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：:Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at nontoxic doses in mice. An...

journal_title：ChemMedChem

authors： Tercel M,Lee HH,Yang S,Liyanage HD,Mehta SY,Boyd PD,Jaiswal JK,Tan KL,Pruijn FB

更新日期：2011-10-04 00:00:00

abstract：:Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace th...

journal_title：ChemMedChem

authors： Hampton SE,Baragaña B,Schipani A,Bosch-Navarrete C,Musso-Buendía JA,Recio E,Kaiser M,Whittingham JL,Roberts SM,Shevtsov M,Brannigan JA,Kahnberg P,Brun R,Wilson KS,González-Pacanowska D,Johansson NG,Gilbert IH

更新日期：2011-10-04 00:00:00

abstract：:Herein we propose the D-Trp-Phe sequence within an inverse type II β-turn as a new kind of pharmacophoric motif for μ-opioid receptor (MOR) cyclopeptide agonists. Initially, we observed that c[Tyr-D-Pro-D-Trp-Phe-Gly] (4), an analogue of endomorphin-1 (H-Tyr-Pro-Trp-Phe-NH₂) lacking the crucial protonatable amino grou...

journal_title：ChemMedChem

authors： Gentilucci L,Tolomelli A,De Marco R,Spampinato S,Bedini A,Artali R

更新日期：2011-09-05 00:00:00

abstract：:A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of t...

journal_title：ChemMedChem

authors： Kamal A,Reddy MK,Ramaiah MJ,Srikanth YV,Rajender,Reddy VS,Kumar GB,Pushpavalli SN,Bag I,Juvekar A,Sen S,Zingde SM,Pal-Bhadra M

更新日期：2011-09-05 00:00:00

abstract：:Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many c...

journal_title：ChemMedChem

authors： Diana P,Stagno A,Barraja P,Carbone A,Parrino B,Dall'Acqua F,Vedaldi D,Salvador A,Brun P,Castagliuolo I,Issinger OG,Cirrincione G

更新日期：2011-07-04 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：:Platinum amidine complexes represent a new class of potential antitumor drugs that contain the imino moiety HN=C(sp(2)) bonded to the platinum center. They can be related to the iminoether derivatives, which were recently shown to be the first Pt(II) compounds with a trans configuration endowed with anticancer activit...

journal_title：ChemMedChem

authors： Michelin RA,Sgarbossa P,Sbovata SM,Gandin V,Marzano C,Bertani R

更新日期：2011-07-04 00:00:00

abstract：:Dopamine (DA) D(3) receptor antagonism might play a significant role in different therapeutic areas. A high number of preclinical studies on DA D(3) receptor antagonists have shown efficacy in animal models of Parkinson's disease, schizophrenia and drug dependence. This Review covers the activities of medicinal chemis...

journal_title：ChemMedChem

authors： Micheli F

更新日期：2011-07-04 00:00:00

abstract：:Ionic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and differen...

journal_title：ChemMedChem

authors： Ferraz R,Branco LC,Prudêncio C,Noronha JP,Petrovski Z

更新日期：2011-06-06 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：:A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyrimidin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new congeners exhibited moderate to good activities against the wild-...

journal_title：ChemMedChem

authors： Yu M,Li Z,Liu S,Fan E,Pannecouque C,De Clercq E,Liu X

更新日期：2011-05-02 00:00:00

abstract：:A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl...

journal_title：ChemMedChem

authors： Zhou B,Li X,Li Y,Xu Y,Zhang Z,Zhou M,Zhang X,Liu Z,Zhou J,Cao C,Yu B,Wang R

更新日期：2011-05-02 00:00:00

abstract：:Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to...

journal_title：ChemMedChem

authors： Sáez-Ayala M,Sánchez-del-Campo L,Montenegro MF,Chazarra S,Tárraga A,Cabezas-Herrera J,Rodríguez-López JN

更新日期：2011-03-07 00:00:00

abstract：:The cytotoxic activity of a series of 23 new isoerianin derivatives with modifications on both the A and B rings was studied. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. The most cytotoxic compound, isoerianin (3), strongly in...

