Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors.


:A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK cells. Further two bicyclic compounds with a rigidified carboxylic acid side chain were included in this study. The results of the biological tests indicated that most ω-imidazole alkanoic and alkenoic acid derivatives exhibit the highest potencies as GABA uptake inhibitors at mGAT3.


Eur J Med Chem


Hack S,Wörlein B,Höfner G,Pabel J,Wanner KT




Has Abstract


2011-05-01 00:00:00














  • Chemistry, biosynthesis and biological activity of terpenoids and meroterpenoids in bacteria and fungi isolated from different marine habitats.

    abstract::The marine environment with its vast biological diversity encompasses many organisms that produce bioactive natural products. Marine microorganisms are rich sources of compounds from many structural classes with a multitude of biological activities. The biosynthesis of microbial natural products depends on a variety o...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Gozari M,Alborz M,El-Seedi HR,Jassbi AR

    更新日期:2021-01-15 00:00:00

  • Exploring nature profits: development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids.

    abstract::Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neur...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Teixeira J,Silva T,Benfeito S,Gaspar A,Garrido EM,Garrido J,Borges F

    更新日期:2013-04-01 00:00:00

  • Homology modeling in tandem with 3D-QSAR analyses: a computational approach to depict the agonist binding site of the human CB2 receptor.

    abstract::CB2 receptor belongs to the large family of G-protein coupled receptors (GPCRs) controlling a wide variety of signal transduction. The recent crystallographic determination of human β2 adrenoreceptor and its high sequence similarity with human CB2 receptor (hCB2) prompted us to compute a theoretical model of hCB2 base...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cichero E,Ligresti A,Allarà M,di Marzo V,Lazzati Z,D'Ursi P,Marabotti A,Milanesi L,Spallarossa A,Ranise A,Fossa P

    更新日期:2011-09-01 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


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

    更新日期:2005-09-01 00:00:00

  • Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives.

    abstract::New anti-tubercular agents, imidazo[1,2-a]pyridine-2-carboxamide derivatives (5a-q) have been designed and synthesized. The structural considerations of the designed molecules were further supported by the docking study with a long-chain enoyl-acyl carrier protein reductase (InhA). The chemical structures of the new c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jose G,Suresha Kumara TH,Nagendrappa G,Sowmya HB,Sriram D,Yogeeswari P,Sridevi JP,Guru Row TN,Hosamani AA,Sujan Ganapathy PS,Chandrika N,Narendra LV

    更新日期:2015-01-07 00:00:00

  • Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflammatory and analgesic activities.

    abstract::The 5,10-dihydro-2-thioxo-pyrimido[4,5-b]quinolines (2a-c) and its oxidized form 3 were prepared and used as key intermediates for the synthesis of thiazolo[3',2':1,2]pyrimido[4,5-b]-quinolines (5a-c), isoxazolo[5'',4'':4',5']thiazolo[3',2':1,2]pyrimido[4,5-b]quinolines (6a-c), 4-chloro-2-methylthio-pyrimido[4,5-b]qui...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: El-Gazzar AB,Youssef MM,Youssef AM,Abu-Hashem AA,Badria FA

    更新日期:2009-02-01 00:00:00

  • Identification of novel aminothiazole and aminothiadiazole conjugated cyanopyridines as selective CHK1 inhibitors.

    abstract::Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential anti-tumor agents. Novel series of cyanopyridyl-aminothiadiazoles (synthesized from reaction of 1-(3-cyano-4,6-diphenylpyridin-2-yl)-3-phenylthiourea (14) with hydrazonoyl halides) and cyanopyridyl-aminothiazolyl-thiadiazoles (synthesized fr...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,收录出版


    authors: Gomha SM,Abdulla MM,Abou-Seri SM

    更新日期:2015-03-06 00:00:00

  • Design, synthesis and biological evaluation of novel 2-methoxyestradiol analogs as dual selective estrogen receptor modulators (SERMs) and antiangiogenic agents.

    abstract::2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological evaluation was performed on their anti-proliferative activities a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lao K,Wang Y,Chen M,Zhang J,You Q,Xiang H

    更新日期:2017-10-20 00:00:00

  • Design, synthesis and antitumor evaluation of new 1,8-naphthalimide derivatives targeting nuclear DNA.

