当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 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.

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.

Abstract：

:Xanthine oxidase (XO), a versatile metalloflavoprotein enzyme, catalyzes the oxidative hydroxylation of hypoxanthine and xanthine to uric acid in purine catabolism while simultaneously producing reactive oxygen species. Both lead to the gout-causing hyperuricemia and oxidative damage of the tissues where overactivity of XO is present. Over the past years, significant progress and efforts towards the discovery and development of new XO inhibitors have been made and we believe that not only experts in the field, but also general readership would benefit from a review that addresses this topic. Accordingly, the aim of this article was to overview and select the most potent recently reported XO inhibitors and to compare their structures, mechanisms of action, potency and effectiveness of their inhibitory activity, in silico calculated physico-chemical properties as well as predicted pharmacokinetics and toxicity. Derivatives of imidazole, 1,3-thiazole and pyrimidine proved to be more potent than febuxostat while also displaying/possessing favorable predicted physico-chemical, pharmacokinetic and toxicological properties. Although being structurally similar to febuxostat, these optimized inhibitors bear some structural freshness and could be adopted as hits for hit-to-lead development and further evaluation by in vivo studies towards novel drug candidates, and represent valuable model structures for design of novel XO inhibitors.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Šmelcerović A,Tomović K,Šmelcerović Ž,Petronijević Ž,Kocić G,Tomašič T,Jakopin Ž,Anderluh M

doi

10.1016/j.ejmech.2017.04.031

subject

Has Abstract

pub_date

2017-07-28 00:00:00

pages

491-516

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30289-1

journal_volume

135

pub_type

杂志文章,评审

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Heparin-polynitroxides: synthesis and preliminary evaluation as cardiovascular EPR/MR imaging probes and extracellular space-targeted antioxidants.

    abstract：:We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which nitroxide moieties are linked either to uronic acid or glycosamine residues of the heparin macromolecule. HPNs have low anticoagulant activity, possess superoxide scavenging properties, bind to the vascular endothelium/extra-cellular mat...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.09.028

    authors： Kleschyov AL,Sen' V,Golubev V,Münnemann K,Hinderberger D,Lackner KJ,Weber S,Terekhov M,Schreiber LM,Münzel T

    更新日期：2012-12-01 00:00:00

  • Predictive QSAR modeling of aldose reductase inhibitors using Monte Carlo feature selection.

    abstract：:This study explores the chemical space and quantitative structure-activity relationship (QSAR) of a set of 60 sulfonylpyridazinones with aldose reductase inhibitory activity. The physicochemical properties of the investigated compounds were described by a total of 3230 descriptors comprising of 6 quantum chemical desc...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.02.043

    authors： Nantasenamat C,Monnor T,Worachartcheewan A,Mandi P,Isarankura-Na-Ayudhya C,Prachayasittikul V

    更新日期：2014-04-09 00:00:00

  • Linked pyridinyl-thiadiazoles: Design and synthesis as potential candidate for treatment of XDR and MDR tuberculosis.

    abstract：:Multi-drug resistant (MDR) and extremely drug resistant (XDR) Mycobacterium tuberculosis strains have turned tuberculosis (TB) as "on the verge of eradication" to "most life threatening" disease. Furthermore, synergy with HIV and other immunosuppressive disease have strengthened its prevalence. This research reports s...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.07.039

    authors： Mahajan NS,Dhawale SC

    更新日期：2015-09-18 00:00:00

  • Health protective effects of carotenoids and their interactions with other biological antioxidants.

    abstract：:Carotenoids are natural pigments attracting attention of physicists, chemists and biologists due to their multiple functions in the nature. While carotenoids have unusually high extinction coefficients, they do not exhibit adequate emission. This fact has resulted in detailed studies of photophysical and photochemical...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2013.09.054

    authors： Jomova K,Valko M

    更新日期：2013-01-01 00:00:00

  • Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review.

    abstract：:Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been gr...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2015.06.026

    authors： Yehye WA,Rahman NA,Ariffin A,Abd Hamid SB,Alhadi AA,Kadir FA,Yaeghoobi M

    更新日期：2015-08-28 00:00:00

  • Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain.

