Antimalarials. 10. Synthesis of 4-substituted primaquine analogues as candidate antimalarials.

abstract：:Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17β-HSD1 inhibitors ...

journal_title：Journal of medicinal chemistry

authors： Marchais-Oberwinkler S,Wetzel M,Ziegler E,Kruchten P,Werth R,Henn C,Hartmann RW,Frotscher M

更新日期：2011-01-27 00:00:00

abstract：:Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of nonantibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at subinhibitor...

journal_title：Journal of medicinal chemistry

authors： Felicetti T,Cannalire R,Pietrella D,Latacz G,Lubelska A,Manfroni G,Barreca ML,Massari S,Tabarrini O,Kieć-Kononowicz K,Schindler BD,Kaatz GW,Cecchetti V,Sabatini S

更新日期：2018-09-13 00:00:00

abstract：:A series of conjugated hyaluronic acid particles (HAP), composed of a hydrophobic anticancer drug core and hydrophilic cyclodextrin/hyaluronic acid shell, were prepared through self-assembling and characterized by (1)H NMR titration, electron microscopy, zeta potential, and dynamic light-scattering experiments. The na...

journal_title：Journal of medicinal chemistry

authors： Yang Y,Zhang YM,Chen Y,Chen JT,Liu Y

更新日期：2013-12-12 00:00:00

abstract：:We disclose the design of a novel series of cyanoguanidines that are potent (IC(50) approximately 10-100 nM) and selective (> or = 100-fold) P2X(7) receptor antagonists against the other P2 receptor subtypes such as the P2Y(2), P2X(4), and P2X(3). We also found that these P2X(7) antagonists effectively reduced nocicep...

journal_title：Journal of medicinal chemistry

authors： Perez-Medrano A,Donnelly-Roberts DL,Honore P,Hsieh GC,Namovic MT,Peddi S,Shuai Q,Wang Y,Faltynek CR,Jarvis MF,Carroll WA

更新日期：2009-05-28 00:00:00

abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...

journal_title：Journal of medicinal chemistry

authors： Villhauer EB,Brinkman JA,Naderi GB,Burkey BF,Dunning BE,Prasad K,Mangold BL,Russell ME,Hughes TE

更新日期：2003-06-19 00:00:00

abstract：:To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...

journal_title：Journal of medicinal chemistry

authors： Brown DG,May-Dracka TL,Gagnon MM,Tommasi R

更新日期：2014-12-11 00:00:00

abstract：:Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformati...

journal_title：Journal of medicinal chemistry

authors： Williams BJ,Curtis NR,McKnight AT,Maguire JJ,Young SC,Veber DF,Baker R

更新日期：1993-01-08 00:00:00

abstract：:Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route inv...

journal_title：Journal of medicinal chemistry

authors： Chaudhary V,Venghateri JB,Dhaked HP,Bhoyar AS,Guchhait SK,Panda D

更新日期：2016-04-14 00:00:00

abstract：:Five new P1-(steroid-21-yl)-P2-(1-beta-D-arabinofuranosylcytosin-5'-yl)pyro phosphates (ara-CDP-steroids), five 1-beta-D-arabinofuranosylcytosine 5'-O-(alkyl)phosphates (ara-CMP-alkyl esters), and two P1-(alkyl)-P2-(1-beta-D-arabinofuranosylcytosin-5'-yl)pyrophosphat e (ara-CDP-alkyl esters) have been prepared and eva...

journal_title：Journal of medicinal chemistry

authors： Hong CI,Kirisits AJ,Nechaev A,Buchheit DJ,West CR

更新日期：1985-02-01 00:00:00

abstract：:Various 2',3'-dideoxy-L-cytidine,2',3'-dideoxy-L-uridine, and 3'-deoxy-L-thymidine analogues have been synthesized and evaluated in vitro as potential anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of 5-fluorocytosine, cytosi...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Luo MZ,Liu MC,Pai SB,Dutschman GE,Cheng YC

更新日期：1994-03-18 00:00:00

abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...

journal_title：Journal of medicinal chemistry

authors： Burke TG,Mi Z

更新日期：1994-01-07 00:00:00

abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...

journal_title：Journal of medicinal chemistry

authors： Kratz F,Warnecke A,Scheuermann K,Stockmar C,Schwab J,Lazar P,Drückes P,Esser N,Drevs J,Rognan D,Bissantz C,Hinderling C,Folkers G,Fichtner I,Unger C

更新日期：2002-12-05 00:00:00

abstract：:The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR-Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to...

journal_title：Journal of medicinal chemistry

authors： Sundén H,Schäfer A,Scheepstra M,Leysen S,Malo M,Ma JN,Burstein ES,Ottmann C,Brunsveld L,Olsson R

更新日期：2016-02-11 00:00:00

abstract：:A series of [(heteroarylamino)phenyl]alkanoic acids having pyridine, quinoline, or pyrimidine as the heteroaryl moiety was prepared as potential antiinflammatory agents. Among them, 2-[4-(2-pyridylamino)phenyl]propionic acid (14b) showed excellent antiinflammatory and analgesic activities with less tendency to cause g...

