5-Cyano-2'-deoxyuridine 5'-phosphate: a potent competitive inhibitor of thymidylate synthetase.

abstract：:2-Amino-3-aroylthiophenes are agonist allosteric enhancers (AE) at the A(1) adenosine receptor (A(1)AR). Here we report the syntheses of three kinds of novel 2-aminothiophenes and assays of their AE activity at the human A(1)AR (hA(1)AR), namely, (1) 2-amino-4,5-diphenylthiophene-3-carboxylates, 3a-h, (2) 2-amino-3-be...

journal_title：Journal of medicinal chemistry

authors： Lütjens H,Zickgraf A,Figler H,Linden J,Olsson RA,Scammells PJ

更新日期：2003-05-08 00:00:00

abstract：:A series of 3-hydroxy-substituted analogues (3-7) of the mu selective opioid antagonist cyprodime has been synthesized in order to evaluate the role of a hydroxy group at C-3 concerning mu opioid antagonist selectivity. Compounds 3-7 were tested in bioassays (electrical stimulated mouse vas deferens preparation and my...

journal_title：Journal of medicinal chemistry

authors： Schmidhammer H,Jennewein HK,Krassnig R,Traynor JR,Patel D,Bell K,Froschauer G,Mattersberger K,Jachs-Ewinger C,Jura P

更新日期：1995-08-04 00:00:00

abstract：:The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr(1)-cyclo(d-Asp(5),Dap(8))]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS after systemic administration. Hence, we synthesized zyklophin analogues to explore the structure-act...

journal_title：Journal of medicinal chemistry

authors： Joshi AA,Murray TF,Aldrich JV

更新日期：2015-11-25 00:00:00

abstract：:The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...

journal_title：Journal of medicinal chemistry

authors： Kruse CH,Holden KG,Pritchard ML,Feild JA,Rieman DJ,Greig RG,Poste G

更新日期：1988-09-01 00:00:00

abstract：:We have identified 5-(3-chlorothiophen-2-yl)-3-(4-trifluoromethylphenyl)-1,2,4-oxadiazole (1d) as a novel apoptosis inducer through our caspase- and cell-based high-throughput screening assay. Compound 1d has good activity against several breast and colorectal cancer cell lines but is inactive against several other ca...

journal_title：Journal of medicinal chemistry

authors： Zhang HZ,Kasibhatla S,Kuemmerle J,Kemnitzer W,Ollis-Mason K,Qiu L,Crogan-Grundy C,Tseng B,Drewe J,Cai SX

更新日期：2005-08-11 00:00:00

abstract：:Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5...

journal_title：Journal of medicinal chemistry

authors： Krecmerová M,Holý A,Pohl R,Masojídková M,Andrei G,Naesens L,Neyts J,Balzarini J,De Clercq E,Snoeck R

更新日期：2007-11-15 00:00:00

abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

journal_title：Journal of medicinal chemistry

authors： Lippke KP,Schunack WG,Wenning W,Müller WE

更新日期：1983-04-01 00:00:00

abstract：:Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the ...

journal_title：Journal of medicinal chemistry

authors： Liu F,Chen X,Allali-Hassani A,Quinn AM,Wigle TJ,Wasney GA,Dong A,Senisterra G,Chau I,Siarheyeva A,Norris JL,Kireev DB,Jadhav A,Herold JM,Janzen WP,Arrowsmith CH,Frye SV,Brown PJ,Simeonov A,Vedadi M,Jin J

更新日期：2010-08-12 00:00:00

abstract：:In this work, we introduce a four-step scoring and filtering procedure, furnishing target specific virtual screening (TS-VS), which serves to minimize false positives resulting from conformational artifacts of the docking process and is optimized to converge on novel chemotypes of estrogen receptor alpha (ERalpha). As...

journal_title：Journal of medicinal chemistry

authors： Knox AJ,Meegan MJ,Sobolev V,Frost D,Zisterer DM,Williams DC,Lloyd DG

更新日期：2007-11-01 00:00:00

abstract：:A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional expe...

journal_title：Journal of medicinal chemistry

authors： Enguehard-Gueiffier C,Hübner H,El Hakmaoui A,Allouchi H,Gmeiner P,Argiolas A,Melis MR,Gueiffier A

更新日期：2006-06-29 00:00:00

abstract：:Fifteen quinolizidine derivatives have been tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. All compounds exhibited from moderate to high antiarrhythmic activity, and five of them (3, 4, 6, 13, and 15) were more active ...

journal_title：Journal of medicinal chemistry

authors： Tasso B,Budriesi R,Vazzana I,Ioan P,Micucci M,Novelli F,Tonelli M,Sparatore A,Chiarini A,Sparatore F

更新日期：2010-06-24 00:00:00

abstract：:Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzym...

journal_title：Journal of medicinal chemistry

authors： Seidler J,McGovern SL,Doman TN,Shoichet BK

更新日期：2003-10-09 00:00:00

abstract：:A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluor...

