SEP 16, 2015 8:00 AM PDT

Diversity-Oriented Synthesis for Discovery of Novel Therapeutics

Speaker

Abstract
Recent evidence demonstrating the importance of structural complexity in advancing compounds to the clinic points to the need for enhancing small molecule screening collections with sp3-rich compounds. The development of diversity-oriented synthesis (DOS) strategies for accessing libraries of sp3-rich compounds containing one or more stereogenic centers will be presented, focusing on library synthesis efforts at H3 Biomedicine as well as previous work at the Broad Institute. The DOS libraries which have been created, span a broad range of molecular frameworks, including macrocycles and medium-sized rings, as well as fused-, bridged- and spirocyclic- ring systems. Preliminary results of high-throughput screening of the H3 compound collection will be discussed, with an emphasis on the identification of novel modulators of pre-mRNA splicing.

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