Substituted-quinoxaline-type piperidine compounds and the uses thereof

• US 9,527,840 B2
• Filed: 02/11/2016
• Issued: 12/27/2016
• Est. Priority Date: 08/31/2007
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P., Shionogi & Co., Ltd.
• Inventors: Fuchino, Kouki, Goehring, R. Richard, Shao, Bin, Taoda, Yoshiyuki, Tsuno, Naoki, Whitehead, John William Frank, Yao, Jiangchao
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US15/041,998
• Publication Number:
  US 20160159785A1
• Time in Patent Office: 320 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/06 Anti-spasmodics
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 451/04 : with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
• CPC Class Codes: C07D 451/14 : containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
• CPC Class Codes: C07D 471/08 : Bridged systems
• CPC Class Codes: C07D 471/14 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 498/08 : Bridged systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The invention relates to Substituted-Quinoxaline-Type Piperidine Compounds, compositions comprising an effective amount of a Substituted-Quinoxaline-Type Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Substituted-Quinoxaline-Type Piperidine Compound.

Claims

1. A compound of Formula (IIE):

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein a is 0.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein h is 0 and R₁ is:

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein R₁ is optionally substituted bicyclo[3.3.1]nonyl.

5. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein R₁ is:

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein each R_z is —

H.

7. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein R₄ is:

(a) —

C(═

Y)YX;

or

(b) —

N(R₉)X.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein X of —

N(R₉)X is —

(C₁-C₆)alkyl substituted with one R₈ group, -(5- or 6-membered)heterocycle substituted with one R₈ group, -phenyl substituted with one R₇ group, or -(5- or 6-membered)heteroaryl substituted with one R₇ group and each R₇ or R₈ is —

C(═

O)OR₉.

9. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein each Y is O.

10. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein R₄ is X and X is -tetrazolyl.

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein a is 1 and R₂ is selected from -halo.

12. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of claim 1.

13. A method for treating pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of claim 1.

14. The compound of claim 1, wherein the compound of Formula (IIE) is a compound of Formula (IIE1):

15. The compound of claim 14 or a pharmaceutically acceptable salt thereof, wherein a is 0.

16. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein h is 0 and R₁ is:

17. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein R₁ is optionally substituted bicyclo[3.3.1]nonyl.

18. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein R₁ is:

19. The compound of claim 18 or a pharmaceutically acceptable salt thereof, wherein each R_z is —

H.

20. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein R₄ is:

(a) —

C(═

Y)YX;

or

(b) —

N(R₉)X.