New naphthopyran analogues of LY290181 as potential tumor vascular-disrupting agents.


:A series of 19 analogues of the antiproliferative naphthopyran LY290181 were prepared for structure-activity relationship studies. We found the best activities for test compounds bearing small substituents at the meta position of the phenyl ring. The mode of action of LY290181 and eight new analogues was studied in detail. The compounds were highly anti-proliferative with IC50 values in the sub-nanomolar to triple-digit nanomolar range. The new analogues led to G2/M arrest due to interruption of the microtubule dynamics. In 518A2 melanoma cells they caused a mitotic catastrophe which eventually led to apoptosis. The naphthopyrans also induced a disruption of the vasculature in the chorioallantoic membrane (CAM) of fertilized chicken eggs as well as in xenograft tumors in mice. In a preliminary therapy trial, the difluoro derivative 2b retarded the growth of resistant xenograft tumors in mice.


Eur J Med Chem


Schmitt F,Gold M,Rothemund M,Andronache I,Biersack B,Schobert R,Mueller T




Has Abstract


2019-02-01 00:00:00












  • Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. structure-activity relationships.

    abstract::Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypan...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cerecetto H,Di Maio R,González M,Risso M,Sagrera G,Seoane G,Denicola A,Peluffo G,Quijano C,Stoppani AO,Paulino M,Olea-Azar C,Basombrío MA

    更新日期:2000-03-01 00:00:00

  • Studies on quinones. Part 46. Synthesis and in vitro antitumor evaluation of aminopyrimidoisoquinolinequinones.

    abstract::In the search of structure-activity relationship studies and to explore the antitumor effect associated with the pyrimidoisoquinolinequinone scaffold, several diversily substituted 8-aminopyrimido[4,5-c]isoquinolinequinones were regioselectively synthesized. Variation in the structure of the nitrogen substituent bonde...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Vásquez D,Rodríguez JA,Theoduloz C,Calderon PB,Valderrama JA

    更新日期:2010-11-01 00:00:00

  • An insight into the biological activities of heterocyclic-fatty acid hybrid molecules.

    abstract::Heterocyclic compounds are the interesting core structures for the development of new bioactive compounds. Fatty acids are derived from renewable raw materials and exhibit various biological activities. Several researchers are amalgamating these two bioactive components to yield bioactive hybrid molecules with some de...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Venepally V,Reddy Jala RC

    更新日期:2017-12-01 00:00:00

  • Synthesis and in vitro evaluation of 1,8-diazaanthraquinones bearing 3-dialkylaminomethyl or 3-(N-alkyl- or N-aryl)carbamoyloxymethyl substituent.

    abstract::A series of 1,8-diazaanthraquinone derivatives carrying a 3-dialkylaminomethyl or a 3-(N-alkyl or aryl)carbamoyloxymethyl substituent was synthesised and their in vitro cytotoxic activities were evaluated against eight human cancer cell lines (HOP62, SK-OV-3, HCT-15, SF295, MCF7, SNU-354, KB-3-1 and KB-V-1). A number ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lee H,Lee SI,Cho J,Choi SU,Yang SI

    更新日期:2003-07-01 00:00:00

  • Design, synthesis, antitumor activities and biological studies of novel diaryl substituted fused heterocycles as dual ligands targeting tubulin and katanin.

    abstract::Microtubule is one of the important targets for cancer treatment. A novel class of diaryl substituted imidazo[4,5-c]pyridin-2-ones and imidazo[4,5-c]pyridines were designed based on combination principles by merging the structures of β-lactams and purine-type compounds known as tubulin polymerization inhibitor and kat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gao F,Liang Y,Zhou P,Cheng J,Ding K,Wang Y

    更新日期:2019-09-15 00:00:00

  • Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.

    abstract::Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged cate...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Li XQ,Xu Q,Luo J,Wang LJ,Jiang B,Zhang RS,Shi DY

    更新日期:2017-08-18 00:00:00

  • Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives.

