Synthesis of 5-beta-D-ribofuranosylnicotinamide and its N-methyl derivative. The isosteric and isoelectronic analogues of nicotinamide nucleoside.

abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...

journal_title：Journal of medicinal chemistry

authors： Na Y,Li VS,Nakanishi Y,Bastow KF,Kohn H

更新日期：2001-10-11 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：:Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and functi...

journal_title：Journal of medicinal chemistry

authors： Duraiswamy AJ,Lee MA,Madan B,Ang SH,Tan ES,Cheong WW,Ke Z,Pendharkar V,Ding LJ,Chew YS,Manoharan V,Sangthongpitag K,Alam J,Poulsen A,Ho SY,Virshup DM,Keller TH

更新日期：2015-08-13 00:00:00

abstract：:(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...

journal_title：Journal of medicinal chemistry

authors： Guenther S,Balzarini J,De Clercq E,Nair V

更新日期：2002-12-05 00:00:00

abstract：:Long chain fatty acid elongase 6 (ELOVL6) catalyzes the elongation of long chain fatty acyl-CoAs and is a potential target for the treatment of metabolic disorders. The ultrahigh throughput screen of our corporate chemical collections resulted in the identification of a novel 3-sulfonyl-8-azabicyclo[3.2.1]octane class...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Takahashi T,Sasaki T,Nagumo A,Shimamura K,Miyamoto Y,Kitazawa H,Kanesaka M,Yoshimoto R,Aragane K,Tokita S,Sato N

更新日期：2009-07-23 00:00:00

abstract：:Iron depletion, using iron chelators targeting transferrin receptor (TfR) and ribonucleotide reductase (RR), is proven to be effective in the treatment of cancer. We synthesized and evaluated novel polyaminocarboxylate-based chelators NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-NETA, C-NE3TA, and N-NE3...

journal_title：Journal of medicinal chemistry

authors： Chong HS,Ma X,Lee H,Bui P,Song HA,Birch N

更新日期：2008-04-10 00:00:00

abstract：:Tacrine and PBT2 (an 8-hydroxyquinoline derivative) are well-known drugs that inhibit cholinesterases and decrease beta-amyloid (Abeta) levels by complexation of redox-active metals, respectively. In this work, novel tacrine-8-hydroxyquinoline hybrids have been designed, synthesized, and evaluated as potential multifu...

journal_title：Journal of medicinal chemistry

authors： Fernández-Bachiller MI,Pérez C,González-Muñoz GC,Conde S,López MG,Villarroya M,García AG,Rodríguez-Franco MI

更新日期：2010-07-08 00:00:00

abstract：:Racemic ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazine-7- carbamate (1a) has shown antitumor activity in a variety of in vivo experiments. The preparation of the R and S isomers gave compounds with significant differences in potency in several biological tests. ...

journal_title：Journal of medicinal chemistry

authors： Temple C Jr,Rener GA

更新日期：1989-09-01 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...

journal_title：Journal of medicinal chemistry

authors： Doll MK,Nichols DE,Kilts JD,Prioleau C,Lawler CP,Lewis MM,Mailman RB

更新日期：1999-03-11 00:00:00

abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...

journal_title：Journal of medicinal chemistry

authors： Xu J,Kullgren B,Durbin PW,Raymond KN

更新日期：1995-07-07 00:00:00

abstract：:Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such stud...

journal_title：Journal of medicinal chemistry

authors： Brouwer C,Jenko K,Zoghbi SS,Innis RB,Pike VW

更新日期：2014-07-24 00:00:00

abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

journal_title：Journal of medicinal chemistry

authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

更新日期：1995-06-23 00:00:00

abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

journal_title：Journal of medicinal chemistry

authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

更新日期：1981-05-01 00:00:00

abstract：:A diverse 5000-compound library was synthesized from commercially available diamines and screened for activity against Mycobacterium tuberculosis in vitro, revealing 143 hits with minimum inhibitory concentration (MIC) equal to or less than 12.5 microM. New prospective scaffolds with antitubercular activity derived fr...

journal_title：Journal of medicinal chemistry

authors： Bogatcheva E,Hanrahan C,Nikonenko B,Samala R,Chen P,Gearhart J,Barbosa F,Einck L,Nacy CA,Protopopova M

更新日期：2006-06-01 00:00:00

abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

journal_title：Journal of medicinal chemistry

authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

更新日期：2016-10-13 00:00:00

abstract：:A series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against Trypanosoma brucei rhodesiense STIB900 and Plasmodium falciparum K1. The dicationic diphenyl compounds exhibited the best activities with IC 50 values against T. b. rhodesiense and P. falciparum in the nanomolar range. Fiv...

journal_title：Journal of medicinal chemistry

authors： Rodríguez F,Rozas I,Kaiser M,Brun R,Nguyen B,Wilson WD,García RN,Dardonville C

更新日期：2008-02-28 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC(50) < 1 mic...

journal_title：Journal of medicinal chemistry

authors： Fontana A,Cimino G,Gavagnin M,González MC,Estornell E

更新日期：2001-07-05 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:2-Phenylcyclopropylmethylamine (PCPMA) analogues have been reported as selective serotonin 2C agonists. On the basis of the same scaffold, we designed and synthesized a series of bitopic derivatives as dopamine D3R ligands. A number of these new compounds show a high binding affinity for D3R with excellent selectivity...

journal_title：Journal of medicinal chemistry

authors： Tan L,Zhou Q,Yan W,Sun J,Kozikowski AP,Zhao S,Huang XP,Cheng J

更新日期：2020-05-14 00:00:00

abstract：:Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hamme...

journal_title：Journal of medicinal chemistry

authors： Johnson CL

更新日期：1976-05-01 00:00:00

abstract：:The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted th...

journal_title：Journal of medicinal chemistry

authors： Stjernlöf P,Gullme M,Elebring T,Andersson B,Wikström H,Lagerquist S,Svensson K,Ekman A,Carlsson A,Sundell S

更新日期：1993-07-23 00:00:00

abstract：:The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamin...

journal_title：Journal of medicinal chemistry

authors： Rose NR,Woon EC,Tumber A,Walport LJ,Chowdhury R,Li XS,King ON,Lejeune C,Ng SS,Krojer T,Chan MC,Rydzik AM,Hopkinson RJ,Che KH,Daniel M,Strain-Damerell C,Gileadi C,Kochan G,Leung IK,Dunford J,Yeoh KK,Ratcliffe PJ

更新日期：2012-07-26 00:00:00

abstract：:Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminometh...

journal_title：Journal of medicinal chemistry

authors： Kung HF,Newman S,Choi SR,Oya S,Hou C,Zhuang ZP,Acton PD,Plössl K,Winkler J,Kung MP

更新日期：2004-10-07 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：:Molecular docking studies of carbohydrate derivatives in protein binding sites are often challenging because of water-mediated interactions and the inherent flexibility of the many terminal hydroxyl groups. Using the recognition process between heat-labile enterotoxin from Escherichia coli and ganglioside GM1 as a par...

journal_title：Journal of medicinal chemistry

authors： Minke WE,Diller DJ,Hol WG,Verlinde CL

更新日期：1999-05-20 00:00:00

abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...

journal_title：Journal of medicinal chemistry

authors： Havlícek L,Hanus J,Veselý J,Leclerc S,Meijer L,Shaw G,Strnad M

更新日期：1997-02-14 00:00:00

abstract：:The inhibition of chicken liver dihydrofolate reductase by a series of substituted benzylpyrimidines has been investigated. From the inhibition constants a quantitative structure-activity relationship has been formulated. This mathematical model is compared with molecular graphics models constructed from the X-ray cry...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Fang ZX,Li RL,Hansch C,Klein T,Langridge R,Kaufman BT

更新日期：1986-05-01 00:00:00

abstract：:In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release ...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Outred DJ,Smith H,Spicer BA

更新日期：1984-11-01 00:00:00