Description
Bropirimine is an immunomodulator with diverse biological activities. It is a toll-like receptor 7 (TLR7) agonist that inhibits RANKL-induced osteoclast differentiation of murine bone marrow-derived macrophages (BMDMs) in a concentration-dependent manner, an effect that is reversed by an anti-IFN-β antibody. Dietary administration of bropirimine (200 mg/kg twice per week) prevents development of transitional cell carcinomas (TCCs) in a mouse model of carcinogen-induced bladder carcinoma. Bropirimine (100 mg/kg) reduces pulmonary collagen accumulation and bronchoalveolar lavage fluid (BALF) monocyte and eosinophil infiltration in a hamster model of bleomycin-induced lung fibrosis. It also delays disease onset and progression and increases plasma IFN levels in a mouse model of experimental autoimmune encephalomyelitis (EAE).
Uses
Bropirimine is an orally active immunostimulant; anticancer agent. Bropirimine is an interferon inducer that is a potentially useful in the the treatment of superficial bladder cancer (transitional cell carcinoma). Studies suggest that Bropirimine has direct antitumor activity rather than a cytokine-mediated antitumor effect.
Uses
Bropirimine, an immunostimulating agent and toll like receptor (TLR7) agonist, is used in comparison with other TLR7 agonists such as imiquimod, R-848, loxoribine in interferon cell signaling research. Bropirimine may be used in experimental autoimmune encephalomyelitis (EAE) and bladder cancer research.
Definition
ChEBI: Bropirimine is a member of pyrimidines.
Biochem/physiol Actions
Bropirimine is an immunostimulating agent. The compound induces production of α and β interferons and enhances NK cell function. Bropirimine has antiproliferative effects in cancer cell lines and tumor growth in in vivo models.
Synthesis
General procedure for the synthesis of 2-amino-5-bromo-4-hydroxy-6-phenylpyrimidines from 2-amino-4-hydroxy-6-phenylpyrimidines: to a suspension of 2-amino-6-phenylpyrimidin-4(3H)-one (200 mg, 1.07 mmol) in glacial acetic acid (2 mL) was added slowly and dropwise at 70 °C with bromine (57.0 μL, 1.12 mmol) in a glacial acetic acid (2 mL) solution. The reaction mixture was cooled to room temperature and stirring was continued for 4 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The resulting residue was ground with ether (10 mL) and recrystallized from ethanol to give 2-amino-5-bromo-4-hydroxy-6-phenylpyrimidine as a colorless solid (171 mg, 60% yield). The melting point of the product was 275-277 °C (literature value: 285-287 °C); high resolution mass spectrometry (HRMS) measured value: M+H+, 264.9847 (C10H9 79BrN3O+, calculated value 264.9845); infrared spectra (νmax, CHCl3, cm-1): 3691, 3607, 3012, 1692, 1602 , 1473, 1440, 1328, 1240; NMR hydrogen spectrum (1H NMR, 400 MHz, DMSO-d6): δ 7.56-7.53 (2H, m, ArH), 7.45-7.43 (3H, m, ArH), 6.87 (2H, br s, NH2); NMR carbon spectrum (13C NMR, 100 MHz. DMSO-d6): δ 158.6 (C), 153.2 (2×C), 136.3 (C), 129.7 (CH), 128.5 (CH), 128.0 (CH), 97.3 (C); mass spectrum (ESI): m/z 264/266 (M+H+, 34/35%). The spectral data of the obtained product are in agreement with literature reports.
Toxics Screening Level
The initial threshold screening level (ITSL) for bropirimine is 15 μg/m3
based
on an annual averaging time.
References
[1] Tetrahedron, 2015, vol. 71, # 39, p. 7339 - 7343
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1315 - 1321
[3] Journal of Medicinal Chemistry, 1980, vol. 23, # 3, p. 237 - 239
[4] Journal of Medicinal Chemistry, 1985, vol. 28, # 12, p. 1864 - 1869
