Claims
- 1. A compound of Formula (I)
- 2. The compound of claim 1 wherein Ar is pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 3. The compound of claim 1 wherein Ar is phenyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 4. The compound of claim 2 or 3 wherein HET is oxazole or pyrazole;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 5. The compound of claim 4 wherein R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 6. The compound of claim 4 wherein R8 is —CONR1bR2b, and R7 and R9 are each independently hydrogen, fluoro, or (C1-C6)alkyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 7. The compound of claim 6 where R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 8. The compound of claim 7 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 9. The compound of claim 7 wherein R1b and R2b are each independently selected from hydrogen, (C3-C6)cycloalkyl, or an (C1-C6)alkyl optionally substituted with one or more fluoro,
or R1b and R2b taken together with the nitrogen to which they are attached form a 4- to 6-membered non-aromatic heterocyclic ring optionally containing one additional heteroatom selected from O and N; a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 10. The compound of claim 9 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 11. The compound of claim 1 where Ar is pyridyl; R1 is hydrogen, halo, or methoxy; R2, R3, R4, R5, R6, R7 and R9 are all hydrogen; X is —O—; m is 1; and R8 is —CONR1bR2b, where R1b and R2b are each independently hydrogen or methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 12. The compound of claim 11 wherein Ar is 3-pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 13. The compound of claim 1 having the Formula (IA)
- 14. The compound of claim 13 wherein Ar is pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 15. The compound of claim 13 wherein Ar is phenyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 16. The compound of claim 14 or 15 wherein R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 17. The compound of claim 14 or 15 wherein R8 is —CONR1bR2b, and R7 and R9 are each independently hydrogen, fluoro, or (C1-C6)alkyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 18. The compound of claim 17 where R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 19. The compound of claim 18 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 20. The compound of claim 18 wherein R1b and R2b are each independently selected from hydrogen, (C3-C6)cycloalkyl or (C1-C6)alkyl optionally substituted with one or more fluoro,
or R1b and R2b taken together with the nitrogen to which they are attached form a 4- to 6-membered non-aromatic heterocyclic ring optionally containing an additional heteroatom selected from O or N; a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 21. The compound of claim 20 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 22. The compound of claim 13 where Ar is pyridyl; R1 is hydrogen, halo, methyl, or methoxy; R2, R3, R4, R5, R6, R7 and R9 are all hydrogen; X is —O—; m is 1; and R8 is —CONR1bR2b, where R1b and R2b are each independently hydrogen or methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 23. The compound of claim 22 wherein Ar is 3-pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 24. The compound of claim 23 where R1 is methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 25. The compound of claim 13 selected from the group consisting of
2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl )-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-acetamide; 2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-oxazol-2-yl)-N,N-dimethyl-acetamide; N,N-diethyl-2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-oxazol-2-yl)-acetamide; 2-[4-(4-{2-[2-(6-chloro-pyridin-3-yl)-2(R)-hydroxy-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N-ethyl-N-(2,2,2-trifluoro-ethyl)-acetamide; 2-[4-(4-{2-[2-(6-chloro-pyridin-3-yl)-2(R)-hydroxy-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-diisopropyl-acetamide; 2-[4-(4-{2-[2-(6-chloro-pyridin-3-yl)-2(R)-hydroxy-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-isobutyramide; 2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-oxazol-2-yl)-N,N-dimethyl-isobutyramide; 2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-oxazol-2-yl)-N,N-dimethyl-butyramide; 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-propionamide; 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-butyramide; and 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-isobutyramide; a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
- 26. The compound of claim 13 selected from the group consisting of
2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-acetamide; 2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylalmino)-ethoxy]-phenyl}-oxazol-2-yl)-N,N-dimethyl-acetamide; N,N-diethyl-2-(4-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-oxazol-2-yl)-acetamide; 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-propionamide; 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-butyramide; and 2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-isobutyramide; a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
- 27. The compound of claim 13 having the Formula (IA-1)
- 28. The compound of claim 27 wherein
R1 is hydrogen, halogen, or (C1-C6)alkyl; R3, R4, R5, R6, R7 and R9 are hydrogen; R8 is —CONR1bR2b, where R1b and R2b are each independently selected from hydrogen, or (C1-C6)alkyl, X is —O—; and m is 1; a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 29. The compound of claim 28 wherein R1 is methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 30. The compound of claim 29 which is
2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-acetamide; or a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
- 31. The compound of claim 29 which is
2-[4-(4-{2-[2(R)-hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N-methyl-acetamide; or a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
- 32. A compound of Formula (IB).
