Amide compounds and their use as flavour modifiers - Patents.com

Abstract

The present disclosure generally provides amide compounds, including cinnamic acid amides, and the use of such compounds and related compounds as flavor modifiers.In some aspects, the present disclosure provides compositions that include such amide compounds, such as compositions that include such amide compounds and one or more additional compounds, such as sweeteners, salts, glutamate, arginate, purine ribonucleotides, etc.In some other aspects, the present disclosure provides methods for reducing or eliminating the amount of sweeteners, salts, glutamate, or arginate in food or beverage products.

Description

[Technical field]

[0001] The present disclosure generally provides amide compounds, including cinnamic acid amides, and the use of such compounds and related compounds as flavor modifiers.In some aspects, the present disclosure provides compositions that include such amide compounds, such as compositions that include such amide compounds and one or more additional compounds, such as sweeteners, salts, glutamate, arginate, purine ribonucleotides, etc.In some other aspects, the present disclosure provides methods for reducing or eliminating the amount of sweeteners, salts, glutamate, or arginate in food or beverage products.

[0002] 2. Description of Related Art The taste system provides sensory information about the chemical composition of the external world. Taste transduction is one of the more sophisticated forms of chemically induced sensation in animals. Taste signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. Mammals are thought to have five basic taste modalities: sweet, bitter, sour, salty and umami / kokumi.

[0003] Umami is the taste most commonly associated with the savory taste of monosodium glutamate (MSG), meat products, cheese, tomatoes, mushrooms, soy sauce, fish sauce, miso, etc. Mammals generally perceive umami as a pleasant sensation. Kokumi is the taste commonly associated with fermented products, soy sauce, fish sauce, and shrimp paste. Many of these typical sources of umami and kokumi are high in glutamic acid and salt, or rely on animal products.

[0004] Excessive sodium intake can lead to a number of health-related problems. One such problem is hypertension. Hypertension is a condition in which high blood pressure on the arterial walls can eventually lead to heart disease and other health problems. Excessive sodium intake also negatively impacts the balance of fluids and minerals in the body. For example, excessive sodium intake can cause calcium loss, which can lead to osteoporosis and other problems. Excessive intake of food products containing glutamic acid can also have certain adverse health effects, as glutamic acid interferes with the function of neurotransmitters. For this reason, it is generally desirable to reduce sodium and glutamic acid intake. In addition, there is an increasing consumer demand for food and beverage products that do not contain animal-derived ingredients, such as animal fats, meat products, or dairy products.

[0005] The enhancement of saltiness, umami, or kokumi provides an alternative approach to partially or completely replace ingredients that are traditionally used to impart saltiness, umami, and / or kokumi.However, the number of compounds that can effectively achieve this, especially those derived from natural sources, is limited.Therefore, there is a continuing need to discover new compounds that are useful as flavor modifiers, especially compounds that enhance saltiness, umami, kokumi, or any combination thereof, among other flavors.

[0006] Summary of the Invention The present disclosure relates to the discovery that certain compounds exhibit desirable and surprising effects of enhancing umami and / or salty taste when used in food or beverage products.

[0007] In a first aspect, the present disclosure provides a flavor-modifying compound, the taste-modifying compound having formula (I): [ka] [In the formula, R 1 is C 6~14 Aryl or C 4~12heteroaryl, each of which is R Y and optionally substituted with one or more substituents independently selected from the group consisting of R 2 is C 1~10 Alkyl, C 2~20 Alkenyl, C 6~14 Aryl or C 1~12 heteroaryl, and the alkyl and alkenyl groups are each R X and each of the aryl and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R Y and optionally substituted with one or more substituents independently selected from the group consisting of X 1 is a direct bond, C 1~6 Alkylene or C 2~6 alkenylene, each of the alkylene and alkenylene groups being R X and optionally substituted with one or more substituents independently selected from the group consisting of X 2 and X 3 One of the groups is -NH- or -N(C 1~6 alkyl)-, and the other is -O-, -NH- or -N(C 1~6 alkyl)-, R X are halogen atoms, oxo, -CN, nitro, -OH, -NH2, -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH2, -O-(C 1~6 alkyl), -NH-(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C(O)-(C 1~6 alkyl), -OC(O)-(C 1~6 alkyl), -NH-C(O)-(C 1~6 alkyl), -C(O)-O-(C 1~6 alkyl), -C(O)-NH-(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl)2, -S(O)2-(C 1~6 alkyl), -OS(O)2-(C 1~6 alkyl), -NH-S(O)2-(C1~6 alkyl), -S(O)2-O-(C 1~6 alkyl), -S(O)2-NH-(C 1~6 alkyl), -S(O)2-N(C 1~6 Alkyl)2, C 3~10 Cycloalkyl, C 2~14 Heterocyclyl, C 6~14 Aryl, C 2~14 Heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Haloalkyl, C 2~6 Haloalkenyl, C 1~6 Haloalkoxy, C 2~6 Haloalkenyloxy, (C 1~6 Alkoxy)-C 1~6 Alkyl, -OC(O)-(C 6~10 aryl), -OC(O)-(C 6~10 Hydroxyaryl) and -OC(O)-((C 1~6 Alkoxy)-C 6~10 aryl), R Y are halogen atoms, oxo, -CN, nitro, -OH, -NH2, -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH2, -O-(C 1~6 alkyl), -NH-(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C(O)-(C 1~6 alkyl), -OC(O)-(C 1~6 alkyl), -NH-C(O)-(C 1~6 alkyl), -C(O)-O-(C 1~6 alkyl), -C(O)-NH-(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl)2, -S(O)2-(C 1~6 alkyl), -OS(O)2-(C 1~6 alkyl), -NH-S(O)2-(C 1~6 alkyl), -S(O)2-O-(C 1~6 alkyl), -S(O)2-NH-(C 1~6 alkyl), -S(O)2-N(C 1~6Alkyl)2, C 3~10 Cycloalkyl, C 2~14 Heterocyclyl, C 6~14 Aryl, C 2~14 Heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Haloalkyl, C 2~6 Haloalkenyl, C 1~6 Haloalkoxy, C 2~6 Haloalkenyloxy, (C 1~6 Alkoxy)-C 1~6 Alkyl, C 1~6 Alkyl and C 2~6 alkenyl, and any adjacent substituents on the aryl or heteroaryl rings can be optionally joined to form a fused carbocyclic or heterocyclic ring having 5-7 members. or a edible acceptable salt thereof.

[0008] In a second aspect, the present disclosure provides the use of any of the flavor modifying compounds of the first aspect and any of its embodiments. In a related aspect, the present disclosure provides a corresponding method of using any of the flavor modifying compounds of the first aspect and any of its embodiments, comprising introducing the flavor modifying compound into an ingestible composition. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product.

[0009] In a third aspect, the disclosure provides the use of any of the compounds of the first aspect and any of its embodiments to modify the flavor of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of using any of the flavor modifying compounds of the first aspect and any of its embodiments to modify the flavor of an ingestible composition, comprising introducing the flavor modifying compound into the ingestible composition. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product.

[0010] In a fourth aspect, the disclosure provides the use of any compound of the first aspect and any embodiment thereof to enhance the saltiness of an ingestible composition. In a related aspect, the disclosure provides the use of any compound of the first aspect and any embodiment thereof to reduce the salt (e.g., sodium chloride) content of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of using any flavor modifying compound of the first aspect and any embodiment thereof to enhance the saltiness of an ingestible composition, comprising introducing the flavor modifying compound into the ingestible composition. In some embodiments of these aspects, the ingestible composition comprises sodium chloride, potassium chloride, or any combination thereof. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product.

[0011] In a fifth aspect, the disclosure provides the use of any compound of the first aspect and any embodiment thereof to enhance the palatability of an ingestible composition. In a related aspect, the disclosure provides the use of any compound of the first aspect and any embodiment thereof to reduce or eliminate the glutamate or aspartate content of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of using any flavor modifying compound of the first aspect and any embodiment thereof to enhance the palatability of an ingestible composition, comprising introducing the flavor modifying compound into the ingestible composition. In some embodiments of these aspects, the ingestible composition is free or substantially free (e.g., 1000 ppm or less) of monosodium glutamate (MSG). In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product.

