Novel Use of Organic Compounds

• US 20090239944A1
• Filed: 06/23/2006
• Published: 09/24/2009
• Est. Priority Date: 06/24/2005
• Status: Abandoned Application

• Current Assignee: DSM IP Assets BV (DSM-Firmenich AG)
• Original Assignee: DSM IP Assets BV (DSM-Firmenich AG)
• Inventors: D'orazio, Daniel, Wolfram, Swen, Wang-Schmidt, Ying, Wehrli, Christof, De Saizieu, Antoine, Schuler, Goede
• Application Number:
  US11/922,558
• Publication Number:
  US 20090239944A1
• Time in Patent Office: Days
• US Class Current: 514/466
• CPC Class Codes: A23K 20/111 Aromatic compounds
• CPC Class Codes: A23K 50/20 for horses
• CPC Class Codes: A23K 50/40 for carnivorous animals, e.g. cats or dogs
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/328 having effect on glycaemic control and diabetes
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention relates to compounds of the formula I

wherein R³ is C_1-6-alkyloxy, C_1-6-acyloxy or aroyloxy; R⁶ is hydrogen or C_1-6-alkyloxy; R⁷ is C_1-6-alkyloxy, C_1-6-acyloxy, aroyloxy or arylacyloxy; R⁸ is hydrogen or C_1-6-alkyloxy; or R⁷ and R⁸ form together a group O-L-O with L being (CR¹R²)_n, with R¹ and R² being independently from each other hydrogen or C_1-5-alkyl and n being an integer from 1 to 3; R¹⁰ is hydrogen or N—C_1-4-acyl, N—C_1-5-alkyl-x-C_x-alkyl with x being an integer from 1 to 5, for use as medicament for the treatment of a disorder connected to impaired glucose metabolism and impaired insulin action such as syndrome X and diabetes type 1 and 2, especially for the treatment of (non-autoimmune) diabetes type 2. The present invention is also directed to dietary compositions such as (fortified) food, beverages, (fortified) feed, food additives, beverage additives, feed additives, clinical nutrition, dietary supplements, functional food, functional feed and nutraceuticals and to pharmaceutical compositions containing such compounds, to methods of treating a disorder connected to impaired glucose metabolism and impaired insulin action in mammals including humans and to the compounds of the formula I themselves. Another object of the present invention is the use of such compounds for the manufacture of a composition for the treatment of a disorder connected to impaired glucose metabolism and impaired insulin action.

Claims

1. A dietary composition containing at least a compound of the formula I

wherein R³ is C_1-6-alkyloxy, C_1-6-acyloxy or aroyloxy;

R⁶ is hydrogen or C_1-6-alkyloxy;

R⁷ is C_1-6-alkyloxy, C_1-6-acyloxy, aroyloxy or arylacyloxy;

R⁸ is hydrogen or C_1-6-alkyloxy;

or R⁷ and R⁸ form together a group O-L-O with L being (CR¹R²)_n, with R¹ and R² being independently from each other hydrogen or C_1-5-alkyl and n being an integer from 1 to 3;

R¹⁰ is hydrogen or N—

C_1-4-acyl, N—

C_1-5-alkyl-x-C_x-alkyl with x being an integer from 1 to 5,

preferably with the proviso that the composition does not contain a compound of formula I wherein R³ is methoxy when R⁶ and R¹⁰ are hydrogen and R⁷ and R⁸ are methoxy.

