Figure 1.
The structures of previous series I and series II.
Figure 2.
General synthesis of compounds (C1–C24).
Reagents and Conditions: i) EtOH, 40% NaOH, 0°C, stir, 30 min; rt, stir, 4 h; ii) EtOH, Phenylhydrazine, 80°C, 5 h.
Table 1.
Substitutes of the synthesized compounds.
Table 2.
B-RafV600E inhibitory activity and anti-proliferation activity of the synthesized compounds (C1–C24) as well as previous compounds C0A and C0B.
Figure 3.
Docking models of representative compounds.
(A) 2D molecular docking modeling of compound C6 with 3PSD. (B) 3D model of the interaction between compound C6 and 3PSD bonding site. (C) 2D molecular docking modeling of compound C18 with 3PSD. (D) 2D molecular docking modeling of compound C5 with 3PSD. The H-bonds (green line) are displayed as dotted lines and the amino acid they act on are labeled in green. The π–cation interactions and π–π interactions are shown as orange lines with their corresponding amino acids labeled in yellow. Other important amino acids are labeled in blue.
Table 3.
The docking calculation of the synthesized compounds (C1–C24) and comparisons.
Figure 4.
The receptor surface model with C6 in 3PSD.
Figure 5.
3D-QSAR of 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-yl)phenol.
Red contours mean high electron density is expected to increase activity while blue contours mean low electron density is better. Green areas mean steric bulk is better while yellow areas mean small groups are helpful.