[0012] In a sixth aspect, the disclosure provides the use of any compound of the first aspect and any embodiment thereof to enhance the kokumi taste of an ingestible composition. In a related aspect, the disclosure provides the use of any compound of the first aspect or any embodiment thereof to reduce or eliminate the glutamyl (e.g., L-glutamyl peptide) content of an ingestible composition. In another related aspect, the disclosure provides the use of any compound of the first aspect or any embodiment thereof to reduce or eliminate the animal (e.g., animal broth or meat) content of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of using any flavor modifying compound of the first aspect and any embodiment thereof to enhance the kokumi taste of an ingestible composition, comprising introducing the flavor modifying compound into the ingestible composition. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product.

[0013] In a seventh aspect, the disclosure provides an ingestible composition comprising any of the compounds of the first aspect. In some embodiments, the compound of the first aspect comprises at least 0.1% by weight, or at least 0.5% by weight, or at least 1.0% by weight of the composition on a dry weight basis (e.g., based on the total weight of the composition excluding the weight of any liquid carrier). In some embodiments, the concentration of the compound of the first aspect in the ingestible composition ranges from 0.1 ppm to 1000 ppm, or from 0.5 ppm to 500 ppm. In some embodiments, the ingestible composition comprises a salty tastant, an umami tastant, a kokumi tastant, or any combination thereof.

[0014] In an eighth aspect, the present disclosure provides a solid composition comprising any compound of the first aspect, wherein the compound of the first aspect comprises at least 0.1 wt.%, or at least 0.5 wt.%, or at least 1.0 wt.% of the solid composition based on the total weight of the composition.

[0015] In a ninth aspect, the present disclosure provides an ingestible composition comprising any of the compounds of the first aspect, wherein the concentration of the compound of the first aspect in the ingestible composition is in the range of 1-1000 ppm. In some embodiments, the ingestible composition is not a naturally occurring composition.

[0016] In a tenth aspect, the present disclosure provides a concentrated flavouring composition comprising any compound of the first aspect.

[0017] In an eleventh aspect, the present disclosure provides a flavored product comprising any of the compositions of the previous four aspects. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, tea, broth, etc. In some other embodiments, the flavored product is a food product, such as yogurt, soup, etc. In some embodiments, the flavored product is a meat analog product.

[0018] Further aspects and embodiments thereof are described in the following detailed description, drawings, abstract and claims.

[0019] The following drawings are presented for the purpose of illustrating various embodiments of the compositions and methods disclosed herein. The drawings are presented for illustrative purposes only and are not intended to describe any preferred compositions or preferred methods or to serve as the basis for any limitations on the scope of the claimed invention. [Brief description of the drawings]

[0020] [Figure 1] FIG. 1 shows a chemical formula representing a compound disclosed herein, in which R1 is C6-14 aryl or C4-12 heteroaryl, each of which is optionally substituted; R2 is C1-10 alkyl, C2-20 alkenyl, C6-14 aryl, or C1-12 heteroaryl, each of which is optionally substituted; and X1 is a direct bond, C1-6 alkylene, or C2-6 alkenylene, each of which is optionally substituted.

[0021] Detailed Description The following detailed description defines various aspects and embodiments provided herein. The description is intended to be read from the perspective of one of ordinary skill in the relevant art. As such, it may not necessarily contain information that is familiar to such a person of ordinary skill in the art.

[0022] definition The following terms and expressions have the meanings indicated below unless otherwise specified herein. This disclosure may use other terms and expressions not expressly defined herein. Such other terms and expressions have the meanings that they have in the context of this disclosure to those skilled in the art. In some cases, terms or expressions may be defined in the singular or plural. In such cases, it is understood that any term in the singular can include its plural counterpart, and vice versa, unless expressly indicated to the contrary.

[0023] As used herein, "solvate" refers to a compound formed by the interaction of one or more solvent molecules with one or more compounds described herein. In some embodiments, the solvate is a ingestibly acceptable solvate, such as a hydrate.

[0024] As used herein, "C a ~C b " or "C a~b " refers to the number of carbon atoms in the specified group. That is, the group can contain from "a" to "b" (inclusive) carbon atoms. Thus, for example, "C1-C4 alkyl" or "C 1~4 An "alkyl" group refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-.

[0025] As used herein, "halogen" or "halo" refers to any one of the radiostable atoms in column 7 of the periodic table of the elements, such as fluorine, chlorine, bromine, or iodine. In some embodiments, "halogen" or "halo" refers to fluorine or chlorine.

[0026] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain that is fully saturated (i.e., contains no double or triple bonds). In some embodiments, the alkyl group has 1 to 20 carbon atoms (wherever found herein, numerical ranges such as "1 to 20" refer to each integer within the given range; for example, "1 to 20 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although this definition also encompasses occurrences of the term "alkyl" where no numerical range is specified). The alkyl group may be a medium size alkyl having 1 to 9 carbon atoms. The alkyl group may be a lower alkyl having 1 to 4 carbon atoms. The alkyl group may be a "C 1~4 By way of example only, "C 1~4 "Alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, and the like. Unless indicated to the contrary, the term "alkyl" refers to a group that is not further substituted. Note that terms such as "butyl," "pentyl," "hexyl," and the like refer to straight chain moieties (and do not include branched chain moieties) unless specifically indicated to the contrary.

[0027] As used herein, "heteroalkyl" refers to a straight or branched hydrocarbon chain containing one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur, in the chain backbone. In some embodiments, heteroalkyl groups have 1-20 carbon atoms, although this definition also encompasses occurrences of the term "heteroalkyl" where no numerical range is specified. Heteroalkyl groups may be medium size heteroalkyl having 1-9 carbon atoms. Heteroalkyl groups may be lower heteroalkyl having 1-4 carbon atoms. Heteroalkyl groups are also referred to as "C 1~4 A heteroalkyl group may be designated as "heteroalkyl" or similar designations. A heteroalkyl group may contain one or more heteroatoms. By way of example only, "C 1~4 "Heteroalkyl" indicates that 1 to 4 carbon atoms are present in the heteroalkyl chain and that one or more heteroatoms are present in the backbone of the chain. Unless otherwise indicated, the term "heteroalkyl" refers to a group that is not further substituted.

[0028] As used herein, "alkenyl" refers to a straight or branched hydrocarbon chain containing one or more double bonds. In some embodiments, an alkenyl group has 2 to 20 carbon atoms, although this definition also encompasses occurrences of the term "alkenyl" where no numerical range is specified. An alkenyl group may be a medium size alkenyl having 2 to 9 carbon atoms. An alkenyl group may be a lower alkenyl having 2 to 4 carbon atoms. An alkenyl group may be a "C 2~4 Alkenyl" or similar designations. 2~4"Alkenyl" indicates that there are 2 to 4 carbon atoms in the alkenyl chain, i.e., the alkenyl chain is selected from the group consisting of ethenyl, propen-1-yl, propen-2-yl, propen-3-yl, buten-1-yl, buten-2-yl, buten-3-yl, buten-4-yl, 1-methyl-propen-1-yl, 2-methyl-propen-1-yl, 1-ethyl-ethen-1-yl, 2-methyl-propen-3-yl, buta-1,3-dienyl, buta-1,2,-dienyl, and buta-1,2-dien-4-yl. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, and hexenyl. Unless otherwise indicated, the term "alkenyl" refers to a group that is not further substituted.

[0029] As used herein, "alkylene" refers to a fully saturated branched or straight chain diradical chemical group containing only carbon and hydrogen (i.e., alkanediyl) attached to the remainder of the molecule through two points of attachment. In some embodiments, alkylene groups have 1-20 carbon atoms, although this definition also encompasses occurrences of the term alkylene where no numerical range is specified. Alkylene groups may be medium size alkylenes having 1-9 carbon atoms. Alkylene groups may be lower alkylenes having 1-4 carbon atoms. An alkylene group is defined as a "C 1~4 As just one example, the alkylene may be designated as "C 1~4 "Alkylene" indicates that there are 1 to 4 carbon atoms in the alkylene chain, i.e., the alkylene chain is selected from the group consisting of methylene, ethylene, ethane-1,1-diyl, propylene, propane-1,1-diyl, propane-2,2-diyl, 1-methyl-ethylene, butylene, butane-1,1-diyl, butane-2,2-diyl, 2-methyl-propane-1,1-diyl, 1-methyl-propylene, 2-methyl-propylene, 1,1-dimethyl-ethylene, 1,2-dimethyl-ethylene and 1-ethyl-ethylene. Unless indicated to the contrary, the term "alkylene" refers to a group that is not further substituted.

