Application of dihydrochromone skeleton compound in preparation of medicine for treating malignant tumors

Abstract

The invention discloses applications of dihydro chromone framework compounds of CPQ-16, CPQ-17, CPQ-20, CPQ-22, CPQ-23 and CPQ-24 in preparing medicine for curing malignant tumors. According to experimental proof, any kind of the six compounds can kill a plurality kinds of tumor cells of human bodies effectively, the tumor cells comprise cervical cancer cells, non-small cell lung cancer cells, breast cancer cells, ovarian carcinoma cells, hepatoma carcinoma cells, nasopharyngeal carcinoma cells, gastric carcinoma cells, laryngocarcinoma cells, pancreatic cancer cells, melanoma cells, bladder cancer cells and leukemia cells. Besides, with increase of dosages of the compounds, injured and killed cancers are increased with the increase of the dosages, and thus the new applications are proofed and discovered in the medicine for curing malignant tumors, and a new application range is exploited. Besides, new medicine is provided for the malignant tumors, and the difficulty in the chemical treatment of diseases that tumor cells are tolerant of chemotherapeutics is solved.

Description

technical field

[0001] The invention relates to the use of a dihydrochromone skeleton compound, in particular to the application of the dihydrochromone skeleton compound in the preparation of medicines for treating malignant tumors. Background technique

[0002] Malignant tumor is a major disease that endangers human health, and it has become the first cause of death among Chinese residents. Chemotherapy is still the main means of treatment for many malignant tumors, but the resistance of tumor cells to chemotherapeutic drugs, including primary drug resistance and acquired drug resistance, has always been the primary problem that plagues and restricts the chemotherapy of malignant tumors in clinical practice. Therefore, it is urgent to find innovative drugs with high anticancer activity. In recent years, natural products and their derivatives have become an important source of innovative anticancer drugs. The development of Class 1 new drugs through total synthesis is of g...

Examples

Embodiment 1

[0029] Embodiment 1: Preparation of dihydrochromone skeleton compound CPQ-16

[0030] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-16 was obtained by column chromatography separation with a yield of 68%. The structural formula is as follows:

[0031]

[0032] 1 H NMR (400MHz, CDCl 3):δ=8.04(dd,J=8.8Hz,J=6.4Hz,1H),7.19(s,1H),6.82(td,J=8.4Hz,J=2.4Hz,1H),6.67(dd,J =10.0Hz,J=2.4Hz,1H),5.15(s,1H),4.57(s,1H),4.38(dd,J=10.0Hz,J=2.8Hz,1H),4.21(q,J=7.2 Hz,2H),2.27(dd,J=13.6Hz,J=8.0Hz,1H),2.12-2.05(m,1H),1.97-1.94(m,4H),1.70(s,3H),1...

Embodiment 2

[0033] Embodiment 2: Preparation of dihydrochromone skeleton compound CPQ-17

[0034] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-17 was separated by column chromatography with a yield of 73%. The structural formula is as follows:

[0035]

[0036] 1 H NMR (400MHz, CDCl 3 ):δ=7.74(s,1H),7.20(s,1H),6.76(s,1H),5.16-5.14(m,1H),4.56(dd,J=8.0Hz,J=1.6Hz,1H) ,4.31(dd,J=10.0Hz,J=3.2Hz,1H),4.21(q,J=7.2Hz,2H),2.28(s,3H),2.24-2.22(m,4H),2.09-1.92( m,5H),1.70(s,3H),1.61(s,3H),1.55(dd,J=13.2Hz,J=3.2Hz,1H),1.40(dt,J=13.6Hz,J=2.8Hz, 1H...

