Synthesis and characterization of quinazoline derivatives: search for hybrid molecule as diuretic and antihypertensive agents

Abstract

To explore the pharmacological and structure-activity relationship of a series of N-substituted-(4-oxo-2-substituted-phenylquinazolin-3-(4H)-yl), substituted benzene sulfonamide derivatives (1-25) were synthesized from substituted anthranilic acids derived amino quinazolines and substituted benzene sulphonamides. All the synthesized compounds were evaluated for their diuretic (by Lipschitz et al. method), antihypertensive activity by non-invasive blood pressure (NIBP) using the tail-cuff method and anti-diabetic potential in rats. Six compounds showing significantly excellent activity were compared with metolazone, prazosin and diazoxide as standards. Compound N-[7-chloro-2-(4-methoxyphenyl)-4-oxoquinazolin-3(4H)-yl]-4 nitrobenzenesulfonamide (20) exhibited most potent of the series.

Biological Activity of Quinazolinones

“…Javaid et al [95] reported a quinazolinone derivative (111; Figure 15) with IC50 value of 0.3 ± 0.01 μM which is about 2800-fold more potent than acarbose reference standard drug. Rahman et al [96] synthesized a series of hybrid compounds consisting of N-substituted-(4-oxo-2-substituted-phenylquinazolin-3-(4H)-yl) substituted benzene sulfonamide derivatives. From this series, compounds (112-116; Figure 15) explored significant antidiabetic activity.…”

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation

“…The 2,3-dihydroquinazolin-4(1H)-ones (2,3-DHQs) are fused heterocyclic compounds which exist in natural products such as luotonins A, B, E, and F [13], tryptanthrin [14], and rutaecarpine [15]. 2,3-DHQs possess a broad range of pharmacological properties such as anti-cancer [16,17], antidepressant [18], antidiabetic [19], antifungal [20], antihypertensive [21,22], analgesic, anti-inflammatory [23,24], antibacterial [25], antioxidant [26], and antiviral [27] activities; they also act as bronchodilator [28], centrally acting muscle relaxant [29], diuretic [30], sedative, and hypnotic [31] agents (Figure 1). Quinazoline derivatives were also reported as bactericides [32], fungicides [33], and insecticides [34].…”

Search for Compounds with Hypoglycemic Activity in the Series of 1-(2-(1H-Tetrazol-5-yl)-R1-Phenyl)-3-R2-phenyl(ethyl)ureas and R1-Tetrazolo[1,5-c]quinazolin-5(6H)-ones

“…Such derivatives, 2- sec -amino-3 H -quinazolin-4-ones, displayed a significant reduction in blood glucose level in streptozotocin and sucrose-loaded rat models [ 6 ] as well as 1-thioxo-1,2,7,8,9,10-hexahydro-3 H -pyrimido[1,6- a ]quinazolin-3-one [ 7 ]. Also, N -substituted-(4-oxo-2-substituted-phenylquinazolin-3-(4 H )-yl), namely N -[7-chloro-2-(4-methoxyphenyl)-4-oxoquin-azolin-3(4 H )-yl]-4 nitrobenzenesulfonamide, exhibited high antidiabetic potential [ 8 ]. In addition, N -4(substituted phenyl)-5-{[(2-phenylquinazolin-4-yl)-oxy]-methyl}-1,3,4-thiadiazol-2-amine derivatives according to docking glide score showed a high potency with regards to hypoglycemic activity [ 9 ].…”