[0030] As used herein, "alkenylene" refers to a straight or branched chain diradical chemical group containing only carbon and hydrogen and containing at least one carbon-carbon double bond, attached to the remainder of the molecule through two points of attachment. In some embodiments, alkenylene groups have 2-20 carbon atoms, although this definition also encompasses occurrences of the term alkenylene where no numerical range is specified. Alkenylene groups may be medium size alkenylenes having 2-9 carbon atoms. Alkenylene groups may be lower alkenylenes having 2-4 carbon atoms. An alkenylene group is also referred to as "C 2~4 Alkenylene" or similar designations. 2~4 "Alkenylene" means that there are 2 to 4 carbon atoms in the alkenylene chain, i.e., the alkenylene chain is selected from the group consisting of ethenylene, ethene-1,1-diyl, propenylene, propene-1,1-diyl, prop-2-ene-1,1-diyl, 1-methyl-ethenylene, but-1-enylene, but-2-enylene, buta-1,3-dienylene, butene-1,1-diyl, buta-1,3-diene-1,1-diyl, buta-2-ene-1,1-diyl, and the like. diyl, but-3-ene-1,1-diyl, 1-methyl-prop-2-ene-1,1-diyl, 2-methyl-prop-2-ene-1,1-diyl, 1-ethyl-ethenylene, 1,2-dimethyl-ethenylene, 1-methyl-propenylene, 2-methyl-propenylene, 3-methyl-propenylene, 2-methyl-propene-1,1-diyl and 2,2-dimethyl-ethen-1,1-diyl. Unless indicated to the contrary, the term "alkenylene" refers to a group that is not further substituted.

[0031] As used herein, "aromatic" means a ring or ring system having a conjugated pi-electron system, and includes both carbocyclic aromatic groups (e.g., phenyl) and heterocyclic aromatic groups (e.g., pyridine). The term includes monocyclic or fused-ring polycyclic groups (i.e., rings which share adjacent pairs of atoms), so long as the entire ring system is aromatic.

[0032] As used herein, "aryl" means an aromatic ring or ring system (i.e., two or more fused rings that share two adjacent carbon atoms) that contains only carbon in the ring backbone. When aryl is a ring system, all rings in the system are aromatic. In some embodiments, aryl groups have 6-18 carbon atoms, although this definition also encompasses occurrences of the term "aryl" where no numerical range is specified. In some embodiments, aryl groups have 6-10 carbon atoms. An aryl group is defined as "a fused ring, which is an aromatic ring or ring system, and is an aromatic ring or ring system, which is an aromatic ring or ring system. 6~10 Aryl, C6-C 10 Examples of aryl groups include, but are not limited to, phenyl, naphthyl, azulenyl, and anthracenyl. In some embodiments, the term "aryl" refers to phenyl. Unless indicated to the contrary, the term "aryl" refers to a group that is not further substituted.

[0033] As used herein, "aralkyl" or "arylalkyl" refers to an aryl group attached as a substituent via an alkylene group, e.g., "C 7~14 arylalkyl" and the like, including, but not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl, and the like. In some embodiments, an alkylene group is a lower alkylene group (i.e., 1~4 alkylene group).

[0034] As used herein, "heteroaryl" refers to an aromatic ring or ring system (i.e., two or more fused rings sharing two adjacent atoms) that contains one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur, in the ring backbone. When a heteroaryl is a ring system, all rings in the system are aromatic. In some embodiments, heteroaryl groups have 5-18 ring members (i.e., the number of atoms that make up the ring backbone, including carbon atoms and heteroatoms), although this definition also encompasses occurrences of the term "heteroaryl" where no numerical range is specified. In some embodiments, heteroaryl groups have 5-10 ring members or 5-7 ring members. Heteroaryl groups may be designated as "5-7 membered heteroaryl," "5-10 membered heteroaryl," or similar designations. Examples of heteroaryl rings include, but are not limited to, furyl, thienyl, phthalazinyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indolyl, isoindolyl, and benzothienyl. Unless otherwise indicated, the term "heteroaryl" refers to a group that is not further substituted.

[0035] As used herein, "carbocyclyl" or "carbocycle" refers to a non-aromatic cyclic ring or ring system containing only carbon atoms in the ring system backbone. When a carbocyclyl is a ring system, two or more rings may be fused, bridged, or connected by a spiro bond. A carbocyclyl may have any degree of saturation, so long as at least one ring in the ring system is not aromatic. Thus, carbocyclyl includes cycloalkyl, cycloalkenyl, and cycloalkynyl. In some embodiments, a carbocyclyl group has 3 to 20 carbon atoms, although this definition also encompasses occurrences of the term "carbocyclyl" where no numerical range is specified. A carbocyclyl group may be a medium sized carbocyclyl having 3 to 10 carbon atoms. A carbocyclyl group may be a carbocyclyl having 3 to 6 carbon atoms. A carbocyclyl group is defined as a "C 3~6 Examples of carbocyclyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,3-dihydro-indene, bicyclo[2.2.2]octanyl, adamantyl, and spiro[4.4]nonanyl. Unless indicated to the contrary, the term "carbocyclyl" refers to a group that is not further substituted.

[0036] As used herein, "heterocyclyl" or "heterocycle" refers to a non-aromatic cyclic ring or ring system containing at least one heteroatom in the ring backbone. Heterocyclyls may be fused, bridged, or spiro-linked. Heterocyclyls may have any degree of saturation, so long as at least one ring in the ring system is not aromatic. The heteroatoms may be present in either the non-aromatic or aromatic rings in the ring system. In some embodiments, heterocyclyl groups have 3-20 ring members (i.e., the number of atoms that make up the ring backbone, including carbon atoms and heteroatoms), although this definition also encompasses occurrences of the term "heterocyclyl" where no numerical range is specified. Heterocyclyl groups may be medium-sized heterocyclyls having 3-10 ring members. Heterocyclyl groups may be heterocyclyls having 3-6 ring members. Heterocyclyl groups may be designated as "3-6 membered heterocyclyl" or similar designations. In preferred 6-membered monocyclic heterocyclyls, the heteroatoms are selected from 1 to a maximum of 3 of O, N or S, and in preferred 5-membered monocyclic heterocyclyls, the heteroatoms are selected from 1 or 2 heteroatoms selected from O, N or S.Examples of heterocyclyl rings include azepinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, morpholinyl, oxiranyl, oxepanyl, thiepanyl, piperidinyl, piperazinyl, dioxopiperazinyl, pyrrolidinyl, pyrrolidionyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxinyl, 1,3-dioxanyl, 1,4-dioxinyl, 1,4-dioxanyl, 1,3-oxathiyl, 1,4-oxathiinyl, 1,4-oxathiyl, 2H-1,2-oxazinyl, trioxanyl, hexahydro-1, These include, but are not limited to, 3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiolyl, 1,3-dithiolanyl, isoxazolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolinyl, thiazolidinyl, 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiazinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl, and tetrahydroquinoline.

[0037] It is to be understood that certain radical naming conventions may include either monoradicals or diradicals depending on the context. For example, if a substituent requires two points of attachment to the rest of the molecule, the substituent is understood to be a diradical. For example, a substituent specified as alkyl requiring two points of attachment includes diradicals such as -CH2-, -CH2CH2-, -CH2CH(CH3)CH2-, etc.

[0038] Whenever a substituent is depicted as a diradical (i.e., having two points of attachment to the remainder of the molecule), it is understood that the substituent may be attached in any orientation unless otherwise indicated. Thus, for example, -AE- or [ka] Substituents depicted as include those that are oriented such that A is attached to the point of attachment at the left end of the molecule as well as when A is attached to the point of attachment at the right end of the molecule.

