Current Medicinal Chemistry - Volume 9, Issue 23, 2002

With the successful completion of the human genome sequencing and the resulting plethora of genetic information now available novel technologies and applications have to be established to translate the huge amount of data generated into successful biological and biomedical research programs. The integration of various drug discovery disciplines within the parallel quest for novel targets and new molecular e Read More

Multi-component reactions (MCRs) enable the facile, automated and high throughput generation of small organic molecules. MCRs have been used to create diversity oriented and biased combinatorial libraries, to accomplish the synthesis of highly complex natural products as well as for the large-scale production of drug candidates. This provides medicinal chemists with a powerful tool to create novel chemical diversity, mat Read More

Recent developments in combinatorial molecular design using virtual screening methods are summarised. These include similarity-based compound clustering techniques, structure-based docking and scoring, and fragment-based de novo design. Three major trends have been identified: i) the design of small targetfocused compound libraries yielding activity-enriched sets of molecules, ii) advanced prediction m Read More

Although resin-based chemistry offers many practical advantages over conventional solution phase for the synthesis of combinatorial libraries, effective monitoring of reactions conducted on the support remains a challenge. A number of techniques have been developed to enable the analysis of solid phase organic synthesis either by monitoring the resin-bound species directly or by the analysis of small quantities of m Read More

Natural products are biologically validated starting points for the design of combinatorial libraries, as they have a proven record of biological relevance. This special role of natural products in medicinal chemistry and chemical biology can be interpreted in the light of new insights about the domain architecture of proteins gained by structural biology and bioinformatics. In order to fulfil the specific requirements of the individ Read More

Polymer-supported catalysts and reagents have found many uses in synthetic organic chemistry. This review discusses the preparation of polymer-supported phosphine ligands and organometallic complexes formed using these and highlights their use in reactions that are of particular interest to medicinal chemists. The scope of the review is limited to phosphine ligands and their metal complexes attached to derivitised polystyr Read More

The Combinatorial Centre of Excellence (CCE) offers a unique opportunity for the exploitation of a broad range of combinatorial methodologies. Many areas of activity are under investigation, including high-throughput X-ray of small molecules, parallel polymer chemistry and the development of new multi-component reactions.

Acceleration of the drug discovery process in pre-clinical pharmaceutical research is a highly desirable goal and combinatorial chemistry united with automation technology promised to accomplish this task. Through the accumulation of experience with automated devices over time it became evident that only by harmonisation and streamlining of work-flow procedures the efficiency of the overall process can be impro Read More