    abstract::Fifteen novel pyridazinone substituted benzenesulfonylurea derivatives (3a-o) were synthesized from corresponding sulfonamides derivatives via novel carbamates (2a-e). These were characterized by elemental analysis and various spectroscopic methods viz. IR, (1)H NMR, (13)C NMR and MS. Blood sugar lowering effect of th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rathish IG,Javed K,Bano S,Ahmad S,Alam MS,Pillai KK

    更新日期:2009-06-01 00:00:00

  • Design, Prins-cyclization reaction promoting diastereoselective synthesis of 10 new tetrahydropyran derivatives and in vivo antinociceptive evaluations.

    abstract::We described in this article the very efficient 2,6-cis ou 2,4,6-cis diastereoselective synthesis (2 or 3 steps, 62-65% global yields) from Prins-cyclization reaction as synthetic key-step to tetrahydropyran rings construction of 10 new congeners compounds (3-12) designed from Naproxen structure. These tetrahydropyran...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Capim SL,Carneiro PH,Castro PC,Barros MR,Marinho BG,Vasconcellos ML

    更新日期:2012-12-01 00:00:00

  • Probing the antiamoebic and cytotoxicity potency of novel tetrazole and triazine derivatives.

    abstract::A series of compounds bearing a Tetrazole and Triazine ring motif conjugated with a SO(2)NH function were synthesized and investigated for their antiamoebic potency. Cytotoxicity of the compounds was checked on human hepatocellular carcinoma cell line HepG2. Incorporation of Triazine ring in place of tetrazole resulte...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wani MY,Bhat AR,Azam A,Choi I,Athar F

    更新日期:2012-02-01 00:00:00

  • Structural modifications at the 6-position of thieno[2,3-d]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia.

    abstract::Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 in...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kim H,Lee C,Yang JS,Choi S,Park CH,Kang JS,Oh SJ,Yun J,Kim MH,Han G

    更新日期:2016-09-14 00:00:00

  • Synthesis and biological characterization of spiro[2H-(1,3)-benzoxazine-2,4'-piperidine] based histone deacetylase inhibitors.

    abstract::Histone Deacetylases (HDACs) have become important targets for the treatment of cancer and other diseases. In previous studies we described the development of novel spirocyclic HDAC inhibitors based on the combination of privileged structures with hydroxamic acid moieties as zinc binding group. Herein, we report furth...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Thaler F,Varasi M,Abate A,Carenzi G,Colombo A,Bigogno C,Boggio R,Zuffo RD,Rapetti D,Resconi A,Regalia N,Vultaggio S,Dondio G,Gagliardi S,Minucci S,Mercurio C

    更新日期:2013-06-01 00:00:00

  • Synthesis of octadecylamine-retinoic acid conjugate for enhanced cytotoxic effects of 5-FU using LDL targeted nanostructured lipid carriers.

    abstract::The aim of the present study was to reduce 5-FU side effects by targeted nanostructured lipid carriers (NLCs) to LDL receptors that are over expressed in colorectal carcinoma and also use of a new synthesized conjugate of retinoic acid as a cytotoxic agent. Fatty acyl amide derivative of retinoic acid was synthesized ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Varshosaz J,Hassanzadeh F,Sadeghi H,Andalib S

    更新日期:2012-08-01 00:00:00

  • Identification of multi-target inhibitors of leukotriene and prostaglandin E2 biosynthesis by structural tuning of the FLAP inhibitor BRP-7.

    abstract::Leukotrienes (LTs) and prostaglandin (PG)E2 are enzymatically produced from arachidonic acid and represent highly bioactive lipid mediators with pro-inflammatory functions. Here, we report on novel multi-target inhibitors that potently and dually interfere with 5-lipoxygenase-activating protein (FLAP) and microsomal p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gür ZT,Çalışkan B,Garscha U,Olgaç A,Schubert US,Gerstmeier J,Werz O,Banoglu E

    更新日期:2018-04-25 00:00:00

  • Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.

    abstract::Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyr...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Garamvölgyi R,Dobos J,Sipos A,Boros S,Illyés E,Baska F,Kékesi L,Szabadkai I,Szántai-Kis C,Kéri G,Őrfi L

