PAR2 Modulators Derived from GB88.

abstract：:A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitr...

journal_title：ACS medicinal chemistry letters

authors： Tukulula M,Njoroge M,Abay ET,Mugumbate GC,Wiesner L,Taylor D,Gibhard L,Norman J,Swart KJ,Gut J,Rosenthal PJ,Barteau S,Streckfuss J,Kameni-Tcheudji J,Chibale K

更新日期：2013-10-01 00:00:00

abstract：:ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse antic...

journal_title：ACS medicinal chemistry letters

authors： Peña-Solórzano D,Scholler M,Bernhardt G,Buschauer A,König B,Ochoa-Puentes C

更新日期：2018-07-25 00:00:00

abstract：:Medicinal chemists have increasing opportunities to transition from the pharmaceutical industry to academic medical centers interested in translational research. This Viewpoint highlights some of the differences between these two cultures and strategies to succeed in academic drug discovery. ...

journal_title：ACS medicinal chemistry letters

authors： Barrow JC

更新日期：2019-04-15 00:00:00

abstract：:Neuromedin U (NMU) and S (NMS) display various physiological activities, including an anorexigenic effect, and share a common C-terminal heptapeptide-amide sequence that is necessary to activate two NMU receptors (NMUR1 and NMUR2). On the basis of this knowledge, we recently developed hexapeptide agonists 2 and 3, whi...

journal_title：ACS medicinal chemistry letters

authors： Takayama K,Mori K,Sohma Y,Taketa K,Taguchi A,Yakushiji F,Minamino N,Miyazato M,Kangawa K,Hayashi Y

更新日期：2015-01-28 00:00:00

abstract：:The solution behavior of auranofin, Et3PAuCl  and Et3PAuI, as well as their interactions with hen egg white lysozyme, single strand oligonucleotide, and ds-DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement, DNA melting and viscometric tests. The cytotoxic effects toward re...

journal_title：ACS medicinal chemistry letters

authors： Marzo T,Cirri D,Gabbiani C,Gamberi T,Magherini F,Pratesi A,Guerri A,Biver T,Binacchi F,Stefanini M,Arcangeli A,Messori L

更新日期：2017-09-06 00:00:00

abstract：:A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocy...

journal_title：ACS medicinal chemistry letters

authors： Kim HL,Sachin K,Jeong HJ,Choi W,Lee HS,Kim DW

更新日期：2015-02-06 00:00:00

abstract：:Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was requ...

journal_title：ACS medicinal chemistry letters

authors： Tatani K,Hiratochi M,Nonaka Y,Isaji M,Shuto S

更新日期：2015-01-28 00:00:00

abstract：:Ataluren was reported to suppress nonsense mutations by promoting the readthrough of premature stop codons, although its mechanism of action (MOA) is still debated. The likely interaction of Ataluren with CFTR-mRNA has been previously studied by molecular dynamics. In this work we extended the modeling of Ataluren's M...

journal_title：ACS medicinal chemistry letters

authors： Tutone M,Pibiri I,Lentini L,Pace A,Almerico AM

更新日期：2019-02-07 00:00:00

abstract：:Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification o...

journal_title：ACS medicinal chemistry letters

authors： Hu Z,Banothu J,Beesu M,Gustafson CJ,Brush MJH,Trautman KL,Salyer ACD,Pathakumari B,David SA

更新日期：2018-12-20 00:00:00

abstract：:This report describes the investigation of a series of 5,7-disubstituted imidazo[5,1-f][1,2,4]triazine inhibitors of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR). Structure-activity relationship exploration and optimization leading to the identification, characterization, and pharmacologica...

journal_title：ACS medicinal chemistry letters

authors： Jin M,Gokhale PC,Cooke A,Foreman K,Buck E,May EW,Feng L,Bittner MA,Kadalbajoo M,Landfair D,Siu KW,Stolz KM,Werner DS,Laufer RS,Li AH,Dong H,Steinig AG,Kleinberg A,Yao Y,Pachter JA,Wild R,Mulvihill MJ

