# US 8,784,782 B2 · Compounds comprising linked heteroaryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions

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- Number: US 8,784,782 B2
- Document ID: US8784782B2
- Status: Granted
- Kind: B2
- Application number: 13/616,585
- Filed: 2012-09-14
- Published: 2013-03-21
- Granted: 2014-07-22
- Earliest claimed: 2005-02-04
- Assignees: Senomyx, Inc.
- Applicants: Catherine Tachdjian; Marketa Lebl-Rinnova; David Wallace
- Inventors: Catherine Tachdjian; Marketa Lebl-Rinnova; David Wallace
- Web page: https://patentgrep.com/patent/US8784782B2

## CPC

- A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals}
- A23L 2/02: containing fruit or vegetable juices
- A23L 2/56: Flavouring or bittering agents (sweeteners A23L2/60)
- A23L 23/00: Soups; Sauces (soya sauce A23L27/50; salad dressings, mayonnaise or ketchup A23L27/60); Preparation or treatment thereof
- A23L 27/204: {Aromatic compounds}
- A23L 27/205: {Heterocyclic compounds}
- A23L 27/26: Meat flavours
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- A61K 31/395: having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The inventions disclosed herein relate to the discovery of the use of compounds having the formula shown below and certain subgenera or species thereof, as flavor or taste modifiers, particularly, savory (“umami”) taste modifiers, savory flavoring agents and savory flavor enhancers in foods, beverages, and other comestible compositions.

## Claims

### Claim 1

A method for modulating the savory taste of a comestible composition comprising combining the comestible composition with a savory flavor modulating amount of at least one compound having the formula:
or a comestibly acceptable salt thereof, so as to form a modified comestible composition; wherein
i) Ar is a monocyclic or bicyclic aryl or heteroaryl radical comprising one or two aromatic rings independently selected from benzene rings and five or six membered heteroaryl rings, each aromatic ring optionally having one, two, or three R20 substituent radicals bound thereto, wherein each R20 radical is independently selected from hydroxyl, NH2, SH, halogen, or a C1-C4 organic radical;
ii) hAr1 is a five or six-membered heteroaryl ring radical comprising at least two ring carbon atoms and one to three ring heteroatoms independently selected from O, N, or S, wherein any remaining members of the heteroaromatic ring are independently selected from CR6, N, NR7;
iii) X is O, S, S(O), SO2, CR8R9, or NR10;
iv) n is the integers zero, one, two, or three;
v) R3, R4, R8 and R9 are independently selected from hydrogen, oxygen, hydroxyl, NH2, SH, halogen, or a C1-C4 organic radical, and R7 and R10 are independently selected from hydrogen, hydroxyl, or a C1-C4 organic radical, and R6 is hydrogen, halogen, or a C1-C4 organic radical; and
vi) hAr2 is a five or six-membered heteroaryl ring having at least one ring carbon atom and at least one ring nitrogen atom, and wherein the remaining members of the heteroaryl ring are independently selected from CR30, CH, N, NR31, O, and S, wherein the number of CR30 is zero, one or two, and each R30 is independently selected from hydroxyl, NH2, NO2, SH, SO3H, P(O)(OH)2, a halogen, or a C1-C4 organic radical, and each R31 is independently selected from hydrogen, or a C1-C4 organic radical.

### Claim 2 (depends on 1)

The method of claim 1, wherein the R20 and R30 radicals are independently selected from the group consisting of hydroxy, SH, NH2, halogen, alkyl, alkoxyl, alkoxy-alkyl, hydroxyalkyl, haloalkyl, CN, CO2H, CHO, COR21, CO2R21, amide, NHR21, NR21R21′, R21, S(O)R21, and SO2R21, wherein R21 is an alkyl.

### Claim 3 (depends on 1)

The method of claim 1, wherein the R20 and R30 radicals are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N(CH3)2, CO2CH3, amide, SEt, SCH3, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups.

### Claim 4 (depends on 1)

The method of claim 1, wherein Ar comprises a benzene, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, thiofuranyl, pyrrolyl, pyrazolyl, oxazolyl, isoxazolyl, benzofuranyl, benzothiofuranyl, or benzopyrrolyl ring.

### Claim 5 (depends on 1)

The method of claim 1, wherein hAr1 has the structure:
wherein R7 is hydrogen or a C1-C4 organic radical,

### Claim 6 (depends on 1)

The method of claim 1, wherein n is one.

### Claim 7 (depends on 1)

The method of claim 1, wherein X is S, NH, or O.

