Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents.

abstract：:Computer-aided drug design could benefit from a greater understanding of how errors arise and propagate in biomolecular modeling. With such knowledge, model predictions could be associated with quantitative estimates of their uncertainty. In addition, novel algorithms could be designed to proactively reduce prediction...

journal_title：ACS medicinal chemistry letters

authors： Faver JC,Ucisik MN,Yang W,Merz KM Jr

更新日期：2013-09-12 00:00:00

abstract：:We present the discovery and optimization of a novel series of inhibitors of bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this paper). Starting from virtual screening hits, the activity of various inhibitory molecules was optimized using a combination of structure-based and rational design appr...

journal_title：ACS medicinal chemistry letters

authors： Xu Y,Brenning B,Clifford A,Vollmer D,Bearss J,Jones C,McCarthy V,Shi C,Wolfe B,Aavula B,Warner S,Bearss DJ,McCullar MV,Schuch R,Pelzek A,Bhaskaran SS,Stebbins CE,Goldberg AR,Fischetti VA,Vankayalapati H

更新日期：2013-12-12 00:00:00

abstract：:Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionali...

journal_title：ACS medicinal chemistry letters

authors： Koehler MF,Bergeron P,Choo EF,Lau K,Ndubaku C,Dudley D,Gibbons P,Sleebs BE,Rye CS,Nikolakopoulos G,Bui C,Kulasegaram S,Kersten WJ,Smith BJ,Czabotar PE,Colman PM,Huang DC,Baell JB,Watson KG,Hasvold L,Tao ZF,Wang

更新日期：2014-03-21 00:00:00

abstract：:Despite several years of research, only a handful of β-secretase (BACE) 1 inhibitors have entered clinical trials as potential therapeutics against Alzheimer's disease. The intrinsic basic nature of low molecular weight, amidine-containing BACE 1 inhibitors makes them far from optimal as central nervous system drugs. ...

journal_title：ACS medicinal chemistry letters

authors： Oehlrich D,Peschiulli A,Tresadern G,Van Gool M,Vega JA,De Lucas AI,Alonso de Diego SA,Prokopcova H,Austin N,Van Brandt S,Surkyn M,De Cleyn M,Vos A,Rombouts FJR,Macdonald G,Moechars D,Gijsen HJM,Trabanco AA

更新日期：2019-07-02 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：:Retinoid X receptor-alpha (RXRα) is implicated in the regulation of many biological processes and also represents a unique intracellular target for pharmacologic interventions. Efforts on discovery of small molecules targeting RXRα have been primarily focused on the molecules that bind to its classical ligand-binding ...

journal_title：ACS medicinal chemistry letters

authors： Chen F,Liu J,Huang M,Hu M,Su Y,Zhang XK

更新日期：2014-05-14 00:00:00

abstract：:The atypical chemokine receptor CXCR7 has been studied in various disease settings including immunological diseases and heart disease. Efforts to elucidate the role of CXCR7 have been limited by the lack of suitable chemical tools with a range of pharmacological profiles. A high-throughput screen was conducted to disc...

journal_title：ACS medicinal chemistry letters

authors： Menhaji-Klotz E,Ward J,Brown JA,Loria PM,Tan C,Hesp KD,Riccardi KA,Litchfield J,Boehm M

更新日期：2020-05-14 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：:Two rigid analogues of 5-ethylindolobenzazepinone 4, a potent cytotoxic agent and inhibitor of tubulin polymerization, were prepared. The first was the indane derivative 5, in which the ethyl group is attached to the benzo moiety. The second was the pyrrolidine analogue 6, in which the ethyl chain was bound to the lac...

journal_title：ACS medicinal chemistry letters

authors： Pons V,Beaumont S,Tran Huu Dau ME,Iorga BI,Dodd RH

更新日期：2011-06-05 00:00:00

abstract：:DNA methylation is known as the prima donna epigenetic mark for its critical role in regulating local gene transcription. Changes in the landscape of DNA methylation across the genome occur during cellular transition, such as differentiation and altered neuronal plasticity, and become dysregulated in disease states su...

journal_title：ACS medicinal chemistry letters

authors： Chua GNL,Wassarman KL,Sun H,Alp JA,Jarczyk EI,Kuzio NJ,Bennett MJ,Malachowsky BG,Kruse M,Kennedy AJ

