Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Benzothiazole compounds and medical application

A technology of benzothiazole and compounds, applied in the field of medicinal chemistry, to achieve the effects of cheap raw materials, easy large-scale production, and easy availability of raw materials

Inactive Publication Date: 2020-10-13
CHINA PHARM UNIV
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there are no reports of compounds that bind to the USP7 C-terminal protein. Therefore, it is urgent to develop USP7 C-terminal domain regulators with high activity and low toxicity, which can be potentially used in the treatment of diseases such as myelodysplastic syndrome and malignant tumors.

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
  • Benzothiazole compounds and medical application
  • Benzothiazole compounds and medical application
  • Benzothiazole compounds and medical application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] N-(2-(furan-2-carboxamide)benzo[d]thiazol-6-yl)isonicotinamide (compound 1)

[0066]

[0067] synthetic route:

[0068]

[0069] Dissolve 2-amino-6-nitrobenzothiazole 1a (1g, 5.13mmol) in pyridine solution (20mL), add fresh furan-2-formyl chloride (758μL, 7.70mmol) dropwise, and heat up to Stir at 40°C for 8 hours. TLC monitored the completion of the reaction and added 1N hydrochloric acid (30 mL) for neutralization, and a large amount of solid precipitated out. After suction filtration, the solid was washed with a small amount of ethyl acetate (2 mL×3) to obtain the crude intermediate 1b, which was directly used in the next step without purification.

[0070] All the obtained crude intermediate 1b was added to methanol (25 mL), 10% palladium / carbon (100 mg) was added, hydrogen gas was introduced and stirred at 50° C. for 7 hours. TLC monitored that the reaction was complete and stopped heating. After cooling to room temperature, the solution was filtered with ...

Embodiment 2

[0073] N-(2-(furan-2-carboxamide)benzo[d]thiazol-6-yl)pyridineamide (Compound 2)

[0074]

[0075] Referring to the method of Example 1, isonicotinic acid was replaced by picolinic acid to obtain compound 2 (off-white solid): 1 HNMR (300MHz, DMSO-d 6 )δ12.80(s,1H),10.80(s,1H),8.77(d,J=4.7Hz,1H),8.60(s,1H),8.20(d,J=7.9Hz,1H),8.15– 8.01(m,2H),7.95(d,J=8.9Hz,1H),7.84–7.60(m,3H),6.77(s,1H).ESI-MS m / z 363.1[M-H] - .

Embodiment 3

[0077] N-(2-(furan-2-carboxamide)benzo[d]thiazol-6-yl)pyrazine-2-carboxamide (compound 3)

[0078]

[0079] Referring to the method of Example 1, isonicotinic acid was replaced by pyrazine-2-carboxylic acid to obtain compound 3 (off-white solid): 1 H NMR (300MHz, DMSO-d 6 )δ12.83(s,1H),10.88(s,1H),9.33(s,1H),8.95(s,1H),8.83(s,1H),8.57(s,1H),8.04(s,1H ), 7.94(d, J=8.9Hz, 2H), 7.86–7.48(m, 2H), 6.76(s, 1H). ESI-MS m / z 364.1[M-H] - .

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 benzothiazole compound and medical application thereof, particularly relates to a benzothiazole compound shown as a formula I and medical application thereof, and especiallyrelates to application of the benzothiazole compound serving as a USP7C-terminal structural domain regulating agent in medicines for preventing and treating myelodysplastic syndromes and malignant tumors. The benzothiazole compound shown in the formula I or the pharmaceutically acceptable salt or solvate of the benzothiazole compound has strong binding force with USP7C-terminal protein; and the protein level of DNMT1 in tumor cells can be reduced, so that the compound can be applied to the preparation of USP7 regulators, has a remarkable anti-tumor cell proliferation effect, and can be used for preparing medicines for preventing or treating myelodysplastic syndrome and malignant tumors.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to benzothiazole compounds and their use in pharmaceuticals, especially to benzothiazole compounds and their use as USP7 C-terminal domain regulators in the prevention and treatment of myelodysplastic syndromes and malignant tumors use in . Background technique [0002] Myelodysplastic syndromes (myelodysplastic syndromes, MDS) are a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells, characterized by abnormal differentiation and development of myeloid cells, manifested as ineffective hematopoiesis, refractory cytopenias, high Risk of conversion to acute myeloid leukemia (AML). The main causes of death of the patients were the complications caused by the disease itself and the death caused by transformation to AML (Cancer 2010,16:2174-2179). According to statistics, in the United States, its prevalence rate is about 0.004-0.005%, and...

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
IPC IPC(8): C07D417/14C07D417/12A61K31/4439A61K31/454A61K31/497A61K31/428A61K31/496A61K31/4725A61K31/5377A61K31/4709A61P35/00A61P35/02
CPCC07D417/14C07D417/12A61P35/00A61P35/02
Inventor 孙宏斌刘胜杰周鑫煜袁浩亮陈彩萍温小安
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com