Abstract
A novel series of hedgehog signaling pathway inhibitors were designed by replacing the pyrimidine nucleus of our earlier reported compounds with 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine scaffold. Among this new class of hedgehog signaling pathway inhibitors, compounds 14 and 18 exhibited promising potency in vitro compared to GDC-0449. Compound 18 was advanced to profile its pharmacokinetic characteristics, and showed moderate pharmacokinetic properties in vivo, indicating that the 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine skeleton is a promising scaffold for further exploration as hedgehog signaling pathway inhibitors.
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Acknowledgments
This work was supported by the National Major Science and Technology Project of China (Innovation and Development of New Drugs, No. 2011ZX09401-008).
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Xin, M., Zhang, L., Shen, H. et al. Design, synthesis, and biological study of 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine derivatives as novel hedgehog signaling pathway inhibitors. Med Chem Res 23, 3784–3792 (2014). https://doi.org/10.1007/s00044-014-0959-3
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DOI: https://doi.org/10.1007/s00044-014-0959-3