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

Piperazine derivatives, preparation process and pharmaceutical use thereof

A pharmacy and compound technology, applied in the field of dipeptidyl peptidase IV inhibitors, can solve problems such as inability to effectively inhibit fat tissue lipolysis

Active Publication Date: 2012-07-11
JIANGSU HENGRUI MEDICINE CO LTD +1
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Insulin-responsive resistance leads to the inability of insulin to activate glucose uptake, oxidation, and storage in muscle tissue, and cannot effectively inhibit lipolysis of adipose tissue and the production and secretion of glucose in the liver

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
  • Piperazine derivatives, preparation process and pharmaceutical use thereof
  • Piperazine derivatives, preparation process and pharmaceutical use thereof
  • Piperazine derivatives, preparation process and pharmaceutical use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] (R)-3-amino-1-(3-trifluoromethyl-imidazo[1,5-a]piperazin-7-yl)-4-(2,4,5-trifluorophenyl)- Butan-1-one hydrochloride

[0115]

[0116] first step

[0117] 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione

[0118] 2,2-Dimethyl-[1,3]dioxane-4,6-dione (5.69g, 39.5mmol) was dissolved in 400mL dichloromethane under stirring, and 2 was added under ice-cooling, 4,5-Trifluorophenylacetic acid (7.15g, 37.6mmol) and p-dimethylaminopyridine (7.35g, 60.2mmol), slowly add 250mL of 1-(3-dimethylamino-propyl)-3-ethyl Dichloromethane solution of base-carbodiimide hydrochloride (8.28g, 43.2mmol), after stirring at room temperature for 36 hours, wash the reaction solution with 5% sodium bisulfate solution (250mL×7) and saturated sodium chloride solution , dried over anhydrous magnesium sulfate, suction filtered, and the filtrate was concentrated under reduced pressure to obtain the title product 2,2-dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[ 1,3] Diox...

Embodiment 2

[0155] (R)-3-amino-1-(1-amino-3-trifluoromethyl-imidazo[1,5-a]piperazin-7-yl)-4-(2,4,5-trifluoro Phenyl)-butan-1-one dihydrochloride

[0156]

[0157] first step

[0158] 1-nitro-3-trifluoromethyl-imidazo[1,5-a]pyrazine

[0159] 3-Trifluoromethyl-imidazo[1,5-a]pyrazine 1h (2g, 10.7mmol) was added to a 25mL single-necked flask, 5mL fuming nitric acid and 5mL concentrated sulfuric acid were added under stirring, and the resulting mixture was heated to 110°C, stirred and reacted for 1.5 hours, and the reaction was completed. After cooling the reaction solution to room temperature, it was poured into 50 mL of concentrated ammonia water cooled in an ice bath. After stirring evenly, it was extracted with ethyl acetate (250 mL×3), and the combined organic phases were Dry over anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and purify the resulting residue by silica gel column chromatography to give the title product 1-nitro-3-trifluoromethyl-imidazo[1,5-...

Embodiment 3

[0175] (R)-3-Amino-1-(1-cyclopentyl-3-trifluoromethyl-imidazo[1,5-a]piperazine-7-)-4-(2,4,5-tri Fluorophenyl)-butan-1-one hydrochloride

[0176]

[0177]

[0178] first step

[0179] 3-cyclopentyl-N*2*-ethylene-N*1*-methylene-propene-1,2,3-triamine

[0180] Dissolve 2-cyanopyrazine 3a (6.3g, 0.06mol) in 80mL of toluene, cool the solution to -10°C, slowly add cyclopentylmagnesium bromide (33mL, 66mmol) dropwise, and stir for 30 minutes after the addition is complete , add dropwise 40mL isopropanol to the reaction solution, stir for 30 minutes, continue to dropwise add 40mL ethanol, at 0°C, add sodium borohydride (3.18g, 84mmol) to the reaction solution, stir overnight at room temperature, add to the reaction solution Add acetone, methanol and water to quench the reaction until no bubbles are generated. Concentrate under reduced pressure to evaporate most of the organic solvent. The aqueous phase is extracted with ethyl acetate (250mL×3). The organic phases are combined,...

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 present invention discloses piperazine derivatives of formula (I), methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as a dipeptidyl peptidase IV inhibitor. The definition of substituents in formula (I) are the same as the description.

Description

technical field [0001] The present invention relates to a new piperazine derivative represented by general formula (I), its preparation method and pharmaceutical composition containing the derivative, and its use as a therapeutic agent, especially as a dipeptidyl peptidase IV inhibitor use. Background technique [0002] Diabetes mellitus is a metabolic disease of multiple etiologies characterized by chronic hyperglycemia accompanied by disturbances in carbohydrate, fat and protein metabolism due to defects in insulin secretion and / or action. Diabetes is a very old disease. It is caused by the absolute or relative lack of insulin in the human body, which causes the blood glucose concentration to rise, and then a large amount of sugar is excreted from the urine, resulting in polydipsia, polyuria, polyphagia, weight loss, and dizziness. , fatigue and other symptoms. [0003] Permanent or uncontrolled hyperglycemia leads to increased morbidity and mortality. Often abnormal gl...

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): C07D487/04A61K31/4985A61P3/10A61P3/04
CPCC07D487/04A61P3/04A61P3/10
Inventor 邓炳初杨方龙王阳沈光远陈天鹏梁金栋
Owner JIANGSU HENGRUI MEDICINE CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com