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

Thieno-pyrimidone DPP-IV (dipeptidyl peptidase) inhibitor

A solvate and compound technology, applied in the field of medicine, can solve problems such as short half-life and inactivation

Active Publication Date: 2012-01-11
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI +1
View PDF5 Cites 22 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Treatment based on GLP-1 can effectively control blood sugar, but as a substrate of DPP-IV, GLP-1 has a short half-life and will be rapidly cut and inactivated by DPP-IV within 1-2 minutes after secretion

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
  • Thieno-pyrimidone DPP-IV (dipeptidyl peptidase) inhibitor
  • Thieno-pyrimidone DPP-IV (dipeptidyl peptidase) inhibitor
  • Thieno-pyrimidone DPP-IV (dipeptidyl peptidase) inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1. Synthesis of Compound 1

[0087]

[0088] synthetic route:

[0089]

[0090] Synthesis of compounds 1-2

[0091] Add urea (1mol, 60g) to a 250ml dry single-necked round-bottomed flask, heat to 160°C under an oil bath to melt, add (0.13mol, 20g) methyl 3-aminothiophene-2-carboxylate, and the mixture is heated to 190- Heating and reacting at 200°C for 3 hours, cooling, adding 500ml of 10% aqueous sodium hydroxide solution, stirring evenly, suction filtration, washing with 5-10% aqueous sodium hydroxide solution, the filtrate was adjusted to pH 6.5 with 2N HCl solution under ice bath, and there was A white solid was precipitated, filtered with suction, washed with ice water, and dried to obtain 12.5 g of a white solid with a yield of 59%.

[0092] 1 H-NMR (400MHz, d 6 -DMSO): δ 6.9 (1H, d, J=5.2Hz), 8.10 (1H, d, J=5.2Hz), 11.60-11.1 (2H, br, s); MS: 169.1 [M+H + ].

[0093] Synthesis of compounds 1-3

[0094] The compound 1-2 (74.3 mmol, 12.5 g) obt...

Embodiment 2

[0105] Example 2. Synthesis of Compound 2

[0106]

[0107] Compound 2-1 was used instead of compound 1-1 in Example 1, and the synthesis method was referred to in Example 1, and compound 2 was prepared as a light yellow solid with a yield of 45%.

[0108] 1 H-NMR (400MHz, CD 3 OD): δ 1.25 (1H, m), 1.75 (1H, m), 1.77 (1H, m), 1.96 (1H, m), 2.03 (1H, m), 2.33 (3H, s), 2.71 (1H , m), 2.81 (1H, s), 2.89 (1H, m), 3.21 (1H, m), 3.42 (2H, m), 5.55 (2H, ABq), 7.08 (1H, d, J=8Hz), 7.39 (1H, t, J=7.6Hz), 7.56 (1H, t, J=7.8Hz), 7.59 (1H, s), 7.69 (1H, d, J=7.6Hz); MS: 380.1 [M+H + ], 402.1[M+Na + ].

Embodiment 3

[0109] Example 3. Synthesis of Compound 3

[0110]

[0111] synthetic route

[0112]

[0113] Synthesis of compound 3-2

[0114] Compound 3-1 (77.5g, 0.5mol), methyl cyanoacetate (99.1g, 1mol) and 50ml methanol were added to a 250ml round-bottomed flask, 1ml DMF and 5ml triethylamine were added dropwise under ice bath, and heated to 70°C The reaction was carried out for 3 hours, the solvent was evaporated under reduced pressure, and the residue was treated with 1 L of cold water and stirred to obtain a gray-brown precipitate, which was filtered with suction, washed with cold water, and dried to obtain 113 g of gray solid compound 3-2 with a yield of 79.6%.

[0115] 1 H-NMR (400MHz, CDCl 3 ): δ6.98 (1H, d, J=5.2Hz), 6.30 (1H, d, J=5.2Hz), 4.0 (2H, s), 3.80 (3H, s); MS: 158.0 [M+H + ].

[0116] Synthesis of compound 3-3

[0117] The compound 3-2 (9.5 g, 6 mmol) obtained in the previous step was dissolved in 300 ml of dry dichloromethane, cooled to -60°C, and 9 g of c...

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 belongs to the technical field of medicines, and in particular relates to a compound taking thieno-pyrimidone as mother nuclide or a salt thereof, a preparation method and a combination of the compound and application of the compound used as a DPP-IV (dipeptidyl peptidase) inhibitor in preventing or treating diseases benefiting from the DPP-IV inhibition. The compound provided by the invention has the advantages that the preparation process is simple, the raw material is easily available, the compound is suitable for large-scale production, and in-vitro experiment verifies that the compound has good selective inhibition action on the DPP-IV, and hardly has any influence on the activities of DPP-VIII and DPP-IX while effectively inhibiting the activity of the DDP-IV, thereby predicting that the medicine prepared from the compound has very low toxicity and an outstanding advantage.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a compound with thienopyrimidinone as a parent nucleus or a salt thereof, a preparation method and composition thereof, and such compounds as dipeptidyl peptidase (DPP-IV) inhibitors in Use in the prevention or treatment of diseases that benefit from DPP-IV inhibition. Background technique [0002] Diabetes Mellitus (DM) is a metabolic disease with multiple etiologies, which is a metabolic disorder caused by the increase of blood sugar caused by the absolute or relative deficiency of insulin. It can be divided into insulin-dependent diabetes mellitus (IDDM, namely type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM, namely type II diabetes), of which type II diabetes is the most common and accounts for the majority of diabetic patients. more than 90 percent. At present, most of the research on diabetes treatment drugs is aimed at type II diabetes. ...

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 Applications(China)
IPC IPC(8): C07D495/04A61K31/519A61P3/10A61P3/06A61P3/08A61P3/00A61P3/04A61P35/00A61P25/00A61P37/00
Inventor 胡文辉张桂成兰小兵杨玲徐宏江
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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