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

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 2; pp. 271 - 275
• Main Authors: Kim, Yu-Yon, Choi, Jaeyul, Choi, Kyungjin, Park, Changhee, Kim, Young Hoon, Suh, Kwee Hyun, Ham, Young Jin, Jang, Sun Young, Lee, Kyu-Hang, Hwang, Kwang Woo
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.01.2019; Elsevier
• Subjects: Anti- tumor activity; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Colony stimulating factor-1; CSF-1R; FMS; Human breast adenocarcinoma cells; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Tumor associated macrophages (TAMs); Colony stimulating factor-1; Anti- tumor activity; FMS; CSF-1R; Human breast adenocarcinoma cells; Tumor associated macrophages (TAMs); METASTASIS; CSF1; Anti-tumor activity; GROWTH; BREAST-CANCER PROGRESSION; TUMOR-ASSOCIATED MACROPHAGES; DIFFERENTIATION
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.11.037

[Display omitted] 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.