更新日期：2019-01-31 00:00:00

abstract：:Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral ...

journal_title：ACS medicinal chemistry letters

authors： Bungard CJ,Williams PD,Schulz J,Wiscount CM,Holloway MK,Loughran HM,Manikowski JJ,Su HP,Bennett DJ,Chang L,Chu XJ,Crespo A,Dwyer MP,Keertikar K,Morriello GJ,Stamford AW,Waddell ST,Zhong B,Hu B,Ji T,Diamond TL,Ba

更新日期：2017-11-13 00:00:00

abstract：:The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinum neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and...

journal_title：ACS medicinal chemistry letters

authors： Cardellina JH 2nd,Vieira RC,Eccard V,Skerry J,Montgomery V,Campbell Y,Roxas-Duncan V,Leister W,Leclair CA,Maloney DJ,Padula D,Pescitelli G,Khavrutskii I,Hu X,Wallqvist A,Smith LA

更新日期：2011-03-10 00:00:00

abstract：:We report the design, synthesis, and biological evaluation of a (64)Cu-labeled histone deacetylase (HDAC) imaging probe, which was obtained by introduction of metal chelator through click reaction of HDAC inhibitor CUDC-101 and then radiolabeled with (64)Cu. The resulting (64)Cu-labeled compound 7 ([(64)Cu]7) was iden...

journal_title：ACS medicinal chemistry letters

authors： Meng Q,Li F,Jiang S,Li Z

更新日期：2013-07-25 00:00:00

abstract：:P-glycoprotein (Pgp) is capable of recognizing and transporting a wide range of chemically diverse compounds in vivo. Overcoming Pgp-mediated efflux can represent a significant challenge when penetration into the central nervous system is required or within the context of developing anticancer therapies. While numerou...

journal_title：ACS medicinal chemistry letters

authors： Gunaydin H,Weiss MM,Sun Y

更新日期：2012-11-06 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：:[This corrects the article DOI: 10.1021/acsmedchemlett.9b00612.]. ...

journal_title：ACS medicinal chemistry letters

authors： Kaiser TM,Dentmon ZW,Dalloul CE,Sharma SK,Liotta DC

更新日期：2020-06-24 00:00:00

abstract：:Derivatization efforts were continued to discover backups for a potent selective PPARγ modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modification...

journal_title：ACS medicinal chemistry letters

authors： Shinozuka T,Tsukada T,Fujii K,Tokumaru E,Matsui Y,Wakimoto S,Ogata T,Araki K,Sawamura R,Watanabe N,Mori M,Tanaka J

更新日期：2019-02-26 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：:A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carbo...

journal_title：ACS medicinal chemistry letters

authors： Pan S,Gray NS,Gao W,Mi Y,Fan Y,Wang X,Tuntland T,Che J,Lefebvre S,Chen Y,Chu A,Hinterding K,Gardin A,End P,Heining P,Bruns C,Cooke NG,Nuesslein-Hildesheim B

更新日期：2013-01-04 00:00:00

abstract：:Abdominal pain and abnormal bowel habits represent major symptoms for irritable bowel syndrome (IBS) patients that are not adequately managed. Although the etiology of IBS is not completely understood, many of the functions of the gastrointestinal (GI) tract are regulated by the enteric nervous system (ENS). Inflammat...

journal_title：ACS medicinal chemistry letters

authors： Schenck Eidam H,Russell J,Raha K,DeMartino M,Qin D,Guan HA,Zhang Z,Zhen G,Yu H,Wu C,Pan Y,Joberty G,Zinn N,Laquerre S,Robinson S,White A,Giddings A,Mohammadi E,Greenwood-Van Meerveld B,Oliff A,Kumar S,Cheung M

更新日期：2018-05-24 00:00:00

abstract：:The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized versio...

journal_title：ACS medicinal chemistry letters

authors： Matsuno K,Masuda Y,Uehara Y,Sato H,Muroya A,Takahashi O,Yokotagawa T,Furuya T,Okawara T,Otsuka M,Ogo N,Ashizawa T,Oshita C,Tai S,Ishii H,Akiyama Y,Asai A

更新日期：2010-07-13 00:00:00

abstract：:A new series of 1,4-naphthoquinones, bearing various cyclic and aliphatic amines on C2, was designed and synthesized to identify antiproliferative agents for triple-negative breast cancer, which represents a clinical challenge without targeted therapies. Among naphthoquinones, 2a and 3a inhibited the proliferation of ...

