Go with the flow: de-orphaning focused combinatorial libraries
نویسندگان
چکیده
The fast pace of drug discovery programs, aided by highthroughput screening campaigns, often relies on the generation of combinatorial libraries to identify new chemical entities. The Ugi 4and 3-component reactions in particular [1], have proven to be robust in producing both tool compounds and drugs [2,3]. Here we report a high-throughput entry into the imidazopyridine scaffold, using a microfluidic-assisted synthesis setup, coupled to a target prediction tool to de-orphan a focused compound library with high success rate, and identify an innovative GPCR-inhibiting chemotype. Combinatorial compounds were correctly identified as ligand-efficient adenosine A1/2B, and adrenergic a1A/B inhibitors with Ki values in the low micromolar range.
منابع مشابه
Go with the flow and accessorize your drugs
The fast pace of drug discovery programs is supported by high-throughput screening campaigns to identify new chemical entities, where the underlying screening compound collections benefit from combinatorial libraries with leadand drug-like properties. We will discuss recent developments in this field from two perspectives by addressing how to (i) assemble focused combinatorial libraries with de...
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