[11C]enzastaurin, the first design and radiosynthesis of a new potential PET agent for imaging of protein kinase C.


:Enzastaurin (LY317615) is a potent and selective protein kinase C (PKC) inhibitor with an IC(50) value of ∼6 nM. [(11)C]Enzastaurin (3-(1-[(11)C]methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of PKC, was first designed and synthesized in 20-25% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide.


Bioorg Med Chem Lett


Wang M,Xu L,Gao M,Miller KD,Sledge GW,Zheng QH




Has Abstract


2011-03-15 00:00:00














  • Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists.

    abstract::Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xue CB,Roderick J,Mousa S,Olson RE,DeGrado WF

    更新日期:1998-12-15 00:00:00

  • Molecular design, chemical synthesis, and evaluation of cytosine-carbohydrate hybrids for selective recognition of a single guanine bulged duplex DNA.

    abstract::The designed cytosine-carbohydrate hybrid molecule selectively recognized and stabilized the bulged duplex DNA possessing the complementary bulged DNA base, guanine, while the nucleotide base itself did not exhibit any such ability. It was also found that the assistance of the carbohydrate to stabilize the interaction...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Idutsu Y,Sasaki A,Matsumura S,Toshima K

    更新日期:2005-10-01 00:00:00

  • Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs.

    abstract::In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, sero...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xu M,Wang Y,Yang F,Wu C,Wang Z,Ye B,Jiang X,Zhao Q,Li J,Liu Y,Zhang J,Tian G,He Y,Shen J,Jiang H

    更新日期:2018-02-15 00:00:00

  • Radiosynthesis and in vivo tumor uptake of 2-deoxy-2-[(18)F]fluoro-myo-inositol.

    abstract::Inositols play an important role in membrane lipid metabolism and mitogenic signaling of most cancer cells. There is paucity of data on the distribution of radiolabelled inositols. Based on work previously carried out on 1-deoxy-1-[(18)F]fluoro-scyllo-inositol ([(18)F]2), we began a program of work to label myo-inosit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Carroll L,Perumal M,Vasdev N,Robins E,Aboagye EO

    更新日期:2012-10-01 00:00:00

  • An approach for differentiating isozymes. Construction of libraries containing short aromatic peptides as part of a method to design selective inhibitors against lipases.

    abstract::Through synthesis and assays of peptidyl substrates, we could select substrates having peptidyl complementary against lipases. The best substrate showed 20-fold improved K(m) relative to non-peptidyl substrate. Using this information, we generated selective inhibitors. Lipase activities with peptidyl substrates were r...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Park S,Yu J

    更新日期:2012-05-01 00:00:00

  • Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

    abstract::A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang SG,Kong LY,Li YH,Cheng XY,Su F,Tang S,Bi CW,Jiang JD,Li YH,Song DQ

    更新日期:2015-09-01 00:00:00

  • 3-(Cyclopropylmethyl)-7-((4-(4-[11C]methoxyphenyl)piperidin-1-yl)methyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine: Synthesis and preliminary evaluation for PET imaging of metabotropic glutamate receptor subtype 2.

    abstract::Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer origin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kumata K,Zhang Y,Ogawa M,Kurihara Y,Mori W,Hu K,Fujinaga M,Nengaki N,Zhang MR

    更新日期:2020-12-01 00:00:00

  • Scaffold oriented synthesis. Part 2: Design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors.

    abstract::We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC(50)=9 ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Gracias V,Ji Z,Akritopoulou-Zanze I,Abad-Zapatero C,Huth JR,Song D,Hajduk PJ,Johnson EF,Glaser KB,Marcotte PA,Pease L,Soni NB,Stewart KD,Davidsen SK,Michaelides MR,Djuric SW

    更新日期:2008-04-15 00:00:00

  • Research on PEGylation of porcine prothrombin for improving biostability and reducing animal immunogenicity.

    abstract::Prothrombin is a vitamin K-dependent serine protease and plays pivotal roles in both procoagulant and anticoagulant pathway of hemostasis. In this study, prothrombin purified from porcine plasma was modified through PEGylation at N-terminal residue using 40 kDa PEG-phenyl-isothiocyanate (PIT-PEG40K). The monoPEGylated...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhou JG,Chen YM

