Synthesis and Antihypertensive Activity of Novel Quinazolin-4(3H)-one Derivatives

Abstract

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).

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

“…A mixture of 6-fluoro 2-(4-fluorophenyl)-benzo[d] [ 1 , 3 ] oxazine-4-one ( 3 ) (0.01 mol) and hydrazine hydrate (0.015 mol) in dry pyridine (30 mL) was heated under reflux for 4 h. Then, the solid was separated and filtered, washed with water, dried and crystallized from ethanol. Isomers were separated by column chromatography using benzene:acetone in 7:3 ratio.…”

“…6-fluoro 2-(4-fluorophenyl)-benzo[d] [ 1 , 3 ] oxazine-4-one ( 3 ) (0.01 mol) and hydrazine hydrate (0.015 mol) were fused together at 250 °C in an oil bath for 0.5 h. The mixture was left to cool then methanol was added to this mixture. The separated solid was collected, filtered, dried, and recrystallized from ethanol.…”

“…Quinazolines belong to a famous class of heterocyclic compounds displaying a diverse and important range of therapeutic activities [ 1 , 2 ]. They are used as antihypertensive [ 3 ], antibacterial [ 4 , 5 ], antiviral [ 6 ], anti-inflammatory [ 7 ], antidiabetic [ 8 ], anticonvulsant, analgesic [ 1 , 9 ] and anticancer medications [ 10 , 11 , 12 , 13 , 14 , 15 ]. Many quinazolines were reported as anticancer agents having multi-target features [ 12 , 13 , 14 ].…”

Quinazoline pharmacophore in therapeutic medicine

“…Although, PARP inhibition did not have any antihypertensive effect, it enforces salient safeguarding upon process of change of hypertensive heart disorder to heart failure in SHRs (Magyar et al, 2014;Bartha et al, 2009). A series of novel substituted quinazolin-4(3H) -one derivatives, with acute LD50>1000 mg/kg, showed enhanced bioactivity than standard drug prazosin, which plays unique role as anti-hypertensive agent through 1 blocking procedure (Pathak et al, 2014). The effect of L-2286 on systolic blood pressure (SBP) was investigated by Magyar et al (2014).…”

Microwave Assisted Synthesis of 4-Phenylquinazolin-2(1H)-one Derivatives that Inhibit Vasopressor Tonus in Rat Thoracic Aorta

“…Quinazolinones are heterocyclic chemical compounds with two structural isomers, namely quinazolin-2(1H)-one and quinazolin-4(3H)-one ( Figure 1); the latter is the most investigated in the literature [5]. Quinazoline derivatives have also demonstrated antihypertensive effects, such as the class of the alpha 1-adrenergic (α1) receptor antagonists used in the treatment of hypertension [6,7]. Drugs such as prazosin or terazosin act on vascular smooth muscle receptors, leading to vasodilation and a consequent reduction in peripheral vascular resistance; these medications are used for the treatment of benign prostatic hyperplasia (BPH) [8].…”