journal_title：ChemMedChem

authors： Messaoudi S,Hamze A,Provot O,Tréguier B,Rodrigo De Losada J,Bignon J,Liu JM,Wdzieczak-Bakala J,Thoret S,Dubois J,Brion JD,Alami M

更新日期：2011-03-07 00:00:00

abstract：:We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moie...

journal_title：ChemMedChem

authors： Labruère R,Gautier B,Testud M,Seguin J,Lenoir C,Desbène-Finck S,Helissey P,Garbay C,Chabot GG,Vidal M,Giorgi-Renault S

更新日期：2010-12-03 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：:It has been 25 years since the development of the first efficient HIV-1/AIDS treatment. Scientists now know more about the HIV-1 infection life cycle, and more than 30 antiretroviral drugs have been developed, including HIV-1 fusion inhibitors. Fundamental work was begun in the early 1990s and led to the development o...

journal_title：ChemMedChem

authors： Cai L,Jiang S

更新日期：2010-11-08 00:00:00

abstract：:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...

journal_title：ChemMedChem

authors： Kamal A,Dastagiri D,Ramaiah MJ,Reddy JS,Bharathi EV,Srinivas C,Pushpavalli SN,Pal D,Pal-Bhadra M

更新日期：2010-11-08 00:00:00

abstract：:Dihydropyrimidine-based compounds belong to the first discovered inhibitors of the human mitotic kinesin Eg5. Although they are used by many research groups as model compounds for chemical genetics, considerably less emphasis has been placed on the improvement of this type of inhibitor, with the exception of two recen...

journal_title：ChemMedChem

authors： Prokopcová H,Dallinger D,Uray G,Kaan HY,Ulaganathan V,Kozielski F,Laggner C,Kappe CO

更新日期：2010-10-04 00:00:00

abstract：:A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI(50) values in the nanomolar range. The active com...

journal_title：ChemMedChem

authors： Ferlin MG,Bortolozzi R,Brun P,Castagliuolo I,Hamel E,Basso G,Viola G

更新日期：2010-08-02 00:00:00

abstract：:Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the...

journal_title：ChemMedChem

authors： Bieda R,Dobroschke M,Triller A,Ott I,Spehr M,Gust R,Prokop A,Sheldrick WS

更新日期：2010-07-05 00:00:00

abstract：:A library of 40,000 compounds was screened for inhibitors of 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) protein from Arabidopsis thaliana using a photometric assay. A thiazolopyrimidine derivative resulting from the high-throughput screen was found to inhibit the IspF proteins of Mycobacterium tuberculosi...

journal_title：ChemMedChem

authors： Geist JG,Lauw S,Illarionova V,Illarionov B,Fischer M,Gräwert T,Rohdich F,Eisenreich W,Kaiser J,Groll M,Scheurer C,Wittlin S,Alonso-Gómez JL,Schweizer WB,Bacher A,Diederich F

更新日期：2010-07-05 00:00:00

abstract：:The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and t...

journal_title：ChemMedChem

authors： Erdélyi M,Navarro-Vázquez A,Pfeiffer B,Kuzniewski CN,Felser A,Widmer T,Gertsch J,Pera B,Díaz JF,Altmann KH,Carlomagno T

更新日期：2010-06-07 00:00:00

abstract：:A small set of aggrecanase inhibitors based on the pyrrolo[3,4-c]quinolin-1-one or oxoisoindoline frameworks bearing a 4-(benzyloxy)phenyl substituent and different zinc binding groups were rationally designed and evaluated in silico by docking studies using the crystal structure of the ADAMTS-5 catalytic domain (PDB ...

journal_title：ChemMedChem

authors： Cappelli A,Nannicini C,Valenti S,Giuliani G,Anzini M,Mennuni L,Giordani A,Caselli G,Stasi LP,Makovec F,Giorgi G,Vomero S

更新日期：2010-05-03 00:00:00

abstract：:A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the ...

