Flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof

Patent metadata

Field	Value
Publication number	US-10060909-B2
Application number	US-201414509761-A
Country	US
Kind code	B2
Filing date	Oct 8, 2014
Priority date	Aug 6, 2003
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The present invention relates to the discovery that certain non-naturally occurring, non-peptide amide compounds and amide derivatives, such as oxalamides, ureas, and acrylamides, are useful flavor or taste modifiers, such as a flavoring or flavoring agents and flavor or taste enhancer, more particularly, savory (the “umami” taste of monosodium glutamate) or sweet taste modifiers,—savory or sweet flavoring agents and savory or sweet flavor enhancers, for food, beverages, and other comestible or orally administered medicinal products or compositions.

First claim

We claim:

1. An amide compound having the following formula:

or a comestibly acceptable salt thereof; wherein
A is phenyl;
m is 1 or 2;
each R 1′ is independently selected from alkyl, alkoxy, alkoxy-alkyl, hydroxyalkyl, CN, CO 2 H, CO 2 R 6 , CHO, COR 6 , SR 6 , fluoro, chloro, cycloalkyl, cycloalkenyl, heterocycle, aryl, haloalkoxy, and heteroaryl;
R 6 is C 1 -C 6 alkyl;
i) R 2 is a C 3 -C 10 branched alkyl or cycloalkyl optionally substituted with one to four substituents each independently selected from alkoxy, alkoxy-alkyl, hydroxyalkyl, OH, NH 2 , NHR 6 , N(R 6 ) 2 , CN, CO 2 H, CO 2 R 6 , CHO, COR 6 , SH, SR 6 , halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl, haloalkyl, haloalkoxy, and heteroaryl; and R 6 is C 1 -C 6 alkyl; or
ii) R 2 is a 1-(1,2,3,4) tetrahydronapthalene ring or an 2,3-dihydro-1H-indene ring having the following formula:

wherein n is 1, 2, or 3, and each R 2′ can be bonded to either the aromatic or non-aromatic ring and is independently selected from hydrogen, fluoro, chloro, NH 2 , NHCH 3 , N(CH 3 ) 2 , CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups,
wherein the amide compound has a molecular weight of 500 grams per mole or less.

2. The amide compound of claim 1 , wherein m is 1.

3. The amide compound of claim 1 , wherein m is 2.

4. The amide compound of claim 3 , wherein each R 1′ is independently selected from fluoro, chloro, SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

5. The amide compound of claim 1 , wherein R 2 is a C 3 -C 10 branched alkyl optionally substituted with one to four substituents independently selected from alkoxy, alkoxy-alkyl, haloalkyl, haloalkoxy, and CO 2 R 6 ; and R 6 is C 1 -C 6 alkyl.

6. The amide compound of claim 5 , wherein R 2 is a C 3 -C 10 branched alkyl optionally substituted with one or two substituents independently selected from hydroxy, fluoro, chloro, CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

7. The amide compound of claim 1 , wherein R 2 is a cycloalkyl ring having 3 to 10 ring carbon atoms optionally substituted with one to four substituents independently selected from alkyl, alkoxy, alkoxy-alkyl, hydroxyalkyl, haloalkyl, haloalkoxy, and halogen.

8. The amide compound of claim 7 , wherein R 2 is a cycloalkyl ring having 5 to 8 ring carbon atoms optionally substituted with one to four substituents independently selected from methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

9. The amide compound of claim 1 , wherein
A is a phenyl ring;
m is 2;
each R 1′ is independently selected from fluoro, chloro, SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; and
R 2 is a C 3 -C 10 branched alkyl optionally substituted with one or two substituents independently selected from fluoro, chloro, CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; or a cycloalkyl ring having 5 to 8 ring carbon atoms optionally substituted with one to four substituents independently selected from fluoro, chloro, CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

10. The amide compound of claim 1 , wherein R 2 is a 1-(1,2,3,4)tetrahydronapthalene ring or an 2,3-dihydro-1H-indene ring having the following formula:

wherein each R 2′ can be bonded to either the aromatic or non-aromatic ring and is independently selected from hydrogen, fluoro, chloro, CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups.

11. The amide compound of claim 10 , wherein R 2 has the following formula:

wherein each R 2′ are independently selected from the group consisting of hydrogen, fluoro, chloro, COOCH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

12. An amide compound having the following formula:

or a comestibly acceptable salt thereof; wherein
(R 1′ ) m -A is

wherein m is 1, 2, or 3, and each R 1′ is independently selected from fluoro, chloro, NH 2 , NHCH 3 , N(CH 3 ) 2 , CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
i) R 2 is a C 3 -C 10 branched alkyl or cycloalkyl optionally substituted with one to four substituents each independently selected from alkoxy, alkoxy-alkyl, hydroxyalkyl, NH 2 , NHR 6 , N(R 6 ) 2 , CN, CO 2 H, CO 2 R 6 , CHO, COR 6 , SH, SR 6 , halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl, and heteroaryl and R 6 is C 1 -C 6 alkyl, or
ii) R 2 is a 1-(1,2,3,4) tetrahydronapthalene ring or an 2,3-dihydro-1H-indene ring having the following formula:

wherein n is 1, 2, or 3, and each R 2′ can be bonded to either the aromatic or non-aromatic ring and is independently selected from hydrogen, fluoro, chloro, NH 2 , NHCH 3 , N(CH 3 ) 2 , CO 2 CH 3 , SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups,
wherein the amide compound has a molecular weight of 500 grams per mole or less.

13. The amide compound of claim 1 , wherein A is phenyl; R 2 is a C 3 -C 10 branched alkyl substituted with one to four substituents each independently selected from alkoxy, alkoxy-alkyl, CO 2 R 6 , COR 6 , and halogen.

14. An amide compound selected from the group consisting of
(R)-methyl 2-(3-chloro-4-methoxybenzamido)-4-methylpentanoate,
4-methoxy-3-methyl-N-(5-methylhexan-3-yl)benzamide,
N-(heptan-4-yl)-2-methylbenzo[d][1,3]dioxole-5-carboxamide,
(S)-methyl 4-methyl-2-(4-methyl-3-(methylthio)benzamido)pentanoate,
4-methoxy-3-methyl-N-(2-methylheptan-4-yl)benzamide,
N-(heptan-4-yl)-6-methylbenzo[d][1,3]dioxole-5-carboxamide,
3,4-dimethyl-N-(2-methylhexan-3-yl)benzamide,
(R)-methyl 4-methyl-2-(5-methylbenzofuran-2-carboxamido)pentanoate,
N-(hexan-3-yl)-4-methoxy-3-methylbenzamide,
N-(heptan-4-yl)-3-methyl-4-(methylthio)benzamide,
N-(hexan-3-yl)-3-methyl-4-(methylthio)benzamide,
methyl 2-(3-chloro-4-methoxybenzamido)hexanoate,
3,4-dimethyl-N-(2-methylheptan-4-yl)benzamide,
N-(hexan-3-yl)-3,4-dimethylbenzamide,
N-(heptan-4-yl)-3,4-dimethylbenzamide,
(R)-methyl 4-methyl-2-(4-(methylthio)benzamido)pentanoate,
4-ethoxy-N-(heptan-4-yl)-3-methylbenzamide,
3,4-dimethyl-N-(5-methylhexan-3-yl)benzamide,
(R)-methyl 4-methyl-2-(4-vinylbenzamido)pentanoate,
4-methoxy-3-methyl-N-(2-methylhexan-3-yl)benzamide,
N-(heptan-4-yl)benzo[d][1,3]dioxole-5-carboxamide,
(R)-methyl 2-(benzo[d][1,3]dioxole-6-carbo

Assignees

• Senomyx Inc

Inventors

• Tachdjian Catherine
• Patron Andrew P
• Adamski-Werner Sara L
• Bakir Farid
• Chen Qing
• Darmohusodo Vincent
• Hobson Stephen Terrence
• Li Xiaodong
• Qi Ming
• Rogers Daniel H
• Rinnova Marketa
• Servant Guy
• Tang Xiao-Qing
• Zoller Mark
• Wallace David
• Xing Amy
• Gubernator Klaus

Classifications

• C07D271/12

  condensed with carbocyclic rings or ring systems · CPC title

• C07D209/42

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• G01N2333/726

  G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH · CPC title

• C07D275/03

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title