Analgesic and immunomodulatory cannabinoids
Disclosed are novel compounds represented by the following structural formula: R-X-Y; and physiologically acceptable salts thereof. R is a tricyclic core of a cannabinoid or substituted cannabinoid. X is a covalent bond, —CH 2 — or —CHR 1 —, wherein R 1 a C1 to C3 substituted or unsubstituted alkyl group. Y is a heterocyclic ring, a substituted heterocyclic ring, a carbocyclic ring, a substituted carbocyclic ring, a fused bicyclic ring system, a substituted fused bicyclic ring system, a bridged bicyclic ring system, a substituted bridged bicyclic ring system, a bridged tricyclic ring system or a substituted bridged tricyclic ring system. Also disclosed is a method of stimulating a CB1 and/or CB2 receptor in a subject. The method comprises administering to the subject a therapeutically effective amount of R-X-Y.
1. A compound represented by the following structural formula:
and physiologically acceptable salts thereof, wherein:
ring A has zero to three endocyclic double bonds;
Z is >C(CH 3 ) 2 or —C═O;
R 2 is —H, —OH, —OCH 3 , —OCH 2 CH 3 , halogen, —CN, —NO 2 , —CH 3 , —C(halogen) 3 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , —CH 2 (halogen), —CH 2 CN, —CH 2 NO 2 , —CH 2 CH 3 , —CH 2 C(halogen) 3 , —CH 2 NH 2 , —CH 2 NHCH 3 or —CH 2 N(CH 3 ) 2 ;
X is a covalent bond; and
Y is a fused bicyclic ring system having only carbon atoms as ring members, a substituted fused bicyclic ring system having only carbon atoms as ring members, a bridged bicyclic ring system having only carbon atoms as ring members, a substituted bridged bicyclic ring system having only carbon atoms as ring members, a bridged tricyclic ring system or a substituted bridged tricyclic ring system.
2. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a fused bicyclic ring system or a substituted fused bicyclic ring system.
3. The compound of claim 1 wherein:
X is a covalent bond; and
Y is represented by the following structural formula:
wherein R 8 is H or CH 3 ; and
R 9 is H, a C1 to C4 alkyl group or a substituted C1 to C4 alkyl group.
4. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a bridged bicyclic ring system, a substituted bridged bicyclic ring system, a bridged tricyclic ring system or a substituted bridged tricyclic ring system.
5. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a substituted or unsubstituted 0,1,1,1,1,1-tricyclic nine-membered ring system, a substituted or unsubstituted 1,3,3-bicyclic nine-membered ring system, a substituted or unsubstituted 1,2,3-bicyclic eight-membered ring system, a substituted or unsubstituted 1,1,1,1,1,1-tricyclic ten-membered ring system, a substituted or unsubstituted 1,1,3-bicyclic nine-membered ring system or a substituted or unsubstituted 1,3-bicyclic six-membered ring system.
6. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a substituted or unsubstituted norbornyl ring system.
7. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a substituted or unsubstituted norbornyl ring system represented by the following formula:
wherein R 10 , R 11 , and R 12 are each independently selected from H, a C1 to C3 alkyl group or a substituted C1 to C3 alkyl group.
8. The compound of claim 7 wherein R 10 , R 11 and R 12 are each independently selected from H or CH 3 .
9. The compound of claim 1 wherein:
X is a covalent bond; and
Y is a substituted or unsubstituted adamantyl ring system.
10. The compound of claim 1 wherein:
X is a covalent bond; and
Y is represented by the following structural formula:
wherein:
R 13 , R 14 , R 15 and R 16 are each independently selected from H, a C1 to C3 alkyl group or a C1 to C3 substituted alkyl group; and
X 1 and X 2 are each >CH—.
11. The compound of claim 10 wherein R 13 is CH 3 ; R 14 , R 15 and R 16 are each H; and X 1 and X 2 are each >CH—.
12. The compound of claim 1 wherein:
X is a covalent bond; and
Y is represented by the following structural formula:
wherein:
R 13 , R 14 , R 15 and R 16 are each independently selected from H, a C1 to C3 alkyl group or a C1 to C3 substituted alkyl group;
X 1 , X 2 and X 3 are each >CH—; and
Y 1 , Y 2 , Y 3 and Y 4 are each >CH 2 .
13. The compound of claim 1 represented by the following structural formula:
14. The compound of claim 1 represented by the following structural formula: