A NK 1 antagonist having the formula (I), wherein Ar 1 and Ar 2 are optionally substituted phenyl or heteroaryl, X 1 is an ether, thio or imino linkage, R 4 and R 5 are not both H or alkyl, and the remaining variables are as defined in the specification, useful for treating a number of disorders, including emesis, depression, anxiety and cough. Pharmaceutical compositions. Methods of treatment and combinations with other agents are also disclosed.
1. A compound having the formula (I):
or a pharmaceutically acceptable salt thereof, wherein
Ar 1 is phenyl, wherein said phenyl can be unsubstituted or substituted with 1 to 3 fluoro;
Ar 2 is bis(trifluoromethyl)phenyl;
X 1 is —O—;
R 1 and R 2 are independently selected from the group consisting of H, C 1 -C 6 alkyl or hydroxyl(C 1 -C 3 alkyl), C 3 -C 8 cycloalkyl, —CH 2 F, —CHF 2 , —CF 3 ;
R 3 is H, C 1 -C 6 alkyl, hydroxyl(C 1 -C 3 alkyl), C 3 -C 8 cycloalkyl, —CH 2 F, —CF 2 H, or —CF 3 ;
R 6 and R 7 are independently selected from H or C 1 -C 6 alkyl;
n 2 is 1 or 2;
R 4 and R 5 together are ═O;
R 18 is C 1 -C 6 alkyl, Cbz or H;
R 32 and R 33 are each H;
or a diaseteromer, enantiomer, stereoisomer, regioisomer, rotamer, or tautomer thereof.
2. The compound according to claim 1 , wherein:
at least one of R 1 or R 2 is C 1 -C 6 alkyl and the other of R 1 or R 2 is H;
R 3 is H;
R 6 and R 7 are H;
R 18 is Cbz or H;
R 32 and R 33 are H; and
n 2 is 2, or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 having the formula: