An efficient synthesis of a hydroxyethylamine (HEA) isostere and its α-aminophosphonate and phosphoramidate derivatives as potential anti-HIV agents.

abstract：:Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl-urea fatty acid (1 g; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl-ureas the prese...

journal_title：ChemMedChem

authors： Murray M,Roseblade A,Chen Y,Bourget K,Rawling T

更新日期：2020-01-17 00:00:00

abstract：:The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pKa lowering approach over the initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading to the design of 6-CF3 dihydrothiazine 8 (N-(3-((4S,6...

journal_title：ChemMedChem

authors： Anan K,Iso Y,Oguma T,Nakahara K,Suzuki S,Yamamoto T,Matsuoka E,Ito H,Sakaguchi G,Ando S,Morimoto K,Kanegawa N,Kido Y,Kawachi T,Fukushima T,Teisman A,Urmaliya V,Dhuyvetter D,Borghys H,Austin N,Van Den Bergh A,Ver

更新日期：2019-11-20 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：:Digital Drug Discovery: Guest Editors Andreas Bender (University of Cambridge) and Nathan Brown (BenevolentAI) present the 20 articles included in this Special Issue on Cheminformatics in Drug Design. As they summarize each article, they also discuss the common themes within in silico drug discovery that these papers ...

journal_title：ChemMedChem

authors： Bender A,Brown N

更新日期：2018-03-20 00:00:00

abstract：:The asymmetric synthesis and receptor pharmacology of (1S,2R,3R,5R,6S)-2-amino-3-Hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (+)-9 (HYDIA) and a few of its O-alkylated derivatives are described. The key step of the synthesis utilizes Sharpless' asymmetric dihydroxylation (AD-beta) for the kinetic resolution of ...

journal_title：ChemMedChem

authors： Woltering TJ,Adam G,Huguenin P,Wichmann J,Kolczewski S,Gatti S,Bourson A,Kew JN,Richards G,Kemp JA,Mutel V,Knoflach F

更新日期：2008-02-01 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：: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：:Steroid derivatives bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized. These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipi...

journal_title：ChemMedChem

authors： Chougnet A,Grinkova Y,Ricard D,Sligar S,Woggon WD

更新日期：2007-05-01 00:00:00

abstract：:Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach...

journal_title：ChemMedChem

authors： Aubele DL,Hom RK,Adler M,Galemmo RA Jr,Bowers S,Truong AP,Pan H,Beroza P,Neitz RJ,Yao N,Lin M,Tonn G,Zhang H,Bova MP,Ren Z,Tam D,Ruslim L,Baker J,Diep L,Fitzgerald K,Hoffman J,Motter R,Fauss D,Tanaka P,Dap

更新日期：2013-08-01 00:00:00

abstract：:The three databases of PubChem, ChemSpider, and UniChem capture the majority of open chemical structure records with February 2018 totals of 95, 63, and 154 million, respectively. Collectively, they constitute a massively enabling resource for cheminformatics, chemical biology, and drug discovery. As meta-portals, the...

journal_title：ChemMedChem

authors： Southan C

更新日期：2018-03-20 00:00:00

abstract：:Human equilibrative nucleoside transporter 1 (hENT1) is a prototypical nucleoside transporter protein ubiquitously expressed on the cell surface of almost all human tissue. Given the role of hENT1 in the transport of nucleoside drugs, an important class of therapeutics in the treatment of various cancers and viral inf...

journal_title：ChemMedChem

authors： Rayala R,Theard P,Ortiz H,Yao S,Young JD,Balzarini J,Robins MJ,Wnuk SF

更新日期：2014-09-01 00:00:00

abstract：:Over the years, a number of dimensionality reduction techniques have been proposed and used in chemoinformatics to perform nonlinear mappings. In this study, four representatives of nonlinear dimensionality reduction methods related to two different families were analyzed: distance-based approaches (Isomap and Diffusi...

journal_title：ChemMedChem

authors： Kireeva NV,Ovchinnikova SI,Tetko IV,Asiri AM,Balakin KV,Tsivadze AY

更新日期：2014-05-01 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：:LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying ...

journal_title：ChemMedChem

authors： Fioravanti R,Romanelli A,Mautone N,Di Bello E,Rovere A,Corinti D,Zwergel C,Valente S,Rotili D,Botrugno OA,Dessanti P,Vultaggio S,Vianello P,Cappa A,Binda C,Mattevi A,Minucci S,Mercurio C,Varasi M,Mai A

更新日期：2020-04-03 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：:The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the ...

journal_title：ChemMedChem

authors： Hoffmann M,Chen X,Hirano M,Arimitsu K,Kimura H,Higuchi T,Decker M

更新日期：2018-12-06 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：:Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment...

journal_title：ChemMedChem

authors： Brunst S,Kramer JS,Kilu W,Heering J,Pollinger J,Hiesinger K,George S,Steinhilber D,Merk D,Proschak E

更新日期：2020-12-06 00:00:00

abstract：:Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino-terminal copper and nickel (ATCUN) binding motifs are known to actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs...

journal_title：ChemMedChem

authors： Libardo MD,Cervantes JL,Salazar JC,Angeles-Boza AM

更新日期：2014-08-01 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：: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

abstract：:Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure-activity relationship study of a small library ...

journal_title：ChemMedChem

authors： Dato FM,Sheikh M,Uhl RZ,Schüller AW,Steinkrüger M,Koch P,Neudörfl JM,Gütschow M,Goldfuss B,Pietsch M

更新日期：2018-09-06 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：:Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conj...

journal_title：ChemMedChem

authors： Zhang FL,Huang Q,Liu JY,Huang MD,Xue JP

更新日期：2015-02-01 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：: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：:Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type ...

journal_title：ChemMedChem

authors： Al-Asri J,Gyémánt G,Fazekas E,Lehoczki G,Melzig MF,Wolber G,Mortier J

更新日期：2016-11-07 00:00:00

abstract：:A series of 1,3,3,4-tetrasubstituted pyrrolidine containing CCR5 receptor antagonists were designed, which were elaborated either by condensation of a lithium salt of 3-(N,N-dibenzyl)aminopropionic acid methyl ester with ethyl benzoformate or by Baylis-Hillman reaction of ethyl acrylate with ethyl benzoformate and sub...

journal_title：ChemMedChem

authors： Ma D,Yu S,Li B,Chen L,Chen R,Yu K,Zhang L,Chen Z,Zhong D,Gong Z,Wang R,Jiang H,Pei G

更新日期：2007-02-01 00:00:00

abstract：:A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimeth...

journal_title：ChemMedChem

authors： Laali KK,Zwarycz AT,Bunge SD,Borosky GL,Nukaya M,Kennedy GD

更新日期：2019-06-18 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