Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole.

abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

journal_title：Journal of medicinal chemistry

authors： Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

更新日期：2013-10-24 00:00:00

abstract：:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...

journal_title：Journal of medicinal chemistry

authors： Xu H,Baidoo K,Gunn AJ,Boswell CA,Milenic DE,Choyke PL,Brechbiel MW

更新日期：2007-09-20 00:00:00

abstract：:The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that ...

journal_title：Journal of medicinal chemistry

authors： LaPlante SR,Carson R,Gillard J,Aubry N,Coulombe R,Bordeleau S,Bonneau P,Little M,O'Meara J,Beaulieu PL

更新日期：2013-06-27 00:00:00

abstract：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Omnaas JR,Lomize A,Heyl DL,Nordan I,Mousigian C,Davis P,Porreca F

更新日期：1994-12-09 00:00:00

abstract：:A new technique for using receptor surface models in quantitative structure-activity relationship (QSAR) analysis is described. Receptor surface models provide compact, quantitative descriptors which capture three-dimensional information about putative receptor/ligand interactions. Receptor surface models can be const...

journal_title：Journal of medicinal chemistry

authors： Hahn M,Rogers D

更新日期：1995-06-09 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 novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform o...

journal_title：Journal of medicinal chemistry

authors： Hayashi Y,Skwarczynski M,Hamada Y,Sohma Y,Kimura T,Kiso Y

更新日期：2003-08-28 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimizatio...

journal_title：Journal of medicinal chemistry

authors： Jiang Y,Andrews SW,Condroski KR,Buckman B,Serebryany V,Wenglowsky S,Kennedy AL,Madduru MR,Wang B,Lyon M,Doherty GA,Woodard BT,Lemieux C,Geck Do M,Zhang H,Ballard J,Vigers G,Brandhuber BJ,Stengel P,Josey JA,Beigelm

更新日期：2014-03-13 00:00:00

abstract：:Prolonged drug-target occupancy has become increasingly important in lead optimization, and biophysical assays that measure residence time are in high demand. Here we report a practical label-free assay methodology that provides kinetic and affinity measurements suitable for most target classes without long preincubat...

journal_title：Journal of medicinal chemistry

authors： Quinn JG,Pitts KE,Steffek M,Mulvihill MM

更新日期：2018-06-28 00:00:00

abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...

journal_title：Journal of medicinal chemistry

authors： Singh P,Kaur S,Kaur J,Singh G,Bhatti R

更新日期：2016-04-28 00:00:00

abstract：:The influence of structure on DT-diaphorase substrate activity, topoisomerase II inhibition activity, and DNA reductive alkylation was studied for the 6-aziridinylpyrrolo[1,2-alpha]benzimidazolequinones (PBIs) and the 6-acetamidopyrrolo[1,2-alpha]benzimidazolequinones (APBIs). The PBIs are reductively activated by DT-...

journal_title：Journal of medicinal chemistry

authors： Skibo EB,Gordon S,Bess L,Boruah R,Heileman MJ

更新日期：1997-04-25 00:00:00

abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

journal_title：Journal of medicinal chemistry

authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

更新日期：1981-06-01 00:00:00

abstract：:The maximum achievable accuracy of in silico models depends on the quality of the experimental data. Consequently, experimental uncertainty defines a natural upper limit to the predictive performance possible. Models that yield errors smaller than the experimental uncertainty are necessarily overtrained. A reliable es...

journal_title：Journal of medicinal chemistry

authors： Kramer C,Kalliokoski T,Gedeck P,Vulpetti A

更新日期：2012-06-14 00:00:00

abstract：:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2...

journal_title：Journal of medicinal chemistry

authors： Monge A,Peña MC,Palop JA,Calderó JM,Roca J,García E,Romero G,del Río J,Lasheras B

更新日期：1994-04-29 00:00:00

abstract：:Monophenolic (2-(dipropylamino)indans and related compounds have been synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different dopamine-rec...

