Pyridinyl cyclohexanecarboxamide cooling compounds

Patent metadata

Field	Value
Publication number	US-9452982-B2
Application number	US-99010306-A
Country	US
Kind code	B2
Filing date	Aug 14, 2006
Priority date	Aug 15, 2005
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

A method of providing a cooling effect to a product includes the incorporation into the product of at least one compound of the formula I

in which m is a number between 0 and 2, X, Y and Z are selected independently from the group consisting of H, halogen, OH, Me, Et, MeO and EtO, and R 1 , R 2 and R 3 together comprise at least 6 carbons, selected such that
(a) (i) R 1 is selected from the group consisting of H, Me, Et, isopropyl and C 4 -C 5 branched alkyl; and
(ii) R 2 and R 3 are independently selected from the group consisting of Me, Et, isopropyl and C 4 -branched alkyl; or
(b) any two or all of R 1 , R 2 and R 3 together form a monocyclic, bicyclic or tricyclic radical having up to 10 carbons.

The compounds confer substantial cooling effects on compositions applied to the skin or taken orally, such as toothpastes, mouthwashes, foodstuffs, beverages, confectionery, tobacco products, skin creams and ointments.

First claim

The invention claimed is:

1. A method of providing a product with a cooling effect when applied to the mouth to give a cooling sensation, comprising the incorporation into the product of at least one compound of the formula I

in which m is 2;
X, Y and Z are H;
R 1 is H and
R 2 and R 3 together form a 3-p-menthyl ring
wherein the at least one compound of formula I is isointensive to 2 ppm menthol at a concentration of 0.004 ppm to 0.05 ppm, and
wherein the product that is applied to the mouth is selected from the group consisting of foodstuffs, tobacco products, beverages, confectionaries, dentifrices, and mouthwashes.

2. The method according to claim 1 , wherein the compound of formula I is used in combination with at least one other cooling compound comprising menthol, menthone, isopulegol, N-ethyl p-menthanecarboxamide, N,2,3-trimethyl-2-isopropylbutanamide, menthyl lactate, menthone glycerine acetal, mono-menthyl succinate, mono-menthyl glutarate, O-menthyl glycerine, menthyl-N,N-dimethylsuccinamate, or 2-sec-butylcyclohexanone.

3. The method according to claim 1 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl)cyclohexanecarboxamide or (2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl)cyclohexanecarboxamide, wherein m =2.

4. The method according to claim 1 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl) ethyl)cyclohexanecarboxamide, (2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl) ethyl)cyclohexanecarboxamide, or (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl) ethyl)cyclohexanecarboxamide.

5. A method according to claim 1 , wherein the position of the carboxamide group moiety on the ring is selected from the 3- and 5- positions.

6. A method according to claim 1 , wherein the position of the carboxamide group moiety on the ring is selected from the 2- and 6- positions.

7. A method according to claim 1 , wherein the position of the carboxamide group moiety on the ring is the 4- position.

8. The method according to claim 1 , wherein the compound of the formula I comprises (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl)ethyl) cyclo-hexane carboxamide.

9. The method of claim 1 wherein the product is applied by inhalation.

10. The method of claim 1 wherein the product is applied by oral ingestion.

11. A product that is applied to the mouth to give a cooling sensation, comprising at least one compound according to the formula I

in which m is 2;
X, Y and Z are H;
R 1 is H and
R 2 and R 3 together form a 3-p-menthyl ring
wherein the at least one compound of formula I is isointensive to 2 ppm menthol at a concentration of 0.004 ppm to 0.05 ppm, and

wherein the product that is applied to the mouth is selected from the group consisting of foodstuffs, tobacco products, beverages, confectionaries, dentifrices, and mouthwashes.

12. The product according to claim 11 , wherein the product is used in combination with at least one other cooling compound comprising menthol, menthone, isopulegol, N-ethyl p-menthanecarboxamide, N,2,3-trimethyl-2-isopropylbutanamide, menthyl lactate, menthone glycerine acetal, mono-menthyl succinate, mono-menthyl glutarate, O-menthyl glycerine, menthyl-N,N-dimethylsuccinamate, or 2-sec-butylcyclohexanone.

13. The product according to claim 11 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl)cyclohexanecarboxamide or (2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl)cyclohexanecarboxamide, wherein m =2.

14. The product according to claim 11 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl) ethyl)cyclohexanecarboxamide, (2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl) ethyl)cyclohexanecarboxamide, or (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl) ethyl)cyclohexanecarboxamide.

15. The product according to claim 11 , wherein the position of the carboxamide group moiety on the ring is selected from the 3- and 5- positions.

16. The product according to claim 11 , wherein the position of the carboxamide group moiety on the ring is selected from the 2- and 6- positions.

17. The product according to claim 11 , wherein the position of the carboxamide group moiety on the ring is the 4- position.

18. The product according to claim 11 , wherein the compound of the formula I comprises (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl)ethyl)cyclo-hexane carboxamide.

19. The product of claim 11 wherein the product is applied by inhalation.

20. The product of claim 11 wherein the product is applied by oral ingestion.

21. A product selected from the group consisting of foodstuff, tobacco product, beverage, confectionary, dentifrice, and mouthwash, comprising an amount of a compound of formula I,

in which m is 2;
X, Y and Z are H;
R 1 is H and
R 2 and R 3 together form a 3-p-menthyl ring

wherein the at least one compound of formula I is isointensive to 2 ppm menthol at a concentration of 0.004 ppm to 0.05 ppm, and wherein the amount of the compound is effective to give a cooling sensation to the mouth.

22. The product according to claim 21 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl) cyclohexanecarboxamide or (2S,5R)-2-isopropyl-5-methyl-N-(pyridinalkyl) cyclohexanecarboxamide, wherein m =2.

23. The product according to claim 21 , wherein the compound of the formula I comprises at least one of (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl) ethyl)cyclohexane carboxamide, (2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl)ethyl) cyclohexane carboxamide, or (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl)ethyl) cyclohexane carboxamide.

24. The product according to claim 21 , wherein the compound of the formula I comprises (1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl)ethyl)cyclo-hexane carboxamide.

Assignees

• Bell Karen Ann
• Galopin Christophe C
• Slack Jay Patrick
• Tigani Lori W
• Givaudan Sa

Inventors

• Bell Karen Ann
• Galopin Christophe C
• Slack Jay Patrick
• Tigani Lori W

Classifications

• A61Q11/00

  Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses · CPC title

• A23L2/56

  Flavouring or bittering agents (sweeteners A23L2/60) · CPC title

• A61K8/4926

  having six membered rings · CPC title

• C07D213/40 Primary

  Acylated substituent nitrogen atom · CPC title

• A61K2800/244

  Endothermic; Cooling; Cooling sensation · CPC title