Quinazolin-4(3H)-one-type piperidine compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9951038-B2
Application number	US-201314758138-A
Country	US
Kind code	B2
Filing date	Dec 23, 2013
Priority date	Dec 27, 2012
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

The present disclosure relates to Quinazolin-4(3H)-one-Type Piperidine Compounds, such as those of Formule (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2 , R 3 , Q, Y 1 , Z, A, B, E, and a are as defined herein; compositions comprising an effective amount of a Quinazolin-4(3H)-one-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 Quinazolin-4(3H)-one-Type Piperidine Compound.

First claim

The invention claimed is:

1. A compound of Formula (Ia′):

or a pharmaceutically acceptable salt or solvate thereof,
wherein
A and B together form a (C 2 -C 6 )bridge, wherein the 6-membered, nitrogen-containing ring that is fused to the benzene ring is in the endo- or exo-configuration with respect to the A-B bridge;
R 3 is H, —(CH 2 ) d C(═Y)YT, or —(CH 2 ) d C(═Y)N(T) 2 ,
Y, each independently, is O or S;
Z is a direct bond;
R 1 is —(C 3 -C 14 )cycloalkyl or —(C 6 -C 14 )bicycloalkyl, each of which is unsubstituted or substituted with R 5 ;
each T is independently selected from
—H, or —(C 1 -C 10 )alkyl, unsubstituted or substituted with 1, or 2 independently selected R 5 groups

each R 5 is independently —(C 1 -C 6 )alkyl;
each R 7 is independently —H, or —(C 1 -C 6 )alkyl;
each d is an integer independently selected from 0, 1, 2, 3, 4, 5, and 6.

2. The compound of claim 1 , wherein R 3 is —(CH 2 ) d C(═Y)YT or —(CH 2 ) d C(═Y)N(T) 2 .

3. The compound of claim 1 , wherein R 3
is —(CH 2 ) d C(═Y)YT, wherein Y is O for each occurrence and d is 1 or 2, and T is —H or unsubstituted —(C 1 -C 6 )alkyl.

4. The compound of claim 1 , wherein R 3 is —(CH 2 ) d C(═Y)N(T) 2 , wherein Y is O, d is 1 or 2.

5. The compound of claim 4 , wherein one T is —H, and the other occurrence of T is —(C 1 -C 6 )alkyl substituted with at least one R 5 .

6. The compound of claim 5 , wherein at least one R 5 in an occurrence of T of R 3 is —C(═O)OR 7 .

7. The compound of claim 1 , wherein R 3 is —H.

8. The compound of claim 1 , wherein A and B together form a bridge such that the bridged-piperidine is:

wherein the piperidine nitrogen is optionally in pharmaceutically acceptable salt form.

9. The compound of claim 8 , wherein the 6-membered, nitrogen-containing ring that is fused to the benzene ring is in the endo-configuration with respect to the A-B bridge.

10. The compound of claim 1 , wherein R 1 is —(C 6 -C 14 )bicycloalkyl, which is unsubstituted or substituted with R 5 wherein R 5 is —OR 7 or ═O.

11. The compound of claim 1 , wherein —Z—R 1 is:

12. The compound of claim 1 , wherein —Z—R 1 is:

R z is —H or —(C 1 -C 6 )alkyl.

13. A compound selected from:

and the pharmaceutically acceptable salts and solvates thereof.

14. The compound of claim 13 selected from:

and the pharmaceutically acceptable salts and solvates thereof.

15. A composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

16. 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 of claim 1 .

17. A method for treating pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound of claim 1 .

Assignees

• Purdue Pharma Lp

Inventors

• Tadesse Dawit

Classifications

• C07D451/14

  containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title