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A series of novel substituted quinazolin-4(3H)-one derivatives were synthesized and screened in vivo for their antihypertensive activities. Out of eighteen synthesized compounds, seven i.e. 2a, 2c, 4a, 4d, 5d, 6a & 6b compounds have shown hypotensive effect and produced bradycardia. These compounds have shown better activity than reference drug Prazosin (which acts as anti-hypertensive agent by α1 blocking action). All the compounds have shown ALD50>1000mg/kg with maximum in 2c & 4d (>1200mg/kg).