Annual Reports in Combinatorial Chemistry and Molecular by Diane M. Coe, Richard Storer (auth.), W. H. Moos, M. R.

By Diane M. Coe, Richard Storer (auth.), W. H. Moos, M. R. Pavia (eds.)

Combinatorial chemistry and molecular variety methods to medical and novel product R & D have exploded within the Nineties. for instance, within the coaching of drug applicants, the automatic, permutational, and combinatorial use of chemical development blocks now permits the new release and screening of unheard of numbers of compounds. Drug discovery - larger, speedier, more cost-effective? certainly extra compounds were made and screened within the Nineties than within the final hundred years of pharmaceutical examine.
the second one quantity during this sequence comprises contributions on equipment, good stages, purification, research, carbohydrates, patent thoughts and strategies, range profiling and combinatorial sequence layout, and finishes with a survey of chemical libraries yielding biologically energetic brokers and a compendium of good part chemistry courses. every one contribution is ready through a well-known professional leading to a top quality account of the hot advances within the field.

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A. Key words: chromatography, HPLC, library, purification, SPE Summary In the early days of combinatorial chemistry, much attention focused on preparation of large libraries for lead discovery. Recently, though, the focus has shifted toward smaller, more focused libraries for lead optimization. These focused libraries generally consist of individual discrete compounds. Biological assay requirements often require compounds of high purity, thus development of automated high throughput purification methods has received new attention in the past several years.

Two groups have now reported preparative HPLC systems where fractionation decisions are based upon output from a mass spectrometer detector. The first preliminary report of such a system came from a collaboration between CombiChem and Sciex [21]. This system bases fractionation decisions on the output of a single ion mass chromatogram for the predicted molecular ion of the desired product. Reverse phase preparative HPLC is used in conjunction with electro spray ionization mass detection. A full report of this work has appeared in early 1998 [22].

42. 118 (1996) 13085-13086. E. , 38 (1997) 1333-1336. , Spraul, M. , Reduction of inhomogeneous line broadening in two-dimensional high-resolution MAS NMR spectra of molecules attached to swelled resins in solid-phase synthesis, 1. Am. Chern. , 119 (1997) 1787-1788. , Pochapsky, S. , MonitOring the progress of solidphase oligosaccharide synthesis by high-resolution magic angle spinning NMR: Observations of enhanced selectivity for f3-glycoside formation from a-J,2-anhydrosugar donors in solid-phase couplings, Angew.

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