Synthesis, local anaesthetic and antiarrhythmic activities of N-alkyl derivatives of proline anilides.


:We describe here the design, synthesis and evaluation of in vivo local anaesthetic and antiarrhythmic activities of a series of N-alkylproline anilides. Most of the compounds demonstrated surface anaesthetic activity higher than that of lidocaine, ropivacaine and bupivacaine. We established that the local anaesthetic activity was sensitive to structural variations in the substitution pattern at the aromatic ring and the type of alkyl group at the proline nitrogen atom. Some of the prepared N-alkylproline anilides possessed significant antiarrhythmic activity with higher therapeutic indexes than the reference drugs.


Eur J Med Chem


Kalinin DV,Pantsurkin VI,Syropyatov BY,Kalinina SA,Rudakova IP,Vakhrin MI,Dolzhenko AV




Has Abstract


2013-05-01 00:00:00












  • Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.

    abstract::We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were eva...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Letribot B,Akué-Gédu R,Santio NM,El-Ghozzi M,Avignant D,Cisnetti F,Koskinen PJ,Gautier A,Anizon F,Moreau P

    更新日期:2012-04-01 00:00:00

  • Synthesis and comparative photodynamic properties of two isosteric alkyl substituted zinc(II) phthalocyanines.

    abstract::The synthesis and photophysical parameters of two novel isosteric cationic zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gauna GA,Marino J,García Vior MC,Roguin LP,Awruch J

    更新日期:2011-11-01 00:00:00

  • Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

    abstract::A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC50 0.03 ± 0.07 μM) against acetylcholinesterase. A series of c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: van Greunen DG,Johan van der Westhuizen C,Cordier W,Nell M,Stander A,Steenkamp V,Panayides JL,Riley DL

    更新日期:2019-10-01 00:00:00

  • Synthesis and preliminary antibacterial evaluation of Linezolid-like 1,2,4-oxadiazole derivatives.

    abstract::In the present study the synthesis of new Linezolid-like molecules has been achieved by substitution of the oxazolidinone central heterocyclic moiety with a 1,2,4-oxadiazole ring. Two series of 1,2,4-oxadiazoles, bearing different side-chains and containing a varying number of fluorine atoms, were synthesized and prel...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Palumbo Piccionello A,Musumeci R,Cocuzza C,Fortuna CG,Guarcello A,Pierro P,Pace A

    更新日期:2012-04-01 00:00:00

  • Discovery of a sulfamate-based steroid sulfatase inhibitor with intrinsic selective estrogen receptor modulator properties.

    abstract::Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ouellet C,Maltais R,Ouellet É,Barbeau X,Lagüe P,Poirier D

    更新日期:2016-08-25 00:00:00

  • Synthesis, antimalarial evaluation and molecular modeling studies of hydroxyethylpiperazines, potential aspartyl protease inhibitors, part 2.

    abstract::The antimalarial acitivity of hydroxyethylamines, synthesized from the reaction of intermediated hydroxyethypiperazines with benzenesulfonyl chlorides or benzoyl chlorides, has been evaluated in vitro against a W2 Plasmodium falciparum clone. Some of the nineteen tested derivatives showed a significant activity in vit...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cunico W,Gomes CR,Facchinetti V,Moreth M,Penido C,Henriques MG,Varotti FP,Krettli LG,Krettli AU,da Silva FS,Caffarena ER,de Magalhães CS

    更新日期:2009-09-01 00:00:00

  • 4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity.

    abstract::Antagonists of signaling receptors are often effective non-toxic therapeutic agents. Over the years, there have been evidences describing the role of serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there are reports on the antiproliferative effects of some serotonin receptor antagonists, the...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Joshi PV,Sayed AA,RaviKumar A,Puranik VG,Zinjarde SS

    更新日期:2017-08-18 00:00:00

  • Cell death triggered by synthetic flavonoids in human leukemia cells is amplified by the inhibition of extracellular signal-regulated kinase signaling.

    abstract::A new class of methyl esters of flavonoids, with different substituents on the B ring were synthesized and evaluated for their antiproliferative activity against the human leukemia cell line HL-60. The presence of either a methyl group (1f) or a chlorine atom (1o) at position 2' of the B ring played an important role ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rubio S,León F,Quintana J,Cutler S,Estévez F

    更新日期:2012-09-01 00:00:00

  • Synthesis and immunofluorescence assay of a new biotinylated paclitaxel.

    abstract::7-(5'-Biotinylamidopropanoyl)paclitaxel was synthesised by chemical methods; its immunofluorescence assay and the cell uptake experiments were performed by use of human leukemia U937 cells. The results indicate that paclitaxel is arresting cell cycle at the G(2)M phase only. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sambaiah T,King KY,Tsay SC,Mei NW,Hakimclahi S,Lai YK,Lieu CH,Hwu JR

