Effect of C7 modifications on benzothiadiazine-1,1-dioxide derivatives on their inhibitory activity and selectivity toward aldose reductase.

abstract：:Structural preorganization to fix bioactive conformations at protein binding sites is a popular strategy to enhance binding affinity during late-stage optimization. The rationale for this enhancement relates to entropic advantages assigned to rigidified versus flexible ligands. We analyzed a narrow series of peptidomi...

journal_title：ChemMedChem

authors： Rühmann EH,Rupp M,Betz M,Heine A,Klebe G

更新日期：2016-02-04 00:00:00

abstract：:A small library of 17 organoruthenium compounds with the general formula [RuII (fcl)(chel)(L)]n+ (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compou...

journal_title：ChemMedChem

authors： Ristovski S,Uzelac M,Kljun J,Lipec T,Uršič M,Zemljič Jokhadar Š,Žužek MC,Trobec T,Frangež R,Sepčić K,Turel I

更新日期：2018-10-22 00:00:00

abstract：:The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Here, we present the efficient synthesis of five Glc-GlcA-Glc sequenced and one Glc-IdoA-Glc sequenced non-glycosaminoglycan, heparin-related trisaccharides with various...

journal_title：ChemMedChem

authors： Lisztes E,Mező E,Demeter F,Horváth L,Bősze S,Tóth BI,Borbás A,Herczeg M

更新日期：2021-01-12 00:00:00

abstract：:We recently reported a vitamin B(12) (B(12)) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B(12) conjugation have on insulin's interaction with the insulin receptor (IR...

journal_title：ChemMedChem

authors： Petrus AK,Allis DG,Smith RP,Fairchild TJ,Doyle RP

更新日期：2009-03-01 00:00:00

abstract：:Src homology 2 (SH2)-domain-mediated interactions with phosphotyrosine (pY)-containing ligands are critical for the regulation of SHP-1 phosphatase activity. Peptides based on a binding site from receptor tyrosine kinase Ros (EGLN-pY2267-MVL, 1) have recently been shown to bind to the SHP-1 N-terminal SH2 domain (N-SH...

journal_title：ChemMedChem

authors： Hampel K,Kaufhold I,Zacharias M,Böhmer FD,Imhof D

更新日期：2006-08-01 00:00:00

abstract：:Herein we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric chemokine receptor 2 (CXCR2) inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2, with IC50 values less than 10 μm ...

journal_title：ChemMedChem

authors： Mehanna WE,Lu T,Debnath B,Lasheen DS,Serya RAT,Abouzid KA,Neamati N

更新日期：2017-07-06 00:00:00

abstract：:Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kina...

journal_title：ChemMedChem

authors： Margutti S,Laufer SA

更新日期：2007-08-01 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：:A panel of new potential Ras ligands was generated by decorating a tricyclic levoglucosenone-derived scaffold with aromatic moieties. Some members of the panel show in vitro inhibitory activity toward the nucleotide exchange process on Ras and are toxic to some human cancer cell lines. ...

journal_title：ChemMedChem

authors： Müller C,Gomez-Zurita Frau MA,Ballinari D,Colombo S,Bitto A,Martegani E,Airoldi C,van Neuren AS,Stein M,Weiser J,Battistini C,Peri F

更新日期：2009-04-01 00:00:00

abstract：:A set of piperonylic acid derived hydrazones with variable isatin moieties was synthesized and evaluated for their inhibitory activity against the enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A/B). The results of in vitro studies revealed IC50 values in the mic...

journal_title：ChemMedChem

authors： Vishnu MS,Pavankumar V,Kumar S,Raja AS

更新日期：2019-07-17 00:00:00

abstract：:Opening up ion channels: We synthesised a series of anthraquinone analogues, called the GoSlo-SR family. Their effects on bladder smooth muscle BK channels were examined and, as shown, shifted voltage dependent activation >-100 mV (at 10 μM). They were more efficacious than NS11021 and could provide a new scaffold for...

journal_title：ChemMedChem

authors： Roy S,Morayo Akande A,Large RJ,Webb TI,Camarasu C,Sergeant GP,McHale NG,Thornbury KD,Hollywood MA

更新日期：2012-10-01 00:00:00

abstract：:Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including ge...

journal_title：ChemMedChem

authors： Mirguet O,Lamotte Y,Chung CW,Bamborough P,Delannée D,Bouillot A,Gellibert F,Krysa G,Lewis A,Witherington J,Huet P,Dudit Y,Trottet L,Nicodeme E

更新日期：2014-03-01 00:00:00

abstract：:Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action. He...

journal_title：ChemMedChem

authors： Patel H,Lucas X,Bendik I,Günther S,Merfort I

更新日期：2015-07-01 00:00:00

abstract：:A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of t...

journal_title：ChemMedChem

authors： Kamal A,Reddy MK,Ramaiah MJ,Srikanth YV,Rajender,Reddy VS,Kumar GB,Pushpavalli SN,Bag I,Juvekar A,Sen S,Zingde SM,Pal-Bhadra M

更新日期：2011-09-05 00:00:00

abstract：:For (64) Cu radiolabeling of biomolecules to be used as in vivo positron emission tomography (PET) imaging agents, various chelators are commonly applied. It has not yet been determined which of the most potent chelators--NODA-GA ((1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid), CB-TE2A (2,2'-(1,4,8,1...

journal_title：ChemMedChem

authors： Litau S,Seibold U,Vall-Sagarra A,Fricker G,Wängler B,Wängler C

更新日期：2015-07-01 00:00:00

abstract：:The Eph-ephrin system, including the EphA2 receptor and the ephrinA1 ligand, plays a critical role in tumor and vascular functions during carcinogenesis. We previously identified (3α,5β)-3-hydroxycholan-24-oic acid (lithocholic acid) as an Eph-ephrin antagonist that is able to inhibit EphA2 receptor activation; it is ...