    abstract：:A series of 3-(4-(aminoalkoxy)benzylidene)-chroman-4-ones 7a-r were designed and synthesized as analogs of homoisoflavonoids which are well known natural products with diverse pharmacological properties related to Alzheimer's disease. The in vitro anti-cholinesterase activity of designed compounds 7a-r against AChE an...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.04.055

    authors： Pourshojaei Y,Gouranourimi A,Hekmat S,Asadipour A,Rahmani-Nezhad S,Moradi A,Nadri H,Moghadam FH,Emami S,Foroumadi A,Shafiee A

    更新日期：2015-06-05 00:00:00

  • Benzofuran-isatin hybrids and their in vitro anti-mycobacterial activities against multi-drug resistant Mycobacterium tuberculosis.

    abstract：:A series of benzofuran-isatin hybrids 6a-n and 7a-g linked by alkyl linkers were designed and synthesized. Among them, hybrids 6a-l and 7a-g were assessed for their in vitro anti-mycobacterial activities against two multi-drug resistant Mycobacterium tuberculosis (MDR-MTB) strains and the cytotoxicity towards CHO cell...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.111678

    authors： Gao F,Ye L,Wang Y,Kong F,Zhao S,Xiao J,Huang G

    更新日期：2019-12-01 00:00:00

  • Design, synthesis and anticancer properties of novel oxa/azaspiro[4,5]trienones as potent apoptosis inducers through mitochondrial disruption.

    abstract：:A series of twenty seven oxa/azaspiro[4,5]trienone derivatives were synthesized and their anticancer properties have been explored. GI50 values of all these compounds were evaluated against four types of human cancer cell lines, i.e. MCF-7 (breast), DU-145 (prostate), A549 (lung) and HepG2 (liver). Five compounds of t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.06.050

    authors： Yugandhar D,Nayak VL,Archana S,Shekar KC,Srivastava AK

    更新日期：2015-08-28 00:00:00

  • Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors.

    abstract：:A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholine...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.12.044

    authors： Wang B,Mai YC,Li Y,Hou JQ,Huang SL,Ou TM,Tan JH,An LK,Li D,Gu LQ,Huang ZS

    更新日期：2010-04-01 00:00:00

  • Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates.

    abstract：:The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymp...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.11.013

    authors： Ibáñez E,Plano D,Font M,Calvo A,Prior C,Palop JA,Sanmartín C

    更新日期：2011-01-01 00:00:00

  • The 4-N-acyl and 4-N-alkyl gemcitabine analogues with silicon-fluoride-acceptor: Application to 18F-Radiolabeling.

    abstract：:The coupling of gemcitabine with functionalized carboxylic acids using peptide coupling conditions afforded 4-N-alkanoyl analogues with a terminal alkyne or azido moiety. Reaction of 4-N-tosylgemcitabine with azidoalkyl amine provided 4-N-alkyl gemcitabine with a terminal azido group. Click reaction with silane buildi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.02.017

    authors： Gonzalez C,Sanchez A,Collins J,Lisova K,Lee JT,Michael van Dam R,Alejandro Barbieri M,Ramachandran C,Wnuk SF

    更新日期：2018-03-25 00:00:00

  • Photocytotoxic oxovanadium(IV) complexes of ferrocenyl-terpyridine and acetylacetonate derivatives.

    abstract：:Oxovanadium(IV) complexes [VO(Fc-tpy)(acac)](ClO4) (1), [VO(Fc-tpy)(nap-acac)](ClO4) (2), [VO(Fc-tpy)(py-acac)](ClO4) (3) and [VO(Ph-tpy)(py-acac)](ClO4) (4) of 4'-ferrocenyl-2,2':6',2"-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2"-terpyridine (Ph-tpy) having monoanionic acetylacetonate (acac), naphthylacetylacetonate...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.01.003

    authors： Balaji B,Balakrishnan B,Perumalla S,Karande AA,Chakravarty AR

    更新日期：2015-03-06 00:00:00

  • Umbelliferone aminoalkyl derivatives, a new class of squalene-hopene cyclase inhibitors.

