Quantitative structure-analysis relationships

B. J. Burke, W. J. Dunn 111, and A. J. Hopfinger,/. Med. Chem., 37, 3775 (1994). Construction of a Molecular Shape Analysis Tliree-Dimeiisional Quantitative Structure-Analysis Relationship for an Analog Series of Pyridobenzodiazepinone Inhibitors of Muscarinic 2 and 3 Receptors. 

Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

Furthermore, QSPR models for the prediction of free-energy based properties that are based on multilinear regression analysis are often referred to as LFER models, especially, in the wide field of quantitative structure-activity relationships (QSAR). 

Poso A, R Juvonen and J Gynther 1995. Comparative Molecular Field Analysis of Compounds wii CYP2A5 Binding Affinity. Quantitative Structure-Activity Relationships 14 507-511. 

GM Crippen. Quantitative structure-activity relationships by distance geometry Systematic analysis of dihydrofolate reductase inhibitors. I Med Chem 23 599-606, 1980. 

Applications of neural networks are becoming more diverse in chemistry [31-40]. Some typical applications include predicting chemical reactivity, acid strength in oxides, protein structure determination, quantitative structure property relationship (QSPR), fluid property relationships, classification of molecular spectra, group contribution, spectroscopy analysis, etc. The results reported in these areas are very encouraging and are demonstrative of the wide spectrum of applications and interest in this area. 

Bis(oxazohnes) figands have been so widely used for the Diels-Alder reaction between N-2-alkenoyl-l,3-oxazolidine-2-one and cyclopentadiene that Lipkowitz and Pradhan developed a QSAR (quantitative structure-activity relationship) using Comparative Molecular Field Analysis (CoMFA) for a set of 23 copper-catalysts containing mainly bis(oxazoline) figands. The generated... 

Gao H, Williams C, Labute P, Bajorath J. Binary quantitative structure-activity relationship (QSAR) analysis of estrogen receptor ligands. / Chem Inf Comput Sci 1999 39 164-8. 

Ekins S, Bravi G, Wikel JH, Wrighton SA. Three dimensional quantitative structure activity relationship (3D-QSAR) analysis of CYP3A4 substrates. J Pharmacol Exp Ther 1999 291 424-33. 

Van der Graaf PH, Nilsson J, Van Schaick EA, Danhof M. Multivariate quantitative structure-pharmacokinetic relationships (QSPKR) analysis of adenosine A1 receptor agonists in rat. J Pharm Sci 1999 88 306-12. 

Tier II analysis Quantitative structure-activity relationships... 

Hansch and Verma contribute to the quantitative structure-activity relationship (QSAR) analysis of heterocyclic topoisomerase I and II inhibitors. These inhibitors, known to inhibit either enzyme, act as antitumor agents and are currently used in chemotherapy and in clinical trials. 

Ekins, S., G. L. Durst, R. E. Stratford, D. A. Thorner, R. Lewis, R. J. Loncharich, and J. H. Wikel. Three-dimensional quantitative structure-permeability relationship analysis for a series of inhibitors of rhinovirus replication, J. Chem. Inf. Comput. Sci. 2001, 41, 1578-1586... 

Multiple linear regression (MLR) is a classic mathematical multivariate regression analysis technique [39] that has been applied to quantitative structure-property relationship (QSPR) modeling. However, when using MLR there are some aspects, with respect to statistical issues, that the researcher must be aware of ... 

QEKIRVRLSA antimicrobial peptide, 26 799-800 Qiana, 19 764 QikProp, 6 18 Qinghai Lake, 5 784 Q parameter, impeller, 16 676 QSAR analysis, 10 327t, 328-329. See also Quantitative structure—activity relationship (QSAR) studies 3D QSAR models... 

The synthesis and antibacterial properties of norfloxacin (2a) were described in 1980 [65]. In this key paper in the evolution of quinolone antibacterial agents, a series of 6,7,8-polysubstituted-l-ethyl-l,4-dihydro-4-oxoquinoline-3-carb-oxylic acids (13) was synthesized, employing previously developed quantitative structure-activity relationships (QSAR) for the corresponding 6-, 7- and 8-monosubstituted derivatives versus Escherichia coli. The QSAR analysis... 

Besides the applications of the electrophilicity index mentioned in the review article [40], following recent applications and developments have been observed, including relationship between basicity and nucleophilicity [64], 3D-quantitative structure activity analysis [65], Quantitative Structure-Toxicity Relationship (QSTR) [66], redox potential [67,68], Woodward-Hoffmann rules [69], Michael-type reactions [70], Sn2 reactions [71], multiphilic descriptions [72], etc. Molecular systems include silylenes [73], heterocyclohexanones [74], pyrido-di-indoles [65], bipyridine [75], aromatic and heterocyclic sulfonamides [76], substituted nitrenes and phosphi-nidenes [77], first-row transition metal ions [67], triruthenium ring core structures [78], benzhydryl derivatives [79], multivalent superatoms [80], nitrobenzodifuroxan [70], dialkylpyridinium ions [81], dioxins [82], arsenosugars and thioarsenicals [83], dynamic properties of clusters and nanostructures [84], porphyrin compounds [85-87], and so on. 

Crebelli, R., Andreoli, C., Carere, A., Conti, G., Conti, L., Cotta-Ramusino, M., Benigni, R. The induction of mitotic chromosome malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (QSAR) analysis with chlorinated aliphatic hydrocarbons. Mutat. Res. 1992, 266, 117-134. 

Cocchi, M., Menziani, M.C., Fanelli, F. and De Benedetti, P.G. (1995) Theoretical quantitative structure-activity relationship analysis of congeneric and non congeneric al-adrenoceptor antagonists a chemometric study. Journal of Molecular Structure (Theochem), 331, 79-93. 

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