Synthesis and characterization of C8 analogs of c-di-GMP
View Patent ↗The invention provides analogs cyclic diguanosine monophosphate (c-di-GMP) having different substituents at the guanine C8 position.
1. A compound of the formula:
wherein:
R 1 and R 2 are each independently selected from —SR a , aryl, and halo; and
each R a is independently H or (C 1 -C 6 )alkyl;
wherein each aryl is optionally substituted with one or more groups independently selected from halo, nitro, cyano, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, and amino;
or a salt thereof.
2. The compound of claim 1 , wherein the compound is
or a salt thereof.
3. The compound of claim 2 , wherein the compound is
or a salt thereof.
4. The compound of claim 2 , wherein the compound is
or a salt thereof.
5. The compound of claim 2 , wherein the compound is
or a salt thereof.
6. The compound of claim 2 , wherein the compound is
or a salt thereof.
7. The compound of claim 2 , wherein the compound is
or a salt thereof.
8. The compound of claim 1 , which is a potassium, sodium or lithium salt of the compound.
9. The compound of claim 8 , which is a potassium salt of the compound.
10. The compound of claim 3 , which is a potassium salt of the compound.
11. A composition comprising a compound as described in claim 1 , or a salt thereof, and an acceptable carrier.
12. The composition of claim 11 , which is a pharmaceutical composition that comprises a compound as described in claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier.
13. The composition of claim 11 , which comprises a bimolecular, tetramolecular or octamolecular complex of the compound as described in claim 1 , or a salt thereof.
14. The composition of claim 13 , which comprises a bimolecular complex of the compound as described in claim 1 , or a salt thereof.
15. The composition of claim 13 , which comprises a tetramolecular complex of the compound as described in claim 1 , or a salt thereof.
16. The composition of claim 13 , which comprises an octamolecular complex of the compound as described in claim 1 , or a salt thereof.
17. A composition comprising a compound as described in claim 2 , or a salt thereof, and an acceptable carrier.
18. The composition of claim 17 , which is a pharmaceutical composition that comprises a compound as described in claim 2 , or a salt thereof, and a pharmaceutically acceptable carrier.
19. A method for synthesizing the compound as described in claim 3 , comprising converting a compound of formula 1
to the compound as described in claim 3 .