Combichem chemistry

CombiCHEM System (Fig. 3.9) For small-scale combinatorial chemistry applications, this barrel-type rotor is available. It can hold two 24- to 96-well microtiter plates utilizing glass vials (0.5-4 mL) at up to 4 bar at 150 °C. The plates are made of Weflon (graphite-doped Teflon) to ensure uniform heating and are sealed by an inert membrane sheet. Axial rotation of the rotor tumbles the microwell plates to admix the individual samples. Temperature measurement is achieved by means of a fiber-optic probe immersed in the center of the rotor. 

Davies, K., Briant, C. Combinatorial chemistry library design using pharmacophore diversity, http //www.netsci.org/ Science / Combichem/feature05. html. 

Some particular features of the analysis of products obtained by combinatorial methods have impaired the use of NMR spectroscopy in the initial phase of the development of this technique. Combinatorial chemistry produces large number of compounds in a very short period of time, in small quantities and instead of using traditional glassware for synthesis employs 96-well microtiter plates to store, transport and sometimes even to synthesize the compounds of interest. Another issue is the need to characterize solution and solid samples, since solid phase synthesis is extensively used in combichem. In this context, the need of an efficient and universal sample analysis remains a challenge. Actually, most combichem programs obtain mass spectrometry and UV (photodiode-array detection) data on their samples but clearly the use of NMR spectroscopy provides a structural characterization unparalleled by the aforementioned techniques. In the last years an increasing number of new NMR methods opened the possibility for the utilization of this analytical technique for monitoring combinatorial chemistry reactions. The first part of this chapter will focus on the recent developments introduced in NMR spectroscopy to overcome these difficulties. 

Davies, E.K. and Briant, C. Combinatorial Chemistry Library Design Using Pharmacophore Diversity. Accessible through URL http //www.awod.com/netsci/Science/Combichem/feature05.html. 

In 1997, Xiao et al. prepared the first C3 -N modified taxane library with 400 compounds by a radio-frequency encoded, solid-phase synthesis method. However, they did not report the biological assay data. Although combichem is a powerful tool in medicinal chemistry, only a few reports have appeared in this field to date, maybe because of the complexity in taxane structure and chemistry. 

In addition to quality control over compound collections, the issue of purity of synthetic libraries derived using combinatorial chemistry quickly came under the microscope. In the early to mid-1990s, combichem became a household word throughout the pharmaceutical industry and was believed to be a key technology that would revolutionize drug discovery. The basis of... 

Mjalli, A. M. M. and Toyonaga, B. E. (1995) Solid support combinatorial chemistry in lead discovery and SAR optimization http //www.netsci.org/Science/ Combichem/feature03.html. Net. Sci. 1. 

Profile Founded in 1994, this privately held company develops and provides integrated discovery chemistry technologies and services in collaboration with pharmaceutical, biotechnology, and fine-chemical companies to accelerate the drug discovery process. In these partnerships, the companies provide the biological capabilities and Combichem provides the chemical expertise of the discovery process. Its mission is to provide a highly efficient and successful approach to the discovery of new drug molecules. 

Borman, S. Rescuing combichem. Diversity-oriented synthesis (DOS) aims to pick up where traditional combinatorial chemistry left off. Chem. Eng. News 2004, S2(40), 32-40. 

Because of the impact of these newer methods, today one rarely sees a separatory funnel in a combichem laboratory. This chemistry is also comparatively "green" in that solvent needs can be greatly reduced and disposal of unwanted materials is simplified. 

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