A new series of N-(6-chlorobenzothiazol-2-yl)- 2-substituted-acetamides (3a–h) and N-(6-chlorobenzothiazol-2-yl)-2-(substituted-benzylidene)hydrazinecarbothioamides (5a–h) were synthesized and characterized by IR, 1 H NMR, mass and elemental analysis. In vivo anticonvulsant and acute toxicity screening of all the synthesized compounds showed morpholino (3f) and imidazolyl (3g) derivatives as promising anticonvulsant lead. Furthermore, In silico druglikeness parameters have also been investigated for filtering out the likelihood of poor drug absorption or brain penetration. 3D four-point pharmacophore measurements of compounds were also carried out to match these with established anticonvulsants agents.