Combichem

RS Pearlman. Novel software tools for addressing chemical diversity. Network Sci 1996. http //www.awod.com/netsci/Science/Combichem/feature08.html... 

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. 

The group of Grieco has presented a method for efficiently performing macrocy-clizations on a solid phase (Scheme 7.31) [48]. The preparation of the macrocyclic peptides required several standard transformations, which are not described in detail herein. The final intramolecular nucleophilic aromatic substitution step was carried out under microwave irradiation at 50 °C in a dedicated CombiCHEM system (see Fig. 3.9) utilizing microtiter plates in a multimode batch reactor. The cycli-zation product was obtained in good yield after a reaction time of 10 min and sub-... 

A recent study concerned the microwave-assisted parallel synthesis of di- and tri-substituted ureas utilizing dedicated 96-well plates in the CombiCHEM system [60], In a typical procedure, modification of the Marshall resin utilized was achieved by treatment with p-nitrophenyl chloroformate and N-methylmorpholine (NMM) in dichloromethane at low temperatures. The resulting resin was further modified by attaching various amines to obtain a set of polymer-bound carbamates (Scheme 7.48). 

ChemDraw Ultra 7.0, Chem3D Ultra 7.0, and ChemFinder Pro 7.0 became available in 2002. E-Notebook Ultra 7.0, BioAssay Pro 7.0, MOPAC, Gaussian GAMESS interfaces, ChemSAR Server Excel, CLogP, Purchasing for Excel, CombiChem/Excel, as well as the full set of Chemlnfo databases, including ChemACX ChemACX-SC, The Merck Index and ChemMSDX have been added to ChemOffice Pro. 

I warmly thank the enthusiastic group of coworkers cited in the references for their intellectual and experimental contributions to this project. I also thank the National Science Foundation, the National Institutes of Health, Warner-Lambert, Combichem, and Merck for funding our work in this area. 

Lynn Caporale is vice president of strategic development at CombiChem, Inc, La Jolla, California. 

Most of the screening technology for CombiChem was developed for the use under conditions of 20 to 40°C and ambient pressure. 

The wealth of analytical techniques that was applied for CombiChem was devoted to biochemical challenges. 

As vitally important as the capabilities for experimental planning, screening, and data analysis are the procedures for preparation of inorganic catalysts. In contrast to the procedures usually applied in conventional catalyst synthesis, the synthetic techniques have to be adapted to the number of catalysts required in the screening process. Catalyst production can become a bottleneck and it is therefore necessary to ensure that HTE- and CombiChem-capable synthesis technologies are applied to ensure a seamless workflow. 

The basis of the single-bead concept is the use of single-shaped bodies as the catalytic material of interest. These particles may in principle be of any shape, but usually spherical particles are applied. In accordance with approaches known from CombiChem, such spherical particles are called beads, although they fulfill veiy different functions in comparison to their application in combinatorial setups... 

Try and classify different approaches of DOE according to their usefulness for different types of work in HTE and CombiChem. Try to rank the approaches and name thepros and cons. 

Derra, S., Combichem Excels at Speed, but Machines Lack Insight, in http // www.dddmag.com/ ShowPR.aspx PUBCODE=016 ACCT=1600000100 ISSUE=0409 RELTYPE=PR ProdCode =00000000 PRODLETT=C 2004. 

One approach to screening subsets of available compounds is to screen sets of compounds that, although not representative of the molecular diversity of the available compound collection, do contain as much structure activity relationship information as possible. An example of this was the Informer Library strategy proposed by CombiChem (which was eventually purchased by DuPont Pharmaceuticals in 1999) (23). Unfortunately, there have been no published applications of this screening strategy that assess its success or failure. 

Approximately 1,200 amines and 300 carboxylic acids were selected for inclusion in the fragment libraries, from which approximately 20 fragment libraries were synthesized. These libraries yielded 2,000 products with sufficient purity (>95%) and quantity (1.2 mL of 30 xM solution), and the product structures were confirmed via ID NMR. This fragment collection became known as the NMR Combicores to denote their purpose and their combichem origin. It was distributed across several major Pfizer research sites and used in multiple fragment screens. 

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