[0039] As used herein, a squiggly bond adjacent to a carbon-carbon double bond indicates that the substituents around the carbon-carbon double bond can be bonded in either the E or Z configuration, or a combination of molecules in either configuration.

[0040] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to "a substituent" includes not only a single substituent but two or more substituents, and so forth.

[0041] As used herein, the terms "for example," "for instance," "such as," or "including" are intended to introduce examples that further clarify a more general subject matter. Unless otherwise expressly indicated, such examples are provided merely as an aid in understanding the embodiments illustrated in this disclosure and are not intended to be limiting in any way. Additionally, these phrases do not imply any kind of preference for the disclosed embodiments.

[0042] As used herein, "comprise" or "comprises" or "comprising" or "comprised of" refers to an open group, i.e., the group can include additional members in addition to those explicitly listed. For example, the phrase "comprising A" means that A must be present, but other members may be present. The terms "include," "have," and "composed of," as well as their grammatical variations, have the same meaning. In contrast, "consist of" or "consists of" or "consisting of" refers to a closed group. For example, the phrase "consisting of A" means that A and only A are present.

[0043] As used herein, "optionally" means that the event described thereafter may or may not occur. In some embodiments, the optional event does not occur. In some other embodiments, the optional event occurs one or more times.

[0044] As used herein, "or" should be given its broadest reasonable interpretation and should not be limited to one or the other. Thus, the phrase "comprising A or B" means that A may be present and B is not present, or B is present and A is not present, or both A and B are present. Furthermore, where A defines, for example, a class that can have multiple members, e.g., A1 and A2, one or more members of the class may be present at the same time.

[0045] As used herein, certain substituents or linking groups having only a single atom may be referred to by the name of the atom. For example, in some cases, the substituent "-H" may be referred to as "hydrogen" or "hydrogen atom", the substituent "-F" may be referred to as "fluorine" or "fluorine atom", and the linking group "-O-" may be referred to as "oxygen" or "oxygen atom".

[0046] The point of attachment of a group is generally indicated by a terminal dash (-) or asterisk (*). For example, groups such as *-CH2-CH3 or -CH2-CH3 both represent an ethyl group.

[0047] Chemical structures are often shown using a "skeletal" form in which the carbon atoms are not explicitly shown and the hydrogen atoms attached to them are omitted entirely. For example, the structure [ka] represents butane (i.e., n-butane). Additionally, aromatic groups such as benzene are represented by showing one of the contributing resonance structures. For example, the structure [ka] represents toluene.

[0048] Other terms, not included in this subsection, are defined elsewhere in this specification.

[0049] Amide Compounds In a first aspect, the present disclosure provides a taste modifying compound, the taste modifying compound having formula (I): [ka] [In the formula, R 1 is C 6~14 Aryl or C 4~12 heteroaryl, each of which is R Y and optionally substituted with one or more substituents independently selected from the group consisting of R 2 is C 1~10 Alkyl, C 2~10 Alkenyl, C 6~14 Aryl or C 1~12 heteroaryl, and the alkyl and alkenyl groups are each R X and each of the aryl and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R Y and optionally substituted with one or more substituents independently selected from the group consisting of X 1 is a direct bond, C 1~6 Alkylene or C 2~6 alkenylene, each of the alkylene and alkenylene groups being R X and optionally substituted with one or more substituents independently selected from the group consisting of X 2 and X 3 One of the groups is -NH- or -N(C 1~6 alkyl)-, and the other is -O-, -NH- or -N(C 1~6 alkyl)-, R X are halogen atoms, oxo, -CN, nitro, -OH, -NH2, -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH2, -O-(C 1~6 alkyl), -NH-(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C(O)-(C 1~6 alkyl), -OC(O)-(C 1~6 alkyl), -NH-C(O)-(C 1~6 alkyl), -C(O)-O-(C 1~6 alkyl), -C(O)-NH-(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl)2, -S(O)2-(C 1~6 alkyl), -OS(O)2-(C 1~6 alkyl), -NH-S(O)2-(C 1~6 alkyl), -S(O)2-O-(C 1~6 alkyl), -S(O)2-NH-(C 1~6alkyl), -S(O)2-N(C 1~6 Alkyl)2, C 3~10 Cycloalkyl, C 2~14 Heterocyclyl, C 6~14 Aryl, C 2~14 Heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Haloalkyl, C 2~6 Haloalkenyl, C 1~6 Haloalkoxy, C 2~6 Haloalkenyloxy, (C 1~6 Alkoxy)-C 1~6 Alkyl, -OC(O)-(C 6~10 aryl), -OC(O)-(C 6~10 Hydroxyaryl) and -OC(O)-((C 1~6 Alkoxy)-C 6~10 aryl), R Y are halogen atoms, oxo, -CN, nitro, -OH, -NH2, -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH2, -O-(C 1~6 alkyl), -NH-(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C(O)-(C 1~6 alkyl), -OC(O)-(C 1~6 alkyl), -NH-C(O)-(C 1~6 alkyl), -C(O)-O-(C 1~6 alkyl), -C(O)-NH-(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl)2, -S(O)2-(C 1~6 alkyl), -OS(O)2-(C 1~6 alkyl), -NH-S(O)2-(C 1~6 alkyl), -S(O)2-O-(C 1~6 alkyl), -S(O)2-NH-(C 1~6 alkyl), -S(O)2-N(C 1~6 Alkyl)2, C 3~10 Cycloalkyl, C 2~14 Heterocyclyl, C 6~14Aryl, C 2~14 Heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Haloalkyl, C 2~6 Haloalkenyl, C 1~6 Haloalkoxy, C 2~6 Haloalkenyloxy, (C 1~6 Alkoxy)-C 1~6 Alkyl, C 1~6 Alkyl and C 2~6 alkenyl, and any adjacent substituents on the aryl or heteroaryl rings can be optionally joined to form a fused carbocyclic or heterocyclic ring having 5-7 members. or a edible acceptable salt thereof.

[0050] As used herein, the term "amide compound" or "flavor modifying compound" refers to a compound of formula (I) as defined above or a edible acceptable salt thereof, or any embodiment thereof as described below.

[0051] X 1 may have any suitable value in accordance with the above definition. In some embodiments, X 1 is R 1 is a direct bond such that X is directly bonded to the adjacent carbonyl carbon. 1 is C 1~6 In some further such embodiments, X is alkylene. 1 is -CH-, -CH-CH-, or -CH-CH-CH-. In some other embodiments, X 1 is C 2~6 In some such embodiments, X is alkenylene. 1 is -CH=CH- in either the Z or E configuration. In some such embodiments, X 1 is -CH=CH- in the Z configuration. In some such embodiments, X 1 is -CH=CH- in the E configuration.

[0052] X2 and X 3 may have any suitable value in accordance with the above definition. In some embodiments, X 2 and X 3 are both -NH-. In some embodiments, X 2 is -O- and X 3 In some embodiments, X is -NH-. 2 is -NH- and X 3 is -O-.

[0053] R 1 may have any suitable value in accordance with the definition above. In some embodiments of any of the above-described embodiments, R 1 is R Y In some further such embodiments, R is phenyl optionally substituted with one or more substituents independently selected from the group consisting of 1 -OH, -O-(C 1~6 Alkyl) and C 1~6 phenyl optionally substituted with one or more substituents independently selected from the group consisting of alkyl, and any two of the substituents on adjacent carbons of the phenyl ring can optionally be joined to form a methylenedioxy fused ring. In some further such embodiments, R 1 is unsubstituted phenyl. In some other such embodiments, R 1 -OH, -O-(C 1~6 Alkyl) and C 1~6 phenyl substituted with one or more substituents independently selected from the group consisting of alkyl, and any two of the substituents on adjacent carbons of the phenyl ring may optionally be joined to form a methylenedioxy fused ring. 1 is C 1~6 In some such embodiments, R is phenyl substituted 1 to 3 times with alkyl, such as methyl, ethyl, isopropyl, or any combination thereof. 1 is phenyl substituted 1 to 3 times with methyl. In some embodiments, R 1 -OH, -O-(C 1~6In some such embodiments, R 1 is phenyl substituted 1-3 times with -OH, -O-CH, -O-CH-CH, or any combination thereof. 1 is 2,3-methylenedioxyphenyl. In some alternative embodiments, R 1 is C 4~12 Heteroaryl is, for example, 2-pyridyl, 3-pyridyl or 4-pyridyl.

