Unlock instant, AI-driven research and patent intelligence for your innovation.

4-Aminoquinazoline hydroxamic acid compounds and their application as antitumor drugs

An aminoquinazoline hydroxime, tumor drug technology, applied in the application field of antitumor drugs, can solve the problems of limited therapeutic range, cell death, cell destruction, etc., and achieves good selective inhibitory activity, weak inhibitory effect, and good inhibition. active effect

Active Publication Date: 2015-08-19
SINOPHARM A THINK PHARMA +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional chemotherapeutic drugs non-specifically block cell division and cause cell death. While killing tumor cells, they also destroy normal human cells
Moreover, many cytotoxic drugs have limited therapeutic range and are likely to cause treatment-related adverse reactions

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 4-Aminoquinazoline hydroxamic acid compounds and their application as antitumor drugs
  • 4-Aminoquinazoline hydroxamic acid compounds and their application as antitumor drugs
  • 4-Aminoquinazoline hydroxamic acid compounds and their application as antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Ⅴ-1 Synthesis of N-hydroxy-7-(quinazoline-4-amino)heptanamide

[0077] 4-Chloroquinazoline (0.164g, 1mmol), 7-aminoheptanoic acid methyl ester hydrochloride (0.21g, 1mmol), KOH (0.14g, 2.5mmol), hydroxylamine hydrochloride (0.7g, 2.5mmol) as raw materials, Ⅴ-1 was synthesized according to the general synthesis method of class V compounds, and the yield was 55.9%.

[0078] ESI-MS[M+H] + :m / z 289.1695

[0079] 1 H NMR (400MHz, DMSO-d 6 )δppm: 1.30(m, 4H), 1.48(m, 2H), 1.60(m, 2H), 1.70-1.80(m, 3H), 1.95(t, 1H, J=8.0Hz), 3.52(m, 2H ),7.49(t,1H,J=8.0Hz),7.66(d,1H,J=8.0Hz),7.75(t,1H,J=8.0Hz),8.27(d,1H,J=8.0Hz), 8.34(s,1H),8.43(s,1H)

Embodiment 2

[0081] Ⅴ-2 Synthesis of N-hydroxy-7-(6,7-dimethoxyethoxyquinazoline-4-amino)heptanamide

[0082] 6,7-dimethoxyethoxy-4-chloroquinazoline (0.312g, 1mmol), methyl 7-aminoheptanoate hydrochloride (0.21g, 1mmol), KOH (0.14g, 2.5mmol), Hydroxylamine hydrochloride (0.7g, 2.5mmol) was used as a raw material, and V-2 was synthesized according to the general synthesis method of class V compounds, with a yield of 65.3%.

[0083] ESI-MS[M+H] + :m / z 437.2449

[0084] 1 H NMR (400MHz, DMSO-d 6 )δppm: 1.32(m, 4H), 1.42-1.63(m, 4H), 1.96(t, 2H, J=8.0Hz), 2.21(t, 1H, J=8.0Hz), 3.34-3.51(m, 7H ),3.73(s,6H),4.25(m,4H),7.15(s,1H),7.91(s,1H),8.38(s,1H),8.64(s,1H)

Embodiment 3

[0086] Ⅴ-3 Synthesis of N-hydroxy-7-(6,7-dimethoxyquinazoline-4-amino)heptanamide

[0087]6,7-dimethoxy-4-chloroquinazoline (0.224g, 1mmol), methyl 7-aminoheptanoate hydrochloride (0.21g, 1mmol), KOH (0.14g, 2.5mmol), hydroxylamine hydrochloride ( 0.7g, 2.5mmol) as raw materials, and synthesized V-3 according to the general synthesis method of class V compounds, with a yield of 66.0%.

[0088] ESI-MS[M+H] + :m / z 349.32

[0089] 1 H NMR (400MHz, DMSO-d 6 )δppm: 1.32(m, 4H), 1.49(m, 2H), 1.61(m, 2H), 1.69(s, 1H), 1.96(t, 2H, J=8.0Hz), 3.48-3.57(m, 3H ),3.88(s,6H),7.06(s,1H),7.66(s,1H),8.06(s,1H),8.32(s,1H)

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a 4-aminoquinazoline hydroxamic acid compound and its application as an antitumor drug. The compound of the invention has good histone deacetylase inhibitory activity, and has a good effect on various human tumor cells. Inhibitory activity, weak inhibitory effect on normal cells, low toxicity, suitable for development as anti-tumor drugs. It also has a good curative effect on the treatment of diseases caused by abnormal gene expression. The 4-aminoquinazoline hydroxamic acid compound has a compound as shown in (V) or a pharmaceutically acceptable salt thereof:.

Description

technical field [0001] The invention relates to a class of 4-aminoquinazoline hydroxamic acid compounds and the application of the compounds as antitumor drugs. Background technique [0002] Tumor is a major disease that threatens human health, and the treatment of tumor has been paid close attention to all over the world. Traditional chemotherapy drugs non-specifically block cell division and cause cell death. While killing tumor cells, they also destroy normal cells in the human body. Moreover, many cytotoxic drugs have a limited therapeutic range and are prone to cause treatment-related adverse reactions. [0003] In recent years, with the continuous improvement of molecular biology technology and the further understanding of tumor pathogenesis at the cellular and molecular levels, as well as the rapid development of technologies such as combinatorial chemistry, structure-based drug design and computer science, tumor biotherapy has become a reality. Great progress has e...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/94A61K31/517A61P35/00
CPCA61K31/517A61P35/00C07D239/94
Inventor 李建其张庆伟贾志丹周斌崔宁梁晓东
Owner SINOPHARM A THINK PHARMA