    abstract::Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liang GB,Wei JH,Jiang H,Huang RZ,Qin JT,Wang HL,Wang HS,Zhang Y

    更新日期:2021-01-15 00:00:00

  • Synthesis and biological evaluation of Schizandrin derivatives as potential anti-cancer agents.

    abstract::A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Amujuri D,Siva B,Poornima B,Sirisha K,Sarma AVS,Lakshma Nayak V,Tiwari AK,Purushotham U,Suresh Babu K

    更新日期:2018-04-10 00:00:00

  • Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine.

    abstract::A number of derivatives of isoxazolo[4,5-d]pyrimidine were prepared with structures similar to that of purine. Condensation of the hydrazide of 4-amino-5-benzoylisoxazolo-3-carboxylic acid 2 with ethyloxalyl chloride followed by cyclization gave 3-oxdiazolo-[1,3,4]-4-amino-5-benzoylisoxazole 7 which, upon cyclization ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wagner E,Al-Kadasi K,Zimecki M,Sawka-Dobrowolska W

    更新日期:2008-11-01 00:00:00

  • Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones.

    abstract::The present work involves design and synthesis of new substituted 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones (4a-s, 5a-h), starting from 4-hydroxybenzaldehyde. The final compounds were screened for their in vivo anticonvulsant activity by MES, scPTZ and 6 Hz methods, while their anti-inflammatory screening was per...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ulloora S,Shabaraya R,Ranganathan R,Adhikari AV

    更新日期:2013-01-01 00:00:00

  • Design and one-pot synthesis of alpha-aminophosphonates and bis(alpha-aminophosphonates) by iron(III) chloride and cytotoxic activity.

    abstract::In this study, we used a solution of FeCl(3) in THF to facilitate the Mannich-type reaction of aldehyde, amine and phosphite compounds to form corresponding alpha-aminophosphonates in a one-pot, three-component reaction. Selected alpha-aminophosphonates were entered into a biological assay test and were studied by doc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rezaei Z,Firouzabadi H,Iranpoor N,Ghaderi A,Jafari MR,Jafari AA,Zare HR

    更新日期:2009-11-01 00:00:00

  • Plant-derived mPGES-1 inhibitors or suppressors: A new emerging trend in the search for small molecules to combat inflammation.

    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


    authors: Khan H,Rengasamy KRR,Pervaiz A,Nabavi SM,Atanasov AG,Kamal MA

    更新日期:2018-06-10 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


    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

  • Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives.

    abstract::A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluate...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Teng YO,Zhao HY,Wang J,Liu H,Gao ML,Zhou Y,Han KL,Fan ZC,Zhang YM,Sun H,Yu P

    更新日期:2016-04-13 00:00:00

  • Synthesis and characterization of binary and ternary complexes of diclofenac with a methyl-beta-CD and monoethanolamine and in vitro transdermal evaluation.

    abstract::Here, we describe the chemical characterization of the inclusion complex between diclofenac (DCF) and methyl-beta-cyclodextrin (M-beta-CD) in the presence or absence of monoethanolamine (MEA). Several techniques were used to analyze the complex both in solution and in the solid state. Solubility of DCF was increased b...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mora MJ,Longhi MR,Granero GE

    更新日期:2010-09-01 00:00:00

  • Synthesis, characterization, antiamoebic activity and cytotoxicity of novel 2-(quinolin-8-yloxy) acetohydrazones and their cyclized products (1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives).

    abstract::A series of 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives were synthesized by the cyclization of novel 2-(quinolin-8-yloxy) acetohydrazones. In vitro antiamoebic activity was performed against HM1: IMSS strain of Entamoeba histolytica. The results showed that all the 2-(quinolin-8-yloxy) acetohydrazones were m...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Hayat F,Salahuddin A,Zargan J,Azam A

    更新日期:2010-12-01 00:00:00

  • Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation.

    abstract::A series of chalcone derivatives were synthesized and evaluated for their μ-calpain and cathepsin B inhibitory activities. Among the tested chalcone derivatives, two compounds, 7 and 11, showed potent inhibitory activities against μ-calpain and cathepsin B and were selected for further evaluation. Compounds 7 and 11 s...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jeon KH,Lee E,Jun KY,Eom JE,Kwak SY,Na Y,Kwon Y

