General Structure-Activity Relationships

Chemical class No. of compounds Active/inactive Mean RBAa) 

By considering the SARs observed in bioassays with knowledge of the crystal structure of receptor-androgen receptor interactions, Fang et al. [30] were able to make statements about the chemical structures most likely to be associated with binding to the AR. These are summarized in Table 18.3. 

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The pharmacological activity of LAs is determined by several physicochemical properties including lipophilicity, protein binding, and pKa which can be explained by their mechanism of action. A general structure - activity relationship was described by Courtney and Strichartz (1987), according to which an increase in the hydrophobicity leads to a parallel increase in anesthetic... 

The data shown in Tables 1 and 2 are intended to provide an indication of the data base constraints within which such a review of the toxicity of heterocycles must be written. Clearly, in the absence of detailed and expensive bioassays of every new chemical, potential toxins cannot be anticipated unless some general structure-activity relationships are established and employed prospectively. An attempt to meet this need, or at least to delineate how it may be met, forms the basis of the present chapter. 

Lee C-C, Liu Y, Reineke TM (2008) General structure-activity relationship for poly(gly-coamidoamine)s the effect of amine density on cytotoxicity and DNA delivery efficiency. Bioconjug Chem 19(2) 428—440... 

There is now an ongoing interest to develop highly selective inhibitors also against certain other phosphodiesterases, because general structure-activity relationships can be transferred from one PDE isoenzyme to others [37]. 

Hansch and Fujita used a Gaussian probability function to characterize the partitioning Step 1 and the Hammett function (log(k/k0) = pa) to describe the rate Step 2 in their model (10,12,13). By appropriate mathematical treatment, they arrived at the following general structure-activity relationship which has come to be termed the Hansch Equation. 

From this, some general structure-activity relationships could be concluded (Fig. 8.54) ... 

Based on the data generated from susceptible-TSM, a general structure-activity relationship can be formulated. The rule-of-thumb is to keep the rings and double bond as planar as possible. The structure-activity rules are shown schematically in Figure 2. Replacement of the vinyl halogens with methyl groups does not decrease activity. The vinyl hydrogen can be replaced with fluorine and the molecule retains the activity. Substitution at the four-position of the thiophene does not adversely affect... 

The general structure-activity relationship for the bithiophenes, 2, appears identical to that for the dihalovinyl derivatives, 1. For example, 3,4-diaryl-2,2 -bithiophenes would be inactive due to steric crowding of the aryl and thiophene rings causing non-planarity of the pi-system. Also, a substituent in the 4-position of the central thiophene ring of 2 causes a decrease in activity. 

These parameters were used as input for the basis for the more general structure-activity relationship (applicable to alcohols and ethers) developed below. 

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