PDE10 inhibitors and related compositions and methods
View Patent ↗Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
1. A compound having the following structure (II):
or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof,
wherein:
R 1 is C 1-6 alkyl, C 1-6 haloalkyl, —(CH 2 ) n O(CH 2 ) m CH 3 or —(CH 2 ) n N(CH 3 ) 2 ;
R 2 is substituted or unsubstituted heterocyclyl, substituted phenyl, or substituted or unsubstituted naphthyl;
R 3 is substituted or unsubstituted heterocyclyl, or substituted or unsubstituted aryl; and
R 4 and R 5 are the same or different and independently hydrogen, C 1-6 alkyl or C 1-6 haloalkyl;
n is 1, 2, 3, 4, 5 or 6; and
m is 0, 1, 2, 3, 4, 5 or 6.
2. The compound of claim 1 wherein R 4 and R 5 are the same or different and independently hydrogen or C 1-6 alkyl.
3. The compound of claim 1 wherein R 4 and R 5 are hydrogen.
4. The compound of claim 1 wherein R 1 is C 1-6 alkyl.
5. The compound of claim 4 wherein R 1 is methyl.
6. The compound of claim 4 wherein R 1 is ethyl.
7. The compound of claim 4 wherein R 1 is isopropyl.
8. The compound of claim 1 wherein R 3 is substituted phenyl.
9. The compound of claim 8 wherein R 3 is 3,4,5-trimethoxyphenyl.
10. The compound of claim 8 wherein R 3 is 4-bromo-3,5-dimethoxyphenyl.
11. The compound of claim 1 wherein R 2 is substituted phenyl.
12. The compound of claim 11 wherein R 2 is 4-morpholinophenyl.
13. The compound of claim 11 wherein R 2 is 4-(1H-pyrazol-1-yl)phenyl.
14. The compound of claim 1 wherein R 2 is substituted or unsubstituted naphthyl.
15. The compound of claim 1 wherein R 2 is substituted or unsubstituted heteroaryl.
16. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.