当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents.

Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents.

Abstract：

:A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a-g and 7a-g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a-g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28-2.98 μM and 0.35-2.78 μM respectively under in vitro assays. In addition, 6a-g and 7a-g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a-g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8-31.2 μg/mL, MIC80 = 15.6-31.2 μg/mL and MIC100 = 15.6-62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Ramírez J,Svetaz L,Quiroga J,Abonia R,Raimondi M,Zacchino S,Insuasty B

doi

10.1016/j.ejmech.2015.01.053

subject

Has Abstract

pub_date

2015-03-06 00:00:00

pages

866-75

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)00073-2

journal_volume

92

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Optimization of troglitazone derivatives as potent anti-proliferative agents: towards more active and less toxic compounds.

    abstract：:Δ2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPARγ-independent manner. We prepared various compounds in order to increase their potency and decrease their toxicity towards non-malignant primary cultured hepatocytes. Many compounds induced viabilities less than 20% at 10 μM on vari...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.06.015

    authors： Bordessa A,Colin-Cassin C,Grillier-Vuissoz I,Kuntz S,Mazerbourg S,Husson G,Vo M,Flament S,Martin H,Chapleur Y,Boisbrun M

    更新日期：2014-08-18 00:00:00

  • Naphthyl quinoxaline thymidine conjugate is a potent anticancer agent post UVA activation and elicits marked inhibition of tumor growth through vaccination.

    abstract：:Anticancer anthracyclines are cytotoxic drugs that can induce antitumor immune response as a secondary effect through immunogenic cell death (ICD) mechanism. However, the immunogenic potency is quite limited, possibly due to that these chemotherapeutic agents are not specifically developed as ICD inducers. Thus, new d...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.03.051

    authors： Yuan Y,Wang Z,Yang R,Qian T,Zhou Q

    更新日期：2019-06-01 00:00:00

  • Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.

    abstract：:Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylen...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.03.035

    authors： Aslam S,Zaib S,Ahmad M,Gardiner JM,Ahmad A,Hameed A,Furtmann N,Gütschow M,Bajorath J,Iqbal J

    更新日期：2014-05-06 00:00:00

  • 3D-QSAR analysis of human immunodeficiency virus entry-1 inhibitors by CoMFA and CoMSIA.

    abstract：:3D-QSAR studies namely CoMFA, CoMFA region focusing and CoMSIA have been carried out on a series (36 compounds) of HIV-1 entry inhibitors. An alignment rule for the compounds was defined using Distill in SYBYL 7.3. Models were validated using a data set obtained by dividing the data set into a training set and test se...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.07.062

    authors： Pirhadi S,Ghasemi JB

    更新日期：2010-11-01 00:00:00

  • A comparative study of the hydrolysis pathways of substituted aryl phosphoramidate versus aryl thiophosphoramidate derivatives of stavudine.

    abstract：:A comparative study of aryl phosphoramidate and aryl thiophosphoramidate derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (d4T) was performed. The study focused on the nature of the substituents and the influence of a thiophosphoramidate in the structure of these derivatives. The rate of alkaline hydrolysis of th...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2004.04.002

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

    更新日期：2004-08-01 00:00:00

  • Promising applications of steroid сonjugates for cancer research and treatment.

    abstract：:The conjugation of biologically active molecules is a powerful tool for drug discovery used to target a variety of multifunctional diseases including cancer. Conjugated drugs can provide combination therapies in a single multi-functional agent and, by doing so, be more specific and powerful than conventional classic t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.113089

    authors： А Zolottsev V,Latysheva АS,Pokrovsky VS,Khan II,Misharin AY

    更新日期：2021-01-15 00:00:00

  • Selenium analogues of raloxifene as promising antiproliferative agents in treatment of breast cancer.

    abstract：:Synthetic protocols for the preparation of selenium analogues of raloxifene were elaborated. General aim of the current research is to improve the positive impact of selenium atom introduction in drug design. Antiproliferative activity on CCL-8 (mouse sarcoma), MDA-MB-435s (human melanoma), MES-SA (human uterus sarcom...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.09.088

    authors： Arsenyan P,Paegle E,Domracheva I,Gulbe A,Kanepe-Lapsa I,Shestakova I

    更新日期：2014-11-24 00:00:00

  • Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants.

    abstract：:In this preliminary study we report the antiviral screening of triazolo[4,5-g]quinoline derivatives (compounds 1-6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective, promising activity in cell-based assays against HIV-1wt and clinically relevant NNRTI resista...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.08.012

    authors： Carta A,Pricl S,Piras S,Fermeglia M,La Colla P,Loddo R

    更新日期：2009-12-01 00:00:00

  • Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents.

