Inhibitors of soluble adenylyl cyclase
Provided are 6-amino substituted 2,6-diamino-4-chloropyrimidine compounds which are specific inhibitors of soluble adenylyl cyclase. The compounds can be formulated with pharmaceutical carriers and used for reducing cyclic AMP levels. The compositions can be used for treatment of various conditions including ocular hypotony.
1. A compound having the following structure:
wherein
X is a substituted or unsubstituted C 1 to C 3 aliphatic group and R 3 is selected from the group consisting of:
wherein n is 0 or 1, and
2. The compound of claim 1 , wherein X is an unsubstituted C 1 to C 3 alkanediyl group having the following structure:
and m is 2 or 3.
3. The compound of claim 1 , wherein X is an unsubstituted C 1 to C 3 aliphatic group having the following structure:
wherein * , individually at each occurrence, indicate R or S stereochemistry.
4. The compound of claim 1 , wherein the compound has one of the following structures:
5. A composition comprising a pharmaceutically acceptable carrier and one or more compounds having the following structure:
wherein
X is a substituted or unsubstituted C 1 to C 3 aliphatic group and R 3 is selected from the group consisting of:
wherein n is 0 or 1, and
or
wherein
R 1 is:
wherein r is 1, 2, 3, 4, or 5;
wherein s is 1, 2, 3, 4, or 5; or
wherein t is 1, 2, 3, 4, or 5, and
R 4 and R 5 are each independently a substituted or unsubstituted C 1 -C 5 alkyl group, and
R 2 is H or a substituted or unsubstituted phenyl group,
with the proviso the compound does not have the following structure:
6. The composition of claim 5 , wherein R 2 is a substituted phenyl group having the following structure:
7. The composition of claim 5 , wherein X is an unsubstituted C 1 to C 3 alkanediyl group having the following structure:
and m is 2 or 3.
8. The composition of claim 5 , wherein X is a C 1 to C 3 aliphatic group having the following structure:
wherein * , individually at each occurrence, indicate R or S stereochemistry.
9. The composition of claim 5 , wherein the one or more compounds is selected from the group consisting of:
and combinations thereof.
10. A method of treatment of ocular hypotony comprising administering to an individual in need of treatment a composition of claim 5 .
11. The method of claim 10 , wherein the individual has been surgically treated for glaucoma.