Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety.

@article{Ndubaku2015DesignOS,
  title={Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety.},
  author={Chudi O Ndubaku and James J Crawford and Joy Drobnick and Ignacio Aliagas and David Campbell and Ping Dong and Laura M Dornan and Sergio Gonzalez Dur{\'o}n and Jennifer A Epler and Lewis J. Gazzard and Christopher E. Heise and Klaus P. Hoeflich and Diana Jakubiak and Hyoung Sul La and Wendy S. C. Lee and Baiwei Lin and Joseph P. Lyssikatos and Jasna Maksimoska and Ronen Marmorstein and Lesley J. Murray and Thomas O'Brien and Angela Jinsook Oh and Sreemathy Ramaswamy and Weiru Wang and Xianrui Zhao and Yu Zhong and Elizabeth Maureen Blackwood and Joachim Rudolph},
  journal={ACS medicinal chemistry letters},
  year={2015},
  volume={6 12},
  pages={
          1241-6
        }
}
Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (1) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing pK a and logP simultaneously. When positioned properly within the scaffold, this group… CONTINUE READING
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