Hydroxy-substituted amino and ammonium derivatives and their medical use
The present invention relates to hydroxy-substituted amino and ammonium derivatives, in particular the compounds of formula 1 or 2, and their medical use, including their use in the treatment, prevention or amelioration of an inflammatory, autoimmune and/or allergic disorder, or a proliferative, neoplastic or dysplastic disease or disorder.
1. A method of inhibiting mast cell degranulation, Akt kinase, delayed-type hypersensitivity, allergic contact dermatitis inflammatory response, or collagen type II-induced arthritis, the method comprising administering an effective amount to a subject in need of such a treatment, a compound of the following formula 1
wherein:
R 1 is a C 10-20 hydrocarbon group;
R 2 is a C 1-4 alkyl group, and R 3 is —H, a C 1-4 alkyl group or R 3 is absent;
R 4 is —H or a C 1-4 alkyl group;
R 5 is a C 2-8 alkyl group, wherein one or more hydrogen atoms of said C 2-8 alkyl group are replaced by —OH, or R 5 is a C 5-7 cycloalkyl group, wherein one ring carbon atom of said C 5-7 cycloalkyl group is optionally replaced by an oxygen atom and wherein one or more hydrogen atoms of said C 5-7 cycloalkyl group are independently replaced by —OH or —CH 2 OH;
X is N + or, if R 3 is absent, X is N; and
p is 1, 2 or 3;
or a pharmaceutically acceptable salt, or solvate thereof.
2. The method of claim 1 , wherein the compound is a compound of the formula 1a, 1b, 1c, or 1d:
3. The method of claim 1 , wherein the compound is administered by an oral route, topical route, or transdermal.
4. The method of claim 1 , wherein the subject is a human.
5. The method of claim 1 , wherein said subject is a nonhuman mammal.
6. The method of claim 1 , wherein the method is inhibiting mast cell degranulation.
7. The method of claim 6 , wherein mast cell degranulation is selected from asthma, asthma related diseases, urticarial, mast cell disease, mast cell activation syndrome (MCAS), IgE mediated disorders, and eczema.
8. The method of claim 1 , wherein the method is inhibiting Akt kinase.
9. The method of claim 1 , wherein the method is inhibiting delayed-type hypersensitivity.
10. The method of claim 1 , wherein the method is inhibiting allergic contact dermatitis inflammatory response.
11. The method of claim 1 , wherein the method is inhibiting collagen type II-induced arthritis.
12. The method of claim 11 , wherein the collagen type II-induced arthritis is rheumatoid arthritis.