## 3 Results and Discussion
The energy of the interactions between protein residue and ligand 3g are tabulated in Table 5.  
Potential surface representation of PDE5 binding site with docked compound 3g is presented in Figure 3, while Figure 4 illustrates the interactions of ligand 3g with receptor PDE5 in the binding site. Figure 3: Potential surface representation catalytic domain of PDE5 with docked compound 3g. (Range of potential: from min. 1.77 mV (blue) to max. 0.541 mV (red)). \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Comp.** & **Pose** & **Total Energy/kcal mol\({}^{-1}\)** & **Van Der Waals Interaction** & **H Bond** & _Elec_ \\ \hline
**3g** & 1 & \(-\)105.62 & \(-\)95.34 & \(-\)10.27 & 0 \\
**3f** & 1 & \(-\)98.66 & \(-\)75.26 & \(-\)23.40 & 0 \\
**3b** & 0 & \(-\)98.44 & \(-\)90.79 & \(-\)7.66 & 0 \\
**3d** & 0 & \(-\)96.70 & \(-\)82.39 & \(-\)14.31 & 0 \\
**3i** & 0 & \(-\)93.07 & \(-\)84.42 & \(-\)8.65 & 0 \\
**3e** & 1 & \(-\)89.18 & \(-\)84.61 & \(-\)4.58 & 0 \\
**3a** & 0 & \(-\)88.90 & \(-\)66.30 & \(-\)22.60 & 0 \\
**3c** & 0 & \(-\)88.78 & \(-\)81.78 & \(-\)7.00 & 0 \\
**3j** & 0 & \(-\)88.49 & \(-\)86.64 & \(-\)1.85 & 0 \\
**3h** & 0 & \(-\)88.09 & \(-\)70.57 & \(-\)17.52 & 0 \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Docking scores for fluorinated pyrazoles in interaction with PDE5. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**H Bond** & **Energy** & **Van Der Waals Interaction** & **Energy** \\ \hline S-Gln817 & \(-\)6.81 & S-Phe820 & \(-\)18.51 \\ S-His613 & \(-\)3.41 & S-Tyr612 & \(-\)10.33 \\  & & S-Val782 & \(-\)8.70 \\  & & S-Phe786 & \(-\)7.90 \\  & & M-Leu765 & \(-\)4.20 \\  & & S-Leu765 & \(-\)4.04 \\  & & S-Met816 & \(-\)4.01 \\ \hline \hline \end{tabular} (M = main chain; S = side chain).  
\end{table} 
Table 5: The energy of the main interactions between protein PDE5 residue and ligand 3g. The binding site of PDE5 was defined according to the inhibitor - halogen derivate of monocyclic pyrimidinones (PDB ID: 5 IO). Molecular docking confirmed the previous findings of characteristic binding interactions of inhibitors with the PDE5 catalytic domain [29]. Key interactions of compound **3g** are bidentate hydrogen bond (H-bond) with the side-chain of Gln817. One H-bond is formed with an oxygen atom of the carbaldehyde, and the second one with the nitrogen atom of pyrazole ring (Figure 4). Based on van der Waals interactions, pyrazole ring interacts with the side chain of Phe820. Side chain of Val782 forms \(\pi\)-\(\pi\) interactions with pyrazole ring and dimethoxyphenyl ring. The same ring is bonded to the Tyr612 by the \(\pi\)-donor hydrogen bond. Interactions of fluorophenyl ring are mediated through the \(\pi\)-\(\sigma\) interactions with Phe786 and \(\pi\)- sulfur interactions with Met816. Figure 4: The main interactions of compound **3g** with residues in catalytic domain of PDE5: **(A)** 3D representation and hydrophobic surface of the binding site, **(B)** 2D representation (green = conventional hydrogen bond, light green = van der Waals, very light green = \(\pi\)-donor hydrogen bond, purple = \(\pi\)-\(\sigma\) interactions, light purple = \(\pi\)-\(\pi\)interactions, pink = alkyl and \(\pi\)-alkyl interactions, brown = \(\pi\)-sulphur bond). Docking results of this study are in accordance with the solved crystal structure of PDE5 catalytic domain in complex with different inhibitors. The catalytic domain of PDE5 includes three subdomains: N-terminal cyclin-fold region, a linker region and a C-terminal helical bundle in which the center is an active site of PDE5 core pocket (Q pocket) of the binding site contains Gln817, Phe820, Val782, Tyr612 [30]. Typical interactions include mono or bidentate hydrogen bonds of inhibitors with Gln817 and mainly \(\pi\)-\(\pi\) interactions of aromatic rings with hydrophobic clamp, which contains residuals, Val782, and Phe820.