A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects.

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：: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：:Metalloproteinases of the astacin family are drawing ever increasing attention as potential drug targets. However, knowledge regarding inhibitors thereof is limited in most cases. Crucial for the development of metalloprotease inhibitors is high selectivity, to avoid side effects brought about by inhibition of off-tar...

journal_title：ChemMedChem

authors： Tan K,Jäger C,Schlenzig D,Schilling S,Buchholz M,Ramsbeck D

更新日期：2018-08-20 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：:Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a small molecule with potent anticancer activity. Like other 1,4-naphthoquinones, it exhibits electrophilic reactivity towards biological nucleophiles. We demonstrate that plumbagin and structurally related 1,4-naphthoquinones with at least one unsubstituted quinoid...

journal_title：ChemMedChem

authors： Chrastina A,Welsh J,Rondeau G,Abedinpour P,Borgström P,Baron VT

更新日期：2020-07-20 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：:The therapeutic potential of photoactive CO-releasing molecules (photoCORMs) have called for close examination of the roles of the ligand(s) and the central metal atoms on the overall photochemical labilization of the metal-CO bonds. Along this line, we have synthesized four metal complexes, namely, [MnBr(azpy)(CO)3 ]...

journal_title：ChemMedChem

authors： Chakraborty I,Carrington SJ,Mascharak PK

更新日期：2014-06-01 00:00:00

abstract：:The serotonin transporter (SERT) is one of the neurotransmitter transporters that plays a critical role in the regulation of endogenous amine concentrations and therefore is an important target for therapeutic agents affecting the central nervous system. The recently published, high resolution X-ray structure of the c...

journal_title：ChemMedChem

authors： Jørgensen AM,Tagmose L,Jørgensen AM,Topiol S,Sabio M,Gundertofte K,Bøgesø KP,Peters GH

更新日期：2007-06-01 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：:Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperid...

journal_title：ChemMedChem

authors： Zuravka I,Roesmann R,Sosic A,Wende W,Pingoud A,Gatto B,Göttlich R

更新日期：2014-09-01 00:00:00

abstract：:We recently reported the synthesis and biological evaluation of a novel series of 5-alkyl-2-(N,N-disubstituted)amino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones (F(2)-N,N-DABOs). These compounds are highly active against both wild-type HIV-1 and the K103N, Y181C, and Y188L mutant strains. Herein we pre...

journal_title：ChemMedChem

authors： Samuele A,Facchini M,Rotili D,Mai A,Artico M,Armand-Ugón M,Esté JA,Maga G

更新日期：2008-09-01 00:00:00

abstract：:3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives were synthesized, and their structures were confirmed by single-crystal X-ray diffraction. This reaction yields the 1,4-dicarboxamide derivatives rather than the 1,2-dicarboxamide derivatives. Their in vitro antitumor activities were evaluated against SGC-79...

journal_title：ChemMedChem

authors： Rao GW,Guo YM,Hu WX

更新日期：2012-06-01 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：:N-Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti-inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator-activated receptor α (PPAR-α). Thus, p...

journal_title：ChemMedChem

authors： Fiasella A,Nuzzi A,Summa M,Armirotti A,Tarozzo G,Tarzia G,Mor M,Bertozzi F,Bandiera T,Piomelli D

更新日期：2014-07-01 00:00:00

abstract：:A series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki-Miyaura coupling and Brønsted-acid-mediated cyclodehydration as key steps. The vascular-disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of mi...

journal_title：ChemMedChem

authors： Joncour A,Liu JM,Décor A,Thoret S,Wdzieczak-Bakala J,Bignon J,Baudoin O

更新日期：2008-11-01 00:00:00

abstract：:To ascertain whether increasing hydrophobicity can enhance the activity of second-generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2'-O-(2S-methoxypropyl)-RNA (2S-MOP)-modified ASOs. Synthesis of the 2S-MOP 5-methyl uridine phosphoramidite was accomplished on a multi-...

journal_title：ChemMedChem

authors： Yu J,Pandey SK,Khatri H,Prakash TP,Swayze EE,Seth PP

更新日期：2014-09-01 00:00:00

abstract：:Chemical biology approaches have a long history in the exploration of the G-protein-coupled receptor (GPCR) family, which represents the largest and most important group of targets for therapeutics. The analysis of the human genome revealed a significant number of new members with unknown physiological function which ...

journal_title：ChemMedChem

authors： Jacoby E,Bouhelal R,Gerspacher M,Seuwen K

更新日期：2006-08-01 00:00:00

abstract：:The clinical use of N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) has been hindered by its lack of bioavailability. N,N'-bis(2-boronic pinacol ester benzyl)ethylenediamine-N,N'-diacetic acid methyl, ethyl, and isopropyl esters 7 a-c, respectively, and their dimesylate salts 8 a-c, are double prodr...

