Nucleic acid related compounds. 65. New syntheses of 1-(beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from vinylsilane precursors. Radioiodine uptake as a marker for thymidine kinase positive herpes viral infections.

abstract：:Monosubstituted derivatives of adenosine 5'-phosphate (AMP) with substituents of 1-3 atoms or group replacements at any of 11 positions have been synthesized and examined as substrates and inhibitors of the rat muscle adenylate kinase isozyme (AK-M), and the rat AK II and III isozymes predominant in poorly differentia...

journal_title：Journal of medicinal chemistry

authors： Hai TT,Picker D,Abo M,Hampton A

更新日期：1982-07-01 00:00:00

abstract：:From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar human vasopressin 1a (hV1a) receptor antagonist 38. Initial optimization of the mouse V1a activities delivered suitable t...

journal_title：Journal of medicinal chemistry

authors： Ratni H,Rogers-Evans M,Bissantz C,Grundschober C,Moreau JL,Schuler F,Fischer H,Alvarez Sanchez R,Schnider P

更新日期：2015-03-12 00:00:00

abstract：:Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κ...

journal_title：Journal of medicinal chemistry

authors： Zhang L,Dewan V,Yin H

更新日期：2017-06-22 00:00:00

abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...

journal_title：Journal of medicinal chemistry

authors： Ehrt C,Brinkjost T,Koch O

更新日期：2016-05-12 00:00:00

abstract：:The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1- 4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero ...

journal_title：Journal of medicinal chemistry

authors： Sanz AM,Gómez-Contreras F,Navarro P,Sánchez-Moreno M,Boutaleb-Charki S,Campuzano J,Pardo M,Osuna A,Cano C,Yunta MJ,Campayo L

更新日期：2008-03-27 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：:The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric...

journal_title：Journal of medicinal chemistry

authors： Cheng JF,Chen M,Wallace D,Tith S,Haramura M,Liu B,Mak CC,Arrhenius T,Reily S,Brown S,Thorn V,Harmon C,Barr R,Dyck JR,Lopaschuk GD,Nadzan AM

更新日期：2006-03-09 00:00:00

abstract：:Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isox...

journal_title：Journal of medicinal chemistry

authors： Hogner A,Greenwood JR,Liljefors T,Lunn ML,Egebjerg J,Larsen IK,Gouaux E,Kastrup JS

更新日期：2003-01-16 00:00:00

abstract：:This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it ...

journal_title：Journal of medicinal chemistry

authors： Fernandes P,Pereira D,Watkins PB,Bertrand D

更新日期：2020-06-25 00:00:00

abstract：:Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dih...

journal_title：Journal of medicinal chemistry

authors： Magedov IV,Frolova L,Manpadi M,Bhoga Ud,Tang H,Evdokimov NM,George O,Georgiou KH,Renner S,Getlik M,Kinnibrugh TL,Fernandes MA,Van slambrouck S,Steelant WF,Shuster CB,Rogelj S,van Otterlo WA,Kornienko A

更新日期：2011-06-23 00:00:00

abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...

journal_title：Journal of medicinal chemistry

authors： DeRuiter J,Borne RF,Mayfield CA

更新日期：1989-01-01 00:00:00

abstract：:Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In t...

journal_title：Journal of medicinal chemistry

authors： Hajduk PJ

更新日期：2006-11-30 00:00:00

abstract：:Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 μM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were depende...

journal_title：Journal of medicinal chemistry

authors： Thiele S,Malmgaard-Clausen M,Engel-Andreasen J,Steen A,Rummel PC,Nielsen MC,Gloriam DE,Frimurer TM,Ulven T,Rosenkilde MM

更新日期：2012-09-27 00:00:00

abstract：:Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein...

journal_title：Journal of medicinal chemistry

authors： Fosso MY,Shrestha SK,Green KD,Garneau-Tsodikova S

更新日期：2015-12-10 00:00:00

abstract：:Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transf...

