Acetamide derivatives
The invention is concerned with a compound of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R3, X and Y are as defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
1. A compound of formula (I)
wherein:
X is —CH 2 — or oxygen;
Y is —(CH 2 ) n —;
R1 is phenyl optionally substituted with halogen;
R2 is lower alkyl;
R3 is trifluoromethyl-phenyl, trifluoromethyl-pyridinyl, trifluoromethyl-pyridazinyl, trifluoromethyl-pyrimidinyl or trifluoromethyl-pyrazinyl; and
n is 0 or 1, provided that n is not 0 when X is oxygen;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein X is —CH 2 —.
3. A compound according to claim 1 , wherein X is oxygen.
4. A compound according to claim 1 , wherein n is 0.
5. A compound according to claim 1 , wherein n is 1.
6. A compound according to claim 1 , wherein R1 is halophenyl.
7. A compound according to claim 1 , wherein R1 is fluoro-phenyl.
8. A compound according to claim 1 , wherein R2 is methyl, ethyl, isopropyl or tert-butyl.
9. A compound according to claim 1 , wherein R2 is methyl, ethyl or isopropyl.
10. A compound according to claim 1 , wherein R3 is trifluoromethyl-phenyl or trifluoromethyl-pyridinyl.
11. A compound according to claim 1 , wherein, wherein R3 is trifluoromethyl-phenyl.
12. A compound according to claim 1 , wherein R3 is trifluoromethyl-pyridinyl.
13. A compound according to claim 1 , wherein the compound is selected from the group consisting of:
2-[Ethyl-(4-fluoro-benzenesulfonyl)-amino]-N-[1-(4-trifluoromethyl-phenyl)-piperidin-3-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[1-(4-trifluoromethyl-phenyl)-piperidin-3-ylmethyl]-acetamide;
2-[Ethyl-(4-fluoro-benzenesulfonyl)-amino]-N-[1-(4-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[1-(4-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[(S)-1-(4-trifluoromethyl-phenyl)-piperidin-3-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[(R)-1-(4-trifluoromethyl-phenyl)-piperidin-3-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-methyl-amino]-N-[4-(4-trifluoromethyl-phenyl)-morpholin-2-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[4-(4-trifluoromethyl-phenyl)-morpholin-2-ylmethyl]-acetamide;
2-[Ethyl-(4-fluoro-benzenesulfonyl)-amino]-N-[4-(4-trifluoromethyl-phenyl)-morpholin-2-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[(R)-4-(4-trifluoromethyl-phenyl)-morpholin-2-ylmethyl]-acetamide;
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[(S)-4-(4-trifluoromethyl-phenyl)-morpholin-2-ylmethyl]-acetamide; and
2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[4-(5-trifluoromethyl-pyridin-2-yl)-morpholin-2-ylmethyl]-acetamide.
14. A process for the manufacture of a compound of formula (I) comprising the reaction of a compound of formula (A)
in the presence of a compound of formula (B)
a coupling agent and a base, wherein R1 to R3 are as defined in claim 1 .
15. A compound according to claim 1 when manufactured by the process of claim 14 .
16. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
17. A method for the treatment of a respiratory disorder, the method comprising administering a therapeutically effective amount of a compound according to claim 1 to a subject in need thereof.
18. The method of claim 17 , wherein the respiratory disorder is selected from the group consisting of chronic obstructive pulmonary disorder (COPD), asthma, allergic rhinitis and bronchospasm.