Compound collection enhancement

The uncontrolled use of parallel or combinatorial synthetic chemistry in hit and lead optimization (and in compound collection enhancement)... 

Jacoby E,Schuffenhauer A, Popov M, etal. (2005) Key aspects of the Novartis compound collection enhancement project for the compilation of a comprehensive chemogenomics drug discovery screening collection. Curr. Top. Med. Cfcem. 5 397-411. 

Scientists at AstraZeneca shared their experiences with their historical compound collections, which prompted them into defining a number of selection criteria in order to filter out compounds of little value for the hit-to-lead process [27]. Subsequently, this led to a compound collection enhancement program. 

In a compound collection enhancement strategy, only very few of the possible structures are eventually produced. Some companies have also generated large virtual databases based on validated reaction protocols, such as Pfizer s Q>Libri with over 10 members [28]. Enamine [29], a Ukrainian provider of test compoimds, has a virtual library with 30 million compoimds based on their experience of a well-performing reaction combined with a large number of available diversity reagents, called the fiill real database. ... 

There are a number of approaches which do not fit into mainstream compound collection enhancement focusing on target, structural features, or synthetic feasibility, but which nonetheless should be discussed here. 

DVS offers a cell-based method for assessing the diversity of compound collections. The orthogonal chemistry space is partitioned into cells, and the occupancy of each cell is easily determined. Diversity voids , or unoccupied regions of chemistry space, are identified with unoccupied cells or cells of low occupancy, which are also easily recognized. Enhancing diversity of a compound collection thus consists of filling empty and low-occupancy cells (see Figure 13.5). 

The carbonyl region spectra of these compounds were enhanced by subtracting out that of MMA. Liquid condensates also collected in the cooler parts of the pyrolysis tube. Representative spectra are shown in Figure 2.6(a) and (b). Further examination of the spectra suggested that a second component was present with MMA evolved below 200 °C in samples (the copolymers N-hydroxylmethyl-methacrylamide and methacrylamide). Subtraction of MMA carbonyl bands in the 1600-1800 cm range revealed the characteristic spectrum of formaldehyde. The evolution profile was similar to that previously observed for occluded methanol [10]. 

---