Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors

  • Bioorg Med Chem Lett. 2020 Jul 1;30(13):127189. doi: 10.1016/j.bmcl.2020.127189.
Seung Chan Kim  1 ,  Pulla Reddy Boggu  2 ,  Ha Na Yu  3 ,  So Young Ki  3 ,  Jun Min Jung  2 ,  Yeon Su Kim  2 ,  Gi Min Park  2 ,  Sang Ho Ma  2 ,  In Su Kim  2 ,  Young Hoon Jung  4
Affiliations
  • 1. School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; R&D Center, CJ HealthCare Corporation, Icheon 17389, Republic of Korea.
  • 2. School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 3. R&D Center, CJ HealthCare Corporation, Icheon 17389, Republic of Korea.
  • 4. School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: [email protected].
PMID: 32371098 DOI: 10.1016/j.bmcl.2020.127189
Abstract

A series of novel quinoxaline derivatives were synthesized and evaluated for their inhibitory activity against c-Met kinase enzyme. Most of the tested compounds exhibited potent inhibitory activity. All the synthesized quinoxaline compounds were further examined against c-Met overexpressed human gastric Cancer cell line (MKN-45), which showed good inhibitory activity. Among the synthesized compounds, compound 4 exhibited better tumor growth inhibition in the animal model study; we also confirmed its acceptable drug property and highly selective target activity.

Keywords
Quinoxaline; Synthesis; c-Met inhibitors; c-Met kinase.