The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug Diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of Benzothiopyran derivatives (7a–7f). The new compounds maintain some Diltiazem pharmacophores. Benzothiopyran has two pharmacophore: the aromatic benzene ring fused with the heterocyclic thiopyrans ring, and the stereo-chemical centers (alkyl ether). In vitro evaluation of Benzothiopyran derivatives (7a–7f) for calcium channel blocking effects revealed moderate activities. Compounds of the current series showed optimum activity when the alkyl ether chain was substituted on the 3-chloro-3,4-dihydro-2H-1-benzothiopyran-4-ol derivatives (7a–7f).