Aminoalcohol derivatives
View Patent ↗The present invention relates to a compound formula [I]: wherein Y is bond, —O—(CH 2 ) n — (in which n is 1, 2, 3 or 4), etc., Z is cyano, tetrazolyl, etc., R 1 is hydrogen, lower alkyl, etc., R 2 is hydrogen or an amino protective group, R 3 is hydrogen or lower alkyl, R 4 is hydrogen or lower alkyl, R 5 and R 8 are each independently hydrogen, halogen, hydroxy, lower alkyl, etc., R 6 is hydrogen, lower alkyl, etc., R 9 is hydrogen or lower alkyl, and i is 1 or 2, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.
1. A compound selected from the group consisting of
(1) 4′-[(2R)-2-[[(2R)-2-Phenyl-2-hydroxyethyl]amino]propyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid,
(2) 4′-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-3-isopropyloxy-1,1′-biphenyl-4-carboxylic acid,
(3) 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]-amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid,
(4) 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-2,3-dimethyl-1,1′-biphenyl-4-carboxylic acid,
(5) 4′-[2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]ethyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid,
(6) 4′-[(2R)-2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]propyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid,
(7) 4′-[2-[[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-3-isopropoxy-1,1′-biphenyl-4-carboxylic acid, and
(8) 4′-[2-[[(2R)-2-Hydroxy-2-phenylethyl]amino]ethyl]-3-isobutyl-1,1′-biphenyl-4-carboxylic acid,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]-amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-Phenyl-2-hydroxyethyl]amino]propyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-3-isopropyloxy-1,1′ -biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-2,3-dimethyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein said compound is 4′-[2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]ethyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]propyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein said compound is 4′-[2-[[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-3-isopropoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein said compound is 4′-[2-[[(2R)-2-Hydroxy-2-phenylethyl]amino]ethyl]-3-isobutyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with pharmaceutically acceptable carriers or excipients.
11. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
12. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-Phenyl-2-hydroxyethyl]amino]propyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
13. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-3-isopropyloxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
14. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-2,3-dimethyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
15. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]ethyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
16. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]propyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
17. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[2-[[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-3-isopropoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
18. The pharmaceutical composition of claim 10 , wherein said compound is 4′-[2-[[(2R)-2-Hydroxy-2-phenylethyl]amino]ethyl]-3-isobutyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
19. A method for treating pollakiuria or urinary incontinence in a human or animal in need thereof which comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
20. The method of claim 19 , wherein said treating pollakiuria or urinary incontinence is in a human in need thereof.
21. The method of claim 19 , wherein said treating pollakiuria or urinary incontinence is in an animal in need thereof.
22. The method of claim 20 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-methoxy-1,1′-biphenyl-4--carboxylic acid or a pharmaceutically acceptable salt thereof.
23. The method of claim 21 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
24. The method of claim 19 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
25. The method of claim 19 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-Phenyl-2-hydroxyethyl]amino]propyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
26. The method of claim 19 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]ammo]propyl]-3-isopropyloxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
27. The method of claim 19 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-2,3-dimethyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
28. The method of claim 19 , wherein said compound is 4′-[2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]ethyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
29. The method of claim 19 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]propyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
30. The method of claim 19 , wherein said compound is 4′-[2-[[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-3-isopropoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
31. The method of claim 19 , wherein said compound is 4′-[2-[[(2R)-2-Hydroxy-2-phenylethyl]amino]ethyl]-3-isobutyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
32. A method for treating overactive bladder in a human or animal in need thereof which comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
33. The method of claim 32 , wherein said treating overactive bladder is in a human in need thereof.
34. The method of claim 32 , wherein said treating overactive bladder is in an animal in need thereof.
35. The method of claim 32 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
36. The method of claim 32 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-Phenyl-2-hydroxyethyl]amino]propyl]-3-methoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
37. The method of claim 32 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-3-isopropyloxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
38. The method of claim 32 , wherein said compound is 4′-[2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]ethyl]-2,3-dimethyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
39. The method of claim 32 , wherein said compound is 4′-[2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]ethyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
40. The method of claim 32 , wherein said compound is 4′-[(2R)-2-[[(2R)-2-(3-Fluorophenyl)-2-hydroxyethyl]amino]propyl]-3-propoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
41. The method of claim 32 , wherein said compound is 4′-[2-[[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-3-isopropoxy-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.
42. The method of claim 32 , wherein said compound is 4′-[2-[[(2R)-2-Hydroxy-2-phenylethyl]amino]ethyl]-3-isobutyl-1,1′-biphenyl-4-carboxylic acid or a pharmaceutically acceptable salt thereof.