A novel, practical, highly efficient, and transition metal free nitrogen insertion reaction for the synthesis of 2,3-disubstituted quinazolinone derivatives was developed. Diverse functionalized 3-indolinone-2-carboxylates and nitrosoarenes with a wide range of substituted nitrosobenzenes, nitrosopyridines, dibenzofuranyl, or dibenzothienyl nitroso compounds worked smoothly to give 2,3-disubstituted quinazolinone derivatives in good to excellent yields (69-98%). A gram-scale reaction was achieved, and an afloqualone analogue was synthesized under the mild reaction conditions.

01 May 2021·Molecular DiversityQ3 · CHEMISTRY

Design, synthesis, crystal structure and in vitro antimicrobial activity of novel 1,2,4-triazolo[1,5-a]pyrimidine-containing quinazolinone derivatives

Q3 · CHEMISTRY

Article

Author: Du, Huan ; Shi, Jun ; Luo, Na ; Huang, Jian ; Ding, Muhan ; Bao, Xiaoping

A series of novel 1,2,4-triazolo[1,5-a]pyrimidine-containing quinazolin-4(3H)-one derivatives (8a-8o) were designed, synthesized and assessed for their in vitro antibacterial and antifungal activities in agriculture. All the title compounds were completely characterized via ¹H NMR, ¹³C NMR, HRMS and IR spectroscopic data. In particular, the molecular structure of compound 8f was further corroborated through a single-crystal X-ray diffraction measurement. The turbidimetric method revealed that some of the compounds displayed noticeable bactericidal potencies against the tested plant pathogenic bacteria. For example, compounds 8m, 8n and 8o possessed higher antibacterial efficacies in vitro against Xanthomonas oryzae pv. oryzae with EC₅₀ values of 69.0, 53.3 and 58.9 μg/mL, respectively, as compared with commercialized agrobactericide bismerthiazol (EC₅₀ = 91.4 μg/mL). Additionally, compound 8m displayed an EC₅₀ value of 71.5 μg/mL toward Xanthomonas axonopodis pv. citri, comparable to control bismerthiazol (EC₅₀ = 60.5 μg/mL). A preliminary structure-activity relationship (SAR) analysis was also conducted, based on the antibacterial results. Finally, some compounds were also found to have a certain antifungal efficacy in vitro at the concentration of 50 μg/mL.

01 Jan 2021·Archives of ToxicologyQ2 · MEDICINE

In vitro assessment of the photo(geno)toxicity associated with Lapatinib, a Tyrosine Kinase inhibitor

Q2 · MEDICINE

Article

Author: Andreu, Inmaculada ; Miranda, Miguel A ; Vayá, Ignacio ; Marín, M Pilar ; García-Lainez, Guillermo

The epidermal growth factor receptors EGFR and HER2 are the main targets for tyrosine kinase inhibitors (TKIs). The quinazoline derivative lapatinib (LAP) is used since 2007 as dual TKI in the treatment of metastatic breast cancer and currently, it is used as an oral anticancer drug for the treatment of solid tumors such as breast and lung cancer. Although hepatotoxicity is its main side effect, it makes sense to investigate the ability of LAP to induce photosensitivity reactions bearing in mind that BRAF (serine/threonine-protein kinase B-Raf) inhibitors display a considerable phototoxic potential and that afloqualone, a quinazoline-marketed drug, causes photodermatosis. Metabolic bioactivation of LAP by CYP3A4 and CYP3A5 leads to chemically reactive N-dealkylated (N-LAP) and O-dealkylated (O-LAP) derivatives. In this context, the aim of the present work is to explore whether LAP and its N- and O-dealkylated metabolites can induce photosensitivity disorders by evaluating their photo(geno)toxicity through in vitro studies, including cell viability as well as photosensitized protein and DNA damage. As a matter of fact, our work has demonstrated that not only LAP, but also its metabolite N-LAP have a clear photosensitizing potential. They are both phototoxic and photogenotoxic to cells, as revealed by the 3T3 NRU assay and the comet assay, respectively. By contrast, the O-LAP does not display relevant photobiological properties. Remarkably, the parent drug LAP shows the highest activity in membrane phototoxicity and protein oxidation, whereas N-LAP is associated with the highest photogenotoxicity, through oxidation of purine bases, as revealed by detection of 8-Oxo-dG.

100 Deals associated with Afloqualone

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KEGG	Wiki	ATC	Drug Bank
D01638	Afloqualone	M03	-

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Indication	Country/Location	Organization	Date
Dystonic Disorders	Japan	Nipro ES Pharma KK	29 May 1987
Spastic paralysis	Japan	Nipro ES Pharma KK	03 Feb 1983

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