Human protein tyrosine phosphatase inhibitors and method of use

1. A compound having the formula:

wherein R is a substituted or unsubstituted thiazolyl unit having the formula:

R 2 and R 3 are each independently chosen from:

i) hydrogen; or

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;

R 4 is a unit chosen from:

i) hydrogen; or

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;

R 1 is substituted or unsubstituted phenyl, said substitutions are independently chosen from one or more halogen, C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl, —OR 11 , —CN, —N(R 11 ) 2 , —CO 2 R 11 , —C(O)N(R 11 ) 2 , —NR 11 C(O)R 11 , —NO 2 , —SO 2 R 11 , phenyl, benzyl, or two substitutions can be taken together to form a cycloalkyl, heterocyclic, or heteroaryl ring comprising from 3-7 atoms, said rings comprising one or more heteroatoms chosen from oxygen, nitrogen, or sulfur; each R 11 is independently hydrogen; substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched, C 3 -C 4 cyclic alkyl or substituted or unsubstituted phenyl or benzyl; or when R 1 is substituted by phenyl or benzyl, said phenyl or benzyl can be further substituted by halogen, C 1 -C 3 linear alkyl, C 1 -C 3 linear alkoxy, —CO 2 R 11 and —NHCOR 16 ; each R 16 is independently hydrogen, methyl, or ethyl;

L has the formula:

—C(O)[C(R 6a R 6b )] x —;

R 6a and R 6b are each independently:

i) hydrogen; or

ii) C 1 -C 4 linear or C 3 -C 4 branched alkyl;

the index x is from 0 to 4; or

a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein the compounds are salts comprising cations chosen from ammonium, sodium, lithium, potassium, calcium, magnesium, and bismuth.

3. The compound according to claim 1 , wherein R has the formula:

4. The compound according to claim 3 , wherein R 2 and R 3 are each hydrogen or substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl.

5. The compound according to claim 3 , wherein R 2 is methyl and R 3 is hydrogen.

6. The compound according to claim 1 , wherein R 1 is chosen from phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, and 3,5-dimethoxyphenyl.

7. The compound according to claim 1 , wherein L has the formula —C(O)CH 2 —.

8. The compound according to claim 1 , wherein L has the formula —C(O)CH 2 CH 2 —.

9. A compound having the formula:

wherein R is a substituted or unsubstituted thiazolyl unit having the formula:

R 2 and R 3 are each independently chosen from:

i) hydrogen; or

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;

R 4 is a unit chosen from:

i) hydrogen;

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl; or

iii) 5-member or 6-member heteroaryl, wherein the heteroaryl ring contains one or more heteroatoms chosen from oxygen, nitrogen, or sulfur;

R 1 is chosen from:

i) hydrogen;

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;

iii) substituted or unsubstituted phenyl; or

iv) substituted or unsubstituted 5-member or 6-member heteroaryl, wherein the heteroaryl ring contains one or more heteroatoms chosen from oxygen, nitrogen, or sulfur;

said substitutions are independently chosen from one or more halogen, C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl, —OR 11 , —CN, —N(R 11 ) 2 , —CO 2 R 11 , —C(O)N(R 11 ) 2 , —NR 11 C(O)R 11 , —NO 2 , —SO 2 R 11 , phenyl, benzyl, or two substitutions can be taken together to form a cycloalkyl, heterocyclic, or heteroaryl ring comprising from 3-7 atoms, said rings comprising one or more heteroatoms chosen from oxygen, nitrogen, or sulfur; each R 11 is independently hydrogen; substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched, C 3 -C 4 cyclic alkyl or substituted or unsubstituted phenyl or benzyl; or when R 1 is substituted by phenyl or benzyl, said phenyl or benzyl can be further substituted by halogen, C 1 -C 3 linear alkyl, C 1 -C 3 linear alkoxy, —CO 2 R 11 and —NHCOR 16 ; each R 16 is independently hydrogen, methyl, or ethyl;

L has the formula:

—SO 2 [C(R 8a R 8b )] z —;

R 8a and R 8b are each independently:

i) hydrogen; or

ii) C 1 -C 4 linear or C 3 -C 4 branched alkyl;

the index x is from 0 to 4; or

a pharmaceutically acceptable salt thereof.

