- Novel antibody-antibiotic conjugate eliminates intracellular S. aureus
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Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical f
- Lehar, Sophie M.,Pillow, Thomas,Xu, Min,Staben, Leanna,Kajihara, Kimberly K.,Vandlen, Richard,DePalatis, Laura,Raab, Helga,Hazenbos, Wouter L.,Hiroshi Morisaki,Kim, Janice,Park, Summer,Darwish, Martine,Lee, Byoung-Chul,Hernandez, Hilda,Loyet, Kelly M.,Lupardus, Patrick,Fong, Rina,Yan, Donghong,Chalouni, Cecile,Luis, Elizabeth,Khalfin, Yana,Plise, Emile,Cheong, Jonathan,Lyssikatos, Joseph P.,Strandh, Magnus,Koefoed, Klaus,Andersen, Peter S.,Flygare, John A.,Wah Tan, Man,Brown, Eric J.,Mariathasan, Sanjeev
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Read Online
- Synthesis, anti-platelet aggregation activity evaluation and structure–activity relationships of a series of novel purine derivatives
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This article described how further extensive variation of the substituents on the purine scaffold of adenosine triphosphate (ATP), and the human anti-platelet aggregation activities were modified in order to find exploitation of the structure–activity relationships (SAR). A series of novel designed 6-alkylamino-2-alkylthio-9-hydroxyalkyl(carbalkoxy) purine derivatives were synthesized via a modification procedure, and the human anti-platelet aggregation activities were evaluated. The SAR of these compounds were analyzed in detail, and the results of the structural requirements of the substituents to improve potency may provide a basis for the development of potent P2Y12 antagonists.
- Li, Shunlai,Zhou, Cheng,Yu, Mingwu,He, Qiwen,Du, Hongguang
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Read Online
- Investigating the role of the geminal dimethyl groups of coenzyme A: Synthesis and studies of a didemethyl analogue
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An analogue 2 of coenzyme A (CoA) has been prepared in which the geminal methyl groups are replaced with hydrogens. An NMR titration study was conducted and shifts in frequency of protons in the pantetheine portion of the molecule upon titration of the adenine base were observed as has been previously reported with CoA. These studies indicate that the geminal dimethyl groups are not essential for adoption of a partially folded conformation in solution. Based on 1H-1H coupling constants, the distribution of conformations about the carbon-carbon bonds in the region of the methyl deletion were estimated. The results suggest that the conformer distribution is similar to that of CoA, but with small increases in population of the anti conformers. A simple model compound containing the didemethyl pantoamide moiety was prepared and subjected to similar conformational analysis. The coupling constants and predicted conformer distribution were almost identical to that of the CoA analogue, indicating that the conformer distribution is controlled by local interactions and not influenced by interactions between distant parts of the CoA molecule. The acetyl derivative of 2 was a fairly good substrate for the acetyl-CoA utilizing enzymes carnitine acetyltransferase, chloramphenicol acetyltransferase, and citrate synthase, with 1.3- to 10-fold increased K(m) values and 2.5- to 11-fold decreases in V(max). The combined results indicate that the geminal dimethyl groups of CoA have modest effects on function and minimal effects on conformation. Copyright (C) 2000 Elsevier Science Ltd.
- Vogel, Kurt W.,Stark, Lucy M.,Mishra, Pranab K.,Yang, Wei,Drueckhammer, Dale G.
