Lead optimization exploration

Additional applications of this technology for rapid lead discovery and lead optimization have been reported [87, 90-93]. It should also be noted that a variety of chemical transformations, in particular in the area of transition-metal catalyzed reactions, have been performed with this or related equipment (Chapt. 11) [25]. Other monomode microwave reactors using related concepts to introduce high-throughput were recently introduced by CEM Corp. (Discover or Explorer line of products, Fig. 12.7.) [81]. At the time of writing this review no published synthetic applications using this microwave reactor were available. 

It is particularly helpful if the adornments project into space into quadrants that fit precisely the needs of the receptor if one is opti-mizinga lead. Alternately, if one is hit seeking, they should project into various quadrants about the centroid so as to allow a fruitful exploration of potential receptor needs. In hit seeking, one often wants molecular flexibility, whereas in lead optimization progressive ri-gidification is often more effective. 

Typically, this wiU involve the synthesis of some hundreds of analogs, in tens of iterative steps [2], In this chapter, we wiU explore how iterative lead optimization might be guided and made optimally efficient by thinking of the process in terms of a mathematical problem. A significant impediment to doing so has been the historical association between lead optimization and the actual discipline of medicinal chemistry defined as ... 

In this chapter, we have discussed a variety of different chemoinformatics approaches to aid the efficient optimization of high-quality compounds in lead optimization and provided some examples of their application. It is clear that these approaches, appropriately applied, have the potential to significantly improve the lead optimization process. No algorithm can wholly replace the skills of an experienced scientist, but the objective rigor that computational approaches bring can augment this expertise to ensure that a wide variety of opportunities are explored and synthetic and... 

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