Coumarins as iNOS inhibitors
View Patent ↗The present invention relates to coumarins of the formula (I): that are useful as inhibitors of nitric oxide synthase. Pharmaceutical compositions and methods of using these compounds as inhibitors of nitric oxide synthase are described herein.
1. A compound of formula (I):
wherein:
A is O,
R is selected from the group consisting of (CH 2 ) n NR 1 R 2 , wherein R 1 and R 2 are the same or different and are selected from the group consisting of hydrogen, C(═NH)NH 2 and C 1 -C 6 alkyl,
n is an integer of from 2-5;
X 1 is hydrogen
X 2 is hydrogen;
X 3 is halogen,
X 4 is hydrogen; and
X 5 is hydrogen
with the proviso that when n is 2, R 1 and R 2 are not both hydrogen or both ethyl and X 3 chlorine,
and the pharmaceutically acceptable salts and optical isomers thereof.
2. The compound according to claim 1 wherein:
A is O;
R is (CH 2 ) n NR 1 R 2 , and
X 3 is halogen.
3. The compound according to claim 2 wherein R 1 R 2 are selected from the group consisting of hydrogen, C 1-6 alkyl, and C(═NH)NH 2 .
4. The compound according to claim 3 wherein X 3 is selected from the group consisting of bromine and chlorine.
5. The compound according to claim 4 wherein the halogen is chlorine.
6. The compound according to claim 1 selected from the group consisting of:
6-Chloro-4-(3-aminopropoxy)-1-benzopyran-2-one,
6-Chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one,
4-(2-Amino-ethoxy)-6-chloro-1-benzopyran-2-one,
4-(3-Amino-propoxy)-6-bromo-1-benzopyran-2-one,
4-(3-Amino-propoxy)-6-fluoro-1-benzopyran-2-one,
6-Chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one,
N-[3-(6-Chloro-2-oxo-2H-1-benzopyran-4-yloxy)-propyl]-guanidine,
N-[3-(6-Chloro-2-oxo-2H-1-benzopyran-4-yloxy)-propyl]-acetamide,
4-(5-Amino-pentyloxy)-6-chloro- 1-benzopyran-2-one.
7. A pharmaceutical composition comprising an effective amount of a compound according to claim 6 and a pharmaceutical acceptable carrier.