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Read Online
- Antiplasmodial Mode of Action of Pantothenamides: Pantothenate Kinase Serves as a Metabolic Activator Not as a Target
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N-Substituted pantothenamides (PanAms) are pantothenate analogues with up to nanomolar potency against blood-stage Plasmodium falciparum (the most virulent species responsible for malaria). Although these compounds are known to target coenzyme A (CoA) bio
- De Villiers, Marianne,Spry, Christina,Macuamule, Cristiano J.,Barnard, Leanne,Wells, Gordon,Saliba, Kevin J.,Strauss, Erick
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Read Online
- METHODS AND COMPOSITIONS FOR PRODRUG FORMS OF SPECTINOMYCIN AND SPECTINAMIDE ANALOGS
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In one aspect, the disclosure relates to substituted spectinomycin analogs, including substituted aminomethyl spectinomycin analogs and substituted spectinamide analogs, with increased tolerability and safety, including improved tolerability to parenteral
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-
Paragraph 0589-0590; 0602; 0609; 0615; 0621
(2020/06/01)
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- PANTETHEINE DERIVATIVES AND USES THEREOF
-
The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
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Paragraph 2121
(2020/06/19)
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- COMPOSITIONS COMPRISING ENZYME CLEAVABLE LINKER PLATFORMS AND CONJUGATES THEREOF
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The present invention relates to a cleavable linker platform. In particular, the invention relates to construction of an enzyme cleavable linker platform conjugated to a drug or a diagnostically relevant compound, a biomolecule, and an enzyme cleavable group, for which cleavage of the enzyme cleavable group leads to release of the drug or diagnostically relevant compound.
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Page/Page column 71; 72
(2021/01/23)
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- Heterocyclic amide compound, pharmaceutical composition containing heterocyclic amide compound, preparation method of heterocyclic amide compound and application of heterocyclic amide compound
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The invention relates to a heterocyclic amide compound, a pharmaceutical composition containing the heterocyclic amide compound, a preparation method of the heterocyclic amide compound and an application of the heterocyclic amide compound serving as an agonist of stimulator of interferon gene (STING). More specifically, the invention relates to the heterocyclic amide compound; the heterocyclic amide compound is capable of stimulating the production of interferon, thereby being used as an immunomodulator for treatment of STING-mediated diseases or disease conditions such as cancer, infectious diseases, inflammation, immune-related diseases and the like.
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Paragraph 0311-0314
(2020/04/17)
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- NEUROSTEROID COMPOUNDS AND METHODS FOR THEIR PREPARATION AND USE IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS
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Described herein is the chemical structure of neurosteroid derivative compounds, methods of synthesizing the derivatives, and their uses in treating disorders, including those of the central nervous system. These compounds are readily synthesized and have improved pharmaceutical properties, including water solubility, compared to known neurosteroids.
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Paragraph 0103; 0144
(2019/11/12)
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- UREA DERIVATIVES AS INHIBITORS OF ASK1
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The present technology is directed to compounds, compositions, and methods related to inhibition of ASK1. In particular, the present compounds (e.g., compounds of Formula I as defined herein) and compositions may be used to treat ASK1-mediated disorders and conditions, including, e.g., fibrotic diseases and acute and chronic liver diseases, among others.
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Paragraph 0121
(2019/06/05)
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- Puerarin derivative with high biological activity as well as preparation method and application thereof
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The invention relates to a puerarin derivative as well as a preparation method and application thereof. The puerarin derivative is characterized in that puerarin is used as a raw material; through five-step reaction, a compound 6 is prepared; then, the co
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Paragraph 0050; 0054; 0055
(2019/02/25)
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- Evaluation of Natural and Synthetic Phosphate Donors for the Improved Enzymatic Synthesis of Phosphate Monoesters
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Undesired product hydrolysis along with large amounts of waste in form of inorganic monophosphate by-product are the main obstacles associated with the use of pyrophosphate in the phosphatase-catalyzed synthesis of phosphate monoesters on large scale. In order to overcome both limitations, we screened a broad range of natural and synthetic organic phosphate donors with several enzymes on a broad variety of hydroxyl-compounds. Among them, acetyl phosphate delivered stable product levels and high phospho-transfer efficiency at the lower functional pH-limit, which translated into excellent productivity. The protocol is generally applicable to acid phosphatases and compatible with a range of diverse substrates. Preparative-scale transformations using acetyl phosphate synthesized from cheap starting materials yielded multiple grams of various sugar phosphates with up to 433 g L?1 h?1 space-time yield and 75% reduction of barium phosphate waste. (Figure presented.).
