Quantitative ligand-based

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

The ALIS quench method for dissociation rate measurement uses little protein and requires no biochemical assay for its implementation, yet the method readily yields quantitative values for the dissociation rates of the protein-ligand complexes. The technique can be used with pools of ligands to provide a quantitative rank ordering of the dissociation rates of all the components of the mixture. Since it is not necessary to know the exact concentrations of the ligands under study, the dissociation rate assessment can be performed using impure compounds, such as unpurified compound mixtures derived from combinatorial chemistry synthesis. The method does not require a foreknowledge of active protein concentration to measure and rank ligands based on their rates of dissociation. As such, the technique is self-contained and does not rely upon an external measure of protein activity as one of its input parameters. 

Although little structural information is available for the CYP enzymes, the amount of experimental data on the substrates and inhibitors is growing rapidly. As a result, ligand-based analyses, quantitative structure-activity relationship... 

Structure-based drug design approaches rely on the availability of structural information about protein-ligand complexes. In contrast, ligand-based approaches rely only on the experimental structure-activity relationships for ligands only. As discussed above, QSAR methods are typically used to find correlations between ligands binding affinities and their chemical descriptors. As an innovative use of QSAR approaches, several so-called receptor-dependent quantitative structure-activity relationship (RD-QSAR) methods have been... 

Bohl CE, Chang C, Mohler ML, Chen J, Miller DD, Swaan PW, et al. A ligand-based approach to identify quantitative structure-activity relationships for the androgen receptor. J Med Chem 2004 47 3765-76. 

---