- Deferasirox (ExJade): An FDA-Approved AIEgen Platform with Unique Photophysical Properties
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Deferasirox, ExJade, is an FDA-approved iron chelator used for the treatment of iron overload. In this work, we report several fluorescent deferasirox derivatives that display unique photophysical properties, i.e., aggregation-induced emission (AIE), excited state intramolecular proton transfer, charge transfer, and through-bond and through-space conjugation characteristics in aqueous media. Functionalization of the phenol units on the deferasirox scaffold afforded the fluorescent responsive pro-chelator ExPhos, which enabled the detection of the disease-based biomarker alkaline phosphatase (ALP). The diagnostic potential of these deferasirox derivatives was supported by bacterial biofilm studies.
- Sedgwick, Adam C.,Yan, Kai-Cheng,Mangel, Daniel N.,Shang, Ying,Steinbrueck, Axel,Han, Hai-Hao,Brewster, James T.,Hu, Xi-Le,Snelson, Dylan W.,Lynch, Vincent M.,Tian, He,He, Xiao-Peng,Sessler, Jonathan L.
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- Synthesis of novel 2,4-Di(o-hydroxyphenyl)-6-substituted amino-1,3,5-triazine
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Seven novel 1,3,5-triazine derivatives were synthesized in good to high yields (69.19-91.15%) by the reaction of substituted guanidine with 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one in ethanol. The products were recrystallized from ethanol or ethanol-DMF mixture and their structures were confirmed by 1H NMR and FT-IR.
- Jiang, Junrong
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- Synthesis of deuterium-labelled isotopomer of deferasirox
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A d4-labeled isotopomer of deferasirox was synthesized as internal standard for use in a LC/mass spectroscopy (MS)/MS method developed for the simultaneous quantitative determination of deferasirox in human serum. d4-deferasirox was synthesized from d8-toluene.
- Havaldar, Freddy H.,Dabholkar, Bhushan Vasant,Mule, Ganesh Baban,Kulkarni, Suhas
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- Excitation Wavelength Dependent Fluorescence of an ESIPT Triazole Derivative for Amine Sensing and Anti-Counterfeiting Applications
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Excitation wavelength dependent (Ex-De) emission materials have potential applications in anti-counterfeiting labels and bioimaging. Nevertheless, few purely organic chromophores are used in these areas. In this study, multiple excited states were incorporated into a molecule that was excited state intramolecular proton transfer (ESIPT) active, with the goal of manipulating the relaxation pathways of the excited states. The triazole derivative exhibits Ex-De photoluminescence (PL), and the maximum PL wavelength is located at 526 nm and 593 nm under a series of excitation wavelengths. Spectral identification indicates that the excimer and ESIPT processes are responsible for the green (526 nm) and orange (593 nm) fluorescence, respectively. Importantly, the quick response code and test strip prepared with this triazole derivative can be used for anti-counterfeiting and food spoilage detection applications, respectively. This research opens the door for developing novel Ex-De materials for anti-counterfeiting purposes.
- Zhang, Yujian,Yang, Heyi,Ma, Huili,Bian, Gaofeng,Zang, Qiguang,Sun, Jingwei,Zhang, Cheng,An, Zhongfu,Wong, Wai-Yeung
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- Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4-Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate
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A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC50 values of 1.268 and 3.254 μm, respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors.
- Amanlou, Massoud,Azizian, Homa,Balalaie, Saeed,Biglar, Mahmood,Fathi Vavsari, Vaezeh,Mahernia, Shabnam,Sadeghi Alavijeh, Nahid,Salehi Ashani, Razieh,Sheysi, Niloofar
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- A triazole based fluorescence "turn-on" sensor for Al(III) and Zn(II) ions
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A triazole derivative containing trifluoromethyl and diphenol unit was synthesized as a fluorescent 'turn-on' chemosensor for Al3+ and Zn2+ ions with high sensitivity, a rapid response time and specific selectivity over other cations.