- Tasnádi, Gábor,Jud, Wolfgang,Hall, Mélanie,Baldenius, Kai,Ditrich, Klaus,Faber, Kurt
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supporting information
p. 2394 - 2401
(2018/05/14)
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- A process for the preparation of [3 - [(2 R) - [(1 R) - 1 - [3, 5 - di (trifluoromethyl) phenyl] ethoxy] - 3 (S)- (4 - fluorophenyl) morpholine - 4 - yl] methyl] - 5 - oxo - 4, 5 - dihydro - [1, 2, 4] - triazole - 1 - yl] phosphine acid animal pen ester new method
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The invention relates to a new method for preparing fosaprepitant intermediate, namely, [3-[(2R)-[(1R)-1-(3, 5-bi (trifluoromethyl) phenyl] ethyoxyl]-3 (S)-(4-fluorophenyl) morpholine 4-group] methyl]-5-oxo-4, 5-dihydro-[1, 2, 4]-triazole-1-group] phosphonic acid-benzyl ester. The compound is an important medicine intermediate, and is used for preparing antiemetic drug fosaprepitant. The new method comprises the steps of: enabling newly prepared phosphorylation agent dibenzyl phosphorus oxychloride and aprepitant to have reaction in organic solvent under the action of steric hindrance alkali, treating the product with methyl alcohol to obtain the fosaprepitant intermediate. The method is simple in operation and low in cost, thus being more suitable for industrial production.
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Paragraph 0022-0025
(2017/08/26)
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- COMPOSITIONS AND METHODS USEFUL FOR TREATING DISEASES CHARACTERIZED BY INSUFFICIENT PANTOTHENATE KINASE ACTIVITY
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Methods and pharmaceutical compositions for use in treating diseases associated with insufficient activity of the pantothenate kinase enzyme (e.g., CASTOR diseases) are disclosed. The methods and compositions involve an effective amount of an active deriv
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Page/Page column 0081; 0305
(2018/01/20)
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- Dissociative reactions of benzonorbornadienes with tetrazines: Scope of leaving groups and mechanistic insights
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Bioorthogonal dissociative reactions boast diverse potential applications in chemical biology and drug delivery. The reaction of benzonorbornadienes with tetrazines to release amines from carbamate leaving groups was recently introduced as a bioorthogonal bond-cleavage reaction. The present study aimed at investigating the scope of leaving groups that are compatible with benzonorbornadienes. Synthesis of several benzonorbornadienes with different releasable groups is reported, and the reaction of these molecules with tetrazine was found to be rapid and afforded high release yields. The tetrazine-induced release of molecules proceeds in a cascade of steps including inverse-electron demand cycloaddition and cycloreversion reactions that form unstable isoindoles/isobenzofuran intermediates and spontaneously eliminate a leaving group of interest. In the case of oxygen-bridged BNBDs at room temperature, we observed the formation of an unproductive byproduct.
- Xu,Galindo-Murillo,Cheatham,Franzini
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p. 9855 - 9865
(2017/12/12)
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- Study of Uridine 5′-Diphosphate (UDP)-Galactopyranose Mutase Using UDP-5-Fluorogalactopyranose as a Probe: Incubation Results and Mechanistic Implications
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Uridine 5′-diphosphate-5-fluorogalactopyranose (UDP-5F-Galp, 7) was synthesized, and its effect on UDP-Galp mutase (UGM) was investigated. UGM facilitated the hydrolysis of 7 to yield UDP and 5-oxogalactose (24), but no 11 was detected. 19F NMR and trapping experiments demonstrated that the reaction involves the initial formation of a substrate-cofactor adduct followed by decomposition of the resulting C5 gem-fluorohydrin to generate a 5-oxo intermediate (10). The results support the current mechanistic proposal for UGM and suggest new directions for designing mechanism-based inhibitors.
