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

Novel condensed imidazole derivatives

a technology of condensed imidazole and derivatives, which is applied in the field of new condensed imidazole derivatives, can solve the problems of no known dppiv inhibitor having a hypoxanthine or imidazopyridazinone structure backbone, and achieve excellent dppiv-inhibiting activity

Inactive Publication Date: 2006-05-11
EISIA R&D MANAGEMENT CO LTD
View PDF12 Cites 91 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to the synthesis of novel condensed imidazole derivatives with excellent DPPIV-inhibiting activity. The invention includes compounds represented by formulas I, Z1, and Z2, as well as salts and hydrates of these compounds. The compounds have been found to have excellent inhibitory activity against DPPIV, a protein that plays a role in the development of diabetes and other metabolic disorders. The invention also includes methods for making these compounds and uses them in the treatment of diabetes and other metabolic disorders.

Problems solved by technology

However, there is no known DPPIV inhibitor having a hypoxanthine or imidazopyridazinone structure backbone.

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
  • Novel condensed imidazole derivatives
  • Novel condensed imidazole derivatives
  • Novel condensed imidazole derivatives

Examples

Experimental program
Comparison scheme
Effect test

production example

Production Example 1

t-Butyl 4-[1-(2-butynyl)-6-methyl-7-oxo-6,7-dihydro-1H-imidazo[4,5-d]pyridazin-2-yl]piperazin-1-carboxylate

(a) t-Butyl 5-methyl-4-oxo-4,5-dihydroimidazo[4,5-d]pyridazine-1-carboxylate

[0605] A mixture consisting of 1.0 g of 5-methyl-3,5-dihydroimidazo[4,5-d]pyridazin-4-one, 16 mg of 4-dimethylaminopyridine, 1.6 g of di-t-butyl dicarbonate, and 5 ml of tetrahydrofuran was stirred at room temperature overnight. Then, a 0.5-ml tetrahydrofuran solution containing 300 mg of di-t-butyl dicarbonate was added to the solution, and the resulting mixture was stirred at room temperature for three hours. 5 ml of t-butyl methyl ether was added to the reaction mixture, and the mixture was cooled with ice. The resulting crystals were collected by filtration to give 1.63 g of the title compound.

[0606]1H-NMR(CDCl3)

[0607]δ 1.72 (s, 9H) 3.93 (s, 3H) 8.38 (s, 1H) 8.54 (s, 1H)

(b) 2-Chloro-5-methyl-1,5-dihydroimidazo[4,5-d]pyridazin-4-one

[0608] 8.4 ml of lithium hexamethyldisilaz...

production example 2

t-Butyl 4-[7-(2-butynyl)-2,6-dichloro-7H-purin-8-yl]piperazine-1-carboxylate

(a) 7-(2-Butynyl)-3-methyl-3,7-dihydropurine-2,6-dione

[0617] 55.3 ml of 1-bromo-2-butyne and 84.9 g of anhydrous potassium carbonate were added to a mixture of 100 g of 3-methyl xanthine [CAS No. 1076-22-8] and 1000 ml of N,N-dimethylformamide. The resulting mixture was stirred at room temperature for 18 hours. 1000 ml of water was added to the reaction solution, and the mixture was stirred at room temperature for 1hour. The resulting white precipitate was collected by filtration. The white solid was washed with water and then t-butyl methyl ether. Thus, 112 g of the title compound was obtained.

[0618]1H-NMR(DMSO-d6)

[0619]δ 1.82 (t, J=2.2 Hz,3H) 3.34 (s, 3H) 5.06 (q, J=2.2Hz, 2H) 8.12 (s, 1H) 11.16 (br.s, 1H)

(b) 7-(2-Butynyl)-8-chloro-3-methyl-3,7-dihydropurine-2,6-dione

[0620] 112 g of 7-(2-butynyl)-3-methyl-3,7-dihydropurine-2,6-dione was dissolved in 2200 ml of N,N-dimethylformamide, and 75.3 g of N-c...

