Alpha-hydroxy, amino and -fluoro derivatives of beta-sulphenyl hydroxamic acids matrix metalloproteinases inhibitors
A hydroxyl, alkyl technology, applied in the field of α-hydroxyl, amino and halogenated derivatives, can solve problems such as no tissue damage
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[0195] The pharmaceutical composition of the present invention can be prepared by mixing the compound of general formula I of the present invention with a solid or liquid pharmaceutically acceptable carrier, and optionally with pharmaceutically acceptable adjuvants and excipients, using standard and conventional techniques. Compositions in solid form include powders, tablets, dispersible granules, capsules, and suppositories; a solid carrier can be at least one substance, and the substance can also act as a diluent, flavoring agent, solubilizer, lubricant, suspending agent , binders, tablet disintegrants and encapsulating agents; inert solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulose substances, Low melting point wax, cocoa butter, etc. Compositions in liquid form include solutions, suspensions and emulsions; for example, the present invention can provide solutions of compounds of the present inve...
Embodiment 1
[0203] Preparation of N-hydroxy-2-hydroxy-2-[(4-methoxybenzenesulfonyl)methyl]-3-(4-phenylbenzenesulfonyl)propionamide
[0204] Step 1 Preparation of 2-[(4-methoxyphenylthio)methyl]ethyl acrylate
[0205] To a mixture of ethyl bromomethacrylate (1.6 g, 8.3 mmol) and 1.0 ml (8.1 mmol) of 4-methoxythiophenol in ethanol cooled in an ice bath, gradually 8 ml of 1M aqueous sodium bicarbonate solution was added dropwise. The reaction mixture was warmed to room temperature and stirred for 6 hours. The mixture was then concentrated, extracted with ethyl acetate, and washed twice with 10% aqueous hydrochloric acid and once with brine; then, it was dried over sodium sulfate and evaporated in vacuo to give a pale yellow oil. Chromatography on silica gel eluting with dichloromethane gave the title compound as a colorless oil.
[0206] 1 H NMR (CDCl 3 )δ7.33, 6.82, 6.07, 5.32, 4.23, 3.78, 3.63, 1.31.
[0207] Step 2 Preparation of 2-(4-methoxybenzenesulfonyl)methyl-oxirane ethyl carb...
Embodiment 2
[0231] Preparation of N-hydroxy-2-hydroxy-2-[(4-methoxybenzenesulfonyl)methyl]-3-(4-fluorobenzenesulfonyl)propionamide
[0232] Following the general procedure outlined in Example 1 (Steps 1 to 7) with non-critical changes, except that p-fluorophenylthiol was used instead of biphenylthiol in Step 3 and stirred together, the title compound was obtained.
[0233] m.p.85-90°C (softening), 110-115°C (decomposition under bubbling conditions);
[0234] 1 H NMR (DMSO-d 6 )δ10.6, 8.86, 7.92-7.87, 7.75-7.72, 7.46-7.40, 7.11-7.08, 5.64, 3.85-3.69.
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