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

1, 3, 4, 5-tetrahydro-2h-pyrido[4,3-b]indole derivatives for the treatment, alleviation or prevention of disorders associated with tau aggregates like alzheimer's disease

A compound, a mixture of technology, applied in 1,3,4,5-tetrahydro-2H-pyrido[4,3 -b] In the field of indole derivatives, the effect of preventing or reducing cognitive deficits and reducing the spread of pathology can be achieved

Active Publication Date: 2020-10-09
AC IMMUNE SA
View PDF10 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, only one kinase inhibitor, nilotinib, is currently being tested in clinical trials

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
  • 1, 3, 4, 5-tetrahydro-2h-pyrido[4,3-b]indole derivatives for the treatment, alleviation or prevention of disorders associated with tau aggregates like alzheimer's disease
  • 1, 3, 4, 5-tetrahydro-2h-pyrido[4,3-b]indole derivatives for the treatment, alleviation or prevention of disorders associated with tau aggregates like alzheimer's disease
  • 1, 3, 4, 5-tetrahydro-2h-pyrido[4,3-b]indole derivatives for the treatment, alleviation or prevention of disorders associated with tau aggregates like alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0183]

[0184] .

[0185] And therefore, Cover the following implementation options:

[0186]

[0187] . In a preferred embodiment, Selected from .

[0188] The following loop can be imagined:

[0189]

[0190] . Preferred embodiments include

[0191] . In these structural formulas, ring G is not completely shown, but only part of the bond Said.

[0192] In a preferred embodiment, A is selected from

[0193] .

[0194] In another preferred embodiment, A is . In a preferred embodiment, A is .

[0195] In a more preferred embodiment, A is selected from

[0196] . In a more preferred embodiment, A is selected from

[0197] .

[0198] In a further preferred embodiment, A is selected from

[0199] .

[0200] In an even more preferred embodiment, A is .

[0201] In the definition of A and its preferred embodiments above,

[0202]

[0203] Can be connected to Q in any available position.

[0204] In the definition of A and its preferred embodiments above,

[0205] By one or mo...

preparation Embodiment 1

[0306]

[0307] Step A

[0308] To 4-fluorophenylhydrazine (1 g, 7.9 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (1.2 g, 8.3 mmol) in 1,4-dioxane (10 mmol) at ice bath temperature mL) in the solution by adding concentrated H 2 SO 4 (1 mL). The reaction mixture was then heated at 110°C for 3 hours. The reaction mixture was cooled to room temperature, and the precipitate was filtered off. The solid was dissolved in water basified with NaOH solution and extracted with DCM (dichloromethane). Separate the organic phase, pass Na 2 SO 4 Dry and remove the solvent to obtain the title compound (950 mg, 59%) as a pale yellow solid.

[0309]

[0310] Step B

[0311] To a solution of the title compound (0.95 g, 4.77 mmol) in THF (tetrahydrofuran) from step A above was added di-tert-butyl dicarbonate (Boc 2 O) (1.5 g), and the mixture was stirred overnight. After the completion of the reaction was confirmed by TLC, the solvent was removed and the Biotage Isolera One purification sy...

preparation Embodiment 2

[0322]

[0323] Step A

[0324] To a solution of the title compound (0.41 g, 1.41 mmol) from Step B of Preparation Example 1 in THF (5 mL) was added sodium hydride (0.067 g, 2.82 mmol), and the suspension was stirred at room temperature for 20 minutes. The reaction mixture was cooled to 0°C again, and methyl iodide (0.24 g, 1.45 mmol) was added. The reaction mixture was stirred for 3 hours. The reaction mixture was dissolved in EtOAc (15 mL) and washed with water and brine, and washed with Na 2 SO 4 dry. Use Biotage Isolera One purification system with EtOAc / hexane gradient (20 / 80 => 80 / 20) The crude product was purified on a silica gel column to obtain the title compound (0.3 g, 70%).

[0325]

[0326] Step B

[0327] To a solution of the title compound (0.3 mg, 0.986 mmol) in dichloromethane from step A above was added 2N HCl (5 mL) in 1,4-dioxane. The reaction mixture was stirred overnight. The reaction mixture was evaporated to remove the solvent and washed with ether to ...

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 relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

Description

[0001] Invention field [0002] The present invention relates to novel compounds that can be used to treat, reduce or prevent a group of disorders and abnormalities associated with Tau (tubulin-related unit) protein aggregates, including but not limited to neurofibrillary tangles (NFT) , Such as Alzheimer's disease (AD). [0003] Background of the invention [0004] Many aging diseases are based on or involve extracellular or intracellular deposits of amyloid or amyloid-like protein, which contribute to the pathogenesis and progression of the disease. The most characteristic amyloid that forms extracellular aggregates is amyloid beta (Aβ). Other examples of amyloid that form extracellular aggregates are prions, ATTR (transthyretin) or ADan (ADanPP). The amyloid-like proteins that mainly form intracellular aggregates include but are not limited to Tau, α-synuclein, TAR DNA binding protein 43 (TDP-43) and Huntingtin (htt). Diseases involving Tau aggregates are usually classified as ...

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): C07D471/04A61K31/437A61P25/28
CPCC07D471/04A61P25/28A61K45/06A61K31/5377A61K31/437C07D491/048C07D471/14
Inventor S.南帕利E.加贝利里J.莫莱特
Owner AC IMMUNE SA
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