Quantitative structure-activity relationships lead compounds

Cruciani G, Crivori P, Carrupt PA, Testa B (2000) Molecular fields in quantitative structure-permeation relationships The VolSurf approach. Theochem 503 17-30 Cruciani G, Pastor M, Clementi S (2000) Handling information from 3D GRID maps for QSAR studies. In Gun-dertofte K, Jorgensen FS (eds) Molecular modelling and prediction of bioactivity, proceedings of the 12th European symposium on quantitative structure-activity relationships (QSAR 98). Plenum Press, New York, pp 73-81 Cruciani G, Pastor M, Guba W (2000) VolSurf A new tool for the pharmacokinetic optimization of lead compounds. Eur J Pharm Sd 11 S29-S39... 

We discuss how the size of a library can he drastically reduced without loss of information or decreases in the chances of finding a lead compound. The approach is based on the use of statistical molecular design (SMD) for the selection oflibrary compounds to synthesise and test, followed by the use of quantitative structure activity relationships (QSARs) for the evaluation of the resulting test data. The use of SMD and QSAR is, in turn, critically dependent on an appropriate translation of the molecular structure to numerical descriptors, the recognition of inhomogeneities (clusters) in both the structural... 

Quantitative structure-activity relationship (QSAR) dates back to the nineteenth century and is a computer-based tool that attempts to correlate variations in structural or molecular properties of compounds with their biological activities. These physicochemical descriptors, which include parameters to account for hydrophobicity, topology, electronic properties, and steric effects, are determined empirically or, more recently, by computational methods. The premise is that the structure of a chemical determines the physiochemical properties and reactivities that underlie its biological and toxicological properties. Being able to predict potential adverse effects not only aids in the designed development of new chemicals but also reduces the need for animal testing. It may ultimately or potentially lead to better... 

Mother nature is a good resource for new molecules over 10000 natural products are isolated each year [ 1 ]. Historically, natural products have provided a good number of leads for the development of new drugs [2], However, since natural products are commonly screened as an extraction mixture, deconvolution of an active component and structural characterization are difficult tasks. In addition, isolation of natural products has a long cycle time and is considered expensive [3], These limitations have prompted efforts to synthesize natural product analogues and natural-product-like compounds for biological screening and quantitative structure-activity relationship (QSAR) studies. 

Another field for assisting in the selection of potential lead compounds or optimized leads is called Quantitative Structure Activity Relationships (QSARs). These methods determine correlations between certain descriptors of the molecular structures and the measured biological activity to produce a predictive model. That model can then be used to predict the activity of other structures prior to actually testing. 

The prototype for a new dmg is called a lead compound. Changing the stmcture of a lead compound is called molecular modification. A random screen (or blind screen) is a search for a pharmacologically active lead compound without having any information about what stmctures might show activity. The technique of relating a property of a series of compounds to biological activity is known as a quantitative structure-activity relationship (QSAR). 

The transfer and the adsorption are strongly influenced by the size of the compound (surface and volume) and by the functional groups present in the molecule (alcohols, aldehydes, ketones, carboxylic acids, amines, mercaptans, halogenated molecules) inducing some polarization effects. Some studies have reported a quantitative structure activity relationship (QSAR) between molecular structure and adsorption parameters (adsorption capacities, energies) [32,37,78]. The reactivity of some compounds leads to oxidation at the adsorbent surface, which plays a catalytic role. Moreover, a mixture of molecules in air... 

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