[0054] R 2 may have any suitable value in accordance with the definition above. In some embodiments of any of the above-described embodiments, R 2 is R Y In some further such embodiments, R is phenyl optionally substituted with one or more substituents independently selected from the group consisting of 2 -OH, -O-(C 1~6 Alkyl) and C 1~6 phenyl optionally substituted with one or more substituents independently selected from the group consisting of alkyl, and any two of the substituents on adjacent carbons of the phenyl ring can optionally be joined to form a methylenedioxy fused ring. In some further such embodiments, R 2 is unsubstituted phenyl. In some further such embodiments, R 2 -OH, -O-(C 1~6 Alkyl) and C 1~6 phenyl substituted with one or more substituents independently selected from the group consisting of alkyl, and any two of the substituents on adjacent carbons of the phenyl ring may optionally be joined to form a methylenedioxy fused ring. 2 is C 1~6 In some such embodiments, R is phenyl substituted 1 to 3 times with alkyl, such as methyl, ethyl, isopropyl, or any combination thereof. 2 is phenyl substituted 1 to 3 times with methyl. In some embodiments, R 2 -OH, -O-(C1~6 In some such embodiments, R 2 is phenyl substituted 1-3 times with -OH, -O-CH, -O-CH-CH, or any combination thereof. In some further such embodiments, R 2 is phenyl substituted mono- or di-with -OH. In some embodiments, R 2 is 2,3-methylenedioxyphenyl. In some alternative embodiments, R 2 is C 4~12 Heteroaryl is, for example, 2-pyridyl, 3-pyridyl or 4-pyridyl.

[0055] In some other embodiments of any of the above embodiments, R 2 is R X C optionally substituted with one or more substituents independently selected from the group consisting of 1~10 In some such embodiments, R 2 -OH, -O-(C 1~6 C optionally substituted with one or more alkyl groups, or any combination thereof 1~10 In some further such embodiments, R 2 is unsubstituted C 1~10 alkyl, for example methyl, ethyl, isopropyl, or sec-butyl. In some other such embodiments, R 2 is C substituted 1 or 2 times by -OH 1~10 Alkyl, for example 4-hydroxybutan-2-yl.

[0056] In some other embodiments of any of the above embodiments, R 2 is R X C optionally substituted with one or more substituents independently selected from the group consisting of 2~10 alkenyl. In some embodiments, R 2 is C substituted by phenyl 2~6 alkenyl, such as (E)-2-phenylethenyl or (Z)-2-phenylethenyl. In some embodiments, R2 is unsubstituted C 2~10 alkenyl, such as (E)-2-buten-2-yl, (Z)-2-buten-2-yl, (E)-propen-1-yl, (Z)-propen-1-yl, (E)-buten-1-yl, (Z)-buten-1-yl, (E)-3-methylbuten-1-yl, (Z)-3-methylbuten-1-yl, (E)-1-methylpropen-1-yl, (Z)-1-methylpropen-1-yl, 2-methylpropen-1-yl, 1,2-dimethyl-propen-1-yl, (E)-1-methylbuten-1-yl, or (Z)-1-methylbuten-1-yl. 2 is (E)-2-buten-2-yl. In some embodiments, R 2 is (Z)-2-buten-2-yl. In some other embodiments, R 2 is C substituted 1 or 2 times by -OH 2~10 alkenyl, such as (E)-4-hydroxybut-2-en-2-yl, (Z)-4-hydroxybut-2-en-2-yl, 3-hydroxybut-1-en-2-yl, or 3,4-dihydroxybut-1-en-2-yl. 2 is a C substituted 1 or 2 times by -OC(O)-CH 2~10 alkenyl, such as (E)-4-acetoxybut-2-en-2-yl or (Z)-4-acetoxybut-2-en-2-yl. In some embodiments, R 2 is C mono- or di-substituted by -OC(O)-phenyl 2~10 alkenyl, where the phenyl is 1 or 2 optionally substituted with -OH, -OCH3 or a combination thereof, for example, (E)-4-(4-methoxybenzoyloxy)-but-2-en-2-yl or (Z)-4-(4-methoxybenzoyloxy)-but-2-en-2-yl.

[0057] When the compounds disclosed herein have at least one chiral center, they can exist as individual enantiomers and diastereomers, or as mixtures of such isomers. In some embodiments related to the second aspect, the sweetening enhancing compound has a significant enantiomeric purity.

[0058] Separation of individual isomers or selective synthesis of individual isomers can be achieved by applying various methods known to those skilled in the art. Unless otherwise indicated (e.g., when the stereochemistry of a chiral center is explicitly indicated), all such isomers and mixtures thereof are included within the scope of the compounds disclosed herein. Furthermore, the compounds disclosed herein may exist in one or more crystalline or amorphous forms. Unless otherwise indicated, all such forms are included within the scope of the compounds disclosed herein, including any polymorphic forms. In addition, some of the compounds disclosed herein may form solvates with water (i.e., hydrates) or common organic solvents. Unless otherwise indicated, such solvates are included within the scope of the compounds disclosed herein.

[0059] Those skilled in the art will recognize that some structures depicted herein may be resonance forms or tautomers of compounds that can be properly represented, even in dynamic terms, by other chemical structures. Those skilled in the art will recognize that such structures may represent only a small portion of a sample of such compounds. Although such resonance forms or tautomers are not depicted herein, such compounds are considered to be within the scope of the depicted structures.

[0060] Isotopes may be present in the compounds described. Each chemical element represented in a compound structure may include any isotope of said element. For example, in a compound structure, it may be explicitly disclosed or understood that a hydrogen atom is present in the compound. At any position of the compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including, but not limited to, hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference to a compound herein encompasses all possible isotopic forms, unless the context clearly indicates otherwise.

[0061] In some embodiments, the compounds disclosed herein are capable of forming acid and / or base salts due to the presence of amino and / or carboxyl groups or groups similar thereto. Physiologically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Physiologically acceptable salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, bases including sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like, with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred. In some embodiments, treating the compounds disclosed herein with an inorganic base results in the loss of a labile hydrogen from the compound to form Li + , Na + , K + , Mg 2+ and Ca 2+Salt forms containing inorganic cations such as amines, dimethylamino acids ...

[0062] Table 1 provides examples of amide compounds of the present disclosure. In some embodiments, the amide compound is Compound 101 or a edible salt thereof. In some embodiments, the amide compound is Compound 102 or a edible salt thereof. In some embodiments, the amide compound is Compound 103 or a edible salt thereof. In some embodiments, the amide compound is Compound 104 or a edible salt thereof. In some embodiments, the amide compound is Compound 105 or a edible salt thereof. In some embodiments, the amide compound is Compound 106 or a edible salt thereof. In some embodiments, the amide compound is Compound 107 or a edible salt thereof. In some embodiments, the amide compound is Compound 108 or a edible salt thereof. In some embodiments, the amide compound is Compound 109 or a edible salt thereof. In some embodiments, the amide compound is Compound 110 or a edible salt thereof. In some embodiments, the amide compound is Compound 111 or a edible salt thereof. In some embodiments, the amide compound is Compound 112 or a edible salt thereof. In some embodiments, the amide compound is compound 113 or a edible salt thereof. In some embodiments, the amide compound is compound 114 or a edible salt thereof. In some embodiments, the amide compound is compound 115 or a edible salt thereof. In some embodiments, the amide compound is compound 116 or a edible salt thereof. In some embodiments, the amide compound is compound 117 or a edible salt thereof. In some embodiments, the amide compound is compound 118 or a edible salt thereof. In some embodiments, the amide compound is compound 119 or a edible salt thereof. In some embodiments, the amide compound is compound 120 or a edible salt thereof. In some embodiments, the amide compound is compound 121 or a edible salt thereof. In some embodiments, the amide compound is compound 122 or a edible salt thereof.In some embodiments, the amide compound is compound 123 or a edible salt thereof. In some embodiments, the amide compound is compound 124 or a edible salt thereof. In some embodiments, the amide compound is compound 125 or a edible salt thereof. In some embodiments, the amide compound is compound 126 or a edible salt thereof. In some embodiments, the amide compound is compound 127 or a edible salt thereof. In some embodiments, the amide compound is compound 128 or a edible salt thereof. In some embodiments, the amide compound is compound 129 or a edible salt thereof. In some embodiments, the amide compound is compound 130 or a edible salt thereof. In some embodiments, the amide compound is compound 131 or a edible salt thereof. In some embodiments, the amide compound is compound 132 or a edible salt thereof. In some embodiments, the amide compound is compound 133 or a edible salt thereof. In some embodiments, the amide compound is compound 134 or a edible salt thereof. In some embodiments, the amide compound is compound 135 or a edible salt thereof. Note that the group "OAc" refers to -OC(O)-CH.