2. The dietary composition according to claim 1, wherein

R³ is methoxy, isopropyloxy, isoprenyloxy, acetyloxy, or benzoyloxy, preferably wherein R³ is methoxy or benzoyloxy;

and/or

wherein R⁶ is hydrogen, methoxy, isopropyloxy or isoprenyloxy, preferably wherein R⁶ is hydrogen or methoxy; and

/or

wherein R⁷ is methoxy, isopropyloxy, isoprenyloxy, acetyloxy, benzoyloxy, (3,4,5-trimethoxy)benzoyloxy or cinnamoyloxy, preferably wherein R⁷ is methoxy or cinnamoyloxy; and

/or

wherein R⁸ is hydrogen, methoxy, isopropyloxy or isoprenyloxy, preferably wherein R⁸ is hydrogen or methoxy;

or

wherein R⁷ and R⁸ form together the group O(—

CH₂)_m—

O with m being 1 or 2, preferably wherein R⁷ and R⁸ form together the group 0-CH₂—

O; and

/or

wherein R¹⁰ is hydrogen, N-acetyl, N-isopropyl-2-aminoethyl, N-isoprenyl-2-aminoethyl or N-acetyl, N-methyl-2-aminoethyl, preferably wherein R¹⁰ is hydrogen or N-acetyl, N-methyl-2-aminoethyl, preferably with the proviso that R³ is not methoxy when R⁶ and R¹⁰ are hydrogen and R⁷ and R⁸ are methoxy.

3. The dietary composition according to claim 1, wherein the compound of the formula I is selected from the group consisting of the compounds of the formula I-1 to I-3 wherein the compound of the formula I-1 is one, in which R³=R⁶=OCH₃, R⁷ and R⁸ form together a group O—

CH₂—

O and R¹⁰=N-acetyl, N-methyl-2-aminoethyl;

the compound of the formula I-2 is one, in which R³=OCH₃, R⁶=R⁸=R¹⁰=H, and R⁷=cinnamoyloxy;

the compound of the formula I-3 is one, in which R³=benzoyloxy, R⁶=R¹⁰=H, and R⁷=R⁸=OCH₃; and

the compound of the formula I-4 is one, in which R³=OCH₃, R⁶=R⁸=R¹⁰=H, and R⁷=(3,4,5-trimethoxy)benzoyloxy.

4. The dietary composition as in claim 1, wherein the dietary composition is (fortified) food, a beverage, (fortified) feed or a corresponding additive, functional food, functional feed, nutraceutical, clinical nutrition or a dietary supplement.

5. A compound of the formula I as defined in claim 1 for the manufacture of a composition for the treatment of a disorder connected to impaired glucose metabolism and impaired insulin action.

6. The composition according to claim 5, wherein the composition is used as a blood glucose controlling agent, as an insulin sensitizer, as a blood lipid lowering agent, as a pancreatic β

-cell function improver, as a diabetes type 2 preventing agent and/or as a Syndrome X preventing agent.

7. A disorder according to claim 5, wherein the disorder connected to impaired glucose metabolism and impaired insulin action is diabetes mellitus or syndrome X, especially non-autoimmune diabetes type 2.

19. A pharmaceutical composition containing at least one compound of the formula I as defined in claim 1 and a conventional pharmaceutical carrier.

20. The pharmaceutical composition according to claim 19, wherein the compound of the formula I is selected from the group consisting of compounds of the formula I-1 to I-4, especially the compounds of the formula I-1 to I-3.

21. A method for the treatment of a disorder connected to impaired glucose metabolism and impaired insulin action in mammals including humans, said method comprising administering an effective dose of a compound of the formula I as defined in claim 1 to mammals including humans which are in need thereof.

22. The method according to claim 21, wherein the disorder connected to impaired glucose metabolism and impaired insulin action in mammals including humans is (non-autoimmune) diabetes type 2.

23. The method according to claim 21, wherein the mammal is a human, a cat, a dog or a horse.

24. Compound of the formula I-1, I-2, I-3 and I-4 as defined in claim 3 for use as medicament.

8. Compounds of the formula I,

wherein R³ is methoxy or benzoyloxy,

R⁶ is hydrogen or methoxy,

R⁷ is methoxy or (3,4,5-trimethoxy)benzoyloxy or cinnamoyloxy,

R⁸ is hydrogen or methoxy,

or R⁷ and R⁸ form together the group O(—

CH₂)_m—

O with m being 1 or 2, and

R¹⁰ is hydrogen or N-acetyl, N-methyl-2-aminoethyl, with the proviso that R³ is not methoxy when R⁶ and R¹⁰ are hydrogen and R⁷ and R⁸ are methoxy.