- Lin, Geng-Min,Sun, He G.,Liu, Hung-Wen
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supporting information
p. 3438 - 3441
(2016/07/26)
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- Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo
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Twenty-nine novel indole-chalcone derivatives were synthesized and evaluated for antiproliferative activity. Among them, 14k exhibited most potent activity, with IC50 values of 3-9 nM against six cancer cells, which displayed a 3.8-8.7-fold increase in activity when compare with compound 2. Further investigation revealed 14k was a novel tubulin polymerization inhibitor binding to the colchicine site. Its low cytotoxicity toward normal human cells and nearly equally potent activity against drug-resistant cells revealed the possibility for cancer therapy. Cellular mechanism studies elucidated 14k arrests cell cycle at G2/M phase and induces apoptosis along with the decrease of mitochondrial membrane potential. Furthermore, good metabolic stability of 14k was observed in mouse liver microsomes. Importantly, 14k and its phosphate salt 14k-P inhibited tumor growth in xenograft models in vivo without apparent toxicity, which was better than the reference compound CA-4P and 2. In summary, 14k deserves consideration for cancer therapy.
- Yan, Jun,Chen, Jie,Zhang, Shun,Hu, Jinhui,Huang, Ling,Li, Xingshu
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p. 5264 - 5283
(2016/07/06)
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- Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry
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Derivatives of ribosyl pyrophosphate have been synthesized, and examined with magnesium salts in the coupling of the ribose unit to various nucleophiles, including pyrazole and 2-chloroimidazole. Only with the magnesium salt present did they generate the ribosyl cation by binding to the leaving group and then couple the ribose derivative with nucleophiles. The role of magnesium salts in phosphorylation of methanol by ATP was also examined. Here a remarkable effect was seen: phosphorylation by ATP was slowed with low concentrations of Mg2+ but accelerated by higher concentrations. Related effects were also seen in the effect of Mg2+ on phosphorylation by ADP. The likely mechanisms explain these effects.
- Gopinath, Purushothaman,Ramalingam, Vijayakumar,Breslow, Ronald
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p. 12011 - 12014
(2015/10/12)
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- STABLE PANTETHEINE DERIVATIVES FOR THE TREATMENT OF PANTOTHENATE KINASE ASSOCIATED NEURODEGENERATION (PKAN) AND METHODS FOR THE SYNTHESIS OF SUCH COMPOUNDS
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The invention relates to (S)-acyl-4'-phosphopantetheine derivatives, methods of their synthesis, and related medical uses of such compounds. Preferred medical uses relate to the treatment of neurodegenerative diseases, such as PKAN.
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Page/Page column 21; 22
(2015/05/19)
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- PAIN RELIEF COMPOUNDS
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The present invention relates to the use of compounds for the treatment or prevention of pain in mammals, in particularly in human beings, and also to a process for preparing these compounds.
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Paragraph 0499-0500
(2015/02/19)
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- Chemical pyrophosphorylation of functionally diverse peptides
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A highly selective and convenient method for the synthesis of pyrophosphopeptides in solution is reported. The remarkable compatibility with functional groups (alcohol, thiol, amine, carboxylic acid) in the peptide substrates suggests that the intrinsic nucleophilicity of the phosphoserine residue is much higher than previously appreciated. Because the methodology operates in polar solvents, including water, a broad range of pyrophosphopeptides can be accessed. We envision these peptides will find widespread applications in the development of mass spectrometry and antibody-based detection methods for pyrophosphoproteins.
