Combinatorial chemistry library design

Davies, K. and Briant, C. Combinatorial chemistry library design using pharmacophore diversity. Netw. Sci. 1995, 1. Available at URL http //www.awod.com/netsci/lssues/ July95 /feature6.html. 

Key Words Combinatorial chemistry library design simulated annealing diversity analysis targeted library design drug-likeness multicriterion optimization. 

Key words LEAP, PGVL, combinatorial chemistry, library design, similarity search, disassembly,... 

Key words PGVL Hub, combinatorial chemistry, library design, reaction, synthesis protocol, reactant, product, enumeration, filtering, Chkl, kinase, inhibitor, SAR, ADME T (Adsorption, Distribution, Metabolism, Excretion, and Toxicity), selectivity, solubility, protein-ligand complex. 

A Polmski, RD Eemstem, S Shi, A Kuki. LiBrain Software for automated design of exploratory and targeted combinatorial libraries. In IM Chaiken, KD Janda, eds. Molecular Diversity and Combinatorial Chemistry Libraries and Drug Discovery. ACS Conf Proc Ser. Washington, DC Am Chem Soc, 1996, pp 219-232. 

Jagtap P, Baloglu E, Barron DM, Bane S, Kingston DG, Design and synthesis of a combinatorial chemistry library of 7-acyl, 10-acyl, and 7,10-diacyl analogues of paclitaxel (taxol) using solid phase synthesis, J. Nat. Prod., 65 1136-1142, 2002. 

Harness JR, Automation of high-throughput synthesis, Automated laboratory workstations designed to perform and support combinatorial chemistry, In Chaiken IM, Janda KD, eds., Molecular Diversity and Combinatorial Chemistry Libraries and Drug Discovery, ACS Conference Proceedings Series, Washington, DC, American Chemical Society, pp. 188-198, 1996. 

An increased interest in molecular similarity (or dissimilarity) has had a beneficial impact on the design of combinatorial chemistry libraries and because of this the diversity of compounds in a library has generally increased. More recently attention has also focused on drug-likeness of libraries (see Section IV.C.). This has brought about a change in the types and increase in the number of descriptors which are used in QSAR studies and this is discussed below. 

All of these demands require comparison of molecules, and therefore computation of molecular similarity is a major task in library design. When combinatorial chemistry started to become an important tool in medicinal chemistry, library design was focused mainly on synthetic accessibility, but today, all aspects of library optimization must be taken into consideration [4—7]. 

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

In the field of combinatorial chemistry, series design techniques can also help to improve the information/cost ratio of the libraries and to work in a more rational way. Indeed, the joint application of QSAR and CombC techniques and methodologies can lead to new promising approaches. 

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