    abstract：:The synthesis is described of several aminoalkyl derivatives of coumarin, obtained in good yields under microwave or high-intensity ultrasound irradiation. These compounds proved uniformly active as inhibitors of squalene-hopene cyclase (SHC) from Alicyclobacillus acidocaldarius. Their design stemmed from our recent f...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2004.06.010

    authors： Cravotto G,Balliano G,Tagliapietra S,Palmisano G,Penoni A

    更新日期：2004-11-01 00:00:00

  • Salicylanilides as inhibitors of the protein tyrosine kinase epidermal growth factor receptor.

    abstract：:A pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase and a putative binding mode of 4-anilinoquinazoline suggest that a salicylic acid function could serve as the pharmacophore replacement of a pyrimidine ring. Superpositions by CAMM of salicylanilid...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2003.09.010

    authors： Liechti C,Séquin U,Bold G,Furet P,Meyer T,Traxler P

    更新日期：2004-01-01 00:00:00

  • Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents.

    abstract：:A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, 11s, 11v, 11x and 11y exhibited potent antiproliferative activity with IC50 value of lower than 10 μM against seven human tumor cell lines, and N-(3-methoxyph...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.05.088

    authors： Su T,Zhu J,Sun R,Zhang H,Huang Q,Zhang X,Du R,Qiu L,Cao R

    更新日期：2019-09-15 00:00:00

  • Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect.

    abstract：:Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-β-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-β-carboline derivatives were designed, synthesized and evaluated for ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.09.028

    authors： Zheng H,Wu Y,Sun B,Cheng C,Qiao Y,Jiang Y,Zhao S,Xie Z,Tan J,Lou H

    更新日期：2018-10-05 00:00:00

  • Synthetic studies on cyclic octapeptides: Yunnanin F and Hymenistatin.

    abstract：:Two biologically active cyclic peptides, Yunnanin F 8 and Hymenistatin 16 were synthesized and the structures were established on the basis of analytical, IR, NMR and mass spectral data. The newly synthesized compounds were screened for their antimicrobial and pharmacological activities. These cyclic octapeptides have...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2004.11.013

    authors： Poojary B,Belagali SL

    更新日期：2005-04-01 00:00:00

  • Design and synthesis of some new pyrazolyl-pyrazolines as potential anti-inflammatory, analgesic and antibacterial agents.

    abstract：:In the present study, an efficient synthesis of some new substituted pyrazoline derivatives linked to a substituted pyrazole scaffold was performed by a multistep reaction sequences and compounds were screened for their anti-inflammatory, analgesic and antibacterial activities. The preliminary results revealed that th...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.07.002

    authors： Viveka S,Dinesha,Shama P,Nagaraja GK,Ballav S,Kerkar S

    更新日期：2015-08-28 00:00:00

  • Synthesis and anti-proliferative activity evaluation of novel benzo[d][1,3] dioxoles-fused 1,4-thiazepines.

    abstract：:Benzo[d][1,3]dioxoles 1,4-thiazepines remarkable antitumor activities, benzo[d][1,3]dioxoles-fused 1,4-thiazepines, which combine two biologically active heterocyclic cores, are expected to be of pharmacological interest, We therefore envisaged that integrating 1,4-thiazepine and benzo[d][1,3]dioxole moieties in one m...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.01.021

    authors： Wu L,Yang X,Peng Q,Sun G

    更新日期：2017-02-15 00:00:00

  • Methylsulfanylpyridine based diheteroaryl isocombretastatin analogs as potent anti-proliferative agents.

    abstract：:Isocombretastatins are the not isomerizable 1,1-diarylethene isomers of combretastatins. Both families of antimitotics are poorly soluble and new analogs with improved water solubility are needed. The ubiquitous 3,4,5-trimethoxyphenyl ring and most of its replacements contribute to the solubility problem. 39 new compo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112933

    authors： Álvarez R,Aramburu L,Gajate C,Vicente-Blázquez A,Mollinedo F,Medarde M,Peláez R

    更新日期：2021-01-01 00:00:00

  • Novel deoxyvasicinone derivatives as potent multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

    abstract：:A series of multitarget ligands was designed by introducing several structurally diverse aminoacetamide groups at position 6 of the deoxyvasicinone group, with the aim of obtaining novel multifunctional anti-Alzheimer's disease agents using deoxyvasicinone as the substrate. In vitro studies showed that almost all of t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.09.008

    authors： Ma F,Du H

    更新日期：2017-11-10 00:00:00

  • 2-[N-Alkyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines as anticancer agents inhibitors of folate enzymes.

