Structure-activity relationship approach

The QSAR (quantitative structure-activity relationship) approach has been considered for the identification of toxicants that bind to steroid and aryl... 

A Quantitative Structure-Activity Relationship Approach to Pesticide Design... 

Hansch analysis Hansch analysis is a common quantitative structure-activity relationship approach in which a Hansch equation predicting biological activity is constructed. The equation arises from a multiple linear regression analysis of both observed biological activities and various molecular property parameters (Hammett, Hansch, and Taft parameters). 

Zvinavashe E, Murk AJ, Rietjens M (2008) Promises and pitfalls of quantitative structure-activity relationship approaches for predicting metabolism and toxicity. Chem Res Toxicol 21(12) 2229-2236... 

Tong, W., Welsh, W.J., Shi, L., Fang, H., and Perkins, R., Structure-activity relationship approaches and applications, Environ. Toxicol. Chem., 22, 1680-1695, 2003. 

Three-Dimensional Quantitative Structure-Activity Relationship Approaches An early study by Seidel et al. showed that a certain 3D feature, such as a torsion angle, can be used to help explain calcium channel activity of a series of DHPs [123], For a set of rigid analogues of nifedipine, their calcium channel affinities (log A)) were correlated with the deviation from 90° of the torsion angle between the two rings (Aa) ... 

Sugai, S., Murata, K., Kitagaki, T, and Toinik, 1. (1990). Studies on eye irritation caused by chemicals in rabbits 1. A quantitative structure-activity relationship approach to primary eye irritation of chemicals in rabbits. J. Toxicol Sci. 15, 246-262,... 

Finally, three examples will demonstrate the structure-activity relationship approach based on comparison of chemical structures. A pyridinium type of ionic liquid is presented in contrast to Paraquat (4), a herbicide which is considered to exhibit substantial toxicological and eco-toxicological risk (due to high acute toxicity and high persistence) and has therefore been banned in many countries. 

A challenging task in material science as well as in pharmaceutical research is to custom tailor a compound s properties. George S. Hammond stated that the most fundamental and lasting objective of synthesis is not production of new compounds, but production of properties (Norris Award Lecture, 1968). The molecular structure of an organic or inorganic compound determines its properties. Nevertheless, methods for the direct prediction of a compound s properties based on its molecular structure are usually not available (Figure 8-1). Therefore, the establishment of Quantitative Structure-Property Relationships (QSPRs) and Quantitative Structure-Activity Relationships (QSARs) uses an indirect approach in order to tackle this problem. In the first step, numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical and artificial neural network models are used to predict the property or activity of interest based on these descriptors or a suitable subset. 

A Quantitative Approach to Biochemical Structure-Activity Relationships. Accounts of nical Research 2 232-239. 

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. JL Fauchere, ed. QSAR Quantitative Structure-Activity Relationships m Drug Design. New York Alan R Liss, 1989, pp 177-181. 

S Hellberg, M Sjostrom, B Skagerberg, S Wold. Peptide quantitative structure-activity relationships, a multivariate approach. I Med Chem 30 1126-1135, 1987. 

Medicinal Chemistry Approaches and the Role of Quantitative Structure Activity Relationships... 

With the development of accurate computational methods for generating 3D conformations of chemical structures, QSAR approaches that employ 3D descriptors have been developed to address the problems of 2D QSAR techniques, that is, their inability to distinguish stereoisomers. Examples of 3D QSAR include molecular shape analysis (MSA) [26], distance geometry,and Voronoi techniques [27]. The MSA method utilizes shape descriptors and MLR analysis, whereas the other two approaches apply atomic refractivity as structural descriptor and the solution of mathematical inequalities to obtain the quantitative relationships. These methods have been applied to study structure-activity relationships of many data sets by Hopfinger and Crippen, respectively. Perhaps the most popular example of the 3D QSAR is the com-... 

Smith PA, Sorich MJ, McKinnon RA, Miners JO. Pharmacophore and quantitative structure-activity relationship modeling complementary approaches for the rationalization and prediction of UDP-glucuronosyltransferase 1A4 substrate selectivity. J Med Chem 2003 46 1617-26. 

Hansch C. Quantitative approaches to biochemical structure-activity relationships. Acc Chem Res 1969 2 232-9. 

Van de Waterbeemd, H., Rose, S. Quantitative approaches to structure-activity relationships. In The Practice of Medical Chemistry, 2nd edn.,... 

Certain computational methodologies such as some approaches to quantitative structure-activity relationship (QSAR) studies use 3D ligand structures [37, 38]. These methods generally assume that a bioactive conformation has been estab-Hshed for a set of molecules and that these conformers can be ahgned in a maimer that reflects the relative orientation they would adopt in a binding site. It is thus... 

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