Kappa opioid agonists and uses thereof

Patent metadata

Field	Value
Publication number	US-11111214-B2
Application number	US-201916529504-A
Country	US
Kind code	B2
Filing date	Aug 1, 2019
Priority date	Jun 28, 2013
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

Provided are compounds of Formula I; and pharmaceutically acceptable salts and solvates thereof:The compounds of Formula I described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry.

First claim

What is claimed is:

1. A compound according to Formula I:

wherein:
R 1 is an optionally substituted phenyl;
R 2 is hydrogen;
R 3 is selected from hydrogen and an optionally substituted alkyl;
R 4 is an optionally substituted phenyl;
R 5 and R 6 taken together with the nitrogen to which they are attached form a pyrrolidinyl or azetidinyl ring substituted with —X-POLY;
X is an optional linker selected from a covalent bond; —C(O)NH—; —C(O)NHCH 2 —; —C(O)NHCH 2 CH 2 —; —OC(O)NH—; —C(O)NH—; —O—; —NHC(O)—; —NHC(O)CH 2 —; —NHC(O)CH 2 (O)—; —NHC(O)CH 2 CH 2 —; or —NHS(O) 2 —; and
POLY is a poly(alkylene oxide) oligomer comprising 2 to 10 alkylene oxide monomers;
or pharmaceutically acceptable salts and solvates thereof.

2. The compound of claim 1 , wherein R 1 is substituted with 1 to 3 halogens.

3. The compound of claim 1 , wherein R 3 is hydrogen.

4. The compound of claim 1 , wherein R 3 is methyl.

5. The compound of claim 1 , wherein the poly(alkylene oxide) oligomer is a poly(ethylene oxide) oligomer.

6. The compound of claim 1 , wherein POLY is end-capped with a hydroxyl group, a lower alkoxy group, or a trifluoromethoxy group.

7. The compound of claim 1 , having a structure selected from:

wherein X is selected from —O—, —OC(O)NH—, and a covalent bond;
POLY is ˜(CH 2 CH 2 O) n —Y,
n is an integer from 2 to 10, and
Y is selected from hydrogen, methyl, or trifluoromethoxy
or pharmaceutically acceptable salts and solvates thereof.

8. The compound of claim 1 , having the structure:

wherein X is selected from —O—, —OC(O)NH—, and a covalent bond;
POLY is —(CH 2 CH 2 O) n —Y,
n is an integer from 2 to 10, and
Y is selected from hydrogen, methyl, or trifluoromethoxy
or pharmaceutically acceptable salts and solvates thereof.

9. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.

10. A composition of matter comprising the compound of claim 1 , wherein the compound is present in a dosage form.

11. A method of treating pain or inflammation comprising administering the compound of claim 1 to a patient in need thereof.

12. A compound having the structure:

wherein R 10 is selected from the group consisting of ˜H, ˜OCH 2 CH 2 OH, ˜OCH 2 CH 2 OCH 3 , ˜NHCH 2 CH 2 OH, and ˜NHCH 2 CH 2 OCH 3 ,
X is an optional linker selected from a covalent bond; —C(O)NH—; —C(O)NHCH 2 —;
—C(O)NHCH 2 CH 2 —; —OC(O)NH—; —C(O)NH—; —O—; —NHC(O)—; and —NHC(O)CH 2 —;

POLY is a poly(alkylene oxide) oligomer comprising 2 to 10 alkylene oxide monomers, or pharmaceutically acceptable salts and solvates thereof.

13. The compound of claim 12 , wherein X-POLY is ˜O—(CH 2 CH 2 O) n —Y, wherein n is 2 to 30, and Y is selected from hydrogen, lower alkyl and trifluoromethoxy.

14. A compound having the following structure:

wherein:
n is an integer of from 1 to 30;
R 10 is selected from the group consisting of ˜H, ˜OCH 2 CH 2 OH, ˜OCH 2 CH 2 OCH 3 , ˜NHCH 2 CH 2 OH, and ˜NHCH 2 CH 2 OCH 3 ;
R 11 is selected from the group consisting of ˜H, ˜CH 3 , and ˜CF 3 , and pharmaceutically acceptable salts and solvates thereof.

Assignees

• Nektar Therapeutics

Inventors

• Anand Neel K
• Duarte Franco J
• Zhang Wen
• Ren Zhongxu

Classifications

• C07D409/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D213/61

  Halogen atoms or nitro radicals · CPC title

• C07D207/12 Primary

  Oxygen or sulfur atoms · CPC title

• C07D241/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D207/09

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title