[0063] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7]

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

Table 1-14

Table 1-15

Table 1-16

Table 1-17

[0064] In some embodiments, the amide compound is present as a free acid or a free base. In some embodiments, the amide compound is Compound 101. In some embodiments, the amide compound is Compound 102. In some embodiments, the amide compound is Compound 103. In some embodiments, the amide compound is Compound 104. In some embodiments, the amide compound is Compound 105. In some embodiments, the amide compound is Compound 106. In some embodiments, the amide compound is Compound 107. In some embodiments, the amide compound is Compound 108. In some embodiments, the amide compound is Compound 109. In some embodiments, the amide compound is Compound 110. In some embodiments, the amide compound is Compound 111. In some embodiments, the amide compound is Compound 112. In some embodiments, the amide compound is Compound 113. In some embodiments, the amide compound is Compound 114. In some embodiments, the amide compound is Compound 115. In some embodiments, the amide compound is Compound 116. In some embodiments, the amide compound is Compound 117. In some embodiments, the amide compound is Compound 118. In some embodiments, the amide compound is Compound 119. In some embodiments, the amide compound is Compound 120. In some embodiments, the amide compound is Compound 121. In some embodiments, the amide compound is Compound 122. In some embodiments, the amide compound is Compound 123. In some embodiments, the amide compound is Compound 124. In some embodiments, the amide compound is Compound 125. In some embodiments, the amide compound is Compound 126. In some embodiments, the amide compound is Compound 127. In some embodiments, the amide compound is Compound 128. In some embodiments, the amide compound is Compound 129. In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134.In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 136. In some embodiments, the amide compound is Compound 137. In some embodiments, the amide compound is Compound 138. In some embodiments, the amide compound is Compound 139. In some embodiments, the amide compound is Compound 140. In some embodiments, the amide compound is Compound 141. In some embodiments, the amide compound is Compound 142. In some embodiments, the amide compound is Compound 143. In some embodiments, the amide compound is Compound 144. In some embodiments, the amide compound is Compound 145. In some embodiments, the amide compound is Compound 146. In some embodiments, the amide compound is Compound 147. In some embodiments, the amide compound is Compound 148. In some embodiments, the amide compound is Compound 149. In some embodiments, the amide compound is Compound 150. In some embodiments, the amide compound is Compound 151. In some embodiments, the amide compound is Compound 152. In some embodiments, the amide compound is Compound 153. In some embodiments, the amide compound is Compound 154. In some embodiments, the amide compound is Compound 155. In some embodiments, the amide compound is Compound 156. In some embodiments, the amide compound is Compound 157. In some embodiments, the amide compound is Compound 158. In some embodiments, the amide compound is Compound 159. In some embodiments, the amide compound is Compound 160. In some embodiments, the amide compound is Compound 161. In some embodiments, the amide compound is Compound 162. In some embodiments, the amide compound is Compound 163. In some embodiments, the amide compound is Compound 164. In some embodiments, the amide compound is Compound 165. In some embodiments, the amide compound is Compound 166. In some embodiments, the amide compound is Compound 167. In some embodiments, the amide compound is Compound 168. In some embodiments, the amide compound is Compound 169.In some embodiments, the amide compound is Compound 170. In some embodiments, the amide compound is Compound 171. In some embodiments, the amide compound is Compound 172. In some embodiments, the amide compound is Compound 173. In some embodiments, the amide compound is Compound 174. In some embodiments, the amide compound is Compound 175. In some embodiments, the amide compound is Compound 176. In some embodiments, the amide compound is Compound 177. In some embodiments, the amide compound is Compound 178. In some embodiments, the amide compound is Compound 179. In some embodiments, the amide compound is Compound 180. In some embodiments, the amide compound is Compound 181. In some embodiments, the amide compound is Compound 182. In some embodiments, the amide compound is Compound 183. In some embodiments, the amide compound is Compound 184. In some embodiments, the amide compound is Compound 185. In some embodiments, the amide compound is Compound 186. In some embodiments, the amide compound is Compound 187. In some embodiments, the amide compound is Compound 188. In some embodiments, the amide compound is Compound 189.

[0065] Solid forms and solutions of flavor-modifying compounds In another aspect, the present disclosure provides various solid forms of the amide compounds (ie, flavor modifying compounds).

[0066] In some embodiments, the amide compound is present as a crystalline solid, either in substantially pure form or in a formulation as described below. The crystalline solid may have any suitable polymorphic form, for example, any polymorphic form obtained by recrystallization in any suitable solvent system according to procedures commonly used in the art of polymorph screening.

[0067] In some other embodiments, the amide compounds exist as amorphous or semi-amorphous solids, i.e., do not possess any regular crystal structure. Such solids can be produced using standard techniques, such as spray drying.

[0068] In some embodiments, the amide compounds exist as solvates, which are pseudomorphic forms of the compounds in which one or more solvent molecules (such as water molecules) are incorporated into the crystal structure. Any suitable solvent or combination of solvents can be used, including, but not limited to, water, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol, ethyl acetate, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and the like. In some embodiments, the present disclosure provides hydrates of the amide compounds. Such solvates can be generated by any suitable means, such as techniques commonly used by those skilled in the art in the field of polymorphism and solvate screening.

[0069] In some other embodiments, the compound exists as a co-crystal with one or more other compounds, such as one or more other sweetener compounds. The amide compound can form a co-crystal with any suitable compound. Non-limiting examples of such suitable compounds include purine ribonucleotides (such as inosine monophosphate (IMP) and guanosine monophosphate (GMP)), arginine salts, glutamates, γ-glutamyl-containing oligopeptides (such as γ-glutamyl-containing tripeptides).

[0070] In some embodiments, the amide compound is in the form of dry particles.Such dry particles can be formed by standard techniques in the art, such as dry granulation, wet granulation, etc.Such particles can also contain a number of additives, including inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate and sodium phosphate; granulating and disintegrating agents such as starch, cellulose-based materials and alginic acid; binders such as gelatin, guar gum and acacia gum; and lubricants such as magnesium stearate, stearic acid and talc.Other additives commonly used in food and beverage products can also be included, as can typical food ingredients.

[0071] In some embodiments, the amide compound is in the form of a liquid solution or liquid suspension. Such compositions may include carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia. The dispersing agent or wetting agent may be a naturally occurring phosphatide, such as lecithin, or a condensation product of an alkylene oxide with a fatty acid, such as polyoxyethylene stearate, or a condensation product of ethylene oxide with a long chain aliphatic alcohol, such as heptadecaethyleneoxycetanol, or a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol, such as polyoxyethylene sorbitol monooleate, or a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol anhydride, such as polyethylene sorbitan monooleate. Such compositions may include one or more colorants, one or more flavorings, and the like. Such liquid suspensions and solutions have a liquid carrier. Generally, the liquid carrier includes water. In some such cases, the liquid composition is an emulsion, such as an oil-in-water or water-in-oil emulsion.Furthermore, in some cases, water may be too polar to dissolve the amide compound to a desired concentration.In such cases, it may be desirable to introduce a water-miscible solvent, such as an alcohol, glycol, polyol, etc., into the solvent to facilitate solubilization of the amide compound.