    更新日期:2011-06-01 00:00:00

  • Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

    abstract::Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for ass...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Han C,Chatterjee A,Noetzel MJ,Panarese JD,Smith E,Chase P,Hodder P,Niswender C,Conn PJ,Lindsley CW,Stauffer SR

    更新日期:2015-01-15 00:00:00

  • Nitrone derivatives of trolox as neuroprotective agents.

    abstract::Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities com...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Balogh GT,Vukics K,Könczöl A,Kis-Varga A,Gere A,Fischer J

    更新日期:2005-06-15 00:00:00

  • Antifungal activity of substituted aurones.

    abstract::Novel antifungals are in high demand as there is a growing resistance to antifungals currently in use. In particular, opportunistic fungal infections caused by Candida spp. are on the rise with infections by this genus accounting for the most severe fungal infections following chemotherapy, implantation procedures, an...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sutton CL,Taylor ZE,Farone MB,Handy ST

    更新日期:2017-02-15 00:00:00

  • Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes.

    abstract::(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the disco...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Finke PE,Oates B,Mills SG,MacCoss M,Malkowitz L,Springer MS,Gould SL,DeMartino JA,Carella A,Carver G,Holmes K,Danzeisen R,Hazuda D,Kessler J,Lineberger J,Miller M,Schleif WA,Emini EA

    更新日期:2001-09-17 00:00:00

  • Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells.

    abstract::We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ronco C,Millet A,Plaisant M,Abbe P,Hamouda-Tekaya N,Rocchi S,Benhida R

    更新日期:2017-05-15 00:00:00

  • Synthesis and structure-activity relationship of potent bicyclic lactam thrombin inhibitors.

    abstract::A simple and versatile method for preparation of (D)-Phe-Pro peptidomimetic bicyclic thiazolidine lactams is presented. These bicyclic lactams have chemical diversity alpha to the lactam carbonyl and, when linked to electrophilic arginines, provide potent thrombin inhibitors. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bachand B,DiMaio J,Siddiqui MA

    更新日期:1999-04-05 00:00:00

  • Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays.

    abstract::A series of potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ren A,Zhu X,Feichtinger K,Lehman J,Kasem M,Schrader TO,Wong A,Dang H,Le M,Frazer J,Unett DJ,Grottick AJ,Whelan KT,Morgan ME,Sage CR,Semple G

    更新日期:2020-03-01 00:00:00

  • Vialinin A and thelephantin G, potent inhibitors of tumor necrosis factor-α production, inhibit sentrin/SUMO-specific protease 1 enzymatic activity.

    abstract::Several p-terphenyl compounds have been isolated from the edible Chinese mushroom Thelephora vialis. Vialinin A, a p-terphenyl compound, strongly inhibits tumor necrosis factor-α production and release. Vialinin A inhibits the enzymatic activity of ubiquitin-specific peptidase 5, one of the target molecules in RBL-2H3...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yoshioka Y,Namiki D,Makiuchi M,Sugaya K,Onose J,Ashida H,Abe N

    更新日期:2016-09-01 00:00:00

  • Degradation of target protein in living cells by small-molecule proteolysis inducer.

    abstract::Ubiquitin-dependent proteolysis of cellular proteins is one of the major pathways to regulate protein function posttranslationally. Here we demonstrate a potentially general method of degrading any targeted proteins by the ubiquitin-dependent proteolysis in living cells, using small-molecule proteolysis inducer (SMPI)...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhang D,Baek SH,Ho A,Kim K

    更新日期:2004-02-09 00:00:00

  • Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

    abstract::A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

    更新日期:2016-04-01 00:00:00

  • Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based inhibitors of human neutrophil elastase.

    abstract::The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3-yl)-benzo[d][1,3]oxazin-4-one is described. A structure-activity relationship study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5-ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl-pipe...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shreder KR,Cajica J,Du L,Fraser A,Hu Y,Kohno Y,Lin EC,Liu SJ,Okerberg E,Pham L,Wu J,Kozarich JW

