Tariquidar-Related Chalcones and Ketones as ABCG2 Modulators.

abstract：:Mitragyna speciosa, also known as kratom, has the potential meet the need for pain medications that lack the addictiveness and overdose risk of classical opioid analgesics, such as morphine. This need is urgent because opioid addiction and overdose deaths have risen throughout diverse segments of U.S. society. Some op...

journal_title：ACS medicinal chemistry letters

authors： Halpenny GM

更新日期：2017-08-08 00:00:00

abstract：:An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible rein...

journal_title：ACS medicinal chemistry letters

authors： Liégeois JF,Lespagnard M,Meneses Salas E,Mangin F,Scuvée-Moreau J,Dilly S

更新日期：2014-01-29 00:00:00

abstract：:Although heparan sulfate (HS) has been implicated in facilitating entry of enveloped viruses including herpes simplex virus (HSV), small molecules that effectively compete with this abundant, cell surface macromolecule remain unknown. We reasoned that entry of HSV-1 involving its glycoprotein D (gD) binding to HS coul...

journal_title：ACS medicinal chemistry letters

authors： Gangji RN,Sankaranarayanan NV,Elste J,Al-Horani RA,Afosah DK,Joshi R,Tiwari V,Desai UR

更新日期：2018-07-16 00:00:00

abstract：:Tak-242 (resatorvid), a Toll-like Receptor 4 (TLR4) inhibitor, has been identified as a potent suppressor of innate inflammation. As a strategy to target Tak-242 to select tissue, four TLR4-inactive prodrugs were synthesized for activation via two different release mechanisms. Two nitrobenzyl Tak-242 prodrugs released...

journal_title：ACS medicinal chemistry letters

authors： Plunk MA,Alaniz A,Olademehin OP,Ellington TL,Shuford KL,Kane RR

更新日期：2020-01-03 00:00:00

abstract：:The discovery and characterization of two classes of kappa opioid receptor agonists that are biased for G protein over βarrestin signaling are described. ...

journal_title：ACS medicinal chemistry letters

authors： Bohn LM,Aubé J

更新日期：2017-07-05 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：: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：:A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against b...

journal_title：ACS medicinal chemistry letters

authors： Wang S,Wang Y,Liu W,Liu N,Zhang Y,Dong G,Liu Y,Li Z,He X,Miao Z,Yao J,Li J,Zhang W,Sheng C

更新日期：2014-02-13 00:00:00

abstract：:Two known cleistriosides and six known cleistetrosides were synthesized and evaluated for anticancer and antibacterial activity. This study, for the first time, reports anticancer activity and comprehensively the antibacterial activity for these oligosaccharide natural products. In addition, two new unnatural cleistet...

journal_title：ACS medicinal chemistry letters

authors： Shi P,Silva MC,Wang HY,Wu B,Akhmedov NG,Li M,Beuning PJ,O'Doherty GA

更新日期：2012-12-13 00:00:00

abstract：:The identification and optimization of the first activators of fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of 1 for potency, metabolic stability, and physical ...

journal_title：ACS medicinal chemistry letters

authors： Collibee SE,Bergnes G,Muci A,Browne WF 4th,Garard M,Hinken AC,Russell AJ,Suehiro I,Hartman J,Kawas R,Lu PP,Lee KH,Marquez D,Tomlinson M,Xu D,Kennedy A,Hwee D,Schaletzky J,Leung K,Malik FI,Morgans DJ Jr,Morgan BP

更新日期：2018-02-13 00:00:00

abstract：:Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathw...

journal_title：ACS medicinal chemistry letters

authors： Flaherty DP,Miller JR,Garshott DM,Hedrick M,Gosalia P,Li Y,Milewski M,Sugarman E,Vasile S,Salaniwal S,Su Y,Smith LH,Chung TD,Pinkerton AB,Aubé J,Callaghan MU,Golden JE,Fribley AM,Kaufman RJ

更新日期：2014-10-29 00:00:00

abstract：:General control nonderepressible 2 (GCN2) is a master regulator kinase of amino acid homeostasis and important for cancer survival in the tumor microenvironment under amino acid depletion. We initiated studies aiming at the discovery of novel GCN2 inhibitors as first-in-class antitumor agents and conducted modificatio...

journal_title：ACS medicinal chemistry letters

authors： Fujimoto J,Kurasawa O,Takagi T,Liu X,Banno H,Kojima T,Asano Y,Nakamura A,Nambu T,Hata A,Ishii T,Sameshima T,Debori Y,Miyamoto M,Klein MG,Tjhen R,Sang BC,Levin I,Lane SW,Snell GP,Li K,Kefala G,Hoffman ID,Ding

更新日期：2019-09-19 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：:SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism dire...

journal_title：ACS medicinal chemistry letters

authors： Rydberg P,Gloriam DE,Zaretzki J,Breneman C,Olsen L

更新日期：2010-03-15 00:00:00

abstract：:A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain),...

journal_title：ACS medicinal chemistry letters

authors： Mahanti M,Pal KB,Sundin AP,Leffler H,Nilsson UJ

更新日期：2019-12-04 00:00:00

abstract：:Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn(2+) ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off-target interactio...

journal_title：ACS medicinal chemistry letters

authors： Vickers CJ,Olsen CA,Leman LJ,Ghadiri MR

更新日期：2012-04-26 00:00:00

abstract：:Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notch1 expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-b...

journal_title：ACS medicinal chemistry letters

authors： Quaglio D,Zhdanovskaya N,Tobajas G,Cuartas V,Balducci S,Christodoulou MS,Fabrizi G,Gargantilla M,Priego EM,Carmona Pestaña Á,Passarella D,Screpanti I,Botta B,Palermo R,Mori M,Ghirga F,Pérez-Pérez MJ