journal_title：ChemMedChem

authors： Tognolini M,Incerti M,Hassan-Mohamed I,Giorgio C,Russo S,Bruni R,Lelli B,Bracci L,Noberini R,Pasquale EB,Barocelli E,Vicini P,Mor M,Lodola A

更新日期：2012-06-01 00:00:00

abstract：:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...

journal_title：ChemMedChem

authors： Kamal A,Dastagiri D,Ramaiah MJ,Reddy JS,Bharathi EV,Srinivas C,Pushpavalli SN,Pal D,Pal-Bhadra M

更新日期：2010-11-08 00:00:00

abstract：:Different Mannich base derivatives have been studied with the aim of addressing the poor aqueous solubility of the recently disclosed 6-phenethyl-2,3,4,5-tetrahydroazepino[4,3-b]indol-1(6H)-one (1), a human butyrylcholinesterase inhibitor (hBChE, IC50 13 nM) and protective agent in NMDA-induced neurotoxicity, in in vi...

journal_title：ChemMedChem

authors： Purgatorio R,de Candia M,Catto M,Rullo M,Pisani L,Denora N,Carrieri A,Nevskaya AA,Voskressensky LG,Altomare CD

更新日期：2020-11-06 00:00:00

abstract：:The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signalling processes and cell proliferation. It has been reported that an improper amplification or activation of these enzymes is a distinctive feature of a number of human cancers, including breast cancers. Thus, the inhibition of Cd...

journal_title：ChemMedChem

authors： Lavecchia A,Cosconati S,Limongelli V,Novellino E

更新日期：2006-05-01 00:00:00

abstract：:The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, h...

journal_title：ChemMedChem

authors： Czerwonka D,Urbaniak A,Sobczak S,Piña-Oviedo S,Chambers TC,Antoszczak M,Huczyński A

更新日期：2020-01-17 00:00:00

abstract：:The disruption of aberrant protein-protein interactions (PPIs) with synthetic agents remains a challenging goal in contemporary medicinal chemistry but some progress has been made. One such dysregulated PPI is that between the anti-apoptotic Bcl-2 proteins, including myeloid cell leukemia-1 (Mcl-1), and the α-helical ...

journal_title：ChemMedChem

authors： Drennen B,Scheenstra JA,Yap JL,Chen L,Lanning ME,Roth BM,Wilder PT,Fletcher S

更新日期：2016-04-19 00:00:00

abstract：:Drug metabolism, toxicity, and their interaction profiles are major issues in the drug-discovery and lead-optimization processes. The cytochromes P450 (CYPs) 2D6 and 2C9 are enzymes involved in the oxidative metabolism of a majority of marketed drugs. Therefore, the prediction of the binding affinity towards CYP2D6 an...

journal_title：ChemMedChem

authors： Rossato G,Ernst B,Smiesko M,Spreafico M,Vedani A

更新日期：2010-12-03 00:00:00

abstract：:Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic-resistant threat, and has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acqu...

journal_title：ChemMedChem

authors： Li C,Teng P,Peng Z,Sang P,Sun X,Cai J

更新日期：2018-07-18 00:00:00

abstract：:An emerging and attractive target for the treatment of Alzheimer's disease is to inhibit the aggregation of beta-amyloid protein (Abeta). We applied the retro-enantio concept to design an N-methylated peptidic inhibitor of the Abeta42 aggregation process. This inhibitor, inrD, as well as the corresponding all-L (inL) ...

journal_title：ChemMedChem

authors： Grillo-Bosch D,Carulla N,Cruz M,Sánchez L,Pujol-Pina R,Madurga S,Rabanal F,Giralt E

更新日期：2009-09-01 00:00:00

abstract：:Metalloproteinases of the astacin family are drawing ever increasing attention as potential drug targets. However, knowledge regarding inhibitors thereof is limited in most cases. Crucial for the development of metalloprotease inhibitors is high selectivity, to avoid side effects brought about by inhibition of off-tar...

journal_title：ChemMedChem

authors： Tan K,Jäger C,Schlenzig D,Schilling S,Buchholz M,Ramsbeck D

更新日期：2018-08-20 00:00:00

abstract：:A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl-modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hy...

journal_title：ChemMedChem

authors： Datta D,Dasgupta S,Pathak T

更新日期：2014-09-01 00:00:00

abstract：:A structure-activity relationship around the amine group of the ambruticin VS series has been developed for antifungal activity. It was shown that the amine can be alkylated through reductive amination without loss of potency. However, if it is converted into either an amide, carbamate, or urea, a significant loss of ...

journal_title：ChemMedChem

authors： Tian ZQ,Wang Z,Xu Y,Tran CQ,Myles DC,Zhong Z,Simmons J,Vetcher L,Katz L,Li Y,Shaw SJ

更新日期：2008-06-01 00:00:00

abstract：:There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bea...

journal_title：ChemMedChem

authors： Maurer A,Leonov A,Ryazanov S,Herfert K,Kuebler L,Buss S,Schmidt F,Weckbecker D,Linder R,Bender D,Giese A,Pichler BJ,Griesinger C

更新日期：2020-03-05 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：:In the present review the crucial role of the guanidinium functional group in facilitating the transport of dendritic polymers through liposomal and cell membranes is discussed, along with other structural features of guanidinylated dendritic polymers that fine-tune their transport properties, and even determine their...

journal_title：ChemMedChem

authors： Theodossiou TA,Pantos A,Tsogas I,Paleos CM

更新日期：2008-11-01 00:00:00