Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

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：:Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in c...

journal_title：ChemMedChem

authors： D'Ambrosio K,Masereel B,Thiry A,Scozzafava A,Supuran CT,De Simone G

更新日期：2008-03-01 00:00:00

abstract：:Src homology 2 (SH2)-domain-mediated interactions with phosphotyrosine (pY)-containing ligands are critical for the regulation of SHP-1 phosphatase activity. Peptides based on a binding site from receptor tyrosine kinase Ros (EGLN-pY2267-MVL, 1) have recently been shown to bind to the SHP-1 N-terminal SH2 domain (N-SH...

journal_title：ChemMedChem

authors： Hampel K,Kaufhold I,Zacharias M,Böhmer FD,Imhof D

更新日期：2006-08-01 00:00:00

abstract：:The less polar π-surface of protein amide groups is exposed in many receptor binding sites, either as part of the backbone or in Gln/Asn side chains. Using quantum chemical calculations and Protein Data Bank (PDB) searches on model systems, we investigate the energetics and geometric preferences for the stacking on am...

journal_title：ChemMedChem

authors： Harder M,Kuhn B,Diederich F

更新日期：2013-03-01 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：:A series of water-soluble (benzoyloxy)methyl esters of acetylsalicylic acid (ASA), commonly known as aspirin, are described. The new derivatives each have alkyl chains containing a nitric oxide (NO)-releasing nitrooxy group and a solubilizing moiety bonded to the benzoyl ring. The compounds were synthesized and evalua...

journal_title：ChemMedChem

authors： Rolando B,Lazzarato L,Donnola M,Marini E,Joseph S,Morini G,Pozzoli C,Fruttero R,Gasco A

更新日期：2013-07-01 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：:We report the synthesis of trifluoromethylated metallocenes (M=Fe, Ru) and related metal-free compounds for comparison of their biological properties with the aim to establish structure-activity relationships toward the anti-proliferative activity of this compound class. All new compounds were comprehensively characte...

journal_title：ChemMedChem

authors： Maschke M,Alborzinia H,Lieb M,Wölfl S,Metzler-Nolte N

更新日期：2014-06-01 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：:Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increas...

journal_title：ChemMedChem

authors： Beck H,Jeske M,Thede K,Stoll F,Flamme I,Akbaba M,Ergüden JK,Karig G,Keldenich J,Oehme F,Militzer HC,Hartung IV,Thuss U

更新日期：2018-05-23 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：: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：:A novel Ru(II) (arene) theranostic complex is presented. It is based on a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of (153) Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at...

journal_title：ChemMedChem

authors： Adriaenssens L,Liu Q,Chaux-Picquet F,Tasan S,Picquet M,Denat F,Le Gendre P,Marques F,Fernandes C,Mendes F,Gano L,Campello MP,Bodio E

更新日期：2014-07-01 00:00:00

abstract：:Some hybrid foldamers of various length, all containing the (4R,5S)-4-carboxy-5-methyloxazolidin-2-one (d-Oxd) moiety alternating with an l-amino acid (l-Val, l-Lys, or l-Ala), were prepared in order to study their preferred conformations and to evaluate their biological activity. Surprisingly, only the longer oligome...

journal_title：ChemMedChem

authors： Del Secco B,Malachin G,Milli L,Zanna N,Papini E,Cornia A,Tavano R,Tomasini C

更新日期：2017-02-20 00:00:00

abstract：:Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives, phenols and sulfamates, respectively, were synthesized by solid-phase parallel chemistry through a seven-step reaction sequence. Following the attachment of a C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements we...

journal_title：ChemMedChem

authors： Ciobanu LC,Poirier D

更新日期：2006-11-01 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：: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：:Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identificati...

journal_title：ChemMedChem

authors： Hatley RJD,Barrett TN,Slack RJ,Watson ME,Baillache DJ,Gruszka A,Washio Y,Rowedder JE,Pogány P,Pal S,Macdonald SJF

更新日期：2019-07-17 00:00:00

abstract：:Herein we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric chemokine receptor 2 (CXCR2) inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2, with IC50 values less than 10 μm ...

journal_title：ChemMedChem

authors： Mehanna WE,Lu T,Debnath B,Lasheen DS,Serya RAT,Abouzid KA,Neamati N

更新日期：2017-07-06 00:00:00

abstract：:Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmod...

journal_title：ChemMedChem

authors： de Souza Pereira C,Costa Quadros H,Magalhaes Moreira DR,Castro W,Santos De Deus Da Silva RI,Botelho Pereira Soares M,Fontinha D,Prudêncio M,Schmitz V,Dos Santos HF,Gendrot M,Fonta I,Mosnier J,Pradines B,Navarro M

更新日期：2020-11-24 00:00:00

abstract：:Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand...

journal_title：ChemMedChem

authors： Zhu J,Ye Y,Ning M,Mándi A,Feng Y,Zou Q,Kurtán T,Leng Y,Shen J

更新日期：2013-07-01 00:00:00

abstract：:Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the ...

journal_title：ChemMedChem

authors： Möller C,Bone W,Cleve A,Klar U,Rotgeri A,Rottmann A,Schultze-Mosgau MH,Wagenfeld A,Schwede W

更新日期：2018-11-06 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：:Given the worldwide spread of bacterial drug resistance, there is an urgent need to develop new compounds that exhibit potent antibacterial activity and that are unimpaired by this phenomenon. Quaternary ammonium compounds have been used for many years as disinfectants, but recent advances have shown that polycationic...

journal_title：ChemMedChem

authors： Thomas B,Duval RE,Fontanay S,Varbanov M,Boisbrun M

更新日期：2019-07-03 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 objective of the study was to generate a reliable model of the homotrimeric structure for the human glutamate transporter EAAT1, based on experimental folding of transporter homologue from Pyrococcus horikoshii. The monomer structure was derived using a fragmental approach and the homotrimer was assembled using pr...

journal_title：ChemMedChem

authors： Pedretti A,De Luca L,Sciarrillo C,Vistoli G

更新日期：2008-01-01 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：: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：:Identification of potent agonists of odorant receptors (ORs), a major class of G protein-coupled receptors, remains challenging due to complex receptor-ligand interactions. ORs are present in both olfactory and non-chemosensory tissues, indicating roles beyond odor detection that may include modulating physiological f...

journal_title：ChemMedChem

authors： Park BB,Lee N,Kim Y,Jae Y,Choi S,Kang N,Hong YR,Ok K,Cho J,Jeon YH,Lee EH,Byun Y,Koo J

更新日期：2017-04-06 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