The discovery of novel human androgen receptor antagonist chemotypes using a combined pharmacophore screening procedure.

abstract：:ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an indole moiety considerably increased stability and gave potent and selective ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances fumitremorgin C and Ko143 in terms of potency and efficacy and are the most potent AB...

journal_title：ChemMedChem

authors： Bauer S,Ochoa-Puentes C,Sun Q,Bause M,Bernhardt G,König B,Buschauer A

更新日期：2013-11-01 00:00:00

abstract：:A novel type of oligonucleotide has been developed, characterized by the attachment of a lysyl moiety to a 2'-O-aminohexyl linker. A protected lysine building block was tethered to 2'-O-aminohexyluridine, and the product was converted into the corresponding phosphoramidite. Up to six modified nucleosides were incorpor...

journal_title：ChemMedChem

authors： Winkler J,Gilbert M,Kocourková A,Stessl M,Noe CR

更新日期：2008-01-01 00:00:00

abstract：:A novel class of isochroman dopamine analogues, originally reported by Abbott Laboratories, have >100-fold selectivity for D₁-like over D₂-like receptors. We synthesized a parallel series of chroman compounds and showed that repositioning the oxygen atom in the heterocyclic ring decreases potency and confers D₂-like r...

journal_title：ChemMedChem

authors： Bonner LA,Laban U,Chemel BR,Juncosa JI,Lill MA,Watts VJ,Nichols DE

更新日期：2011-06-06 00:00:00

abstract：:Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and i...

journal_title：ChemMedChem

authors： Brullo C,Rapetti F,Alfei S,Maric I,Rizzelli F,Mapelli M,Rosano C,Viale M,Bruno O

更新日期：2020-06-04 00:00:00

abstract：:The design of compounds selective for the MT1 melatonin receptor is still a challenging task owing to the limited knowledge of the structural features conferring selectivity for the MT1 subtype, and only few selective compounds have been reported so far. N-(Anilinoalkyl)amides are a versatile class of melatonin recept...

journal_title：ChemMedChem

authors： Rivara S,Pala D,Lodola A,Mor M,Lucini V,Dugnani S,Scaglione F,Bedini A,Lucarini S,Tarzia G,Spadoni G

更新日期：2012-11-01 00:00:00

abstract：:Some hybrid foldamers of various length, all containing the (4R,5S)-4-carboxy-5-methyloxazolidin-2-one (d-Oxd) moiety alternating with an l-amino acid (l-Val, l-Lys, or l-Ala), were prepared in order to study their preferred conformations and to evaluate their biological activity. Surprisingly, only the longer oligome...

journal_title：ChemMedChem

authors： Del Secco B,Malachin G,Milli L,Zanna N,Papini E,Cornia A,Tavano R,Tomasini C

更新日期：2017-02-20 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：:The synthesis of SCF3 as well as SeCF3 isosteres of two OCF3 -containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF3 and SeCF3 groups are more lipoph...

journal_title：ChemMedChem

authors： Ghiazza C,Billard T,Dickson C,Tlili A,Gampe CM

更新日期：2019-09-04 00:00:00

abstract：:Herein we describe the synthesis and conformational analysis of a series of bicyclic thymidine derivatives and their evaluation as inhibitors of thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt), based on previously discovered bicyclic sugar nucleosides. With a K(i) value of 2.3 microm, 1-[3-amin...

journal_title：ChemMedChem

authors： Van Daele I,Munier-Lehmann H,Hendrickx PM,Marchal G,Chavarot P,Froeyen M,Qing L,Martins JC,Van Calenbergh S

更新日期：2006-10-01 00:00:00

abstract：:The clinical use of N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) has been hindered by its lack of bioavailability. N,N'-bis(2-boronic pinacol ester benzyl)ethylenediamine-N,N'-diacetic acid methyl, ethyl, and isopropyl esters 7 a-c, respectively, and their dimesylate salts 8 a-c, are double prodr...

journal_title：ChemMedChem

authors： Thiele NA,Sloan KB

更新日期：2016-08-05 00:00:00

abstract：:New geiparvarin derivatives modified at the unsaturated alkenyloxy bridge, where a hydrogen atom replaces the 3'-methyl group, were synthesized and evaluated against a panel of human tumor cell lines in vitro. These compounds demonstrated an increase in growth inhibitory activity relative to the parent compound, geipa...

journal_title：ChemMedChem

authors： Chimichi S,Boccalini M,Salvador A,Dall'Acqua F,Basso G,Viola G

更新日期：2009-05-01 00:00:00

abstract：:Quorum sensing has been implicated in the control of pathologically relevant bacterial behavior such as secretion of virulence factors, biofilm formation, sporulation, and swarming motility. The AI-2 quorum sensing pathway is found in both gram-positive and gram-negative bacteria. Therefore, antagonizing AI-2 quorum s...

