Structure-activity relationship research

Chapter 12 gives an overview about pattern recognition applications in chemistry. Chapters 13 to 20 extensively describe applications in spectral analysis, chromatography, electrochemistry, material classification, Structure-activity-relationship research, clinical chemistry, environmental chemistry and classification of analytical methods. 

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. 

J. P. Hu and co-workers. Structure Activity Relationship oJFlavonoids with Superoxide S cavenging Activity, Biological Trace Element Research, Vol. 47, The Humana Press Inc., Clifton, N.J., pp. 327—331, 1995. 

Exploratory research on structure activity relationships in the meperidine series revealed the interesting fact that the oxygen atom and carbonyl group of this molecule could often be interchanged. That is, the so-called "reversed meperidine" (C) still exhibits analgesic activity in experimental animals. (Note that, except for the interchange, the rest of the molecule is unchanged.)... 

The structure activity relationships ( SAR) of newly synthesized analogues of nucleosides, xanthine heterocycles, and nonxanthine heterocycles have been explored at the ARs. Potent and selective AR antagonists have been prepared for all four subtypes [3, 4], and selective agonists are known for three subtypes [1]. Thus, numerous pharmacological tools are available for in vitro and in vivo use (Table 2). Potent and selective A2b AR agonists are yet to be repotted, although several research groups have identified lead compounds. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

Anderson, G.M. Braun, G. Braun, U. Nichols, D.E. and Shulgin, A.T. Absolute configuration and psychotomimetic activity. In Barnett, G. Trsic, M. and Willette, R., eds. Quasar Quantitative Structure Activity Relationships of Analgesics, Narcotic Antagonists, and Hallucinogens. National Institute on Drug Abuse Research Monograph 22. Rockville, MD the Institute, 1978. pp. 8-15. 

Makriyannis A, Banijamali A, Van der Schyf C, Jarrell H. The role of cannabinoid stereochemistry and absolute configuration and the orientation of A9-THC in the membrane bilayer. Structure-activity relationships of cannabinoids. In Rapaka RS, Makriyannis A, eds. Interactions of Cannabinoids with Membranes. National Institute on Drug Abuse Research Monograph 79. Rockville, MD US Department of Health and Human Services, 1987. 

Among the possible alternative methods, in vitro assay (for ATMs) and quantitative structure-activity relationships (QSARs) models (for ANTMs) are the most applied approaches in the toxicological and ecotoxicological evaluation of chemicals profiles, even in the field of environmental research and risk assessment. 

Pearlman, R. S. (1980) Molecular surface areas and volumes and their use in structure/activity relationships. In Physical Chemical Properties of Drugs. Yalkowsky, S.H., Sinkula, A.A., Valvani, S.C., Eds., Medicinal Research Series, Vol. 10, pp. 321-317, Marcel Dekker, New York. 

Figure 8.1 Environmental degradation scheme tor tributyltin and triphenyltin compounds. (Modified from Smith, P.J. 1978b. Structure/Activity Relationships for Di- and Triorganotin Compounds. I.T.R.I. Rep. 569. 16 pp. Avail, from International Tin Research Institute, Greenford, Middlesex, U.K. and Eisler, R. 1989. Tin hazards to fish, wildlife, and invertebrates a synoptic review. U.S. Fish Wildl. Serv. Biol. Rep. 85(1.15). 83 pp.

Smith, P.J. 1978b. Structure/Activity Relationships for Di- and Triorganotin Compounds. I.T.R.I. Rep. 569. 16 pp. Avail, from International Tin Research Institute, Greenford, Middlesex, U.K. 

Anderson, G. M., Ill, Castagnoli, N., Jr., and Kollman, P. A. (1978) Quantitative structure-activity relationships in the 2,4,5-ring substituted phenylisopropylamines. In NIDA Research Monograph Series 22, edited by G. Barnett, M. Trsic, and R. Willette, pp. 199-217. U. S. Govt. Printing Office, Washington, D. C. 

The basic paradigm underlying the field of research broadly referred to as quantitative structure-activity relationship (QSAR) modeling is that the structure of the chemical determines its activity ... 

Baeten, A., Tafazoli, M., Kirsch-Volders, M., and Geerlings, P. 1999. Use of the HSAB principle in quantitative structure-activity relationships in toxicological research Application to the genotoxicity of chlorinated hydrocarbons. Int. J. Quantum Chem. 74 351-355. 

P. Stutz, H. Aschauer, J. Hildebrandt, C. Lam, H. Loibner, I. Macher, D. Scholz, E. Schiltze, and H. Vyplel, in A. Nowotny (Ed.), Endotoxin Research Series, Vol. 1, Cellular and Molecular Aspects of Endotoxin Reactions Chemical Synthesis of Endotoxin Analogs and Some Structure Activity Relationships, p. 129. Elsevier, Amsterdam, 1990. 

Williams GM, Mori H, McQueen CA. 1989. Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals. Mutation Research 221 263-286. 

Fujino, T., Une, M., Imanaka, T., Inoue, K. and Nishimaki-Mogami, T. (2004) Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation. Journal of Lipid Research, 45, 132-138. 

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