更新日期：2010-08-30 00:00:00

abstract：:A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure-activity relationship studies identified (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl)benzamide 7c as a potent and selective agonist of hGPR139 with ...

journal_title：ACS medicinal chemistry letters

authors： Dvorak CA,Coate H,Nepomuceno D,Wennerholm M,Kuei C,Lord B,Woody D,Bonaventure P,Liu C,Lovenberg T,Carruthers NI

更新日期：2015-07-20 00:00:00

abstract：:Several chemical probes have been developed for use in fluorescence polarization screening assays to aid in drug discovery for the bromodomain and extra-terminal domain (BET) proteins. However, few of those have been characterized in the literature. We have designed, synthesized, and thoroughly characterized a novel f...

journal_title：ACS medicinal chemistry letters

authors： Paulson CN,Guan X,Ayoub AM,Chan A,Karim RM,Pomerantz WCK,Schönbrunn E,Georg GI,Hawkinson JE

更新日期：2018-10-31 00:00:00

abstract：:Hsp90 C-terminal inhibitors represent a novel and alternative chemotherapeutic approach for the treatment of cancer. Novobiocin was the first natural product identified as an Hsp90 C-terminal inhibitor; however, it manifests poor antiproliferative activity. In contrast to N-terminal inhibitors, novobiocin does not ind...

journal_title：ACS medicinal chemistry letters

authors： Garg G,Zhao H,Blagg BS

更新日期：2014-12-12 00:00:00

abstract：:An active site mapping of human cathepsin B with dipeptide nitrile inhibitors was performed for a combinatorial approach by introducing several points of diversity and stepwise optimizing the inhibitor structure. To address the occluding loop of cathepsin B by a carboxylate moiety, click chemistry to generate linker-c...

journal_title：ACS medicinal chemistry letters

authors： Schmitz J,Li T,Bartz U,Gütschow M

更新日期：2015-12-28 00:00:00

abstract：:Visible light-mediated photocatalysis, which relies on the ability of photocatalysts to absorb low-energy visible light and engage in single-electron transfer (SET) or energy transfer (ET) processes with organic substrates, has emerged as one of the fastest growing fields in organic synthesis. This catalytic platform ...

journal_title：ACS medicinal chemistry letters

authors： Li P,Terrett JA,Zbieg JR

更新日期：2020-09-21 00:00:00

abstract：:Potent JNK3 isoform selective inhibitors were developed from a thiophenyl-pyrazolourea scaffold. Through structure activity relationship (SAR) studies utilizing enzymatic and cell-based assays, and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies, potent and highly selective JNK3 inhibitors with...

journal_title：ACS medicinal chemistry letters

authors： Feng Y,Park H,Bauer L,Ryu JC,Yoon SO

更新日期：2020-12-13 00:00:00

abstract：:With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic...

journal_title：ACS medicinal chemistry letters

authors： Fernández A

更新日期：2020-08-17 00:00:00

abstract：:Myeloperoxidase (MPO) is a key antimicrobial enzyme, playing a normal role in host defense, but also contributing to inflammatory conditions including neuroinflammatory diseases such as Parkinson's and Alzheimer's. We synthesized and characterized more than 50 quinazolin-4(1H)-one derivatives and showed that this clas...

journal_title：ACS medicinal chemistry letters

authors： Li Y,Ganesh T,Diebold BA,Zhu Y,McCoy JW,Smith SM,Sun A,Lambeth JD

更新日期：2015-08-31 00:00:00

abstract：:In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt1-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified...

journal_title：ACS medicinal chemistry letters

authors： Ballet S,Betti C,Novoa A,Tömböly C,Nielsen CU,Helms HC,Lesniak A,Kleczkowska P,Chung NN,Lipkowski AW,Brodin B,Tourwé D,Schiller PW

更新日期：2014-04-10 00:00:00

abstract：:We report a series of lipidated α-AApeptides that mimic the structure and function of natural antimicrobial lipopeptides. Several short lipidated α-AApeptides show broad-spectrum activity against a range of clinically related Gram-positive and Gram-negative bacteria as well as fungus. Their antimicrobial activity and ...

