Opioid agonists and uses thereof

Patent metadata

Field	Value
Publication number	US-10865186-B2
Application number	US-201816109456-A
Country	US
Kind code	B2
Filing date	Aug 22, 2018
Priority date	Nov 27, 2013
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds 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 selected from the formula:

wherein:
R 2 is an substituted alkyl;
(i) R 1 and R 3 are taken together with their intervening atoms to form a fused, substituted thiazole and R 5 is hydrogen, where R 1 and R 3 are positions 4 and 5 of the thiazole, wherein the thiazole is substituted with —X-POLY at position 2 of the thiazole; or
(ii) R 3 and R 5 are taken together with their intervening atoms to form a fused, substituted thiazole and R 1 is hydrogen, where R 1 and R 3 are positions 4 and 5 of the thiazole, wherein the thiazole is substituted with —X-POLY at position 2 of the thiazole;
is a double bond;
G is ═O;
X is a spacer moiety selected from a covalent bond, —C(O)—, —NHC(O)—, —NH—, —CH 2 CHOHCH 2 NH—, and —O—;
POLY is a poly(alkylene oxide) oligomer;

or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , wherein R 5 is hydrogen.

3. The compound of claim 1 , wherein R 2 is alkyl or cyclopropylmethyl.

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

5. The compound of claim 1 , wherein the compound of Formula I is selected from the formulae:

and
wherein n is an integer from 1 to 30.

6. The compound of claim 5 , wherein n is an integer from 1 to 10.

7. The compound of claim 1 , wherein R 3 and R 5 are taken together with their intervening atoms to form the substituted thiazole.

8. A compound, selected from
(6S,10R,12R)-2-(2,5,8,11,14-pentaoxahexadecan-16-ylamino)-7-(cyclopropylmethyl)-10,12-dimethyl-7,8,9,10-tetrahydro-6,10-methanothiazolo[4′,5′:4,5]benzo[1,2-d]azocin-5(6H)-one; and
(7S,11R,12R)-2-(2,5,8,11,14-pentaoxahexadecan-16-ylamino)-8-(cyclopropylmethyl)-11,12-dimethyl-8,9,10,11-tetrahydro-7,11-methanothiazolo[5′,4′:3,4]benzo[1,2-d]azocin-6(7H)-one;

or pharmaceutically acceptable salts 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. The compound of claim 1 , wherein the poly(alkylene oxide) oligomer is a poly(alkylene glycol) oligomer.

Assignees

• Nektar Therapeutics

Inventors

• Duarte Franco J
• Anand Neel K
• Sharma Pankaj
• Singh Devendrapratap

Classifications

• C07D513/08

  Bridged systems · CPC title

• C07D221/26 Primary

  Benzomorphans · CPC title

• C07D401/12

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

• A61P25/04

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