Derivative of highly active tetra cyclic anthroquinones antibiotics and preparation and application thereof

Abstract

The invention relates to a derivative of tetra cyclic anthroquinones antibiotics with anti-cancer activity, namely, the compound shown by formula (I). The derivative of the tetra cyclic anthroquinones antibiotics has the activity equal to or even higher than that of the known medicines such as doxorubicin, daunorubicin and the like at cell level and simultaneously has better tolerance than the doxorubicin on animal bodies.

Description

1. Technical field

[0001] The present invention relates to derivatives of tetracyclic anthraquinone antibiotics with anticancer activity, their preparation method and application in preparation of medicines for treating tumors or cancers. 2. Technical background

[0002] Tetracyclic anthraquinone antibiotics are widely used anticancer drugs, especially Doxorubicin and Daunorubicin. Doxorubicin has a significant effect on many solid tumors, including: liver cancer, gastric cancer, breast cancer, lung cancer, ovarian cancer and a variety of blood cancers; daunorubicin is one of the most effective drugs for the treatment of leukemia. However, their clinical application is limited due to their severe side effects such as myelosuppression, cardiotoxicity, and gastrointestinal adverse reactions. So far, many of their derivatives have been isolated or synthesized from nature, trying to find a new generation of anticancer drugs with high activity and low toxicity. The doxorubicin ...

Examples

Embodiment 1、3

[0078] Embodiment 1,3'-pyrrolyl doxorubicin

[0079] Add 3.076g of doxorubicin (Doxorubicin) hydrochloride into a 1L three-necked flask, add 300ml of distilled water, 300ml of 1,2-dichloroethane, 30ml of 2,5-dimethoxytetrahydrofuran and 6ml of glacial acetic acid. Under the protection of argon, it was heated to reflux for 45 minutes, and the reaction was completed. The reaction solution was cooled to room temperature, poured into 200 ml of ice water, and allowed to stand for liquid separation. The organic phase was washed once with 200ml of saturated brine, dried over anhydrous magnesium sulfate, filtered and spin-dried; the aqueous phase was stirred in an ice bath by adding 100ml of 5% aqueous sodium bicarbonate solution, extracted with chloroform (50ml×3), combined the chloroform layers, and the chloroform layers Wash once with 100 ml of saturated brine, filter and spin off the solvent, combine the obtained crude product with the above obtained crude product, and purify by ...

Embodiment 2

[0081] Example 2, 3'-pyrrolyl-5-Iminodaunomycin, MS: 576 (M-1).

Embodiment 3

[0082] Example 3, 3'-pyrrolyl-Idarubicin, MS: 547 (M-1).

1. Technical field

[0001] The present invention relates to derivatives of tetracyclic anthraquinone antibiotics with anticancer activity, their preparation method and application in preparation of medicines for treating tumors or cancers. 2. Technical background

[0002] Tetracyclic anthraquinone antibiotics are widely used anticancer drugs, especially Doxorubicin and Daunorubicin. Doxorubicin has a significant effect on many solid tumors, including: liver cancer, gastric cancer, breast cancer, lung cancer, ovarian cancer and a variety of blood cancers; daunorubicin is one of the most effective drugs for the treatment of leukemia. However, their clinical application is limited due to their severe side effects such as myelosuppression, cardiotoxicity, and gastrointestinal adverse reactions. So far, many of their derivatives have been isolated or synthesized from nature, trying to find a new generation of anticancer drugs with high activity and low toxicity. The doxorubicin ...

Examples

Embodiment 1、3

[0078] Embodiment 1,3'-pyrrolyl doxorubicin

[0079] Add 3.076g of doxorubicin (Doxorubicin) hydrochloride into a 1L three-necked flask, add 300ml of distilled water, 300ml of 1,2-dichloroethane, 30ml of 2,5-dimethoxytetrahydrofuran and 6ml of glacial acetic acid. Under the protection of argon, it was heated to reflux for 45 minutes, and the reaction was completed. The reaction solution was cooled to room temperature, poured into 200 ml of ice water, and allowed to stand for liquid separation. The organic phase was washed once with 200ml of saturated brine, dried over anhydrous magnesium sulfate, filtered and spin-dried; the aqueous phase was stirred in an ice bath by adding 100ml of 5% aqueous sodium bicarbonate solution, extracted with chloroform (50ml×3), combined the chloroform layers, and the chloroform layers Wash once with 100 ml of saturated brine, filter and spin off the solvent, combine the obtained crude product with the above obtained crude product, and purify by ...

Embodiment 2

[0081] Example 2, 3'-pyrrolyl-5-Iminodaunomycin, MS: 576 (M-1).

Embodiment 3

[0082] Example 3, 3'-pyrrolyl-Idarubicin, MS: 547 (M-1).

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