journal_title：Journal of medicinal chemistry

authors： Hino K,Nakamura H,Nagai Y,Uno H,Nishimura H

更新日期：1983-02-01 00:00:00

abstract：:Novel classical antifolates (3 and 4) and 17 nonclassical antifolates (11-27) were synthesized as antitumor and/or antiopportunistic infection agents. Intermediates for the synthesis of 3, 4, and 11-27 were 2,4-diamino-5-alkylsubstituted-7H-pyrrolo[2,3-d]pyrimidines, 31 and 38, prepared by a ring transformation/ring a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Jain HD,Queener SF,Kisliuk RL

更新日期：2008-08-14 00:00:00

abstract：:A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-...

journal_title：Journal of medicinal chemistry

authors： Bedford CD,Harris RN 3rd,Howd RA,Goff DA,Koolpe GA,Petesch M,Miller A,Nolen HW 3rd,Musallam HA,Pick RO

更新日期：1989-02-01 00:00:00

abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

journal_title：Journal of medicinal chemistry

authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-11-08 00:00:00

abstract：:The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with th...

journal_title：Journal of medicinal chemistry

authors： Aebi JD,Deyo DT,Sun CQ,Guillaume D,Dunlap B,Rich DH

更新日期：1990-03-01 00:00:00

abstract：:Study of surface representations of the inhibitor-bound thrombin P-1 pocket revealed a lipophilic recess in this pocket which is not occupied by any known inhibitor. Solid-phase synthesis was used to generate benzylamides of D-diphenylAlaPro by aminolysis of Boc dipeptide Kaiser resin. The resulting amides inhibited t...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Witherup KM,Tucker TJ,Brady SF,Sisko JT,Naylor-Olsen AM,Lewis SD,Lucas BJ,Vacca JP

更新日期：1998-03-26 00:00:00

abstract：:The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...

journal_title：Journal of medicinal chemistry

authors： Mariani A,Bartoli A,Atwal M,Lee KC,Austin CA,Rodriguez R

更新日期：2015-06-11 00:00:00

abstract：:Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B,...

journal_title：Journal of medicinal chemistry

authors： Shen J,Zhang T,Zhu SJ,Sun M,Tong L,Lai M,Zhang R,Xu W,Wu R,Ding J,Yun CH,Xie H,Lu X,Ding K

更新日期：2019-08-08 00:00:00

abstract：:The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular sub...

journal_title：Journal of medicinal chemistry

authors： Salvadori S,Bianchi C,Lazarus LH,Scaranari V,Attila M,Tomatis R

更新日期：1992-12-11 00:00:00

abstract：:We present a novel protein-ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does n...

journal_title：Journal of medicinal chemistry

authors： Sherman W,Day T,Jacobson MP,Friesner RA,Farid R

更新日期：2006-01-26 00:00:00

abstract：:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...

journal_title：Journal of medicinal chemistry

authors： Bijelic A,Theiner S,Keppler BK,Rompel A

更新日期：2016-06-23 00:00:00

abstract：:We report on the design, synthesis, and evaluation of a series of furanyl-salicyl-nitroxide derivatives as effective chemical probes for second-site screening against phosphotyrosine phosphatases (PTPs) using NMR-based techniques. The compounds have been tested against a panel of PTPs to assess their ability to inhibi...

journal_title：Journal of medicinal chemistry

authors： Vazquez J,Tautz L,Ryan JJ,Vuori K,Mustelin T,Pellecchia M

更新日期：2007-05-03 00:00:00

abstract：:2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We ha...

journal_title：Journal of medicinal chemistry

authors： Kühler TC,Swanson M,Christenson B,Klintenberg AC,Lamm B,Fägerhag J,Gatti R,Olwegård-Halvarsson M,Shcherbuchin V,Elebring T,Sjöström JE

更新日期：2002-09-12 00:00:00

abstract：:Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid dis...

journal_title：Journal of medicinal chemistry

authors： Wu J,Zhang Y,Maida LE,Santos RG,Welmaker GS,LaVoi TM,Nefzi A,Yu Y,Houghten RA,Toll L,Giulianotti MA

更新日期：2013-12-27 00:00:00

abstract：:In this study, we developed an assignment-free approach for rapid identification of ligand-binding sites in target proteins by using NMR. With a sophisticated cell-free stable isotope-labeling procedure that introduces (15)N- or (13)C-labels to specific atoms of target proteins, this approach requires only a single se...

journal_title：Journal of medicinal chemistry

authors： Kodama Y,Takeuchi K,Shimba N,Ishikawa K,Suzuki E,Shimada I,Takahashi H

更新日期：2013-11-27 00:00:00

abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Fry DW,Kraker AJ,Denny WA

更新日期：1994-03-04 00:00:00

abstract：:Autophagy is a lysosome-dependent mechanism of intracellular degradation for maintaining cellular homeostasis. Dysregulation of autophagy has been verified to be closely linked to a number of human diseases. Consequently, targeting autophagy has been highlighted as a novel therapeutic strategy for clinical utility. Mo...

journal_title：Journal of medicinal chemistry

authors： He S,Li Q,Jiang X,Lu X,Feng F,Qu W,Chen Y,Sun H

更新日期：2018-06-14 00:00:00