Benzoxazinone derivatives for treatment of skin diseases
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.
1. A compound according to Formula I
wherein R is —S—CH 3 or —Cl, or a pharmaceutically acceptable salt thereof.
2. The compound 6-Ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one.
3. The compound 2-(2-Chlorophenyl)-6-ethoxy-7-methoxy-3,1-benzoxazin-4-one.
4. A method for treatment of a skin disease selected from Netherton syndrome, atopic dermatitis, contact dermatitis, eczema, psoriasis, acne, epidermal hyperkeratosis, acanthosis, epidermal inflammation, dermal inflammation and pruritus comprising: administrating a therapeutically active amount of a compound according to claim 1 , to a subject in need of such treatment.
5. The method according to claim 4 , wherein the skin disease is Netherton syndrome.