Claims for Patent: 8,796,299

Summary for Patent: 8,796,299

Title:	NK1 antagonists
Abstract:	A NK1 antagonist having the formula (I), wherein Ar1 and Ar2 are optionally substituted phenyl or heteroaryl, X1 is an ether, thio or imino linkage, R4 and R5 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):	Sunil Paliwal, Gregory A. Reichard, Cheng Wang, Dong Xiao, Hon-Chung Tsui, Neng-Yang Shih, Juan D. Arredondo, Michelle Laci Wrobleski, Anandan Palani
Assignee:	Merck Sharp and Dohme LLC, Opko Health Inc
Application Number:	US13/625,799
Patent Claims:	1. A method for treating a physiological disorder, symptom or disease in a patient, comprising administering to the patient an effective amount of at least one compound of Formula I: or a pharmaceutically-acceptable salt thereof, wherein Ar1 is phenyl; X2 is —O—; R1 and R2 are each independently selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C3alkyl), C3-C8 cycloalkyl, —CH2F, —CHF2 and —CF3; or R1 and R2, together with the carbon atom to which they are both attached, form a C3 to C6 alkylene ring; or R1 and R2, together with the carbon atom to which they are both attached, form a C═O group; R3 is selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C3 alkyl), C3-C8 cycloalkyl, —CH2F, —CHF2 and —CF3; each R6 is independently selected from the group consisting of H, C1-C6 alkyl and —OH; each R7 is independently selected from the group consisting of H and C1-C6 alkyl; n2 is 2; R4 and R5, together with the carbon atom to which they are both attached, form a 5- or 6-membered heterocycloalkyl ring selected from the group consisting of: wherein said 5- or 6-membered heterocycloalkyl ring is optionally substituted with from 1 to 6 substitutents independently selected from the group consisting of R30 and R31; R18 is H, C1-C6 alkyl, C3-C8 cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, hydroxy(C2-C6)alkyl or —P(O)(OH)2; R30 and R31 are each independently selected from the group consisting of H and C1-C2 alkyl, or R30 and R31, together with the carbon atom to which they are both attached, form ═O; R32 and R33 are each independently selected from the group consisting of H and C1-C6 alkyl; or a, where the physiological disorder, symptom or disease is asthma, emesis, nausea, depression, anxiety, cough or migraine. 2. The method according to claim 1, wherein the compound is selected from: or a pharmaceutically acceptable salt thereof. 3. The method according to claim 1, wherein the compound is: or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1, wherein the physiological disorder, symptom or disease is emesis and nausea. 5. The method according to claim 1, wherein the physiological disorder, symptom or disease is cough. 6. The method according to claim 1, wherein R1 and R2 are each independently selected from the group consisting of H and C1-C6 alkyl. 7. The method according to claim 6, wherein R1 and R2 are each independently selected from the group consisting of H and CH3. 8. The method according to claim 1, wherein R3 is H or C1-C6 alkyl. 9. The method according to claim 8, wherein R3 is H. 10. The method according to claim 1, wherein each R6 is independently H or C1-C6 alkyl. 11. The method according to claim 10, wherein each R6 is H. 12. The method according to claim 1, wherein each R7 is H. 13. The method according to claim 1, wherein R18 is H or C1-C6 alkyl. 14. The method according to claim 13, wherein R18 is H. 15. The method according to claim 1, wherein R32 and R33 are each H.