Claims
- 1. A compound of formula (I)
- 2. A compound according to claim 1 of formula (II),
- 3. A compound according to claim 1 wherein A is aryl.
- 4. A compound according to claim 3 wherein R1 is hydroxy.
- 5. A compound according to claim 4 wherein R2 is carboxy.
- 6. A compound according to claim 5 wherein R3, R4, and R5 are independently selected from the group consisting of hydrogen, alkoxy, amido, arylcarbonylamino, cyano and hydroxy.
- 7. A compound according to claim 6 wherein R6 is aryl.
- 8. A compound according to claim 6 wherein R6 is cycloalkyl.
- 9. A compound according to claim 6 wherein R6 is heteroaryl.
- 10. A method for inhibiting protein tyrosine phosphatase at physiological pH comprising administering a therapeutically effective amount of a compound of claim 1.
- 11. A method for inhibiting protein tyrosine phosphatase at about pH 6.5 to about pH 8.5 comprising administering a therapeutically effective amount of a compound of claim 1.
- 12. The method of claim 11 wherein the pH is about 7.5.
- 13. A method for treating diseases in a patient in recognized need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 1.
- 14. The method of claim 13 wherein the disease is selected from the group consisting of type II diabetes, obesity, impaired glucose tolerance and insulin resistance.
- 15. A composition comprising a compound of claim 1 in combination with a therapeutically acceptable excipient.
- 16. A method for inhibiting protein tyrosine phosphatase at physiological pH comprising administering a therapeutically effective amount of a compound of claim 2.
- 17. A method for inhibiting protein tyrosine phosphatase at about pH 6.5 to about pH 8.5 comprising administering a therapeutically effective amount of a compound of claim 2.
- 18. The method of claim 17 wherein the pH is about 7.5.
- 19. A method for treating diseases in a patient in recognized need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 2.
- 20. The method of claim 19 wherein the disease is selected from the group consisting of type II diabetes and obesity, impaired glucose tolerance and insulin resistance.
- 21. A composition comprising a compound of claim 2 in combination with a therapeutically acceptable excipient.
- 22. A compound selected from the group consisting of
2-((carboxycarbonyl)-2-((E)-2-carboxyethenyl)anilino)benzoic acid; 2-(2-((1E)-3-((tert-butoxycarbonyl)amino)-1-propenyl)(carboxycarbonyl)anilino)benzoic acid; 2-((carboxycarbonyl)-2,3-dimethylanilino)benzoic acid; 2-((carboxycarbonyl)-4-chloro-3-methylanilino)benzoic acid; 2-(2-(aminocarbonyl)(carboxycarbonyl)anilino)benzoic acid; 2-((7-(aminomethyl)-5,6,7,8-tetrahydro-1-naphthalenyl)(carboxycarbonyl)amino)benzoic acid; 2-((6-(aminomethyl)-5,6,7,8-tetrahydro-1-naphthalenyl)(carboxycarbonyl)amino)benzoic acid; 2-((carboxycarbonyl)-4-(2,3-diamino-3-oxopropyl)anilino)benzoic acid; and 2-((carboxycarbonyl)(5-(2,3-diamino-3-oxopropyl)-5,6,7,8-tetrahydro-1-naphthalenyl)amino)benzoic acid.
- 23. A compound selected from the group consisting of
2-((carboxycarbonyl)(1-naphthyl)amino)benzoic acid; 2-((carboxycarbonyl)(2-naphthyl)amino)benzoic acid; 2-((carboxycarbonyl)-4-methoxyanilino)benzoic acid; 2-((carboxycarbonyl)(1-naphthyl)amino)-5-methoxybenzoic acid; 2-((carboxycarbonyl)-2-chloro-5-methoxyanilino)benzoic acid; 2-((carboxycarbonyl)-2-((1E)-3-ethoxy-3-oxo-1-propenyl)anilino)benzoic acid; 2-(4-((2S)-2-((tert-butoxycarbonyl)amino)-3-(((4-(methoxycarbonyl)cyclohexyl)methyl)amino)-3-oxopropyl)(carboxycarbonyl)anilino)benzoic acid; 2-(4-((2S)-2-((tert-butoxycarbonyl)amino)-3-(((4-carboxycyclohexyl)methyl)amino)-3-oxopropyl)(carboxycarbonyl)anilino)benzoic acid; 2-((carboxycarbonyl)-2-iodoanilino)benzoic acid; 2-((carboxycarbonyl)-2-((1E)-3-(1,3-oxazinan-3-yl)-3-oxo-1-propenyl)anilino)benzoic acid; 2-((carboxycarbonyl)-3-(trifluoromethyl)anilino)benzoic acid; 2-((carboxycarbonyl)(cyclobutyl)amino)benzoic acid; 2-((7-(benzyloxy)-1-naphthyl)(carboxycarbonyl)amino)benzoic acid; 2-((carboxycarbonyl)-2-(2-hydroxyethyl)anilino)benzoic acid; 2-((carboxycarbonyl)-2-methylanilino)benzoic acid; 2-((carboxycarbonyl)(2-methyl-1H-indol-1-yl)amino)benzoic acid; 2-((carboxycarbonyl)(7-hydroxy-1-naphthyl)amino)benzoic acid; 2-((carboxycarbonyl)(7-((6-phenylhexyl)oxy)-1-naphthyl)amino)benzoic acid; 2-((1,1′-biphenyl)-2-yl(carboxycarbonyl)amino)benzoic acid; 2-((1,1′-biphenyl)-4-yl(carboxycarbonyl)amino)benzoic acid; 2-((carboxycarbonyl)(5,6,7,8-tetrahydro-1-naphthalenyl)amino)benzoic acid; 2-((carboxycarbonyl)(cyclohexyl)amino)benzoic acid; 2-((carboxycarbonyl)(2,3-dihydro-1,4-benzodioxin-6-yl)amino)benzoic acid; 2-((carboxycarbonyl)(3-methylcyclohexyl)amino)benzoic acid; 2-[(carboxycarbonyl)(2-hydroxy-1-naphthyl)amino]benzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentyl-1-naphthylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentyl-3-(2-hydroxyethane)-phenylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-6-{[N-acetyl-3-(1-naphthyl)alanyl]amino}hexanoic