Mapping the catechol binding site in dopamine D₁ receptors: synthesis and evaluation of two parallel series of bicyclic dopamine analogues.

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：:The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electro...

journal_title：ChemMedChem

authors： Bock C,Surur AS,Beirow K,Kindermann MK,Schulig L,Bodtke A,Bednarski PJ,Link A

更新日期：2019-05-06 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：: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：:Based on the crystal structures of human alpha-GalCer-CD1d and iNKT-alpha-GalCer-CD1d complexes, nonglycosidic analogues of alpha-GalCer were synthesized. They activate iNKT cells resulting in dendritic cell maturation and the priming of antigen-specific T and B cells. Therefore, they are attractive adjuvants in vacci...

journal_title：ChemMedChem

authors： Reddy BG,Silk JD,Salio M,Balamurugan R,Shepherd D,Ritter G,Cerundolo V,Schmidt RR

更新日期：2009-02-01 00:00:00

abstract：:A series of cis-configured epoxides and aziridines containing hydrophobic moieties and amino acid esters were synthesized as new potential inhibitors of the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays revealed the N-benzyl-3-phenyl-substituted aziridines 11 and 17 as the most potent inhibito...

journal_title：ChemMedChem

authors： Degel B,Staib P,Rohrer S,Scheiber J,Martina E,Büchold C,Baumann K,Morschhäuser J,Schirmeister T

更新日期：2008-02-01 00:00:00

abstract：:The present work describes some recent approaches to novel 3-oxabicyclo[3.2.0]heptane-type nucleosides structurally similar to the potent anti-HIV agent stavudine (d4T). To gain knowledge at the molecular level relevant for further synthetic designs, the lack of activity of these compounds was investigated by computat...

journal_title：ChemMedChem

authors： Figueras A,Miralles-Llumà R,Flores R,Rustullet A,Busqué F,Figueredo M,Font J,Alibés R,Maréchal JD

更新日期：2012-06-01 00:00:00

abstract：:Modern organizations conducting drug-discovery programs frequently apply high-throughput screening to generate novel hit structures for the indications of interest. Systematic hit-to-lead processes have been established at most pharmaceutical companies to ensure a smooth conversion of hits into high-quality lead struc...

journal_title：ChemMedChem

authors： Steinmeyer A

更新日期：2006-01-01 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：:Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and β-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interp...

journal_title：ChemMedChem

authors： Qi X,Li J,Wei W,Su T,Zuo G,Pan X,Zhang J,Dong W

更新日期：2017-01-20 00:00:00

abstract：:Over the years, the 2-substituted imidazoline nucleus has been demonstrated to be a bioversatile structural motif. In this study, novel imidazoline derivatives bearing a 3- and/or 4-hydroxy- or methoxy-substituted phenyl ring, linked by an ethylene bridge to position 2 of an N-benzyl- or N-phenethyl-substituted imidaz...

journal_title：ChemMedChem

authors： Mammoli V,Bonifazi A,Dal Ben D,Giannella M,Giorgioni G,Piergentili A,Pigini M,Quaglia W,Thomas A,Newman AH,Ferré S,Sanchez-Soto M,Keck TM,Del Bello F

更新日期：2016-08-19 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：:Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD)-dependent enzyme that catalyzes the demethylation of histone H3 and regulates gene expression. Because it is implicated in the regulation of diseases such as acute myeloid leukemia, potent LSD1-specific inhibitors have been pursued. Trans-2-ph...

journal_title：ChemMedChem

authors： Niwa H,Sato S,Handa N,Sengoku T,Umehara T,Yokoyama S

更新日期：2020-05-06 00:00:00

abstract：:A structure-activity relationship around the amine group of the ambruticin VS series has been developed for antifungal activity. It was shown that the amine can be alkylated through reductive amination without loss of potency. However, if it is converted into either an amide, carbamate, or urea, a significant loss of ...

journal_title：ChemMedChem

authors： Tian ZQ,Wang Z,Xu Y,Tran CQ,Myles DC,Zhong Z,Simmons J,Vetcher L,Katz L,Li Y,Shaw SJ

更新日期：2008-06-01 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：: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：:Abnormally high corticosteroid levels are responsible for the onset of serious hormone-related diseases, and the inhibition of their biosynthesis by targeting cytochrome P450 (CYP) isoforms CYP11B1 and CYP11B2 has emerged as a promising strategy to restore healthy physiological levels of corticosteroids. With the aim ...

journal_title：ChemMedChem

authors： Gobbi S,Hu Q,Zimmer C,Belluti F,Rampa A,Hartmann RW,Bisi A

更新日期：2016-08-19 00:00:00

abstract：:Computer-guided drug design is a powerful tool for drug discovery. Herein we disclose the use of this approach for the discovery of dual FMS-like receptor tyrosine kinase-3 (FLT3)-Aurora A inhibitors against cancer. An Aurora hit compound was selected as a starting point, from which 288 virtual molecules were screened...

journal_title：ChemMedChem

authors： Chang Hsu Y,Ke YY,Shiao HY,Lee CC,Lin WH,Chen CH,Yen KJ,Hsu JT,Chang C,Hsieh HP

更新日期：2014-05-01 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 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：: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：:Octa-O-bis-(R,R)-Tartarate Ditellurane (SAS) is a new Te(IV) compound, comprised of two tellurium atoms, each liganded by four oxygen atoms from two carboxylates and two alkoxides of two tartaric acids. Unlike many other Te(IV) compounds, SAS was highly stable in aqueous solution. It interacted with thiols to form an ...

journal_title：ChemMedChem

authors： Yosef S,Brodsky M,Sredni B,Albeck A,Albeck M

更新日期：2007-11-01 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：:Efavirenz (EFV), an antiretroviral that interacts clinically with co-administered drugs via activation of the pregnane X receptor (PXR), is extensively metabolized by the cytochromes P450. We tested whether its primary metabolite, 8-hydroxyEFV (8-OHEFV) can activate PXR and potentially contribute to PXR-mediated drug-...

journal_title：ChemMedChem

authors： Narayanan B,Lade JM,Heck CJS,Dietz KD,Wade H,Bumpus NN

更新日期：2018-04-06 00:00:00

abstract：:Despite significant advances made in the last decade in the understanding of molecular mechanisms of sepsis and in the development of clinically relevant therapies, sepsis remains the leading cause of mortality in intensive care units with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane pat...

journal_title：ChemMedChem

authors： Borio A,Holgado A,Garate JA,Beyaert R,Heine H,Zamyatina A

更新日期：2018-11-06 00:00:00

abstract：:The CXCR3 receptor, a class A G protein-coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure-b...

journal_title：ChemMedChem

authors： Admas TH,Bernat V,Heinrich MR,Tschammer N

更新日期：2016-03-17 00:00:00

abstract：:The application of covalent inhibitors has experienced a renaissance within drug discovery programs in the last decade. To leverage the superior potency and drug target residence time of covalent inhibitors, there have been extensive efforts to develop highly specific covalent modifications to decrease off-target liab...

journal_title：ChemMedChem

authors： Vance NR,Witkin KR,Rooney PW,Li Y,Pope M,Spies MA

更新日期：2018-12-06 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：: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：: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