Combinatorial chemistry, drug synthesis

Keifer P, Eligh-resolution NMR techniques for solid-phase synthesis and combinatorial chemistry, Drug Discovery Today, 2(11) 468 478, 1997. 

Combinatorial chemistry, parallel synthesis, and solid-phase synthesis will continue to become more efficient and productive tools for the synthesis of compound libraries. Despite their still incomplete status, rationales about library diversity, drug-likeness, promiscuity... 

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 has played an increasing role in drug discovery. Wacker et al. extended the Madelung indole process successfully to solid phase library synthesis for the preparation of 2,3-disubstituted indoles. A number of examples follow in the table. 

Combinatorial chemistry, a new chapter of organic synthesis, is now developing rapidly. This new approach to synthesizing large designed or random chemical libraries through application of solid phase synthetic methods, promises to revolutionize the process of drug discovery in the pharmaceutical industry.24... 

Combinatorial chemistry has become of increasing importance, particularly within drug companies, in allowing the very rapid synthesis of large numbers of candidate molecules which require characterization and testing for their effectiveness. An important part of the characterization of any molecule is the determination of its molecular weight and LC-MS has been used extensively for this purpose. With... 

Miniaturization and parallelization key approaches for drug development apparatus for combinatorial chemistry UHTS 1536 titer-plate format modular construction of apparatus applications of UHTS fine-chemical synthesis by micro reactors numbering-up nature as model general advantages of micro flow vision of plants-on-a-desk [233]. 

P. A. Keifer 1998, (New methods for obtaining high resolution NMR spectra of solid-phase-synthesis resins, natural products, and solution-state combinatorial chemistry libraries), Drugs Future 23, 301-307. 

---