Recent insight into the biological activities of synthetic xanthone derivatives.

Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity

Introduction: Xanthine oxidase (XO) is a versatile molybdoflavoprotein, widely distributed, occurring in milk, kidney, lung, heart, and vascular endothelium. Catalysis by XO to produce uric acid and reactive oxygen species leads to many diseases. Anti hyperuricemic therapy by xanthine oxidase inhibitors has been mainly employed for the treatment of gout.Area covered: This review covers the patent literature (2011–2015) and also presents the interesting strategies/rational approaches employed for the design of xanthine oxidase inhibitors reported recently.Expert opinion: Recent literature indicates that various non purine scaffolds have been extensively investigated for xanthine oxidase inhibition. The significant potential endowed by heteroaryl based compounds, in particularly fused heterocycles clearly highlights their clinical promise and the need for detailed investigation. Studies by various research groups have also revealed that the flavone framework is open for isosteric replacements and st...

An updated patent review: Xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).

A ketone-assisted ruthenium-catalyzed selective amination of xanthones and chromones C–H bonds with sulfonyl azides is described. The reactions proceed efficiently with a broad range of substrates with excellent functional group compatibility. This protocol provides direct access to 1-aminoxanthones, 5-aminochromones, and 5-aminoflavonoid derivatives known to exhibit potent anticancer activity.

Ru(II)-catalyzed selective C-H amination of xanthones and chromones with sulfonyl azides: synthesis and anticancer evaluation.

Intermolecular C-O Addition of Carboxylic Acids to Arynes: Synthesis of o-Hydroxyaryl Ketones, Xanthones, 4-Chromanones, and Flavones.

Discovery of novel xanthone derivatives as xanthine oxidase inhibitors.

First identification of xanthone sulfonamides as potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a functional protein existing in almost all aerobic organisms. In the field of agricultural chemicals, HPPD is acknowledged to be one of the crucial targets for herbicides at present due to its unique bio-function in plants. In the Auto Core Fragment in silico Screening (ACFIS) web server, a potential HPPD inhibitor featuring 1,2,3-benzotriazine-4-one was screened out via a pharmacophore-linked fragment virtual screening (PFVS) method. Molecular simulation studies drove the process of "hit-to-lead" optimization, and a family of 1,2,3-benzotriazine-4-one derivatives was synthesized. Consequently, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-5-methyl-3-(2-methylbenzyl)benzo[d][1,2,3]triazin-4(3H)-one (15bu) was identified to be the best HPPD inhibitor (IC50 = 36 nM) among the 1,2,3-benzotriazine-4-one derivatives, which had over 8-fold improvement of enzyme inhibition compared with the positive control mesotrione (IC50 = 289 nM). Crystallography information for the AtHPPD-15bu complex revealed several important interactions of the ligand bound upon the target protein, i.e., the bidentate chelating interaction of the triketone motif with the metal ion of AtHPPD, a tight π-π stacking interaction consisting of the1,2,3-benzotriazine-4-one moiety and two benzene rings of Phe-424 and Phe-381, and the polydirectional hydrophobic contacts consisting of the ortho-CH3-benzyl group of the core scaffold and some hydrophobic residues. Furthermore, compound 15bu displayed 100% inhibition against the five species of target weeds at the tested dosage, which was comparable to the weed control of mesotrione. Collectively, the fused 1,2,3-benzotriazine-4-one-triketone hybrid is a promising chemical tool for the development of more potent HPPD inhibitors and provides a valuable lead compound 15bu for herbicide innovation.

Pharmacophore-Oriented Discovery of Novel 1,2,3-Benzotriazine-4-one Derivatives as Potent 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

The present invention relates to the field of medical technology, and in particular relates to a category of novel sulphonyl substituted xanthene ketone compounds that have a structural formula shown as follows, a preparation method and application thereof The compound has high inhibitory activity for ACAT1/ACAT2; most of the compounds have high inhibitory activity for acyl coenzyme A cholesterol acyltransferase (ACAT) The compounds can be used for preparing anti-atherosclerosis drug combination Furthermore, the compounds can be used as a preventive or a treating agent of such diseases as angina, myocardial infarction, cerebral infarction, apoplexy, Alzheimer's disease, acute coronary syndrome, PTCA or restenosis of coronary artery after a bracket is arranged The compounds can be used as a treating agent to adjust the function of sebaceous glands of the skin and inhibit the excessive generation of sebum And the compounds can be used for treating such diseases as acne-like damage caused by oily skin, acne, seborrhea and corticosteroids

Novel sulfonyl substituted benzophenone oxide compounds, prepraring method and application thereof

The present study deals with the first total synthesis of a new antifungal cyclic octapeptide, tunicyclin D, cyclo[VNIPPWHG], where all the amino acids are L-configuration, by a two-step solid-phase/solution synthesis strategy. The linear octapeptide was assembled by a solid-phase peptide synthesis (SPPS) method. Subsequently cyclization and deprotection were achieved in solution with high efficiency and reproducibility. The final product was purified by preparative RP-HPLC, and its structure was identified by ESI-MS, 1 H NMR, 13 C NMR, and HR-QTOF-MS.

Weifeng Wu

Papers

Discovery of novel xanthone derivatives as xanthine oxidase inhibitors.

First identification of xanthone sulfonamides as potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.

Pharmacophore-Oriented Discovery of Novel 1,2,3-Benzotriazine-4-one Derivatives as Potent 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

Novel sulfonyl substituted benzophenone oxide compounds, prepraring method and application thereof

First total synthesis of antifungal cyclopeptide tunicyclin d by a solid-phase method