Structure-based design, synthesis, and antimicrobial activity of indazole-derived SAH/MTA nucleosidase inhibitors.

abstract：:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a...

journal_title：Journal of medicinal chemistry

authors： Fleysher MH,Bernacki RJ,Bullard GA

更新日期：1980-12-01 00:00:00

abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...

journal_title：Journal of medicinal chemistry

authors： Mellini P,Kokkola T,Suuronen T,Salo HS,Tolvanen L,Mai A,Lahtela-Kakkonen M,Jarho EM

更新日期：2013-09-12 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：:The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates. Because inhibiting FAAH has a clear therapeutic potential, we previously developed β-lactam-type inhibitors of hFAAH. Here, we report the synthesis of five n...

journal_title：Journal of medicinal chemistry

authors： Feledziak M,Muccioli GG,Lambert DM,Marchand-Brynaert J

更新日期：2011-10-13 00:00:00

abstract：:A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were ...

journal_title：Journal of medicinal chemistry

authors： Hamulakova S,Janovec L,Hrabinova M,Spilovska K,Korabecny J,Kristian P,Kuca K,Imrich J

更新日期：2014-08-28 00:00:00

abstract：:Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles. Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dime...

journal_title：Journal of medicinal chemistry

authors： Sarges R,Howard HR,Koe BK,Weissman A

更新日期：1989-02-01 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Lau K,Barker JJ,Brookfield F,Chen Y,Chen Y,Eigenbrot C,Ellebrandt C,Ismaili MH,Johnson A,Kordt D,MacKinnon CH,McEwan PA,Ortwine DF,Stein DB,Wang X,Winkler D,Yuen PW,Zhang Y,Zarrin AA,Pei Z

更新日期：2014-07-10 00:00:00

abstract：:Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to o...

journal_title：Journal of medicinal chemistry

authors： Hiesinger K,Dar'in D,Proschak E,Krasavin M

更新日期：2021-01-14 00:00:00

abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...

journal_title：Journal of medicinal chemistry

authors： Weiss JT,Dawson JC,Fraser C,Rybski W,Torres-Sánchez C,Bradley M,Patton EE,Carragher NO,Unciti-Broceta A

更新日期：2014-06-26 00:00:00

abstract：:The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to...

journal_title：Journal of medicinal chemistry

authors： Yoshimoto M,Hansch C

更新日期：1976-01-01 00:00:00

abstract：:Endosomal toll-like receptors (TLRs) 7 and 8 recognize viral single-stranded RNAs, a class of imidazoquinoline compounds, 8-oxo-adenosines, 8-aminobenzodiazepines, pyrimidines, and guanosine analogues. Substantial evidence is present linking chronic inflammation mediated specifically by TLR7 to the progression of auto...

journal_title：Journal of medicinal chemistry

authors： Padilla-Salinas R,Anderson R,Sakaniwa K,Zhang S,Nordeen P,Lu C,Shimizu T,Yin H

更新日期：2019-11-27 00:00:00

abstract：:A series of dihydrobenzopyrans and tetrahydroquinolines was synthesized and pharmacologically tested for their ability to inhibit P-glycoprotein mediated daunomycin efflux in multidrug resistant CCRF-CEM vcr1000 cells. Several compounds exhibit activities in the range of the reference compounds verapamil and propafeno...

journal_title：Journal of medicinal chemistry

authors： Hiessböck R,Wolf C,Richter E,Hitzler M,Chiba P,Kratzel M,Ecker G

更新日期：1999-06-03 00:00:00

abstract：:Following the recent discoveries that some L-nucleosides are more or equal potent than their D-counterparts, we synthesized 2'-deoxy-2',2'-difluoro-L-erythro-pentofuranosyl nucleosides as potential antiviral agents. The target compounds were synthesized via the key intermediates 7a or 7b from L-gulono gamma-lactone. C...

journal_title：Journal of medicinal chemistry

authors： Kotra LP,Xiang Y,Newton MG,Schinazi RF,Cheng YC,Chu CK

更新日期：1997-10-24 00:00:00

abstract：:A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3K...

journal_title：Journal of medicinal chemistry

authors： Thakur A,Tawa GJ,Henderson MJ,Danchik C,Liu S,Shah P,Wang AQ,Dunn G,Kabir M,Padilha EC,Xu X,Simeonov A,Kharbanda S,Stone R,Grewal G

更新日期：2020-04-23 00:00:00

abstract：:A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-tria...

journal_title：Journal of medicinal chemistry

authors： Ferreira SB,Sodero AC,Cardoso MF,Lima ES,Kaiser CR,Silva FP,Ferreira VF

更新日期：2010-03-25 00:00:00

abstract：:A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...

journal_title：Journal of medicinal chemistry

authors： Jiang JB,Johnson MG,Defauw JM,Beine TM,Ballas LM,Janzen WP,Loomis CR,Seldin J,Cofield D,Adams L

更新日期：1992-11-13 00:00:00

abstract：:Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we h...

journal_title：Journal of medicinal chemistry

authors： Chinen LK,Galen KP,Kuan KT,Dyszlewski ME,Ozaki H,Sawai H,Pandurangi RS,Jacobs FG,Dorshow RB,Rajagopalan R

更新日期：2008-02-28 00:00:00

abstract：:Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthe...

journal_title：Journal of medicinal chemistry

authors： Barthel BL,Rudnicki DL,Kirby TP,Colvin SM,Burkhart DJ,Koch TH

更新日期：2012-07-26 00:00:00

abstract：:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting...

journal_title：Journal of medicinal chemistry

authors： Hübner H,Haubmann C,Utz W,Gmeiner P

更新日期：2000-02-24 00:00:00

abstract：:Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...

journal_title：Journal of medicinal chemistry

authors： Gamage SA,Figgitt DP,Wojcik SJ,Ralph RK,Ransijn A,Mauel J,Yardley V,Snowdon D,Croft SL,Denny WA

更新日期：1997-08-01 00:00:00

abstract：:Histone deacetylase 6 (HDAC6) removes the acetyl group from lysine residues in a number of non-histone substrates and plays important roles in microtubule dynamics and chaperone activities. There is growing interest in identifying HDAC6-selective inhibitors as chemical biology tools and ultimately as new therapeutic a...

journal_title：Journal of medicinal chemistry

authors： Lin X,Chen W,Qiu Z,Guo L,Zhu W,Li W,Wang Z,Zhang W,Zhang Z,Rong Y,Zhang M,Yu L,Zhong S,Zhao R,Wu X,Wong JC,Tang G

更新日期：2015-03-26 00:00:00

abstract：:Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergol...

journal_title：Journal of medicinal chemistry

authors： Crider AM,Lu CK,Floss HG,Cassady JM,Clemens JA

更新日期：1979-01-01 00:00:00

abstract：:Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...

journal_title：Journal of medicinal chemistry

authors： Caliendo G,Grieco P,Perissutti E,Santagada V,Saviano G,Tancredi T,Temussi PA

更新日期：1997-02-14 00:00:00

abstract：:Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tubercu...

journal_title：Journal of medicinal chemistry

authors： Yu M,Nagalingam G,Ellis S,Martinez E,Sintchenko V,Spain M,Rutledge PJ,Todd MH,Triccas JA

更新日期：2016-06-23 00:00:00

abstract：:Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response. ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Ballard P,Bardelle C,Cockerill M,Colclough N,Critchlow SE,Debreczeni J,Fairley G,Fillery S,Graham MA,Goodwin L,Guichard S,Hudson K,Ward RA,Whittaker D

更新日期：2015-03-26 00:00:00

abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...

journal_title：Journal of medicinal chemistry

authors： Temple C Jr,Rener GA,Waud WR,Noker PE

更新日期：1992-10-02 00:00:00

abstract：:S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P5 modulation due to the absence of tool molecules wit...

journal_title：Journal of medicinal chemistry

authors： Hobson AD,Harris CM,van der Kam EL,Turner SC,Abibi A,Aguirre AL,Bousquet P,Kebede T,Konopacki DB,Gintant G,Kim Y,Larson K,Maull JW,Moore NS,Shi D,Shrestha A,Tang X,Zhang P,Sarris KK

更新日期：2015-12-10 00:00:00

abstract：:The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This eff...

journal_title：Journal of medicinal chemistry

authors： Wright SW,Petraitis JJ,Abelman MM,Batt DG,Bostrom LL,Corbett RL,Decicco CP,Di Meo SV,Freimark B,Giannaras JV

更新日期：1994-09-16 00:00:00

abstract：:Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors...

journal_title：Journal of medicinal chemistry

authors： Tahirovic YA,Geballe M,Gruszecka-Kowalik E,Myers SJ,Lyuboslavsky P,Le P,French A,Irier H,Choi WB,Easterling K,Yuan H,Wilson LJ,Kotloski R,McNamara JO,Dingledine R,Liotta DC,Traynelis SF,Snyder JP

更新日期：2008-09-25 00:00:00

abstract：:The preparation and testing of the two racemic diastereoisomers and the four optically active enantiomers of the title compound in in vitro and in vivo models for determining potential antipsychotic activity are described. Both racemic diastereoisomers and two of the four chiral enantiomers are potent and long-acting ...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Ewing FE,Harbert CA,Weissman A,Koe BK

更新日期：1980-08-01 00:00:00