Structure-activity relationships steric factors

Quantitative structure-activity relationships represent an attempt to correlate activities with structural descriptors of compounds. These physicochemical descriptors, which include hydrophobicity, topology, electronic properties, and steric effects, are determined empirically or, more recently, by computational methods. The success of a QSAR method depends on two factors the training dataset obtained by testing a group of chemicals and the descriptors obtained from some easily measurable or calculable property of the chemicals. 

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. 

To establish an exact structure-activity relationship all of these factors have to be taken into consideration. The steric problems present the greatest difficulty. Structure-activity relationships have been carried out mainly on the 6(7)-acylamino and cephem-3-methyl structure variations, which is far from enough, and it is the task of chemists to synthesize other derivatives for the biologists. 

A useful technique for analyzing structure-activity relationships which has come into use within the past five or so years is that pioneered by Corwin Hansch (19). Its underlying concept is that the relative biological activity of a derivative depends on the difference in hydrophobic, electronic, or steric factors between the derivative and the parent compound. The contribution of each effect to activity is assumed to be independently additive so that one has a linear free energy relationship. Equations of the form below are expected ... 

Integrating various factors, namely Taft s steric factor, resonance, inductive, Verloop steric parameters with the partition behaviour of drug molecules Hansch and Fuj ita exploited these principles in determining the establishing quantitative structure-activity relationship (QSAR) of drugs, which has rmdergone a sea change both in expansion and improvement with the help of computer researched softwares. 

A new structure-activity relationship, Xjj =yS+l, where y is a negative constant, S is the total steric effect, and 4 is the total inductive effect, correlated strongly with available measurements of ozonolysis. New rate coefficients were measured for ozonolysis of a number of unsaturated heteroatomic compounds and it has been emphasized that the inductive effect rather than the steric effect is important in predicting their reactivity %, the inductive effect index, was compared with the Taft a constant and rates of reaction of hydroxyl radical with a given species it correlated strongly in both cases (which should be unaffected by steric factors) suggesting a universal response by olefinic species towards electrophilic addition. ... 

Structure-activity relationships have been probed by the use of EPR. Thus rate constants, determined by EPR linewidth analysis, were in good agreement with those obtained by optical spectroscopy. This method not only provides rate data but also provides structural features which may allow the determination of structure-activity relationships combining kinetic, structural, and steric factors. The rearrangement rates of a range of 2-aryl-3,3-dimethylmethylenecyclopropanes have been measured in order to calculate and determine s values for a range of substituents. A range of substituents named super stabilizers were identified (43). ... 

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