- 33. The compound of claim 32 wherein Ar is pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 34. The compound of claim 32 wherein Ar is phenyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 35. The compound of claim 33 or 34 wherein R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 36. The compound of claim 33 or 34 wherein R8 is —CONR1bR2b, and R7 and R9 are each independently hydrogen, fluoro, or (C1-C6)alkyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 37. The compound of claim 36 where R5 and R6 are both hydrogen, X is —O— and m is 1;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 38. The compound of claim 37 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 39. The compound of claim 36 wherein R1b and R2b are each independently selected from hydrogen, (C3-C6)cycloalkyl, or an (C1-C6)alkyl optionally substituted with one or more fluoro,
or R1b and R2b taken together with the nitrogen to which they are attached form a 4- to 6-membered non-aromatic heterocyclic ring optionally containing an additional heteroatom selected from O or N; a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 40. The compound of claim 39 wherein R3 and R4 are both hydrogen;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 41. The compound of claim 32 where Ar is pyridyl; R1 is hydrogen, halo, methyl, or methoxy; R2, R3, R4, R5, R6, R7 and R9 are all hydrogen; X is —O—; m is 1; and R8 is —CONR1bR2b, where R1b and R2b are each independently hydrogen or methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 42. The compound of claim 41 wherein Ar is 3-pyridyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 43. The compound of claim 42 where R1 is methyl;
a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 44. The compound of claim 32 selected from the group consisting of
2-(3-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-pyrazol-1-yl)-N,N-dimethyl-acetamide; N-ethyl-2-(3-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-pyrazol-1-yl)-N-methyl-acetamide; 2-(3-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-pyrazol-1-yl)-1-morpholin-4-yl-ethanone; 2-(3-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-pyrazol-1-yl)-1-pyrrolidin-1-yl-ethanone; and N-cyclopentyl-2-(3-{4-[2-(2(R)-hydroxy-2-pyridin-3-yl-ethylamino)-ethoxy]-phenyl}-pyrazol-1-yl)-acetamide; a pharmaceutically acceptable salt thereof, or a solvate or hydrate of said compound or said salt.
- 45. A pharmaceutical composition comprising (1) a compound of claim 1, a pharmaceutically acceptable salt thereof or a hydrate or solvate of said compound or said salt; and (2) a pharmaceutically acceptable excipient, diluent, or carrier.
- 46. The pharmaceutical composition of claim 45 further comprising an additional pharmaceutical agent.
- 47. The pharmaceutical composition of claim 46 wherein said additional pharmaceutical agent is selected from the group consisting of an apolipoprotein-B secretion/microsomal triglyceride transfer protein inhibitor, a MCR-4 agonist, a cholecystokinin-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a cannabinoid receptor antagonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a 5HT2c agonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, an anorectic agent, a Neuropeptide-Y antagonist, a thyromimetic agent, a dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, a human agouti-related protein, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or inverse agonist, and a neuromedin U receptor agonist.
- 48. A method for treating a disease, condition or disorder modulated by a 3 adrenergic receptor agonist in animals comprising the step of administering to an animal in need of such treatment a therapeutically effective amount of a compound of claim 1; a pharmaceutically acceptable salt thereof, a prodrug of said compound or said salt, or a solvate or hydrate of said compound, said salt or said prodrug.
- 49. The method of claim 48 wherein said disease, condition, or disorder modulated by a β3 adrenergic agonist is selected from the group consisting of weight loss, obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, esophagitis, duodenitis, Crohn's disease, proctitis, asthma, intestinal motility disorder, ulcer, gastritis, hypercholesterolemia, cardiovascular disease, urinary incontinence, depression, prostate disease, dyslipidemia, fatty liver, and airway inflammatory disorder.
- 50. A method for treating a disease, condition or disorder modulated by a β3 adrenergic agonist in animals comprising the step of administering to an animal in need of such treatment two separate pharmaceutical compositions comprising
(i) a first composition comprising a compound of claim 1, a pharmaceutically acceptable salt thereof or a hydrate or solvate of said compound or said salt, and a pharmaceutically acceptable excipient, diluent, or carrier, and (ii) a second composition comprising at least one additional pharmaceutical agent and a pharmaceutically acceptable excipient, diluent, or carrier.
- 51. The method of claim 50 wherein said at least one additional pharmaceutical agent is an anti-obesity agent.
- 52. The method of claim 51 wherein said anti-obesity agent is selected from the group consisting of an apolipoprotein-B secretion/microsomal triglyceride transfer protein inhibitor, a MCR-4 agonist, a cholecystokinin-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a cannabinoid receptor antagonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a 5HT2c agonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, an anorectic agent, a Neuropeptide-Y antagonist, a thyromimetic agent, a dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, a human agouti-related protein, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or inverse agonist, and a neuromedin U receptor agonist.
- 53. The method of claim 50 wherein said first composition and said second composition are administered simultaneously.
- 54. The method of claim 50 wherein said first composition and said second composition are administered sequentially and in any order.
- 55. An intermediate compound having Formula (I-a)
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application Nos. 60/360,251, filed on Feb. 27, 2002, and 60/432,074, filed on Dec. 9, 2002, and incorporated herein by reference in their entirety.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60360251 |
Feb 2002 |
US |
|
60432074 |
Dec 2002 |
US |