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Available Compounds (available + compound)

Distribution by Scientific Domains

Chemistry	83%

Selected Abstracts

Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-, oligomers

ANNALS OF NEUROLOGY, Issue 6 2006
Matthew Townsend PhD
Objective Despite progress in defining a pathogenic role for amyloid , protein (A,) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble A, oligomers that have recently been shown to mediate synaptic dysfunction. Methods Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo -inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of A, on synaptic function and memory recall. Results Scyllo -inositol, but not its stereoisomer, chiro -inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human A,. Cerebroventricular injection into rats of the soluble A, oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo -inositol via the drinking water fully prevented oligomer-induced errors. Interpretation A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble A, oligomers through a mechanism that restores hippocampal synaptic plasticity. Ann Neurol 2006;60:668,676 [source]

The Use of N -Type Ligands in the Enantioselective Liquid,Liquid Extraction of Underivatized Amino Acids

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 27 2010
Bastiaan J. V. Verkuijl
Abstract The first palladium based extraction system using chiral N -based ligands in the enantioselective liquid,liquid extraction (ELLE) of underivatized amino acids, is presented. The system shows the highest selectivity for the ELLE of methionine with metal complexes as hosts reported to date. Furthermore, the host can be prepared in situ from commercially available compounds. The dependency of the system on parameters such as pH, organic solvent, and temperature has been established. The intrinsic selectivity was deduced by determination of the association constants of the palladium complex with the tryptophan enantiomers. [source]

Polyurethane- and Polystyrene-Supported 2,2,6,6-Tetramethyl- piperidine-1-oxyl (TEMPO); Facile Preparation, Catalytic Oxidation and Application in a Membrane Reactor

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 18 2008
Muhammad Afzal Subhani
Abstract In this contribution, the facile synthesis of two new polymer-supported 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) catalysts and their application in the catalytic oxidation of alcohols to carbonyl compounds are described. For attachment of the TEMPO group to the polymer an isocyanate functionalized polymer is chosen. This new approach facilitates the synthesis in comparison with previously existing methods which generally require deprotonation of TEMPO prior to reaction with the polymer. Following this approach, polyurethane (PU)- and polystyrene (PS)-based TEMPO catalysts are prepared in a one-step reaction from commercially available compounds. Both polymer-supported catalysts showed promising yields for a variety of substrates using inorganic and/or organic co-oxidants in biphasic and/or monophasic systems. The recyclability of the corresponding catalysts was studied in repetitive batch experiments using filtration or distillation depending on the support type. Furthermore, application of the homogeneous polyurethane-supported TEMPO for the selective oxidation of benzyl alcohol in a continously operated membrane reactor is demonstrated. [source]

Selection criteria for drug-like compounds

MEDICINAL RESEARCH REVIEWS, Issue 3 2003
Ingo Muegge
Abstract The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large-scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of ,drug-likeness' of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug-like. Various approaches have been devised to address the drug-likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture ,chemical wisdom' in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non-drugs. Here we review computational techniques to address the drug-likeness of compound selections and offer an outlook for the further development of the field. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 302-321, 2003 [source]

,tieredScreen' , Layered Virtual Screening Tool for the Identification of Novel Estrogen Receptor Alpha Modulators

MOLECULAR INFORMATICS, Issue 5 2010
Yidong Yang
Abstract A novel tiered Structure-Based (SB) Virtual Screening (VS) workflow called tieredScreen was designed and implemented. The automated protocol utilises diverse computational tools in a synergistic manner to reduce false positives and increase the likelihood of converging on putative active molecules. The performance of the novel VS workflow was validated using the Directory of Useful Decoys (DUD) Estrogen Receptor , (ER,) antagonist dataset, and successfully deployed for the identification of novel antagonists of ER, from a screening collection of ca. 160,000 commercially available compounds. As well as yielding nanomolar (nM) active ligands identified previously through a docking only protocol, from a selection of eight virtual hits suggested by tieredScreen, four novel nM ER, binding chemotypes were identified and biologically validated , demonstrating the applicability of a tiered intervention for virtual screening. [source]

Perfluorocyclobutyl-containing Amphiphilic Block Copolymers Synthesized by RAFT Polymerization

CHINESE JOURNAL OF CHEMISTRY, Issue 11 2009
Yongjun Chen
Abstract Amphiphilic block copolymers containing hydrophobic perfluorocyclobutyl-based (PFCB) polyacrylate and hydrophilic poly(ethylene glycol) (PEG) segments were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. The PFCB-containing acrylate monomer, p -(2-(p -tolyloxy)perfluorocyclobutoxy)-phenyl acrylate, was first synthesized from commercially available compounds in good yields, and this kind of acrylate monomer can be homopolymerized by free radical polymerization or RAFT polymerization. Kinetic study showed the 2,2,-azobis(isobutyronitrile) (AIBN) initiated and cumyl dithiobenzoate (CDB) mediated RAFT polymerization was in a living fashion, as suggested by the fact that the number-average molecular weights (Mn) increased linearly with the conversions of the monomer, while the polydispersity indices kept less than 1.10. The block polymers with narrow molecular weight distributions (Mw/Mn,1.21) were prepared through RAFT polymerization using PEG monomethyl ether capped with 4-cyanopentanoic acid dithiobenzoate end group as the macro chain transfer agent (mPEG-CTA). The length of the hydrophobic segment can be tuned by the feed ratio of the PFCB-based acrylate monomer and the extending of the polymerization time. The micellization behavior of the block copolymers in aqueous media was investigated by the fluorescence probe technique. [source]