Design, synthesis, docking, and biological evaluation of some novel 5-chloro-2-substituted sulfanylbenzoxazole derivatives as anticonvulsant agents.

In view of their expected anticonvulsant activity, some novel derivatives of 5-chloro-2-substituted sulfanylbenzoxazoles ( 5- 15f) were synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole-induced seizures in mice. The molecular docking was performed for all the synthesized compounds to assess their binding affinities to KCNQ2 receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling were correlated with that obtained from the biological screening. These data revealed that compounds 15f, 7c, 15b, and 15d showed the highest binding affinities toward KCNQ2 receptor along with the highest anticonvulsant activities in experimental mice. The highest active compounds showed relative potencies of 0.98, 0.94, 0.91, and 0.83, respectively, in comparing to phenobarbital sodium. [ABSTRACT FROM AUTHOR]