Design, synthesis, and biological study of 6,7-dihydro-5H-pyrano[2,3-d]pyrimidine derivatives as novel hedgehog signaling pathway inhibitors

作者：Xin Minhang^*; Zhang Liandi; Shen Han; Wen Jun; Tu Chongxing; Liu Zhaoyu; Cheng Lingfei; Zhao Xinge

来源：Medicinal Chemistry Research, 2014, 23(8): 3784-3792.

DOI：10.1007/s00044-014-0959-3

• Hedgehog signaling pathway
• Inhibitors
• 6,7-Dihydro-5H-pyrano[2,3-d]pyrimidine
• Novel

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.

• 出版日期2014-8
• 单位西安交通大学