    更新日期:2002-04-01 00:00:00

  • Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein.

    abstract::Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 pocket of the protein. Significantly, target molecules were accessed in just two synthetic steps, sugge...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lanning ME,Yu W,Yap JL,Chauhan J,Chen L,Whiting E,Pidugu LS,Atkinson T,Bailey H,Li W,Roth BM,Hynicka L,Chesko K,Toth EA,Shapiro P,MacKerell AD Jr,Wilder PT,Fletcher S

    更新日期:2016-05-04 00:00:00

  • Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene modulation in human leukemia cells and effects on clonogenic potential of murine promyelocytic blasts.

    abstract::The pure enantiomers of the N-(2-, 3-, and 4-(2-aminocyclopropyl)phenyl)benzamides hydrochlorides 11a-j were prepared and tested against LSD1 and MAO enzymes. The evaluation of the regioisomers 11a-j highlighted a net increase of the anti-LSD1 potency by shifting the benzamide moiety from ortho to meta and mainly to p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Valente S,Rodriguez V,Mercurio C,Vianello P,Saponara B,Cirilli R,Ciossani G,Labella D,Marrocco B,Monaldi D,Ruoppolo G,Tilset M,Botrugno OA,Dessanti P,Minucci S,Mattevi A,Varasi M,Mai A

    更新日期:2015-04-13 00:00:00

  • Synthesis, X-ray crystal structure and anti-tumor activity of calix[n]arene polyhydroxyamine derivatives.

    abstract::Calixarene-based compounds are highly effective therapeutic agents against cancer. This study aims to prepare a series of calix [n]arene (n = 4, 6, 8) polyhydroxyamine derivatives (3a-3m) and to study their potential antitumor activities. The single crystal structure of calixs[4]arene derivative 3a was determined thro...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: An L,Han LL,Zheng YG,Peng XN,Xue YS,Gu XK,Sun J,Yan CG

    更新日期:2016-11-10 00:00:00

  • Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment.

    abstract::Targeted therapy has become an effective strategy of precision medicine for improving cancer treatment. Selectivity improvement is always popular in modern oncology because of decreased side effects in conventional cancer chemotherapy. The use of antibody-drug conjugates (ADC), a robust strategy for targeted therapy, ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Zhuang C,Guan X,Ma H,Cong H,Zhang W,Miao Z

    更新日期:2019-02-01 00:00:00

  • Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates.

    abstract::A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piper...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Dias Viegas FP,de Freitas Silva M,Divino da Rocha M,Castelli MR,Riquiel MM,Machado RP,Vaz SM,Simões de Lima LM,Mancini KC,Marques de Oliveira PC,Morais ÉP,Gontijo VS,da Silva FMR,D'Alincourt da Fonseca Peçanha D,Castro NG,N

    更新日期:2018-03-10 00:00:00

  • Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes.

    abstract::We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM agains...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pagire SH,Pagire HS,Lee GB,Han SJ,Kwak HJ,Kim JY,Kim KY,Rhee SD,Ryu JI,Song JS,Bae MA,Park MJ,Kim D,Lee DH,Ahn JH

    更新日期:2015-08-28 00:00:00

  • Novel tacrine platinum(II) complexes display high anticancer activity via inhibition of telomerase activity, dysfunction of mitochondria, and activation of the p53 signaling pathway.

    abstract::In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CH3OH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)] (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'-dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10-phenan...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Qin QP,Wang SL,Tan MX,Wang ZF,Luo DM,Zou BQ,Liu YC,Yao PF,Liang H

    更新日期:2018-10-05 00:00:00

  • Molecular structure of the NQTrp inhibitor with the Alzheimer Aβ1-28 monomer.

    abstract::The self-assembly of the amyloid-β (Aβ) peptide of various amino acid lengths into senile plaques is one hallmark of Alzheimer's disease pathology. In the past decade, many small molecules, including NQTrp, have been identified to reduce aggregation and toxicity. However, due to the heterogeneity of the conformational...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tarus B,Nguyen PH,Berthoumieu O,Faller P,Doig AJ,Derreumaux P

    更新日期:2015-02-16 00:00:00

  • Quantitative structure activity relationship studies of diaryl furanones as selective COX-2 inhibitors.

