Benzoxazinone derivatives for treatment of skin diseases

A technology for benzoxazine and skin diseases, which is applied in the field of inhibiting the activity of skin proteases, and can solve the problem of not reporting compound selectivity data

Active Publication Date: 2016-11-16
SIXERA PHARMA
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] WO 2004 / 108139 describes some substituted benzoxazinone and thienoxazinone compounds as inhibitors of KLK7, but does not report any selectivity data for the described compounds

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
  • Benzoxazinone derivatives for treatment of skin diseases
  • Benzoxazinone derivatives for treatment of skin diseases
  • Benzoxazinone derivatives for treatment of skin diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Selectivity of substituted 3,1-benzoxazin-4-ones as inhibitors of human proteases

[0051] Determination of the ICs of some substituted 3,1-benzoxazin-4-ones against a panel of human proteases 50 value.

[0052] KLK7 test

[0053] Material: recombinant human KLK7, substrate S-2586 (chromogenic substrate, cat.no.820894)

[0054] KLK7 activity was measured under the following conditions: 37°C, in 10mM sodium phosphate pH 7.2, 0.5M NaCl, KLK7 final concentration 2.5μg / mL (100nM), 1.0mM substrate, 5% DMSO inhibitor concentrations were 0μM, respectively. 0.1 μM, 0.5 μM, 1.0 μM and 5.0 μM, using a 96-well plate to measure the absorbance at 405 nm with a microplate reader (Spectramax).

[0055] KLK5 test

[0056] Material: recombinant human KLK5, substrate S-2288 (chromogenic substrate, cat.no.820852)

[0057] KLK5 activity was determined under the following conditions: 37°C, inhibition in 0.1mM Tris (trishydroxymethylaminomethane), pH 8.0, 0.15M NaCl, KLK5 final concentr...

Embodiment 2

[0081] Synthesis of 6-ethoxy-7-methoxy-2-(2-methylmercaptophenyl)-3,1-benzoxazin-4-one

[0082]

Embodiment 3

[0084] Synthesis of 2-(2-chlorophenyl)-6-ethoxy-7-methoxy-3,l-benzoxazin-4-one

[0085] Same as Example 2 but using in the third step

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 methods and compositions for inhibiting the activity of skin proteases, especially human kallikrein 7 (KLK7), human kallikrein 5 (KLK5), and human kallikrein 14 (KLK14). More specifically, the invention relates to the use of substituted 3,1 -benzoxazin-4-ones being selective inhibitors of human skin kallikreins for the treatment of skin diseases, more specifically for the treatment of inflammatory skins diseases, especially Netherton syndrome.

Description

technical field [0001] The present invention relates to methods and compositions for inhibiting the activity of skin proteases, in particular human kallikrein 7 (KLK7), human kallikrein 5 (KLK5) and human kallikrein 14 (KLK14 ). More specifically, the present invention relates to the use of substituted 3,1-benzoxazin-4-ones as selective inhibitors of human skin kallikrein for the treatment of skin diseases, more specifically for Treatment of inflammatory skin disorders, especially Netherton syndrome. Background technique [0002] KLK7 (hK7, or cornified chymotrypsin (SCCE), Swissprot P49862) is an S1 serine protease of the kallikrein gene family that exhibits chymotrypsin-like activity. KLK7 is mainly expressed in the skin and appears to play an important role in skin physiology (Egelrud. 1993. Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved indesquamation. J. Invest. Dermatol. 101, 200-204; Skytt et ...

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): C07D265/20A61K31/536A61P17/04A61P17/06
CPCA61K31/536C07D265/22C07D498/04A61K31/539A61P17/00A61P17/02A61P17/04A61P17/06A61P29/00A61P37/08
Inventor F·沃格贝里G·莱昂纳德松
Owner SIXERA PHARMA
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