4-amino-7,8-dihydropteridines, pharmaceutical compositions containing them and their use for the treatment of diseases which are caused by an increased nitric oxide level
The present invention relates to the area of NO synthase inhibition and, more particularly, relates to novel 4-amino-7,8-dihydropteridines, pharmaceutical compositions containing said compounds, and the use of said compounds in the treatment of a disorder characterized by a disturbed nitric oxide level.
1. A compound of formula I, stereoisomeric and tautomeric forms and mixtures thereof, and physiologically tolerated salts, and esters thereof:
wherein:
R 1 is chosen from hydrogen,
R 2 is chosen from, independently of R 1 , hydrogen, (C 1 -C 20 )-alkyl, and cycloalkylalkyl,
R 4 is chosen from phenyl, (C 1 -C 20 )-alkylphenyl, and (C 2 -C 20 )-alkyl, which is optionally substituted with —OH, alkyloxy or halogen,
R 11 is chosen from (C 1 -C 5 )-alkyl, which is optionally substituted,
R 12 and R 13 are independently chosen from hydrogen, and (C 1 -C 5 )-alkyl, which is optionally substituted.
2. The compound of claim 1 , wherein:
R 1 is hydrogen,
R 2 is chosen from hydrogen, (C 1 -C 20 )-alkyl and cycloalkylalkyl,
R 4 is chosen from phenyl, (C 1 -C 20 )-alkylphenyl and (C 12 -C 20 )-alkyl which is optionally substituted with —OH, alkyloxy or halogen,
R 11 is methyl, and
R 12 and R 13 are independently of each other chosen from hydrogen and methyl.
3. The compound of claim 1 , wherein:
R 1 and R 2 are hydrogen,
R 4 is 1,2-dihydroxypropyl
R 11 is chosen from methyl and ethyl, and
R 12 and R 13 are independently of each other chosen from hydrogen and methyl.
4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable acid addition salt thereof.