- Marmelstein, Alan M.,Yates, Lisa M.,Conway, John H.,Fiedler, Dorothea
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supporting information
p. 108 - 111
(2014/01/23)
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- Synthesis of methylerythritol phosphate analogues and their evaluation as alternate substrates for IspDF and IspE from Agrobacterium tumefaciens
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The methylerythritol phosphate biosynthetic pathway, found in most Bacteria, some parasitic protists, and plant chloroplasts, converts d-glyceraldehyde phosphate and pyruvate to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where it
- Krasutsky, Sergiy G.,Urbansky, Marek,Davis, Chad E.,Lherbet, Christian,Coates, Robert M.,Poulter, C. Dale
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p. 9170 - 9178
(2015/02/19)
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- Covalent inhibition of serine β-lactamases by novel hydroxamic acid derivatives
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The effectiveness of β-lactam antibiotics is greatly limited by the ability of bacteria to produce β-lactamases. These enzymes catalyze the hydrolysis of β-lactams and thus loss of their antibiotic activity. The search for inhibitors of β-lactamases began soon after β-lactams were introduced into medical practice and continues today. Some time ago, we introduced a new class of covalent serine β-lactamase inhibitors, the O-aryloxycarbonyl hydroxamates, that inactivated these enzymes by a unique mechanism in which the active site became cross-linked. We describe in this paper some new variants of this class of inhibitor. First, we investigated compounds in which more polar hydroxamates were incorporated. These were generally not more active than the original compounds against representative class A and class C β-lactamases, but one of them, 1-(benzoyl)-O- (phenoxycarbonyl)-3-hydroxyurea, was significantly more stable in solution, thus revealing a useful platform for further design. Second, we describe a series of O-(arylphosphoryl) hydroxamates that are also irreversible inactivators of class A and class C β-lactamases, by phosphorylation of the enzyme, as revealed by mass spectra. These compounds did not, however, cross-link the enzyme active site. A striking feature of their structure-activity profile was that hydroxamate remained the leaving group on enzyme phosphorylation rather than aryloxide, even though the aryloxide was intrinsically the better leaving group, as indicated by pKa values and demonstrated by the products of hydrolysis in free solution. Model building suggested that this phenomenon arises from the relative affinity of the enzyme active site components for the two leaving groups. The results obtained for both groups of inhibitors are important for further optimization of these inhibitors.
- Tilvawala, Ronak,Pratt
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p. 3712 - 3720
(2013/07/27)
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- Triazole phosphohistidine analogues compatible with the Fmoc-strategy
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Phosphorylation of histidine is essential for bacterial two-component signalling; its importance to modulation of eukaryotic protein function remains undefined. Until recently, no immunochemical probes of this post-translational modification existed, however triazole phosphonate analogues of this modified amino acid have now been applied to the generation of site-specific antibodies. The protecting group strategy used in the original report is incompatible with standard protocols for Fmoc-solid phase peptide synthesis. In this paper, we report the application of P(iii) chemistry to generate the complementary dibenzyl and di-tert-butyl phosphonate esters. These forms of the triazole analogue are fully compatible with standard Fmoc-SPPS and are therefore ideal for wider application by the chemical and biochemical community.
- Mcallister, Tom E.,Webb, Michael E.
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scheme or table
p. 4043 - 4049
(2012/06/15)
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- Template-directed synthesis in 3′- and 5′-direction with reversible termination
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Extending both ways: A method for DNA-templated synthesis on solid support is described. Controlled, stepwise chain extension was demonstrated both in the direction favored by nature (3'-extension; see scheme) and in the direction typical for conventional DNA synthesizers (5'-extension). Copyright
- Kaiser, Andreas,Spies, Sebastian,Lommel, Tanja,Richert, Clemens
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supporting information; experimental part
p. 8299 - 8303
(2012/09/07)
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- Formal synthesis of 4-diphosphocytidyl-2-C-methyl d-erythritol from d-(+)-arabitol
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2-C-Methyl-d-erythritol-4-phosphate (MEP) is a key chemical intermediate of the non-mevalonate pathway for isoprenoid biosynthesis employed by many pathogenic microbes. MEP is also the precursor for the synthesis of 4-diphosphocytidyl-2-C-methyl d-erythri
- Odejinmi, Sina I.,Rascon, Rafael G.,Chen, Wyman,Lai, Kent
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p. 8937 - 8941
(2012/10/29)
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- AROYLQUINOLINE COMPOUNDS
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A serious of nitro heterocyclic derivatives including a structure of formula (I) are provided. In formula (I), P, Q and R1 to R8 are defined in the specification. The derivatives disclosed in the present invention are characterized in inhibiting tubulin p
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Page/Page column 15-16
(2011/11/13)
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- N-PYRAZOLYL CARBOXAMIDES AS CRAC CHANNEL INHIBITORS
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The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.
