Claims
- 1. A compound of Formula (I) the stereoisomers and prodrugs thereof, and the pharmaceutically acceptable salts of said compounds, and stereoisomers, wherein:Ar is phenyl; R is —NR9SO2R10, or —SO2R9; R1 is hydrogen, —(C1-C6)alkyl, halogen, —(C1-C6)alkoxy, or hydroxy; R2, R3, R4are, independently, hydrogen, or —(C1-C6)alkyl; R5 is an aromatic 5- or 6-membered ring heterocycle having from 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, or nitrogen; R6 and R7 are, independently, hydrogen, halogen, cyano, —(C1-C6)acyl, —CO2R9, —NR9R10, hydroxy, —(C1-C6)alkoxy, —CONR9R10, —NR9SO2R10, —SO2NR9R10, or —SO2R9; —(C1-C6)alkyl, optionally substituted with —(C3-C8)cycloalkyl, halogen, aryl, —(C1-C6)alkoxy, —(C1-C6)haloalkyl, alkylalkoxy, hydroxy, —NR9SO2R10, —SO2NR9R10, —SO2R9, or heterocycle; —(C3-C8)cycloalkyl, optionally substituted with —(C1-C6)alkyl, —(C3-C8)cycloalkyl, halogen, aryl, —(C1-C6)alkoxy, —(C1-C6)haloalkyl, alkylalkoxy, hydroxy, —NR9R10, —NR9SO2R10, —SO2NR9R10, —SO2R9, or heterocycle; aryl, optionally substituted with —(C1-C6)alkyl, —(C3-C7)cycloalkyl, halogen, aryl, —(C1-C6)alkoxy,—(C1-C6)haloalkyl, alkylalkoxy, hydroxy, —NR9R10, —NR9SO2R10, —SO2NR9R10, —SO2R9, or heterocycle; or heterocycle, optionally substituted with —(C1-C6)alkyl, —(C3-C8)cycloalkyl, halogen, aryl, —(C1-C6)alkoxy, —(C1-C6)haloalkyl, alkylalkoxy, hydroxy, —NR9R10, —NR9SO2R10, —SO2NR9R10, —SO2R9, or heterocycle; R8 is hydrogen, —(C1-C4)alkyl, or halogen; and R9 and R10 are, independently, hydrogen, —(C1-C6)alkyl, alkylalkoxy, —(C3-C8)cycloalkyl, —(C1-C6)haloalkyl, —(C1-C6)alkoxy, aryl, or heterocycle; X is a direct bond or oxygen; and Y is a direct bond, —(C1-C6)alkyl, —OCH2—, —CH2O—, or oxygen; provided that when R is —NR9SO2R10, and R6 and R7 are both hydrogen, then R5 is not imidazolyl.
- 2. A compound according to claim 1 wherein Ar is phenyl; R is —NR9SO2R10; R1 is hydrogen, hydroxy, or halogen; R2, R3, R4, and R8 are hydrogen; X is oxygen; Y is a direct bond; and R5 is a five- or six-membered ring heterocycle selected from the group consisting of dihydropyridazinoyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinonyl, pyridazinyl, pyridyl, pyrimidinonyl, pyrimidyl, thiadiazoyly, thiazolinyl, thiazolyl, triazinyl, and triazolyl.
- 3. A compound according to claim 2 selected from the group consisting of:(R)-N-[2-chloro-5-(2-{2-[4-(2-ethyl-oxazol-4-yl)-phenoxy]-ethylamino}-1-hydroxy-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(2-{2-[4-(2-ethyl-thiazol-4-yl)-phenoxy]-ethylamino}-1hydroxy-ethyl)phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-isopropyl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-isopropyl-oxazol-4-yl)-phenoxy]-ethylamino)-ethyl)phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-methyl-oxazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-methyl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-(2-chloro-5-{1-hydroxy-2-[2-(4-oxazol-4-yl-phenoxy)-ethylamino]-ethyl}-phenyl)-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-phenyl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-pyridin-3-yl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hyroxy-2-{2-[4-(2-pyridin-4-yl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-(2-chloro-5-{1-hydroxy-2-[2-(4-thiazol-4-yl-phenoxy)-ethylamino]-ethyl}-phenyl)-methanesulfonamide; and (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-trifluoromethyl-1H-imidazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; a stereoisomer or prodrug thereof, or a pharmaceutically acceptable salt of said compound, stereoisomer, or prodrug.