example

Example 1

Ethyl [7-(2-chlorophenyl)-1-methyl-6-oxo-8-(piperazin-1-yl)-6,7-dihydro-1H-purin-2-yloxy]acetate trifluoroacetate

(a) [7-Benzyl-2,6-dioxo-1,2,6,7-tetrahydropurin-3-yl]methyl 2,2-dimethylpropionate

[0629] 8.66 g of 7-benzylxanthine was dissolved in 300 ml of N,N-dimethylformamide, and 1.57 g of sodium hydride and 7.7 ml of chloromethyl pivalate were added thereto. The resulting mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate, and washed with water and 1N hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography. Thus, 2.66 g of the title compound was obtained from the fraction eluted with hexane-ethyl acetate (1:1).

[0630]1H-NMR(CDCl3)

[0631]δ 1.18 (s, 9H) 5.45 (s, 2H) 6.06 (s, 2H) 7.34-7.39 (m, 5H) 7.58 (s, 1H) 8.18 (s, 1H)

(b) [7-Benzyl-l-methyl-2,6-dioxo-1,2,6,7-tetrah...

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 related to compounds represented by the following formula, or salts or hydrates thereof wherein, T1 represents a 4- to 12-membered heterocyclic group containing one or two nitrogen atoms in the ring, which is a monocyclic or bicyclic structure that may have one or more substituents; X represents a C1-6 alkyl group which may have one or more substituents, or such; Z1 and Z2 each independently represent a nitrogen atom or a group represented by the formula —CR2—; R1 and R2 independently represent a hydrogen atom, a C1-6 alkyl group which may have one or more substituents, or a C1-6 alkoxy group which may have one or more substituents, or such. These are novel compounds that exhibit an excellent

Description

TECHNICAL FIELD [0001] The present invention relates to novel condensed imidazole derivatives useful as dipeptidyl peptidase-IV (DPPIV) inhibitors and uses thereof. BACKGROUND ART [0002] Dipeptidyl peptidase IV (DPPIV) is a serine protease which specifically hydrolyzes dipeptide —X-Pro (X=arbitrary amino acid) from the free N terminus of a polypeptide chain. [0003] Glucose-dependent, insulin secretion-stimulating hormones, known as incretins (GLP-1: Glucagon-Like Peptide-1 and GIP: Glucose-dependent Insulinotropic Polypeptide) secreted in the digestive tract following meals are rapidly hydrolyzed and inactivated by DPPIV. When the hydrolysis by DPPIV is suppressed, the action of incretin (GLP-1 and GIP) is enhanced, which in turn increases the glucose-stimulated secretion of insulin from the β cells of the pancreas. This has been shown to improve hyperglycemia in the oral glucose tolerance test (see Diabetologia November 1999, 42(11), 1324-31). In addition, GLP-1 is known to be invo...

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(United States)
IPC IPC(8): A61K31/551A61K31/522A61K31/503A61K31/4745C07D473/02C07D487/02C07D471/04A61K31/496A61K31/5025A61K31/5377A61K31/541A61P1/00A61P3/04A61P3/06A61P3/10A61P9/00A61P15/00A61P15/08A61P19/02A61P19/10A61P29/00A61P31/18A61P35/00A61P37/00A61P37/02A61P37/08A61P43/00C07D473/04C07D473/06C07D473/18C07D473/22C07D473/24C07D473/30C07D473/36C07D473/40C07D487/04C07D491/14
CPCC07D471/04C07D473/04C07D473/06C07D473/18C07D473/30C07D473/36C07D473/40C07D487/04C07D491/14A61P1/00A61P15/00A61P15/08A61P19/02A61P19/10A61P29/00A61P3/00A61P3/04A61P31/18A61P35/00A61P3/06A61P37/00A61P37/02A61P37/08A61P43/00A61P9/00A61P3/10
Inventor YOSHIKAWA, SEIJIEMORI, EITAMATSUURA, EUMIYOSHICLARK, RICHARDIKUTA, HIRONORIKIRA, KAZUNOBUYASUDA, NOBUYUKINAGAKURA, TADASHIYAMAZAKI, KAZUTO
Owner EISIA R&D MANAGEMENT CO LTD
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