Phenethanolamine derivatives, compositions, and their use as agonists at atypical beta-adrenoreceptors
The present invention disclosed compounds of Formula I. The present invention also discloses beta-3 agonists of formula I and methods for treating beta-3 mediated diseases and condition using the compounds of formula I, in particular methods for treating diabetes or obesity.
1. A compound of formula (I), or a pharmaceutically acceptable derivative thereof:
wherein X is oxygen or sulfur, and where the heterocycle containing X is substituted meta or para to the depicted NH;
R 1 is hydrogen or C 1-6 alkyl;
R represents substituents selected from C 1-6 alkyl, halogen, trifluoromethyl, and C 1-6 alkoxy; and
n represents an integer from 0–4.
2. A compound of claim 1 wherein the heterocycle containing X is substituted meta to the depicted NH.
3. A compound of claim 1 wherein R 1 is hydrogen or methyl.
4. A compound of claim 1 wherein when R 1 is other than hydrogen, the stereochemisty around the carbon to which R 1 is bonded, is R.
5. A compound of claim 1 wherein R is chlorine, fluorine, or CF 3 .
6. A compound of claim 1 wherein n is 0, 1, or 2.
7. A compound of claim 1 wherein n is 0.
8. A compound of claim 1 wherein the stereochemisty around the carbon to which the depicted OH is bonded, is R.
9. A compound of claim 1 wherein said compound is selected from the group consisting of
2-(3-{2R-[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]propylamino}phenyl)furan-3-carboxylic acid;
2-(3-{[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]ethylamino}phenyl)furan-3-carboxylic acid;
2-(4-{2R-[2-(3-Chlorophenyl)-2R-hydroxylethylamino]propylamino}phenyl)furan-3-carboxylic acid;
2-(3-{2R-[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]propylamino}phenyl)thiophene-3-carboxylic acid;
2-(3-{[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]ethylamino}phenyl)thiophene-3-carboxylic acid;
2-(4-{2R-[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]propylamino}phenyl)thiophene-3-carboxylic acid;
and pharmaceutically acceptable derivatives thereof.
10. A compound of claim 1 wherein said compound is selected from the group consisting of
2-(3-{[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]ethylamino}phenyl)furan-3-carboxylic acid;
2-(3-{[2-(3-Chlorophenyl)-2R-hydroxyl-ethylamino]ethylamino}phenyl)thiophene-3-carboxylic acid;
and pharmaceutically acceptable derivatives thereof.
11. A pharmaceutical formulation comprising a compound of claim 1 and one or more pharmaceutically acceptable carrier.