Novel Methods

One of the problems when applying classical QSAR techniques is the right choice of the method and the descriptor combination. In principle, two general approaches might be undertaken to overcome this issue, which normally is pursued on a trial and error basis. One is to automatically combine feature selection algorithms with classification and regression tools and the other is to combinatorially explore the descriptor/method space. The latter was recently introduced by the group of Tropsha (combinatorial QSAR) [47]. 

Selection of a reference compound set on the basis of maximum diversity and/or active/inactive. 

Calculation of a set of descriptors for both the training set and the reference set. Calculation of similarity values for each compound of the training set to each compound of the reference set this leads to a given number of similarity values (equal to the number of reference compounds used) for each compound of the training set, which are assigned as SIBAR descriptors. 

Validation of the model using cross-validation procedures and external test sets. 

P-gp inhibitors from our in-house library C P-gp substrates from the literature D chemicals), models derived by using reference sets related to the target P-gp (B, C) gave highest internal (leave-one-out cross-validation) and external (test set) predictivity [49]. 

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A Novel Method for Off-Line Defect Characterization and Sizing from Standard b-Scan Data. 

We present a novel method, called VIGRAL, to size and position the reflecting surface of a flaw. The method operates on standard B-scan recorded with traditional transducers, to extract Time-of-Flight (ToF) information which is then back-projected to reconstruct the reflecting surface of the flaw and characterize its radiation pattern. The VIGRAL method locates and sizes flaws to within k/2, and differentiates between flat and volumetric defects. 

G.Krug, R.Aharoni, V.Orjelik, A novel method for sizing defects from off- line B-scan data . Proceedings of Ultrasonic World Congress,Yokogama, 1997, 122-124. 

Grundmeier G, Sohmidt W and Stratmann M 2000 Corrosion proteotion by organio ooatings eleotroohemioal meohanism and novel methods of investigation Eleotroohim. Acfa 45 2515... 

R. Elber. Novel methods for molecular dynamics simulations. Curr. Opin. Struc. Biol., 6 232-235, 1996. 

A year later, a novel method of encoding chemical structures via typewriter input (punched paper tape) was described by Feldmann [42]. The constructed typewriter had a special character set and recorded on the paper tape the character struck and the position (coordinates) of the character on the page. These input data made it possible to produce tabular representations of the structure. 

The formation of 2.6-octadienol (27) by the reaction of 1,3-butadiene with water has attracted attention as a novel method for the commercial production of n-octanol, which has a considerable market. However, the reaction of water under the usual conditions is very sluggish. The addition of CO2 facilitates the telomerizdtion of water and 2,6-octadienol (27) is obtained as a major pro-duct[31]. In the absence of CO2, only 1,3,7-octatriene (7) is formed. Probably octadienyl carbonate is formed, which is easily hydrolyzed to give 27. A com-... 

The 1967 Nobel Prize in chemistry was shared by Manfred Eigen a German chemist who developed novel methods for measur ing the rates of very fast re actions such as proton transfers... 

The insulating value and mechanical properties of rigid plastic foams have led to the development of several novel methods of buUding constmction. Polyurethane foam panels may be used as unit stmctural components (220) and expanded polystyrene is employed as a concrete base in thin-sheU constmction (221). 

An on-line concentration, isolation, and Hquid chromatographic separation method for the analysis of trace organics in natural waters has been described (63). Concentration and isolation are accompHshed with two precolumns connected in series the first acts as a filter for removal of interferences the second actually concentrates target solutes. The technique is appHcable even if no selective sorbent is available for the specific analyte of interest. Detection limits of less than 0.1 ppb were achieved for polar herbicides (qv) in the chlorotriazine and phenylurea classes. A novel method for deterrnination of tetracyclines in animal tissues and fluids was developed with sample extraction and cleanup based on tendency of tetracyclines to chelate with divalent metal ions (64). The metal chelate affinity precolumn was connected on-line to reversed-phase hplc column, and detection limits for several different tetracyclines in a variety of matrices were in the 10—50 ppb range. 

Workers at the General Electric Co. have described a new procedure using low viscosity cycHc intermediates to prepare polycarbonate composites (14,15). This work is discussed in the section dealing with novel methods. 

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

Only once in 15 years does a truly novel method of size reduction become successful. The roll press is a truly successful example of a novel mill, and stirred-bead mills are older mills that have reached a new state of development. Many more methods are proposed and studied some of these are described below The information may be useful to judge other novel methods that may be proposed. 

BJ Berne, JE Straub. Novel methods of sampling phase space in the simulation of biological systems. Cuit Opm Struct Biol 7 181-189, 1997. 

Novel Methods for Making Carbon and Ceramic Materials and Artefacts... 

So, by the 1990s, Professor Rao had been active in several of the major aspects which, together, were beginning to define materials chemistry crystal defects, phase transitions, novel methods of synthesis. Yet, although he has been president of the Materials Research Society of India, he does not call himself a materials chemist but remains a famous solid-state chemist. As with many new conceptual categories, use of the new terminology has developed sluggishly. 

Novel methods for making carbon and ceramic materials and artefacts... 

Odele, O., and Macchietto, S. (1993). Computer aided molecular design A novel method for optimal solvent selection. Fluid Phase Equilibria, 82,47-54. 

The Roussel group has described recently a novel method for the synthesis of 2,2-dimethyl-A" -3-keto steroids. Thus addition of potassium t-butoxide to a solution of 19-nortestosterone (25) in tetrahydrofuran containing methyl iodide and hexamethylphosphorous triamide at —70° affords the 2,2-dimethyl compound (26) in good yield.Methylation of A" -3-ketone by the classical conditions, namely addition of methyl iodide to a solution of the steroid and potassium /-butoxide, leads to the 4,4-dimethyl product. 

R. F. Cracknell, D. Nicholson, N. G. Parsonage, H. Evans. Rotational insertion bias a novel method for simulating dense phases of structured particles, with particular application to water. Mol Phys 77 931-943, 1990. 

Novel Methods for Selective Huorination of Organic Compounds. Design and Synthesis of Fluorinated Antimetabolites Kollonitsch, J Isr J Chem 17, 53-59 50... 

White and Weingarton (64) have recently described a novel method for the preparation of the enamines of the hindered ketones. The method involves the treatment of the ketone with an excess of the amine and a Lewis acid such as TiCl4. 

Synthesis of hetarylethylenes using novel methods for C=C double-bond formation 98ACR584. 

A novel method of forming 2-aryl derivatives of 5,6-dihydro-1,3-4H-oxazine (35) consists in reacting 3-azidopropanol with aromatic aldehydes/ ... 

To overcome these limitations, there has been a great deal of investigation of novel methods, one of them focused on the search for alternative solvents [6, 7]. Table 5.3-1 gives different approaches to biphasic catalysis, with some of their respective advantages and limitations. 

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