- Bian, Gao-Feng,Guo, Yun,Lv, Xiao-Jing,Zhang, Cheng
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- In vitrostudies of deferasirox derivatives as potential organelle-targeting traceable anti-cancer therapeutics
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We report here strategic functionalization of the FDA approved chelator deferasirox (1) in an effort to produce organelle-targeting iron chelators with enhanced activity against A549 lung cancer cells. Derivative 8 was found to have improved antiproliferative activity relative to 1. Fluorescent cell imaging revealed that compound 8 preferentially localises within the lysosome.
- Han, Hai-Hao,He, Xiao-Peng,Huang, Dan-Ying,Li, Jia,Sedgwick, Adam C.,Sen, Sajal,Sessler, Jonathan L.,Steinbrueck, Axel,Zang, Yi,Zhao, Michael Y.
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supporting information
p. 5678 - 5681
(2021/06/16)
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- Synthesis and biological evaluation of 1,2,4-oxadiazole core derivatives as potential neuroprotectants against acute ischemic stroke
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Here, we report the synthesis and neuroprotective capacity of 27 compounds with a bisphenol hydroxyl-substituted 1,2,4-triazole core or 1,2,4-oxadiazole core for stroke therapy. In vitro studies of the neuroprotective effects of compounds 1–27 on sodium nitroprusside (SNP)-induced apoptosis in PC12 cells indicate that compound 24 is the most effective compound conferring potent protection against oxidative injury. Compound 24 inhibits reactive oxygen species (ROS） accumulation and restores the mitochondrial membrane potential (MMP). Moreover, further analysis of the mechanism showed that compound 24 activates the antioxidant defence system by promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increasing the expression of haem oxygenase 1 (HO-1). An in vivo study was performed in a rat model of transient focal cerebral ischaemia generated by the intraluminal occlusion of the middle cerebral artery (MCAO). Compound 24 significantly reduced brain infarction and improved neurological function. Overall, compound 24 potentially represents a promising compound for the treatment of stroke.
- Shi, Jinguo,Wang, Yang,Chen, Jianwen,Lao, Yaoqiang,Huang, Ping,Liao, Liping,Jiang, Caibao,Li, Xinhua,Wen, Jin,Zhou, Shujia,Zhang, Jingxia
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- Synthesis of 2-(2-Hydroxyaryl)-4H-benzo[e][1,3]oxazin-4-ones by Palladium-Catalyzed C(sp2)?H Hydroxylation via Electro-chemical Oxidation
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An electrochemical direct ortho-hydroxylation of 2-aryl-4H-benzo[e][1,3]oxazin-4-ones was developed with Pd(OAc)2 as catalyst, oxazine ring as a directing group and Oxone as the hydroxylation reagent. A series of hydroxylation products were obtained under mild conditions, and the yields were from medium to good. This method is characterized by good functional group tolerance and a wide range of substrates. More importantly, use anodic oxidation to avoid the use of potentially toxic and polluting oxidants. A gram-scale direct electrochemical hydroxylation of 2-phenyl-4H-benzo[e][1,3]oxazin-4-one was performed, and the hydroxylation product was applied to synthesize the drug deferasirox. In addition, the single crystal of 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one was obtained and determined by X-ray diffraction. Finally, the reaction mechanism was proposed and verified by cyclic voltammetry (CV). This protocol also provides an alternative electrochemical hydroxylation methodology for the functionalization of molecules. (Figure presented.).
- Wu, Hongfeng,An, Qi,He, Chaoyin,Fan, Xiaodong,Guo, Weihao,Zuo, Minghui,Xu, Chunzhao,Guo, Rui,Chu, Wenyi,Sun, Zhizhong
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p. 2459 - 2465
(2020/04/29)
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- Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential neuroprotectant against ischemic brain injury
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A series of 1,2,4-triazole derivatives 1–14 was synthesized to investigate their neuroprotective effects and mechanisms of action. Compounds 5–11 noticeably protected PC12 cells from the cytotoxicity of H2O2 or sodium nitroprusside (SNP). Compound 11 was the most effective derivative. Compound 11 chelated Fe (II) iron, scavenged reactive oxygen species (ROS), and restored the mitochondrial membrane potential (MMP). Moreover, it enhanced the activity of the antioxidant defense system by increasing the serum level of superoxide dismutase (SOD) and promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Compound 11 caused certain improvements in behavior, the cerebral infarction area, and serum levels of biochemical indicators (TNF-α, IL-1β, SOD and MDA) in a rat MCAO model. The lethal dose (LD50) of compound 11 in mice receiving intraperitoneal injections was greater than 400 mg/kg. Meanwhile, pharmacokinetic experiments revealed high bioavailability of this compound after both oral and intravenous administration (F = 60.76%, CL = 0.014 mg/kg/h) and a longer half-life (4.26 and 5.11 h after oral and intravenous administration, respectively). Based on these findings, compound 11 may be a promising neuroprotectant for the treatment of ischemic stroke.
