Compounds, compositions, and methods for the treatment of inflammatory, degenerative, and neurodegenerative diseases

Patent metadata

Field	Value
Publication number	US-2020255366-A1
Application number	US-202016859791-A
Country	US
Kind code	A1
Filing date	Apr 27, 2020
Priority date	Feb 9, 2015
Publication date	Aug 13, 2020
Grant date	—

Abstract

This disclosure provides compounds, pharmaceutical compositions, and methods of use for the prevention and treatment of inflammatory diseases or degenerative diseases including neurodegenerative diseases. Embodiments of the present disclosure provide compounds related to very long chain polyunsaturated fatty acids, pharmaceutical compositions containing the provided compounds, and methods of treating a subject with a condition or disease using provided compounds or pharmaceutical compositions.

First claim

What is claimed:

1 . A pharmaceutical composition comprising a compound of having the general structure A or B, wherein n is a number selected from a group consisting of 0 to 19 and the compound is a carboxylic acid or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

2 . The composition of claim 1 , wherein n is a number selected from a group consisting of 0 to 13.

3 . The composition of claim 1 , wherein n is selected from a group consisting of 1, 3, 5, 7, 9, 11 or 13.

4 . The composition of claim 1 , wherein n is selected from a group consisting of 0, 2, 4, 6, 8, 10 or 12.

5 . A compound having the general structure C or D,

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

6 . The compound of claim 5 , wherein n is a number selected from a group consisting of 0 to 13.

7 . The compound of claim 5 , wherein n is selected from a group consisting of 1, 3, 5, 7, 9, 11 or 13.

8 . The compound of claim 5 , wherein n is selected from a group consisting of 0, 2, 4, 6, 8, 10 or 12.

9 . The compound of claim 5 , wherein n is 9 or 11.

10 . The compound of claim 5 , wherein the R group is methyl or ethyl.

11 . The compound of claim 5 , wherein the R group is a metal cation selected from a group consisting of sodium, potassium, magnesium, zinc, and calcium cation.

12 . The compound of claim 5 , wherein the R group is part of a phospholipid with the overall structure E or F, having the following formula:

13 . A compound having the general structure G or H,

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

14 . The compound of claim 13 , wherein n is a number selected from a group consisting of 0 to 13.

15 . The compound of claim 13 , wherein n is selected from a group consisting of 1, 3, 5, 7, 9, 11 or 13.

16 . The compound of claim 13 , wherein n is selected from a group consisting of 0, 2, 4, 6, 8, 10 or 12.

17 . The compound of claim 13 , wherein n is 9 or 11.

18 . The compound of claim 13 , wherein the R group is methyl or ethyl.

19 . The compound of claim 13 , wherein the R group is a metal cation selected from a group consisting of sodium, potassium, magnesium, zinc, and calcium cation.

20 . The compound of claim 13 , wherein the compound is selected from a group consisting of I, J, K, or L, having one of the following structures:

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

21 . The compound of claim 13 , wherein the compound is selected from a group consisting of (S,16Z,19Z,22Z,25Z,27E,31Z)-29-hydroxytetratriaconta-16,19,22,25,27,31-hexaenoic acid that has the following structure (OR═OH), its sodium salt (OR═ONa), or its methyl ester (OR═OMe):

22 . A compound having the general structure M or N,

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

23 . The compound of claim 22 , wherein n is a number selected from a group consisting of 0 to 13.

24 . The compound of claim 22 , wherein n is selected from a group consisting of 1, 3, 5, 7, 9, 11 or 13.

25 . The compound of claim 22 , wherein n is selected from a group consisting of 0, 2, 4, 6, 8, 10 or 12.

26 . The compound of claim 22 , wherein n is 9 or 11.

27 . The compound of claim 22 , wherein the R group is methyl or ethyl.

28 . The compound of claim 22 , wherein the R group is a metal cation selected from a group consisting of sodium, potassium, magnesium, zinc, and calcium cation.

29 . The compound of claim 22 , wherein the compound is selected from a group consisting of O, P, Q, R, S, T, U, V having one of the following structures:

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

30 . The compound of claim 22 , wherein the compound is selected from the group consisting of: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydotriaconta-14,17,21,23,25,29-hexaenoic acid; sodium (14Z,17Z,20R,21E,23E, 25Z,27S,29Z)-20,27-dihydroxydotriaconta-14,17,21,23,25,29-hexaenoate; methyl (14Z,17Z, 20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydotriaconta-14,17,21,23,25,29-hexaenoate;
(16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetratriaconta-16,19,23,25,27,31-hexaenoic acid; sodium (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetratriaconta-16,19,23,25,27,31-hexaenoate; or methyl (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxy-tetratriaconta-16,19,23,25,27,31-hexaenoate, which have the following structures:

31 . A compound having the general structure X or Z:

wherein:
n is a number selected from a group consisting of 0 to 19; and
the R group is selected from a group consisting of methyl, ethyl, alkyl, or a cation forming a pharmaceutically acceptable salt selected from a group consisting of:
ammonium cation, iminium cation, or a metal cation.

32 . The compound of claim 31 , wherein n is a number selected from a group consisting of 0 to 13.

33 . The compound of claim 31 , wherein n is selec

Assignees

• Univ Louisiana State
• Univ Southern California

Inventors

• Bazan Nicolas G
• Petasis Nicos A

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/232

  having three or more double bonds, e.g. etretinate · CPC title

• C07F9/106

  Adducts, complexes, salts of phosphatides · CPC title

• A61K31/685

  one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin · CPC title

• C07C69/732

  of unsaturated hydroxy carboxylic acids · CPC title