journal_title：Journal of medicinal chemistry

authors： Hacksell U,Arvidsson LE,Svensson U,Nilsson JL,Wikström H,Lindberg P,Sanchez D,Hjorth S,Carlsson A,Paalzow L

更新日期：1981-04-01 00:00:00

abstract：:Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid fun...

journal_title：Journal of medicinal chemistry

authors： Bollinger M,Manzenrieder F,Kolb R,Bochen A,Neubauer S,Marinelli L,Limongelli V,Novellino E,Moessmer G,Pell R,Lindner W,Fanous J,Hoffman A,Kessler H

更新日期：2012-01-26 00:00:00

abstract：:4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...

journal_title：Journal of medicinal chemistry

authors： Seiler MP,Floersheim P,Markstein R,Widmer A

更新日期：1993-04-16 00:00:00

abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...

journal_title：Journal of medicinal chemistry

authors： Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

更新日期：2004-12-16 00:00:00

abstract：:G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional re...

journal_title：Journal of medicinal chemistry

authors： Perrone R,Nadai M,Frasson I,Poe JA,Butovskaya E,Smithgall TE,Palumbo M,Palù G,Richter SN

更新日期：2013-08-22 00:00:00

abstract：:The efficacious dose of a drug is perhaps the most holistic metric reflecting its therapeutic potential. Dose is predicted at many stages in drug discovery and development. Prior to the 1990s, dose prediction was limited to the drug "working" at a reasonable dose and dose regimen in an animal model. Through the early ...

journal_title：Journal of medicinal chemistry

authors： Maurer TS,Smith D,Beaumont K,Di L

更新日期：2020-06-25 00:00:00

abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...

journal_title：Journal of medicinal chemistry

authors： Monn JA,Thurkauf A,Mattson MV,Jacobson AE,Rice KC

更新日期：1990-03-01 00:00:00

abstract：:The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be...

journal_title：Journal of medicinal chemistry

authors： Mungall WS,Lemmen LJ,Lemmen KL,Dethmers JK,Norling LL

更新日期：1978-07-01 00:00:00

abstract：:Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Van Aerschot A,Janssen G,Claes P,Balzarini J,De Clercq E,Herdewijn P

更新日期：1990-02-01 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：:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 co...

journal_title：Journal of medicinal chemistry

authors： Kukolja S,Pfeil JL,Draheim SE,Ott JL

更新日期：1985-12-01 00:00:00

abstract：:(E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in s...

journal_title：Journal of medicinal chemistry

authors： Kumar A,Coe PL,Jones AS,Walker RT,Balzarini J,De Clercq E

更新日期：1990-09-01 00:00:00

abstract：:Pleuromutilin and its derivatives are antibacterial drugs that inhibit protein synthesis in bacteria by binding to ribosomes. To promote rational design of pleuromutilin based drugs, 19 pleuromutilin conjugates with different nucleoside fragments as side chain extensions were synthesized by a click chemistry protocol....

journal_title：Journal of medicinal chemistry

authors： Lolk L,Pøhlsgaard J,Jepsen AS,Hansen LH,Nielsen H,Steffansen SI,Sparving L,Nielsen AB,Vester B,Nielsen P

更新日期：2008-08-28 00:00:00

abstract：:G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A se...

journal_title：Journal of medicinal chemistry

authors： Setoh M,Ishii N,Kono M,Miyanohana Y,Shiraishi E,Harasawa T,Ota H,Odani T,Kanzaki N,Aoyama K,Hamada T,Kori M

更新日期：2014-06-26 00:00:00

abstract：:Reaction of 6-deoxy-2,3,5-tris-O-(p-nitrobenzoyl)-L-talofuranosyl bromide (1) with the trimethylsilyl derivative of hypoxanthine, followed by removal of blocking groups, afforded 9- (6) and 7-(6'-deoxy-alpha-L-talofuranosyl)hypoxanthine (7). A study of the published optical rotations and circular dichroic (CD) spectra...

journal_title：Journal of medicinal chemistry

authors： Nelson V,El Khadem HS

更新日期：1983-10-01 00:00:00