Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use

A kind of compound, the technology of di-ester, is applied in the prodrug of methyl hydrogen fumarate, its pharmaceutical composition, and its use field, can solve problems such as poor water solubility

Inactive Publication Date: 2011-07-13
XENOPORT
View PDF24 Cites 65 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, DMF exhibi

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
  • Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use
  • Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use
  • Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0480] (N,N-Diethylcarbamoyl)methylmethyl(2E)but-2-ene-1,4-dioate (1)

[0481]

[0482] According to General Procedure A, methyl hydrogen fumarate (MHF) (0.39 g, 3.00 mmol) dissolved in NMP was mixed with 2-chloro-N,N-diethylacetamide (0.44 g, 3.00 mmol) at about 55 °C ) in CsHCO 3 (0.69 g, 3.60 mmol) gave 0.37 g ( 51% yield) of the title compound (1). M.p.: 53-56°C. 1 H NMR (CDCl 3 , 400MHz): δ6.99-6.90(m, 2H), 4.83(s, 2H), 3.80(s, 3H), 3.39(q, J=7.2Hz, 2H), 3.26(q, J=7.2Hz, 2H), 1.24(t, J=7.2Hz, 3H), 1.14(t, J=7.2Hz, 3H). MS(ESI): m / z 244.13(M+H) + .

Embodiment 2

[0484] Methyl[N-benzylcarbamoyl]methyl(2E)but-2-ene-1,4-dioate (2)

[0485]

[0486] According to General Procedure A, methyl hydrogen fumarate (MHF) (0.50 g, 3.85 mmol) dissolved in NMP was mixed with N-benzylchloroacetamide (0.84 g, 4.61 mmol) in CsHCO at about 55 °C. 3 Reaction in the presence of (0.89 g, 4.61 mmol) afforded 0.56 g (53% yield) of the title compound (2) as a white solid after purification by mass-directed preparative HPLC and lyophilization. 1 H NMR (CDCl 3 , 400MHz): δ7.36-7.26(m, 5H), 6.94-6.88(m, 2H), 6.19(br s, 1H), 4.73(s, 2H), 4.51(d, J=5.6Hz, 2H) , 3.81(s, 3H). MS(ESI): m / z 278.04(M+H) + .

Embodiment 3

[0488] Methyl 2-morpholin-4-yl-2-oxoethyl(2E)but-2-ene-1,4-dioate (3)

[0489]

[0490] According to General Procedure A, methyl hydrogen fumarate (MHF) (0.50 g, 3.84 mmol) dissolved in NMP was mixed with 4-(chloroacetyl)morpholine (0.75 g, 4.61 mmol) in CsHCO at about 55 °C. 3 Reaction in the presence of (0.89 g, 4.61 mmol) afforded 0.34 g (35% yield) of the title compound (3) as a white solid after purification by mass-directed preparative HPLC and lyophilization. M.p.: 124-126°C; 1 H NMR (CDCl 3 , 400MHz): δ6.97-6.91(m, 2H), 4.84(s, 2H), 3.82(s, 3H), 3.72-3.70(m, 4H), 3.64-3.62(m, 2H), 3.46-3.41 (m, 2H). MS(ESI): m / z 258.04(M+H) + .

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

Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions comprising the prodrugs of methyl hydrogen fumarate, and methods of using the prodrugs of methyl hydrogen fumarate and the pharmaceutical compositions thereof for treating diseases such as psoriasis, asthma, multiple sclerosis, inflammatory bowel disease, and arthritis are disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application 61 / 090,163, filed August 19, 2008, entitled "Prodrugs of Methyl Hydrogen Fumarate, Pharmaceutical Compositions Thereof, and Methods of Use," which is hereby incorporated by reference in its entirety Apply. technical field [0003] The application discloses a prodrug of methyl hydrogen fumarate, a pharmaceutical composition comprising the methyl hydrogen fumarate prodrug, and a prodrug of methyl hydrogen fumarate and a pharmaceutical composition thereof for the treatment of diseases such as Usage in diseases of psoriasis, asthma, multiple sclerosis, inflammatory bowel disease, and arthritis. Background technique [0004] Esters of fumaric acid (FAE) are approved in Germany for the treatment of psoriasis, are being evaluated in the United States for the treatment of psoriasis and multiple sclerosis, and have been proposed for the treatment of various immun...

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): A61P17/06A61P9/10A61P19/02A61K31/16C07C69/60C07C69/96
CPCC07D295/185C07D263/20C07D207/16C07D295/18C07C235/06C07C69/96C07C271/64C07C235/10C07D285/12C07C259/06C07C69/78C07C2101/14C07C69/75C07C275/50C07C69/60C07C235/08C07C235/12C07C2601/14A61P1/00A61P1/04A61P11/00A61P11/06A61P17/00A61P17/06A61P19/00A61P19/02A61P25/00A61P25/16A61P25/28A61P29/00A61P9/00A61P9/10
Inventor A·冈加克赫德卡X·戴N·泽朗古尔P·A·沃斯克
Owner XENOPORT
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
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap