Synthesis and copper-dependent antimycoplasmal activity of amides and amidines derived from 2-amino-1,10-phenanthroline.

abstract：:Insulin secretion by pancreatic β-cells in response to glucose or other secretagogues is tightly coupled to membrane potential. Various studies have highlighted the prospect of enhancing insulin secretion in a glucose-dependent manner by blocking voltage-gated potassium channels (K(v)) and calcium-activated potassium ...

journal_title：Journal of medicinal chemistry

authors： Nguyen TT,Folch B,Létourneau M,Truong NH,Doucet N,Fournier A,Chatenet D

更新日期：2014-03-27 00:00:00

abstract：:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-d...

journal_title：Journal of medicinal chemistry

authors： Ajmera S,Danenberg PV

更新日期：1982-08-01 00:00:00

abstract：:Phenacyl-riphenylphosphorane (1a) and several analogs substituted in the meta position of the phenacyl group lowered blood glucose levels in 48-hr fasted rats. The corresponding phosphonium salts had comparable hypoglycemic activity. Two compounds (1a and 1b) were also hypoglycemic in fed rats, but hypoglycemia could ...

journal_title：Journal of medicinal chemistry

authors： Blank B,DiTullio NW,Deviney L,Roberts JT,Saunders HL

更新日期：1975-09-01 00:00:00

abstract：:Significant efforts have been reported on the development of influenza antivirals including inhibitors of the RNA-dependent RNA polymerase PA N-terminal (PAN) endonuclease. Based on recently identified, highly active metal-binding pharmacophores (MBPs) for PAN endonuclease inhibition, a fragment-based drug development...

journal_title：Journal of medicinal chemistry

authors： Credille CV,Morrison CN,Stokes RW,Dick BL,Feng Y,Sun J,Chen Y,Cohen SM

更新日期：2019-11-14 00:00:00

abstract：:Pyrazolo[3,4-d]pyrimidines are potent protein kinase inhibitors with promising antitumor activity but suboptimal aqueous solubility, consequently worth being further optimized. Herein, we present the one-pot two-step procedure for the synthesis of a set of pyrazolo[3,4-d]pyrimidine prodrugs (1a-8a and 9a-e) with highe...

journal_title：Journal of medicinal chemistry

authors： Vignaroli G,Iovenitti G,Zamperini C,Coniglio F,Calandro P,Molinari A,Fallacara AL,Sartucci A,Calgani A,Colecchia D,Mancini A,Festuccia C,Dreassi E,Valoti M,Musumeci F,Chiariello M,Angelucci A,Botta M,Schenone S

更新日期：2017-07-27 00:00:00

abstract：:Comparative binding energy analysis, a technique to derive receptor-based three-dimensional quantitative structure-activity relationships (3D-QSAR), is herein extended to consider both affinity and selectivity in the derivation of the QSAR model. The extension is based on allowing multiple structurally related recepto...

journal_title：Journal of medicinal chemistry

authors： Murcia M,Morreale A,Ortiz AR

更新日期：2006-10-19 00:00:00

abstract：:N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both P...

journal_title：Journal of medicinal chemistry

authors： Rackham MD,Brannigan JA,Rangachari K,Meister S,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EW

更新日期：2014-03-27 00:00:00

abstract：:Anaplastic lymphoma kinase (ALK) is a valid target for anticancer therapy; however, potent ALK inhibitors suitable for clinical use are lacking. Because the majority of described kinase inhibitors bind in the ATP pocket of the kinase domain, we have characterized this pocket in ALK using site-directed mutagenesis, inh...

journal_title：Journal of medicinal chemistry

authors： Gunby RH,Ahmed S,Sottocornola R,Gasser M,Redaelli S,Mologni L,Tartari CJ,Belloni V,Gambacorti-Passerini C,Scapozza L

更新日期：2006-09-21 00:00:00

abstract：:Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A(1) and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside deri...

journal_title：Journal of medicinal chemistry

authors： Jacobson KA,Gao ZG,Tchilibon S,Duong HT,Joshi BV,Sonin D,Liang BT

更新日期：2005-12-29 00:00:00

abstract：:The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...

journal_title：Journal of medicinal chemistry

authors： Jadhav A,Ferreira RS,Klumpp C,Mott BT,Austin CP,Inglese J,Thomas CJ,Maloney DJ,Shoichet BK,Simeonov A

更新日期：2010-01-14 00:00:00

abstract：:In a search for improved multiple drug resistance (MDR) modulators, we identified a novel series of substituted pyrroloquinolines that selectively inhibits the function of P-glycoprotein (Pgp) without modulating multidrug resistance-related protein 1 (MRP1). These compounds were evaluated for their toxicity toward dru...

journal_title：Journal of medicinal chemistry

authors： Lee BD,Li Z,French KJ,Zhuang Y,Xia Z,Smith CD

更新日期：2004-03-11 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...

journal_title：Journal of medicinal chemistry

authors： De Croos PZ,Sangdee P,Stockwell BL,Kar L,Thompson EB,Johnson ME,Currie BL

更新日期：1990-12-01 00:00:00

abstract：:Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor associated with the pathogenesis of autoimmune diseases. Allosteric inhibition of RORγt is conceptually new, unique for this specific nuclear receptor, and offers advantages over traditional orthosteric inhibition. Here, we report a highly...

journal_title：Journal of medicinal chemistry

authors： Meijer FA,Doveston RG,de Vries RMJM,Vos GM,Vos AAA,Leysen S,Scheepstra M,Ottmann C,Milroy LG,Brunsveld L

更新日期：2020-01-09 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...

journal_title：Journal of medicinal chemistry

authors： Patel S,Cohen F,Dean BJ,De La Torre K,Deshmukh G,Estrada AA,Ghosh AS,Gibbons P,Gustafson A,Huestis MP,Le Pichon CE,Lin H,Liu W,Liu X,Liu Y,Ly CQ,Lyssikatos JP,Ma C,Scearce-Levie K,Shin YG,Solanoy H,Stark KL,Wa

更新日期：2015-01-08 00:00:00

abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

journal_title：Journal of medicinal chemistry

authors： Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

更新日期：1995-05-26 00:00:00

abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...

journal_title：Journal of medicinal chemistry

authors： O'Hara F,Burns AC,Collins MR,Dalvie D,Ornelas MA,Vaz AD,Fujiwara Y,Baran PS

更新日期：2014-02-27 00:00:00

abstract：:Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. We investigated the reactivity of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate, FeSO(4...

journal_title：Journal of medicinal chemistry

authors： Bousejra-El Garah F,Wong MH,Amewu RK,Muangnoicharoen S,Maggs JL,Stigliani JL,Park BK,Chadwick J,Ward SA,O'Neill PM

更新日期：2011-10-13 00:00:00

abstract：:A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two compounds exhibit ant...

journal_title：Journal of medicinal chemistry

authors： Drakulić BJ,Juranić ZD,Stanojković TP,Juranić IO

更新日期：2005-08-25 00:00:00

abstract：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...

journal_title：Journal of medicinal chemistry

authors： Teng P,Huo D,Nimmagadda A,Wu J,She F,Su M,Lin X,Yan J,Cao A,Xi C,Hu Y,Cai J

更新日期：2016-09-08 00:00:00

abstract：:Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibi...

journal_title：Journal of medicinal chemistry

authors： Pearce BC,Parker RA,Deason ME,Dischino DD,Gillespie E,Qureshi AA,Volk K,Wright JJ

更新日期：1994-02-18 00:00:00

abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

更新日期：1984-03-01 00:00:00

abstract：:The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. ...

journal_title：Journal of medicinal chemistry

authors： Skotnicki JS,Schaub RE,Weiss MJ,Dessy F

更新日期：1977-12-01 00:00:00

abstract：:sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2...

journal_title：Journal of medicinal chemistry

authors： Nakazato A,Ohta K,Sekiguchi Y,Okuyama S,Chaki S,Kawashima Y,Hatayama K

更新日期：1999-03-25 00:00:00

abstract：:Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroide...

journal_title：Journal of medicinal chemistry

authors： Bochis RJ,Olen LE,Waksmunski FS,Mrozik H,Eskola P,Kulsa P,Wilks G,Taylor JE,Egerton JR,Ostlind DA,Olson G

更新日期：1981-12-01 00:00:00

abstract：:Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human...

journal_title：Journal of medicinal chemistry

authors： Bhatia PA,Brooks CD,Basha A,Ratajczyk JD,Gunn BP,Bouska JB,Lanni C,Young PR,Bell RL,Carter GW

更新日期：1996-09-27 00:00:00

abstract：:Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...

journal_title：Journal of medicinal chemistry

authors： Lucas SCC,Atkinson SJ,Bamborough P,Barnett H,Chung CW,Gordon L,Mitchell DJ,Phillipou A,Prinjha RK,Sheppard RJ,Tomkinson NCO,Watson RJ,Demont EH

更新日期：2020-05-28 00:00:00

abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...

journal_title：Journal of medicinal chemistry

authors： Krieger V,Hamacher A,Gertzen CGW,Senger J,Zwinderman MRH,Marek M,Romier C,Dekker FJ,Kurz T,Jung M,Gohlke H,Kassack MU,Hansen FK

更新日期：2017-07-13 00:00:00

abstract：:In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated...

journal_title：Journal of medicinal chemistry

authors： Benz S,Nötzli S,Siegel JS,Eberli D,Jessen HJ

更新日期：2013-12-27 00:00:00