Biphenyl derivatives
2 Assignments
0 Petitions
Accused Products
Abstract
This invention provides biphenyl derivatives of formula I:
- wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
-
Citations
64 Claims
-
1-43. -43. (canceled)
-
44. A compound of the formula:
- 45. Biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenyl-carbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
47. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
48. A pharmaceutical composition comprising:
-
(a) a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof;
(b) a therapeutically effective amount of a steroidal anti-inflammatory agent; and
(c) a pharmaceutically acceptable carrier.
-
-
49. A pharmaceutical composition comprising an isotonic aqueous solution comprising from about 0.05 μ
- g/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
50. A pharmaceutical composition comprising:
-
(a) biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenyl-carbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof; and
(b) a pharmaceutically acceptable carrier;
wherein the pharmaceutical composition is a dry powder. - View Dependent Claims (51)
-
-
52. A pharmaceutical composition comprising:
-
(a) micronized particles of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof; and
(b) dry lactose having a particle size between about 1 μ
m and about 100 μ
m.
-
-
53. A pharmaceutical composition comprising:
-
(a) biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenyl-carbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof; and
(b) a propellant. - View Dependent Claims (54)
-
-
55. A method of treating a pulmonary disorder, the method comprising administering to a patient in need of treatment a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
56. A method of treating a pulmonary disorder, the method comprising administering to a patient in need of treatment a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof;
- and a therapeutically effective amount of a steroidal anti-inflammatory agent.
-
57. A method of treating chronic obstructive pulmonary disease, the method comprising administering to a patient in need of treatment a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenyl-carbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
58. A method of treating chronic obstructive pulmonary disease, the method comprising administering to a patient in need of treatment about 10 μ
- g/day to about 200 μ
g/day of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenyl-carbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
- g/day to about 200 μ
-
59. A method of treating asthma, the method comprising administering to a patient in need of treatment a therapeutically effective amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
60. A method of treating asthma, the method comprising administering to a patient in need of treatment about 10 μ
- g/day to about 200 μ
g/day of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
- g/day to about 200 μ
-
61. A method of producing bronchodilation in a patient, the method comprising administering to the patient a bronchodilation-producing amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
62. A method of antagonizing a muscarinic receptor in a biological system or sample having a muscarinic receptor, the method comprising contacting the biological system or sample with a muscarinic receptor antagonizing-amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
63. A method of agonizing a β
-
2 adrenergic receptor in a biological system or sample having a β
2 adrenergic receptor, the method comprising contacting the biological system or sample with a β
2 adrenergic receptor agonizing-amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
2 adrenergic receptor in a biological system or sample having a β
-
64. A method of antagonizing a muscarinic receptor and agonizing a β
-
2 adrenergic receptor in a biological system or sample having a muscarinic receptor and a β
2 adrenergic receptor, the method comprising contacting the biological system or sample with a muscarinic receptor antagonizing- and β
2 adrenergic receptor agonizing-amount of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a pharmaceutically acceptable salt or solvate thereof.
-
2 adrenergic receptor in a biological system or sample having a muscarinic receptor and a β
Specification