 0.916 LogP\({}_{\mathrm{calc}}\) + 0.979 & 0.916 & 0.682 \\ XLOGP2 & logP\({}_{\mathrm{TLC}}\) = 0.889 LogP\({}_{\mathrm{calc}}\) + 1.926 & 0.889 & 0.675 \\ XLOGP3 & logP\({}_{\mathrm{TLC}}\) = 0.937 LogP\({}_{\mathrm{calc}}\) + 1.157 & 0.937 & 0.565 \\ \hline \end{tabular}
\end{table} 
Table 5: Correlation equation for the experimental (logPTLC) and theoretical (logPcalc) values of lipophilicity for derivatives **3–18**. Lipophilicity is connected with other parameters which determine bioavailability. The first rules defining oral availability were described by [PERSON] and [PERSON] [67; 68; 69]. According to [PERSON]'s rule, lipophilicity should be less than 5. Only the experimental lipophilicity of derivatives **7** and **15** meets this condition. However, the logPTLC of compounds **8**, **9**, and **17** is slightly greater than 5 (Table 1). Almost all derivatives meet the criteria that the number of donors (HDs) and acceptors (HAs) of the hydrogen bond are less than 5 and 10, respectively. Only compounds **15**-**16** do not meet both rules. The molecular weight (M) of derivatives **3**-**18** is higher than 500, which means that none of tested compounds meets the mass criterion. [PERSON]'s rules connect good oral bioavailability with topological polar surface (TPSA) and the number of rotatable bonds (RTs). Most of the tested monotriazoles **3**-**10** meet the Veber criteria, except for compounds **7**-**8** for which the TPSA value is more than 140 A. None of the bistriazole derivatives **11**-**18** meets the Veber criteria. In summary, monotriazole derivatives **3**-**10** show moderate oral availability, and bistriazole derivatives **11**-**18** are characterized by low oral availability. Multilinear regression (MLR) was used to determine the correlation equation between the experimental lipophilicity and the calculated parameters.