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Acid Analogues (acid + analogue)
Selected AbstractsOne-Pot Tandem 1,4,1,2-Addition of Phosphites to ,,,-Unsaturated Imines for the Synthesis of Glutamic Acid Analogues.CHEMINFORM, Issue 12 2006Kristof Moonen Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Synthesis and Biological Activities of Aryl-Ether-, Biaryl-, and Fluorene-Aspartic Acid and Diaminopropionic Acid Analogues as Potent Inhibitors of the High-Affinity Glutamate Transporter EAAT-2.CHEMINFORM, Issue 8 2006Alexander Greenfield Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF. [source] Synthesis and Biological Activities of Novel Aryl Indole-2-carboxylic Acid Analogues as PPAR, Partial Agonists.CHEMINFORM, Issue 7 2006James F. Dropinski Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF. [source] Structure,Activity Relationship of Triaryl Propionic Acid Analogues on the Human EP3 Prostanoid Receptor.CHEMINFORM, Issue 4 2004Michel Gallant Abstract For Abstract see ChemInform Abstract in Full Text. [source] Carboxylic Acid Analogues of Fosmidomycin.CHEMINFORM, Issue 38 2003Thomas Kurz Abstract For Abstract see ChemInform Abstract in Full Text. [source] Novel Lipoic Acid Analogues that Inhibit Nitric Oxide Synthase.CHEMINFORM, Issue 35 2002Jeremiah J. Harnett No abstract is available for this article. [source] Synthesis, Biological Evaluation, and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPAR, and PPAR, Agonist ActivityCHEMMEDCHEM, Issue 5 2007Giuseppe Fracchiolla Dr. Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis, and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid analogues, some of which are potent PPAR, agonists as well as PPAR, agonists. The stereochemistry of these compounds plays an important role in determining their activity; the S,isomers were observed to be more active than the corresponding R,isomers. Interestingly, for one of these analogues, the stereoselectivity toward PPAR, was reversed, and for this reason docking experiments were performed to rationalize this peculiar behavior. [source] Investigating Carboxylic Acid Analogues of Ambruticin through Semi-SynthesisCHEMMEDCHEM, Issue 10 2006Yuan Xu Systemic fungal infections have increased significantly in recent years and this is important particularly for immunocompromised patients. A series of ambruticin carboxylic acid analogues have been synthesised through semi-synthesis and tested for their antifungal activity. The results suggest that the carboxylic acid is not crucial for potency, with the tetrazole 16 analogue showing similar antifungal activity to ambruticin VS-3 4. [source] Conformational and functional analysis of the lipid binding protein Ag-NPA-1 from the parasitic nematode Ascaridia galliFEBS JOURNAL, Issue 1 2005Rositsa Jordanova Ag-NPA-1 (AgFABP), a 15 kDa lipid binding protein (LBP) from Ascaridia galli, is a member of the nematode polyprotein allergen/antigen (NPA) family. Spectroscopic analysis shows that Ag-NPA-1 is a highly ordered, ,-helical protein and that ligand binding slightly increases the ordered secondary structure content. The conserved, single Trp residue (Trp17) and three Tyr residues determine the fluorescence properties of Ag-NPA-1. Analysis of the efficiency of the energy transfer between these chromophores shows a high degree of Tyr-Trp dipole-dipole coupling. Binding of fatty acids and retinol was accompanied by enhancement of the Trp emission, which allowed calculation of the affinity constants of the binary complexes. The distance between the single Trp of Ag-NPA-1 and the fluorescent fatty acid analogue 11-[(5-dimethylaminonaphthalene-1- sulfonyl)amino]undecanoic acid (DAUDA) from the protein binding site is 1.41 nm as estimated by fluorescence resonance energy transfer. A chemical modification of the Cys residues of Ag-NPA-1 (Cys66 and Cys122) with the thiol reactive probes 5-({[(2-iodoacetyl)amino]ethyl}amino) naphthalene-1-sulfonic acid (IAEDANS) and N,N,-dimethyl- N -(iodoacetyl)- N,-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD), followed by MALDI-TOF analysis showed that only Cys66 was labeled. The observed similar affinities for fatty acids of the modified and native Ag-NPA-1 suggest that Cys66 is not a part of the protein binding pocket but