2-thioxanthine derivatives acting as mpo-inhibitors
A technology of thioxanthine and compound, which is applied in the directions of active ingredients of heterocyclic compounds, medical preparations containing active ingredients, anti-inflammatory agents, etc., can solve the problems of rising treatment costs and the like
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Embodiment 1
[0168] Example 1 3-(2-ethoxy-2-methylpropyl)-2-thioxanthine
[0169] (a) 2-Bromo-1,1-diethoxy-2-methylpropane
[0170] This product was synthesized according to a modified procedure described in US 3,652,579.
[0171] Bromine water (2.95 mL, 57.6 mmol) was added dropwise to a solution of isobutyraldehyde (4.82 g, 66.8 mmol) in EtOH (22 mL), and the resulting mixture was stirred at room temperature for 40 min. More bromine water (0.3 mL, 5.86 mmol) was added. The reaction mixture was neutralized by adding calcium carbonate (3.5 g, 25.3 mmol). The remaining calcium carbonate was filtered off, and the filtrate was poured onto a mixture of ice and water. CH for aqueous phase 2 Cl 2 Extracted by Na 2 SO 4 Dry, filter and concentrate. The title product was obtained in 67% (10.10 g) yield after vacuum distillation.
[0172] 1 H NMR (400MHz, DMSO-d 6 )δppm4.43(s, 1H), 3.80-3.73(m, 2H), 1.64(s, 6H), 1.15(t, 6H).
[0173] (b) 2-Ethoxy-2-methylpropanal
[0174] This prod...
Embodiment 2
[0181] Example 2 3-(2-propoxy-2-methylpropyl)-2-thioxanthine
[0182] (a) 2-bromo-2-methyl-1,1-dipropoxypropane
[0183]2-Bromo-2-methyl-1,1-dipropoxypropane was prepared according to a modified method described in US 3,652,579.
[0184] Isobutyraldehyde (7.2 g, 0.10 mol) and 1-propanol (12 mL) were cooled in an ice bath. Bromine (4.4 mL, 0.086 mol) was added dropwise over 20 minutes. Stirring was continued for 5 minutes at ambient temperature and then for 30 minutes at 55°C. Calcium carbonate (3 g, 0.030 mol) was added in portions. The resulting mixture was stirred at ambient temperature for 1 h. The mixture was filtered and the solid was washed with ether. Water (15 mL) was then added. The organic phase was separated, dried over sodium sulfate and concentrated in vacuo at ambient temperature. The crude product (13.5 g, 53%) was used in the next step without further purification.
[0185] 1 H NMR (CDCl 3 )δppm4.40 (s, 1H), 3.73-3.79 (m, 2H), 3.51-3.57 (m, 2H), 1.7...
Embodiment 3
[0195] Example 3 3-(2-methoxy-2-methylpropyl)-2-thioxanthine
[0196] (a) 2-methoxy-2-methylpropanal
[0197] This product was synthesized according to the procedure described in US 3,652,579.
[0198] (b) 4-[(2-methoxy-2-methylpropyl)amino]-1H-imidazole-5-carboxamide
[0199] 5-Amino-4-imidazolecarboxamide hydrochloride (0.162g, 1.0mmol) and 2-methoxy-2-methylpropanal (0.204g, 2.0mmol) obtained from Example 3 (a) were mixed in Mix in methanol (3 mL) at room temperature. Acetic acid (141 μL, 2.46 mmol) was then added, the mixture was stirred for 30 min, followed by the addition of NaCNBH 3 (0.063 g, 1.0 mmol). After 3 h, additional 2-methoxy-2-methylpropanal (0.060 g, 0.59 mmol) was added. The reaction mixture was stirred at room temperature for 17 h, then concentrated, and subjected to flash silica gel chromatography (CHCl 3 :MeOH=5:1) for purification. The title compound was obtained in 73% yield (0.155 g) as an oil. MS (ESI) m / z 213 (M+1).
[0200] (c) 3-(2-m...
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