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 descriptors and 3224 molecular descriptors. A subset of 5 descriptors was selected from the aforementioned pool by means of Monte Carlo (MC) feature selection coupled to multiple linear regression (MLR). Predictive QSAR models were then constructed by MLR, support vector machine and artificial neural network, which afforded good predictive performance as deduced from internal and external validation. The investigated models are capable of accounting for the origins of aldose reductase inhibitory activity and could be utilized in predicting this property in screening for novel and robust compounds.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Nantasenamat C,Monnor T,Worachartcheewan A,Mandi P,Isarankura-Na-Ayudhya C,Prachayasittikul Vdoi
10.1016/j.ejmech.2014.02.043subject
Has Abstractpub_date
2014-04-09 00:00:00pages
352-9eissn
0223-5234issn
1768-3254pii
S0223-5234(14)00163-9journal_volume
76pub_type
杂志文章abstract::Type 2 diabetes (T2D) is a lifestyle disease affecting millions of people worldwide. Various therapies are available for the management of T2D and dipeptidyl peptidase-IV (DPP-IV) inhibition has emerged as a promising therapy for the treatment of type 2 diabetes (T2D). Here we report design, synthesis and in vitro eff...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.11.041
更新日期:2015-01-27 00:00:00
abstract::In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compoun...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.04.012
更新日期:2019-07-01 00:00:00
abstract::Salification of new drug substances in order to improve physico-chemical or solid-state properties (e.g. dissolution rate or solubility, appropriate workup process, storage for further industrial and marketing development) is a well-accepted procedure. Amino acids, like aspartic acid, lysine or arginine take a great p...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2013.11.045
更新日期:2014-03-03 00:00:00
abstract::SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) is a lipid phosphatase that produce phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) from phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3), and is involved in many diseases such as neurodegenerative diseases. A recent report demonstrating that SHIP2 inhibit...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.07.071
更新日期:2018-09-05 00:00:00
abstract::ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically. Aiming to explore new potent inhibitors, a series of 2-amino-4-(1-piperidine) pyridine derivatives that stabilized a novel DFG-shifted conformation in the kinase domain of ALK were d...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.06.043
更新日期:2019-10-01 00:00:00
abstract::Selective COX-2 inhibitors have attracted much attention in recent times in the design of non-steroidal anti-inflammatory agents (NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of diaryl furanones that acts as selective COX-2 inhibitor using Molecu...
journal_title:European journal of medicinal chemistry
pub_type: 更正并重新发布的文章,杂志文章
doi:10.1016/j.ejmech.2004.06.005
更新日期:2004-10-01 00:00:00
abstract::Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 microM. In particular,...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2007.09.009
更新日期:2008-06-01 00:00:00
abstract::A series of 4'-[1,2,3]triazole-2'-deoxy-2'-fluoro-β-d-arabinofuranosylcytosines (9-17) were prepared by Cu(I)-mediated [3 + 2] cycloaddition reactions (CuAAC) of 1-(4'-azido-2'-deoxy-2'-fluoro-β-d-arabinofuranosyl)cytosine (1) with appropriate alkynes in good yields. Their structures were fully established by (1)H NMR...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.02.042
更新日期:2013-05-01 00:00:00
abstract::The monoamine oxidase (MAO) enzymes are of considerable pharmacological interest and inhibitors are used in the clinic for the treatment of major depressive disorder and Parkinson's disease. A limited number of studies have shown that the quinone class of compounds possesses MAO inhibition properties. Most notable amo...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.04.055
更新日期:2017-07-28 00:00:00
abstract::Frequency of tuberculosis and malaria is progressively increasing worldwide. New emerging strain of bacterium and resistance to currently available drugs make this field more conscientious and alarming. In this connection a series of substituted quinolinyl chalcones and substituted quinolinyl pyrimidines were synthesi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.10.011
更新日期:2009-05-01 00:00:00
abstract::Sigma 1 receptors are associated with neurodegenerative and psychiatric disorders. These receptors, via their chaperoning functions that counteract endoplasmic reticulum stress and block neurodegeneration, may serve as a target for a new generation of antidepressants or neuroprotective agents. The involvement of these...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.10.053
更新日期:2015-01-07 00:00:00
abstract::The oxidation of bioorganic materials by air and, particularly, the oxidative stress involved in the cell loss and other pathologies associated with neurodegenerative diseases (NDs) are of enormous social and economic importance. NDs generally involve free radical reactions, beginning with the formation of an initiati...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.03.061
更新日期:2017-06-16 00:00:00
abstract::A series of 3-O-acylated (-)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert-butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (-)-epigallocatechins penta-O-tert-butyldimethylsi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.10.011
更新日期:2010-12-01 00:00:00
abstract::We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as α7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for α7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitutio...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.11.001
