Chemical structure activity relations

Szabo S, Reynolds ES, Unger SH. 1982. Structure-activity relations between alkyl nucleophilic chemicals causing duodenal ulcer and adrenocortical necrosis. J Pharmacol Exp Ther 223 68-76. 

Snell, E. E., Chemical structure in relation to biological activities of vitamin B8. Vitamins and Hormones 16, 77-125 (1958). 

Albert, A. 1973. Structure-activity relations. In Selective Toxicity the Physico-Chemical Basis of Therapy. London Chapman and HaU chapter 7. 

The toxicology of a solvent is determined by many factors, such as bioavailabihty, metabolism, and the presence of structural features that may attenuate or enhance the reactivity of the parent molecule. Despite the structure-activity data available for many classes of commercial chemical substances, chemists have not recognized the use of structure-activity relations as a rational approach for choosing or designing new, less toxic commercial chemical substances. With qualitative structure-activity relationships, comparing the structures of the substances in the series with corresponding effects on the toxicity makes the correlation between toxic effect and structure. Through these, it may then be possible to predict a relationship between structure and toxicity... 

Mathre, D.E. (1971) Mode of action of oxathiin systemic fungicides. Structure-activity relations. J. Agric. Food Chem. 19(5), 872-874. McCall, P.J., Swann, R.L., Laskowski, D.A., Unger, S.M., Vrona, S.A., Dishburger, H.J. (1980) Estimation of chemical mobility in soil from liquid chromatographic retention times. Bull. Environ. Contam. Toxicol. 24, 190-195. 

Schmieder PK, Ankley G, Mekenyan O, Walker JD, Bradbury S. 2003. Quantitative structure-activity relation models for prediction of estrogen receptor binding affinity of structurally diverse chemicals. Environ Toxicol Chem 22 1844-1854. 

Structure-activity relations within chemical series have helped establish whether specific scaffolds and substitutions are an integral part of the Kvl.5 pharmacophore, or simply help display it. Frequently, property changes unrelated to Kvl.5 activity, such as unacceptable pharmacokinetic profiles, have prevented a thorough understanding of a particular pharmacophore. Other times, detailed pharmacophore characterization is compromised by a need to preserve or improve desirable properties in addition to Kvl.5 activity, such as oral bioavailability [43] or P-glycoprotein susceptibility, a predictor of reduced brain exposure [50]. 

Other Examples of the Use of Principal Properties Characterization by principal properties has been reported for classes of compounds in applications other than organic synthesis Aminoacids, where principal properties have been used for quantitative structure-activity relations (QSAR) of peptides [64], Environmentally hazardous chemicals, for toxicity studies on homogeneous subgroups [65]. Eluents for chromatography, where principal properties of solvent mixtures have been used for optimization of chromatographic separations in HPLC and TLC [66],... 

The PLS method was developed by H. Wold [71] and has been further developed and extended to chemical systems by S. Wold [72], A tutorial paper on the method is given in [73]. An important area of application of PLS is in the field of quantitative structure-activity relations [64a, 74]. The applications of PLS for multivariate calibration in analytical chemistry has been thoroughly treated by Martens and Naes [75]. As we shall see, PLS is also a very useful in organic synthesis. 

The relationship between a chemical s structure and its biological action has been studied extensively for over a century (16). In cases where there is not a complete understanding of the mechanism/mode of action or where the influence of functional groups is not known or obvious, there is a vast body of knowledge on how different structural features within a class of chemicals may correlate with various levels of hazard. Structure-activity relations (SAR) or their mathematical treatment. Quantitative SAR (QSAR) have been developed for myriad endpoints including cancer, developmental and reproductive effects, aquatic toxicity, boiling points, water solubility and many others hazard endpoints. An instructor therefore has many opportunities to incorporate the concept of SAR at several points in the curriculum. 

Brezonik, P. L. (1990) Principles of Linear Free Energy and Structure Activity Relations and Their Application to Chemicals in Aquatic Systems. In Aquatic Chemical Kinetics, W. Stumm, Ed., Wiley-Interscience, New York. 

Applications of pattern recognition methodology to chemical problems were first reported in the 1960 s (20,21) with studies of mass spectra. Since then papers have described work in a variety of areas (22,23) including mass spectrometry, infrared spectroscopy, NMR spectroscopy, electrochemistry, materials science and mixture analysis, and the modeling of chemical experiments. Diagnosis of pathological conditions from sets of measurements made on complex biological mixtures, e.g., serum, have been reported (24). The successes in these areas have led to the belief that these methods should prove useful in the development of structure-activity relations. 

An extensive screening of structure-activity relations revealed ( 1 ) the outstanding properties of N,N -disubstituted PD. It is generally accepted that the presence of N-sec.alkyls accounts for better antiozonant protection than that of N-prim. and N-tert.alkyls or N-aryls (21). This may be one of the clues to decipher the chemical pathways of the antiozonant mechanism. The final effect is moreover fully dependent on the composition of the vulcanizate. The structure of commercially used antiozonants is an optimum compromise of efficiency, physical properties and toxicity. N, N -Disec.alkyl-1-4-PD are used in the U.S.A., N-sec.alkyl-N -aryl-l,4-PD are preferred in Europe. N,N -Diaryl derivaties are not applied as antiozonants in NR, BR, IR, or SBR. One of the reasons may be their low solubility in rubber vulcanizates (22). It does not allow them to reach a concentration level in the rubber bulk which is able to act as a long-term operative store of a stabilizer ready to supply the rubber surface slowly but continuously with active compounds by migration and to maintain the protective effect without inefficient quick blooming of an incompatible PD. A chemical reason accounting for the minority antiozonant role of N,N -diaryl PD is discussed later. 

J, J. Kaufman, bit. ]. Quantum Chem., 16(2), 221 (1979). Quantum Chemical and Physico-Chemical Influences on Structure-Active Relations and Drug Design. 

To study the structure-activity relation of the metallocene dihalides, the influence of chemical variation upon the tumor-inhibiting activity was investigated. Principally, a metallocene dihalide molecule offers thfee different positions to be modified (Figure 1) (i) At the position of the central metal atom M, one... 

In the 1980s, our group began to screen microbes for insecticidal compounds that could be used in practice, or become lead compounds for the generation of new carbon skeletons. As a result, various strains were found to exhibit insecticidal, convulsive and paralytic activities against silkworms. This chapter deals with the procedures used for isolation of bioactive strains and their active principles. An overview of their chemical structures, activities, synthesis, and structurally related compounds is also given. 

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