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

N1-cyclic amine-N5-substituted phenyl biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same

A phenylbiguanide and substituent technology, applied in the field of N1-cyclic amine-N5-substituted phenylbiguanide derivatives, can solve the problems of large tablets, lactic acidosis, and difficulty in swallowing by patients

Active Publication Date: 2014-05-28
IMMUNOMET THERAPEUTICS
View PDF2 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a result, the pills are too large for patients to swallow
In addition, since the single extended-release tablets currently on the market contain only about 750 mg of metformin, two or more extended-release tablets are required
In addition, phenformin, which belongs to the same biguanide class, has been completely banned since the 1970s due to serious side effects such as lactic acidosis

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
  • N1-cyclic amine-N5-substituted phenyl biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same
  • N1-cyclic amine-N5-substituted phenyl biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same
  • N1-cyclic amine-N5-substituted phenyl biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093] Embodiment 1: the synthesis of N1-piperidine cyanoguanidine

[0094] Piperidine (92.8ml, 0.940mol) was dissolved in butanol (300ml), concentrated hydrochloric acid (81.7ml, 0.940mol) was added to the resulting solution and stirred at 0°C for 30 minutes. Sodium dicyanamide (92.0 g, 1.03 mol) was added to the resulting mixed solution, and the resulting reaction mixture was stirred under reflux for 24 hours. After confirming that the reaction was finished, the reaction mixture was filtered, and the sodium chloride formed in the filtration was removed, and the filtrate was concentrated under reduced pressure. Distilled water (100 ml) was added to the concentrate, followed by stirring at room temperature for 1 hour. The formed solid was filtered, the filter cake was washed with distilled water (2×20 ml), and then dried under reduced pressure to obtain the target compound as a white solid (93.3 g, 65%).

[0095] 1 H NMR (600MHz, DMSO-d 6 )δ7.01 (br, s, 2H), 3.39 (m, 4H), ...

Embodiment 2

[0096] Embodiment 2: the synthesis of N1-azetidine cyanoguanidine

[0097]

[0098] The title compound (1.13 g, 52%) was prepared as a white solid as described in Example 1, but substituting azetidine for the piperidine used in Example 1.

[0099] 1 H NMR (600MHz, DMSO-d 6 )δ6.92 (br, s, 2H), 3.91 (t, J=7.8Hz, 4H), 2.16 (tt, J=7.8, 7.8Hz, 2H); LC-MSm / z125.2[M+1] + ; mp 188-189°C.

Embodiment 3

[0100] Embodiment 3: N1-pyrrolidine cyanidine

[0101]

[0102] The title compound (24.5 g, 63%) was prepared as a white solid as described in Example 1, but substituting pyrrolidine for the piperidine used in Example 1.

[0103] 1 H NMR (600MHz, DMSO-d 6 )δ6.88 (br, s, 2H), 3.24 (m, 4H), 1.80 (m, 4H); LC-MS m / z139.2[M+1] + ; mp 232-235°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

An N1-cyclic amine-N5-substituted phenyl biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs.; Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

Description

technical field [0001] The present invention relates to: an N1-cyclic amine-N5-substituted phenyl biguanide derivative, which can inhibit the proliferation of cancer cells, cancer metastasis and cancer recurrence, and also inhibit diabetes and New town metabolic disease has excellent curative effect even if its dose is less than that of conventional medicine; a method for preparing the derivative; and a drug combination containing the N1-cycloamine-N5-substituted phenylbiguanide derivative as an active ingredient thing. Background technique [0002] AMPK is an enzyme whose function is to control metabolic pathways to maintain a balance between nutrient supply and energy demand, and thereby maintain energy balance in cells and throughout the body. In the state of hypoxemia or hypoglycemia, the ratio of intracellular AMP / ATP increases and AMPK is activated. Activated AMPK causes fatty acid oxidation to generate greater amounts of ATP and inhibits anabolism that requires ATP ...

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): C07C279/26A61P35/00C07C277/02A61K31/155
CPCC07D207/04C07D211/06C07D295/215C07D205/04C07D223/04C07D257/04A61P1/16A61P15/08A61P19/10A61P21/00A61P29/00A61P3/04A61P35/00A61P35/02A61P3/06A61P35/04A61P9/10A61P3/10C07C279/26A61K31/155C07D207/06C07D211/14C07D295/14
Inventor 金圣旭闵昌熙朴世焕金德李枝鲜金用恩吴柱勳
Owner IMMUNOMET THERAPEUTICS
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