A kind of 9,10-oxazinone camptothecin derivative and its application
A derivative, camptothecin technology, applied in the field of camptothecin derivatives, can solve the problem of lack of effective drugs and achieve the effects of reducing the concentration of IL-6 and TNF-α, low drug toxicity, and good therapeutic effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0060] Compound 1 preparation of
[0061] 1) The TFA solution of 10-hydroxycamptothecin (100mg, 0.27mmol) and HMTA (80mg, 0.55mmol) was heated and refluxed for 20 hours under the protection of argon. After the reaction was complete, the reaction solution was concentrated, and the concentrated residue Add 20mlH 2 O, then stirred at room temperature for 1 hour, then added 80ml of water to dilute, and washed with saturated NaHCO 3 Solution Adjust the pH of the reaction solution to 8-9, wash the aqueous phase with ethyl acetate, then adjust the pH of the aqueous phase to 1.5, then extract the aqueous phase with ethyl acetate (20ml*5), combine the organic phases, and wash them with 1N hydrochloric acid 、H 2 The organic phase was washed with O and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated, and the residue was separated by flash column chromatography to obtain compound A (methanol / dichloromethane 1:50 as the eluent system);
[0062] 2) Compo...
Embodiment 2
[0069] Compound 2: preparation of
[0070] Compound 1 (120mg, 026mmol), Sc(OTf) 3 (78mg, 0.16mmol) and DMAP (94mg, 0.78mmol) were dissolved in dry dichloromethane solvent, the reaction mixture was stirred at room temperature for 30 minutes, then Boc-glycine (136mg, 0.78mmol) was added, and the reaction mixture was stirred for 30 minutes Minutes, then DCC (272mg, 1.3mmol) was added, the reaction mixture was stirred overnight at room temperature, then filtered through diatomaceous earth, the filtrate was concentrated and separated by flash column chromatography to obtain compound D (methanol / dichloromethane 1:100 as the elution system).
[0071] TFA (1ml) was added to a solution of compound D (95mg, 0.15mmol) in dichloromethane, and the reaction mixture was stirred at room temperature for 30 minutes, then the reaction solvent was removed, and the residue was dissolved in DMF (2ml), and added to the reaction solution Succinic anhydride (97mg, 0.97mmol) and 4-picoline (73mg, 0...
PUM
| Property | Measurement | Unit |
|---|---|---|
| solubility (mass) | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More