当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system.

Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system.

Abstract：

:The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (Ki = 23.1 nM, partial agonist) and CB2R (Ki = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC50 = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC50 = 2.5 μΜ). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC50 values (0.28-0.62 μΜ). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Chicca A,Arena C,Bertini S,Gado F,Ciaglia E,Abate M,Digiacomo M,Lapillo M,Poli G,Bifulco M,Macchia M,Tuccinardi T,Gertsch J,Manera C

doi

10.1016/j.ejmech.2018.05.019

subject

Has Abstract

pub_date

2018-06-25 00:00:00

pages

155-171

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(18)30423-9

journal_volume

154

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Phenyl phosphoramidate derivatives of stavudine as anti-HIV agents with potent and selective in-vitro antiviral activity against adenovirus.

    abstract：:Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, nephritis, and gastroenteritis in immunocompromised patients, including HIV-infected individuals. Here we report the identification of halo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2003.12.002

    authors： Uckun FM,Pendergrass S,Qazi S,Samuel P,Venkatachalam TK

    更新日期：2004-03-01 00:00:00

  • Substituted quinolinyl chalcones and quinolinyl pyrimidines as a new class of anti-infective agents.

    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

    authors： Sharma M,Chaturvedi V,Manju YK,Bhatnagar S,Srivastava K,Puri SK,Chauhan PM

    更新日期：2009-05-01 00:00:00

  • Discovery of anxiolytic 2-ferrocenyl-1,3-thiazolidin-4-ones exerting GABAA receptor interaction via the benzodiazepine-binding site.

    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

    authors： Pejović A,Denić MS,Stevanović D,Damljanović I,Vukićević M,Kostova K,Tavlinova-Kirilova M,Randjelović P,Stojanović NM,Bogdanović GA,Blagojević P,D'hooghe M,Radulović NS,Vukićević RD

    更新日期：2014-08-18 00:00:00

  • Selective apoptosis-inducing activity of synthetic hydrocarbon-stapled SOS1 helix with d-amino acids in H358 cancer cells expressing KRASG12C.

    abstract：:Lung cancer is one of the most malignant tumors with the highest morbidity and mortality. Most of them are non-small cell lung cancer (NSCLC). KRASG12C gene mutation is an important driving factor for NSCLC. However, the development of high-affinity inhibitors targeting KRASG12C mutants remains a daunting challenge. H...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.111844

    authors： Xu LL,Li CC,An LY,Dai Z,Chen XY,You QD,Hu C,Di B

    更新日期：2020-01-01 00:00:00

  • Antimicrobial study of newly synthesized 6-substituted indolo[1,2-c]quinazolines.

    abstract：:A new series of indolo[1,2-c]quinazoline derivatives were prepared in good yield through reaction of 2-(o-aminophenyl)indole with a variety of arylaldehydes. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectral studies and elemental analysis. All the title compo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.11.038

    authors： Rohini R,Muralidhar Reddy P,Shanker K,Hu A,Ravinder V

    更新日期：2010-03-01 00:00:00

  • Antifungal activities of novel non-azole molecules against S. cerevisiae and C. albicans.

    abstract：:Because of the increasing number of immunocompromised patients and due to problems with antifungal treatment, especially with the most widely used antifungals, azoles, there is an urgent need for new, potent and safe antifungals with fewer cytochrome P450 (CYP)-mediated interactions with other drugs. In the present st...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.10.053

    authors： Tani N,Rahnasto-Rilla M,Wittekindt C,Salminen KA,Ritvanen A,Ollakka R,Koskiranta J,Raunio H,Juvonen RO

    更新日期：2012-01-01 00:00:00

  • Synthesis and antibacterial study of unsaturated Mannich ketones.

    abstract：:Several Mannich ketones of 2-arylmethylenecycloalkanones were synthesised using the classical acid-catalysed Mannich reaction. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus lute...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01264-8

    authors： Lóránd T,Kocsis B,Sohár P,Nagy G,Kispál G,Krane HG,Schmitt H,Weckert E

    更新日期：2001-09-01 00:00:00

  • Design, synthesis and biological evaluation of novel potent STAT3 inhibitors based on BBI608 for cancer therapy.

    abstract：:Persistently activated signal transducer and activator of transcription 3 (STAT3) plays an important role in the development of multiple cancers, and therefore is a potential therapeutic target for cancer prevention. Herein, we report the rational design, synthesis, and biological evaluation of novel potent STAT3 inhi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112428

    authors： Feng KR,Wang F,Shi XW,Tan YX,Zhao JY,Zhang JW,Li QH,Lin GQ,Gao D,Tian P

    更新日期：2020-09-01 00:00:00

  • Enaminonitrile in heterocyclic synthesis: synthesis and antimicrobial evaluation of some new pyrazole, isoxazole and pyrimidine derivatives incorporating a benzothiazole moiety.