9. The compound of the formula I according to claim 8, wherein R³ and R⁶ are both OCH₃, R⁷ and R⁸ form together a group O—

CH₂—

O and R¹⁰ is N-acetyl, N-methyl-2-aminoethyl.

25. Compound of the formula I as defined in claim 8 for use as medicament.

10. Compounds of the formula I,

wherein R³ is C_1-6-acyloxy or aroyloxy,

R⁶ is hydrogen or d-₆-alkyloxy,

R⁷ is C_1-6-alkyloxy, Ci.₆-acyloxy, aroyloxy or arylacyloxy,

R⁸ is hydrogen or C_1-6-alkyloxy,

or R⁷ and R⁸ form together a group O-L-O with L being (CR¹R²)_n, with R¹ and R² being independently from each other hydrogen or C_1-5-alkyl and n being an integer from 1 to 3;

R¹⁰ is hydrogen or N—

C_1-4-acyl, N—

C_1-5-alkyl-x-C_x-alkyl with x being an integer from 1 to 5;

preferably with the proviso that R³ is not methoxy when R⁶ and R¹⁰ are hydrogen and R⁷ and R⁸ are methoxy,

for use as medicament for the treatment of a disorder connected to impaired glucose metabolism and impaired insulin action.

11. Compound of the formula I according to claim 10, wherein R³ is methoxy, isopropy-loxy, isoprenyloxy, acetyloxy, or benzoyloxy, especially wherein R³ is methoxy or benzoyloxy.

12. Compound of the formula I according to claim 10, wherein R⁶ is hydrogen, methoxy, isopropyloxy or isoprenyloxy, especially wherein R⁶ is hydrogen or methoxy.

13. Compound of the formula I according to claim 10, wherein R⁷ is methoxy, isopropyloxy, isoprenyloxy, acetyloxy, benzoyloxy, (3,4,5-trimethoxy)benzoyloxy or cinnamoyloxy, especially wherein R⁷ is methoxy or cinnamoyloxy.

14. Compound of the formula I according to claim 10, wherein R⁸ is hydrogen, methoxy, isopropyloxy or isoprenyloxy, especially wherein R⁸ is hydrogen or methoxy.

15. Compound of the formula I according to claim 10, wherein R⁷ and R⁸ form together the group O(—

CH₂)_m—

O with m being 1 or 2.

16. Compound of the formula I according to claim 10, wherein R¹⁰ is hydrogen, N-acetyl, N-isopropyl-2-aminoethyl, N-isoprenyl-2-aminoethyl or N-acetyl, N-methyl-2-aminoethyl, especially wherein R¹⁰ is hydrogen or N-acetyl, N-methyl-2-aminoethyl.

17. Compound of the formula I according to claim 10, wherein it is selected from the group of compounds I-1 to I-3, wherein the compound of the formula I-1 is one, in which R³=R⁶=OCH₃, R⁷ and R⁸ form together a group O—

CH₂—

O and R¹⁰=N-acetyl, N-methyl-2-aminoethyl;

the compound of the formula I-2 is one, in which R³=OCH₃, R⁶=R⁸=R¹⁰=H, and R⁷=cinnamoyloxy;

the compound of the formula I-3 is one, in which R³=benzoyloxy, R⁶==R¹⁰=H, and R⁷=R⁸=OCH₃; and

the compound of the formula I-4 is one, in which R³=OCH₃, R⁶=R⁸=R¹⁰=H, and R⁷=(3,4,5-trimethoxy)benzoyloxy.

18. The compound of the formula I as defined in claim 10 as blood glucose controlling agent, as insulin sensitizer, as blood lipid lowering agent, as pancreatic β

-cell function improver, as (non-autoimmune) diabetes type 2 preventing agent and/or as Syndrome X preventing agent.