    abstract：:Based on our previous results on the ascertained potent growth inhibition effect against a panel of 60 human tumors cell lines at National Cancer Institute of Bethesda (NCI), we have synthesized a novel series of thirty-one 2-[N-methyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines (1-31). The lead comp...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.01.048

    authors： Piras S,Carta A,Briguglio I,Corona P,Paglietti G,Luciani R,Costi MP,Ferrari S

    更新日期：2014-03-21 00:00:00

  • Synthesis, characterization and anticancer screening of some novel piperonyl-tetrazole derivatives.

    abstract：:A series of new 1,2-substituted tetrazole derivatives were synthesized and evaluated on MCF-7 (ER positive), MDA-MB-231 and ZR-75 (ER negative) breast cancer cell lines. Out of the fourteen compounds, three compounds 10, 12 and 14 showed higher inhibitory effects on MCF-7 cells. Whereas, compound 8 exhibited higher in...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.11.008

    authors： Arshad M,Bhat AR,Pokharel S,Kim JE,Lee EJ,Athar F,Choi I

    更新日期：2014-01-01 00:00:00

  • Development of novel 4-aminopyridine derivatives as potential treatments for neurological injury and disease.

    abstract：:The amine position of the K+ channel blocker 4-aminopyridine was functionalized to form amide, carbamate and urea derivatives in an attempt to identify novel compounds which restore conduction in injured spinal cord. Eight derivatives were tested in vitro, using a double sucrose gap chamber, for the ability to restore...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.04.017

    authors： Smith DT,Shi R,Borgens RB,McBride JM,Jackson K,Byrn SR

    更新日期：2005-09-01 00:00:00

  • Novel series of 6-(2-substitutedacetamido)-4-anilinoquinazolines as EGFR-ERK signal transduction inhibitors in MCF-7 breast cancer cells.

    abstract：:Epidermal growth factor receptor (EGFR) signaling pathway has been previously investigated for its significant role in the progression of different types of malignant tumors, where development of small molecules targeting EGFR is well known strategy for design of antitumor agents. Herein, we report the design and synt...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.06.024

    authors： Ismail RSM,Abou-Seri SM,Eldehna WM,Ismail NSM,Elgazwi SM,Ghabbour HA,Ahmed MS,Halaweish FT,Abou El Ella DA

    更新日期：2018-07-15 00:00:00

  • Prenylflavonoids and prenyl/alkyl-phloroacetophenones: synthesis and antitumour biological evaluation.

    abstract：:Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.06.025

    authors： Basabe P,de Román M,Marcos IS,Diez D,Blanco A,Bodero O,Mollinedo F,Sierra BG,Urones JG

    更新日期：2010-09-01 00:00:00

  • Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.

    abstract：:Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resis...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.02.047

    authors： Desplat V,Vincenzi M,Lucas R,Moreau S,Savrimoutou S,Pinaud N,Lesbordes J,Peyrilles E,Marchivie M,Routier S,Sonnet P,Rossi F,Ronga L,Guillon J

    更新日期：2016-05-04 00:00:00

  • Optimisation of correlation weights of SMILES invariants for modelling oral quail toxicity.

    abstract：:The SMILES (simplified molecular input line entry system) nomenclature was used to elucidate the molecular structure in constructing the quantitative structure-property/activity relationships (QSPR/QSAR) for predicting quail toxicity after oral exposure. The presence of chemical elements in different electronic states...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.11.018

    authors： Toropov AA,Benfenati E

    更新日期：2007-05-01 00:00:00

  • Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity.

    abstract：:Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinat...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112116

    authors： Froux L,Elbahnsi A,Boucherle B,Billet A,Baatallah N,Hoffmann B,Alliot J,Zelli R,Zeinyeh W,Haudecoeur R,Chevalier B,Fortuné A,Mirval S,Simard C,Lehn P,Mornon JP,Hinzpeter A,Becq F,Callebaut I,Décout JL

    更新日期：2020-03-15 00:00:00

  • Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring.

    abstract：:Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having tra...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.01.037

    authors： Kumari G,Nutan,Modi M,Gupta SK,Singh RK

    更新日期：2011-04-01 00:00:00