- Chen, Jianwen,Jiang, Caibao,Lao, Yaoqiang,Li, Xinhua,Liang, Jie,Liao, Liping,Shi, Jinguo,Wang, Yang,Wen, Jin,Zhang, Jingxia,Zhou, Shujia
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- NEW PYRIDINE AND PYRIMIDINE SUBSTITUTED TRIAZINE UV ABSORBERS
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A compound of formula (1), wherein V, W, X and Y represent N or CH, at least one of V, W, X and Y being N and at least two of V, W, X and Y being CH; and R1, R2 and R3 are each independently of the other hydrogen, C1-C8alkyl, C1-C8alkoxy, nitro, cyano, trifluoromethyl, halogen or hydroxy; with the proviso that the compounds of formulae (101) and (102) are excluded, provides good lightfastness properties to textile fibre materials, in particular PES fibre materials.
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(2020/05/15)
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- A PROCESS FOR THE PREPARATION OF DEFERASIROX
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The present invention provides an improved process for the preparation of Deferasirox of Formula - I substantially free from 'hydrazino impurity' by the condensation of 2-(2-hydrophenyl)-4H-1,3-benzoxazin-4-one of Formula - IV with 4-hydrazino benzoic acid of Formula - V in a polar solvent.
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(2019/02/06)
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- A triazole derivative metal ion fluorescent probe and its preparation method and application
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The invention relates to a triazole derivative containing trifluoromethyl-phenyl and a diphenyl unit, a preparation method and an application of the triazole derivative as a fluorescence sensor, which are suitable for detection of metal aluminium ions and zinc ions. In a fluorescence ion probe prepared by the above compound, hydroxy and triazole combine the effective effect of the metal, phenolic hydroxyl and triazole and metal can form a stable complex, a single bond rotation of the phenolic hydroxyl group connected with triazole is inhibited after coordination, molecule coplanarity is enhanced, a rigid system is formed, chelating is caused for enhancing the fluorescence effect, and the detection on the metal ion probe can be finally realized.
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Paragraph 0008; 0021; 0032; 0033; 0035; 0036
(2018/11/03)
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- 1,2,4-triazole compound, salt thereof and applications of compound and salt
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The invention discloses a 1,2,4-triazole compound, salt thereof and applications of the compound and salt. The compound has a structural formula shown in the description, wherein R represents hydrogen, phenyl or substituted phenyl, and a substituted group of substituted phenyl is selected from carboxyl, an ester group, C1-4 alkyl, C1-4 alkoxy groups, C1-4 halogenated alkyl, C1-4 halogenated alkoxygroups, C2-4 alkynyl, halogen, cyano groups, acyl, nitryl or hydroxyl. The compound has high insecticidal activity for aphids, part of compound has the insecticidal activity for aphids equivalent tothat of a commercial insecticide dinotefuran, and the compound can be used for controlling lepidoptera pests, coleoptera pests, heteropteran pests, diptera pests, orthoptera pests and homoptera pests.
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Paragraph 0023; 0025
(2018/11/22)
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- PREPARATION OF NOVEL DEFERASIROX ANALOGUES FOR ANTIMALARIAL ACTIVITY
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The present invention relates to processes for the preparation of novel deferasirox analogues for antimalarial activity. The present invention further provides process for synthesis of novel deferasirox analogues.