[0072] In some embodiments, the amide compound is in the form of a solution, i.e., solvated in a liquid carrier. In some embodiments, the liquid carrier is an aqueous carrier. In some such embodiments, the solution comprises a food-acceptable salt of the amide compound, such as a hydrochloride, a potassium salt or a sodium salt. Such a solution can be diluted to any suitable concentration.

[0073] Uses and Methods In certain aspects, the present disclosure provides uses and methods of using amide compounds (in any form according to the aforementioned aspects and embodiments thereof).

[0074] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments). In some embodiments, the use comprises modifying the flavor of an ingestible composition, such as a food or beverage product. In a related aspect, the disclosure provides for a corresponding method of using an amide compound (according to any of the above embodiments), comprising introducing the amide compound into an ingestible composition. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product. Such ingestible compositions may have any suitable form or contain any suitable additional ingredients according to the embodiments below. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115. In some embodiments, the amide compound is compound 119. In some embodiments, the amide compound is compound 127. In some embodiments, the amide compound is compound 128. In some embodiments, the amide compound is compound 129. In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0075] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to modify the flavor of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of modifying the flavor of an ingestible composition, comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product. Such ingestible compositions may have any suitable form or contain any suitable additional ingredients according to the embodiments below. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115. In some embodiments, the amide compound is compound 119. In some embodiments, the amide compound is compound 127. In some embodiments, the amide compound is compound 128. In some embodiments, the amide compound is compound 129. In some embodiments, the amide compound is compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0076] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to enhance the saltiness of an ingestible composition. In a related aspect, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to reduce the salt (e.g., sodium chloride) content of an ingestible composition. In some embodiments, the presence of the amide compound in the ingestible composition can reduce the concentration of salt (e.g., sodium chloride) in the ingestible composition by 5% to 20%, or 5% to 30%, or 5% to 40%, or 5% to 50%, or 5% to 60%, or 5% to 70%, or 5% to 80%, or 5% to 90%, resulting in a composition having a similar perceived salt content as an equivalent composition without the amide compound and a standard concentration of salt. In a related aspect, the disclosure provides a corresponding method of enhancing the saltiness of an ingestible composition, comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. Such ingestible compositions can have any suitable form or contain any suitable additional ingredients according to the embodiments described below. In some embodiments of these aspects, the ingestible composition comprises sodium chloride, potassium chloride, or any combination thereof. In some embodiments, the ingestible composition comprises sodium chloride. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115. In some embodiments, the amide compound is compound 119. In some embodiments, the amide compound is compound 127. In some embodiments, the amide compound is compound 128. In some embodiments, the amide compound is compound 129. In some embodiments, the amide compound is compound 130. In some embodiments, the amide compound is compound 131. In some embodiments, the amide compound is compound 132.In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0077] In certain aspects, the disclosure provides the use of an amide compound (according to any of the above embodiments) to enhance the palatability of an ingestible composition. In a related aspect, the disclosure provides the use of an amide compound (according to any of the above embodiments) to reduce or eliminate the glutamate content of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of enhancing the palatability of an ingestible composition, comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. Such ingestible compositions may have any suitable form or contain any suitable additional ingredients according to the embodiments described below. In some embodiments of these aspects, the ingestible composition is free or substantially free (e.g., 1000 ppm or less) of monosodium glutamate (MSG). In some embodiments, the presence of the amide compound in the ingestible composition reduces the concentration of glutamate in the ingestible composition by 5% to 20%, or 5% to 30%, or 5% to 40%, or 5% to 50%, or 5% to 60%, or 5% to 70%, or 5% to 80%, or 5% to 90%, resulting in a composition having a similar perceived glutamate content as an equivalent composition without the amide compound and a standard concentration of glutamate. In some embodiments, the ingestible composition includes a purine ribonucleotide, such as inosine monophosphate (IMP), guanosine monophosphate (GMP), hypoxanthine, inosine, or any combination thereof. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is Compound 115. In some embodiments, the amide compound is Compound 119. In some embodiments, the amide compound is Compound 127. In some embodiments, the amide compound is Compound 128. In some embodiments, the amide compound is Compound 129.In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0078] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to enhance the kokumi taste of an ingestible composition. In a related aspect, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to reduce or eliminate the gamma-glutamyl-containing oligopeptide content of an ingestible composition. In a related aspect, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to reduce or eliminate the animal content (e.g., animal broth, meat, etc.) of an ingestible composition. In a related aspect, the disclosure provides for a corresponding method of enhancing the kokumi taste of an ingestible composition, comprising introducing an amide compound (according to any of the above embodiments) to the ingestible composition. Such ingestible compositions may have any suitable form or contain any suitable additional ingredients according to the embodiments described below. In some embodiments of these aspects, the ingestible composition is free or substantially free (e.g., 1000 ppm or less) of gamma-glutamyl-containing oligopeptides, such as gamma-glutamyl-containing tripeptides. In some embodiments, the presence of the amide compound in the ingestible composition reduces the concentration of γ-glutamyl tripeptide in the ingestible composition by 5% to 20%, or 5% to 30%, or 5% to 40%, or 5% to 50%, or 5% to 60%, or 5% to 70%, or 5% to 80%, or 5% to 90%, resulting in a composition having a similar perceived γ-glutamyl tripeptide content as an equivalent composition without the amide compound and a standard concentration of γ-glutamyl tripeptide. In some embodiments, the ingestible composition comprises one or more γ-glutamyl peptides, for example, one or more γ-glutamyl tripeptides. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115.In some embodiments, the amide compound is Compound 119. In some embodiments, the amide compound is Compound 127. In some embodiments, the amide compound is Compound 128. In some embodiments, the amide compound is Compound 129. In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0079] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to enhance the perceived juiciness of an ingestible composition. In a related aspect, the disclosure provides a corresponding method of enhancing the perceived juiciness of an edible composition, comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. Such ingestible compositions may have any suitable form or contain any suitable additional ingredients according to the embodiments below. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product, e.g., a meat or dairy analog. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115. In some embodiments, the amide compound is compound 119. In some embodiments, the amide compound is compound 127. In some embodiments, the amide compound is compound 128. In some embodiments, the amide compound is Compound 129. In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0080] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to enhance the perceived fattiness of an ingestible composition. In a related aspect, the disclosure provides for a corresponding method of enhancing the perceived fattiness of an edible composition, comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. In certain related aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to reduce the fat content of an ingestible composition. In some embodiments, the presence of the amide compound in the ingestible composition can reduce the concentration of fat in the ingestible composition by 5% to 20%, or 5% to 30%, or 5% to 40%, or 5% to 50%, or 5% to 60%, or 5% to 70%, or 5% to 80%, or 5% to 90%, resulting in a composition having a similar perceived fat content as an equivalent composition without the amide compound and a standard concentration of fat. Such ingestible compositions can have any suitable form or contain any suitable additional ingredients according to the embodiments described below. In some embodiments, the ingestible composition is a flavored product, such as a flavored food or beverage product, e.g., a meat or dairy analog. In some embodiments, the amide compound is Compound 102. In some embodiments, the amide compound is Compound 103. In some embodiments, the amide compound is Compound 104. In some embodiments, the amide compound is Compound 105. In some embodiments, the amide compound is Compound 106. In some embodiments, the amide compound is Compound 115. In some embodiments, the amide compound is Compound 119. In some embodiments, the amide compound is Compound 127. In some embodiments, the amide compound is Compound 128. In some embodiments, the amide compound is Compound 129. In some embodiments, the amide compound is Compound 130. In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135.In some embodiments, the amide compound is compound 168.

