Cannabinoid receptor ligands and uses thereof
Compounds of Formula (I) and (II) that act as cannabinoid receptor ligands and their uses in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals are described herein
1. A compound of Formula (I) or (II)
wherein
A is nitrogen and B is carbon;
R 0 is 2-chlorophenyl, 2-fluorophenyl, 2,4-dichlorophenyl, 2-fluoro-4-chlorophenol, 2-chloro-4-fluorophenyl, or 2,4-difluorophenyl;
R 1 is 4-chlorophenyl, 4-cyanophenyl, or 4-fluorophenyl;
X is —C(R 2a )(R 2b ), where R 2a and R 2b are each independently hydrogen, (C 1 –C 4 )alkyl, or halo-substituted (C 1 –C 4 )alkyl;
R 3a and R 3b are each independently hydrogen, (C 1 –C 4 )alkyl, or halo-substituted (C 1 –C 4 )alkyl; and
R 4 is a chemical moiety selected from the group consisting of (C 1 –C 8 )alkyl, aryl, heteroaryl, aryl(C 1 –C 4 )alkyl, a 3- to 8-membered partially or fully saturated carbocyclic ring(s), heteroaryl(C 1 –C 3 )alkyl, 5–6 membered lactone, 5- to 6-membered lactam, and a 3- to 8-membered partially or fully saturated heterocycle, where said chemical moiety is optionally substituted with one or more substituents;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
2. The compound of claim 1 wherein R 4 is a chemical moiety selected from the group consisting of (C 1 –C 8 )alkyl, aryl(C 1 –C 4 )alkyl, 3- to 6-membered partially or fully saturated carbocyclic ring(s), and 3- to 8-membered partially or fully saturated heterocycle, where said chemical moiety is optionally substituted with one or more substituents;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
3. The compound of claim 2 wherein R 4 is (C 1 –C 8 )alkyl, halo-substituted (C 1 –C 8 )alkyl, cyclopentyl, cyclohexyl, piperidin-1-yl, pyrrolidin-1-yl, or morpholin-1-yl;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
4. The compound of claim 1 , 2 or 3 wherein said compound is a compound of Formula (I);
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
5. The compound of claim 4 wherein R 2a and R 2b are hydrogen;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
6. The compound of claim 1 selected from the group consisting of
3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-6-isopropyl-2,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one;
3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-6-(2,2,2-trifluoro-ethyl)-2,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one;
3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-6-(2,2-difluoro-ethyl)-2,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one; and
3-(4-chloro-phenyl)-2-(2-chloro-phenyl )-6-(2-fluoro-ethyl )-2,4,5,6-tetrahydro-pyrazolo[3,4-c]pyrid in-7-one;
or a solvate or hydrate of said compound.
7. The compound of claim 1 , 2 or 3 wherein said compound is a compound of Formula (II);
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
8. A compound of Formula (III) or (IV)
wherein
A is nitrogen and B is carbon; R 0a , R 0b , R 1c and R 1b are each independently halo, (C 1 –C 4 )alkoxy, (C 1 –C 4 )alkyl, halo-substituted (C 1 –C 4 )alkyl, or cyano;
n and m are each independently 0, 1 or 2;
X is —C(R 2a )(R 2b ), where R 2a and R 2b are each independently hydrogen, (C 1 –C 4 )alkyl, or halo-substituted (C 1 –C 4 )alkyl;
R 3a and R 3b are each independently hydrogen, (C 1 –C 4 )alkyl, or halo-substituted (C 1 –C 4 )alkyl; and
R 4 is a chemical moiety selected from the group consisting of (C 1 –C 8 )alkyl, aryl, heteroaryl, aryl(C 1 –C 4 )alkyl, a 3- to 8-membered partially or fully saturated carbocyclic ring(s), heteroaryl(C 1 –C 3 )alkyl, 5–6 membered lactone, 5- to 6-membered lactam, and a 3- to 8-membered partially or fully saturated heterocycle, where said chemical moiety is optionally substituted with one or more substituents,
a pharmaceutically acceptable salt thereof, a solvate or hydrate of said compound or said salt.
9. The compound of claim 8 wherein R 4 is a chemical moiety selected from the group consisting of (C 1 –C 8 )alkyl, aryl(C 1 –C 4 )alkyl, 3- to 8-membered partially or fully saturated carbocyclic ring(s), and 3- to 8-membered partially or fully saturated heterocycle, where said chemical moiety is optionally substituted with one or more substituents;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
10. The compound of claim 9 wherein R 4 is (C 1 –C 8 )alkyl, halo-substituted (C 1 –C 8 )alkyl, cyclopentyl, cyclohexyl, piperidin-1-yl, pyrrolidin-1-yl, or morpholin-1-yl;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
11. The compound of claim 10 wherein R 4 is halo-substituted (C 1 –C 8 )alkyl;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
12. The compound of claim 8 , 9 , 10 or 11 wherein said compound is a compound of Formula (III);
a pharmaceutically acceptable salt thereof, a solvate or hydrate of said compound or said salt.
13. The compound of claim 12 wherein R 2a and R 2b are hydrogen;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
14. The compound of claim 8 , 9 , 10 or 11 wherein said compound is a compound of Formula (IV);
a pharmaceutically acceptable salt thereof, a solvate or hydrate of said compound or said salt.
15. The compound of claim 14 wherein R 2a and R 2b are hydrogen;
a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
16. A pharmaceutical composition comprising (1) a compound of claim 1 , or a solvate or hydrate of said compound or said salt; and (2) a pharmaceutically acceptable excipient, diluent, or carrier.
17. A compound having the following structure