    abstract：:Several naphthalimide polyamine conjugates were synthesized and evaluated for in vitro cytotoxicity against human leukemia K562, murine melanoma B16, Chinese hamster ovary CHO cell lines. Both triamine moieties and the length of spacers were crucial in elevating the potency of 1,8-naphthalimide. The typical compounds ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.02.044

    authors： Tian ZY,Xie SQ,Du YW,Ma YF,Zhao J,Gao WY,Wang CJ

    更新日期：2009-01-01 00:00:00

  • Synthesis and anticancer activity of new dihydropyrimidinone derivatives.

    abstract：:A series of dihydropyrimidinone derivatives bearing various N-heterocyclic moieties was designed and synthesized. Twelve new compounds were screened for their cytotoxic activity using 60 cancer cell lines according to NCI (USA) protocol. Compound 19 showed a significant activity against NCI-H460, SK-MEL-5, and HL-60 (...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.07.004

    authors： Mostafa AS,Selim KB

    更新日期：2018-08-05 00:00:00

  • Covalent binding design strategy: A prospective method for discovery of potent targeted anticancer agents.

    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

    authors： Wang L,Zhao J,Yao Y,Wang C,Zhang J,Shu X,Sun X,Li Y,Liu K,Yuan H,Ma X

    更新日期：2017-12-15 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

  • Design, synthesis and biological evaluation of novel N-[4-(2-fluorophenoxy)pyridin-2-yl]cyclopropanecarboxamide derivatives as potential c-Met kinase inhibitors.

    abstract：:Three series of novel 4-phenoxypyridine derivatives containing 4-methyl-6-oxo-1,6-dihydropyridazine- 3-carboxamide, 5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide and 4-methyl-3,5-dioxo-2,3,4,5- tetrahydro-1,2,4-triazine-6-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activitive...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112244

    authors： Liu J,Gong Y,Shi J,Hao X,Wang Y,Zhou Y,Hou Y,Liu Y,Ding S,Chen Y

    更新日期：2020-05-15 00:00:00

  • Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison of anti-platelet agglutination activities of spirostanol glycosides.

    abstract：:Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(00)00151-3

    authors： Tobari A,Teshima M,Koyanagi J,Kawase M,Miyamae H,Yoza K,Takasaki A,Nagamura Y,Saito S

    更新日期：2000-05-01 00:00:00

  • Structure-activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme.

    abstract：:Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-â and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-â clearance, and its validation as a pot...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.12.005

    authors： Charton J,Gauriot M,Totobenazara J,Hennuyer N,Dumont J,Bosc D,Marechal X,Elbakali J,Herledan A,Wen X,Ronco C,Gras-Masse H,Heninot A,Pottiez V,Landry V,Staels B,Liang WG,Leroux F,Tang WJ,Deprez B,Deprez-Poulain R

    更新日期：2015-01-27 00:00:00

  • An investigation into the role of surfactants in controlling particle size of polymeric nanocapsules containing penicillin-G in double emulsion.

    abstract：:Preparation, characterization and drug release behavior of loaded polybutyl adipate (PBA) nanocapsules with penicillin-G are described here. The nanocapsules were produced using a double emulsion solvent evaporation technique, using dichloromethane as an organic solvent and Tween and Span as surfactants. In this proce...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.09.045

    authors： Khoee S,Yaghoobian M

    更新日期：2009-06-01 00:00:00

  • Molecular design, synthesis and biological research of novel pyridyl acridones as potent DNA-binding and apoptosis-inducing agents.

    abstract：:A series of novel pyridyl acridone derivatives comprised of a pseudo-five-cyclic system to extend the π-conjugated acridone chromophore, were designed and synthesized as potent DNA binding antitumor compounds. Most synthesized compounds displayed good activity against human leukemia K562 cells in MTT tests, with compo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.02.003

    authors： Zhang B,Chen K,Wang N,Gao C,Sun Q,Li L,Chen Y,Tan C,Liu H,Jiang Y

    更新日期：2015-03-26 00:00:00

  • Pharmaceutical salts and cocrystals involving amino acids: a brief structural overview of the state-of-art.

    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

    authors： Tilborg A,Norberg B,Wouters J

    更新日期：2014-03-03 00:00:00

  • Polypharmacological drug actions of recently FDA approved antibiotics.

    abstract：:The current epidemic of antibiotic resistant bacterial infections has fueled the demand for novel antibiotics exhibiting both antibacterial efficacy and anti-drug resistance. This need has not been fully satisfied by the conventional "one target-one molecule" approach. Consequently, there has been rising interest in t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.112931

    authors： Wetzel C,Lonneman M,Wu C

    更新日期：2021-01-01 00:00:00

  • Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I.

