Small compound library

Sometimes, a straightforward natural product isolation route, irrespective of bioactivity, is also applied, which results in the isolation of a number of natural compounds small compound library) suitable for undergoing any bioactivity screening. However, the process can be slow, inefficient and labour intensive, and it does not guarantee that a lead from screening would be chemically workable or even patentable. 

A number of library design tools have been developed by Merck s molecular modeling group to facilitate the design of compound libraries for various purposes, such as small compound libraries in support of specific medicinal chemistry projects or large compound... 

Chen C, Ahlberg Randall LA, Miller RB, Jones AD, Kurth MJ, Analogous organic synthesis of small-compound libraries Validation of combinatorial chemistry in small-molecule synthesis, J. Am. Chem. Soc., 116 2661-2662, 1994. 

For these reasons it is not advisable to analyze small-compound libraries by direct injection of the library. On the other hand, the mass spectra of libraries containing several hundreds to thousands of compounds tend to show the expected gaussian-like mass distribution around the average molecular mass. This kind of fingerprinting , which was advanced especially for the analysis of large-peptide libraries, may be accepted for synthesis control of a library, but the evaluation of mass spectra yields only qualitative information. Exact assignment of the compounds is impossible. 

Chel994 Chen, C., Randall, L.A.A., Miller, R.B., Jones, A.D. and Kurth, M.J., Analogous Organic Synthesis of Small-Compound Libraries Validation of Combinatorial Chemistry in Small-Molecule Synthesis, J. Am. Chem. Soc., 116 (1994) 2661-2662. 

The term enumeration when applied to a combinatorial library refers to the process by which the cormection tables for the product structures in a real or virtual library are produced. It should be noted that a single compound can be considered as a library of one and so enumeration can equally well be applied in this case. However, whereas it is considered reasonable for a chemist to draw the structure of a single compoimd manually (which may have taken days, if not months or years, to synthesise), it is clearly not practical to do so even for small combinatorial libraries. Hence the need for automated tools to perform this procedure. 

The challenge in the synthesis of chemical libraries is the vast number of different, potentially drug-like small molecules which is estimated to be as high as 1060. As all of these molecules can never be synthesized and tested, it is essential to define criteria for the composition of libraries spanning the biologically relevant areas of the chemical space most efficiently. An important criterion of a compound library is its chemical diversity, a term describing the similarity or dissimilarity of all library components. Thus, chemical diversity expresses how well a library represents all theoretical possibilities within the chemical property space. A library with low... 

MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain McKILLOP Advanced Problems in Organic Reaction Mechanisms OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries... 

The issue of parallel versus sequential synthesis using multimode or monomode cavities, respectively, deserves special comment. While the parallel set-up allows for a considerably higher throughput achievable in the relatively short timeframe of a microwave-enhanced chemical reaction, the individual control over each reaction vessel in terms of reaction temperature/pressure is limited. In the parallel mode, all reaction vessels are exposed to the same irradiation conditions. In order to ensure similar temperatures in each vessel, the same volume of the identical solvent should be used in each reaction vessel because of the dielectric properties involved [86]. As an alternative to parallel processing, the automated sequential synthesis of libraries can be a viable strategy if small focused libraries (20-200 compounds) need to be prepared. Irradiating each individual reaction vessel separately gives better control over the reaction parameters and allows for the rapid optimization of reaction conditions. For the preparation of relatively small libraries, where delicate chemistries are to be performed, the sequential format may be preferable. This is discussed in more detail in Chapter 5. 

With this set of five optimized reaction conditions in hand (Fig. 5.6), the production of a small DHPM library was performed. As a set of structurally diverse representative building blocks, 17 individual CH-acidic carbonyl compounds, 25 aldehydes, and 8 ureas/thioureas were chosen. Combination of all these building blocks would lead to a library of 3400 individual DHPMs. To demonstrate the practicability of the presented concept, a representative subset library of 48 DHPM analogues involving all of the aforementioned building blocks was generated [2],... 

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