Brivudine

Brivudine is a thymidine analogue with antiviral activity, indicated for the early treatment of acute herpes zoster.

Brivudine is used in the treatment of herpes zoster. Although not approved in the U.S. or Canada, it is approved in several European countries.|Brivudine is a uridine derivative and nucleoside analog with pro-apoptotic and chemosensitizing properties. In vitro, bromovinyl-deoxyuridine (BVDU) has been shown to downregulate the multifunctional DNA repair enzyme APEX nuclease 1, resulting in the inhibition of DNA repair and the induction of apoptosis. In addition, this agent may inhibit the expression of STAT3 (signal transducer and activator of transcription 3), which may result in the downregulation of vascular endothelial growth factor (VEGF). BVDU has also been found to inhibit the upregulation of chemoresistance genes (Mdr1 and DHFR) during chemotherapy. Overall, the gene expression changes associated with BVDU treatment result in the decrease or prevention of chemoresistance. In addition, this agent has been shown to enhance the cytolytic activity of NK-92 natural killer cells towards a pancreatic cancer cell line in vitro.

To a solution of (E)-5- (2-CARBOXYVINYL)-2 -DEOXYURIDINE (5.777 g, 19.37 mmol) in dimethylforamide (29 mL) was added K2CO3 (5.890 g, 42.61 mmol) and the suspension stirred at room temperature for 15 mins. A solution of N-bromosuccinimide (3.655 g, 20.53 mmol) was added dropwise over 30 mins at 20°C. The resulting suspension was filtered and the solid washed with DMF. The combined filtrate and washings were evaporated to dryness in vacuo and the residue dissolved in MEOH. To this silica gel was added and the suspension evaporated to dryness and the solid applied to the top of chromatographic column. The column was eluted with CHLOROFORM/METHANOL 92/8 to give a white solid (5787g, 71.9percent). Crystallisation from water gave a white powder. IH-NMR (DMSO-d6 ; 300 MHz) 8 11.59 (1H, bs, NH-3), 8.08 (1H, s, H-6), 7.25 (1H, d, 3J=13. 6 Hz, H-5B), 6.85 (1H, D, J=13. 6 Hz, H-5A), 6.13 (1H, T, 3J=6. 5 Hz, H-L ), 5.29 (1H, bs, OH-3'), 5. 13 (1H, bs, OH-5'), 4.24 (1H, M, H-3'), 3.79 (1H, m, H-4'), 3.66 (2H, M, H-5'), 2. 51 (1H, m, H-2'), 2.14 (1H, M, H-2 ). 13C-NMR (DMSO-D6 ; 75 MHz): 6 40.2 (C-2'), 61.3 (C-5), 70.3 (C-4'), 84.8 (C-3'), 87.8 (C-1'), 108.9 (C-5B), 110. 0 (C-5), 130.3 (C-5A), 149.6, 162.1 (C-2, C4).E-5-(2-Bromovinyl)-2'-deoxy-L-uridine (7). 20.07 g (47.87 mmol) 2, 3'-anhydro-2'-deoxy-5'-O-benzoyl-5-(E)-bromovinyluridine are suspended in 400 ml ethanol and mixed with a solution of 4.78 g (120 mmol) sodium hydroxide in 95 ml water. This is heated for 2.5 h to boiling, thereafter the reaction is terminated (DC-control with dichloromethane/methanol 10:1). After neutralisation with hydrochloric acid, the solvent is distilled off until dry and the residue is extracted several times with acetone/acetic ester mixture (1:1). 13.5 g (84.6percent) product are obtained.

Molecular Weight:333.13
XLogP3:-0.4
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:332.00078
Monoisotopic Mass:332.00078
Topological Polar Surface Area:99.1
Heavy Atom Count:19
Complexity:450
Defined Atom Stereocenter Count:3
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes