A series of novel oxadiazole derivatives were designed, synthesized, and evaluated for their pharmacological effects. All target compounds were subjected to analysis using 1H NMR, 13C NMR, and mass spectrometry. They showed a strong affinity to the AT1 receptor and effectively lowered blood pressure in spontaneously hypertensive rats at a nanomolar level. Compounds IV1 and IV2 were particularly effective, demonstrating comparable or greater potency in reducing blood pressure compared to Losartan. Therefore, compounds IV1 and IV2 have the potential to be developed as antihypertension medications.