Series of compounds for treatment of skin diseases and other conditions

Patent metadata

Field	Value
Publication number	US-11414366-B2
Application number	US-201916600536-A
Country	US
Kind code	B2
Filing date	Oct 13, 2019
Priority date	Oct 14, 2018
Publication date	Aug 16, 2022
Grant date	Aug 16, 2022

Abstract

Compounds and methods related to the prevention and treatment of diseases and conditions, some of which are facilitated by melanogenesis are disclosed. Specifically, the present subject matter includes a series of compounds and compositions and their use for anti-melanogenic and antioxidant activity. This subject matter also includes the treatment of skin disorder due to acne vulgaris and related inflammatory and post inflammatory hyperpigmentation. Methods for synthesizing contemplated compounds are also disclosed.

First claim

The invention claimed is:

1. A compound of formula I:

wherein R is selected from the group consisting of 1′-(4′-hydroxy)phenyl; 1′-(3′-hydroxy)phenyl; 1′-(2′,4′-dihydroxy)phenyl; 1′-(3′,5′-dihydroxy)phenyl with E and Z geometry.

2. A composition comprising (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

3. A method for inhibiting the production of melanin comprising administering to a subject in need thereof a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

4. A method for preventing and treating diseases and conditions related to the overproduction or uneven distribution of melanin comprising administering to a subject in need thereof an effective amount of a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

5. A method for whitening or lightening skin comprising administering to a subject in need thereof a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

6. A method for preventing melanin synthesis which is a symptom of a condition, disorder, or disease that is associated with tyrosinase inhibition, the method comprising administering to a subject in need thereof an effective amount of a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

7. A method for preventing melanin synthesis which is a symptom of a condition, disorder, or disease that is associated with non-tyrosinase inhibition, the method comprising administering to a subject in need thereof an effective amount of a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

8. A method for treating diseases and conditions caused by free radicals, oxidative stress, UV rays, or inflammation, the method comprising administering to a subject in need thereof an effective amount of a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

9. A method for inhibiting the browning and color changes in fruits, vegetables, juices and other food products comprising administering a composition comprising at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

10. The method of claim 6 , wherein the condition, disorder, or disease is selected from the group consisting of suntan, hyper pigmentation spots caused by skin aging, melasma, liver diseases, thermal burns and topical wounds, skin pigmentation due to inflammatory conditions caused by fungal, microbial and viral infections, vitiligo, carcinoma, or melanoma.

11. A method for suppressing the activity of Propionibacterium (p-acnes) comprising administering to a patient in need thereof a composition comprising at least one the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

12. A method for deactivating the activity of proinflammatory cytokines, the method comprising administering to a patient in need thereof a composition consisting of at least one of the following compounds: (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)phenol (1); (E/Z)-3-(2,6-dimethylhepta-1,5-dienyl)phenol (2); (E/Z)-4-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (3); (E/Z)-5-(2,6-dimethylhepta-1,5-dienyl)benzene-1,3-diol (4) or a pharmaceutically acceptable salt thereof.

13. The method of claim 8 , wherein said diseases and conditions are selected from the group consisting of suntan, post inflammatory hyperpigmentation (PIH), hyper pigmentation spots caused by melasma, liver diseases, thermal burns and topical wounds, skin pigmentation due to inflammatory conditions caused by fungal, microbial and viral infections, vitiligo, carcinoma, or melanoma.

14. The method of claim 13 , wherein the post inflammatory hyperpigmentation (PIH) is derived from acne, atopic dermatitis, allergic contact dermatitis, incontinent pigmentation, lichen planus, lupus erythematosus, morphea, mechanical trauma, ionizing or nonionizing radiation, burns, laser or drug therapies, skin infection or combinations thereof.

Assignees

• Unigen Inc

Inventors

• Nandy Sandip K
• Horm Teresa
• Dawkins Kelly Rose

Classifications

• A23B2/746

  with singly-bound oxygen · CPC title

• A23B70/10

  by addition of preservatives · CPC title

• C07C39/225

  with at least one hydroxy group on a condensed ring system · CPC title

• C07D213/06

  containing only hydrogen and carbon atoms in addition to the ring nitrogen atom · CPC title

• A61P35/00

  Antineoplastic agents · CPC title