更新日期：2019-02-26 00:00:00

abstract：:We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM). Cocrystalli...

journal_title：ACS medicinal chemistry letters

authors： Farand J,Kropf JE,Blomgren P,Xu J,Schmitt AC,Newby ZE,Wang T,Murakami E,Barauskas O,Sudhamsu J,Feng JY,Niedziela-Majka A,Schultz BE,Schwartz K,Viatchenko-Karpinski S,Kornyeyev D,Kashishian A,Fan P,Chen X,Lansdon EB

更新日期：2019-11-19 00:00:00

abstract：:Reactive oxygen species, contributing to oxidant-antioxidant imbalance, initiate damage to the airways cells, inflammatory processes, and further pathophysiological effects. Enhancing antioxidant properties is the main prophylactic and therapeutic challenge. In this work, a newly synthesized and biocompatible structur...

journal_title：ACS medicinal chemistry letters

authors： Wiśniewski M,Bieniek A,Roszek K,Czarnecka J,Bolibok P,Ferrer P,da Silva I,Terzyk AP

更新日期：2018-11-19 00:00:00

abstract：:Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound...

journal_title：ACS medicinal chemistry letters

authors： Maurya R,Soni A,Anand D,Ravi M,Raju KS,Taneja I,Naikade NK,Puri SK,Wahajuddin,Kanojiya S,Yadav PP

更新日期：2012-12-11 00:00:00

abstract：:Herein we describe the design and synthesis of a series of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) for Alzheimer's disease (AD) that achieve good alignment of potency, metabolic stability, and low MDR efflux ratios, while also maintaining favorable physicochemical properties. Specifically, incorporation...

journal_title：ACS medicinal chemistry letters

authors： Pettersson M,Johnson DS,Humphrey JM,Butler TW,Am Ende CW,Fish BA,Green ME,Kauffman GW,Mullins PB,O'Donnell CJ,Stepan AF,Stiff CM,Subramanyam C,Tran TP,Vetelino BC,Yang E,Xie L,Bales KR,Pustilnik LR,Steyn SJ,Wood K

更新日期：2015-04-03 00:00:00

abstract：:1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against P. falciparum malaria in clinical trials. Based on our previous quantitative structure...

journal_title：ACS medicinal chemistry letters

authors： Xue J,Diao J,Cai G,Deng L,Zheng B,Yao Y,Song Y

更新日期：2013-02-14 00:00:00

abstract：:Carbazoles represent a family of tricyclic compounds that widely appeared in nature. Numerous studies have revealed a diverse array of bioactivity associated with this scaffold. In the present study, a novel and highly efficient methodology for preparing 1,3-dihydroxy-2-carboxycarbazole from indole-3-acetic acid and M...

journal_title：ACS medicinal chemistry letters

authors： Liu K,Zhang S

更新日期：2015-07-10 00:00:00

abstract：:An original design and synthesis of fluorescent ligands for melatonin receptor studies is presented and consists in the fusion of the endogenous ligand with the fluorescent BODIPY core. Probes I-IV show high affinities for MT1 and MT2 melatonin receptors and exhibit fluorescence properties compatible with cell observa...

journal_title：ACS medicinal chemistry letters

authors： Thireau J,Marteaux J,Delagrange P,Lefoulon F,Dufourny L,Guillaumet G,Suzenet F

更新日期：2013-11-20 00:00:00

abstract：:Rapid detection and precise evaluation of myocardial viability is necessary to aid in clinical decision making whether to recommend revascularization for patients with myocardial infarction (MI). Three novel 18F-labeled 1-hydroxyanthraquinone derivatives were synthesized, characterized, and evaluated as potential necr...

journal_title：ACS medicinal chemistry letters

authors： Ji AY,Jin QM,Zhang DJ,Zhu H,Su C,Duan XH,Bian L,Sun ZP,Ni YC,Zhang J,Yang Z,Yin ZQ

更新日期：2016-12-28 00:00:00

abstract：:Herein, we report the structure-activity relationships within a series of mGlu7 PAMs based on a pyrazolo[1,5-a]pyrimidine core with excellent CNS penetration (Kps > 1 and Kp,uus > 1). Analogues in this series proved to display a range of Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual mGlu...

journal_title：ACS medicinal chemistry letters

authors： Abe M,Seto M,Gogliotti RG,Loch MT,Bollinger KA,Chang S,Engelberg EM,Luscombe VB,Harp JM,Bubser M,Engers DW,Jones CK,Rodriguez AL,Blobaum AL,Conn PJ,Niswender CM,Lindsley CW

更新日期：2017-09-01 00:00:00

abstract：:A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a new mechanism diuretic. Robust ph...

journal_title：ACS medicinal chemistry letters

authors： Walsh SP,Shahripour A,Tang H,Teumelsan N,Frie J,Zhu Y,Priest BT,Swensen AM,Liu J,Margulis M,Visconti R,Weinglass A,Felix JP,Brochu RM,Bailey T,Thomas-Fowlkes B,Alonso-Galicia M,Zhou X,Pai LY,Corona A,Hampton C,H

更新日期：2015-05-07 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：:A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure-activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds...

journal_title：ACS medicinal chemistry letters

authors： Prime ME,Brookfield FA,Courtney SM,Gaines S,Marston RW,Ichihara O,Li M,Vaidya D,Williams H,Pedret-Dunn A,Reed L,Schaertl S,Toledo-Sherman L,Beconi M,Macdonald D,Muñoz-Sanjuan I,Dominguez C,Wityak J

更新日期：2012-08-09 00:00:00

abstract：:The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylatio...

journal_title：ACS medicinal chemistry letters

authors： Borgström B,Huang X,Chygorin E,Oredsson S,Strand D

更新日期：2016-04-25 00:00:00