Tyrosine phosphatase inhibitors
View Patent ↗A compound of the formula (I): wherein X 1 and X 2 are the same or different and each is a bond or a spacer having 1 to 20 atom(s) in the main chain; one of R 1 and R 2 is a cycle group having substituent(s) selected from 1) an optionally substituted carboxy-C 1-6 alkoxy group and 2) an optionally substituted carboxy-C 1-6 aliphatic hydrocarbon group, wherein the cycle group optionally has additional substituent(s), and the other is an optionally substituted cycle group or a hydrogen atom; and R 3 , R 4 and R 5 are the same or different and each is a hydrogen atom or a substituent, or R 4 may link together with R 3 or R 5 to form an optionally substituted ring; provided that when R 3 is a hydrogen atom, R 4 is a hydrogen atom and R 5 is methyl, X 2 —R 2 is not 4-cyclohexylphenyl; when R 3 is 4-methoxyphenyl, R 4 is a hydrogen atom and R 5 is methyl, X 2 —R 2 is not 4-methoxyphenyl; and when R 1 or R 2 is a hydrogen atom, the adjacent X 1 or X 2 is not a C 1-7 alkylene; or a salt thereof exhibits a protein tyrosine phosphatase inhibitory action and is useful as a prophylactic or therapeutic agent for diabetes or the like.
1. A compound of the formula:
wherein X 1 and X 2 are;
one of R 1 and R 2 is a C 6-14 aryl group having substituent(s) selected from 1) an optionally substituted carboxy-C 1-6 alkoxy group and 2) an optionally substituted carboxy-C 1-6 aliphatic hydrocarbon group, wherein the C 6-14 aryl group optionally has additional substituent(s), and the other is an optionally substituted C 6-14 group or a hydrogen atom; and
R 3 , R 4 and R 5 are the same or different and each is a hydrogen atom or a substituent, or R 4 may link together with R 3 or R 5 to form an optionally substituted ring;
provided that when R 3 is a hydrogen atom, R 4 is a hydrogen atom and R 5 is methyl, X 2 —R 2 is not 4-cyclohexylphenyl; when R 3 is 4-metboxyphenyl, R 4 is a hydrogen atom and R 5 is methyl, X 2 —R 2 is not 4-methoxyphenyl;
or a salt thereof.
2. The compound according to claim 1 , wherein one of R 1 and R 2 is a C 6-14 aryl group having substituent(s) selected from 1) an optionally substituted carboxy-C 1-6 alkoxy group and 2) an optionally substituted carboxy-C 1-6 aliphatic hydrocarbon group, wherein the C 6-14 aryl group optionally has additional substituent(s), and the other is an optionally substituted C 6-14 group.
3. The compound according to claim 1 , wherein R 1 or R 2 is a C 6-14 aryl substituted with a carboxy-(C 6-14 aryl-substituted)C 1-6 alkoxy group or a C 1-6 alkoxy-carbonyl-(C 6-14 aryl-substituted)C 1-6 alkoxy group.
4. The compound according to claim 1 , wherein one of R 1 and R 2 is a C 6-14 aryl substituted with a carboxy-(C 6-14 aryl-substituted) C 1-6 alkoxy group or a C 1-6 alkoxy-carbonyl-(C 6-14 alyl-substituted)C 1-6 alkoxy group, and the other is an optionally substituted C 6-14 aryl.
5. The compound according to claim 1 , wherein R 3 , R 4 and R 5 are the same or different and each is a hydrogen atom or a hydrocarbon group.
6. The compound according to claim 1 , wherein each R 3 and R.4 is a hydrogen atom.
7. The compound according to claim 1 , wherein R 5 is a C 1-6 alkyl.
8. A prodrug of the compound according to claim 1 .
9. A pharmaceutical composition comprising the compound according to claim 1 or a prodrug thereof.
10. A method for preparing a compound of the formula:
wherein A is a cycle group and the other symbols in the formula have the same meanings as claim 1 or a salt thereof, which comprises reacting a compound of the formula:
wherein the symbols in the formula have the same meanings as above or a salt thereof with a compound of the formula:
H—Y
wherein Y is an optionally substituted carboxy-C 1p-6 alkoxy group.