更新日期:2016-01-01 00:00:00
abstract::On the basis of the affinities at the alpha1a-, alpha1b- and alpha1d-adrenoceptors and the 5-HT1A receptor of a previous series of sixteen 2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes ortho monosubstituted at the phenoxy moiety, a number of ortho disubstituted analogues were designed, synthesized in both the enan...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2006.04.004
更新日期:2006-09-01 00:00:00
abstract::Several 9-benzyl-N6-cycloalkyl-2-phenyladenines, 9-benzyl-N6-cycloalkyl-2-phenyl-8-azaadenines and 4-cycloalkylamino-1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5-c]pyridines were prepared and assayed as A1 adenosine receptor ligands. The 1H-1,2,3-triazolo[4,5-c]pyridines were obtained starting from N,N-diethyl-1-benzyl-4-c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2003.09.003
更新日期:2003-11-01 00:00:00
abstract::Activating mutations of REarrange during Transfection (RET) kinase frequently occur in human thyroid and lung cancers. An enormous effort has been devoted to discover potent and selective inhibitors of RET. Selective and potent inhibitors against constitutively active RET mutants are rare to date as identification of ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.10.050
更新日期:2017-01-05 00:00:00
abstract::A series of novel (5-oxazolyl)phenyl amine derivatives were synthesized and their antiviral activities against the hepatitis C virus (HCV) and the coxsackie virus B3 (CVB3) and B6 (CVB6) were evaluated in vitro. Bioassays showed that the synthesized compounds 17a1, 17a4, 17a6, 17b1, 17d1, 17e2 and 17g3 exhibited poten...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.07.053
更新日期:2013-11-01 00:00:00
abstract::Several pentacyclic triterpenoic acids have shown noteworthy antitumor activity, among them betulinic acid as well as oleanolic acid and derivatives thereof. Glycyrrhetinic acid (GA) exhibits some cytotoxic activity albeit this compound is not as active as betulinic acid, but GA came in the focus of scientific interes...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.11.024
更新日期:2014-01-24 00:00:00
abstract::There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl- and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no i...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.07.047
更新日期:2019-11-01 00:00:00
abstract::Cancer remains the most serious disease that threatens human health. Molecularly targeted cancer therapies, specifically small-molecule protein kinase inhibitors, form an important part of cancer therapy. Targeted covalent modification represents a proven approach to drug discovery with the recent FDA approvals of afa...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.09.024
更新日期:2017-12-15 00:00:00
abstract::Herein, we report on the synthesis, spectral, crystallographic and electrochemical properties of a small library of N-substituted 2-ferrocenyl-1,3-thiazolidin-4-ones, designed as novel GABAA benzodiazepine-binding site ligands. The anxiolytic properties of the title compounds were evaluated in several different in viv...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.05.062
更新日期:2014-08-18 00:00:00
abstract::Levamisole, the imidazo[2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but dif...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.02.064
更新日期:2011-06-01 00:00:00
abstract::The synthesis of some novel imidazole-based dicationic sulfonophanes incorporating various spacer units is described. All the sulphonophanes exhibit good antibacterial and antifungal activity against five bacterial strains Bacillus subtilis, Staphylococcus aureus, Vibrio cholera, Escherichia coli, Proteus vulgaris and...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.03.063
更新日期:2011-07-01 00:00:00
abstract::The synthesis of some 4-S-(4(1)-amino-5(1)-oxo-6(1)-substituted benzyl-4(1),5(1)-dihydro-1(1),2(1),4(1)-triazin-3-yl)mercaptoacetyl-3-arylsydnones by the reaction of 3-aryl-4-bromoacetylsydnones with 6-substituted-4-amino-3-mercapto-1,2,4-triazin-5-ones is described. The IR, (1)H NMR, mass spectra and elemental analys...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.02.003
更新日期:2008-12-01 00:00:00
abstract::Structure-activity relationships for rigid analogues of combretastatin A-4 (CA-4) were investigated, leading to the discovery of a series of 3,4-diaryl-1,2,5-oxadiazole-N-oxides. Among them, 7n' and 7n'' showed remarkable antiproliferative activities against three cancer cell lines in nanomolar concentrations. Interes...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.05.036
更新日期:2019-09-15 00:00:00
abstract::Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR)...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.09.032
更新日期:2018-10-05 00:00:00
abstract::Vesicular Glutamate Transporters (VGLUTs) allow the loading of presynapic glutamate vesicles and thus play a critical role in glutamatergic synaptic transmission. VGLUTs have proved to be involved in several major neuropathologies and directly correlated to clinical dementia in Alzheimer and Parkinson's disease. Accor...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.03.056
更新日期:2014-05-06 00:00:00
abstract::Inflammation comprises the reaction of the body to injury, in which a series of changes of the terminal vascular bed, blood, and connective tissue tends to eliminate the injurious agent and to repair the damaged tissue. It is a complex process, which involves the release of diverse regulatory mediators. The current an...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.12.059
更新日期:2018-06-10 00:00:00
abstract::Metallodrugs offer potential for unique mechanism of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to t...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.04.007
更新日期:2017-12-15 00:00:00