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


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]


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.


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