acid; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-[(1E)-3-amino-3-oxo-1-propenyl]-N-(tert-butoxycarbonyl)-N-pentyl-L-phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-isopropyl-N-pentylphenylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-6-{[N-acetyl-3-(1-piperidinyl)phenylalanyl]amino}hexanoic acid; 2-{(carboxycarbonyl)[2-(3-methyl-1-piperidinyl)phenyl]amino}benzoic acid; 2-{(carboxycarbonyl)[5-hydroxy-2-(1-piperidinyl)phenyl]amino}benzoic acid; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-[(1E)-3-amino-3-oxo-1-propenyl]-N-(methylsulfonyl)-N-pentyl-L-phenylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(3-amino-3-oxopropyl)-N-[(isopropylamino)carbonyl]-N-pentyl-L-phenylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-[(1E)-3-amino-3-oxo-1-propenyl]-N-[(isopropylamino)carbonyl]-N-pentyl-L-phenylalaninamide; 2-((carboxycarbonyl){2-[4-(hydroxymethyl)-1-piperidinyl]phenyl}amino)benzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentyl-4-(1-piperidinyl)phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl-N-methyl-4-nitro-L-phenylalaninamide; N-(3-carboxypropanoyl)-L-phenylalanyl-3-[(1E)-3-amino-3-oxo-1-propenyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentyl-L-phenylalaninamide; 3-(4-benzoylphenyl)-N-(tert-butoxycarbonyl)-L-alanyl-3-{4-[(carboxycarbonyl)(2-carboxyphenyl)amino]phenyl}-N˜1˜-pentyl-L-alaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(2-hydroxyethyl)-N-[4-(methylsulfonyl)benzyl]phenylalaninamide; 2-[[7-(aminocarbonyl)-1-naphthyl](carboxycarbonyl)amino]benzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-isopropyl-N-[4-(methylsulfonyl)benzyl]phenylalaninamide 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-acetyl-6-(3-isopropylbenzyl)-4-[4-(methylsulfonyl)benzyl]-2,3,5-piperazinetrione; 2-[(carboxycarbonyl)(7-hydroxy-1-naphthyl)amino]-4-hydroxybenzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethyl-N-{5-oxo-5-[(1-phenylethyl)amino]pentyl}phenylalaninamide; N-(methoxycarbonyl)-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentylnaphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(cyclohexylmethyl)-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-[(1R)-1-(4-nitrophenyl)ethyl]naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-[4-(methylsulfonyl)benzyl]naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-(3,4,5-trifluorobenzyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(cyclooctylmethyl)-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-[(1R)-1-(4-bromophenyl)ethyl]-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-(3-phenylpropyl)naphthylalaninamide; methyl 3-{4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl}-N-(methoxycarbonyl)alanyl-L-norleucinate; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(2-fluorobenzyl)-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-chlorobenzyl)-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-bromobenzyl)-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-(4-nitrobenzyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-[4-(aminosulfonyl)benzyl]-N-(methoxycarbonyl)naphthylalaninamide; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-N-({4-[(methylamino)carbonyl]cyclohexyl}methyl)naphthylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(2-hydroxyethyl)-N-(4-nitrobenzyl)phenylalaninamide; 2-[(carboxycarbonyl)(7-hydroxy-1-naphthyl)amino]-4-cyanobenzoic acid; 4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-{4-[(ethylamino)sulfonyl]benzyl}-N-(methoxycarbonyl)naphthylalaninamide; N-(tert-butoxycarbonyl)-L-phenylalanyl-3-[(1E)-3-amino-3-oxo-1-propenyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-pentyl-L-phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(2-hydroxyethyl)-N-[(1S)-1-(4-nitrophenyl)ethyl]phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-chlorobenzyl)-3-(2-hydroxyethyl)phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-bromobenzyl)-3-(2-hydroxyethyl)phenylalaninamide; 2-[(carboxycarbonyl)(7-hydroxy-1-naphthyl)amino]-4-{[4-(dimethylamino)benzoyl]amino}benzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethyl-N-(4-nitrobenzyl)phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethyl-N-[(1R)-1-(4-nitrophenyl)ethyl]phenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-chlorobenzyl)-3-ethylphenylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-nitrobenzyl)naphthylalaninamide; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-[(1R)-1-(4-bromophenyl)ethyl]-3-(2-hydroxyethyl)phenylalaninamide; 4-[(butylamino)carbonyl]-2-[(carboxycarbonyl)(7-hydroxy-1-naphthyl)amino]benzoic acid; N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-{5-[(3-hydroxyphenyl)amino]-5-oxopentyl}-3-(1-piperidinyl)phenylalaninamide; 2-((carboxycarbonyl){4-[2-hydroxy-3-(pentylamino)propyl]phenyl}amino)benzoic acid; 2-((carboxycarbonyl){4-[3-(pentylamino)butyl]-1-naphthyl}amino)benzoic acid; and 2-((carboxycarbonyl){4-[3-(pentylamino)propyl]-1-naphthyl}amino)benzoic acid.
Parent Case Info
[0001] This application claims priority to the provisional application Serial No. 60/228,651 filed on Aug. 29, 2000.
Provisional Applications (1)
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Number |
Date |
Country |
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60228651 |
Aug 2000 |
US |