Embodiment 3

[0037] Embodiment 3: Preparation of dihydrochromone skeleton compound CPQ-20

[0038] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-20 was obtained by column chromatography separation with a yield of 91%. The structural formula is as follows:

[0039]

[0040] 1 H NMR (400MHz, CDCl 3 ):δ=8.02(dd,J=8.8Hz,J=6.4Hz,1H),7.18(s,1H),6.81(td,J=8.4Hz,J=2.4Hz,1H),6.66(dd,J =9.6Hz,J=2.0Hz,1H),5.16-5.09(m,2H),4.56(s,1H),4.37(dd,J=10.4Hz,J=2.8Hz,1H),4.20(m,2H ),2.30-2.24(m,1H),2.10-1.96(m,9H),1.68(s,3H),1.60-1.54(m,7H),1.43-1.38(m,1H),1...

technical field

[0001] The invention relates to the use of a dihydrochromone skeleton compound, in particular to the application of the dihydrochromone skeleton compound in the preparation of medicines for treating malignant tumors. Background technique

[0002] Malignant tumor is a major disease that endangers human health, and it has become the first cause of death among Chinese residents. Chemotherapy is still the main means of treatment for many malignant tumors, but the resistance of tumor cells to chemotherapeutic drugs, including primary drug resistance and acquired drug resistance, has always been the primary problem that plagues and restricts the chemotherapy of malignant tumors in clinical practice. Therefore, it is urgent to find innovative drugs with high anticancer activity. In recent years, natural products and their derivatives have become an important source of innovative anticancer drugs. The development of Class 1 new drugs through total synthesis is of g...

Examples

Embodiment 1

[0029] Embodiment 1: Preparation of dihydrochromone skeleton compound CPQ-16

[0030] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-16 was obtained by column chromatography separation with a yield of 68%. The structural formula is as follows:

[0031]

[0032] 1 H NMR (400MHz, CDCl 3):δ=8.04(dd,J=8.8Hz,J=6.4Hz,1H),7.19(s,1H),6.82(td,J=8.4Hz,J=2.4Hz,1H),6.67(dd,J =10.0Hz,J=2.4Hz,1H),5.15(s,1H),4.57(s,1H),4.38(dd,J=10.0Hz,J=2.8Hz,1H),4.21(q,J=7.2 Hz,2H),2.27(dd,J=13.6Hz,J=8.0Hz,1H),2.12-2.05(m,1H),1.97-1.94(m,4H),1.70(s,3H),1...

Embodiment 2

[0033] Embodiment 2: Preparation of dihydrochromone skeleton compound CPQ-17

[0034] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-17 was separated by column chromatography with a yield of 73%. The structural formula is as follows:

[0035]

[0036] 1 H NMR (400MHz, CDCl 3 ):δ=7.74(s,1H),7.20(s,1H),6.76(s,1H),5.16-5.14(m,1H),4.56(dd,J=8.0Hz,J=1.6Hz,1H) ,4.31(dd,J=10.0Hz,J=3.2Hz,1H),4.21(q,J=7.2Hz,2H),2.28(s,3H),2.24-2.22(m,4H),2.09-1.92( m,5H),1.70(s,3H),1.61(s,3H),1.55(dd,J=13.2Hz,J=3.2Hz,1H),1.40(dt,J=13.6Hz,J=2.8Hz, 1H...

Embodiment 3

[0037] Embodiment 3: Preparation of dihydrochromone skeleton compound CPQ-20

[0038] In the reaction tube, add 0.02mmol hexahydropyridine catalyst and 0.1mmol chromone electron-deficient diene compound successively, namely 0.2mmol long-chain alkenal, namely 0.02mmol acidic additive o-fluorobenzoic acid and 1mL solvent 1,4-dioxane were reacted under normal pressure and 25°C under stirring, and the reaction was monitored by TLC. After 12 hours, the reaction was completed. The solvent was recovered under reduced pressure, and the residue was passed through The target product CPQ-20 was obtained by column chromatography separation with a yield of 91%. The structural formula is as follows:

[0039]

[0040] 1 H NMR (400MHz, CDCl 3 ):δ=8.02(dd,J=8.8Hz,J=6.4Hz,1H),7.18(s,1H),6.81(td,J=8.4Hz,J=2.4Hz,1H),6.66(dd,J =9.6Hz,J=2.0Hz,1H),5.16-5.09(m,2H),4.56(s,1H),4.37(dd,J=10.4Hz,J=2.8Hz,1H),4.20(m,2H ),2.30-2.24(m,1H),2.10-1.96(m,9H),1.68(s,3H),1.60-1.54(m,7H),1.43-1.38(m,1H),1...

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