    abstract：:A new series of 2-substituted imino-3-substituted-5- heteroarylidene-1,3-thiazolidine-4-ones as the potent bidentate PTP1B inhibitors were designed and synthesized in this paper. All of the new compounds were characterized and identified by spectra analysis. The biological screening test against PTP1B showed that some...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.05.060

    authors： Meng G,Zheng M,Wang M,Tong J,Ge W,Zhang J,Zheng A,Li J,Gao L,Li J

    更新日期：2016-10-21 00:00:00

  • The synthesis and biological evaluation of novel Danshensu-cysteine analog conjugates as cardiovascular-protective agents.

    abstract：:A series of novel amide and thioester conjugates between Danshensu and cysteine derivatives have been designed and synthesized based on the strategy of "medicinal chemical hybridization". Pharmacological evaluation indicated that the amide conjugates 3a/4a/17a and thioester conjugates 6a-d exhibited obvious protective...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.07.016

    authors： Jia Y,Dong X,Zhou P,Liu X,Pan L,Xin H,Zhu YZ,Wang Y

    更新日期：2012-09-01 00:00:00

  • 2-Aminothiazole: A privileged scaffold for the discovery of anti-cancer agents.

    abstract：:Cancer has been the second heath killer being next only to cardiovascular diseases in human society. Although many efforts have been taken for cancer therapy and many achievements have been yielded in the diagnosis and treatment of cancer, the current first-line anti-cancer agents are insufficient owing to the emergen...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.112953

    authors： Wan Y,Long J,Gao H,Tang Z

    更新日期：2021-01-15 00:00:00

  • Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside.

    abstract：:Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavaila...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.02.082

    authors： Palacios M,Tampe R,Del Campo M,Zhong TY,López MN,Salazar-Onfray F,Becker MI

    更新日期：2018-04-25 00:00:00

  • The new facile and straightforward method for the synthesis of 4H-1,2,3-thiadiazolo[5,4-b]indoles and determination of their antiproliferative activity.

    abstract：:A series of 4H-1,2,3-thiadiazolo[5,4-b]indoles were synthesized by novel tandem of oxidative cyclization of 3-alkoxycarbonylhydrazonoindoline-2-thiones, 1,5-H-shift and elimination of tert-butoxy(ethoxy)carbonyl group. The simple method for their modifications by the reactions with electrophilic agents were elaborated...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.11.011

    authors： Belskaya NP,Lugovik KI,Bakulev VA,Bauer J,Kitanovic I,Holenya P,Zakhartsev M,Wölfl S

    更新日期：2016-01-27 00:00:00

  • Repurposing ibuprofen to control Staphylococcus aureus biofilms.

    abstract：:Drug repurposing arises as an interesting alternative to overcome the limited efficacy of current available antibiotics by reducing time, cost and risk associated with drug innovation. In this study, the activity of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), was evaluated on the control of pre-establis...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.01.046

    authors： Oliveira IM,Borges A,Borges F,Simões M

    更新日期：2019-03-15 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

    doi：10.1016/j.ejmech.2010.08.040

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

    更新日期：2010-11-01 00:00:00

  • Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1-b]thiazole derivatives.

    abstract：:Design and synthesis of a new series of 5,6-diarylimidazo[2,1-b]thiazole derivatives possessing terminal aryl sulfonamide moiety are described. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 8a, 8b, 8n, 8q, 8t, ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.03.065

    authors： Abdel-Maksoud MS,Kim MR,El-Gamal MI,Gamal El-Din MM,Tae J,Choi HS,Lee KT,Yoo KH,Oh CH

    更新日期：2015-05-05 00:00:00

  • Prenylflavonoids and prenyl/alkyl-phloroacetophenones: synthesis and antitumour biological evaluation.

    abstract：:Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.06.025

    authors： Basabe P,de Román M,Marcos IS,Diez D,Blanco A,Bodero O,Mollinedo F,Sierra BG,Urones JG

    更新日期：2010-09-01 00:00:00

  • Non-chelating p-phenylidene-linked bis-imidazoline analogs of known influenza virus endonuclease inhibitors: Synthesis and anti-influenza activity.

    abstract：:A novel chemotype topologically similar to known influenza virus PA endonuclease inhibitors has been designed. It was aimed to reproduce the extended topology of the known metal-chelating ligands with a p-phenylidene-linked bis-imidazoline scaffold. It was envisioned that aromatic groups introduced to this scaffolds v...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.10.063

    authors： Dar'in D,Zarubaev V,Galochkina A,Gureev M,Krasavin M

    更新日期：2019-01-01 00:00:00

  • Optimisation of correlation weights of SMILES invariants for modelling oral quail toxicity.

    abstract：:The SMILES (simplified molecular input line entry system) nomenclature was used to elucidate the molecular structure in constructing the quantitative structure-property/activity relationships (QSPR/QSAR) for predicting quail toxicity after oral exposure. The presence of chemical elements in different electronic states...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.11.018

    authors： Toropov AA,Benfenati E

    更新日期：2007-05-01 00:00:00