SAR information

The last step is to optimize the lead compounds. The computational methods in combination with SAR information has proved to be a powerful approach to determine areas on the molecule to expand, contract, or modify. Analogs of the lead compound are ranked using one or all of the following methods 1) qualitative predictions using molecular mechanics... 

The integration of combinatorial chemistry, structure-based library design and virtual screening [268, 269] also resulted in successful applications [270, 271]. It ultimately should result in broader SAR information about directionality and physicochemical requirements of acceptable building blocks. This concept is based on feasible scaffolds for exploring protein subsites using parallel or combinatorial synthesis. 

Two rounds of targeted libraries (2x44 and 2x88) were designed, synthesized, and assayed within 6 months. This effort led to a new lead matter 1819-1 with improved potency ( 10 folds), kinase selectivity (>100 folds), and better solubility ( 1 log unit or 10 folds) when compared with the original HTS hit Cpd-1. The extensive SAR information spanned by those 264... 

Chemists who design chemicals to contain carboxylate functionality can use the SAR information in Figure 4.1 to design carboxylic acids such that the likelihood for teratogenicity is minimized. Safer carboxylic acids would be those that contain, for... 

The problem is how to define different in the above question. If the molecules of the training set are too similar to those of the test set, this aspect of the validation is not very challenging for the model and, conversely, if they are too different from each other, there is a risk of depriving the training set of some key SAR information. Therefore, molecules kept for the test set should be neither too similar nor too different from the training set compounds. 

Encoding techniques offer a powerful approach to rapidly dissecting out significant SAR information from an entire library. Among the methods available, the chemically... 

As we mentioned earlier, betulin 4 differs from BA 1 only by a C-28 hydroxymethyl group rather than a carboxylic acid. To further verify our SAR information, diverse acid anhydrides were reacted with 4 and dihydrobetulin 25 to yield a group of 3,28-disubstituted compounds 26-37 (Table 13.2).35... 

Tanimoto index > 0.9 but may be very different in terms of activity (chemically similar, biologically diverse), while completely different strucmres are known to have the same biological activity (chemically diverse, biologically similar). This intrinsic drawback to the computational screening of virtual libraries should always be considered when interpreting screening results of a computationally designed library, and real data should be used to refine any virtual SAR information based on chemical similarity or dissimilarity. 

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