    更新日期:2009-08-15 00:00:00

  • Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.

    abstract::A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Verma S,Nagarathnam D,Shao J,Zhang L,Zhao J,Wang Y,Li T,Mull E,Enyedy I,Wang C,Zhu Q,Altieri M,Jordan J,Dang TT,Reddy S

    更新日期:2005-04-15 00:00:00

  • Antifungal Sordarins. Part 4: synthesis and structure--activity relationships of 3',4'-fused alkyl-tetrahydrofuran derivatives.

    abstract::A series of Sordarin derivatives bearing alkyl substituted tetrahydrofuran rings fused to C3'-C4' bond of the sugar moiety have been prepared and their antifungal properties evaluated. Most of them show remarkable antifungal activity against Candida spp and Cryptococcus neoformans. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bueno JM,Chicharro J,Fiandor JM,Gómez de las Heras F,Huss S

    更新日期:2002-07-08 00:00:00

  • Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor.

    abstract::Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F(1)F(0)-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodia...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cleary J,Johnson KM,Opipari AW Jr,Glick GD

    更新日期:2007-03-15 00:00:00

  • 4,4-Disubstituted cyclohexylamine based CCR5 chemokine receptor antagonists as anti-HIV-1 agents.

    abstract::A series of 4,4-disubstituted cyclohexylamine based CCR5 antagonists has been designed and synthesized. Their antiviral structure-activity relationship has been extensively explored. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Duan M,Aquino C,Dorsey GF Jr,Ferris R,Kazmierski WM

    更新日期:2009-09-01 00:00:00

  • 'Naked-eye' quinoline-based 'reactive' sensor for recognition of Hg²⁺ ion in aqueous solution.

    abstract::A new 'naked-eye' quinoline-based 'reactive' ratiometric fluorescent probe was prepared. The reactive stoichiometry of the probe with Hg²⁺ ion was 2:1. The probe exhibited high selectivity towards Hg²⁺ ion to other metal ions with a 410-fold increase in absorbance intensity ratio (A₄₀₂/A₃₄₀) in aqueous solution over a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhang Y,Yan Y,Chen S,Gao Z,Xu H

    更新日期:2014-12-01 00:00:00

  • Synthesis and HIV-1 integrase inhibitory activities of caffeoylglucosides.

    abstract::Caffeoylglucosides, which have a glucose ring as a central linker, were synthesized from methyl D-glucosides, and their anti-HIV-1 activities were tested. Among them, four dicaffeoylglucosides (IC50 = 29.1+/-35.1 microM), 6a, 6b, 9b and 10b, showed HIV-1 integrase inhibitory activity as potent as L-chicoric acid. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kim SN,Lee JY,Kim HJ,Shin CG,Park H,Lee YS

    更新日期:2000-08-21 00:00:00

  • Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

    abstract::Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Huang SC,Adhikari S,Afroze R,Brewer K,Calderwood EF,Chouitar J,England DB,Fisher C,Galvin KM,Gaulin J,Greenspan PD,Harrison SJ,Kim MS,Langston SP,Ma LT,Menon S,Mizutani H,Rezaei M,Smith MD,Zhang DM,Gould AE

    更新日期:2016-02-15 00:00:00

  • Anti-HIV activity of stilbene-related heterocyclic compounds.

    abstract::Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-kappaB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalaz...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bedoya LM,del Olmo E,Sancho R,Barboza B,Beltrán M,García-Cadenas AE,Sánchez-Palomino S,López-Pérez JL,Muñoz E,San Feliciano A,Alcamí J

    更新日期:2006-08-01 00:00:00

  • Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

    abstract::The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Manning T,Mikula R,Wylie G,Phillips D,Jarvis J,Zhang F

    更新日期:2015-02-01 00:00:00

  • Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry.

    abstract::We have synthesized and evaluated a series of 1,4-disubstituted-triazole derivatives for inhibition of the rat Na(V)1.6 sodium channel isoform, an isoform thought to play an important role in controlling neuronal firing. Starting from a series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Rivara M,Patel MK,Amori L,Zuliani V

    更新日期:2012-10-15 00:00:00