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

Glucosylceramide Synthase Inhibitors For The Treatment Of Diseases

A technology of compounds and mixtures, applied in metabolic diseases, nervous system diseases, urinary system diseases, etc., can solve the problems of uncomfortable patients and unable to solve neurological manifestations

Inactive Publication Date: 2018-01-26
BIOMARIN PHARMA INC
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

One treatment strategy is to provide patients with the defective enzyme; however, enzyme replacement therapy is not suitable for all patients and does not address the neurological manifestations of the disease in patients with types 2 and 3

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
  • Glucosylceramide Synthase Inhibitors For The Treatment Of Diseases
  • Glucosylceramide Synthase Inhibitors For The Treatment Of Diseases
  • Glucosylceramide Synthase Inhibitors For The Treatment Of Diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0081] The following paragraphs represent various embodiments of the compounds disclosed herein, wherein suitable substituents are independently selected as outlined in the Summary of the Invention and described below. Accordingly, compounds of the formulas defined by any combination of the broader and narrower definitions of these substituents listed herein are provided. In each case, the embodiments include the compounds as well as both single stereoisomers or mixtures of stereoisomers and pharmaceutically acceptable salts thereof.

[0082] The compounds described herein and their corresponding pharmaceutically acceptable salts may exist in isotopically labeled forms wherein one or more atoms of the compound are replaced by atoms having the same atomic number but an atomic mass different from that normally found in nature. Examples of isotopes that may be incorporated into the compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulf...

Embodiment 1

[0394]

[0395] To a solution of compound 1A (1.7 g, 10 mmol) in 1,4-dioxane (60 mL) and water (10 mL) was added 4-fluorophenylacetic acid (1.4 g, 10 mmol), K 2 CO 3 (4.14g, 30mmol) and Pd(dppf)Cl 2 (366 mg, 0.5 mmol). The mixture was stirred overnight at 90 °C under nitrogen. After allowing the resulting solution to cool to room temperature, it was filtered on celite. After removing the solvent, the residue was diluted with water (950 mL), extracted with ethyl acetate (100 mL x 3). The organic layer was washed with water (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give crude product. The crude product was purified by flash column chromatography on silica gel (ethyl acetate / petroleum ether, 10% v / v) to obtain compound 1B. 1 H-NMR (CDCl 3 ,400MHz): δ(ppm)2.42(s,3H),7.12(t,J=8.8Hz,2H),7.14-7.17(m,1H),7.31(d,J=8.4Hz,1H),7.35( d, J=8.8Hz, 2H), 7.52-7.55 (m, 2H).

[0396] AlCl at 0°C 3 (1.74g, 13mmol) in anhydrous dichlor...

Embodiment 2

[0403]

[0404] Compound 2 was synthesized using the method described for compound 1 using intermediate D instead of intermediate A. LC-MS (ESI) m / z: 548[M+H] + ; 1 H-NMR (CD 3 OD,400MHz): δ(ppm)0.69-0.78(m,4H),2.05-2.06(m,2H),2.20-2.22(m,2H),3.20-3.27(m,2H),3.52-3.56(m ,1H),3.68-3.74(m,2H),3.81-3.85(m,2H),4.69-4.72(m,1H),4.94(d,J=2.8Hz,1H),5.11(d,J=4.0 Hz,2H),7.20-7.25(m,4H),7.33(t,J=8.4Hz,1H),7.47(d,J=8.0Hz,1H),7.53(s,1H),7.58(d,J =8.4Hz, 1H), 7.69-7.72(m, 2H).

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

Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to US Provisional Application No. 62 / 131,703, filed March 11, 2015, the entire contents of which are incorporated herein by reference in their entirety. field of invention [0003] Described herein are compounds, methods of making the compounds, pharmaceutical compositions and medicaments containing the compounds, and methods of using the compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS). Background of the invention [0004] Glucosylceramide synthase (GCS) is catalyzed in the biosynthesis of glucosphingolipids (GSL) based on glucosylceramide, the formation of glucosylceramide by transferring glucose from UDP-glucose (UDP-Glc) to ceramide Key enzyme that initiates the glycosylation step. GCS is a transmembrane, type III integrin located in the medial / middle Golgi apparatus. Glycosphingolipids (GSLs) are consid...

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): C07D265/02A61K31/535A61P35/00
CPCC07D265/02C07D217/26C07D311/76C07D409/04C07D413/12C07D495/04C07D498/04A61P13/12A61P25/00A61P29/00A61P3/04A61P31/00A61P35/00A61P3/06A61P39/02A61P43/00A61P9/10A61P3/10C07D413/14A61K31/536A61K31/5365C07D311/94
Inventor 兵·王
Owner BIOMARIN PHARMA INC
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