Structure-activity relationship index similarity

Another index for evaluating presence of activity cliffs is the SAR Index (or Structure-Activity Relationship Index), defined as a function of two separately calculated scores that assess intraclass diversity and activity differences of similar compounds [Peltason and Bajorath, 2007] ... 

The next step was made by Klebe et al. [50]. Two 3D-QSAR methods were applied to get three-dimensional quantitative structure-activity relationships using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities toward Factor Xa to yield statistically reliable models of good predictive power [51-54] the widely used CoMFA method (for steric and electrostatic properties) and the comparative molecular similarity index analysis (CoMSlA) method (for steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties). These methods allowed the consideration of various physicochemical properties, and the resulting contribution maps could be intuitively interpreted. 

Lobato, M., Amat, L., Besalil, E. and Carbd-Dorca, R. (1997). Structure-Activity Relationships of a Steroid Family Using Quantum Similarity Measures and Topological Quantum Similarity Indexes. Quant.Struct.-Act.Relat., 16,465-472. 

Molecular Similarity and QSAR. - In a first contribution on the design of a practical, fast and reliable molecular similarity index Popelier107 proposed a measure operating in an abstract space spanned by properties evaluated at BCPs, called BCP space. Molecules are believed to be represented compactly and reliably in BCP space, as this space extracts the relevant information from the molecular ab initio wave functions. Typical problems of continuous quantum similarity measures are hereby avoided. The practical use of this novel method is adequately illustrated via the Hammett equation for para- and me/a-substituted benzoic acids. On the basis of the author s definition of distances between molecules in BCP space, the experimental sequence of acidities determined by the well-known a constant of a set of substituted congeners is reproduced. Moreover, the approach points out where the common reactive centre of the molecules is. The generality and feasibility of this method will enable predictions in medically related Quantitative Structure Activity Relationships (QSAR). This contribution combines the historically disparate fields of molecular similarity and QSAR. 

In recent years there has been a notable increase in research on structure-activity relationships (SARs), also called quantitative structure-activity relationships (QSARs), used to assess the toxicity of substances for which there are few experimental data. This approach involves establishing mathematical relationships derived from computer modeling, based on known toxicity data of similar (or dissimilar) types of compounds, octanol-water partition coefficients, molar connectivity index values, and other parameters. A detailed discussion on this subject is beyond the scope of this book. 

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