Computational structural correlation and bioavailability studies of Dronedarone impurity

(5-Amino-2-butyl-3-benzo furanyl) [4-[3-(dibutyl amino) propoxy] phenyl] methanone (DND-1) is a process-related impurity of Dronedarone (DND). In the current work, the optimized geometry and geometrical data were computed and compared the same with experimental data available in the literature. Different physiochemical parameters of DND-1 were assessed computationally to evaluate its drug-likeness, medicinal chemistry friendliness and toxicity aspects. Both DND and DND-1 have comparable but very less water solubility. Their inhibitory action towards various cytochromes is more or less similar, except for the cytochrome CYP2C19. The log KP values were calculated at -4.56 and -3.83Cm/S for DND and DND-1 respectively indicating good chances of skin permeation with the latter being more potent. The polar surface area is computed using the TPSA technique while considering sulfur as a polar atom. The TPSA value of DND is slightly above the critical value of 90 [Å]2 while the impurity molecule DND-1 has a much lower TPSA. This is because DND-1 has a primary amine in place of the highly polar sulphonamide group of DND. This further enhances the BBB permeation and subsequent CNS penetration of DND-1. Therefore DND-1 can be a better CNS drug compared to DND.