Patent
A first aspect of the invention is a compound (sometimes also referred to herein as an “active agent” or “active compound”) of Formula Ia, or more particularly Formula Ib, or a pharmaceutically acceptable salt or prodrug thereof. Compositions thereof and methods of using the same (e.g. for the treatment of a neurological disease) are also described.
1. A compound of Formula Ib:
wherein:
R is:
N(R′)OR′, CH 2 OCH 3 , CH 2 OCH 2 CH 3 , CH 2 OCH(CH 3 ) 2 , CH 2 OCD 3 , CH 2 OCD 2 CD 3 , CH 2 OCD 2 CH 3 , CH 2 OCD(CH 3 ) 2 , CH 2 OCD(CD 3 ) 2 , CH 2 OCF 2 H, CH 3 , CD 3 , CF 3 , CH 2 F, CH 2 CH 3 , (CH 2 ) 2 CH 3 , CH(CH 3 ) 2 , (CH 2 ) 3 CH 3 , C(CH 3 ) 3 ;
each R′ is independently selected H or lower alkyl, unsubstituted or substituted with 1-3 electron-withdrawing or electron-donating groups;
X′ is a covalent bond or a linker that consist of one, two, or three connected atoms and which atoms may or may not be substituted;
Y′ is an aromatic or heteroaromatic moiety, unsubstituted or substituted with 1-3 electron-withdrawing or electron-donating groups; and
Z′ is H, F, Cl, Br, I, CF 3 , CN, OCF 3 , or N 3 ;
or a pharmaceutically acceptable salt or prodrug thereof.
2. The compound of claim 1 , wherein X′ is a covalent bond.
3. The compound of claim 1 wherein Z′ is F, Cl, or OCF 3 .
4. The compound of claim 1 wherein R is —CH 2 OCH 3 .
5. The compound of claim 1 , wherein said compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
6. The compound of claim 1 in the D-amino acid configuration, the L-amino acid configuration, or as a racemic mixture thereof.
7. The compound of claim 1 in the D-amino acid configuration.
8. A pharmaceutical composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.
9. The composition of claim 8 further comprising at least one neurological active agent in addition to said compound of Formula Ib.
10. The composition of claim 8 in oral administration form.
11. A method of treating a neurological disorder in a mammalian subject in need thereof, comprising administering said subject a compound of claim 1 in a treatment effective amount, wherein said neurological disorder is acute or chronic pain, migraine, neuropathic pain, fibromyalgia, bipolar disorders, convulsions, a seizure disorder, mania, epilepsy, epileptogenesis, dyskinesia, tremors, anxiety, depression, or ischemia.
12. The method of claim 11 , wherein said neurological disorder is epilepsy.
13. The method of claim 11 , wherein said neurological disorder is neuropathic pain.
14. The method of claim 11 , wherein said subject is a human subject.
15. The method of claim 11 , further comprising concurrently administering said subject at least one neurological active agent in addition to said compound of Formula Ib in a treatment effective amount.