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In addition, a graphical representation has been designed to simultaneously monitor potency changes for multiple analog series as a consequence of defined substitutions.
The NBH approach is based upon numerical values and thus well suited for potency prediction during compound optimization considering multiple analog series.
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Furthermore, we have extended the concept of MMPs to matched molecular series, i.e., analog series with different molecular core structures but corresponding substitution patterns [5, 6].
Each row contains an individual analog series, i.e., compounds sharing the same core.
Entry 10: A graphical data structure termed combinatorial analog graph (CAG) is introduced to systematically organize analog series on the basis of substitution patterns and identify subsets of analogs having high in SAR information content.
Large structural changes were made leading to multiple analogs with comparable or improved potency.
The preliminary structure activity data obtained with these new analogs suggest the importance of the length of the methylene linker in the bis-analog series.
The method is also applicable to explore other aspects of SAR transfer such as comparative learning from multiple compound series with varying degrees of chemical exploration, which often results in suggestions for the design of new analogs.
Fig. 1 Protocol for acquiring multiple tilt series.
There are multiple case series that support their effectiveness.
Multiple case series for proprietary technologies have been published.
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