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

Novel 3-phenyl-azetidine derivatives useful as modulators of cortical catecholaminergic neurotransmission

A technology of azetidine and azetidine, applied in the field of new 3-phenyl-azetidine derivatives, can solve the problem of unreported 3-phenyl-azetidine derivatives, etc. question

Inactive Publication Date: 2011-10-19
NSAB FILIAL AF NEUROSEARCH SVERIGE
View PDF10 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the 3-phenyl-azetidine derivatives of the present invention have not been reported

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 3-phenyl-azetidine derivatives useful as modulators of cortical catecholaminergic neurotransmission
  • Novel 3-phenyl-azetidine derivatives useful as modulators of cortical catecholaminergic neurotransmission
  • Novel 3-phenyl-azetidine derivatives useful as modulators of cortical catecholaminergic neurotransmission

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0127] 3-(2,3-Difluorophenyl)-1-ethylazetidin-3-ol

[0128] 1,3-Dichloro-2-(2,3-difluorophenyl)propan-2-ol (6.0 g, 24.89 mmol) was dissolved in acetonitrile (90 ml), transferred to 6 different microwave vials, Each vial contained an equal amount (1.0 g, 2.49 mmol). Sodium bicarbonate (1.04 g, 12.44 mmol (total 6.27 g, 74.67 mmol)) was added to each tube and the tube was sealed. Ethylamine in tetrahydrofuran (2.0M, 2.07ml, 4.15mmol) was added through the septum (total 12.44ml, 24.89mmol), and the mixture was heated under microwave irradiation at 120°C for 30min. Ethylamine in tetrahydrofuran (2.0M, 1.03ml, 2.07mmol (a total of 6.22ml, 12.44mmol), the mixture was heated under microwave irradiation at 120°C for 30min. A solution of water (100ml) and tert-butyl methyl ether (100ml) was added thereto, and the organic phase was collected. Using tert-butyl methyl ether (100ml) to extract the aqueous phase and dry the combined organic phase (Na 2 SO 4 ) and evaporate. The crude p...

Embodiment 2

[0130] 3-(3,4-Difluorophenyl)-1-ethylazetidin-3-ol

[0131] 3-(3,4-difluorophenyl)azetidin-3-ol (0.3g, 1.62mmol) triethylamine (0.68ml, 4.87mmol) and iodoethane (0.19ml, 2.44mmol ) in tetrahydrofuran (15ml) was stirred at ambient temperature for 15 hours. The solvent was evaporated, aqueous hydrochloric acid (50 mL. 10%) was added and the mixture was washed with tert-butyl methyl ether (2 x 50 mL). The aqueous phase was made basic by addition of aqueous sodium hydroxide (5M) and extracted with tert-butyl methyl ether (2 x 50ml). The combined organic phases were dried (Na 2 SO 4 ), evaporated under reduced pressure to give the crude product (0.26 g). Purification by flash column chromatography (ethyl acetate / methanol 1:1) on silica gel afforded 0.2 g (58%) of the title compound. Amine conversion to fumarate, recrystallization from methanol / ether: M.p. 177-179°C. MS m / z (relative intensity, 70 eV) 213 (M+, 1), 141 (86), 127 (45), 114 (58), 58 (bp).

Embodiment 3

[0133] 3-(3,5-Difluorophenyl)-1-ethylazetidin-3-ol

[0134] Dissolve 1,3-dichloro-2-(3,5-difluorophenyl)propan-2-ol (1.0g, 4.15mmol) in acetonitrile (10ml), add sodium bicarbonate (1.39g, 16.59mmol and ethylamine in water (70%, 0.33ml, 4.15mmol), the mixture was refluxed for 10 hours. Water (50ml) and tert-butyl methyl ether (50ml) were added, and the organic phase was collected. The aqueous phase was extracted with tert-butyl methyl ether (50ml, The combined organic phases were extracted with aqueous hydrochloric acid (10%, 50 ml). The aqueous phase was basified, extracted with tert-butyl methyl ether (2×50 ml), dried (Na 2 SO 4 ) and evaporated to give 0.35 g of crude product. Purification by flash column chromatography (ethyl acetate / MeOH 1:0→1:1) on silica gel afforded the title compound (0.2 g, 23%). Amine conversion to fumarate, recrystallization from ethanol / diethyl ether / diisopropyl ether: M.p. 140-141°C. MS m / z (relative intensity, 70 eV) 213 (M+, 1), 156 (36), 14...

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 3-phenyl-azetidine derivatives, useful for modulating extracellular levels of catecholamines, dopamine and norepinephrine, in cerebral cortical areas of the mammalian brain, and more specifically for the treatment of central nervous system disorders. In other aspects the invention relates to pharmaceutical compositions comprising the 3-phenyl-azetidine derivatives of the invention and to the use of these compounds for therapeutic applications.

Description

technical field [0001] The present invention relates to novel 3-phenyl-azetidine derivatives suitable for modulating the extracellular levels of catecholamines, dopamine and norepinephrine in the cerebral cortex regions of the mammalian brain, more particularly for the therapeutic Disorders of the central nervous system. [0002] In other aspects, the invention relates to pharmaceutical compositions comprising the 3-phenyl-azetidine derivatives of the invention and the use of these compounds in therapeutic applications. Background technique [0003] The cerebral cortex contains several major areas involved in higher functions such as thinking, feeling, memory and planning. Biogenic amines, namely dopamine, norepinephrine and serotonin, are important for cortical function in mammals. The ascending dopamine and norepinephrine pathways innervate the cortex. The serotonergic neurons of the CNS project to virtually all regions of the brain including the cerebral cortex. Prima...

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): C07D205/04A61K31/397A61P25/00
CPCA61P1/00A61P3/00A61P3/04A61P15/00A61P15/10A61P21/00A61P25/00A61P25/04A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/30A61P43/00C07D205/04
Inventor C·索内松L·斯万松F·彼德森
Owner NSAB FILIAL AF NEUROSEARCH SVERIGE
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