Inhibition of human DHODH by 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids identified by structure-guided fragment selection.

abstract：:Loperamide (1a), an opioid receptor agonist, is in clinical use as an antidiarrheal agent. Carbon/silicon exchange (sila-substitution) at the 4-position of the piperidine ring of 1a (R3 COH→R3 SiOH) leads to sila-loperamide (1b). Sila-loperamide was synthesized in a multistep procedure, starting from triethoxyvinylsil...

journal_title：ChemMedChem

authors： Geyer M,Wellner E,Jurva U,Saloman S,Armstrong D,Tacke R

更新日期：2015-05-01 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：:3-Deazaneplanocin A (DzNep) is a potential epigenetic drug for the treatment of various cancers. DzNep has been reported to deplete histone methylations, including oncogenic EZH2 complex, giving rise to epigenetic modifications that reactivate many silenced tumor suppressors in cancer cells. Despite its promise as an ...

journal_title：ChemMedChem

authors： Tam EK,Nguyen TM,Lim CZ,Lee PL,Li Z,Jiang X,Santhanakrishnan S,Tan TW,Goh YL,Wong SY,Yang H,Ong EH,Hill J,Yu Q,Chai CL

更新日期：2015-01-01 00:00:00

abstract：:Cardiotoxicity is a common side effect of a large variety of drugs that is often caused by off-target human ether-à-go-go-related gene (hERG) potassium channel blockade. In this study, we designed and synthesized a series of derivatives of the class III antiarrhythmic agent E-4031. These compounds where evaluated in a...

journal_title：ChemMedChem

authors： Vilums M,Overman J,Klaasse E,Scheel O,Brussee J,IJzerman AP

更新日期：2012-01-02 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：:In an approach to design drugs with higher affinity for π-π stacking and electrostatic interactions with targeted biomolecules, complexes of the type [{cis-Pt(A)2 (L)}2 -μ-{trans-1,4-dach}](NO3 )4 ((A)2 =(NH3 )2 or ethylenediamine (en), L=quinoline (quin) or benzothiazole (bztz), dach=trans-1,4-diaminocyclohexane) wer...

journal_title：ChemMedChem

authors： Ma ES,Daniel AG,Farrell NP

更新日期：2014-06-01 00:00:00

abstract：:Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substitu...

journal_title：ChemMedChem

authors： Rey J,Hu H,Kyle F,Lai CF,Buluwela L,Coombes RC,Ortlund EA,Ali S,Snyder JP,Barrett AG

更新日期：2012-11-01 00:00:00

abstract：:The Pathogen Box is a 400-strong collection of drug-like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition...

journal_title：ChemMedChem

authors： Veale CGL

更新日期：2019-02-19 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：:Dual inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO), two key enzymes involved in pro-inflammatory eicosanoid biosynthesis, represents a new strategy for treating inflammatory disorders. Herein we report the discovery of 2,4-thiazolidinedione-based mPGES-1/5-LO dual inhibitors ...

journal_title：ChemMedChem

authors： Lauro G,Terracciano S,Cantone V,Ruggiero D,Fischer K,Pace S,Werz O,Bruno I,Bifulco G

更新日期：2020-03-18 00:00:00

abstract：:Into the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc ) of the cellular prion protein (PrPC ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a li...

journal_title：ChemMedChem

authors： Massignan T,Sangiovanni V,Biggi S,Stincardini C,Elezgarai SR,Maietta G,Andreev IA,Ratmanova NK,Belov DS,Lukyanenko ER,Belov GM,Barreca ML,Altieri A,Kurkin AV,Biasini E

更新日期：2017-08-22 00:00:00

abstract：:Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery. Lactose-funct...

journal_title：ChemMedChem

authors： Murthy RV,Bavireddi H,Gade M,Kikkeri R

更新日期：2015-05-01 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：:Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...

journal_title：ChemMedChem

authors： Ziegler K,Hauser DR,Unger A,Albrecht W,Laufer SA

更新日期：2009-11-01 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：:Silent Night: Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX(1)R/OX(2)R) orexin receptor antagonist featuring a 1,4-diazepane central constraint that blocks orexin signaling in vivo. In telemet...

journal_title：ChemMedChem

authors： Whitman DB,Cox CD,Breslin MJ,Brashear KM,Schreier JD,Bogusky MJ,Bednar RA,Lemaire W,Bruno JG,Hartman GD,Reiss DR,Harrell CM,Kraus RL,Li Y,Garson SL,Doran SM,Prueksaritanont T,Li C,Winrow CJ,Koblan KS,Renger JJ,C

更新日期：2009-07-01 00:00:00

abstract：:Although the advantages of sp3 -rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp2 -rich components. Compounds that are sp3 -rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp3 -rich lib...

journal_title：ChemMedChem

authors： Karaki F,Umemoto S,Ashizawa K,Oki T,Sato N,Ogino T,Ishibashi N,Someya R,Miyano K,Hirayama S,Uezono Y,Fujii H

更新日期：2019-11-06 00:00:00

abstract：:Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N-terminal side chain (1), C-terminal side chain (2), or the C-terminus (3) to a...