is located close to it. Ag-NPA-1 is one of the most abundant proteins in A. galli and it is distributed extracellularly mainly as shown by immunohistology and immunogold electron microscopy. This suggests that Ag-NPA-1 plays an important role in the transport of fatty acids and retinoids. [source] Structure,hepatoprotective activity relationship of 3,4-dihydroxycinnamic acid (caffeic acid) derivativesJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2001V. Pérez-Alvarez Abstract 3,4-Dihydroxycinnamic acid (caffeic acid, CAF) is a natural product containing a catechol group with an ,,,-unsaturated carboxylic acid chain that has shown hepatoprotective properties. The aim of this work was to determine the importance of the 4-hydroxy, 3-hydroxy, 3,4-dihydroxy substituents and the double bond moiety on the hepatic pharmacological effects of the molecule. We compared the ability of the caffeic, 4-hydroxycinnamic, 3-hydroxycinnamic, cinnamic and 3,4-dihydroxyhydrocinnamic (a caffeic acid analogue without the double bond) acids at a dose of 50 mg kg,1, p.o., to reduce the liver damage produced by CCl4 (4 g kg,1, p.o.) intoxication in the rat. Cinnamic acid, the non-hydroxylated analogue, only modestly protected the experimental animals challenged with CCl4, suggesting that hydroxyl groups participate in the pharmacological properties of CAF. The 3,4-dihydroxyhydrocinnamic derivative did not show any significant differences when compared with the CAF effect in this model, suggesting that the double bond does not account for the liver pharmacological properties of CAF. In contrast, the 4-hydroxy substituent seems to be very important for hepatoprotective activity because the 4-hydroxy analogue improved almost every hepatic injury marker altered by CCl4, and in a better way than CAF did. Copyright © 2001 John Wiley & Sons, Ltd. [source] A novel tandem quadrupole mass spectrometer allowing gaseous collisional activation and surface induced dissociationJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2001Shabaz Mohammed Abstract A novel tandem quadrupole mass spectrometer is described that enables gaseous collision-induced dissociation (CID) and surface-induced dissociation (SID) experiments. The instrument consists of a commercially available triple quadrupole mass spectrometer connected to an SID region and an additional, orthogonal quadrupole mass analyser. The performance of the instrument was evaluated using leucine-enkephalin, allowing a comparison between CID and SID, and with previous reports of other SID instruments. The reproducibility of SID data was assessed by replicate determinations of the collision energy required for 50% dissociation of leucine-enkephalin; excellent precision was observed (standard deviation of 0.6 eV) though, unexpectedly, the reproducibility of the equivalent figure for CID was superior. Several peptides were analysed using SID in conjunction with liquid secondary-ion mass spectrometry or electrospray; a comparison of the fragmentation of singly protonated peptide ions and the further dissociation of y-type fragments was consistent with the equivalence of the latter fragments to protonated peptides. Few product ions attributable to high-energy cleavages of amino acid side-chains were observed. The SID properties were investigated of a series of peptides differing only in the derivatization of a cysteine residue; similar decomposition efficiencies were observed for all except the cysteic acid analogue, which demonstrated significantly more facile fragmentation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Synthesis of Components for the Generation of Constitutional Dynamic Analogues of Nucleic AcidsHELVETICA CHIMICA ACTA, Issue 1 2008David Abstract The introduction of dynamic covalent polymers, in which the monomer units are linked by reversible covalent bonds and can undergo component exchange, opens up new possibilities for the generation of functional materials. Extending this approach to the generation of dynamic biopolymers in aqueous media, which are able to adapt constitution (sequence, length) to external factors (e.g., environment, medium, template), would provide an alternative approach to the de novo design of functional dynamic bio-macromolecules. As a first step