Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands.

abstract：:Detailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy and mas...

journal_title：ChemMedChem

authors： Ceccarelli SM,Schlotterbeck G,Boissin P,Binder M,Buettelmann B,Hanlon S,Jaeschke G,Kolczewski S,Kupfer E,Peters JU,Porter RH,Prinssen EP,Rueher M,Ruf I,Spooren W,Stämpfli A,Vieira E

更新日期：2008-01-01 00:00:00

abstract：:The natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL's potency, we designed...

journal_title：ChemMedChem

authors： Wang X,Qian J,Zhu P,Hua R,Liu J,Hang J,Meng C,Shan W,Miao J,Ling Y

更新日期：2020-10-21 00:00:00

abstract：:Over the years, a number of dimensionality reduction techniques have been proposed and used in chemoinformatics to perform nonlinear mappings. In this study, four representatives of nonlinear dimensionality reduction methods related to two different families were analyzed: distance-based approaches (Isomap and Diffusi...

journal_title：ChemMedChem

authors： Kireeva NV,Ovchinnikova SI,Tetko IV,Asiri AM,Balakin KV,Tsivadze AY

更新日期：2014-05-01 00:00:00

abstract：:Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...

journal_title：ChemMedChem

authors： Ziegler K,Hauser DR,Unger A,Albrecht W,Laufer SA

更新日期：2009-11-01 00:00:00

abstract：:Indolicidin (IR13), a 13-residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires ...

journal_title：ChemMedChem

authors： Ghosh A,Kar RK,Jana J,Saha A,Jana B,Krishnamoorthy J,Kumar D,Ghosh S,Chatterjee S,Bhunia A

更新日期：2014-09-01 00:00:00

abstract：:A series of pyrazolo[3,4-d]pyrimidines, previously found to be Src inhibitors, was tested for their ability to inhibit proliferation of three Bcr-Abl-positive human leukemia cell lines (K-562, KU-812, and MEG-01), on the basis of the experimental evidence that various Src inhibitors are also active against Bcr-Abl kin...

journal_title：ChemMedChem

authors： Manetti F,Pucci A,Magnani M,Locatelli GA,Brullo C,Naldini A,Schenone S,Maga G,Carraro F,Botta M

更新日期：2007-03-01 00:00:00

abstract：:Discovered as a modulator of the toxic response to environmental pollutants, aryl hydrocarbon receptor (AhR) has recently gained attention for its involvement in various physiological and pathological pathways. AhR is a ligand-dependent transcription factor activated by a large array of chemical compounds, which inclu...

journal_title：ChemMedChem

authors： Dolciami D,Gargaro M,Cerra B,Scalisi G,Bagnoli L,Servillo G,Fazia MAD,Puccetti P,Quintana FJ,Fallarino F,Macchiarulo A

更新日期：2018-02-06 00:00:00

abstract：:We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH...

journal_title：ChemMedChem

authors： Casiraghi A,Longhena F,Straniero V,Faustini G,Newman AH,Bellucci A,Valoti E

更新日期：2020-07-20 00:00:00

abstract：:A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective...

journal_title：ChemMedChem

authors： Weik S,Luksch T,Evers A,Böttcher J,Sotriffer CA,Hasilik A,Löffler HG,Klebe G,Rademann J

更新日期：2006-04-01 00:00:00

abstract：:Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl-urea fatty acid (1 g; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl-ureas the prese...

journal_title：ChemMedChem

authors： Murray M,Roseblade A,Chen Y,Bourget K,Rawling T

更新日期：2020-01-17 00:00:00

abstract：:Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channe...

journal_title：ChemMedChem

authors： Quadri M,Matera C,Silnović A,Pismataro MC,Horenstein NA,Stokes C,Papke RL,Dallanoce C

更新日期：2017-08-22 00:00:00

abstract：:With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide. LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeut...

journal_title：ChemMedChem

authors： Skovstrup S,Le Quement ST,Hansen T,Jakobsen TH,Harmsen M,Tolker-Nielsen T,Nielsen TE,Givskov M,Taboureau O

更新日期：2013-01-01 00:00:00

abstract：:Singling out the truth: A combined application of STD-NMR, molecular docking, and CORCEMA-ST calculations is described as an attractive, easily applicable tool for the identification and validation of the binding site for allosteric ligands, with potential application as an aid in drug discovery research. ...

journal_title：ChemMedChem

authors： Zhang W,Li R,Shin R,Wang Y,Padmalayam I,Zhai L,Krishna NR

更新日期：2013-10-01 00:00:00

abstract：:Nucleoside analogues are extensively used as antiviral and anticancer agents. Their efficiency is dependent on their metabolism into the ultimately active nucleoside triphosphates. Often one step or even more in the metabolism of the nucleoside to the triphosphate is inefficient. To overcome this hurdle, prodrugs of t...

journal_title：ChemMedChem

authors： Weinschenk L,Gollnest T,Schols D,Balzarini J,Meier C

更新日期：2015-05-01 00:00:00

abstract：:Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Herein we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary N-substituted 7-amino...

journal_title：ChemMedChem

authors： Abdelkarim H,Neelarapu R,Madriaga A,Vaidya AS,Kastrati I,Karumudi B,Wang YT,Taha TY,Thatcher GRJ,Frasor J,Petukhov PA

更新日期：2017-12-19 00:00:00

abstract：:Herbal medicines (HMs) are an important source of drugs. In this study, an efficient strategy integrating ultrafiltration LC-MS, microplate bioassays, and molecular docking was proposed to screen high-potency enzyme inhibitors from HMs. Using this strategy, the structure-activity relationships (SARs) including binding...