journal_title：ChemMedChem

authors： Yeoh YQ,Horsley JR,Yu J,Polyak SW,Jovcevski B,Abell AD

更新日期：2020-08-19 00:00:00

abstract：:A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)...

journal_title：ChemMedChem

authors： Woodland A,Thompson S,Cleghorn LA,Norcross N,De Rycker M,Grimaldi R,Hallyburton I,Rao B,Norval S,Stojanovski L,Brun R,Kaiser M,Frearson JA,Gray DW,Wyatt PG,Read KD,Gilbert IH

更新日期：2015-11-01 00:00:00

abstract：:The protozoan parasite Plasmodium falciparum causes the most severe and prevailing form of malaria in sub-Saharan Africa. Previously, we identified the plasmodial lactate transporter, PfFNT, a member of the microbial formate-nitrite transporter family, as a novel antimalarial drug target. With the pentafluoro-3-hydrox...

journal_title：ChemMedChem

authors： Walloch P,Hansen C,Priegann T,Schade D,Beitz E

更新日期：2020-12-18 00:00:00

abstract：:Seasonal influenza infections are associated with an estimated 250-500 000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have pro...

journal_title：ChemMedChem

authors： Sagong HY,Bauman JD,Nogales A,Martínez-Sobrido L,Arnold E,LaVoie EJ

更新日期：2019-06-18 00:00:00

abstract：:Herein we describe the optimization of a phenotypic hit against Plasmodium falciparum based on an aminoacetamide scaffold. This led to N-(3-chloro-4-fluorophenyl)-2-methyl-2-{[4-methyl-3-(morpholinosulfonyl)phenyl]amino}propanamide (compound 28) with low-nanomolar activity against the intraerythrocytic stages of the m...

journal_title：ChemMedChem

authors： Norcross NR,Wilson C,Baragaña B,Hallyburton I,Osuna-Cabello M,Norval S,Riley J,Fletcher D,Sinden R,Delves M,Ruecker A,Duffy S,Meister S,Antonova-Koch Y,Crespo B,de Cózar C,Sanz LM,Gamo FJ,Avery VM,Frearson JA,Gray

更新日期：2019-07-17 00:00:00

abstract：:Intraoperative imaging technologies recently entered the operating room, and their implementation is revolutionizing how physicians plan, monitor, and perform surgical interventions. In this work, we present a novel surgical imaging reporter system: intraoperative chemiluminescence imaging (ICI). To this end, we have ...

journal_title：ChemMedChem

authors： Büchel GE,Carney B,Shaffer TM,Tang J,Austin C,Arora M,Zeglis BM,Grimm J,Eppinger J,Reiner T

更新日期：2016-09-20 00:00:00

abstract：:The in silico design, synthesis, and biological evaluation of ten potent type II dehydroquinase inhibitors are described. These compounds contain an anhydroquinate core, incorporated as a mimic of the enolate reaction intermediate. This substructure is attached by a variety of linking units to a terminal phenyl group ...

journal_title：ChemMedChem

authors： Payne RJ,Peyrot F,Kerbarh O,Abell AD,Abell C

更新日期：2007-07-01 00:00:00

abstract：:Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives, phenols and sulfamates, respectively, were synthesized by solid-phase parallel chemistry through a seven-step reaction sequence. Following the attachment of a C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements we...

journal_title：ChemMedChem

authors： Ciobanu LC,Poirier D

更新日期：2006-11-01 00:00:00

abstract：:β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the or...

journal_title：ChemMedChem

authors： Orioli M,Vistoli G,Regazzoni L,Pedretti A,Lapolla A,Rossoni G,Canevotti R,Gamberoni L,Previtali M,Carini M,Aldini G

更新日期：2011-07-04 00:00:00

abstract：:Cyclic RGD-containing functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe the synthesis and in vitro screening of these RGD derivatives, as well as the determination of thei...

journal_title：ChemMedChem

authors： Manzoni L,Belvisi L,Arosio D,Civera M,Pilkington-Miksa M,Potenza D,Caprini A,Araldi EM,Monferini E,Mancino M,Podestà F,Scolastico C

更新日期：2009-04-01 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：:Two acyclic cucurbit[n]uril (CB[n])-type molecular containers that differ in the length of the (CH2 )n linker (M2C2: n=2, M2C4: n=4) between their aromatic sidewalls and sulfonate solubilizing groups were prepared and studied. The inherent solubilities of M2C2 (68 mm) and M2C4 (196 mm) are higher than the analogue wit...

journal_title：ChemMedChem

authors： Sigwalt D,Moncelet D,Falcinelli S,Mandadapu V,Zavalij PY,Day A,Briken V,Isaacs L

更新日期：2016-05-06 00:00:00

abstract：:Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with t...

journal_title：ChemMedChem

authors： Marko AJ,Dukh M,Patel NJ,Missert JR,Ohulchanskyy T,Tabaczynski WA,Ohkubo K,Fukuzumi S,Yao R,Sajjad M,Pandey RK

更新日期：2019-08-20 00:00:00