    更新日期:2016-01-27 00:00:00

  • Recent developments of quinolone-based derivatives and their activities against Escherichia coli.

    abstract::Escherichia coli (E. coli) is the most common pathogen in both hospital and community settings, and is capable of causing infections that can lead to serious consequences. Quinolones, one of the most common antibiotics in clinical use, are effective weapons to treat E. coli infections. However, the resistance of E. co...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Gao F,Wang P,Yang H,Miao Q,Ma L,Lu G

    更新日期:2018-09-05 00:00:00

  • New dimeric cyclodiphosph(V)azane complexes of Cr(III), Co(II), Ni(II), Cu(II), and Zn(II): preparation, characterization and biological activity studies.

    abstract::The complexes of type [CrLCl](2).3.5H(2)O and [ML(H(2)O)](2).nH(2)O in which M = Co(II); n = 1, Ni(II); n = 4, Cu(II); n = 0.5 and Zn(II); n = 2 ions and L is 1,3-dimethyl-2,4-dioxo-2',4'-bis(2iminothiophene)cyclodiphosph(V)azane, were prepared and their structures characterized by elemental analysis, IR, (1)H NMR, (3...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Alaghaz AN,Ammar RA

    更新日期:2010-04-01 00:00:00

  • Synthesis and antitumor activities of naturally occurring oleanolic acid triterpenoid saponins and their derivatives.

    abstract::Twenty-six naturally occurring oleanolic acid saponins and their derivatives, 16 of which were synthesized in this study, were preliminarily evaluated against human cancer cells. From SAR studies, the presence of α-l-rhamnosyl residue at the terminal of both C-3 and C-28 position for oleanolic acid bidesmosides was im...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liu Q,Liu H,Zhang L,Guo T,Wang P,Geng M,Li Y

    更新日期:2013-06-01 00:00:00

  • Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents.

    abstract::Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared w...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Li JF,Huang RZ,Yao GY,Ye MY,Wang HS,Pan YM,Xiao JT

    更新日期:2014-10-30 00:00:00

  • Novel 8-arylated purines as inhibitors of glycogen synthase kinase.

    abstract::A series of 8-arylated purine derivatives bearing either an aniline or an alkyl amide at position 6 were found to inhibit glycogen synthase kinase-3, with good selectivity over ten kinases. Molecular modeling studies indicated that the most active compounds (8a and 8e), adopt a planar conformation, close to the shape ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ibrahim N,Mouawad L,Legraverend M

    更新日期:2010-08-01 00:00:00

  • A review of anti-infective and anti-inflammatory chalcones.

    abstract::Chalcones, considered as the precursors of flavonoids and isoflavonoids, are abundant in edible plants, and have also been shown to display a diverse array of pharmacological activities. The purpose of this review is to provide an overview of the pharmacological activity of synthetic and naturally occurring chalcones....

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Nowakowska Z

    更新日期:2007-02-01 00:00:00

  • Synthesis, spectral characterization and bio-analysis of some organotin(IV) complexes.

    abstract::Five novel organotin(IV) derivatives have been synthesized by refluxing trimethyl, triethyl, tributyl, and triphenyl and tribenzyltin chloride with Schiff base derived from salicylaldehyde and adenine. These compounds were characterized by spectroscopic (IR, (1)H, (13)C, (119)Sn-NMR, (119m)Sn Mössbauer) techniques and...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rehman W,Baloch MK,Badshah A

    更新日期:2008-11-01 00:00:00

  • Structure-activity relationship studies of acridones as potential antipsoriatic agents. 2. Synthesis and antiproliferative activity of 10-substituted hydroxy-10H-acridin-9-ones against human keratinocyte growth.

    abstract::A series of 10-substituted hydroxy-10H-acridin-9-ones were synthesized and studied as potential antipsoriatic agents. The antiproliferative activity of the novel derivatives, which can be considered as aza-analogues of the antipsoriatic drug anthralin, was determined using the human keratinocyte cell line HaCaT. Struc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Putic A,Stecher L,Prinz H,Müller K