- 4. A compound according to claim 3 selected from the group consisting of:(R)-N-[2-chloro-5-(2-{4-(2-ethyl-oxazol-4-yl)-phenoxy]-ethylamino}-1-hydroxy-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(2-{4-(2-ethyl-thiazol-4-yl)-phenoxy]-ethylamino}-1-hydroxy-ethyl)-phenyl]-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-(4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; (R)-N-(2-chloro-5-{1-hydroxy-2-[2-(4-thiazol-4-yl-phenoxy)-ethylamino]ethyl}-phenyl)-methanesulfonamide; (R)-N-[2-chloro-5-(1-hydroxy-2-{2-[4-(2-methyl-oxazol-4-yl)-phenoxy]-ethylamino}-ethyl)-phenyl]-methanesulfonamide; and (R)-N-(2-chloro-5-{1-hydroxy-2-[2-(4-oxazol-4-yl-phenoxy)-ethylamino]-ethyl}-phenyl)-sulfonamide; a stereoisomer or prodrug thereof, or a pharmaceutically acceptable salt of said compound, stereoisomer, or prodrug.
- 5. A method of treating a β3 adrenergic receptor-mediated disease, condition, or disorder in a mammal in need of such treatment which method comprises administering to said mammal a therapeutically effective amount of a compound of claim 1, a stereoisomer or prodrug thereof, or a pharmaceutically acceptable salt of said compound, stereoisomer, or prodrug; wherein the β3 adrenergic receptor-mediated disease, condition, or disorder is selected form the group consisting of obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, esophagitis, duodenitis, Crohn' Disease, proctitis, asthma, intestinal motility disorder, ulcer, gastritis, hypercholesterolemia, urinary incontinence, depression, prostate disease, dyslipidemia, and airway inflammatory disorder.
- 6. A method of increasing lean meat content in an edible animal which method comprises administering to said edible animal a lean meat increasing amount of a compound of claim 1, a stereoisomer, or prodrug thereof, or a pharmaceutically acceptable salt of the compound, stereoisomer, or prodrug.
- 7. A pharmaceutical composition which comprises a compound of claim 1, a stereoisomer or prodrug thereof, or a pharmaceutically acceptable salt of said compound, stereoisomer, or prodrug, and a pharmaceutically acceptable carrier, vehicle, or diluent.
- 8. A method of treating a β3 adrenergic receptor-mediated disease, condition, or disorder in a mammal in need of such treatment which method comprises administering to said mammal a therapeutically amount of a composition of claim 7; wherein β3 adrenergic receptor-mediated disease, condition, or disorder is selected form the group consisting of obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, esophagitis, duodenitis, Crohn' Disease, proctitis, asthma, intestinal motility disorder, ulcer, gastritis, hypercholesterolemia, urinary incontinence, depression, prostate desease, dyslipidemia, and airway inflammatory disorder.
- 9. A method of increasing lean meat content in an edible animal which method comprises administering to said edible animal a lean meat increasing amount of a pharmaceutical composition of claim 7.
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of pending U.S. patent application No. 09/981,551 filed on Oct. 17, 2001 now U.S. Pat. No. 6,566,377 which claims the benefit of U.S. Provisional Patent Application No. 60/242,274 filed Oct. 20, 2000, both of which are incorporated herein by reference in their entirety.
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Provisional Applications (1)
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Number |
Date |
Country |
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60/242274 |
Oct 2000 |
US |