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(2017/01/02)
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- IRON COMPLEXING AGENT AND USES THEREOF IN THE TREATMENT AND PREVENTION OF COLORECTAL CANCER
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A complex comprising a non-absorbable portion attached to an iron chelator moiety, a composition comprising the complex and the use of the complex in the treatment of colorectal cancer. In one embodiment the non-absorbable portion is a polymer such as a polysaccharide, including chitosan, chitin, cellulose or pectin. In one embodiment the iron chelator moiety comprises at least one functional group selected from catechol, hydroxamate or carboxylate, or any combination thereof.
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Paragraph 0060-0062
(2016/10/31)
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- PROCESS FOR THE PREPARATION OF DEFERASIROX
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The present invention provides improved process for the preparation of Deferasirox of formula (I).
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Paragraph 0043
(2014/02/16)
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- Process for the preparation, of 2-(2-hydroxyphenyl)-benz [1, 3] oxazin-4-one and its use for preparation of 4-[3, 5-bis (2-hydroxyphenyl)-lH-l , 2, 4-triazolTl-yl] benzoic acid
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The invention provides a novel process for the synthesis of 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one, the process comprising of reacting the salicylic acid with salicylamide in the presence of p-toluenesulfonyl chloride, base and solvent. The use of 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one in the preparation of Deferasirox is also disclosed in the invention.
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Paragraph 0020
(2014/02/15)
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- PROCESS FOR THE PRODUCTION OF DEFERASIROX
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A new process is described for the preparation of deferasirox, 4-[(3Z,5E)-3,5-bis(6- oxo-1 -cyclohexa-2,4-dienylidene)-1,2,4-triazolidin-1 -yl]benzoic acid, having the following structural formula (I).
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(2012/10/18)
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- PROCESS FOR THE PREPARATION OF DEFERASIROX
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The present invention provides improved process for the preparation of Deferasirox of formula (I).
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(2012/06/15)
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- Synthesis and characterization of related substances of deferasirox, an iron (Fe3+) chelating agent
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Deferasirox is an orally active iron chelating agent, and during process development for deferasirox, we observed six related substances (impurities), namely deferasirox methyl ester, deferasirox salicylyl derivative, deferasirox ethyl ester, deferasirox methoxy carbonyl derivative, bis(salicyl)imide, and deferasirox-2-isomer. The present work describes the detection, origin, synthesis, and characterization of these related substances.
- Rao, Vascuri Janardhana,Mukkanti, Kagga,Vekariya,Gupta, P. Badrinadh,Islam, Aminul
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p. 3200 - 3210
(2012/11/13)
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- NEW TRIAZINE DERIVATIVE, ULTRAVIOLET ABSORBER, AND RESIN COMPOSITION
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To provide a novel triazine-based compound exhibiting an ultraviolet blocking effect even in the long-wavelength region and being useful as an ultraviolet absorber with excellent light resistance, and to provide an ultraviolet absorber and a resin composition, which can maintain a long-wavelength ultraviolet-blocking effect for a long period of time. A compound represented by the following formula (1): wherein each of R1a, R1b, R1c, R1d and R1e independently represents a hydrogen atom or a monovalent substituent excluding OH, provided that at least one substituent represents a substituent having a Hammett's σp value of 0.3 or more and substituents may combine with each other to form a ring, and each of R1g, R1h, R1i, R1j, R1k, R1m, R1n and R1p independently represents a hydrogen atom or a monovalent substituent, provided that substituents may combine with each other to form a ring.
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(2012/06/18)
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- A PROCESS FOR THE PREPARATION OF 2-(2-HYDROXYPHENYL)-BENZ[1,3]OXAZIN-4-ONE AND ITS USE FOR PREPARATION OF 4-[3, 5-BIS (2-HYDROXYPHENYL)-1H-1, 2, 4-TRIAZOL-1-YL] BENZOIC ACID
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The invention provides a novel process for the synthesis of 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one, the process comprising of reacting the salicylic acid with salicylamide in the presence of p-toluenesulfonyl chloride, base and solvent. The use of 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one in the preparation of Deferasirox is also disclosed in the invention
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- PROCESS FOR THE PREPARATION OF 4-[3,5-BIS(2-HYDROXYPHENYL)-1H-1,2,4-TRIAZOL-1-YL]-BENZOIC ACID AND ITS AMINE SALTS
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The present invention relates to an improved process for the preparation of 4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid compound of formula (1) and process for its purification.
