Orally active purine-based inhibitors of the heat shock protein 90
Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently
Biamonte, Marco A.,Shi, Jiandong,Hong, Kevin,Hurst, David C.,Zhang, Lin,Fan, Junhua,Busch, David J.,Karjian, Patricia L.,Maldonado, Angelica A.,Sensintaffar, John L.,Yang, Yong-Ching,Kamal, Adeela,Lough, Rachel E.,Lundgren, Karen,Burrows, Francis J.,Timony, Gregg A.,Boehm, Marcus F.,Kasibhatla, Srinivas R.
p. 817 - 828
(2007/10/03)
Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures
Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold