Hydroxybenzoic acid derivatives, methods and uses thereof

Patent metadata

Field	Value
Publication number	US-11078222-B2
Application number	US-201716475277-A
Country	US
Kind code	B2
Filing date	Dec 29, 2017
Priority date	Dec 29, 2016
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The present disclosure relates to the design and synthesis of new mitochondriotropic antioxidant compounds based on hydroxybenzoic acids and analogues. Furthermore, this disclosure is also related to the methods and uses of the hydroxybenzoic based derivatives and analogues, for example, in the field of human and animal diseases, for instance to treat mitochondrial dysfunction or mitochondrial deficiencies, and cosmetics, for instance to prevent or delay skin aging.

First claim

The invention claimed is:

1. A compound of formula I

or a salt, tautomer, or stereoisomer thereof,
wherein
R′, R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from each other;
R′, R 2 , R 3 , R 4 and R 5 are selected from H, halogen, hydroxyl, methyl, methoxyl, amino, carboxylic acid, or nitro group;
R 6 is a secondary amide or tertiary amide;
R 7 is an alkyl chain, an alkenyl chain, an alkynyl chain, a substituted aryl, or a secondary amide;
Z − is an acceptable anion; and
wherein the alkyl chain, the alkenyl chain or the alkynyl chain is a C 5 -C 30 chain.

2. The compound of claim 1 , wherein the compound has the following formula:

3. The compound of claim 1 , wherein the compound has the following formula:

4. The compound of claim 1 , wherein
R 7 is a secondary amide of R 8 -(C=O)NH-R 9 amide,
R 8 and R 9 are independently selected from each other and
R 8 and R 9 are an alkyl chain, an alkenyl chain, an alkynyl chain or an substituted aryl.

5. The compound of claim 1 , wherein the substituted aryl is an alkane-aryl substituted, alkene-aryl substituted, or alkyne-aryl substituted.

6. The compound of claim 1 , wherein the alkyl chain, the alkenyl chain or the alkynyl chain is a C 6 -C 14 chain.

7. The compound of claim 1 , wherein R 1 and R 5 are H.

8. The compound of claim 1 , wherein R 2 and R 3 are OH.

9. The compound of claim 1 , wherein R 4 is H or OH.

10. The compound of claim 1 , wherein R 7 is a C 6 alkyl chain.

11. The compound of claim 4 wherein R 8 and R 9 are independently of each other a C 5 alkyl chain or a C 6 alkyl chain.

12. The compound of claim 1 , wherein the compound is 6-(3,4-dihydroxybenzamido)hexyltriphenylphosphonium bromide.

13. The compound of claim 1 , wherein the compound is 6-(3,4,5-trihydroxybenzamido)hexyltriphenylphosphonium bromide.

14. The compound of claim 1 , wherein the compound is 5-(6-(3,4,5-trihydroxybenzamido)hexylamino) carbonylpentyl]triphenylphosphonium bromide.

15. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, adjuvant, excipient, or diluent or mixtures thereof.

16. The composition of claim 15 , wherein the pharmaceutically acceptable carrier is saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea or mixtures thereof.

17. The composition of claim 15 , wherein the adjuvant is oil-in-water emulsion adjuvant, aluminium adjuvant, a TLR-4 ligand, a saponin, or mixtures thereof.

18. The composition of claim 15 , wherein the excipient is glucose, lactose, sucrose, glycerol monostearate, sodium chloride, glycerol, propylene, glycol, water, ethanol or mixtures thereof.

Assignees

• Univ Do Porto
• Centro De Neurociencias E Biologia Celular

Inventors

• Martins Borges Maria Fernanda
• Gouveia Simõës Da Silva Oliveira Paulo Jorge
• Santos Teixeira José Carlos
• Cagide Fagin Fernando
• Gomes Oliveira Ana Catarina

Classifications

• A61K8/55

  Phosphorus compounds · CPC title

• C07F9/5442 Primary

  Aromatic phosphonium compounds (P-C aromatic linkage) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07F9/5456 Primary

  Arylalkanephosphonium compounds · CPC title