    abstract：:Enaminonitrile 2 was used as key intermediate for the synthesis of polyfunctionally substituted heterocycles (e.g. pyrazoles, isoxazole, pyrimidines, thiazolo[3,2-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, pyrido[1,2-a]pyrimidine, 1,5-benzodiazepine, and pyrazolo[1,5-a]pyrimidine) incorporating benzothiazole moiety via...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.07.024

    authors： Bondock S,Fadaly W,Metwally MA

    更新日期：2009-12-01 00:00:00

  • Aminopropylindenes derived from Grundmann's ketone as a novel chemotype of oxidosqualene cyclase inhibitors.

    abstract：:A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann's ketone. Screening on OSCs from five different organisms revealed interesting activities and selectivities ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.03.002

    authors： Lange S,Keller M,Müller C,Oliaro-Bosso S,Balliano G,Bracher F

    更新日期：2013-05-01 00:00:00

  • Design, synthesis and biological evaluation of some novel thienopyrimidines and fused thienopyrimidines as anti-inflammatory agents.

    abstract：:Some new substituted thienopyrimidine derivatives comprising thioxo, thioalkyl and pyrazolyl derivatives as well as fused thienotriazolopyrimidine and thienopyrimidinotriazine ring systems were prepared from 3-benzyl-2-hydrazino-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide 4. The designed compounds ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.07.007

    authors： Rizk OH,Shaaban OG,El-Ashmawy IM

    更新日期：2012-09-01 00:00:00

  • Synthesis, anti-HIV-1 integrase, and cytotoxic activities of 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives.

    abstract：:Several 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives 13-28 and 35-44 have been synthesized and tested as potential HIV-1 integrase (IN) inhibitors. Compounds 15-17, 19, 21-28, 36 and 41 inhibited IN with IC(50) values in the range of 3.3-63.0 microM. The compounds 13, 15, 16, 21-24 and 26-...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.08.013

    authors： Brzozowski Z,Sławiński J,Saczewski F,Sanchez T,Neamati N

    更新日期：2008-06-01 00:00:00

  • Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

    abstract：:To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G120...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.12.060

    authors： Geng K,Xia Z,Ji Y,Zhang RR,Sun D,Ai J,Song Z,Geng M,Zhang A

    更新日期：2018-01-20 00:00:00

  • New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold: synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies.

    abstract：:Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8-amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative activities against ten melanoma cell lines were tested. Compounds 1l, 2l, 3c, and 4c showed the highest potency against A375P cell line with IC50 values in sub...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.06.060

    authors： Koh EJ,El-Gamal MI,Oh CH,Lee SH,Sim T,Kim G,Choi HS,Hong JH,Lee SG,Yoo KH

    更新日期：2013-01-01 00:00:00

  • Palladium(II) and platinum(II) complexes of a symmetric Schiff base derived from 2,6,diformyl-4-methylphenol with N-aminopyrimidine: synthesis, characterization and detection of DNA interaction by voltammetry.

    abstract：:The two new mononuclear complexes were prepared by reacting symmetric Schiff base, containing pyrimidine rings and the metal chlorides of Pd(II) and Pt(II) in methanol. The mononuclear structure of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, IR, UV-Vis, NMR, DTA/TGA and API...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.06.016

    authors： Sönmez M,Celebi M,Yardim Y,Sentürk Z

    更新日期：2010-09-01 00:00:00

  • Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption.

    abstract：:Oral absorption of compounds depends on many physiological, physiochemical and formulation factors. Two important properties that govern oral absorption are in vitro permeability and solubility, which are commonly used as indicators of human intestinal absorption. Despite this, the nature and exact characteristics of ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.12.006

    authors： Newby D,Freitas AA,Ghafourian T

    更新日期：2015-01-27 00:00:00

  • Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties.

    abstract：:New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibact...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.07.049

    authors： Thomas KD,Adhikari AV,Chowdhury IH,Sandeep T,Mahmood R,Bhattacharya B,Sumesh E

    更新日期：2011-10-01 00:00:00

  • Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2.

    abstract：:Human carboxylesterase 2 (hCE2), one of the major carboxylesterases in the human intestine and various tumour tissues, plays important roles in the oral bioavailability and treatment outcomes of ester- or amide-containing drugs or prodrugs, such as anticancer agents CPT-11 (irinotecan) and LY2334737 (gemcitabine). In ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.02.020

    authors： Zou LW,Li YG,Wang P,Zhou K,Hou J,Jin Q,Hao DC,Ge GB,Yang L

    更新日期：2016-04-13 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

    doi：10.1016/j.ejmech.2015.12.050

    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

  • 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

    doi：10.1016/j.ejmech.2017.08.014

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

    更新日期：2017-10-20 00:00:00

  • Design, synthesis and structure-activity relationships of novel 15-membered macrolides: Quinolone/quinoline-containing sidechains tethered to the C-6 position of azithromycin acylides.

