PMC is routinely used as a tool in lead discovery and optimization, and it allows the medicinal chemist to prosecute multiple structurally distinct series concurrently and to develop rich SAR quickly.  Furthermore, it allows the design team to draw conclusions based on data associated with a matrix of compounds instead of a single compound.  The use of PMC was an important strategy to develop SAR for the CHK1 program.  The efficient exploration of chemical space was accomplished by applying creative organic chemistry in the parallel synthesis environment.  Five innovative libraries will be described in this presentation.  Each library is a multistep reaction and features one of the following:   A 3+2 cycloaddition of enol ethers with N-aminopyridinium salts to provide pyrazolo[1,5-a]pyridines, the cyclocondensation of 2-aminoheterocycles with alpha bromo hemiacetals derived from an enol ether to give imidazoheterocycles, the ring opening of aziridines with nitrogen and oxygen nucleophiles to give amino pyrrolidines, and the 3+2 cycloaddition of an azomethine ylid with nitro alkenes to form amino pyrrolidines.

Use of parallel medicinal chemistry to generate structure activity relationship data for the CHK1 project

246th National Meeting (2013)

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