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91.
High throughput screening (HTS) for complex diseases is challenging. This stems from the fact that complex phenotypes are difficult to adapt to rapid, high throughput assays. We describe the recent development of high throughput and high-content screens (HCS) for neurodegenerative diseases, with a focus on inherited neurodegenerative disorders, such as Huntington's disease. We describe, among others, HTS assays based on protein aggregation, neuronal death, caspase activation and mutant protein clearance. Furthermore, we describe high-content screens that are being used to prioritize hits identified in such HTS assays. These assays and screening approaches should accelerate drug discovery for neurodegenerative disorders and guide the development of screening approaches for other complex disease phenotypes. 相似文献
92.
The matrix isolation technique has been combined with infrared spectroscopy and theoretical calculations to explore the reaction of (CH3)2Zn with O3 over a range of time scales. Upon twin jet deposition, an initial cage pair complex was observed, along with formation of the novel H3COZnCH3 species. Subsequent UV irradiation destroyed the complex and greatly increased the yield of H3COZnCH3. An extensive set of bands were seen for this molecule, and (18)O spectroscopic data were obtained as well. The identification of this species was supported by theoretical calculations at the B3LYP/6-311++g(d,2p) level. Merged jet deposition led to a very different set of products, including H2CO, CH3OH and C2H6, identifications that were confirmed by (18)O substitution. In addition, a new variable length concentric deposition technique was developed to permit study of the time scales between twin (relatively short) and merged (relatively longer) reaction times. Mechanistic inferences for this reaction are discussed. 相似文献
93.
Venkata Swamy Tangeti Ramesh Varma K. G. V. Siva Prasad K. V. V. V. Satyanarayana 《合成通讯》2016,46(7):613-619
An efficient method was developed for the synthesis of dihydrofuran substituted coumarin from a one-pot, four-component reaction of 2-hydroxy aromatic aldehydes, 6-methyl, 4-hydroxy pyranone, aromatic aldehyde, and pyridinium ylide in the presence of tri-ethylamine under microwave irradiation. The reaction proceeds under solvent-free conditions to afford C3-dihydrofuran substituted coumarin in a diastereoselective manner in good yields (71–89%). 相似文献
94.
An efficient method was developed for the diastereoselective synthesis of novel fused dihydro-1H-furo[2,3-c]pyrazole by a one-pot, four-component reaction of β-keto ester, hydrazine, aromatic aldehyde, and pyridinium ylide in the presence of triethylamine under microwave irradiation in solvent-free conditions in good yields. The merits of this cascade Knoevenagel condensation/Michael addition/cyclization sequence include its high atom economy, good yields, and efficiency of producing three new bonds (two C–C and one C–O) and two stereocenters in a single operation. 相似文献
95.
Rajender S. Varma 《Journal of heterocyclic chemistry》1999,36(6):1565-1571
Microwave-enhanced solvent-free synthetic approach is described that features simplicity, manipulative ease of the operation and conservation of solvents as the main advantages. This eco-friendly approach, which has found application in facile organic functional group transformations, is applied to rapid assembly of heterocyclic compounds. A variety of solid state reactions are described that occur rapidly at ambient pressure under solventless conditions and provide ready access to intermediates such as enamines and α-tosyloxyketones which can be transformed in situ to biologically significant heterocyclic compounds such as isoflav-3-enes, flavones, quinolones, 2-aroylbenzo[b]furans and thiazoles in one-pot operation. Multicomponent reactions under these solvent-free conditions can be adapted for high speed parallel synthesis and are exemplified by assembly of dihydropyrimidine-2(1H)-ones (Biginelli reaction) and imidazo[1,2-a]annulated pyridines, pyrazines and pyrimidines (Ugi reaction) which may have potential in building a library of such compounds. 相似文献
96.
Ananthalakshmi N. R Wadgaonkar P. P Sivaram S. Varma I. K. 《Journal of Thermal Analysis and Calorimetry》1999,58(3):533-539
The paper describes the effect of molecular mass and copolymer composition on thermal behaviour of homopolymers and copolymers of glycidyl methacrylate and methyl methacrylate. The polymerisation was done by using group transfer polymerization (GTP) and free radical techniques. A multistep decomposition was observed in polymers prepared by free radical technique indicating the presence of weak linkages in the backbone. Copolymers prepared by GTP had fewer weak sites and degraded in single step by a random chain scission.This revised version was published online in November 2005 with corrections to the Cover Date. 相似文献
97.
I.K. Varma 《Macromolecular Symposia》2004,210(1):121-129
Hydroxy-terminated azido polymers such as poly(glycidyl azide), poly bis(azidomethyl oxetane) and poly(azidomethyl methyloxetane) have been investigated in the past in propellent formulations and as fuels in rocket technology. The high energy released upon the decomposition of the azido group is responsible for their specialized application as high-energy binders. The present paper describes the synthesis and characterization of new low molecular mass azido polymer i.e. poly(allyl azide). The curing reaction was carried out by using 1,3-cyclic dipolar addition reaction. The dipolarophiles, such as dimethylene glycol dimethacrylate (EGDMA) and addition polyimides (bismaleimides, bisnadimides and bisitaconimides) were used for curing of azido polymers. The curing reaction was monitored by FT-IR and differential scanning calorimetry. Curing was carried out at 40°C for 16 h (EGDMA) or 2 days (bismaleimide) and then at 60°C by using different phr of dipolarophiles. The heat of exothermic transition, due to decomposition of azide groups and thermal polymerization of addition polyimides, was very high and an improvement in thermal stability of cured resins was observed. 相似文献
98.
Marco Apostolo Andrea Tredici Massimo Morbidelli Arvind Varma 《Journal of polymer science. Part A, Polymer chemistry》1997,35(6):1047-1059
Traveling polymerization fronts in unstirred solutions of methylmethacrylate, methacrylic acid, or acrylamide with some free radicals initiators (through thermal decomposition) have been observed experimentally. A local heating of the initial reactant mixture, under suitable conditions, leads to a reaction front that propagates along the space coordinate with a constant velocity. In this article, a physical interpretation of this phenomenon is provided through a mathematical model that accounts for the depolimerization reaction and is based on the constant pattern approach. Moreover, an approximate explicit analytic expression for the velocity of propagation of the polymerization front is proposed. The theoretical values are compared with those measured experimentally as a function of the initiator concentration for different addition polymerization systems. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35:1047–1059, 1997 相似文献
99.
Rajni Madan R. C. Anand Indra K. Varma 《Journal of polymer science. Part A, Polymer chemistry》1997,35(14):2917-2924
Metathesis polymerization of N-phenyl-exo-norbornene dicarboximide and ortho/meta/para methyl substituted phenyl nadimides was carried out using WCl6/tetramethyltin. Structural characterization was done by FTIR, 1H- and 13C-NMR. A mixture of cis and trans double bond structures were introduced in the backbone during polymerization. The cis content was higher (52 to 65%). In the DSC scan of poly(N-o-tolyl nadimide), two exotherms were observed at 240 and 270°C while in other samples only one exothermic transition was observed above 240°C. These exotherms disappeared in the second heating cycle. The Tg of the polymers, as determined in the second heating cycle, was highest in poly(N-o-tolyl nadimide) and lowest in poly(N-m-tolyl nadimide). The polymers were stable up to 443 ± 3°C and decomposed above this temperature in a single step. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2917–2924, 1997 相似文献
100.