QSAR analysis

As shown in Table VI, activity was strongly related to the group of Rj and R2. When Rj is H, and CHj, and R2 is from H to propyl, the compounds show higher activity. When R2 is a bulky group, such as tert-butyl or benzyl, the activity decreased. Therefore, the volume of compoimd may be an important factor for activity. To further explore the structural requirements for the activity of our compounds, quantitative structure-activity relationships (QSAR) analysis was performed. 

Compound Mortality (%) (500 mg/L) Activity (pLCjo mmol/L) AlogP Dipole Mopac 

The equation explained that AlogP and Dipole Mopac are the most important factors for the activity of our compounds. The lower AlogP and Dipole Mopac value will result in higher bioactivities. 

Yamamoto, J. E. Casida, Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor, Springer-Verlag, Tokyo, 

Okumura, K. Matsuda, M. Akamatsu, D. B. Sattelle, K. Komai, Brain Res., 

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Hopfinger et al. [53, 54] have constructed 3D-QSAR models with the 4D-QSAR analysis formahsm. This formalism allows both conformational flexibility and freedom of alignment by ensemble averaging, i.e., the fourth dimension is the dimension of ensemble sampling. The 4D-QSAR analysis can be seen as the evolution of Molecular Shape Analysis [55, 56]. 

CODESSA reads molecular structure files or output files created by other software packages as the starting point for QSAR analysis. It can import computational results from AMPAC, MOPAC, and Gaussian as well as structures in a number of common formats. 

Comparative QSAR analysis of derivatives of heterocycles as nonsteroid ligands of estrogen receptors 99CRV723. 

Neither of these mechanisms of toxic action is susceptible to the kind of QSAR analysis referred to earlier, the employment of which depends on knowledge of the structure of particular binding sites. 

A Brief Review of the QSAR Technique. Most of the 2D QSAR methods employ graph theoretic indices to characterize molecular structures, which have been extensively studied by Radic, Kier, and Hall [see 23]. Although these structural indices represent different aspects of the molecular structures, their physicochemical meaning is unclear. The successful applications of these topological indices combined with MLR analysis have been summarized recently. Similarly, the ADAPT system employs topological indices as well as other structural parameters (e.g., steric and quantum mechanical parameters) coupled with MLR method for QSAR analysis [24]. It has been extensively applied to QSAR/QSPR studies in analytical chemistry, toxicity analysis, and other biological activity prediction. On the other hand, parameters derived from various experiments through chemometric methods have also been used in the study of peptide QSAR, where partial least-squares (PLS) analysis has been employed [25]. 

Partitioning methods occasionally struggle to provide the accuracy associated with more powerful, albeit less informative techniques such as machine learning and statistical approaches. For this reason, there is a continuing need for the application of more accurate and informative classification techniques to QSAR analysis. The goal of a classifier is to produce a model that can separate new, untested compounds into classes with a training set of already classified compounds. 

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. 

One of the best-known techniques for QSAR analysis of classification data is discriminant analysis [71,72]. If a single descriptor is adequate to discrimi-... 

Murcia-Soler M, Perez-Gimenez F, Naldo-Molina R, Salabert-Salvador MT, Garcla-March FJ, Cercos-del-Pozo RA et al. QSAR analysis of hypoglycaemic agents using the topological indices. J Chem Inf Comput Sci 2001 41 1345-54. 

Yarim M, Moro S, Huber R, Meier PJ, Kaseda C, Kashima T, et al. Application of QSAR analysis to organic anion transporting polypeptide la5 (Oatpla5) substrates. Bioorg Med Chem 2005 13 463-71. 

BeUo-Ramirez AM, Nava-Ocampo AA (2004) A QSAR analysis of toxicity of Aconitinn alkaloids. Fund Clin Pharmacol 18 699-704... 

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. 

Table 2 Selected perfluorinated compounds (PFCs) for the QSARs analysis... 

Table 3 QSARs analysis of PFCs using VEGA and ToxTree... 

From the preliminary list of 16 compounds of concern, 14 compounds have been selected for the application of in silico methods because metals, and generally inorganic compounds, cannot be subjected to QSARs analysis. 

Kulkarni, A., Han, Y., and Hopfinger, A. J., Predicting Caco-2 cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis, /. Chem. Inf. Comput. Sci., 2002, 42, 331-342. 

Hydrophobicity (log P) is related to the desolvation of the ligand, and it is assumed that the desolvation of the ligands going from water to octanol parallels that of going from water to a cleft or pocket of a receptor. Thus, log P may be an important term in establishing quantitative relationships between structure and activity (26). In order to examine the influence of the lipohilic character of the 4-PIOL analogs on the affinity for the GABAa receptor, QSAR analysis was performed (24). 

Compound 330 (Figure 31) is a potent and very selective cyclooxygenase-2 (COX-2) inhibitor <1997BMCL57>. Three-dimensional quantity-structure activity relationship (3-D QSAR) analysis of this compound and other members of a series of 5,6-diarylthiazolo[3,2-A][l,2,4]triazoles has been carried out <2004MI5>. 

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... 

Thorium metal, 24 759-761 in alloys, 24 760-761 preparation of, 24 759-760 properties of, 24 760-761 reactions of, 24 761 Thorium nitrate, 24 757, 766 Thorium oxalates, 24 768-769 Thorium oxide, 21 491 Thorium oxides, 24 757, 761-762 Thorium oxyhalides, 24 762 Thorium perchlorate, 24 764 Thorium phosphates, 24 765-766 Thorium pnictides, 24 761 Thorium sulfate, 24 764 Thorium-uranium fuel cycle, 24 758-759 Thorocene, 24 772 Thorotrast, 24 775-776 3A zeolite. See Zeolite 3A Three-boiling beet sugar crystallization scheme, 23 463-465 Three-color photography, 19 233-234 3D models, advantages of, 19 520-521 3D physical design software, 19 519-521 3D QSAR models, 10 333. See also QSAR analysis... 

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... 

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. 

Ligand-Based and Receptor-Based Pharmacophore Modeling and QSAR Analysis... 

As for the modeling of in vitro and in vivo potencies and selectivities, some interesting models were obtained on a subset of representative ligands. In fact, the QSAR analysis of functional activities for this set of compounds, although numerically limited, yields successful correlations [97]. Among these linear correlations, the following equation constitutes a significant example ... 

Finally, very recently Pallavicini et al., in continuation of a previous study on ortho-monosubstituted compounds, designed and synthesized a series of 2-[(2-phenox-yethyl) aminomethyl]-l,4-benzodioxanes ortho-disubstituted at the phenoxy moiety [99]. The disubstituted analogues were tested for their binding affinities at the three oq-AR subtypes and for the 5-HT1A-R. The affinity values of the new compounds were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known oq-AR antagonist WB-4101 (Scheme 8.1), and of the ortho-monosubstituted derivatives. The results suggested some distinctive aspects in the interaction of the phenoxy moiety of monosubstituted and disubstituted compounds with the cqa-AR and the 5-HTiA receptors. A classical (Hansch) QSAR analysis was applied to the whole... 

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