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Effects of Antithrombotic and Results of Drug Screening
Published in Josef Hladovec, Antithrombotic Drugs in Thrombosis Models, 2020
Antithrombotics that were among the first to be tested under clinical conditions in the prevention of venous thrombosis were antimalarics, particularly hydroxychloroquine.724 Their activity was probably due to the inhibition of phospholipase A2 activity, and thus, to a decrease in arachidonic acid availability. In contrast to this supposed mechanism of action directed chiefly against platelet functions, the drugs were effective in preventing postoperative venous thrombosis.725 Studies in animal models were carried out with the chemically related quinazoline derivative BL-3459. At an oral dose of 150 mg/kg the drug was highly effective in arterial electric current-induced rat and dog thrombosis, prevented death after arachidonic acid and endotoxin DIC in mice, and inhibited laser-induced thrombosis in the microcirculation of the rabbit ear chamber.155, 636 The drug was also effective in rabbits with an AV anastomosis at a dose as low as 1 mg/kg i.p.726
Adrenergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Bunazosin, an α1 adrenoceptor antagonist and a member of the quinazoline class is used mainly in treating hypertension (Hara et al., 2006). Additionally, it finds its use as hypotensive medicament in the field of ophthalmology, hence therapeutically used for treating ischemic retinal diseases like retinal vascular occlusive diseases and glaucoma associated with ocular circulation disturbances as it produces a direct neuroprotective effect and improves the ocular circulation. Instillation of bunazosin in rabbit eyes has showed an apparent improvement in optic nerve head blood flow impairment and perseverance of visual evoked potentials (VEP) implicit time probably by inhibiting NO synthase; in rats through Na+ channel action, glutamate induced neuronal death was reduced; in humans, an elevation in the velocity of blood in the retinal and choroidal areas and optic nerve head were observed (Hara et al., 2006).
Prospects of Pre-clinical [6.6.0] Bicyclic Nitrogen Heterocycles in the Treatment of Tuberculosis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Neha P. Agre, Mariam S. Degani, Sanjib Bhakta
Quinazoline is a bioisostere of quinoline with additional nitrogen in position 3 of the ring, as depicted in Figure 5. Structural representation of the quinazoline scaffold.
TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Aiyun Li, Li Guan, Wanzhen Su, Ning Zhao, Xuwen Song, Jin Wang, Xiaoxiao Tang, Weize Li, Xiangying Jiao
The development of drugs to inhibit TXNIP expression could be an attractive approach for T2DM treatment. Recently, a compound named SRI-37330 was reported to inhibit TXNIP23. SRI-37330 is a quinazoline sulphonamide derivative; in addition to the quinazoline structure, a nitrogen-containing heterocycle is found in the molecule. Based on structural analysis and simplified compounds, we retained the quinazoline ring and nitrogen-containing heterocycle, and aimed to enrich compound libraries that could inhibit TXNIP. Here, 20 compounds were designed by combining unsubstituted quinazoline with different nitrogen-containing heterocycles through carbon chains of different lengths (Scheme 1). Subsequent in vitro pharmacological experiments and in silico physiochemical and pharmacokinetics prediction demonstrated that the compounds D-2 and C-1, especially the compound D-2, had better pancreatic β cell protective activity via inhibition of TXNIP expression and would be promising lead candidates for the treatment of T2DM.
Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?
Published in Expert Opinion on Drug Discovery, 2022
Alane Beatriz Vermelho, Giseli Capaci Rodrigues, Alessio Nocentini, Felipe R. P. Mansoldo, Claudiu T. Supuran
Quinazoline derivatives are potential selective TcCA inhibitors. In a recent study, most of the 4-oxoquinazoline sulfonamides showed nanomolar TcCA inhibition activity in vitro, whereas the 6-methyl-3-allyl 4-oxoquinazoline derivative was the most effective compound [80]. Using two N-nitrosulfonamides derivatives, 26 and 27 (Figure 3), Bonardi et al. [81] demonstrated that N-nitrosulfonamides and their salts are promising and innovative compounds for the management of Chagas disease, strongly inhibiting TcCA in vitro and in vivo. Several such compounds showed better activity than the reference drug benznidazole (Bnz) against the epimastigotes forms of T. cruzi in both the Dm28c clone, Y strain, and the trypomastigote Dm28c-Luc clone form of the parasite [81]. For intracellular amastigotes, these compounds showed lower efficacy (Figure 3). However, these two derivatives possessed higher toxicity than Bnz for Raw 267.4 macrophages and Vero cells. The antimicrobial behaviors of silver-containing compounds have long been investigated, with various antimicrobial mechanisms of action proposed. The biologically active silver ion (Ag+) damages critical enzymes in the cell membranes of pathogens [81].
LSD1 inhibitors for anticancer therapy: a patent review (2017-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Yi-Xin Lv, Sheng Tian, Zhou-Dong Zhang, Tao Feng, Huan-Qiu Li
Quinazoline derivatives have historically been used as important synthetic chemotherapeutic and antimicrobial agents [62–64]. For the first time, Speranzini et al. discovered a novel LSD1 inhibitor, compound 33, based on the quinazoline scaffold [65]. Compound 33 had a potent inhibitory effect on LSD1 with an IC50 value of 0.24 μM (Figure 12a). Furthermore, in 2021, a patent was filed for a series of 4-arylthio quinazoline derivatives [66]. With an IC50 value of 0.69 μM, compound 34 exhibited the best activity against LSD1. Furthermore, compound 34 inhibited gastric cancer cells (MGC-803, BGC-823, and SGC-7901), breast cancer cells (MCF-7), lung cancer cells (H1650, A549, H1957, and H460), esophageal cancer cells (EC-109), liver cancer cells (HepG2), and leukemia cells (THP-1). Meanwhile, compound 34 has no obvious inhibitory effect on normal gastric mucosal epithelial cells (GES-1), a cell line with low toxicity to normal cells and high safety.