Therapeutic compounds
The invention provides compounds of formulae (I), (II), (III), and (IV): and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers and Alzheimer's disease.
1. A compound of formula II:
wherein:
R 1 is H, halo, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, or (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 )alkoxy, and oxo (═O);
the bond represented by --- is a single bond or a double bond;
D is
and
at least one of one of R 2 , R 3 , and R 4 is COOH, B(OH) 2 , or SO 3 H; and the remaining R 2 , R 3 , and R 4 are each independently selected from H, COOH, B(OH) 2 , SO 3 H, halo, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, or (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 )alkoxy, and oxo (═O);
or a salt thereof.
2. The compound of claim 1 wherein R 1 is H, halo, hydroxy, cyano, nitro, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, or (C 1 -C 6 )alkanoyloxy, wherein each (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 )alkoxy, and oxo (═O).
3. The compound of claim 1 wherein R 1 is halo, hydroxy, cyano, nitro, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, or (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 )alkoxy, and oxo (═O).
4. The compound of claim 1 wherein the bond represented by --- is a single bond.
5. The compound of claim 1 wherein the bond represented by --- is a double bond.
6. The compound of claim 1 wherein D is
7. The compound of claim 1 wherein D is
8. The compound of claim 1 wherein one of R 2 , R 3 , and R 4 is COOH.
9. The compound of claim 1 wherein one of R 2 , R 3 , and R 4 is SO 3 H.
10. The compound of claim 1 wherein at least one of one of R 2 , R 3 , and R 4 is COOH or SO 3 H; and the remaining R 2 , R 3 , and R 4 are each independently selected from COOH, SO 3 H, halo, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, or (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 )alkoxy, and oxo (═O).
11. The compound of claim 1 which is:
or a salt thereof.
12. A compound selected from:
2-(1-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)vinyl)pyrimidine-5-carboxylic acid, and
2-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl]pyrimidine-2-carboxylic acid, salts thereof.
13. A composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.
14. A method for inhibiting colon cancer cell growth comprising contacting the cell in vitro or in vivo with an effective amount of a compound as described in claim 1 , or a salt thereof.
15. A method for treating colon cancer in a mammal comprising administering to the mammal an effective amount of compound as described in claim 1 , or a pharmaceutically acceptable salt thereof.
16. A method for activating RXR in a cell comprising contacting the cell in vitro or in vivo with an effective amount of a compound as described in claim 1 , or a salt thereof.
17. The compound:
or a salt thereof.