towards this goal, various mono- and bifunctionalised (hetero- and homotopic) nucleic acid-derived building blocks of type I,X have been synthesised for the generation of dynamic main-chain and side-chain reversible nucleic acid analogues. Hydrazide- and/or acetal (protected carbonyl)-functionalised components were selected, which differ in terms of flexibility, length, net formal charge, and hydrazide/acetal substituents, in order to explore how such factors may affect the properties (structure, solubility, molecular recognition features) of the polymer products that may be generated by polycondensation. [source] Synthesis of N-protected 14C-Labelled (2E)-5-amino-5-methylhex-2-enoic acid analoguesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2001Claus U. Jessen Abstract A novel method of preparing N-protected (2E)-5-amino-5-methylhex-2-enoic acids has been developed based on the synthesis of 3-methyl-3-amino-butanol. The method was used to synthesise 14C-labelled compounds of (1) via synthesis of triethylphosphono[1- 14C]acetate. Copyright © 2001 John Wiley & Sons, Ltd. [source] Use of 19F NMR spectroscopy to probe enzymatic oxidation of fluorine-tagged sulfidesMAGNETIC RESONANCE IN CHEMISTRY, Issue 8 2002Behnaz Behrouzian Abstract A novel 19F NMR-based method for monitoring the enzymatic oxidation of thia fatty acid analogues is presented. Our approach is based on the observation that methyl ,-monofluorinated 9-thia- and 10-thiaoctadecanoates and their S -oxide and S -dioxide derivatives are easily distinguishable via their 1H-decoupled 19F spectra. These long-range substituent effects were used to probe the regio- and chemoselectivity of stearoyl ACP (acyl carrier protein) ,9 desaturase-mediated sulfoxidation. The results clearly demonstrate that mono-oxygenation of a 10-thia analogue ACP ,9 desaturase was more efficient than that of a 9-thia substrate. A product previously undetected by TLC was observed for the first time in the product mixture obtained from 18-fluoro-9-thiaoctadecanoyl-ACP. Copyright © 2002 John Wiley & Sons, Ltd. [source] Current trends in QSAR on NO donors and inhibitors of nitric oxide synthase (NOS),,MEDICINAL RESEARCH REVIEWS, Issue 4 2002Christos A. Kontogiorgis Abstract This article evaluates the quantitative structure-activity relationships (QSAR) of nitric oxide (NO) radical donors and nitric oxide synthases (NOS) inhibitors, using the C-QSAR program of Biobyte. Furoxans, triazines, amidoximes, tetrazoles, imidazoles and N,,2-nitroarylamino acid analogues were included in this survey. In nine out of seventeen cases, the clog P plays a significant part in the QSAR of the NO radical donors and of the NOS inhibition. Many of the compounds must be interacting with a hydrophobic space in a non-specific way. In some cases molecular refractivity CMR/MR as well as sterimol parameters (B1 and L) are important. Electronic effects, with the exception of the Hammett's constant , and the Swain,Lupton parameter F, are not found to govern the biological activity. Stereochemical and electronic features are also found to be important. Indicator variables were used after the best model was found to account for the usual structural features. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 4, 385,418, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10012 [source] N,N,N,,N,-Tetramethylethylenediammonium,succinate,succinic acid (1/1/1)ACTA CRYSTALLOGRAPHICA SECTION C, Issue 4 2004Giuseppe Bruno In the title compound, C6H18N22+·C4H4O42,·C4H6O4, the components lie on centres of symmetry in space group , such that the asymmetric unit contains three half-molecules. Despite the different mode (with respect to other dicarboxylic acids) adopted by the intermolecular self-interaction of succinic acid derivatives, the overall structure of the title compound consists of anionic layers that are typical of the packing structures exhibited by other dicarboxylic acid analogues. [source] Synthesis, Characterization, and Folding Behavior of ,-Amino Acid Derived PolyisocyanidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 10 2006Sander J. Wezenberg Abstract Helical polymers of isocyanopeptides derived from ,-amino acids have been synthesized and their architectures have been studied in detail. Similar