Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Fused aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes

An alkyl, hydroxyl technology, applied in the field of substituted fused amino piperidines, can solve problems such as DPP-IV inhibitors that have not been extensively studied

Inactive Publication Date: 2007-10-31
MERCK & CO INC
View PDF132 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, DPP-IV inhibitors have not been extensively studied for uses other than diabetes

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
  • Fused aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
  • Fused aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
  • Fused aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0240]

[0241] (2R,3R)-7-(pyrrolidin-1-ylcarbonyl)-3-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydropyrido-[1,2 -a] Benzimidazol-2-amine bis(trifluoroacetic acid) salt

[0242] Step A: 4-[5-[(tert-Butoxycarbonyl)amino]-2-oxo-4-(2,4,5-trifluorophenyl)piperidin-1-yl]-3-nitrobenzene Methyl formate

[0243] A septum-capped dry flask was charged with 1.0 g (2.9 mmol) of intermediate 1, 1.1 g (4.4 mmol) of methyl 4-bromo-3-nitrobenzoate, 49 mg (0.26 mmol) of iodine Cuprous chloride, 700 mg (5.1 mmol) potassium carbonate and 10 mL dry toluene. To the resulting suspension was added 0.055 mL (0.51 mmol) of N,N'-dimethylethylenediamine, and the mixture was heated to reflux for 16 hours. The mixture was then cooled to room temperature, then diluted with 100 mL of ethyl acetate, washed sequentially with 1N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and brine (100 mL each), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by fl...

Embodiment 2

[0253]

[0254] (2R,3R)-8-(methylsulfonyl)-3-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydropyrido-[1,2-a] Benzimidazol-2-amine bis(trifluoroacetic acid) salt

[0255] Step A: 2-Bromo-4-(methylthio)aniline

[0256] To a solution of 1.0 ml (8.0 mmol) 4-(methylthio)aniline in 40 ml of a 3:1 acetonitrile / carbon tetrachloride mixture was added 1.6 g (8.8 mmol) of N-bromosuccinimide. The reaction mixture was heated at reflux for 30 minutes, then cooled to room temperature and concentrated in vacuo. To the residue was added 100 mL of ethyl acetate and the organic solution was washed sequentially with saturated aqueous sodium bicarbonate and saturated brine (100 mL each), dried over sodium sulfate, filtered and evaporated in vacuo to give a viscous oil. The crude product was purified by flash chromatography (silica gel, 0 to 30% ethyl acetate / hexanes gradient) on a Biotage Horizon(R) system to afford the title compound. 1 H NMR (CDCl 3 ): δ7.45(s, 1H), 7.15(dd, J=8.3, 2.0Hz, 1H), 6...

Embodiment 29

[0269]

[0270] (7R,8R)-1-Chloro-7-(2,4,5-trifluorophenyl)-6,7,8,9-tetrahydropyrido[4',3':4,5]imidazo [1,2-a]pyridin-8-amine tris(trifluoroacetic acid) salt

[0271] Step A: [(7R,8R)-2-Epoxy-7-(2,4,5-trifluorophenyl)-6,7,8,9-tetrahydropyrido[4',3':4 ,5] tert-butyl imidazo[1,2-a]pyridin-8-yl]carbamate

[0272] To a solution of 48 mg of the Boc-protected intermediate of Example 27 in 2 mL of acetone was added m-chloroperbenzoic acid (28 mg). After stirring for 2 hours, the reaction mixture was concentrated and the residue was purified by reverse phase HPLC (YMC Pro-C18 column, gradient elution, 0% to 65% acetonitrile / water with 0.1% TFA). The residue was dissolved in ethyl acetate (10 mL), washed sequentially with saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL), dried over anhydrous sodium sulfate, filtered and concentrated. LC / MS 435.1 (M+1).

[0273] Step B: [(7R,8R)-1-Chloro-7-(2,4,5-trifluorophenyl)-6,7,8,9-tetrahydropyrido[4',3':4, 5] tert-butyl imidazo...

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 is directed to novel substituted fused aminopipeiridines of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme (''DPP-IV inhibitors'') and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

Description

field of invention [0001] The present invention relates to novel substituted fused aminopiperidines which are inhibitors of dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of dipeptidyl peptidase-IV Diseases in which enzymes are involved, such as diabetes, especially type II diabetes. The present invention also relates to pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions in the prevention or treatment of diseases in which dipeptidyl peptidase-IV enzymes are involved. Background of the invention [0002] Diabetes mellitus is a disease of many etiological factors characterized by elevated plasma glucose levels or hyperglycemia in the fasted state or following administration of glucose during an oral glucose tolerance test. Persistent or uncontrolled hyperglycemia is associated with increased and early morbidity and mortality. Often abnormal glucose homeostasis is di...

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): C07D211/06
CPCC07D471/04C07D471/14A61P25/22A61P25/28A61P3/04A61P3/06A61P43/00A61P9/00A61P3/10
Inventor S·D·埃蒙森A·马斯特拉基奥J·M·科克斯
Owner MERCK & CO INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
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