### Claim 8 (depends on 1)

The method of claim 1, wherein R3, R4, R6, R7, R8, R9, and R10 are hydrogen.

### Claim 9 (depends on 1)

The method of claim 1, wherein hAr2 comprises a pyridyl, pyrazinyl, or pyrimidinyl ring.

### Claim 10 (depends on 1)

The method of claim 1, wherein the compound has structural Formula (IA):
and wherein
i) n′ is zero, one, two, or three, and each R20 is independently selected from the group consisting of hydroxy, SH, NH2, a halogen, or a C1-C4 organic radical,
ii) n″ is zero, one, or two, and each R30 is independently selected from the group consisting of hydroxy, SH, NH2, a halogen, or a C1-C4 organic radical,
iii) X is NH, O, S, S(O), SO2, or CH2,
iv) Ar is a phenyl, pyridyl, pyrazinyl, pyrimidinyl, furanyl, thiofuranyl, pyrrolyl, benzofuranyl, benzothiofuranyl, or benzopyrrolyl ring,
v) hAr1 has the structure:
(1) X1 is NH, O, or S,
(2) X2 is N or CR6 wherein R6 is hydrogen, a halogen, or a C1-C4 organic radical,
(3) X3 is N or CR6 wherein R6 is hydrogen, a halogen, or a C1-C4 organic radical, and
vi) hAr2 is a a pyridyl, pyrazinyl, or pyrimidinyl ring.

### Claim 11 (depends on 10)

The method of claim 10, wherein the R20 and R30 radicals are independently selected from hydroxy, SH, NH2, a halogen, alkyl, alkoxyl, alkoxy-alkyl, hydroxyalkyl, haloalkyl, CN, CO2H, CHO, COR32, CO2R32, amide, NHR32, NR32R32′ or SR32 radical, wherein R32 and R32′ are independently selected alkyls.

### Claim 12 (depends on 10)

The method of claim 10, wherein the R20 and R30 radicals are independently selected from the group consisting of a hydroxy, fluoro, chloro, NH2, NHCH3, N(CH3)2, CO2CH3, amide, SEt, SCH3, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy group.

### Claim 13 (depends on 10)

The method of claim 10, wherein Ar is a phenyl ring, n′ is one or two, and each R20 is independently selected from the group consisting of methyl, ethyl, isopropyl, trifluoromethyl, methoxy, trifluoromethoxy, and ethoxy.

### Claim 14 (depends on 10)

The method of claim 10, wherein X is S, NH, or 0.

### Claim 15 (depends on 10)

The method of claim 10, wherein X1 is NH.

### Claim 16 (depends on 10)

The method of claim 10, wherein X2 is N or CH.

### Claim 17 (depends on 10)

The method of claim 10, wherein X3 is N or CH.

### Claim 18 (depends on 10)

The method of claim 10, wherein X1 is NH, and X2 and X3 are N.

### Claim 19 (depends on 10)

The method of claim 10, wherein hAr2 has the structure:

### Claim 20 (depends on 19)

The method of claim 19 wherein each R30 is independently selected from the group consisting of a hydroxy, fluoro, chloro, NH2, NHCH3, N(CH3)2, CO2CH3, amide, SEt, SCH3, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy.

### Claim 21 (depends on 10)

The method of claim 10, wherein the pyridine radical is a 2-pyridine radical having the structure:

### Claim 22 (depends on 21)

The method of claim 21 wherein n″ is 0 or 1.

### Claim 23 (depends on 1)

The method of claim 1, wherein the compound is selected from the group consisting of:
2-((3-(2,3-dimethoxyphenyl)-1H-1,2,4-triazol-5-ylthio)methyl)pyridine;
2-((5-(2-methoxy-4-methylphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;
2-((5-(2,4-dimethylphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;
2-((5-(4-Ethylphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;
2-((5-(4,5-dimethylfuran-2-yl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;
2-((5-(4-Ethyl-2-methylphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine; and
2-((5-(4-ethyl-2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine.

### Claim 24 (depends on 1)

The method of claim 1 wherein the comestible composition comprises at least a savory flavor modulating amount of monosodium glutamate.

### Claim 25 (depends on 1)

The method of claim 1, wherein the modified comestible composition is a food or beverage for human consumption.

### Claim 26 (depends on 1)

The method of claim 1, wherein the compound is present in the modified comestible composition at a concentration from about 0.01 ppm to about 30 ppm.

### Claim 27 (depends on 1)

The method of claim 1, wherein the compound is present in the modified comestible composition in a concentration from about 0.1 ppm to about 3 ppm.