Lipophilic Isosteres of a ?-? Stacking Interaction: New Inhibitors of the Bcl-2-Bak Protein-Protein Interaction.
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ABSTRACT:
SUBMITTER: Yusuff N
PROVIDER: S-EPMC4025652 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Lipophilic Isosteres of a π-π Stacking Interaction: New Inhibitors of the Bcl-2-Bak Protein-Protein Interaction.
Yusuff Naeem N Doré Michaël M Joud Carol C Visser Michael M Springer Clayton C Xie Xiaoling X Herlihy Kara K Porter Dale D Touré B Barry BB
ACS medicinal chemistry letters 20120527 7
The discovery of new Bcl-2 protein-protein interaction antagonists is described. We replaced the northern fragment of ABT737 (π-π stacking interactions) with structurally simplified hydrophobic cage structures with much reduced conformational flexibility and rotational freedom. The binding mode of the compounds was elucidated by X-ray crystallography, and the compounds showed excellent oral bioavailability and clearance in rat PK studies. ...[more]
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