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Use of succinyl hydrazine compounds and compositions thereof in preparation of drug for treating leukemia

A compound, leukemia technology, applied in the field of medicine, can solve problems such as drug resistance

Inactive Publication Date: 2007-07-04
INST OF HEMATOLOGY & BLOOD HOSPITAL CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while achieving good curative effect, drug resistance also arises

Method used

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  • Use of succinyl hydrazine compounds and compositions thereof in preparation of drug for treating leukemia
  • Use of succinyl hydrazine compounds and compositions thereof in preparation of drug for treating leukemia
  • Use of succinyl hydrazine compounds and compositions thereof in preparation of drug for treating leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Preparation of succinic acid mono(p-bromophenyl)amide (compound V)

[0063] p-Bromoaniline (7.08g, 40mmol) and succinic anhydride (4.48g, 40mmol) were dissolved in 300ml chloroform and stirred at room temperature, reacted overnight, and needle-like crystals were precipitated, and the product V9.80g was obtained by filtration, with a yield of 88.44%.

Embodiment 2

[0065] Preparation of 1-(p-bromophenyl)amide 4-methyl succinate (compound VI)

[0066] The product V (5g, 18mmol) and iodomethane (3.33g, 23mmol) were dissolved in 100ml DMF, potassium bicarbonate (2.35g, 23mmol) was added, and stirred at room temperature for 16 hours. The reaction solution was diluted with dichloromethane, washed repeatedly, Washed with sodium bicarbonate and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 5.0 g of product VI with a yield of 95.45%.

Embodiment 3

[0068] Preparation of succinic acid 1-(p-bromophenyl)amide 4-hydrazide (compound VII)

[0069] The product VI (38g, 13mmol) was dissolved in 150ml of ethanol, hydrazine hydrate (0.72g, 144mmol) was added, and left at room temperature for one day, white crystals were precipitated, and 3.5g of product VII was obtained by filtration, with a yield of 87.72%.

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Abstract

The invention relates to succinyl hydrazine compounds derivative and medical compound containing them; and the application of it in preparing medicine that resists leukemia. The succinyl hydrazine compounds derivative shows inhibiting action to BCR-Ab1 tyrosine kinase activity through pharmacological test. It is characterized by high effecivity and low toxicity, and can be widly used to prepare medicine that treats chronic granulocytic leukemia (CML) and philadelphia chromosome positive acute lymphoblastic leukemia, especially medicine treating patient that generates drug resistance to Gleevec.

Description

technical field [0001] The invention belongs to the technical field of medicine, more specifically, relates to a succinyl hydrazide compound with anti-tumor activity and a preparation method thereof, and a composition containing the succinyl hydrazide compound in the preparation and treatment of chronic myelogenous leukemia (CML ) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) drugs. Background technique [0002] Ph chromosome: t(9;22)(q34;q11) exists in 95% of chronic myeloid leukemia (CML) and 10~25% of adult acute lymphoblastic leukemia (ALL). The proto-oncogene c-ABL on chromosome 9 is translocated to the BCR region (breakpoint polymerization region) on chromosome 22, resulting in BCR-ABL chimeric gene and expression of BCR-ABL protein. Compared with the normal ABL gene protein, the tyrosine kinase activity of this protein is out of regulation, leading to malignant transformation of cells. In the chronic stage of CML, it can be controlled by cy...

Claims

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Application Information

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IPC IPC(8): C07C243/34A61P7/04A61K31/16
Inventor 齐静杨纯正彭晖纪庆王建祥王彩云
Owner INST OF HEMATOLOGY & BLOOD HOSPITAL CHINESE ACAD OF MEDICAL SCI
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