Therapeutic compounds
The invention provides compounds formula (I) and salts thereof: wherein the bond represented by ---- is a single bond or a double bond, and R1 has any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.
1. A compound of formula (I), or a salt thereof:
wherein:
R 1 is H or (C 1 -C 6 )alkyl;
the bond represented by ---- is a single bond or a double bond;
ring A is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, —NR a R b , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (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, —NR a R b , and oxo (═O); and
R a and R b are each independently H or (C 1 -C 6 )alkyl; or R a and R b taken together with the nitrogen to which they are attached form a ring selected from aziridine, azetidino, pyrrolidino, and morpholino.
2. The compound of claim 1 which is a compound of formula (Ia) or (Ib), or a pharmaceutically acceptable salt thereof:
wherein:
R 1 is H or (C 1 -C 6 )alkyl;
ring A is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, —NR a R b , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (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, —NR a R b , and oxo (═O); and
R a and R b are each independently H or (C 1 -C 6 )alkyl; or R a and R b taken together with the nitrogen to which they are attached form a ring selected from aziridine, azetidino, pyrrolidino, and morpholino.
3. The compound of claim 1 which is a compound of formula (Ic) or (Id), or a salt thereof:
wherein:
R 1 is H or (C 1 -C 6 )alkyl;
ring A is optionally substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, —NR a R b , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (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, —NR a R b , and oxo (═O); and
R a and R b are each independently H or (C 1 -C 6 )alkyl; or R a and R b taken together with the nitrogen to which they are attached form a ring selected from aziridine, azetidino, pyrrolidino, and morpholino.
4. The compound of claim 1 wherein R 1 is H.
5. The compound of claim 1 wherein R 1 is (C 1 -C 6 )alkyl.
6. The compound of claim 1 wherein ring A is not substituted.
7. The compound of claim 1 wherein ring A is substituted with one or more groups independently selected from halo, hydroxy, nitro, cyano, —NR a R b , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (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, —NR a R b , and oxo (═O).
8. The compound of claim 1 wherein ring A is substituted with one or more groups independently selected from halo, hydroxy, cyano, (C 3 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 3 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (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, (C 1 -C 6 )alkoxy, —NR a R b , and oxo (═O).
9. The compound of claim 1 wherein ring A is substituted with one or more groups independently selected from halo, hydroxy, cyano, (C 3 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkanoyloxy, wherein each (C 3 -C 6 )alkyl, (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, (C 1 -C 6 )alkoxy, —NR a R b , and oxo (═O).
10. The compound of claim 1 selected from the group consisting of:
and salts thereof.
11. A pharmaceutical composition comprising a compound as described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
12. A method for inhibiting or relieving one or more symptoms of Alzheimer's disease, Parkinson's disease, diabetes, cancer, or a psychotic disorder in an animal comprising administering a compound as described in claim 1 or a pharmaceutically acceptable salt thereof, to the animal.
13. A method for inhibiting or relieving one or more symptoms of cancer in an animal comprising administering a compound as described in claim 1 or a pharmaceutically acceptable salt thereof, to the animal.