10. The compound according to claim 9 , wherein L is chosen from:

i) —SO 2 CH 2 —;

i) —SO 2 CH 2 CH 2 —; or

i) —SO 2 CH 2 CH 2 CH 2 —.

11. The compound according to claim 9 , wherein R 4 is a heteroaryl unit chosen from 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol-4-yl, [1,2,4]triazol-5-yl, imidazol-2-yl, imidazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [1,3,4]oxadiazol-2-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, [1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl, and [1,3,4]thiadiazol-2-yl.

12. The compound according to claim 9 , wherein R 4 is thiophen-2-yl or thiophen-3-yl.

13. The compound according to claim 9 , wherein R 1 is substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl.

14. The compound according to claim 9 , wherein R 1 is substituted or unsubstituted phenyl.

15. The compound according to claim 9 , wherein R 1 is substituted or unsubstituted 5-member or 6-member heteroaryl.

16. A compound having the formula:

wherein R 4 is chosen from:

i) hydrogen;

ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;

iii) substituted or unsubstituted phenyl; or

iv) substituted or unsubstituted 5-member or 6-member heteroaryl, wherein the heteroaryl ring contains one or more heteroatoms chosen from oxygen, nitrogen, or sulfur;

R 1 is substituted or unsubstituted 5-member or 6-member heteroaryl, wherein the heteroaryl ring contains one or more heteroatoms chosen from oxygen, nitrogen, or sulfur; said substitutions are independently chosen from one or more halogen, C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl, —OR 11 , —CN, —N(R 11 ) 2 , —CO 2 R 11 , —C(O)N(R 11 ) 2 , —NR 11 C(O)R 11 , —NO 2 , —SO 2 R 11 , phenyl, benzyl, or two substitutions can be taken together to form a cycloalkyl, heterocyclic, or heteroaryl ring comprising from 3-7 atoms, said rings comprising one or more heteroatoms chosen from oxygen, nitrogen, or sulfur; each R 11 is independently hydrogen; substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched, C 3 -C 4 cyclic alkyl or substituted or unsubstituted phenyl or benzyl; or when R 1 is substituted by phenyl or benzyl, said phenyl or benzyl can be further substituted by halogen, C 1 -C 3 linear alkyl, C 1 -C 3 linear alkoxy, —CO 2 R 11 and —NHCOR 16 ; each R 16 is independently hydrogen, methyl, or ethyl.

17. The compound according to claim 16 , wherein R 1 is chosen from 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol-4-yl, [1,2,4]triazol-5-yl, imidazol-2-yl, imidazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [1,3,4]oxadiazol-2-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, [1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl, and [1,3,4]thiadiazol-2-yl.

18. The compound according to claim 16 , wherein R 1 is a phenyl or benzyl substituted 5-member or 6-member heteroaryl, wherein the heteroaryl ring contains one or more heteroatoms chosen from oxygen, nitrogen, or sulfur; wherein the phenyl ring or benzyl aryl ring can be further substituted with halogen, C 1 -C 3 linear alkyl, C 1 -C 3 linear alkoxy, —CO 2 R 11 and —NHCOR 16 ; each R 16 is independently hydrogen, methyl, or ethyl.

19. The compound according to claim 16 , wherein R 4 is substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl.

20. The compound according to claim 16 , wherein R 1 is [1,3,4]thiadiazol-2-yl substituted with methyl, ethyl, propyl, benzyl, 3-methoxybenzyl, naphthalen-1-ylmethyl, (methoxycarbonyl)methyl, or (2-methylthiazol-4-yl)methyl.