Arylpyrrolidine derivatives as NK-1 /SSRI antagonists

• US 20060020011A1
• Filed: 07/18/2005
• Published: 01/26/2006
• Est. Priority Date: 07/20/2004
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Wu, Yong-Jin, Bronson, Joanne J., He, Huan
• Granted Patent: US 7,138,423 B2
• Time in Patent Office: Days
• US Class Current: 514/406
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present disclosure relates to chemical compounds and their use in treatment of human diseases. A particular embodiment relates to compounds of Formula (I) or an isomer, a pharmaceutically acceptable salts or solvates thereof or a pharmaceutically acceptable formulation comprising said compounds are useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Claims

1. A compound of Formula (I)

2. The compound of claim 1, wherein X is oxygen.

3. The compound of claim 1 wherein R¹ is phenyl.

4. The compound of claim 1 wherein R¹ is indolyl.

5. The compound of claim 2 wherein R² and R³ are each CF₃ and R⁴ is H.

6. The compound of claim 5 wherein R⁵ is H.

7. The compound of claim 6, wherein R¹ is phenyl.

8. The compound of claim 7 wherein R¹ and —

CH₂X group are trans to each other.

9. A pharmaceutical composition comprising a compound of claim 1, together with at least one pharmaceutically acceptable excipient.

10. A method for the treatment or prevention of physiological disorders mediated by tachykinins and/or by the selective inhibition of the serotonin re-uptake transporter protein comprising administration of an effective amount of a compound according to claim 1.

11. A method of treating a subject afflicted with a condition mediated by substance P and other neurokinins and/or by selective inhibition of the serotonin reuptake transporter protein comprising administration of an effective amount of a compound according to claim 1.

12. A method for the treatment or prevention of depression and/or anxiety which method comprises administration to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1.