to their ,-amino acid analogues, the helical conformation in these macromolecules is stabilized by internal hydrogen-bonding arrays along the polymeric backbone. Unexpectedly, the flexibility of the ,-peptide side arms results in a rearrangement of the initial macromolecular architecture, leading to a more stable helical structure possessing a better defined hydrogen-bonding pattern, as was concluded from IR and temperature-dependent circular dichroism studies. Based on these results we propose a dynamic helical model for the ,-amino acid derived polyisocyanopeptides; this model is in contrast to the kinetically stable helical macromolecules that are formed upon polymerization of ,-amino acid based isocyanopeptides. [source] Synthesis, Biological Evaluation, and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPAR, and PPAR, Agonist ActivityCHEMMEDCHEM, Issue 5 2007Giuseppe Fracchiolla Dr. Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis, and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid analogues, some of which are potent PPAR, agonists as well as PPAR, agonists. The stereochemistry of these compounds plays an important role in determining their activity; the S,isomers were observed to be more active than the corresponding R,isomers. Interestingly, for one of these analogues, the stereoselectivity toward PPAR, was reversed, and for this reason docking experiments were performed to rationalize this peculiar behavior. [source] Investigating Carboxylic Acid Analogues of Ambruticin through Semi-SynthesisCHEMMEDCHEM, Issue 10 2006Yuan Xu Systemic fungal infections have increased significantly in recent years and this is important particularly for immunocompromised patients. A series of ambruticin carboxylic acid analogues have been synthesised through semi-synthesis and tested for their antifungal activity. The results suggest that the carboxylic acid is not crucial for potency, with the tetrazole 16 analogue showing similar antifungal activity to ambruticin VS-3 4. [source] Oligonucleotide N3,,P5, Phosphoramidates and Thio -Phoshoramidates as Potential Therapeutic AgentsCHEMISTRY & BIODIVERSITY, Issue 3 2010Sergei Abstract Nucleic acids analogues, i.e., oligonucleotide N3,,P5, phosphoramidates and N3,,P5, thio -phosphoramidates, containing 3,-amino-3,-deoxy nucleosides with various 2,-substituents were synthesized and extensively studied. These compounds resist nuclease hydrolysis and form stable duplexes with complementary native phosphodiester DNA and, particularly, RNA strands. An increase in duplexes' melting temperature, ,Tm, relative to their phosphodiester counterparts, reaches 2.2,4.0° per modified nucleoside. 2,-OH- (RNA-like), 2,- O -Me-, and 2,- ribo -F-nucleoside substitutions result in the highest degree of duplex stabilization. Moreover, under close to physiological salt and pH conditions, the 2,-deoxy- and 2,-fluoro-phosphoramidate compounds form extremely stable triple-stranded complexes with either single- or double-stranded phosphodiester DNA oligonucleotides. Melting temperature, Tm, of these triplexes exceeds Tm values for the isosequential phosphodiester counterparts by up to 35°. 2,-Deoxy-N3,,P5, phosphoramidates adopt RNA-like C3,- endo or N -type nucleoside sugar-ring conformations and hence can be used as stable RNA mimetics. Duplexes formed by 2,-deoxy phosphoramidates with complementary RNA strands are not substrates for RNase H-mediated cleavage in vitro. Oligonucleotide phosphoramidates and especially thio -phosphoramidates conjugated with lipid groups are cell-permeable and demonstrate high biological target specific activity in vitro. In vivo, these compounds show good bioavailability and efficient biodistribution to all major organs, while exerting acceptable toxicity at therapeutically relevant doses. Short oligonucleotide N3,,P5, thio -phosphoramidate conjugated to 5,-palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor. GRN163L is not an antisense agent; it is a direct competitive inhibitor of human telomerase, which directly binds to the active site of the enzyme and thus inhibits its activity. This compound is currently in multiple Phase-I and Phase-I/II clinical trials as potential broad-spectrum anticancer agent. [source] | ||||||||||||||||||||||