    更新日期:2016-10-04 00:00:00

  • Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents.

    abstract::A series of forty different pyrazole containing benzimidazole hybrids (6-45) have been designed, synthesized and evaluated for their potential anti-proliferative activity against three human tumor cell lines - lung (A549), breast (MCF-7), and cervical (HeLa). Some of the compounds, specifically 9, 17, and 28, showed p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Reddy TS,Kulhari H,Reddy VG,Bansal V,Kamal A,Shukla R

    更新日期:2015-08-28 00:00:00

  • Synthesis, molecular modeling and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as anti-tumor agents.

    abstract::A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and el...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liu K,Lu X,Zhang HJ,Sun J,Zhu HL

    更新日期:2012-01-01 00:00:00

  • Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.

    abstract::Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with bi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gul R,Rauf MK,Badshah A,Azam SS,Tahir MN,Khan A

    更新日期:2014-10-06 00:00:00

  • Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3'-C-methyl-ribonucleosides as antitumor agents.

    abstract::A series of N6-aminopurine-9-β-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N6-position with a small group like hydroxy, methoxy or amino group or at C2(N6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N6-Hydrazino-9-β-D-ribofuranos...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cappellacci L,Petrelli R,Franchetti P,Vita P,Kusumanchi P,Kumar M,Jayaram HN,Zhou B,Yen Y,Grifantini M

    更新日期:2011-05-01 00:00:00

  • pH and reduction dual-responsive dipeptide cationic lipids with α-tocopherol hydrophobic tail for efficient gene delivery.

    abstract::A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-s...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liu Q,Su RC,Yi WJ,Zheng LT,Lu SS,Zhao ZG

    更新日期:2017-03-31 00:00:00

  • Tetracyclic indolines as a novel class of β-lactam-selective resistance-modifying agent for MRSA.

    abstract::Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relatio...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhu Y,Cleaver L,Wang W,Podoll JD,Walls S,Jolly A,Wang X

    更新日期:2017-01-05 00:00:00

  • Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds.

    abstract::Lapachol is an abundant prenyl naphthoquinone occurring in Brazilian Bignoniaceae that was clinically used, in former times, as an antimalarial drug, despite its moderate effect. Aiming to search for potentially better antimalarials, a series of 1,2,3-triazole derivatives was synthesized by chemical modification of la...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Brandão GC,Rocha Missias FC,Arantes LM,Soares LF,Roy KK,Doerksen RJ,Braga de Oliveira A,Pereira GR

    更新日期:2018-02-10 00:00:00

  • Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study.

    abstract::Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not onl...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bai Y,He X,Bai Y,Sun Y,Zhao Z,Chen X,Li B,Xie J,Li Y,Jia P,Meng X,Zhao Y,Ding Y,Xiao C,Wang S,Yu J,Liao S,Zhang Y,Zhu Z,Zhang Q,Zhao Y,Qin F,Zhang Y,Wei X,Zeng M,Liang J,Cuan Y,Shan G,Fan TP,Wu B

    更新日期:2019-12-01 00:00:00

  • Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.

    abstract::A novel series of non-peptide proteasome inhibitors bearing the 1, 4-naphthoquinone scaffold and boronic acid warhead was developed. In the biological evaluation on the chymotrypsin-like activity of human 20S proteasome, five compounds showed IC50 values in the nanomolar range. Docking experiments into the yeast 20S p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ge Y,Li A,Wu J,Feng H,Wang L,Liu H,Xu Y,Xu Q,Zhao L,Li Y

    更新日期:2017-03-10 00:00:00

  • Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease.

    abstract::A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wang D,Hu M,Li X,Zhang D,Chen C,Fu J,Shao S,Shi G,Zhou Y,Wu S,Zhang T

    更新日期:2019-04-15 00:00:00

  • Further studies on 2-arylacetamide pyridazin-3(2H)-ones: design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists.

    abstract::Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Giovannoni MP,Schepetkin IA,Cilibrizzi A,Crocetti L,Khlebnikov AI,Dahlgren C,Graziano A,Dal Piaz V,Kirpotina LN,Zerbinati S,Vergelli C,Quinn MT

    更新日期:2013-06-01 00:00:00