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Page/Page column 77
(2010/11/05)
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- Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite
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UDP-Galactopyranose mutase (UGM or Glf), which catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose, is implicated in the viability and virulence of multiple pathogenic microorganisms. Here we report the synthesis of high-affinity ligands for UGM homologues from Klebsiella pneumoniae and Mycobacterium tuberculosis. The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site.
- Dykhuizen, Emily C.,Kiessling, Laura L.
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supporting information; experimental part
p. 193 - 196
(2009/06/28)
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- Development of synthetic methodology suitable for the radiosynthesis of combretastatin A-1 (CA1) and its corresponding prodrug CA1P
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Synthetic methodology has been established suitable for the preparation of combretastatin A-1 (CA1) and its corresponding phosphate prodrug salt (CA1P) in high specific activity radiolabeled form. Judicious selection of appropriate phenolic protecting groups to distinguish positions on the A-ring from the B-ring of the stilbenoid was paramount for the success of this project. Methylation of the C-4' phenolic moiety by removal of the tert- butyldimethylsilyl protecting group in the presence of methyl iodide was accomplished in excellent yield without significant Z to E isomerization. This step (carried out with 12C-methyl iodide as proof of concept in this study) represents the process in which a 14C radioisotope could be incorporated in an actual radiosynthesis. CA1 is a natural product isolated from the African bush willow tree (Combretum caffrum) that has important medicinal value due, in part, to its ability to inhibit tubulin assembly. As a prodrug, CA1P (OXi4503) is in human clinical trials as a vascular disrupting agent.
- Shirali, Anupama,Sriram, Madhavi,Hall, John J.,Nguyen, Benson L.,Guddneppanavar, Rajsekhar,Hadimani, Mallinath B.,Ackley, J. Freeland,Siles, Rogelio,Jelinek, Christopher J.,Arthasery, Phyllis,Brown, Rodney C.,Murrell, Victor Leon,McMordie, Austin,Sharma, Suman,Chaplin, David J.,Pinney, Kevin G.
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experimental part
p. 414 - 421
(2009/12/05)
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- DIAZONAMIDE ANALOGS WITH IMPROVED SOLUBILITY
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Diazonamide A analogs, and the salts, esters and conjugates thereof, having improved aqueous solubility are provided. Also provided are pharmaceutical compositions, and methods for preparing and using such compounds and compositions for the treatment of proliferative diseases.
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Page/Page column 17; 27; 31
(2009/07/10)
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- Chemoenzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-d-erythritol: a substrate for IspE
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Enantiomerically pure 2-C-methyl-d-erythritol 4-phosphate 1 (MEP) is synthesized from 1,2-O-isopropylidene-α-d-xylofuranose via facile benzylation in good yield. Subsequently, 1 is used for enzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-d-erythritol
- Narayanasamy, Prabagaran,Eoh, Hyungjin,Crick, Dean C.
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p. 4461 - 4463
(2008/09/21)
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- N,N-Dichloro poly(styrene-co-divinyl benzene) sulfonamide polymeric beads: an efficient and recyclable reagent for the synthesis of dialkyl chlorophosphates from dialkylphosphites at room temperature
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An efficient and operationally simple method is developed for the synthesis of dialkyl chlorophosphates from dialkylphosphites using a new chlorine bearing reagent, N,N-dichloro poly(styrene-co-divinyl benzene) sulfonamide in the form of polymeric beads. The reagent afforded dialkyl chlorophosphates at room temperature, and is recyclable.
- Gupta, Hemendra K.,Mazumder, Avik,Garg, Prabhat,Gutch, Pranav K.,Dubey, Devendra K.
