Diversomers

Moroder, L. Lutz, J. Grams, F. Rudolph-Bohner, S. Osapay, G. Goodman, M. Kolbeck, W. A New Efficient Method for the Synthesis of 1,4-Ben-zodiazepine-2,5-dione Diversomers, Biopolymers 1996, 38, 295. 

Recent literature contains a multitude of examples of synthetic organic methodologies which have been optimized and applied to the solid-phase synthesis of combinatorial libraries [2]. In fact, the production of a number of these libraries has been realized on such systems as the Multipin SPOC [8], the DIVERSOMER [9] and the OntoBLOCK [10], All three apparatuses allow the automated production of spatially dispersed combinatorial libraries and facilitate the isolation, identification, screening and archiving of single compounds in distinct physical locations which are crucial factors during lead discovery and optimization. 

Scheme 3. Examples of libraries synthesized using the DIVERSOMER system.

The synthesis ofnon-oligomeric compounds such as highly substituted benzodiazepines 3, hydantoins 4 and quinolones 5 (Scheme 3) has been successfully automated at Parke-Davis using the DIVERSOMER system [9],... 

DIVERSOMER Technologies Inc. and Parke-Davis Pharmaceutical Research,... 

Workers at Parke-Davis reported the DIVERSOMER method in 1993 [63,64] which utilized proprietary reactors in combination with a Tecan robot. This technology has been implemented to generate libraries ofhydantoins [63-66,95], benzodiazepines [63-66, 95], and quinolones [67,96,97] by solid-phase synthesis. 

Hobbs De Witt S, Kiely JS, Stankovic CJ, Schroeder MC, Reynolds Cody DM, Pavia MR, Diversomers an approach to nonpeptide, nonoligomeric chemical diversity, Proc. Natl. Acad. Sci. USA, 90 6909-6913, 1993. 

Moroder L, Lutz J, Grams F, Rudolph-Bohner S, Osapay G, Goodman M, Kolbeck W, A new efficient method for the synthesis of 1,4-benzodiazepine-2, 5-dione diversomers, Biopolymers, 38 295-300, 1996. 

E. Diversomer Technology by Parke-Davis Pharmaceutical Research Division... 

The Diversomer 8-pin Synthesizer is one of the first examples of a technology developed entirely by researchers in a pharmaceutical company and successfully... 

DeWitt SH, Czarnik AW, Combinatorial organic synthesis using Park-Davis Diversomer method, Accounts Chem. Res., 29 114-122, 1996. 

DeWitt SH, Schroeder MC, Stankovic CJ, Czarnik AW, Diversomer technology solid phase synthesis, automation, and integration for the generation of chemical diversity, Drug. Dev. Res., 33 116-124, 1994. 

Such companies typically have 100-plus in vitro tests for lead compounds, which they test against collections of receptors and intracellular molecules of pharmacological interest. They will also offer their screening capabilities to partners and such companies include Aurora, Diversomer, Orchid, Pharmacopeia and others. These companies can be considered as library value-adders, because they take libraries whose value is meaningless without identified leads and add value by filtering those libraries through appropriate screening assays. 

SH DeWitt, JS Kiely, CJ Stankovic, MC Schroeder, DMR Cody, MR Pavia. DIVERSOMERS an approach to non-peptide non-oligomeric chemical diversity. Proc Natl Acad Sci USA 90 6909-6913, 1993. 

In 1993, DeWitt et al. described the Diversomer apparatus [57-59], which is one of the first reaction apparatus designed exclusively for the parallel synthesis of small molecules. Pipetting machines dispense reagents and solvents into vials that are located in a custom-... 

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