Discovery of Alternative Chemotherapy Options for Leishmaniasis via Computational Studies of Asteraceae.

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：:An efficient stereocontrolled synthesis afforded alkoxymethylenephosphonate (MP) analogues of lysophosphatidic acid (LPA) and phosphatidic acid (PA). The pharmacological properties of MP-LPA and MP-PA analogues were characterized for LPA receptor subtype-specific agonist and antagonist activity using Ca(2+)-mobilizati...

journal_title：ChemMedChem

authors： Gajewiak J,Tsukahara R,Tsukahara T,Fujiwara Y,Yu S,Lu Y,Murph M,Mills GB,Tigyi G,Prestwich GD

更新日期：2007-12-01 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：: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：:A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a n...

journal_title：ChemMedChem

authors： Humbeck L,Weigang S,Schäfer T,Mutzel P,Koch O

更新日期：2018-03-20 00:00:00

abstract：:We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdraw...

journal_title：ChemMedChem

authors： Desai J,Wang Y Dr,Wang K Dr,Malwal SR Dr,Oldfield E

更新日期：2016-10-06 00:00:00

abstract：:In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl-linked acrylamide conjugates were designed, synthesized, and evaluated for cytotoxic activity against various human cancer cell lines, anti-tubulin activity and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6-fluorobenzo[d]...

journal_title：ChemMedChem

authors： Kamal A,Ashraf M,Khan MN,Nimbarte VD,Faazil S,Subba Reddy NV,Taj S

更新日期：2014-03-28 00:00:00

abstract：:Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Herein we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary N-substituted 7-amino...

journal_title：ChemMedChem

authors： Abdelkarim H,Neelarapu R,Madriaga A,Vaidya AS,Kastrati I,Karumudi B,Wang YT,Taha TY,Thatcher GRJ,Frasor J,Petukhov PA

更新日期：2017-12-19 00:00:00

abstract：:HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves...

journal_title：ChemMedChem

authors： Bhattacharya AK,Rana KC,Pannecouque C,De Clercq E

更新日期：2012-09-01 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：: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：:The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the ...

journal_title：ChemMedChem

authors： Santos GB,Ganesan A,Emery FS

更新日期：2016-10-19 00:00:00

abstract：:There has been significant interest in spleen tyrosine kinase (Syk) owing to its role in a number of disease states, including autoimmunity, inflammation, and cancer. Ongoing therapeutic programs have resulted in several compounds that are now in clinical use. Herein we report our optimization of the imidazopyrazine c...

journal_title：ChemMedChem

authors： Lovering F,Aevazelis C,Chang J,Dehnhardt C,Fitz L,Han S,Janz K,Lee J,Kaila N,McDonald J,Moore W,Moretto A,Papaioannou N,Richard D,Ryan MS,Wan ZK,Thorarensen A

更新日期：2016-01-19 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：: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：: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：:The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the...

journal_title：ChemMedChem

authors： Liou JP,Mahindroo N,Chang CW,Guo FM,Lee SW,Tan UK,Yeh TK,Kuo CC,Chang YW,Lu PH,Tung YS,Lin KT,Chang JY,Hsieh HP

更新日期：2006-10-01 00:00:00

abstract：:Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell...

journal_title：ChemMedChem

authors： Yan TL,Bai LF,Zhu HL,Zhang WM,Lv PC

更新日期：2017-07-06 00:00:00

abstract：:Recently we reported on aryl-fluorosulfates as possible stable and effective electrophiles for the design of lysine covalent, cell permeable antagonists of protein-protein interactions (PPIs). Here we revisit the use of aryl-sulfonyl fluorides as Lys-targeting moieties, incorporating these electrophiles in XIAP (X-lin...

journal_title：ChemMedChem

authors： Gambini L,Udompholkul P,Salem AF,Baggio C,Pellecchia M

更新日期：2020-11-18 00:00:00

abstract：:First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to...

journal_title：ChemMedChem

authors： Ciriminna R,Fidalgo A,Meneguzzo F,Presentato A,Scurria A,Nuzzo D,Alduina R,Ilharco LM,Pagliaro M

更新日期：2020-08-28 00:00:00

abstract：:We recently reported a vitamin B(12) (B(12)) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B(12) conjugation have on insulin's interaction with the insulin receptor (IR...

journal_title：ChemMedChem

authors： Petrus AK,Allis DG,Smith RP,Fairchild TJ,Doyle RP

更新日期：2009-03-01 00:00:00

abstract：:P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-...

journal_title：ChemMedChem

authors： Liu B,Qiu Q,Zhao T,Jiao L,Li Y,Huang W,Qian H

更新日期：2015-02-01 00:00:00

abstract：:Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prep...

journal_title：ChemMedChem

authors： Bayer T,Chakrabarti A,Lancelot J,Shaik TB,Hausmann K,Melesina J,Schmidtkunz K,Marek M,Erdmann F,Schmidt M,Robaa D,Romier C,Pierce RJ,Jung M,Sippl W

更新日期：2018-08-10 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：:A small library of 17 organoruthenium compounds with the general formula [RuII (fcl)(chel)(L)]n+ (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compou...

journal_title：ChemMedChem

authors： Ristovski S,Uzelac M,Kljun J,Lipec T,Uršič M,Zemljič Jokhadar Š,Žužek MC,Trobec T,Frangež R,Sepčić K,Turel I

更新日期：2018-10-22 00:00:00

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：:A severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26 b based on the antibio...

journal_title：ChemMedChem

authors： Tietze LF,von Hof JM,Krewer B,Müller M,Major F,Schuster HJ,Schuberth I,Alves F

更新日期：2008-12-01 00:00:00

abstract：:A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective...

journal_title：ChemMedChem

authors： Weik S,Luksch T,Evers A,Böttcher J,Sotriffer CA,Hasilik A,Löffler HG,Klebe G,Rademann J

更新日期：2006-04-01 00:00:00

abstract：:The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor...

journal_title：ChemMedChem

authors： Fershtat LL,Makhova NN

更新日期：2017-05-09 00:00:00

abstract：:Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs ...

journal_title：ChemMedChem

authors： Liu Z,Ma S

更新日期：2017-06-07 00:00:00