journal_title：ChemMedChem

authors： Fritzson I,Svensson B,Al-Karadaghi S,Walse B,Wellmar U,Nilsson UJ,da Graça Thrige D,Jönsson S

更新日期：2010-04-06 00:00:00

abstract：:alpha,beta-Unsaturated carbonyl compounds as potential drug candidates is a controversial topic since their potential Michael acceptor activity can lead to cell damage and cytotoxicity. Nevertheless, the alpha,beta-unsaturated carbonyl functionality can be employed as a tool to fine tune biological activity by directl...

journal_title：ChemMedChem

authors： Amslinger S

更新日期：2010-03-01 00:00:00

abstract：:Here we report the synthesis of a number of compounds structurally related to arginine methyltransferase inhibitor 1 (AMI-1). The structural alterations that we made included: 1) the substitution of the sulfonic groups with the bioisosteric carboxylic groups; 2) the replacement of the ureidic function with a bis-amidi...

journal_title：ChemMedChem

authors： Castellano S,Milite C,Ragno R,Simeoni S,Mai A,Limongelli V,Novellino E,Bauer I,Brosch G,Spannhoff A,Cheng D,Bedford MT,Sbardella G

更新日期：2010-03-01 00:00:00

abstract：:S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel pr...

journal_title：ChemMedChem

authors： Agamennone M,Cesari L,Lalli D,Turlizzi E,Del Conte R,Turano P,Mangani S,Padova A

更新日期：2010-03-01 00:00:00

abstract：:There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library a...

journal_title：ChemMedChem

authors： Spinks D,Shanks EJ,Cleghorn LA,McElroy S,Jones D,James D,Fairlamb AH,Frearson JA,Wyatt PG,Gilbert IH

更新日期：2009-12-01 00:00:00

abstract：:2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. Th...

journal_title：ChemMedChem

authors： Galletti P,Quintavalla A,Ventrici C,Giannini G,Cabri W,Penco S,Gallo G,Vincenti S,Giacomini D

更新日期：2009-12-01 00:00:00

abstract：:4H-1,2,4-Benzothiadiazine-1,1-dioxides with various substituents in positions 3, 5, and 7 were synthesized and tested as K(ATP) channel agonists in artificial cell systems (CHO cells transfected with SUR1/Kir6.2, and HEK 293 transfected with SUR2B/Kir6.1) as model systems for insulin-secreting pancreatic beta-cells an...

journal_title：ChemMedChem

authors： Lachenicht S,Fischer A,Schmidt C,Winkler M,Rood A,Lemoine H,Braun M

更新日期：2009-11-01 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：:An emerging and attractive target for the treatment of Alzheimer's disease is to inhibit the aggregation of beta-amyloid protein (Abeta). We applied the retro-enantio concept to design an N-methylated peptidic inhibitor of the Abeta42 aggregation process. This inhibitor, inrD, as well as the corresponding all-L (inL) ...

journal_title：ChemMedChem

authors： Grillo-Bosch D,Carulla N,Cruz M,Sánchez L,Pujol-Pina R,Madurga S,Rabanal F,Giralt E

更新日期：2009-09-01 00:00:00

abstract：:Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilay...

journal_title：ChemMedChem

authors： Alakoskela JM,Vitovic P,Kinnunen PK

更新日期：2009-08-01 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：:The role of beta-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.Medicinal chemists a...

journal_title：ChemMedChem

authors： Gaber HM,Bagley MC

更新日期：2009-07-01 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：:Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impairments of the NO-sGC signaling pathway have been implicated in the pathogenesis of cardiovascular and other diseases. Direct stimulation of sGC represents a promising therapeutic strategy particularly for the treat...

journal_title：ChemMedChem

authors： Mittendorf J,Weigand S,Alonso-Alija C,Bischoff E,Feurer A,Gerisch M,Kern A,Knorr A,Lang D,Muenter K,Radtke M,Schirok H,Schlemmer KH,Stahl E,Straub A,Wunder F,Stasch JP

更新日期：2009-05-01 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