Imidazoimidazoles and triazoles as anti-inflammatory agents
A technology of carbon atoms and alkyl groups, applied in the field of treatment of inflammatory diseases, can solve the problems of lack of selectivity, unsatisfactory therapeutic use of small molecules, lack of specificity, etc.
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Embodiment 1
[1060] A solution of amino-ester XIII and 3,5-dichlorophenyl isothiocyanate (1:1 molar ratio) in 1,4-dioxane was heated at 90°C in N2 for 10 hours. The mixture was concentrated to obtain the thiohydantoin derivative XIV. Product use 1 H NMR and mass spectrometer identification.
[1061] With PPh 3 To a solution of (9.0 mmol) in toluene (20 mL) was added azide XV (9.0 mmol) under nitrogen. After stirring at room temperature overnight, thiohydantoin XIV (4.5 mmol) was added. Mixture in N 2 The medium is sealed in a pressure tube and heated at 130-140°C for 3-4 days, concentrated and purified by silica gel chromatography to obtain the product XVI. Product use 1 H NMR and mass spectrometer identification.
[1062] Trifluoroacetic acid (TFA, 5-6 equivalents) is added to the dichloroethane solution containing XVI. The mixture was heated in N2 at 90°C overnight. The residue was placed in EtOAc, and saturated NaHCO 3 Washing, dehydration (Na 2 SO 4 ) And concentration. The residue was pur...
Embodiment 2
[1064] A dichloromethane solution (20 mL) containing compound 1 (1.82 g, 4.04 mmol) was cooled to 0°C and a small amount of N-iodosuccinimide (1.43 g, 6.04 mmol) was added thereto. Pyridine p-toluenesulfonate (100 mg, 0.40 mmol) was added and the mixture was stirred at 0°C for 3 hours, during which time additional N-iodosuccinimide (400 mg, 1.68 mmol) was added to complete the reaction. The mixture was diluted with dichloromethane, with 10% Na 2 SO 3 The solution is washed, dehydrated and concentrated. The residue was purified by silica gel chromatography to obtain a mixture of title compound 2 (1.86 g) and 2a (0.53 g). Product use 1 H NMR and mass spectrometer identification.
[1065] Using more than 2 molar equivalents of N-iodosuccinimide, using the same procedure described above, a single product of diiodide 2a can also be produced from 1. Example 3
Embodiment 3
[1066] A solution of compound 2 (33 mg, 0.0572 mmol) in THF was treated with 2.0 M cyclopentylmagnesium bromide (57 μl, 0.114 mmol) at -30°C in nitrogen. After the mixture was stirred at -30°C for 2 hours, a solution containing tosyl cyanide (70 mg, 0.367 mmol) in THF (0.5 mL) was added. The mixture was stirred at -30°C for 1 hour and at room temperature overnight. Saturated NH 4 The Cl solution was quenched at 0°C. Extraction with EtOAc followed by silica gel chromatography gave compound 3 as a foam (9.5 mg, 35%). Product use 1 H NMR and mass spectrometer identification.
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