Structure-activity relationships lead optimization

Modulated topochromatic vectors involve primary sites, grouped or not in equivalence sites, and also condens sites, cosites and complex equivalence sites. Condensed sites s are used to take account of the eventual gaps in the population. Introducing these sites in the description leads to a new S/HS generation in order to define the structural area associated with the experimental population where predictions will be conducted (lOf). Interaction sites Si and equivalence sites 5, are used to search for an optimal Structure-Activity relationship 5, account for some additivity deviations while 5, reflect regularities in information evolving. Modulated topochromatic vectors constitute a DARC/PELCO... 

The third step is to optimize the lead molecule through iterative chemical synthesis and biological testing, aiming to obtain molecules with the required potency (typically nanomolar), selectivity, bioavailability, and DMPK (drug metabolism and pharmacokinetics) properties. This step usually requires considerable time and resources usually the synthesis of hundreds of compounds is needed to deduce a robust SAR (structure-activity relationship). Such resources can be considerably reduced and the... 

Successful HTS campaigns often result in multiple lead pharmacophores that must be individually optimized through structure-activity relationship (SAR) studies. 

From interesting new ligands, a substructure or similarity search will reveal compounds that can be tested by the same NMR methods, so that some knowledge about the structure-activity relationship is built up. This can lead to optimization of the ligand and to increased binding affinity, although improvement by more than an order of magnitude... 

Lead optimization Application of early ADMET predictive techniques, structure-activity relationships and medicinal chemistry testing of homologs... 

Normally it is hardly feasible nor necessary to explore a certain parameter space to the full theoretically possible extent. Rather certain areas of parameter space are examined. These areas can be determined by intuition, synthetic accessibility or by structure-activity-relationships and structure-activity-hypotheses. Consider for example structure 6 to, be a lead compound which needs to be optimized with respect to an activity profile consisting of two components, i.e. potency and oral effectivity (gastro-intestinal absorption). Let us for simplicity assume that we want to confine ourselves to variations of the substituent in 4-position (7) and that we... 

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