We report here the preparation of three new benzthiazole analogues using the scaffold hoping technique. All the benzthiazole analogues were predicated for their ADME profiles and toxicity studies. All the compounds were found to follow the Lipinski’s rule of 5 with safe toxicity profile (Class IV compound) against immunotoxicity, mutagenicity and toxicity. All of the compounds were designed, followed by their molecular docking against Heat Shock Protein HSP-90 (ALPHA) (PDB code: 2XJX). One of the appealing cancer targets demonstrated an efficient binding within the binding site of HSP-90. Analogue 3a with docking score = −6.771 kcal/mol have shown stronger H-bond with amino acid (Thr184 and Gly97) showing an efficient binding within the binding site of HSP-90 in comparison with the native ligand Onalespib (XJX) a potent inhibitor of Hsp90.