Directed combinatorial chemistry

Hogan JC Jr. Directed combinatorial chemistry. Nature 1996 384 suppl ... 

The Integration of Structure-Based Design and Directed Combinatorial Chemistry for New Pharmaceutical Discovery... 

Bone, R. Salemme, F.R. The integration of structure-based design and directed combinatorial chemistry for new pharmaceutical discovery. In Structure-Based Drug Design Veerapandian, P., Ed. Marcel Dekker, Inc. New York, 1997 525-539. 

JC Hogan. Combinatorial chemistry in drug discovery. Nat Biotechnol. 15(4) 328-330, 1997 JC Hogan. Directed combinatorial chemistry. Nature 384(6604 Suppl) 17-19, 1996. 

Real and virtual compound libraries Wild and elicited natural products Random and directed combinatorial chemistry Rationally designed molecules (from below)... 

The four major sources of starting material for drug screens are chemical libraries, natural products, specifically designed medicinal chemistry-derived drugs often modified and synthesized using directed combinatorial chemistry—and computationally designed drugs. 

The DCCA CL concept provides a unifying framework within which the various entities and processes considered above can be brought together in a coherent fashion. It emphasizes that informed diversity is the goal, not diversity by sheer number. It opens the way to the development of instructed, target- or property-directed combinatorial chemistry, i.e., of smart combinatorial chemistry, where the sought-after property does the driving ... 

Scheme 16. Directed combinatorial chemistry usingchemoenzymatically synthesized oligosaccharide building blocks.

Woodyer, R., van der Donk, W.A. and Zhao, H.M. (2006) Optimizing a biocatalyst for improved NAD(P)H regeneration directed evolution of phosphite dehydrogenase. Combinatorial Chemistry High Throughput Screening, 9, 237-245. 

Abstract. The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands. 

Fig. 18.3 Variation-based strategies. Left The SHAPES Linking Library [11] consists of drug-like scaffolds connected by linkers that are amenable to combinatorial chemistry (dashed line). Hits are followed up by synthesizing a combinatorial library in which the scaffolds are systematically varied. Center Directed Combinatorial Librari es [12] are comprised of scaffolds containing multiple sites for substituents. Hits are followed up by...

Enjalbal, C. Manx, D. Martinez, J. Combarieu, R. Aubagnac, J.-L. Mass Spectrometry and Combinatorial Chemistry New Approaches for Direct Support-Bound Compound Identification. Comb. Chem. High Throughput Screening 2001, 4,363-373. 

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