Combinatorial Chemistry Review

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Chemical Building Block
One of a number of interchangeable reagents which can be used in combinatorial library synthesis, part of the structure of which becomes incorporated into the final product, i.e. its residue.

A collection of two or more library members, building blocks or reagents; preferred notation in the Journal of Combinatorial Chemistry and convenient for describing synthetic procedures on pools of compounds.

Process of releasing a compound from a solid support, thereby permitting assay or analysis of the compound by solution-phase methods. Dissolution of the compound following cleavage, rather than the cleavage step itself, may be rate-limiting.

Group of compounds which are related by structural or behavioral properties. Organizing a set of compounds into clusters is often used in assessing the diversity of those compounds, or in developing SAR (structure-activity relationship) models.

Combinatorial Chemistry
The use of chemical methods to generate all possible combinations of chemicals starting with a subset of compounds. The building blocks may be peptides, nucleic acids or small molecules. The libraries of compounds formed by this methodology are used to probe for new pharmaceutical reagents.

Combinatorial Organic Synthesis
A key feature of combinatorial techniques is that compound synthesis can be designed such that a range of structures can be produced simultaneously as mixtures in the same reaction vessel or individually in parallel using semi- automated synthesis. The repetitive nature of the synthetic processes involved in most combinatorial applications lends itself to automation or semi- automation. This key feature means that the bench chemist can single- handedly prepare tens, hundreds, or thousands of compounds of known structures in the time that it would take to prepare only a few pure entities by orthodox methodology.

Combinatorial Library
A set of compounds prepared by combinatorial chemistry. May consist of a collection of pools or sub-libraries.

Property of a solid support prepared from polymeric materials with interconnected strands. Often results from the inclusion of multifunctional monomers in the polymerization reaction, e.g. divinylbenzene in polystyrene production. In such cases, the degree of crosslinking is often quoted as the proportion of the multifunctional monomer in the reaction mixture. The extent of crosslinking is important for physical properties of the solid support, such as the propensity to swell in different solvents.

Cyclative Cleavage
Cleavage resulting from intramolecular reaction at the linker which results in a cyclized product. The cleavage may also act as a purification if resin-bound side-products are incapable of cyclizing, and thus remain attached to the solid support on release of the desired material.

Custom Synthesis
used for the production of organic drug compounds to the specification of the client for the their specific development and research needs.