Applications of combinatorial chemistry are very wide. For example in pharmaceutical companies for drug designs. For illustrate this, one a practical example:
Transition-state analog HIV protease inhibitors.
Extensive efforts toward the rational design of aspartyl protease inhibitors such as renin and HIV
have led to the discovery of several transition-states analog mimics. These templates can serve as
the central unit around which molecular diversity can be generated by application of appropriate chemistries.
Recently, solid phase synthesis of hydroxyethylamine and 1,2-diol transition-state pharmacophore units and their
utility for synthesis of HIV protease inhibitors have been reported by two different groups.
The first instance, bifunctional linker are used by Wang to serve the dual purpose of protecting the hydroxyl group of these BBs and providing point for attachment on solid support.
Thus, one linker possesses a vinyl ether group at one end and a free carboxylate group at the other.
The vinyl ether moiety is reacted with diamino alcohol BB 1 under acid-catalysed conditions to form an
acetal protecting group and the carboxylic acid group is used for ester-type linkage to the solid support.
The other linker possesses a methyl ketone and carboxylic groups at the two ends, with the ketone group forming
a ketal with diol 3. Resulting intermediates 2 and 4 are now well suited for a bi-directional solid phase synthesis
strategy for preparing C2 symmetric HIV protease inhibitors. The two terminal amino groups of 2 and 4 are deprotected
and reacted with a variety of carboxylic acid, sulfonyl chlorides, isocyanates, and chloroformates to extend the
core unit in both directions and generate a wide variety of aspartyl protease inhibitors. The authors claim that a
library of 300 discrete analogs was prepared and screened against HIV protease to identify several potent inhibitors.