    abstract：:In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may mo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112222

    authors： Fan BZ,Hiasa H,Lv W,Brody S,Yang ZY,Aldrich C,Cushman M,Liang JH

    更新日期：2020-05-01 00:00:00

  • Conformation and recognition of DNA damaged by antitumor cis-dichlorido platinum(II) complex of CDK inhibitor bohemine.

    abstract：:A substitution of the ammine ligands of cisplatin, cis-[Pt(NH3)2Cl2], for cyclin dependent kinase (CDK) inhibitor bohemine (boh), [2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine], results in a compound, cis-[Pt(boh)2Cl2] (C1), with the unique anticancer profile which may be associated with some features of t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.03.041

    authors： Novakova O,Liskova B,Vystrcilova J,Suchankova T,Vrana O,Starha P,Travnicek Z,Brabec V

    更新日期：2014-05-06 00:00:00

  • Synthesis and biological evaluation of novel alkylated polyamine analogues as potential anticancer agents.

    abstract：:A new class of polyamine analogues modified by alkylation at the terminal of the polyamine chain has been synthesized and their structures were determined by 1H NMR, 13C NMR, ESI-MS and elemental analysis. As the representative compound, 3f displayed a broad spectrum of anti-cancer effects by MTT assays. Tumor xenogra...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.10.069

    authors： Li M,Wang Y,Ge C,Chang L,Wang C,Tian Z,Wang S,Dai F,Zhao L,Xie S

    更新日期：2018-01-01 00:00:00

  • Synthesis of 3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazolo(thiadiazoles and thiadiazines) as anti-inflammatory and molluscicidal agents.

    abstract：:A series of fused and non fused 1,2,4-triazoles with (2,4-dichlorophenoxy) moiety are prepared utilizing 3-((2,4-dichlorophenoxy)methyl)-4-amino-4H-1,2,4-triazole-5-thiol (3). The latter on reaction with carboxylic acids, ethylchloroformate, ethylcyanoacetate and sodium nitrite gives five membered fused triazole deriv...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.01.030

    authors： El Shehry MF,Abu-Hashem AA,El-Telbani EM

    更新日期：2010-05-01 00:00:00

  • Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors.

    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

    authors： Celik İ,Ayhan-Kılcıgil G,Guven B,Kara Z,Gurkan-Alp AS,Karayel A,Onay-Besikci A

    更新日期：2019-07-01 00:00:00

  • Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells.

    abstract：:Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.10.025

    authors： Ullah S,Kang D,Lee S,Ikram M,Park C,Park Y,Yoon S,Chun P,Moon HR

    更新日期：2019-01-01 00:00:00

  • Discovery of a new selective inhibitor of A Disintegrin And Metalloprotease 10 (ADAM-10) able to reduce the shedding of NKG2D ligands in Hodgkin's lymphoma cell models.

    abstract：:Hodgkin's lymphoma (HL) is the most common malignant lymphoma in young adults in the western world. This disease is characterized by an overexpression of ADAM-10 with increased release of NKG2D ligands, involved in an impaired immune response against tumor cells. We designed and synthesized two new ADAM-10 selective i...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.01.053

    authors： Camodeca C,Nuti E,Tepshi L,Boero S,Tuccinardi T,Stura EA,Poggi A,Zocchi MR,Rossello A

    更新日期：2016-03-23 00:00:00

  • Design and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations.

    abstract：:SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112469

    authors： Luo S,Xu S,Liu J,Ma F,Zhu YZ

    更新日期：2020-08-15 00:00:00

  • Design, synthesis and biological evaluation of a novel class of potent TGR5 agonists based on a 4-phenyl pyridine scaffold.

    abstract：:TGR5, a GPCR, is involved in energy and glucose homeostasis, and as such, is a target for the treatment of diabetes, obesity and other metabolic syndromes. A new class of TGR5 agonists based on a 4-phenyl pyridine scaffold was designed, synthesized and evaluated in vitro and in vivo. Extensive structure-activity relat...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.07.050

    authors： Zhu J,Ning M,Guo C,Zhang L,Pan G,Leng Y,Shen J

    更新日期：2013-11-01 00:00:00

  • Organometallic compounds in the discovery of new agents against kinetoplastid-caused diseases.

    abstract：:The development of safe and affordable antiparasitic agents effective against neglected tropical diseases is a big challenge of the drug discovery. The drugs currently employed have limitations such as poor efficacy, drug resistance or side effects. Thus, the search for new promising drugs is more and more crucial. Me...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2018.05.044

    authors： Ravera M,Moreno-Viguri E,Paucar R,Pérez-Silanes S,Gabano E

    更新日期：2018-07-15 00:00:00