    更新日期:2010-11-01 00:00:00

  • New thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety as anticancer agents.

    abstract::A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer activity. The cytotoxicity evaluation of synthesized compounds against cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ansari M,Shokrzadeh M,Karima S,Rajaei S,Fallah M,Ghassemi-Barghi N,Ghasemian M,Emami S

    更新日期:2020-01-01 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

  • Covalent allosteric modulation: An emerging strategy for GPCRs drug discovery.

    abstract::Designing covalent allosteric modulators brings new opportunities to the field of drug discovery towards G-protein-coupled receptors (GPCRs). Targeting an allosteric binding pocket can allow a modulator to have protein subtype selectivity and low drug resistance. Utilizing covalent warheads further enables the modulat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Bian Y,Jun JJ,Cuyler J,Xie XQ

    更新日期:2020-11-15 00:00:00

  • Novel potent and selective alphavbeta3/alphavbeta5 integrin dual antagonists with reduced binding affinity for human serum albumin.

    abstract::The binding of lead compounds and drugs to human serum albumin (HSA) is a ubiquitous problem in drug discovery since it modulates the availability of the leads and drugs to their intended target, which is linked to biological efficacy. In our continuing efforts to identify small molecule alpha(V)beta(3) and alpha(V)be...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Raboisson P,Manthey CL,Chaikin M,Lattanze J,Crysler C,Leonard K,Pan W,Tomczuk BE,Marugán JJ

    更新日期:2006-07-01 00:00:00

  • Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation.

    abstract::We report the design of hetero-bifunctional small molecules that selectively target p38α and p38β for degradation. These proteolysis targeted chimeras (PROTACs) are based on an ATP competitive inhibitor of p38α and p38β, which is linked to thalidomide analogues to recruit the Cereblon E3 ubiquitin ligase complex. Comp...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Donoghue C,Cubillos-Rojas M,Gutierrez-Prat N,Sanchez-Zarzalejo C,Verdaguer X,Riera A,Nebreda AR

    更新日期:2020-09-01 00:00:00

  • Synthesis and biological evaluation of a new series of 2-amino-3-aroyl thiophene derivatives as agonist allosteric modulators of the A1 adenosine receptor. A position-dependent effect study.

    abstract::The 2-amino-3-(p-chlorobenzoyl)thiophene scaffold has been widely employed as a pharmacophore for the identification of small molecules acting as allosteric modulators at the adenosine A1 receptor. A new series of 2-amino-3-(p-chlorobenzoyl)-4-benzyl-5-arylthiophene derivatives, characterized by the absence as well as...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Romagnoli R,Baraldi PG,Lopez-Cara C,Cruz-Lopez O,Moorman AR,Massink A,IJzerman AP,Vincenzi F,Borea PA,Varani K

    更新日期:2015-08-28 00:00:00

  • β-Glucuronidase-responsive prodrugs for selective cancer chemotherapy: an update.

    abstract::The design of novel antitumor agents allowing the destruction of malignant cells while sparing healthy tissues is one of the major challenges in medicinal chemistry. In this context, the use of non-toxic prodrugs programmed to be selectively activated by beta-glucuronidase present at high concentration in the microenv...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tranoy-Opalinski I,Legigan T,Barat R,Clarhaut J,Thomas M,Renoux B,Papot S

    更新日期:2014-03-03 00:00:00

  • Synthesis and anti-oxidant activity evaluation of (±)-Anastatins A, B and their analogs.

    abstract::Two novel flavonoids (±)-Anastatins A and B as well as 14 analogs, which containing a benzofuran moiety, were synthesized by using halogenation, Suzuki coupling reaction and an oxidation/Oxa-Michael reaction cascade as the key steps. The structures of the new flavonoids were confirmed by 1H NMR, 13C NMR and HRMS. The ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pan G,Li X,Zhao L,Wu M,Su C,Li X,Zhang Y,Yu P,Teng Y,Lu K

    更新日期:2017-09-29 00:00:00