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(2011/04/13)
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- SOLID STATE FORMS OF DEFERASIROX SALTS AND PROCESS FOR THE PREPARATION THEREOF
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Provided herein are novel solid state forms of deferasirox salts, process for the preparation, pharmaceutical compositions, and method of treating thereof. The solid state forms of deferasirox salts are useful for preparing deferasirox (I) in high purity.
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(2011/05/05)
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- CRYSTALLINE FORM OF 2-(2-HYDROXY PHENYL)BENZ[E][1,3]OXAZIN-4-ONE, PROCESS FOR THE SAME AND USE FOR PRODUCING 4-(3,5-BIS(2-HYDROXYPHENYL)-1H-1,2,4-TRIAZOL-1-YL)BENZOIC ACID
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The present invention relates to a crystalline form of 2-(2-hydroxyphenyl) benz [e] [1, 3] oxazin-4-one, a process for production thereof and its use in the preparation of 4- (3, 5-bis (2-hydroxyphenyl)-1H-1, 2, 4-triazol-1-yl) benzoic acid. The improved process for the preparation 4-(3,5-bis (2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl) benzoic acid (Deferasirox), wherein salicylic chloride is reacted with salicylamide in presence of a solvent to give acyl compound, which is heated to higher temperature in-situ to undergo cyclization to obtain crystalline form of 2-(2-hydroxyphenyl) benz [e] [1, 3] oxazin-4-on and further reaction with hydrazino benzoic acid to give 4-(3,5- bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl)benzoic acid.
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(2010/04/06)
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- Complex formation of ICL670 and related ligands with FeIII and FeII
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Complex formation of 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (ICL670, H3Lx), 4-[3,5-bis(2-hydroxyphenyl)-1,2,4- triazol-1-yl]benzosulfonic acid (H3Ly), and 3,5-bis(2-hydroxyphenyl)-1-phenyl-1,2,4-triazole (H2Lz) with Fe3+ and Fe2+ was investigated in H2O and in H2O/DMSO mixtures by potentiometry, spectrophotometry and cyclic voltammetry. ICL670 has previously been considered as a promising drug for an oral treatment of iron overload. In this paper, the stability and redox properties of the various FeII and FeIII complexes were elucidated with a particular focus on their potential involvement in the generation of oxidative stress. The overall stability constants of [Fe III(Lx)] and [FeIII(Lx) 2]3- (25 °C, 0.1 M KCl in H2O) are log β1 = 22.0 and log β2 = 36.9, respectively. The affinity of these ligands for Fe2+ is remarkably poor. In particular, the 1:2 complexes [FeIII(Lx)2]4- and [FeII(Ly)2]4- were found to be less stable. As a consequence, the redox chemistry of the [Fe III(Lx)]/[FeII(Lx)]- and the [FeIII(Lx)2]3-/[Fe II(Lx)2]4- couples differs significantly. [FeIII(Lx)2]3- is a very weak oxidizing agent (E1/2 is approximately -0.6 V versus NHE) and reduction of [FeIII(Lx)2]3- is not anticipated under physiological conditions. The reduction potential of the [FeIII(Lx)]/[FeII(Lx)]- couple is considerably less negative and was estimated to be +0.1 V (versus NHE). The possible roles of the various Fe complexes as catalysts for the Fenton reaction in biological media are discussed. The crystal structures of H 3LX, Na[Fe(Lz)2]·4EtOH, Na[Al(Lz)2]· 4EtOH, and [Cu(Lz) (pyridine)]2 were investigated by single-crystal X-ray diffraction, and the possible influence of the particular steric requirements of these ligands on the stability of the metal complexes has been analyzed. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).
- Steinhauser, Stefan,Heinz, Uwe,Bartholomae, Mark,Weyliermueller, Thomas,Nick, Hanspeter,Hegetschweiler, Kaspar
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p. 4177 - 4192
(2007/10/03)
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- Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators
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The use is described of 3,5-diphenyl-1,2,4-triazoles of the formula I in which R1-R5are as defined in the description. The compounds have useful pharmaceutical properties and are particularly active as iron chelators. They can be used for the treatment of iron overload in warm-blooded animals.
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