Deuterated compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11046650-B2
Application number	US-201916720645-A
Country	US
Kind code	B2
Filing date	Dec 19, 2019
Priority date	Aug 21, 2015
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

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-A or 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 is —CD 3 ;
R 4 is —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 at least one of R 2 , R 5 , R 6 , R 7 , or R 8 is deuterium.

3. The compound of claim 1 , wherein the compound is of Formula II-A, or a pharmaceutically acceptable salt thereof.

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

5. 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.

6. A compound of the following structure:

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.

8. A pharmaceutical composition comprising the compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.

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

10. A composition comprising a compound of claim 1 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of about 80% or greater.

11. A composition comprising a compound of claim 1 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of 90% or greater.

12. A composition comprising a compound of claim 3 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of about 50% or greater.

13. A composition comprising a compound of claim 3 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of about 80% or greater.

14. A composition comprising a compound of claim 3 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of 90% or greater.

15. A composition comprising a compound of claim 5 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of about 80% or greater.

16. A composition comprising a compound of claim 5 , wherein each position of deuterium enrichment in the compound comprises deuterium in an amount of 90% or greater.

17. A composition comprising a compound of claim 6 , wherein each position of deuterium enrichment in R 3 and R 4 comprises deuterium in an amount of about 50% or greater.

18. A composition comprising a compound of claim 6 , wherein each position of deuterium enrichment in R 3 and R 4 comprises deuterium in an amount of about 90% or greater.

19. A composition comprising a compound of claim 6 , wherein each position of deuterium enrichment in R 3 and R 4 comprises deuterium in an amount of 95% or greater.

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title