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scheme or table
p. 6704 - 6706
(2009/04/07)
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- Soluble precipitable porphyrins for use in targeted molecular brachytherapy
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In a new therapy that aims to concentrate and immobilize therapeutic radionuclides in nanoscale assemblies within solid tumors, a soluble precipitable reagent (SPR) is administered as the radionuclide carrier and is converted to non-diffusible precipitate
- Yao, Zhen,Borbas, K. Eszter,Lindsey, Jonathan S.
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p. 436 - 451
(2008/09/17)
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- Synthesis and analysis of substrate analogues for UDP-galactopyranose mutase: Implication for an oxocarbenium ion intermediate in the catalytic mechanism
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(Chemical Equation Presented) UDP-D-galactofuranose (2), which is essential for both cell growth and virulence in many pathogenic microorganisms, is converted from UDP-D-galactopyranose (UDP-Galp, 1) by the flavin adenine dinucleotide (FAD)-dependent enzyme UDP-galactopyranose mutase (UGM). Here, we report the synthesis of UDP-GalOH (13) and show it as an inhibitor for UGM with a binding affinity similar to that of 1. These results are more consistent with a mechanism involving an oxocarbenium ion intermediate in UGM catalysis.
- Itoh, Kenji,Huang, Zhishu,Liu, Hung-Wen
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p. 879 - 882
(2007/10/03)
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- METHODS FOR TREATING ARTHRITIS USING TRIHETEROCYCLIC COMPOUNDS
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The present invention relates to methods for treating or preventing arthritis comprising administering a Triheterocyclic Compound. In one embodiment, the present invention relates to methods of using Triheterocyclic Compounds for treating or preventing rh
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Page/Page column 114
(2008/06/13)
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- Synthesis and structure-activity relationships of truncated bisubstrate inhibitors of aminoglycoside 6′-N-acetyltransferases
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Truncated aminoglycoside-coenzyme A bisubstrate analogues were efficiently prepared using a convergent approach where the amine and the thiol are coupled in one pot with the addition of a linker, without the need for protecting groups. These derivatives were tested for their effect on the activity of the resistance-causing enzyme aminoglycoside 6′-N-acetyltransferase Ii, and key structure-activity relationships are reported. Moreover, one of the inhibitors is able to block aminoglycoside resistance in cells expressing this enzyme.
- Gao, Feng,Yan, Xuxu,Shakya, Tushar,Baettig, Oliver M.,Ait-Mohand-Brunet, Samia,Berghuis, Albert M.,Wright, Gerard D.,Auclair, Karine
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p. 5273 - 5281
(2007/10/03)
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- N-tert-butyl-N-chlorocyanamide: A mild and efficient chlorinating agent for the synthesis of dialkyl/diaryl chlorophosphates
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An efficient reagent for the synthesis of dialkyl/diaryl chlorophosphates has been developed. N-tert-Butyl-N-chlorocyanamide acts as a chlorinating agent both in polar as well in non-polar medium and the transformation of dialkyl/diaryl phosphites to the dialkyl/diaryl chlorophosphates takes place rapidly under mild conditions in quantitative yields. Copyright
- Kumar, Vinod,Kaushik, Mahabir Parshad
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p. 312 - 313
(2007/10/03)
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- Novel zwitterionic reverse micelles for encapsulation of proteins in low-viscosity media
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Large proteins remain inaccessible to structural NMR studies because of their unfavorable relaxation properties. Their solubilization in the aqueous core of reverse micelles, in a low-viscosity medium, represents a promising approach, provided that their
- Doussin, Sylvain,Birlirakis, Nicolas,Georgin, Dominique,Taran, Frederic,Berthault, Patrick
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p. 4170 - 4175
(2007/10/03)
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- Triheterocyclic compounds, compositions, and methods for treating cancer or viral diseases
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The present invention relates to novel Triheterocyclic Compounds, compositions comprising a Triheterocyclic Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Triheterocyclic Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, treating or preventing a viral infection, or inhibiting the replication and/or infectivity of a virus.
