2. Academic Validation
  3. Synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel FMS inhibitors

Synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel FMS inhibitors

  • Bioorg Med Chem Lett. 2019 Jan 15;29(2):271-275. doi: 10.1016/j.bmcl.2018.11.037.
Yu-Yon Kim 1,  Jaeyul Choi 2,  Kyungjin Choi 3,  Changhee Park 4,  Young Hoon Kim 5,  Kwee Hyun Suh 6,  Young Jin Ham 7,  Sun Young Jang 8,  Kyu-Hang Lee 9,  Kwang Woo Hwang 10
Affiliations

Affiliations

  • 1 Host Defense Modulation Lab, Collage of Pharmacy, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 06974, Republic of Korea; Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 2 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 3 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 4 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 5 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 6 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 7 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 8 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 9 Hanmi Research Center, Hanmi Pharm. Co. Ltd., 550 Dongtangiheung-Ro, Hwaseong-Si, Gyeonggi-Do 18469, Republic of Korea. Electronic address: [email protected].
  • 10 Host Defense Modulation Lab, Collage of Pharmacy, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 06974, Republic of Korea. Electronic address: [email protected].
PMID: 30522957 DOI: 10.1016/j.bmcl.2018.11.037
Abstract

Colony stimulating factor-1 receptor (CSF-1R or FMS) and it ligand, CSF-1, signaling regulates the differentiation and function of tumor-associated macrophages (TAMs) that play an important role in tumor progression. Derivatives of thieno[3,2-d]pyrimidine were synthesized and evaluated as kinase inhibitors of FMS. The most representative compound 21 showed strong activity (IC50 = 2 nM) against FMS kinase and served as candidate for proof of concept. Anti-tumor activity alone and/or in combination with paclitaxel was examined via a tumor cell growth inhibition assay and via an in vitro tumor invasion assay using human breast adenocarcinoma cells.

Keywords

Anti- tumor activity; CSF-1R; Colony stimulating factor-1; FMS; Human breast adenocarcinoma cells; Tumor associated macrophages (TAMs).

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