Download MendeleyStructure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors.
Kiryanov, A., Natala, S., Jones, B., McBride, C., Feher, V., Lam, B., Liu, Y., Honda, K., Uchiyama, N., Kawamoto, T., Hikichi, Y., Zhang, L., Hosfield, D., Skene, R., Zou, H., Stafford, J., Cao, X., Ichikawa, T.(2017) Bioorg Med Chem Lett 27: 1311-1315
- PubMed: 28169164
- DOI: https://doi.org/10.1016/j.bmcl.2016.10.009
- Primary Citation of Related Structures:
5TA6, 5TA8 - PubMed Abstract:
Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.
Organizational Affiliation:
Takeda California, 10410 Science Center Drive, San Diego 92121, USA. Electronic address: [email protected].
