Combinatorial chemistry compound libraries

Solid phase peptide synthesis, as described by Merrifleld in 1963 [7], has opened the way for supported organic synthesis as a widely employed technique facilitating the preparation of a large number of compounds. These techniques lie behind combinatorial chemistry and library synthesis. Solid supports such as cross-linked polystyrene beads have been widely used [8]. The success of this approach relies mostly on the ease of product purification and isolation, usually by simple operations such as washing and filtration, which makes automation possible. At the... 

Memfield s concept of a solid phase method for peptide synthesis and his devel opment of methods for carrying it out set the stage for an entirely new way to do chem ical reactions Solid phase synthesis has been extended to include numerous other classes of compounds and has helped spawn a whole new field called combinatorial chemistry Combinatorial synthesis allows a chemist using solid phase techniques to prepare hun dreds of related compounds (called libraries) at a time It is one of the most active areas of organic synthesis especially m the pharmaceutical industry... 

The major impetus for the development of solid phase synthesis centers around applications in combinatorial chemistry. The notion that new drug leads and catalysts can be discovered in a high tiuoughput fashion has been demonstrated many times over as is evidenced from the number of publications that have arisen (see references at the end of this chapter). A number of )proaches to combinatorial chemistry exist. These include the split-mix method, serial techniques and parallel methods to generate libraries of compounds. The advances in combinatorial chemistry are also accompani by sophisticated methods in deconvolution and identification of compounds from libraries. In a number of cases, innovative hardware and software has been developed tor these purposes. 

Combinatorial chemistry (Section 27.18) A method for carrying out a large number of reactions on a small scale in the solid phase so as to generate a library of related compounds for further study, such as biological testing. 

Although the reciprocal approach potentially enables the screening of large numbers of compounds, only the advent of combinatorial chemistry brought about the tools required for the synthesis of large libraries of potential selectors in a very short period of time. In addition, using the methods of combinatorial chemistry, novel strategies different from those of the reciprocal approach could also be developed. 

To speed the process of drug discovery, combinatorial chemistry> has been developed to prepare what are called combinatorial libraries, in which anywhere from a few dozen to several hundred thousand substances are prepared simultaneously. Among the early successes of combinatorial chemistry is the development of a benzodiazepine library, a class of aromatic compounds much used as antianxiety agents. 

Precisely defined collections of different chemical compounds are denominated as chemical libraries that can be efficiently prepared by methods of combinatorial chemistry. Each chemical compound owes specific structural, steiic, and electronic properties that determine all possible interactions of the small molecule with a given protein or receptor. The molecule s properties are based on the steiic arrangement of functional groups, including the conformations that can be attained by a specific structure. 

Combinatorial Chemistry. Figure 2 Chemical libraries are prepared either by parallel synthesis or by the split-and-recombine method. In the latter case, coupling m building blocks in m separated reaction flasks through n synthetic cycles on a beaded polymer carrier generates a combinatorial library with nf individual compounds and one compound per bead. 

Colony-stimulating Factors Combinatorial Chemistry Compartment Competitive Antagonists Complement System Complement-type Repeat Complex Disease Compound Libraries Compound Optimization Computational Biology Computerized Tomography COMT... 

---