journal_title：ChemMedChem

authors： Song HP,Wang H,Liang JX,Qian C,Wu SQ,Xu WJ,Wu B,Liu XG,Li P,Yang H

更新日期：2016-12-06 00:00:00

abstract：:The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in c...

journal_title：ChemMedChem

authors： Marighetti F,Steggemann K,Hanl M,Wiese M

更新日期：2013-01-01 00:00:00

abstract：:Despite various inhibitors targeting the zinc center(s) of enzymes, drugs that target zinc fingers have not been examined in detail. We previously developed a dithiol compound named SN-1 that has an inhibitory effect on the function of zinc finger transcription factors, but its mechanism of action has not yet been elu...

journal_title：ChemMedChem

authors： Koga R,Radwan MO,Ejima T,Kanemaru Y,Tateishi H,Ali TFS,Ciftci HI,Shibata Y,Taguchi Y,Inoue JI,Otsuka M,Fujita M

更新日期：2017-12-07 00:00:00

abstract：:3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives were synthesized, and their structures were confirmed by single-crystal X-ray diffraction. This reaction yields the 1,4-dicarboxamide derivatives rather than the 1,2-dicarboxamide derivatives. Their in vitro antitumor activities were evaluated against SGC-79...

journal_title：ChemMedChem

authors： Rao GW,Guo YM,Hu WX

更新日期：2012-06-01 00:00:00

abstract：:A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a n...

journal_title：ChemMedChem

authors： Humbeck L,Weigang S,Schäfer T,Mutzel P,Koch O

更新日期：2018-03-20 00:00:00

abstract：:The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recen...

journal_title：ChemMedChem

authors： Xiong XF,Poulsen MH,Hussein RA,Nørager NG,Strømgaard K

更新日期：2014-12-01 00:00:00

abstract：:Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a small molecule with potent anticancer activity. Like other 1,4-naphthoquinones, it exhibits electrophilic reactivity towards biological nucleophiles. We demonstrate that plumbagin and structurally related 1,4-naphthoquinones with at least one unsubstituted quinoid...

journal_title：ChemMedChem

authors： Chrastina A,Welsh J,Rondeau G,Abedinpour P,Borgström P,Baron VT

更新日期：2020-07-20 00:00:00

abstract：:Following the discovery of a type III allosteric modulator of cyclin-dependent kinase 2 (CDK2) characterized by a hexahydrocyclopenta[c]quinolone scaffold, three different series of its derivatives were synthesized and biologically evaluated. Docking of the synthesized compounds into the allosteric pocket of CDK2 allo...

journal_title：ChemMedChem

authors： Carlino L,Christodoulou MS,Restelli V,Caporuscio F,Foschi F,Semrau MS,Costanzi E,Tinivella A,Pinzi L,Lo Presti L,Battistutta R,Storici P,Broggini M,Passarella D,Rastelli G

更新日期：2018-12-20 00:00:00

abstract：:AFMC-AIMECS meetings are internationally organized biannually by the Asian Federation for Medicinal Chemistry (AFMC) and are focused on recent studies in drug discovery and development both in academia and industry. Member organizations of the AFMC are the Pharmaceutical Society of Japan, the Chinese Pharmaceutical As...

journal_title：ChemMedChem

authors： Olgac A,Yalcin I,Aki-Yalcin E

更新日期：2020-01-07 00:00:00

abstract：:Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery. Lactose-funct...

journal_title：ChemMedChem

authors： Murthy RV,Bavireddi H,Gade M,Kikkeri R

更新日期：2015-05-01 00:00:00

abstract：:Computer-guided drug design is a powerful tool for drug discovery. Herein we disclose the use of this approach for the discovery of dual FMS-like receptor tyrosine kinase-3 (FLT3)-Aurora A inhibitors against cancer. An Aurora hit compound was selected as a starting point, from which 288 virtual molecules were screened...

journal_title：ChemMedChem

authors： Chang Hsu Y,Ke YY,Shiao HY,Lee CC,Lin WH,Chen CH,Yen KJ,Hsu JT,Chang C,Hsieh HP

更新日期：2014-05-01 00:00:00

abstract：:Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prep...

journal_title：ChemMedChem

authors： Bayer T,Chakrabarti A,Lancelot J,Shaik TB,Hausmann K,Melesina J,Schmidtkunz K,Marek M,Erdmann F,Schmidt M,Robaa D,Romier C,Pierce RJ,Jung M,Sippl W

更新日期：2018-08-10 00:00:00

abstract：:The natural product acivicin inhibits the glutaminase activity of cytidine triphosphate (CTP) synthetase and is a potent lead compound for drug discovery in the area of neglected tropical diseases, specifically trypanosomaisis. A 2.1-Å-resolution crystal structure of the acivicin adduct with the glutaminase domain fro...

journal_title：ChemMedChem

authors： Oliveira de Souza J,Dawson A,Hunter WN

更新日期：2017-04-20 00:00:00

abstract：:Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide he...

journal_title：ChemMedChem

authors： Hartung IV,Pühler F,Neuhaus R,Scholz A,Siemeister G,Geisler J,Hillig RC,von Ahsen O,Hitchcock M

更新日期：2015-12-01 00:00:00

abstract：:Dual inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO), two key enzymes involved in pro-inflammatory eicosanoid biosynthesis, represents a new strategy for treating inflammatory disorders. Herein we report the discovery of 2,4-thiazolidinedione-based mPGES-1/5-LO dual inhibitors ...

journal_title：ChemMedChem

authors： Lauro G,Terracciano S,Cantone V,Ruggiero D,Fischer K,Pace S,Werz O,Bruno I,Bifulco G

更新日期：2020-03-18 00:00:00