Diversity-Oriented Synthesis as a Strategy for Fragment
Evolution against GSK3β

Wang, Yikai; Wach, Jean-Yves; Sheehan, Patrick; Zhong, Cheng; Zhan, Chenyang; Harris, Richard; Almo, Steven
C.; Bishop, Joshua; Haggarty, Stephen J.; Ramek, Alexander; Berry, Kayla
N.; O’Herin, Conor; Koehler, Angela N.; Hung, Alvin W.; Young, Damian W.

doi:10.1021/acsmedchemlett.6b00230.s001

ml6b00230_si_001.pdf (640.99 kB)

Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

journal contribution

posted on 2016-07-14, 00:00 authored by Yikai Wang, Jean-Yves Wach, Patrick Sheehan, Cheng Zhong, Chenyang Zhan, Richard Harris, Steven C. Almo, Joshua Bishop, Stephen J. Haggarty, Alexander Ramek, Kayla N. Berry, Conor O’Herin, Angela N. Koehler, Alvin W. Hung, Damian W. Young

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure–activity relationship, and finally lead to the synthesis of a more potent compound.