|Abstract:||A NK.sub.1 antagonist having the formula (I), ##STR00001## wherein Ar.sup.1 and Ar.sup.2 are optionally substituted phenyl or heteroaryl, X.sup.1 is an ether, thio or imino linkage, R.sup.4 and R.sup.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.|
|Inventor(s):||Paliwal; Sunil (Monroe Township, NJ), Reichard; Gregory A. (Ann Arbor, MI), Wang; Cheng (Summit, NJ), Xiao; Dong (Warren, NJ), Tsui; Hon-Chung (East Brunswick, NJ), Shih; Neng-Yang (Warren, NJ), Arredondo; Juan D. (Montclair, NJ), Wrobleski; Michelle Laci (Whitehouse Station, NJ), Palani; Anandan (Bridgewater, NJ)|
|Assignee:||Opko Health, Inc. (Miami, FL)|
|Filing Date:||Dec 14, 2010|
|Claims:||1. A compound having the formula (I): ##STR00256## or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is phenyl, wherein said phenyl can be unsubstituted or substituted with 1 to 3 fluoro; Ar.sup.2 is bis(trifluoromethyl)phenyl; X.sup.1 is --O--; R.sup.1 and R.sup.2 are independently selected from the group consisting of H, C.sub.1-C.sub.6 alkyl or hydroxyl(C.sub.1-C.sub.3 alkyl), C.sub.3-C.sub.8 cycloalkyl, --CH.sub.2F, --CHF.sup.2, --CF.sub.3; R.sup.3 is H, C.sub.1-C.sub.6 alkyl, hydroxyl(C.sub.1-C.sub.3 alkyl), C.sub.3-C.sub.8 cycloalkyl, --CH.sub.2F, --CF.sub.2H, or --CF.sub.3; R.sup.6 and R.sup.7 are independently selected from H or C.sub.1-C.sub.6 alkyl; n.sub.2 is 1 or 2; R.sup.4 and R.sup.5 together are .dbd.O; R.sup.18 is C.sub.1-C.sub.6 alkyl, Cbz or H; R.sup.32 and R.sup.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.sup.1 or R.sup.2 is C.sub.1-C.sub.6alkyl and the other of R.sup.1 or R.sup.2 is H; R.sup.3 is H; R.sup.6 and R.sup.7 are H; R.sup.18 is Cbz or H; R.sup.32 and R.sup.33 are H; and n.sub.2 is 2, or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 having the formula: ##STR00257##