journal_title：Journal of medicinal chemistry

authors： Higley CA,Wilde RG,Maduskuie TP,Johnson AL,Pennev P,Billheimer JT,Robinson CS,Gillies PJ,Wexler RR

更新日期：1994-10-14 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 variety of derivatives of 2-pyridinecarboxaldehyde 1-oxide benzenesulfonylhydrazone, containing substituents on the benzene or pyridine rings as well as on the nitrogen atom which is bonded directly to the sulfonyl group, have been synthesized. The antineoplastic activity of these compounds has been assessed in mice...

journal_title：Journal of medicinal chemistry

authors： Loh W,Cosby LA,Sartorelli AC

更新日期：1980-06-01 00:00:00

abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...

journal_title：Journal of medicinal chemistry

authors： Xu Y,Jiang G,Tsukahara R,Fujiwara Y,Tigyi G,Prestwich GD

更新日期：2006-08-24 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML ac...

journal_title：Journal of medicinal chemistry

authors： Sang F,Ding Y,Wang J,Sun B,Sun J,Geng Y,Zhang Z,Ding K,Wu LL,Liu JW,Bai C,Yang G,Zhang Q,Li LY,Chen Y

更新日期：2016-02-11 00:00:00

abstract：:We report a three-dimensional model of the alpha5beta1 integrin headgroup bound to the most potent and selective ligand (SJ749) known to date. The model was built using the comparative protein modeling method, and it is consistent with experimental data. From this study, we identified two potentially important regions...

journal_title：Journal of medicinal chemistry

authors： Marinelli L,Meyer A,Heckmann D,Lavecchia A,Novellino E,Kessler H

更新日期：2005-06-30 00:00:00

abstract：:A series of 3-imino-2-indolones are the first published, high-affinity antagonists of the galanin GAL3 receptor. One example, 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for GAL3 over a b...

journal_title：Journal of medicinal chemistry

authors： Konkel MJ,Lagu B,Boteju LW,Jimenez H,Noble S,Walker MW,Chandrasena G,Blackburn TP,Nikam SS,Wright JL,Kornberg BE,Gregory T,Pugsley TA,Akunne H,Zoski K,Wise LD

更新日期：2006-06-29 00:00:00

abstract：:Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto th...

journal_title：Journal of medicinal chemistry

authors： Bergeron RJ,Wiegand J,Bharti N,McManis JS

更新日期：2012-08-23 00:00:00

abstract：:omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric p...

journal_title：Journal of medicinal chemistry

authors： Leydet A,Barragan V,Boyer B,Montéro JL,Roque JP,Witvrouw M,Este J,Snoeck R,Andrei G,De Clercq E

更新日期：1997-01-31 00:00:00

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 00:00:00

abstract：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...

journal_title：Journal of medicinal chemistry

authors： Haginoya N,Kobayashi S,Komoriya S,Yoshino T,Suzuki M,Shimada T,Watanabe K,Hirokawa Y,Furugori T,Nagahara T

更新日期：2004-10-07 00:00:00

abstract：:6-Chloropurine derivatives of gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 3a, gamma-(Z)-ethylidene-2-methoxy-3-(4-nitro)benzyloxybutenolide 3b, gamma-(Z)-ethylidene-2-(4-nitro)benzyloxy-3-methoxybutenolide 3c, gamma-(Z)-ethylidene-2,3-di(4-nitro)benzyloxybutenolide 3d, and dimethylphosphono-gamma-(Z)-ethylidene-2,3-d...

journal_title：Journal of medicinal chemistry

authors： Hakimelahi GH,Mei NW,Moosavi-Movahedi AA,Davari H,Hakimelahi S,King KY,Hwu JR,Wen YS

更新日期：2001-05-24 00:00:00

abstract：:The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rea...

journal_title：Journal of medicinal chemistry

authors： Dorey G,Dubois L,Prodo de Carvalho LP,Potier P,Dodd RH

更新日期：1995-01-06 00:00:00

abstract：:Although the illness malaria is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the vector Anopheles, thus perpetuating the plasmodial cycle. Fight against malaria is more than ever a current problem, and the solution will probably go through the development...

journal_title：Journal of medicinal chemistry

authors： Dechy-Cabaret O,Benoit-Vical F

更新日期：2012-12-13 00:00:00

abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...

journal_title：Journal of medicinal chemistry

authors： Wilman DE,Cox PJ,Goddard PM,Hart LI,Merai K,Newell DR

更新日期：1984-07-01 00:00:00

abstract：:Synthesis and biological activity of 17-esters of 6-dehydro-16-methylene-17 alpha-hydroxyprogesterone are presented. A systematic study of the influence of the alteration of halogen at 6 and the acyl group at 17 on the progestational and antiandrogenic activities of the resulting structures is described. A convenien...

journal_title：Journal of medicinal chemistry

authors： Shapiro EL,Weber L,Harris H,Miskowicz C,Neri R,Herzog HL

更新日期：1972-07-01 00:00:00

abstract：:sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms was alternatively replaced by a methine or converted into an a...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,Uricchio V,Colabufo NA,Niso M,Perrone R

更新日期：2009-12-10 00:00:00