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US 6,143,765 AGranted
Pharmaceutical compositions and methods for modulating signal transduction
AssigneeSugen, Inc.
InventorsPeng Cho Tang, Gerald McMahon
Life of this patent
Estimating the term…
Abstract
The present invention relates to organic molecules capable of inhibiting protein tyrosine phosphatase activity. The invention further relates to the use of such molecules to modulate or regulate signal transduction by inhibiting protein tyrosine phosphatase activity. Finally, the invention relates to the use of such molecules to treat various disease states including diabetes mellitus.
Claims22
A method of inhibiting protein tyrosine phosphatase activity which comprises administering to a mammal an effective amount of a compound having the formula:
- ##STR103## or a pharmaceutically acceptable salt thereof;
- wherein A represents (i) a substituted or unsubstituted monocyclic five or six membered ring having 1-4 hetero ring atoms, at least one of which is nitrogen, the remainder of which are selected from nitrogen, oxygen or sulfur, selected from the group consisting of pyrrole, imidazole, thiazole, isothiazole, isoxazole, furazan, pyrrolidine, piperidine, imidazolidine, piperazine, oxazole, tetrazole, pyrazole, oxadiazole;
- (ii) a substituted or unsubstituted monocyclic or fused bicyclic six to ten membered ring having 1 to 4 hetero ring atoms, one of which is nitrogen and the remainder of which are nitrogen, oxygen or sulfur, selected from the group consisting of indole, quinoxaline, quinoline, isoquinoline, quinazoline, purine;
- or (iii) a substituted or unsubstituted monocyclic or fused polycyclic saturated or unsaturated ring having three to 15 atoms, which are carbon, sulfur, nitrogen or oxygen.
1 more element
A method of modulating signal transduction which comprises administering to a mammal an effective amount of a compound having the formula:
- ##STR105## or a pharmaceutically acceptable salt thereof;
- wherein A represents (i) a substituted or unsubstituted monocyclic five or six membered ring having 1-4 hetero ring atoms, at least one of which is nitrogen, the remainder of which are selected from nitrogen, oxygen or sulfur, selected from the group consisting of pyrrole, imidazole, thiazole, isothiazole, isoxazole, furazan, pyrrolidine, piperidine, imidazolidine, piperazine, oxazole, tetrazole, pyrazole, oxadiazole;
- (ii) a substituted or unsubstituted monocyclic or fused bicyclic six to ten membered ring having 1 to 4 hetero ring atoms, one of which is nitrogen and the remainder of which are nitrogen, oxygen or sulfur, selected from the group consisting of indole, quinoxaline, quinoline, isoquinoline, quinazoline, purine;
- or (iii) a substituted or unsubstituted monocyclic or fused polycyclic saturated or unsaturated ring having three to 15 atoms, which are carbon, sulfur, nitrogen or oxygen.
1 more element
A method of treating a disease state caused by dysfunctional signal transduction which comprises administering to a mammal an effective amount of a compound having the formula:
- ##STR107## or a pharmaceutically acceptable salt thereof;
- wherein A represents (i) a substituted or unsubstituted monocyclic five or six membered ring having 1-4 hetero ring atoms, at least one of which is nitrogen, the remainder of which are selected from nitrogen, oxygen or sulfur, selected from the group consisting of pyrrole, imidazole, thiazole, isothiazole, isoxazole, furazan, pyrrolidine, piperidine, imidazolidine, piperazine, oxazole, tetrazole, pyrazole, oxadiazole;
- (ii) a substituted or unsubstituted monocyclic or fused bicyclic six to ten membered ring having 1 to 4 hetero ring atoms, one of which is nitrogen and the remainder of which are nitrogen, oxygen or sulfur, selected from the group consisting of indole, quinoxaline, quinoline, isoquinoline, quinazoline, purine;
- or (iii) a substituted or unsubstituted monocyclic or fused polycyclic saturated or unsaturated ring having three to 15 atoms, which are carbon, sulfur, nitrogen or oxygen.
1 more element
A method of inhibiting protein tyrosine phosphatase activity which comprises administering to a mammal an effective amount of a compound selected from the group consisting of:
- 1-Methyl-2-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Allyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Acetamidophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminosulfonylphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Ethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Fluorophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Methyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Carboxymethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Benzyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Cyclohexyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(3-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-[4-(n-Hexanoylamino)phenyl]-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- and
- 5-[(5-nitrothiazol-2-yl)mercapto]-1-phenyltetrazole;
- or a pharmaceutically acceptable salt thereof.
15 more elements
A method of modulating signal transduction which comprises administering to a mammal an effective amount of a compound selected from the group consisting of:
- 1-Methyl-2-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Allyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Acetamidophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminosulfonylphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Ethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Fluorophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Methyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Carboxymethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Benzyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Cyclohexyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(3-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-[4-(n-Hexanoylamino)phenyl]-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- and
- 5-[(5-nitrothiazol-2-yl)mercapto]-1-phenyltetrazole;
- or a pharmaceutically acceptable salt thereof;
- said effective amount being sufficient to regulate protein tyrosine phosphatase activity.
16 more elements
A method of treating a disease state caused by dysfunctional signal transduction which comprises administering to a human an effective amount of a compound selected from the group consisting of:
- 1-Methyl-2-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Allyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Acetamidophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Aminosulfonylphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Ethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Fluorophenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(4-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Methyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Carboxymethyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Benzyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-Cyclohexyl-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-(3-Hydroxyphenyl)-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- 1-[4-(n-Hexanoylamino)phenyl]-5-[(5-nitrothiazol-2-yl)mercapto]tetrazole;
- and
- 5-[(5-nitrothiazol-2-yl)mercapto]-1-phenyltetrazole;
- or a pharmaceutically acceptable salt thereof;
- said amount being sufficient to regulate protein tyrosine phosphatase activity.
16 more elements
Dependencies are inferred from the claim text.