Deuterated tetramethyl dioic acids, compositions comprising them and uses thereof
This invention relates to deuterated tetramethyl dioic acids, compositions comprising them and uses thereof in the treatment of Metabolic Syndrome and any diseases, disorders or symptoms associated therewith.
1. A deuterium enriched composition of a compound of general formula (I), including any salts, esters or anhydrides thereof:
wherein
L is a straight or branched C 8 -C 16 alkylene; optionally interrupted by at least one moiety selected from O, S, NH, C 5 -C 10 cycloalkylene, C 5 -C 10 cycloheteroalkylene, C 6 -C 18 arylene, C 6 -C 18 heteroarylene;
each of R 1 -R 8 is independently selected from H, D, CH 3 and CD 3 ; wherein at least one of R 1 -R 8 is D or CD 3 ; and
the abundance of deuterium at any D- or CD 3 -occupied position in the compound of the composition is substantially greater than the 0.015% natural abundance of deuterium.
2. A deuterium enriched composition according to claim 1 , wherein said compound of general formula (I), including any salts, esters or anhydrides thereof is:
wherein
L is a straight or branched C 8 -C 16 alkylene; optionally interrupted by at least one moiety selected from O, S, NH, C 5 -C 10 cycloalkylene, C 5 -C 10 cycloheteroalkylene, C 6 -C 18 arylene, C 6 -C 18 heteroarylene;
each of R 1 -R 4 is independently H or D;
each of R 5 -R 8 is independently CH 3 or CD 3 ;
wherein when R 1 -R 4 are H, at least one of R 5 -R 8 is CD 3 ; or when R 5 -R 8 are CH 3 , at least one of R 1 -R 4 is D.
3. A deuterium enriched composition according to claim 1 , wherein said compound of general formula (I), including any salts, esters or anhydrides thereof is:
wherein
L is a straight or branched C 8 -C 16 alkylene; optionally interrupted by at least one moiety selected from O, S, NH, C 5 -C 10 cycloalkylene, C 5 -C 10 cycloheteroalkylene, C 6 -C 18 arylene, C 6 -C 18 heteroarylene;
each of R 1 -R 4 is independently CH 3 or CD 3 , and at least one of R 1 -R 4 is CD 3 ; and
each of R 5 -R 8 is independently H.
4. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 1 -R 4 is D.
5. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 5 -R 8 is CD 3 .
6. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 1 -R 4 is CD 3 .
7. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 5 -R 8 is D.
8. A deuterium enriched composition according to claim 1 , wherein, in said compound, L is any one of —(CH 2 ) 10 — and —(CH 2 ) 12 —.
9. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 1 -R 4 is D and at least one of R 5 -R 8 is CD 3 .
10. A deuterium enriched composition according to claim 1 , wherein, in said compound, at least one of R 1 -R 4 is CD 3 and at least one of R 5 -R 8 is D.
11. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 2 = R 3 = R 4
R 5 = R 6 = R 7 = R 8
II
D
CH 3
III
H
CD 3
IV
D
CD 3 .
12. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 2
R 3 = R 4
R 5 = R 6
R 7 = R 8
V
D
H
CH 3
CH 3
VI
D
H
CD 3
CH 3
VII
D
H
CH 3
CD 3
VIII
D
H
CD 3
CD 3
IX
D
D
CD 3
CH 3 .
13. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 3
R 2 = R 4
R 5 = R 6
R 7 = R 8
X
D
H
CH 3
CH 3
XI
D
H
CD 3
CH 3
XII
D
H
CD 3
CD 3 .
14. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 3
R 2 = R 4
R 5 = R 7
R 6 = R 8
XIII
D
H
CH 3
CH 3 .
15. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 2 = R 3 = R 4
R 5 = R 6 = R 7 = R 8
XIV
CD 3
H.
16. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 2
R 3 = R 4
R 5 = R 6
R 7 = R 8
XV
CD 3
CH 3
H
H.
17. A deuterium enriched composition according to claim 1 , wherein said compound is:
Compound
R 1 = R 3
R 2 = R 4
R 5 = R 6
R 7 = R 8
XVI
CD 3
CH 3
H
H.
18. A composition comprising a deuterium enriched composition of a compound according to claim 1 or any salts, esters or anhydrides thereof.
19. A method of treating a disease, condition, symptom or disorder associated with Metabolic Syndrome in a subject, said method comprising administering to said subject an effective amount of at least one deuterium enriched composition as defined in claim 1 .
20. A method according to claim 19 , wherein said disease, condition or disorder associated with Metabolic Syndrome is selected from dyslipidemia, diabetes, obesity, cancer, hypertension and neurodegeneration.
21. A deuterium enriched composition of a compound according to claim 1 , wherein said compound is 2,2,15,15-tetramethyl(D12)-hexadecanedioic acid or any salt, ester or anhydride thereof.
22. A deuterium enriched composition of a compound according to claim 1 , wherein said compound is 2,2,17,17-tetramethyl(D12)-octadecanedioic acid or any salt, ester or anhydride thereof.
23. An isolated deuterium enriched compound of general formula (I):
wherein each of R 1 -R 4 is independently CD 3 and each of R 5 -R 8 is independently hydrogen and L is a straight C 12 alkyl chain, which is 2,2,15,15-tetramethyl(D12)-hexadecanedioic acid or any salt, ester or anhydride thereof.
24. An isolated deuterium enriched compound of general formula (I):
wherein each of R 1 -R 4 is independently CD 3 and each of R 5 -R 8 is independently hydrogen and L is a straight C 14 alkyl chain, which is 2,2,17,17-tetramethyl(D12)-octadecanedioic acid or any salt, ester or anhydride thereof.
25. A deuterium-enriched composition according to claim 1 wherein D at a specified position in the compound indicates at least 50.1% incorporation of deuterium at that position in the composition.