journal_title：ChemMedChem

authors： Li M,Ni N,Chou HT,Lu CD,Tai PC,Wang B

更新日期：2008-08-01 00:00:00

abstract：:Given the number of monogenic ocular diseases and the number of non-monogenic degenerative ocular diseases for which gene therapy is considered as a treatment, the development of effective therapeutic delivery strategies for DNA is a critical research goal. In this work, nonviral nanoparticles (NPs) composed of glycol...

journal_title：ChemMedChem

authors： Mitra RN,Han Z,Merwin M,Al Taai M,Conley SM,Naash MI

更新日期：2014-01-01 00:00:00

abstract：:Uropathogenic E. coli (UPEC) employ the mannose-binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half-life in vivo. In a rational design strategy, we obtained an X-ra...

journal_title：ChemMedChem

authors： Jarvis C,Han Z,Kalas V,Klein R,Pinkner JS,Ford B,Binkley J,Cusumano CK,Cusumano Z,Mydock-McGrane L,Hultgren SJ,Janetka JW

更新日期：2016-02-17 00:00:00

abstract：:N-Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti-inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator-activated receptor α (PPAR-α). Thus, p...

journal_title：ChemMedChem

authors： Fiasella A,Nuzzi A,Summa M,Armirotti A,Tarozzo G,Tarzia G,Mor M,Bertozzi F,Bandiera T,Piomelli D

更新日期：2014-07-01 00:00:00

abstract：:Polo-like kinase 1 (PLK1) plays crucial functions in multiple stages of mitosis and is considered to be a potential drug target for cancer therapy. The functions of PLK1 are mediated by its N-terminal kinase domain and C-terminal polo-box domain (PBD). Most inhibitors targeting the kinase domain of PLK1 have a selecti...

journal_title：ChemMedChem

authors： Shan HM,Shi Y,Quan J

更新日期：2015-01-01 00:00:00

abstract：:Iron is essential for the pathogenicity and virulence of Mycobacterium tuberculosis, which synthesises salicyl-capped siderophores (mycobactins) to acquire this element from the host. MbtA is the adenylating enzyme that catalyses the initial reaction of mycobactin biosynthesis and is solely expressed by mycobacteria. ...

journal_title：ChemMedChem

authors： Ferguson L,Wells G,Bhakta S,Johnson J,Guzman J,Parish T,Prentice RA,Brucoli F

更新日期：2019-10-04 00:00:00

abstract：:Myotonic dystrophy is the most common form of adult-onset muscular dystrophy, originating in a CTG repeat expansion in the DMPK gene. The expanded CUG transcript sequesters MBNL1, a key regulator of alternative splicing, leading to the misregulation of numerous pre-mRNAs. We report an RNA-targeted agent as a possible ...

journal_title：ChemMedChem

authors： Luu LM,Nguyen L,Peng S,Lee J,Lee HY,Wong CH,Hergenrother PJ,Chan HY,Zimmerman SC

更新日期：2016-07-05 00:00:00

abstract：:The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor...

journal_title：ChemMedChem

authors： Fershtat LL,Makhova NN

更新日期：2017-05-09 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：:In the present study the importance of the active site histidine residue (His) for the activity of epoxide- or aziridine-based cysteine protease inhibitors is examined theoretically. To account for all important effects, QM/MM hybrid approaches are employed which combine quantum mechanical (QM) methods that are necess...

journal_title：ChemMedChem

authors： Mladenovic M,Schirmeister T,Thiel S,Thiel W,Engels B

更新日期：2007-01-01 00:00:00

abstract：:Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD)-dependent enzyme that catalyzes the demethylation of histone H3 and regulates gene expression. Because it is implicated in the regulation of diseases such as acute myeloid leukemia, potent LSD1-specific inhibitors have been pursued. Trans-2-ph...

journal_title：ChemMedChem

authors： Niwa H,Sato S,Handa N,Sengoku T,Umehara T,Yokoyama S

更新日期：2020-05-06 00:00:00

abstract：:A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the desi...

journal_title：ChemMedChem

authors： Yang Y,Zhang S,Wu B,Ma M,Chen X,Qin X,He M,Hussain S,Jing C,Ma B,Zhu C

更新日期：2012-05-01 00:00:00

abstract：:Nanoscale materials hold great promise in the therapeutic field. In particular, as carriers or vectors, they help bioactive molecules reach their primary targets. Furthermore, by themselves, certain nanomaterials-regarded as protective-can modulate particular metabolic pathways that are deregulated in pathological sit...

journal_title：ChemMedChem

authors： Bianco A,Muller S

更新日期：2016-01-19 00:00:00

abstract：:To ascertain whether increasing hydrophobicity can enhance the activity of second-generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2'-O-(2S-methoxypropyl)-RNA (2S-MOP)-modified ASOs. Synthesis of the 2S-MOP 5-methyl uridine phosphoramidite was accomplished on a multi-...

journal_title：ChemMedChem

authors： Yu J,Pandey SK,Khatri H,Prakash TP,Swayze EE,Seth PP

更新日期：2014-09-01 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：: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：: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：:Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin ch...

journal_title：ChemMedChem

authors： Meirelles MA,Braga CB,Ornelas C,Pilli RA

更新日期：2019-08-06 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