Heterocyclic compound having inhibitory activity on 11-beta-hydroxysteroid dehydrogenase type I
A technology of compounds and compositions, applied in the field of heterocyclic compounds with type I 11β-hydroxysteroid dehydrogenase inhibitory activity, capable of solving problems such as not describing 11β-HSD-1 inhibitory activity
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Embodiment 1
[0258] [Formula 16]
[0259]
[0260] Under ice cooling, methylhydrazine (13.5 ml) was added dropwise to the compound 1 (50.0 g) / ethanol solution, and then the reaction solution was stirred at room temperature for 1 hour and refluxed for 4 hours. The solvent was removed under reduced pressure to give a solid. The solid was washed with hexane to obtain compound 2 (34.2 g).
[0261] To a compound 2 (20.0 g) / dimethylformamide (200 ml) solution were added potassium carbonate (48.7 g) and benzyl bromide (15.4 ml), and the resulting mixture was stirred at room temperature for 4 hours. Insolubles were removed by filtration, and the filtrate was poured into a solution of ethyl acetate and 0.1N aqueous HCl and extracted with ethyl acetate. The extract was sequentially washed with 0.1N HCl aqueous solution, H 2 O and brine, then dried over sodium sulfate, concentrated in vacuo. The residue was purified by silica gel column chromatography to obtain Compound 3 (24.0 g).
[0262] U...
Embodiment 2
[0267] [Formula 18]
[0268]
[0269] To compound A-4 (1.00 g) / ethanol (10 ml) solution was added 5% Pd-C (174 mg), and the resulting mixture was stirred under H2 atmosphere (1 atm) for four hours. Insolubles were removed by filtration using Celite, and the filtrate was concentrated in vacuo to give compound 5 (711 mg) as a solid.
[0270] Potassium carbonate (165 mg) and bromocyclohexane (59 μl) were added to a compound 5 (110 mg) / dimethylformamide (1.5 ml) solution, and the resulting solution was stirred at 150° C. for 1.5 hours by using a microwave. The reaction solution was poured into a solution of 0.1N aqueous HCl and ethyl acetate and extracted with ethyl acetate. Extract with H 2 O, washed with brine, dried over magnesium sulfate, concentrated in vacuo. The residue was purified by silica gel column chromatography to obtain Compound A-6 (16 mg).
Embodiment 3
[0272] [Formula 19]
[0273]
[0274] Compound 2 was reacted with phosphorus oxychloride to obtain compound 6. Compound A-2 was obtained by reacting compound 6 with thiophenol in the presence of cesium carbonate.
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