    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


    authors: Shahapurkar S,Pandya T,Kawathekar N,Chaturvedi SC

    更新日期:2004-10-01 00:00:00

  • Synthesis, characterization, oxidative degradation, antibacterial activity and acetylcholinesterase/butyrylcholinesterase inhibitory effects of some new phosphorus(V) hydrazides.

    abstract::Some new phosphorus(V) hydrazides 1a-12a were synthesized and characterized by (1)H, (13)C, (31)P NMR, IR spectroscopy and elemental analysis. Moreover, the interaction of Cu(M)(2)·nH(2)O with 1a, 3a and 7a gave 4,4'-bis(morpholine)diazene (1b). In fact, in these reactions, copper(II) ions acted as oxidizing agent. Th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gholivand K,Hosseini Z,Farshadian S,Naderi-Manesh H

    更新日期:2010-11-01 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

  • Prodrug strategy for cancer cell-specific targeting: A recent overview.

    abstract::The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tiss...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Zhang X,Li X,You Q,Zhang X

    更新日期:2017-10-20 00:00:00

  • Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques.

    abstract::Twenty-eight structurally diverse cytochrome 3A4 (CYP3A4) inhibitors have been subjected to quantitative structure-activity relationship (QSAR) studies. The analyses were performed with electronic, spatial, topological, and thermodynamic descriptors calculated using Cerius 2 version 10 software. The statistical tools ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Roy K,Pratim Roy P

    更新日期:2009-07-01 00:00:00

  • Polyamine-based analogs and conjugates as antikinetoplastid agents.

    abstract::Naturally occurring polyamines: putrescine, spermidine and spermine are crucial for Kinetoplastid growth and persistence. These aliphatic polycations are either biosynthesized or internalized into Kinetoplastid by active transport. Impairing the polyamine metabolism using polyamine derivatives is an interesting path i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Jagu E,Pomel S,Pethe S,Loiseau PM,Labruère R

    更新日期:2017-10-20 00:00:00

  • Evaluation of rat intestinal absorption data and correlation with human intestinal absorption.

    abstract::The absorption of 111 drug and drug-like compounds was evaluated from 111 references based on the ratio of urinary excretion of drugs following oral and intravenous administration to intact rats and biliary excretion of bile duct-cannulated rats. Ninety-eight drug compounds for which both human and rat absorption data...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhao YH,Abraham MH,Le J,Hersey A,Luscombe CN,Beck G,Sherborne B,Cooper I

    更新日期:2003-03-01 00:00:00

  • Structural analysis of inhibition of Mycobacterium tuberculosis methionine aminopeptidase by bengamide derivatives.

    abstract::Natural product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases for their cellular effects. Using bengamides as a template, several derivatives were designed and synthesized as inhibitors of methionine aminopeptidases of Mycobacterium tuberculosis, and initial a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lu JP,Yuan XH,Ye QZ

    更新日期:2012-01-01 00:00:00

  • Synthesis of some new pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents.

    abstract::Treatment of 6-aminothiouracil (1) with 2,3-dichloroquinoxaline (2) in ethanol/TEA afforded 6-amino-2-(3-chloroquinoxalin-2-ylthio)pyrimidin-4(3H)-one (3), which was refluxed in DMF to give 2-aminopyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline-4-one (4). Compound 4 was utilized as a key intermediate for the synthesis o...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Abu-Hashem AA,Gouda MA,Badria FA

    更新日期:2010-05-01 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

  • Diversity-oriented synthesis of furo[3,2-f]chromanes with antimycobacterial activity.

    abstract::We previously reported the synthesis and the antimycobacterial activity of 4-(7,7-dimethyl-7H-furo[3,2-f]chromen-2-yl)pyridine. From this result, we sought to design simple synthetic accesses to related structures allowing the preparation of a diverse set of analogues. Two approaches were investigated. From 3-(2-bromo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Alvey L,Prado S,Saint-Joanis B,Michel S,Koch M,Cole ST,Tillequin F,Janin YL

    更新日期:2009-06-01 00:00:00

  • Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors.

    abstract::Structure-based pharmacophore models were built by using LigandScout and used for virtual screening of the SPECS database to identify new potential 11beta-HSD1 inhibitors. As a refinement of the results obtained from virtual 3D pharmacophore screening, the best fitting virtual hits were subjected to docking study. The...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yang H,Shen Y,Chen J,Jiang Q,Leng Y,Shen J

    更新日期:2009-03-01 00:00:00

  • New bis-N9-(methylphenylmethyl)purine derivatives: synthesis and antitumor activity.

    abstract::A series of ortho-, meta- and para-bis-N9-(methylphenylmethyl)purine derivatives 4-15 were obtained by two-step synthesis from various substituted chloropurines with alpha,alpha'-dichloroxylenes. These bis-N9-(methylphenylmethyl)purines 4-15 were evaluated for the primary cytotoxic activity against a panel of NCI-H460...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kode N,Chen L,Murthy D,Adewumi D,Phadtare S

    更新日期:2007-03-01 00:00:00