journal_title：ChemMedChem

authors： Thiele NA,Sloan KB

更新日期：2016-08-05 00:00:00

abstract：:ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an indole moiety considerably increased stability and gave potent and selective ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances fumitremorgin C and Ko143 in terms of potency and efficacy and are the most potent AB...

journal_title：ChemMedChem

authors： Bauer S,Ochoa-Puentes C,Sun Q,Bause M,Bernhardt G,König B,Buschauer A

更新日期：2013-11-01 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：:Blocking the 2-C-methyl-d-erythrithol-4-phosphate pathway for isoprenoid biosynthesis offers new ways to inhibit the growth of Plasmodium spp. Fosmidomycin [(3-(N-hydroxyformamido)propyl)phosphonic acid, 1] and its acetyl homologue FR-900098 [(3-(N-hydroxyacetamido)propyl)phosphonic acid, 2] potently inhibit 1-deoxy-d...

journal_title：ChemMedChem

authors： Sooriyaarachchi S,Chofor R,Risseeuw MD,Bergfors T,Pouyez J,Dowd CS,Maes L,Wouters J,Jones TA,Van Calenbergh S,Mowbray SL

更新日期：2016-09-20 00:00:00

abstract：:The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovasc...

journal_title：ChemMedChem

authors： Schuller HM,Kabalka G,Smith G,Mereddy A,Akula M,Cekanova M

更新日期：2006-06-01 00:00:00

abstract：:N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator-activated receptor-α (PPAR-α). Com...

journal_title：ChemMedChem

authors： Vitale R,Ottonello G,Petracca R,Bertozzi SM,Ponzano S,Armirotti A,Berteotti A,Dionisi M,Cavalli A,Piomelli D,Bandiera T,Bertozzi F

更新日期：2014-02-01 00:00:00

abstract：:The synthesis of a novel group of quinacridine-based ligands (MMQs) is described along with an evaluation of their G-quadruplex binding properties. A set of biophysical assays was applied to characterize their interaction with DNA quadruplexes: FRET-melting experiments and equilibrium microdialysis were used to evalua...

journal_title：ChemMedChem

authors： Hounsou C,Guittat L,Monchaud D,Jourdan M,Saettel N,Mergny JL,Teulade-Fichou MP

更新日期：2007-05-01 00:00:00

abstract：:Following the discovery of a type III allosteric modulator of cyclin-dependent kinase 2 (CDK2) characterized by a hexahydrocyclopenta[c]quinolone scaffold, three different series of its derivatives were synthesized and biologically evaluated. Docking of the synthesized compounds into the allosteric pocket of CDK2 allo...

journal_title：ChemMedChem

authors： Carlino L,Christodoulou MS,Restelli V,Caporuscio F,Foschi F,Semrau MS,Costanzi E,Tinivella A,Pinzi L,Lo Presti L,Battistutta R,Storici P,Broggini M,Passarella D,Rastelli G

更新日期：2018-12-20 00:00:00

abstract：:In solution, amphoteric compounds exist in anionic, uncharged, zwitterionic and cationic forms. The importance of zwitterionic drugs is currently under-represented in the literature. Herein, the acid-base parameters, lipophilicity and solubility of such compounds are discussed to deepen the molecular-level understandi...

journal_title：ChemMedChem

authors： Mazák K,Noszál B

更新日期：2020-07-03 00:00:00

abstract：:Greater than the sum of its parts: Artemisinins are currently in phase I-II clinical trials against breast, colorectal and non-small-cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin-polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies an...

journal_title：ChemMedChem

authors： La Pensée L,Sabbani S,Sharma R,Bhamra I,Shore E,Chadwick AE,Berry NG,Firman J,Araujo NC,Cabral L,Cristiano ML,Bateman C,Janneh O,Gavrila A,Wu YH,Hussain A,Ward SA,Stocks PA,Cosstick R,O'Neill PM

更新日期：2013-05-01 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：:A historical overview of key events that led, 50 years ago, to the foundation of the European Federation for Medicinal Chemistry (EFMC), and the impact this had on promoting and structuring medicinal chemistry as a discipline in Europe. EFMC, together with the growing number of newly established national medicinal che...

journal_title：ChemMedChem

authors： Differding E

更新日期：2020-12-15 00:00:00

abstract：:Iron is essential for the pathogenicity and virulence of Mycobacterium tuberculosis, which synthesises salicyl-capped siderophores (mycobactins) to acquire this element from the host. MbtA is the adenylating enzyme that catalyses the initial reaction of mycobactin biosynthesis and is solely expressed by mycobacteria. ...

journal_title：ChemMedChem

authors： Ferguson L,Wells G,Bhakta S,Johnson J,Guzman J,Parish T,Prentice RA,Brucoli F

更新日期：2019-10-04 00:00:00