Treatment of amyotrophic lateral sclerosis

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H;

R 2 is H and

R 3 is —R 10 , —OR 10 , —SR 10 , —S(O)R 10 , —SO 2 R 10 , —OSO 2 R 10 , —C(O)R 10 , —C(O)OR 10 , —OC(O)R 10 , —OC(O)OR 10 , —C(O)N(R 10 ) 2 , —OC(O)N(R 10 ) 2 , a suitable amino protecting group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, or sulfur;

wherein R 10 is hydrogen, halogen, optionally substituted C 1-20 alkyl, optionally substituted phenyl, optionally substituted arylalkyl or monocyclic aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein R 10 optionally is substituted with substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, nitro, hydroxy, amino, C 1-6 alkylamino, cyano, isocyano, isocyanato, and isothiocyanato substituents,

providing that R 3 is not benzimidazolyl and

providing that R 3 is not benzothiazolyl;

m is 0-5;

each R 4 is independently —R 11 , —SR 11 , —CN, —S(O)R 11 , —SO 2 R 11 , —OSO 2 R 11 , —N(R 11 ) 2 , —NR 11 C(O)R 11 , —NR 11 C(O)(CO)R 11 , —NR 11 C(O)N(R 11 ) 2 , —NR 11 C(O)OR 11 , —N(R 11 )S(O)R 11 , —N(R 11 )SO 2 R 11 , —N(R 11 )SO 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —OC(O)OR 11 , —C(O)N(R 11 ) 2 , —OC(O)N(R 11 ) 2 , or a 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring optionally containing 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,

wherein R 11 is halogen, optionally substituted C 1-20 alkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted arylalkyl or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein R H optionally is substituted with substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, nitro, hydroxy, amino, C 1-6 alkylamino, cyano, isocyano, isocyanato, and isothiocyanato substituents; and,

providing where R 3 is H and m=1 or 2, R 4 is —R 12 , —OR 12 , —SR 12 , CN, —S(O)R 12 , —SO 2 R 12 , —OSO 2 R 12 , N(R 12 ) 2 , —NR 12 C(O)R 12 , —NR 12 C(O)(CO)R 12 , —NR 12 C(O)N(R 12 ) 2 , —NR 12 C(O)OR 12 , —N(R 12 )S(O)R 12 , —N(R 12 )SO 2 R 12 , —N(R 12 )SO 2 OR 12 , —C(O)R 12 , —C(O)OR 12 , —OC(O)R 12 , —OC(O)OR 12 , —C(O)N(R 12 ) 2 , —OC(O)N(R 12 ) 2 , or a 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring optionally containing 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

wherein R 12 is halogen, optionally substituted C 5-20 alkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted arylalkyl or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein R 12 optionally is substituted with substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, nitro, hydroxy, amino, C 1-6 alkylamino, cyano, isocyano, isocyanato, and isothiocyanato substituents,

providing where R 3 is H, m=2 and at least one R 4 is halogen, the at least one R 4 that is halogen is mew or ortho to the C—O bond; and

providing where R 3 is H, m=1, and R 4 is bromine, R 4 is meta to the C—O bond.

2. The compound of claim 1 , wherein m is 2 and said di-substituted phenyl moiety is

3. The compound of claim 2 , wherein said phenyl moiety is

4. The compound of claim 1 , wherein R 3 is selected from the group consisting of hydrogen and substituted or unsubstituted C 1-6 alkyl.

5. The compound of claim 1 of any one of the formulae:

6. A pharmaceutical composition for treating ALS comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable excipient.

7. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering a therapeutically effective amount of a compound of claim 1 to a subject with ALS.

8. The compound of claim 1 wherein R 3 is selected from

9. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

R 2 is H and

R 3 is R 10 , —OR 10 , —SR 10 , —S(O)R 10 , —SO 2 R 10 , —OSO 2 R 10 , —C(O)R 10 , —C(O)OR 10 , —OC(O)R 10 , —OC(O)OR 10 , —C(O)N(R 10 ) 2 , —OC(O)N(R 10 ) 2 , a suitable amino protecting group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen or sulfur,

wherein R 10 is halogen, optionally substituted C 1-20 alkyl, optionally substituted phenyl, optionally substituted arylalkyl or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein R 10 optionally is substituted with substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, nitro, hydroxy, amino, C 1-6 alkylamino, cyano, isocyano, isocyanato, and isothiocyanato substituents,

providing that R 3 is not benzimidazolyl and

providing that R 3 is not benzothiazolyl;

m is 0-5; and

each R 4 is independently R 11 , —OR 11 , —SR 11 , —CN, —S(O)R 11 , —SO 2 R 11 , —OSO 2 R 11 , —N(R 11 ) 2 , —NO 2 , —NR 11 C(O)R 11 , —NR 11 C(O)(CO)R 11 , —NR 11 C(O)N(R 11 ) 2 , —NR 11 C(O)OR 11 , —N(R 11 )S(O)R 11 , —N(R 11 )SO 2 R 11 , —N(R 11 )SO 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —OC(O)OR 11 , —C(O)N(R 11 ) 2 , —OC(O)N(R 11 ) 2 , or a 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring optionally containing 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,

wherein R 11 is halogen, optionally substituted C 1-20 alkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted arylalkyl or aryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein R 11 optionally is substituted by substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, nitro, hydroxy, amino, C 1-6 alkylamino, cyano, isocyano, isocyanato, and isothiocyanato substituents.

10. The compound of claim 9 , wherein m is 2 and said di-substituted phenyl moiety is

11. The compound of claim 10 , wherein said phenyl moiety is

12. The compound of claim 9 , wherein R 3 is selected from the group consisting of hydrogen and substituted or unsubstituted C 1-6 alkyl.

13. The compound of claim 9 of any one of the formulae:

14. The compound of claim 9 wherein R 3 is selected from

15. A pharmaceutical composition for treating ALS comprising a therapeutically effective amount of a compound of claim 9 and a pharmaceutically acceptable excipient.