Bexarotene analogs
The present invention relates to analogs of bexarotene and methods of use thereof.
1. A compound having the structural formula:
wherein R 1 is hydrogen, halogen, or CO 2 H;
R 2 is halogen, or CO 2 H;
R 3 is CO 2 H; and
R 4 is hydrogen, halogen, or CO 2 H; or a pharmaceutically acceptable salt thereof.
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a halogen.
3. The compound or pharmaceutically acceptable salt of claim 2 , wherein R 4 is a halogen.
4. The compound or pharmaceutically acceptable salt of claim 3 , wherein said halogen is selected from the group consisting of F, Br, Cl, and I, and said halogen is the same as the halogen at R 1 or different from the halogen at R 1 .
5. The compound or pharmaceutically acceptable salt of claim 3 , wherein R 2 is a halogen.
6. The compound or pharmaceutically acceptable salt of claim 5 , wherein said halogen is selected from the group consisting of F, Br, CI, and I, and said halogen is the same as the halogen at R 1 and/or R 4 or different from the halogen at R 1 and/or R 4 .
7. The compound of claim 1 wherein R 1 is H, R 2 is F, R 3 is COOH, and R 4 is F.
8. A compound having the structural formula:
or a pharmaceutically acceptable salt thereof wherein R 2 and R 1 are defined as:
Compound #
R 1
R 2
10
Cl
H
11
Br
H
12
I
H
10a
H
Cl
11a
H
Br
12a
H
I
10b
Cl
Cl
11b
Br
Br
12b
I
I.
9. The compound of claim 1 which is a compound of formula:
or a pharmaceutically acceptable salt thereof having the following substituents at each of positions R 1 , R 2 , R 3 , R 4 :
Compound #
R 1
R 2
R 3
R 4
4
H
CO 2 H
CO 2 H
H
5
H
CO 2 H
CO 2 H
CO 2 H
6
F
F
CO 2 H
H
7
H
F
CO 2 H
F.
10. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable carrier.