journal_title：Journal of medicinal chemistry

authors： Kaiser C,Oh HJ,Garcia-Slanga BJ,Sulpizio AC,Hieble JP,Wawro JE,Kruse LI

更新日期：1986-11-01 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：:Studies indicate that MAO-B is induced in peripheral inflammatory diseases. To target peripheral tissues using MAO-B inhibitors that do not permeate the blood-brain barrier (BBB) the MAO-B-selective inhibitor deprenyl was remodeled by replacing the terminal acetylene with a CO2H function, and incorporating a para-OCH2...

journal_title：Journal of medicinal chemistry

authors： Gealageas R,Devineau A,So PPL,Kim CMJ,Surendradoss J,Buchwalder C,Heller M,Goebeler V,Dullaghan EM,Grierson DS,Putnins EE

更新日期：2018-08-23 00:00:00

abstract：:Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mi...

journal_title：Journal of medicinal chemistry

authors： Akcan M,Stroud MR,Hansen SJ,Clark RJ,Daly NL,Craik DJ,Olson JM

更新日期：2011-02-10 00:00:00

abstract：:Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other haloge...

journal_title：Journal of medicinal chemistry

authors： Yu Z,Zhou J,Ji X,Lin G,Xu S,Dong X,Zhao W

更新日期：2020-09-10 00:00:00

abstract：:A series of 3-aryloxindole derivatives were synthesized and evaluated as activators of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising maxi-K openers to emerge from this study were (+/-)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trif...

journal_title：Journal of medicinal chemistry

authors： Hewawasam P,Erway M,Moon SL,Knipe J,Weiner H,Boissard CG,Post-Munson DJ,Gao Q,Huang S,Gribkoff VK,Meanwell NA

更新日期：2002-03-28 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：:Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical prop...

journal_title：Journal of medicinal chemistry

authors： Koeberle SC,Fischer S,Schollmeyer D,Schattel V,Grütter C,Rauh D,Laufer SA

更新日期：2012-06-28 00:00:00

abstract：:The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 ...

journal_title：Journal of medicinal chemistry

authors： Maddirala AR,Klein R,Pinkner JS,Kalas V,Hultgren SJ,Janetka JW

更新日期：2019-01-24 00:00:00

abstract：:Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them...

journal_title：Journal of medicinal chemistry

authors： Cheng D,Valente S,Castellano S,Sbardella G,Di Santo R,Costi R,Bedford MT,Mai A

更新日期：2011-07-14 00:00:00

abstract：:A series of inhibitors of the malarial aspartic proteases Plm I and II have been synthesized with L-mannitol as precursor. These inhibitors are characterized by either a diacylhydrazine or a five-membered oxadiazole ring replacing backbone amide functionalities. Molecular dynamics simulations were applied in the desig...

journal_title：Journal of medicinal chemistry

authors： Ersmark K,Nervall M,Hamelink E,Janka LK,Clemente JC,Dunn BM,Blackman MJ,Samuelsson B,Aqvist J,Hallberg A

更新日期：2005-09-22 00:00:00

abstract：:On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molec...

journal_title：Journal of medicinal chemistry

authors： Lu H,Silverman RB

更新日期：2006-12-14 00:00:00

abstract：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Dajani EZ,Pappo R,Gasiecki AF,Bianchi RG,Woods EM

更新日期：1983-06-01 00:00:00

abstract：:An alpha-sialoside linked to acrylamide by a short connector (5-acetamido-2-O-(N-acryloyl-8-amino-5-oxaoctyl)-2,6-anhydro-3,5-d ideoxy-D-galacto-alpha-nonulopyranosonoic acid, 1) was prepared. Compound 1 formed high molecular weight copolymers with acrylamide, derivatives of acrylamide, and/or vinylpyrrolidone upon ph...

journal_title：Journal of medicinal chemistry

authors： Lees WJ,Spaltenstein A,Kingery-Wood JE,Whitesides GM

更新日期：1994-09-30 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：: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