Lead optimization pharmaceutical industry applications

The pharmaceutical industry has pioneered in the application of computer-assisted drug design methods in product research. To a significant degree this is a consequence of the direct use of computational chemistry in enhancing the efficiency of the chemical lead optimization process. 

The NMR techniques described in the last section provide the foundation for many of the advanced applications of NMR in the pharmaceutical industry. The challenges of this industry have lead to the optimization of hardware and experimental design to answer specific questions. Some of the most important questions and the NMR applications that have been developed to answer them will be described in the next sections. 

In this chapter, three kinds of multistep BIA production systems are reviewed (shown in Table 1.2). These microbial systems should open a new field in which microbial cells can be given the ability for low-cost production of many diverse alkaloids. The bacterial platform for BIA fermentation has been established, but further applications face problems. Further metabolic engineering (such as optimization and modification of the pathway) may overcome the productivity of alkaloids and enhance the field of applications for microbial alkaloid fermentation. The widespread application may lead to further progress with microbial systems for use in the pharmaceutical industry, which needs a diverse chemical library to develop more advanced tools for chemical therapy. 

Building blocks that render unique physicochemical properties and metabolic stability to drug candidates play a key role in advancing lead generation, hit-to-lead, and lead optimization programs in the pharmaceutical industry. One such example is the 3-azabicyclo[3.1.0]-hex-2-yl moiety (Figure 11.3), derivatives of which have found applications in the synthesis of therapeutic targets. ... 

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