Cannabinoid receptor ligands
View Patent ↗Compounds of Formula I: and/or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions containing such compounds exhibit anti-inflammatory and immunomodulatory activity, and can be effective in treating cancer and inflammatory, immunomodulatory or respiratory diseases or conditions.
1. A compound of Formula I:
or a pharmaceutically acceptable salt of said compound, wherein:
A is selected from the group consisting of phenyl and naphthyl;
B is B1:
Y is —CH 2 —;
L 1 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, —S—, and —CF 2 —;
L 2 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, —S—, and —CF 2 —;
L 3 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, —S—, and —CF 2 —;
R 1 is selected from the group consisting of fluorophenyl, pyridyl, trifluoromethoxyphenyl, and methoxyphenyl;
R 2 is selected from the group consisting of H and alkyl;
R 4 is H or alkyl;
R 5 is H;
R 6 is selected from the group consisting of hydrogen, alkyl, haloalkyl, and cycloalkyl;
each X is independently selected from H, halogen, —CN, —OH, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl; and
m is an integer of from 0 to 4.
2. The compound according to claim 1 , wherein:
R 1 is selected from the group consisting of fluorophenyl, pyridyl, trifluoromethoxyphenyl, and methoxyphenyl;
L 1 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, and —CF 2 —;
L 2 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, and —CF 2 —;
L 3 is selected from the group consisting of —C(O)—, —CH 2 —, —S(O 2 )—, —S(O)—, and —CF 2 —;
R 2 is H, methyl, or ethyl;
R 5 is H;
R 6 is H, (C 1 -C 6 )alkyl, (C 3 -C 5 )cycloalkyl, or haloalkyl; and
X is independently selected from the group consisting of H, halogen, alkyl, haloalkyl, (C 3 -C 5 )cycloalkyl, —OH, alkoxy, haloalkoxy and —CN.
3. The compound according to claim 1 , wherein A is represented by Formula A1:
4. The compound according to claim 1 , wherein L 1 , L 2 , and L 3 are independently —S(O 2 )—, or —CH 2 —.
5. The compound according to claim 1 , wherein L 1 , L 2 , and L 3 are each —S(O 2 )—.
6. The compound according to claim 1 , wherein R 1 is selected from the group consisting of 2-fluorophenyl, 2-pyridyl, 4-methoxyphenyl, and 4-trifluoromethoxyphenyl.
7. The compound according to claim 1 , wherein R 6 is selected from the group consisting of —CH 3 , —CF 3 , and cyclopropyl.
8. The compound according to claim 1 , represented by Formula IV:
wherein X is selected from the group consisting of H, F, Cl, Br, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —OH, and —CN;
R 1 is selected from the group consisting of 2-fluorophenyl, 2-pyridyl, 4-methoxyphenyl, and 4-trifluoromethoxyphenyl;
R 2 is selected from the group consisting of H and ethyl; and
R 6 is selected from the group consisting of methyl, trifluoromethyl, and cyclopropyl.
9. The compound according to claim 1 , represented by Formula IV:
wherein X is selected from the group consisting of H, F, Cl, Br, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —OH, and —CN;
R 1 is selected from the group consisting of 2-fluorophenyl, 2-pyridyl, 4-methoxyphenyl, and 4-trifluoromethoxyphenyl;
R 2 is selected from the group consisting of H and ethyl; and
R 6 is selected from the group consisting of methyl, trifluoromethyl, and cyclopropyl.
10. The compound according to claim 1 , wherein R 5 is H, n=1, m=1, L 2 is —S(O 2 )—, and L 1 , L 3 , R 1 , R 6 , —A—X, —B—N(R 5 )— and X are as set forth in the following Table:
R 1
—A—X
—B—N(R 5 )
(with linking
(with linking points
(with linking points to L 2
Cmpd
point to L 1 )
R 6
X
L 1
L 3
to L 1 , L 2 and X)
and L 3 )
P
CH 3
Cl
—S(O 2 )—
—S(O 2 )—
Q
CF 3
Cl
—S(O 2 )—
—S(O 2 )—
T
CF 3
Cl
—S(O 2 )—
—S(O 2 )—
W
CF 3
Cl
—S(O 2 )—
—S(O 2 )—
X
CF 3
Cl
—S(O 2 )—
—S(O 2 )—
Y
CF 3
CF 3
—S(O 2 )—
—S(O 2 )—
Z
CF 3
CF 3
—S(O 2 )—
—S(O 2 )—
AA
CF 3
CF 3
—S(O 2 )—
—S(O 2 )—
AB
CF 3
OCF 3
—S(O 2 )—
—S(O 2 )—
AC
CF 3
OCH 3
—S(O 2 )—
—S(O 2 )—
AD
CF 3
H
—S(O 2 )—
—S(O 2 )—
AE
CF 3
F
—S(O 2 )—
—S(O 2 )—
AF
CH 3
Cl
—S(O 2 )—
—S(O 2 )—
AG
Cl
—S(O 2 )—
—S(O 2 )—
AH
CF 3
OH
—S(O 2 )—
—S(O 2 )—
AI
CF 3
OCF 3
—S(O 2 )—
—CH 2 —
AJ
CF 3
OCF 3
—S(O 2 )—
—S(O 2 )—
.
11. The compound according to claim 1 , wherein R 5 is H, n=1, m=1, L 2 is —S(O 2 )—, and L 1 , L 3 , R 1 , R 6 , —A—X, —B—N(R 5 )— and X are as set forth in the following Table:
R 1
—A—X
—B—N(R 5 )
(with linking
(with linking points
(with linking points to L 2
Cmpd
point to L 1 )
R 6
X
L 1
L 3
to L 1 , L 2 and X)
and L 3 )
AA
CF 3
CF 3
—S(O 2 )—
—S(O 2 )—
.
12. A compound having the following structure:
or a stereoisomer thereof, or a salt of said compound or said stereoisomer.
13. A pharmaceutical composition comprising one or more compounds according to claim 1 , and one or more pharmaceutically acceptable carriers.
14. A compound of claim 1 in purified form.