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

Substituted pyrimidin-4-one derivatives

A kind of technology of pyrimidinone and derivatives, applied in the field of substituted pyrimidin-4-one derivatives

Inactive Publication Date: 2011-05-25
MITSUBISHI TANABE PHARMA CORP +1
View PDF1 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although hyperphosphorylation of tau leads to destabilization of the neuronal cytoskeleton, it is very likely that the pathological consequences of abnormal GSK3β activity are not solely due to pathological phosphorylation of tau protein because of the activation of this kinase as described above. Hyperactivity affects survival through regulation of apoptotic and anti-apoptotic factor expression

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
  • Substituted pyrimidin-4-one derivatives
  • Substituted pyrimidin-4-one derivatives
  • Substituted pyrimidin-4-one derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0150] Example 1 (Compound 3 of Table 1)

[0151] (+ / -)-4-Oxo-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-carboxylic acid N- (4-Chloro-2-methoxy-phenyl)-amide

[0152] 1.1(+ / -)-4-oxo-2-(pyrimidin-4-yl)-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-carboxylic acid ester

[0153] To 23.50g (121.99mmol) of 2-amino-3,4,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester hydrochloride (1:1) (such as Journal of Medicinal Chemistry (1994), 37( 17), synthesized as described in 2774-2782) to a suspension in 240 mL of toluene was added 27.91 mL (121.99 mmol) of sodium methoxide (25% wt. in methanol). The reaction mixture was stirred at room temperature for 30 minutes. 23.68 g (121.99 mmol) of ethyl 3-(pyrimidin-4-yl)-3-oxopropanoate were added, and the resulting mixture was stirred under reflux for 16 hours. The mixture was dissolved in water, and the resulting solid was filtered, rinsing with ether. The residue was purified by flash chromatography (2% ...

Embodiment 2

[0163] Example 2 (Compound 4 of Table 1)

[0164] (+ / -)-9-Methyl-4-oxo-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine- 9-Formic acid N-(4-chloro-2-methoxy-phenyl)-amide

[0165] At 0°C, to 0.100g (0.24mmol) of 4-oxo-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine -9-Formic acid N-(4-chloro-2-methoxy-phenyl)-amide ( Example 1 ) was added to a suspension in 1.00 mL of dimethylformamide, and 0.010 g (0.24 mmol) of sodium hydroxide was added, and the resulting mixture was stirred at room temperature for 2 hours. 0.020 mL (0.24 mmol) of methyl iodide was added, and the mixture was stirred at room temperature for 1 hour. The mixture was dissolved in water and dichloromethane. The organic phase is washed with saturated aqueous sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography (cyclohexane / ethyl acetate in the ratio 80 / 20 to 70 / 30) to give 0.053 g (51%) of a solid.

[0166] M...

Embodiment 3

[0169] Embodiment 3 (compound 5 of table 1)

[0170] 4-Oxo-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-carboxylic acid N-(2-methoxy -benzyl)amide

[0171] By a method similar to that described in Example 1 (step 1.2), using 2-methoxy-benzylamine instead of 4-chloro-2-methoxy-aniline, 0.085 g of the title compound (62%) was obtained, which It is white powder.

[0172] Mp: 181-183°C.

[0173] RMN 1 H(DMSO-d 6 ;400MHz)

[0174] δ(ppm): 9.32(s, 1H), 8.79(m, 1H), 7.82(d, 1H), 7.53(m, 1H), 7.31(m, 3H), 6.87(m, 2H), 4.45(m , 2H), 4.10-3.85(m, 3H), 3.65(s, 3H), 2.61(m, 1H), 2.08(m, 3H).

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

A pyrimidone derivative represented by formula (I) or a salt thereof: wherein: Y represents two hydrogen atoms, a sulphur atom, an oxygen atom; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom; R2 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R3 represents a phenyl-group, a phenyl-CH2- group, a C1-6 alkyl-O-C(O)- group, a phenyl-C(O)- group, a 5-10 membered heterocyclic group, a phenyl-CH2-O-C(O)- group, a -C(O)-5-10 membered heterocyclic group, these groups being optionnally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-6 alkoxy group, a C1-2 perhalogenated alkoxy group, a C1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C1-6 monoalkylamino group or a C2-12 dialkylamino-group, an acetoxy group, an aminosulfonyl group; R4 represents a hydrogen atom, a halogen atom, a hydroxyl group, a C1-6 alkyl group; m represents 0 to 2, in the form of a free base or of an addition salt with an acid.

Description

field of invention [0001] The present invention relates to compounds for use as active ingredients of medicaments for the prophylactic and / or therapeutic treatment of neurodegenerative diseases caused by abnormal activity of GSK3β. Background technique [0002] GSK3β (Glycogen Synthase Kinase 3β) is a proline-directed serine / threonine kinase that plays an important role in the control of metabolism, differentiation and survival. It was originally identified as an enzyme capable of phosphorylating and thereby inhibiting glycogen synthase. Later, it was recognized that GSK3β was identical to tau protein kinase 1 (TPK1), an enzyme that phosphorylates tau protein in an epitope also found in Alzheimer's disease ( Alzheimer's disease) and several taupathies are hyperphosphorylated. [0003] Interestingly, protein kinase B (AKT) phosphorylation of GSK3β leads to loss of its kinase activity, and this inhibition has been hypothesized to mediate some of the effects of neurotrophins....

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): C07D471/04A61K31/519A61P25/00
CPCC07D471/04A61P13/12A61P17/00A61P17/14A61P19/00A61P19/08A61P21/00A61P21/02A61P25/00A61P25/02A61P25/16A61P25/18A61P25/24A61P25/28A61P27/00A61P27/02A61P27/06A61P3/10A61P33/06A61P35/00A61P3/04A61P35/02A61P37/00A61P7/00A61P9/00A61P9/10Y02A50/30C07D403/04A61K31/519
Inventor 奥德·费约尔阿利斯泰尔·洛克黑德穆拉德·萨迪朱利恩·瓦切菲利普·耶切
Owner MITSUBISHI TANABE PHARMA CORP
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