journal_title：ACS medicinal chemistry letters

authors： Badolato M,Carullo G,Caroleo MC,Cione E,Aiello F,Manetti F

更新日期：2019-02-15 00:00:00

abstract：:We encountered a dilemma in the course of studying a series of antagonists of the G-protein coupled receptor CC chemokine receptor-2 (CCR2): compounds with polar C3 side chains exhibited good ion channel selectivity but poor oral bioavailability, whereas compounds with lipophilic C3 side chains exhibited good oral bio...

journal_title：ACS medicinal chemistry letters

authors： Yang MG,Xiao Z,Cherney RJ,Tebben AJ,Batt DG,Brown GD,Chen J,Cvijic ME,Dabros M,Duncia JV,Galella M,Gardner DS,Khandelwal P,Ko SS,Malley MF,Mo R,Pang J,Rose AV,Santella JB 3rd,Shi H,Srivastava A,Traeger SC,Wang

更新日期：2019-01-16 00:00:00

abstract：:Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide a...

journal_title：ACS medicinal chemistry letters

authors： Hubble VB,Bartholomew KR,Weig AW,Brackett SM,Barlock SL,Mattingly AE,Nemeth AM,Melander RJ,Melander C

更新日期：2020-08-12 00:00:00

abstract：:We report here the total synthesis of B-973 (five steps), a recently identified α7 nAChR ago-PAM, its enantiomeric resolution, and its electrophysiological characterization in Xenopus oocytes to identify (-)-B-973B as the bioactive enantiomer. The asymmetric synthesis of B-973B was accomplished in 99% ee, and X-ray cr...

journal_title：ACS medicinal chemistry letters

authors： Garai S,Raja KS,Papke RL,Deschamps JR,Damaj MI,Thakur GA

更新日期：2018-10-11 00:00:00

abstract：:A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them,...

journal_title：ACS medicinal chemistry letters

authors： Bi C,Zhang N,Yang P,Ye C,Wang Y,Fan T,Shao R,Deng H,Song D

更新日期：2017-01-05 00:00:00

abstract：:The renal outer medullary potassium channel (ROMK or Kir1.1) is a putative drug target for a novel class of diuretics that could be used for the treatment of hypertension and edematous states such as heart failure. An internal high-throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5) as a p...

journal_title：ACS medicinal chemistry letters

authors： Tang H,Walsh SP,Yan Y,de Jesus RK,Shahripour A,Teumelsan N,Zhu Y,Ha S,Owens KA,Thomas-Fowlkes BS,Felix JP,Liu J,Kohler M,Priest BT,Bailey T,Brochu R,Alonso-Galicia M,Kaczorowski GJ,Roy S,Yang L,Mills SG,Garcia M

更新日期：2012-03-28 00:00:00

abstract：:Synthesis of a strict structural analogue of albaconazole in which the quinazolinone ring is fused by a thiazole moiety led to the discovery of a new triazole with broad-spectrum antifungal activity. Compound I exhibited high in vitro activity against pathogenic Candida species and filamentous fungi and showed prelimi...

journal_title：ACS medicinal chemistry letters

authors： Guillon R,Pagniez F,Picot C,Hédou D,Tonnerre A,Chosson E,Duflos M,Besson T,Logé C,Le Pape P

更新日期：2013-01-17 00:00:00

abstract：:WaterMap and MM-GB/SA scoring methods were applied to an extensive congeneric series of small-molecule SRC inhibitors with high-quality enzyme data and well characterized binding modes to compare the performance of these scoring methods in this data set and to provide insight into the relative strengths of each method...

journal_title：ACS medicinal chemistry letters

authors： Kohlmann A,Zhu X,Dalgarno D

更新日期：2012-01-06 00:00:00

abstract：:The 2-fluoroalkoxy substituted catechol-aporphines 6, 8a-f and 11-monohydroxyaporphines 11a-e were synthesized and found to have high in vitro affinity and selectivity for the dopamine D(2) receptors. The catechol aporphines, 8b and 8d, and the monohydroxy aporphines, 11a-d, were identified as candidates for developme...

journal_title：ACS medicinal chemistry letters

authors： Sromek AW,Si YG,Zhang T,George SR,Seeman P,Neumeyer JL

更新日期：2011-03-10 00:00:00