Focused compound libraries

XuE, L, Godden, J.W., Stahura, F.L, and Bajorath, J. A dual fingerprint-based metric for the design of focused compound libraries and analogs. 

Smaller compound sets and focused compound libraries can be used to screen more broadly for physiological phenotypes. In the typical high-content screening experiment, the effects of compounds on cellular assays are captured... 

Key Words Chemical diversity compound design diversity-oriented synthesis druglike compounds molecular properties natural products rule of five structure-activity relationship target-focused compound libraries. 

A new concept for combinatorial experimentation has been completed. Whilst it aims at the synthesis of focused compound libraries and at selecting the right reagent choices to conduct synthesis, it organizes around the same scaleable process used throughout the chemical synthesis process. Within this concept, variations of... 

Ligand-based Design of Focused Compound Libraries... 

The screening of either diverse or focused compound libraries can deliver a single molecule that has at least minimal activity at each of the targets of interest. To date, there have not been many reported examples of DMLs derived via the HTS approach. This could be due to the fact that HTS has only become the de rigeur method of lead generation... 

Preparation of a focused compound library The collection of chemically diverse compounds normally tested in an HTS (a few hundred thousands) can be replaced or complemented with analogues of known ligands, if these are known in-house or are available from public sources. The analogues are identified in the corporate collection by using the known ligands as queries in 2DLBVS. 

Scaffold diversity is an important parameter to characterize any compound collection. Organic synthesis is expected to provide efficient approaches to create three-dimensionally complex and structurally diverse small molecules. Branching pathways in DOS is an elegant approach to access scaffold diversity that could lead to small, yet diverse, focused compound libraries. Branching cascades strategy has successfully demonstrated the power and application of cascade or domino reactions in compound collection synthesis to build rapidly complex scaffolds for library synthesis. Further synthesis endeavors toward branching pathways... 

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