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US 2009/0156635 A1Published application
Biaryloxymethylarenecarboxylic acids as glycogen synthase activators
OwnerPaul Gillespie, Robert Alan Goodnow, JR. +1inventors
InventorsPaul Gillespie, Robert Alan Goodnow, JR., Jefferson Wright Tilley
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Abstract
The present invention relates to compounds of formula (I) wherein Ar, Ar2, R2, R3, R4, m, p and s are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases that are associated with the activation of the glycogen synthase enzyme, such as diabetes.
Claims13
A compound of formula (I)
- wherein
- Ar is a phenyl ring;
- Ar2 is a substituted or unsubstituted cyclic ring selected from the group consisting of benzo[1,3]dioxol-5-yl, furan-2-yl, isoquinolin-5-yl, isoxazol-4-yl, 1-naphthyl, pyrazol-1-yl, pyrazol-4-yl, pyridin-3-yl, thiophen-2-yl, thiophen-3-yl and phenyl and where substituted the substituents are selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, lower alkoxy and trifluoro-methoxy;
- R2 and R3 are independently selected from the group consisting of lower alkyl, lower alkoxy, trifluoromethyl, halogen, hydroxy, amino, alkylamino, diakylamino, cyano and nitro;
- R4 is hydroxy or an amino acid attached through a nitrogen atom of the amino acid;
- m is 0, 1, 2, 3 or 4;
- p is 0, 1 or 2, and
- s is 0, 1 or 2 or a pharmaceutically acceptable salt thereof,
- provided that when Ar2 is phenyl, the phenyl ring is substituted by at least one substituent selected from the group consisting of acetamido, aminocarbonyl, benzloxy, hydroxyl-lower alkyl, lower-alkoxy-lower alkyl, phenoxy, phenyl, pyrazol-1-yl and trifluoromethoxy and when Ar2 is substituted or unsubstituted phenyl, there are not two lower alkyl substituents ortho to the point of attachment of the Ar2 ring.
6 more elements
A compound selected from the group consisting of
- 3-(3′-Acetylamino-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(4-Benzo[1,3]dioxol-5-yl-phenoxymethyl)-benzoic acid;
- 3-(3′-Carbamoyl-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-[4-(2-Chloro-pyridin-3-yl)-phenoxymethyl]-benzoic acid;
- 3-[4-(6-Chloro-pyridin-3-yl)-phenoxymethyl]-benzoic acid;
- 3-[4-(3,5-Dimethyl-isoxazol-4-yl)-phenoxymethyl]-benzoic acid;
- 3-[4-(2-Fluoro-pyridin-3-yl)-phenoxymethyl]-benzoic acid;
- 3-[4-(6-Fluoro-pyridin-3-yl)-phenoxymethyl]-benzoic acid;
- 3-(4-Furan-2-yl-phenoxymethyl)-benzoic acid;
- 3-(3′-Hydroxymethyl-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(4-Isoquinolin-5-yl-phenoxymethyl)-benzoic acid;
- 3-(2′-Methoxymethyl-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(3′-Methoxymethyl-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(4-Naphthalen-1-yl-phenoxymethyl)-benzoic acid;
- 3-(2′-Phenoxy-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(3′-Pyrazol-1-yl-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(4-Pyridin-3-yl-phenoxymethyl)-benzoic acid;
- 3-(4-Thiophen-3-yl-phenoxymethyl)-benzoic acid;
- 3-(2′-Trifluoromethoxy-biphenyl-4-yloxymethyl)-benzoic acid;
- 3-(4′-Trifluoromethoxy-biphenyl-4-yloxymethyl)-benzoic acid;
- [3-(3′-Acetylamino-biphenyl-4-yloxymethyl)-phenyl]-acetic acid;
- [3-(3′-Hydroxymethyl-biphenyl-4-yloxymethyl)-phenyl]-acetic acid;
- [3-(2′-Methoxymethyl-biphenyl-4-yloxymethyl)-phenyl]-acetic acid;
- {3-[4-(2-Methoxy-pyridin-3-yl)-phenoxymethyl]-phenyl}-acetic acid;
- and
- [3-(2′-Trifluoromethoxy-biphenyl-4-yloxymethyl)-phenyl]-acetic acid
23 more elements
A pharmaceutical composition comprising a compound of the formula
- wherein
- Ar is a phenyl ring;
- Ar2 is a substituted or unsubstituted cyclic ring selected from the group consisting of benzo[1,3]dioxol-5-yl, furan-2-yl, isoquinolin-5-yl, isoxazol-4-yl, 1-naphthyl, pyrazol-1-yl, pyrazol-4-yl, pyridin-3-yl, thiophen-2-yl, thiophen-3-yl and phenyl and where substituted the substituents are selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, lower alkoxy and trifluoro-methoxy;
- R2 and R3 are independently selected from the group consisting of lower alkyl, lower alkoxy, trifluoromethyl, halogen, hydroxy, amino, alkylamino, diakylamino, cyano and nitro;
- R4 is hydroxy or an amino acid attached through a nitrogen atom of the amino acid;
- m is 0, 1, 2, 3 or 4;
- p is 0, 1 or 2, and
- s is 0, 1 or 2 or a pharmaceutically acceptable salt thereof,
- provided that when Ar2 is phenyl, the phenyl ring is substituted by at least one substituent selected from the group consisting of acetamido, aminocarbonyl, benzloxy, hydroxyl-lower alkyl, lower-alkoxy-lower alkyl, phenoxy, phenyl, pyrazol-1-yl and trifluoromethoxy and when Ar2 is substituted or unsubstituted phenyl, there are not two lower alkyl substituents ortho to the point of attachment of the Ar2 ring,
- together with a pharmaceutically acceptable carrier and/or excipient.
7 more elements
Dependencies are inferred from the claim text.