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

Aminopyran deuterated derivative, composition and application thereof

A composition and compound technology, applied in the field of dipeptidyl peptidase IV inhibitors, can solve problems such as diabetes burden

Active Publication Date: 2020-06-09
SICHUAN HAISCO PHARMA CO LTD
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Diabetes treatment places a heavy burden on families and society

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
  • Aminopyran deuterated derivative, composition and application thereof
  • Aminopyran deuterated derivative, composition and application thereof
  • Aminopyran deuterated derivative, composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1: (2R,3S)-4,4,5,6-tetradeutero-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydro Pyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)tetrahydropyran-3-amine (Compound 1)(2R,3S)-4,4,5,6 -tetradeuterio-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)tetrahydropyran-3-amine

[0117]

[0118] The first step: N-deutero-N-[(2R,3S)-4,4,6-trideuterium-2-(2,5-difluorophenyl)-5-oxo-6-(trifluoro Methyl) tetrahydropyran-3-yl] tert-butyl carbamate (1B)

[0119] tert-butylN-deuterio-N-[(2R,3S)-4,4,6-trideuterio-2-(2,5-difluorophenyl)-5-oxo-6-(trifluoromethyl)tetrahydropyran-3-yl]carbamate

[0120]

[0121] Compound 1A was synthesized according to the method of WO2015192701.

[0122] Sodium metal (6mg, 0.26mmol) was added to a microwave tube filled with heavy water (10mL), compound 1A (500mg, 1.27mmol) was dissolved in deuterated acetonitrile (5mL), added to the microwave tube, and heated at 85°C Under the microwa...

Embodiment 2

[0152] Example 2: (2R, 3S, 5R, 6S)-5-deutero-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo [3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)tetrahydropyran-3-amine (compound 2)

[0153] (2R,3S,5R,6S)-5-deuterio-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)- 6-(trifluoromethyl)tetrahydropyran-3-amine

[0154]

[0155] The first step: N-[(2R, 3S, 5R, 6S)-5-deutero-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-di tert-butyl hydropyrrolo[3,4-C]pyrazolpyrimidin-5-yl)-6-(trifluoromethyl)tetrahydropyran-3-yl]carbamate (2B)

[0156] tert-butylN-[(2R,3S,5R,6S)-5-deuterio-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol- 5-yl)-6-(trifluoromethyl)tetrahydropyran-3-yl]carbamate

[0157]

[0158] Compound 2A and Compound 1C were synthesized by referring to WO2015192701. Compound 1A (395mg, 1.00mmol) and Compound 1C (281mg, 1.50mmol) were added to a reaction flask filled with chloroform (10mL), heated and stirr...

Embodiment 3

[0165] Example 3: (2R, 3S, 5R, 6S)-5-deutero-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl )-6-(trifluoromethyl)-2-(2-,4,5-trifluorophenyl)tetrahydropyran-3-amine (Compound 3)

[0166] (2R,3S,5R,6S)-5-deuterio-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)-2-(2 ,4,5-trifluorophenyl)tetrahydropyran-3-amine

[0167]

[0168] The first step: N-[(2R, 3S, 5R, 6S)-5-deutero-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazole- 5-yl)-6-(trifluoromethyl)-2-(2,4,5-trifluorophenyl)tetrahydropyran-3-yl]carbamate tert-butyl ester (3B)

[0169] tert-butylN-[(2R,3S,5R,6S)-5-deuterio-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl) -2-(2,4,5-trifluorophenyl)tetrahydropyran-3-yl]carbamate

[0170]

[0171] Compound 2A and Compound 1C were synthesized by referring to WO2015192701. Compound 3A (413mg, 1.00mmol) and Compound 1C (281mg, 1.50mmol) were added to a reaction flask filled with chloroform (10mL), heate...

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 relates to an aminopyran deuterated derivative, a composition and application thereof, specifically to an aminopyran derivative represented by a general formula (I) or a pharmaceuticallyacceptable salt or a stereoisomer thereof, a pharmaceutical composition containing the derivative or the pharmaceutically acceptable salt or the stereoisomer thereof, and an application of the derivative or the pharmaceutically acceptable salt or the stereoisomer thereof or the pharmaceutical composition as a therapeutic agent, especially as a dipeptidyl peptidase IV (DPP-IV) inhibitor.

Description

technical field [0001] The present invention relates to an aminopyran deuterated derivative and its composition and application, in particular to an aminopyran derivative represented by the general formula (I) or a pharmaceutically acceptable salt thereof or a stereoisomer thereof and containing the aminopyran derivative Pharmaceutical compositions of derivatives or pharmaceutically acceptable salts thereof or stereoisomers thereof, and their use as therapeutic agents, in particular as dipeptidyl peptidase IV (DPP-IV) inhibitors. Background technique [0002] Diabetes is a major medical problem worldwide. Diabetes is generally divided into type I diabetes (or insulin-dependent diabetes mellitus, IDDM) and type II diabetes (or non-islet-dependent diabetes mellitus, NIDDM). The most common type of diabetes is type II diabetes, which accounts for approximately 90% of all diabetes worldwide. Due to modern unhealthy lifestyles, such as reduced exercise and high-calorie diet, th...

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): C07D487/04A61P3/10A61P27/02A61P25/00A61P13/12A61P5/50A61P3/06A61P3/04A61P9/10A61P9/12A61K31/4162
CPCC07D487/04A61P3/10A61P27/02A61P25/00A61P13/12A61P5/50A61P3/06A61P3/04A61P9/10A61P9/12C07B2200/05
Inventor 张晨王健民黄正刚李瑶严庞科郑伟
Owner SICHUAN HAISCO PHARMA CO LTD