Library design, computational aspects

Although the above-mentioned aspects of computational library design are multifaceted and complex, they can be tackled systematically using a comprehensive library design tool that employs the principle of multicriterion... 

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]. 

Computational Aspects of Library Design and Combinatorial Chemistry... 

This paper reviews recent advances on computational aspects of molecular diversity, with particular emphasis on methodology and applications. There are probably as many different definitions of diversity as the number of researchers who are active in the field, and it is our belief that theoretically the subject borders on religion. However, many of the concepts described herein are now routinely employed in combinatorial library design, and the choice of methods has definitive and measurable practical implications. The article is divided into three main sections that address issues... 

The business plan can serve as a suggestion on the material that should be gathered, analyzed, and organized. A design project may involve mostly library search and computation, but a laboratory component would be splendid. The following aspects should be covered ... 

Another aspect in many companies is the diversity of the compound pool. Typically, it contains many molecules with high structural similarity because they were prepared during lead optimization in which only slight variations on the architecture of the molecules were performed. The design and synthesis of diverse combinatorial libraries according to computational methods described in Chapter 1.6, and may contribute towards improving the overall diversity of a compound collection with respect to lead finding. 

With increasing importance being attached to the early detection of compounds likely to be problematic from an absorption, distribution, metabolism, and excretion (ADME) viewpoint, " at RPR we sought to apply computational measures for the prediction of intestinal absorption—a key requirement for an orally bioavailable compound—during the design of lead optimization libraries. To this end, we implemented the popular rule-of-5 criteria described by Lipinski et al. compound is deemed to fail the rule-of-5 check (and thereby to be possibly deficient from an oral absorption/permeability aspect) if it possesses two or more of the following features ... 

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