Deuterated compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-12240816-B2
Application number	US-202318504672-A
Country	US
Kind code	B2
Filing date	Nov 8, 2023
Priority date	Aug 21, 2015
Publication date	Mar 4, 2025
Grant date	Mar 4, 2025

Abstract

The present invention provides for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.

First claim

We claim:

1. A compound of Formula II-B:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from —NH 2 , —NHD, or —ND 2 ;
R 2 is selected from hydrogen or deuterium;
R 3 and R 4 are independently selected from —CH 3 , —CH 2 D, —CHD 2 , or —CD 3 ; and
R 5 , R 6 , R 7 , and R 8 are each independently selected from hydrogen or deuterium.

2. The compound of claim 1 , wherein R 1 is —NH 2 .

3. The compound of claim 2 , wherein R 2 is hydrogen.

4. The compound of claim 3 , wherein R 3 is —CH 3 .

5. The compound of claim 4 , wherein R 4 is —CH 3 .

6. The compound of claim 1 , wherein R 8 is hydrogen and at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , or R 7 is or contains deuterium.

7. The compound of claim 1 , wherein each of R 5 , R 6 , R 7 , and R 8 is as defined in an entry set forth in the table below:

Entry
R 5
R 6
R 7
R 8

i
H
H
H
H

ii
H
H
H
D

iii
H
H
D
H

iv
H
D
H
H

v
D
H
H
H

vi
H
H
D
D

vii
H
D
H
D

viii
D
H
H
D

ix
H
D
D
H

x
D
H
D
H

xi
D
D
H
H

xii
H
D
D
D

xiii
D
H
D
D

xiv
D
D
H
D

xv
D
D
D
H

xvi
D
D
D
D

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein the compound is of the following structure:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of about 50% or greater.

10. The compound of claim 8 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of 90% or greater.

11. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable adjuvant, carrier, or vehicle.

12. The pharmaceutical composition according to claim 11 , in combination with an additional therapeutic agent.

13. A method of treating, preventing, or reducing a risk of a disease, disorder, condition, or cosmetic indication in which aldehyde toxicity is implicated in a subject in need thereof, comprising administering topically or systemically to the subject a composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt or a pharmaceutical composition thereof.

14. The method according to claim 13 , wherein the disease, disorder, or condition is an ocular disorder.

15. The method of claim 14 , wherein the ocular disorder is macular degeneration or Stargardt disease.

16. The method of claim 14 , wherein the ocular disorder is selected from the group consisting of dry eye syndrome, cataracts, keratoconus, bullous and other keratopathy, Fuch's endothelial dystrophy, allergic conjunctivitis, ocular cicatricial pemphigoid, conditions associated with PRK healing and other corneal healing, conditions associated with tear lipid degradation or lacrimal gland dysfunction, uveitis, scleritis, ocular Stevens Johnson Syndrome, and ocular rosacea.

17. The method of claim 13 , wherein the disease, disorder, or condition is a skin disease, disorder, or condition selected from the group consisting of psoriasis, topical (discoid) lupus, contact dermatitis, atopic dermatitis, allergic dermatitis, radiation dermatitis, acne vulgaris, Sjogren-Larsson Syndrome and other ichthyosis, and the cosmetic indication is selected from the group consisting of solar elastosis/wrinkles, skin tone firmness, puffiness, eczema, smoke or irritant induced skin changes, dermal incision, and a skin condition associated with a burn or wound.

18. The method of claim 13 , wherein the disease, disorder, or condition is an autoimmune, immune-mediated, inflammatory, cardiovascular, or neurological disease, or diabetes, metabolic syndrome, or a fibrotic disease.

19. The method of claim 13 , wherein the disease, disorder, or condition is selected from the group consisting of lupus, scleroderma, asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, inflammatory bowel disease, sepsis, atherosclerosis, ischemic-reperfusion injury, Parkinson's disease, Alzheimer's disease, succinic semialdehyde dehydrogenase deficiency, multiple sclerosis, and amyotrophic lateral sclerosis.

20. The method of claim 13 , wherein the disease, disorder, or condition is an age-related disease, disorder, or condition.

Assignees

• Aldeyra Therapeutics Inc

Inventors

• Brady Todd
• Young Scott
• Kinney William A
• Macdonald Susan

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P39/00

  General protective or antinoxious agents · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title