journal_title：ACS medicinal chemistry letters

authors： Hu Y,Amin MN,Padhee S,Wang RE,Qiao Q,Bai G,Li Y,Mathew A,Cao C,Cai J

更新日期：2012-07-12 00:00:00

abstract：:Translational readthrough-inducing drugs (TRIDs) rescue the functional full-length protein expression in genetic diseases, such as cystic fibrosis, caused by premature termination codons (PTCs). Small molecules have been developed as TRIDs to trick the ribosomal machinery during recognition of the PTC. Herein we repor...

journal_title：ACS medicinal chemistry letters

authors： Tutone M,Pibiri I,Perriera R,Campofelice A,Culletta G,Melfi R,Pace A,Almerico AM,Lentini L

更新日期：2020-02-18 00:00:00

abstract：:A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigat...

journal_title：ACS medicinal chemistry letters

authors： Angeli A,di Cesare Mannelli L,Trallori E,Peat TS,Ghelardini C,Carta F,Supuran CT

更新日期：2018-04-09 00:00:00

abstract：:Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carbox...

journal_title：ACS medicinal chemistry letters

authors： Waterson AG,Kennedy JP,Patrone JD,Pelz NF,Feldkamp MD,Frank AO,Vangamudi B,Souza-Fagundes EM,Rossanese OW,Chazin WJ,Fesik SW

更新日期：2014-11-11 00:00:00

abstract：:The multistep preparation of (11)C-levetiracetam ((11)C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the im...

journal_title：ACS medicinal chemistry letters

authors： Cai H,Mangner TJ,Muzik O,Wang MW,Chugani DC,Chugani HT

更新日期：2014-08-19 00:00:00

abstract：:Two series of novel LOXL2 enzyme inhibitors are described: benzylamines substituted with electron withdrawing groups at the para-position and 2-substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin-4-yl)methanamine 20 (hLOXL2 IC50 = 126 nM), was shown to be selective for LOXL2 over LOX and ...

journal_title：ACS medicinal chemistry letters

authors： Hutchinson JH,Rowbottom MW,Lonergan D,Darlington J,Prodanovich P,King CD,Evans JF,Bain G

更新日期：2017-03-01 00:00:00

abstract：:Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor α2β1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin α2β1 with IC50s in the low nanomolar r...

journal_title：ACS medicinal chemistry letters

authors： Halland N,Blum H,Buning C,Kohlmann M,Lindenschmidt A

更新日期：2014-01-10 00:00:00

abstract：:Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of...

journal_title：ACS medicinal chemistry letters

authors： Johansson NG,Turku A,Vidilaseris K,Dreano L,Khattab A,Ayuso Pérez D,Wilkinson A,Zhang Y,Tamminen M,Grazhdankin E,Kiriazis A,Fishwick CWG,Meri S,Yli-Kauhaluoma J,Goldman A,Boije Af Gennäs G,Xhaard H

更新日期：2020-02-17 00:00:00

abstract：:Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Comp...

journal_title：ACS medicinal chemistry letters

authors： Yu M,Wang Y,Zhu J,Bartberger MD,Canon J,Chen A,Chow D,Eksterowicz J,Fox B,Fu J,Gribble M,Huang X,Li Z,Liu JJ,Lo MC,McMinn D,Oliner JD,Osgood T,Rew Y,Saiki AY,Shaffer P,Yan X,Ye Q,Yu D,Zhao X,Zhou J,Ols

更新日期：2014-06-30 00:00:00

abstract：:The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported ...

journal_title：ACS medicinal chemistry letters

authors： Pippin AB,Voll RJ,Li Y,Wu H,Mao H,Goodman MM

更新日期：2017-11-15 00:00:00

abstract：:All eight of the major active metabolites of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221, compound 1), an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 that has entered the clinic for the treatment of type 2 diabetes, were synthetically prepared and confirmed...

journal_title：ACS medicinal chemistry letters

authors： Li A,Yuan CC,Chow D,Chen M,Emery MG,Hale C,Zhang X,Subramanian R,St Jean DJ Jr,Komorowski R,Véniant M,Wang M,Fotsch C

更新日期：2011-09-13 00:00:00