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Page/Page column 50
(2010/02/14)
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- N, N′-Dichloro bis(2,4,6-trichlorophenyl) urea (CC-2): An efficient reagent for synthesis of dialkyl chlorophosphates
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An efficient and simple method is described for the preparation of dialkyl chlorophosphates by the use of new positive chlorine bearing reagent namely N,N′-dichloro bis(2,4,6-trichlorophenyl) urea.
- Shakya,Dubey,Pardasani, Deepak,Palit, Meehir,Gupta
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p. 821 - 823
(2007/10/03)
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- Trichloroisocyanuric acid: An efficient reagent for the synthesis of dialkyl chlorophosphates from dialkyl phosphites
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A mild and operationally simple method for the synthesis of dialkyl chlorophosphates is described. Trichloroisocyanuric acid is used as an effective reagent for the rapid conversion of dialkyl phosphites to their corresponding dialkyl chlorophosphates under mild conditions.
- Acharya,Gupta,Shakya,Kaushik
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p. 5293 - 5295
(2007/10/03)
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- TRIHETEROCYCLIC COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATING CANCER OR VIRAL DISEASES
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The present invention relates to novel Triheterocyclic Compounds, formula (I): and pharmaceutically acceptable salts thereof, where in: Q1 is -O-, -S- or -N(R1)-; Q2 is -C(R3)- or -N-; Q3 is -C (Rsub
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- Reaction of chlorides of phosphoric, sulfonic, and carboxylic acids on solid potassium carbonate surface under PTC circumstances
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Simple syntheses of phosphoric (4) and carboxylic (6) acid anhydrides have been elaborated by means of solid potassium carbonate in phase-transfer catalytic acylation. Behavior of various acid chlorides, phosphoric (1), sulfonic (2), and carboxylic (8), have also been studied toward potassium carbonate in the presence of lipophilic quaternary ammonium salt.
- Jaszay, Zsuzsa M.,Petnehazy, Imre,Toe, Laszlo
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p. 447 - 450
(2007/10/03)
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- Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase.
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The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.
- Dardonville, Christophe,Gilbert, Ian H
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p. 552 - 559
(2007/10/03)
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- An efficient synthesis of GDP-hexanolamine, a key tool for the purification of fucosyltransferases
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A new efficient synthesis of GDP-hexanolamine from hexanolamine is reported with an overall yield of 71%. The pyrophosphate formation, the key step of this preparation, was achieved through a sequential GMP activation procedure based on polytrifluoroacetylation of GMP followed by activation of the phosphate group by 1-methylimidazole.
- Vincent, Stéphane P,Gastinel, Louis N
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p. 1039 - 1042
(2007/10/03)
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- Synthesis of injectable antifungal Sch 59884
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A synthesis for the preparation of multikilogram quantities of the injectable antifungal Sch 59884 is described.
- Lee, Gary M.,Eckert, Jefrey,Gala, Dinesh,Schwartz, Martin,Renton, Paul,Pergamen, Edward,Whttington, Michael,Schumacher, Doris,Heimark, Larry,Shipkova, Petia
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p. 622 - 629
(2013/09/07)
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- New insights into the mechanism of CDP-D-tyvelose 2-epimerase: An enzyme-catalyzing epimerization at an unactivated stereocenter
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Tyvelose is a 3,6-dideoxyhexose found in the O-antigen of Yersinia pseudotuberculosis IVA and is the only member of this class of sugars to be produced directly from another 3,6-dideoxyhexose, paratose. The C-2 epimerization required for this conversion h
- Hallis,Zhao,Liu
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p. 10493 - 10503
(2007/10/03)
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- Quinazolinone compounds
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Phosphate derivatives are disclosed of quinazolinone compounds having structural formula (I) or a pharmaceutically acceptable salt thereof, wherein X' represent hydroxyl, alkyl, alkoxy, or O-Z where Z is a phosphate or phosphate derivative; Y' represents
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