[0081] In certain aspects, the disclosure provides for the use of an amide compound (according to any of the above embodiments) to reduce the amount of alcohol in an ingestible composition. In a related aspect, the disclosure provides for a method of reducing the amount of alcohol in an ingestible composition comprising introducing an amide compound (according to any of the above embodiments) into the ingestible composition. In some embodiments, the ingestible composition is a beverage product, such as a low-alcohol or alcohol-free beverage product, including but not limited to low-alcohol beer, alcohol-free beer, low-alcohol flavored seltzer beverages, or alcohol-free seltzer beverages. In other embodiments, the edible product is a food product, such as a confectionery product or candy product. In some embodiments, the presence of the amide compound in the ingestible composition reduces the concentration of alcohol in the ingestible composition by 5% to 20%, or 5% to 30%, or 5% to 40%, or 5% to 50%, or 5% to 60%, or 5% to 70%, or 5% to 80%, or 5% to 90%, resulting in a composition having a similar perceived alcohol content as an equivalent composition without the amide compound and a standard concentration of alcohol. In some embodiments, the presence of the amide compound in the ingestible composition can completely eliminate or substantially eliminate (e.g., reduce by at least 95%, or at least 97%, or at least 99%) alcohol, resulting in a product having a similar perceived alcohol content as an equivalent product without the amide compound and a standard concentration of alcohol. In some embodiments, the amide compound is compound 102. In some embodiments, the amide compound is compound 103. In some embodiments, the amide compound is compound 104. In some embodiments, the amide compound is compound 105. In some embodiments, the amide compound is compound 106. In some embodiments, the amide compound is compound 115. In some embodiments, the amide compound is compound 119. In some embodiments, the amide compound is compound 127. In some embodiments, the amide compound is compound 128. In some embodiments, the amide compound is compound 129. In some embodiments, the amide compound is compound 130.In some embodiments, the amide compound is Compound 131. In some embodiments, the amide compound is Compound 132. In some embodiments, the amide compound is Compound 133. In some embodiments, the amide compound is Compound 134. In some embodiments, the amide compound is Compound 135. In some embodiments, the amide compound is Compound 168.

[0082] Ingestible Composition The uses and methods described above generally involve the use or incorporation of an amide compound into an ingestible composition having one or more additional components or ingredients. For example, in at least one embodiment, the present disclosure provides an ingestible composition comprising any of the amide compounds of the above-mentioned embodiments.

[0083] The ingestible composition may include the amide compound (according to any of the above embodiments) in any suitable concentration. In some embodiments, the amide compound is present in an amount sufficient to enhance the taste of the ingestible composition (e.g., enhance umami, enhance kokumi, or enhance saltiness). Thus, in some embodiments, the ingestible composition includes the amide compound at a concentration of 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 150 ppm or less, or 100 ppm or less, or 50 ppm or less, or 40 ppm or less, or 30 ppm or less, or 20 ppm or less, or 10 ppm or less. In some embodiments, the amide compound is present in a minimum amount, such as 0.1 ppm, 0.5 ppm, or 1 ppm.Thus, in some embodiments, the ingestible composition may contain from 1 ppm to 1000 ppm, or from 1 ppm to 900 ppm, or from 1 ppm to 800 ppm, or from 1 ppm to 700 ppm, or from 1 ppm to 600 ppm, or from 1 ppm to 500 ppm, or from 1 ppm to 400 ppm, or from 1 ppm to 300 ppm, or from 1 ppm to 200 ppm, or from 1 ppm to 150 ppm, or from 1 ppm to 1000 ppm. 0ppm, or 1ppm~50ppm, or 1ppm~40ppm, or 1ppm~30ppm, or 1ppm~20ppm, or 0.5ppm~1000ppm, or 0.5ppm~900ppm, or 0.5ppm~800ppm, or 0.5ppm~700ppm, or 0.5ppm~600ppm, or 0.5ppm~500ppm, or 0.5ppm~400ppm, or 0.5ppm~ 300ppm, or 0.5ppm~200ppm, or 0.5ppm~150ppm, or 0.5ppm~100ppm, or 0.5ppm~50ppm, or 0.5ppm~40ppm, or 0.5ppm~30ppm, or 0.5ppm~20ppm, or 0.1ppm~1000ppm, or 0.1ppm~900ppm, or 0.1ppm~800ppm, or 0.1ppm~700ppm, or at a concentration in the range of 0.1 ppm to 600 ppm, or 0.1 ppm to 500 ppm, or 0.1 ppm to 400 ppm, or 0.1 ppm to 300 ppm, or 0.1 ppm to 200 ppm, or 0.1 ppm to 150 ppm, or 0.1 ppm to 100 ppm, or 0.1 ppm to 50 ppm, or 0.1 ppm to 40 ppm, or 0.1 ppm to 30 ppm, or 0.1 ppm to 20 ppm.

[0084] In some embodiments of any of the above-described embodiments, the ingestible composition comprises a salty tastant and an amide compound (according to any of the above embodiments). In some embodiments, the salty tastant is sodium chloride, potassium chloride, or a combination thereof. In some such embodiments, the salty tastant is sodium chloride. In some other embodiments, the salty tastant is potassium chloride. In some embodiments, the ingestible composition comprises a salty tastant at a lower concentration than a similar salty composition that does not include the amide compound (according to any of the above embodiments). In some such embodiments, the concentration of the salty tastant is more than 10% lower, more than 20% lower, more than 30% lower, more than 40% lower, more than 50% lower, more than 60% lower, or more than 70% lower, or more than 80% lower, or more than 90% lower than the concentration of the salty tastant in a similar salty composition that does not include the amide compound (according to any of the above embodiments). In some embodiments, the salty tastant is present in an amount between 0.001 weight percent and 1.0 weight percent, or between 0.001 weight percent and 0.9 weight percent, or between 0.001 weight percent and 0.8 weight percent, or between 0.001 weight percent and 0.7 weight percent, or between 0.001 weight percent and 0.6 weight percent, or between 0.001 weight percent and 0.5 weight percent, or between 0.001 weight percent and 0.4 weight percent, or between 0.001 weight percent and 0.3 weight percent, or between 0.001 weight percent and 0.2 weight percent, or between 0.001 weight percent and It is present in the ingestible composition at a concentration ranging from 0.1 weight percent, or from 0.01 weight percent to 1.0 weight percent, or from 0.01 weight percent to 0.9 weight percent, or from 0.01 weight percent to 0.8 weight percent, or from 0.01 weight percent to 0.7 weight percent, or from 0.01 weight percent to 0.6 weight percent, or from 0.01 weight percent to 0.5 weight percent, or from 0.01 weight percent to 0.4 weight percent, or from 0.01 weight percent to 0.3 weight percent, or from 0.01 weight percent to 0.2 weight percent, or from 0.01 weight percent to 0.1 weight percent.

[0085] In some embodiments of any of the above-described embodiments, the ingestible composition comprises an umami tastant and an amide compound (according to any of the above embodiments). In some embodiments, the umami tastant is glutamate, arginate, purine ribonucleotides, or combinations thereof. In some such embodiments, the salt tastant is monosodium glutamate (MSG). In some embodiments, the umami tastant is a purine ribonucleotide (e.g., inosine monophosphate (IMP), guanosine monophosphate (GMP), hypoxanthine, inosine, or any combination thereof). In some embodiments, the umami tastant is inosine monophosphate (IMP), guanosine monophosphate (GMP), or combinations thereof. In some embodiments, the ingestible composition comprises an umami tastant at a lower concentration than a similar umami composition that does not include an amide compound (according to any of the above embodiments). In some such embodiments, the concentration of the umami tastant is more than 10% lower, more than 20% lower, more than 30% lower, more than 40% lower, more than 50% lower, more than 60% lower, or more than 70% lower, or more than 80% lower, or more than 90% lower than the concentration of the umami tastant in a similar umami composition that does not include the amide compound (according to any of the above embodiments). In some embodiments, the umami tastant is present in the ingestible composition at a concentration ranging from 1 ppm to 1000 ppm, or 1 ppm to 900 ppm, or 1 ppm to 800 ppm, or 1 ppm to 700 ppm, or 1 ppm to 600 ppm, or 1 ppm to 500 ppm, or 1 ppm to 400 ppm, or 1 ppm to 300 ppm, or 1 ppm to 200 ppm, or 1 ppm to 100 ppm, or 1 ppm to 75 ppm, or 1 ppm to 50 ppm, or 1 ppm to 25 ppm, or 1 ppm to 10 ppm, based on the total weight of the ingestible composition. In some embodiments where the umami tastant is monosodium glutamate, the ingestible composition comprises 10 ppm or less, or 5 ppm or less, or 1 ppm or less of monosodium glutamate based on the total weight of the ingestible composition.

[0086] In certain embodiments, the ingestible composition comprises a fat, such as an animal or vegetable fat, and an amide compound (according to any of the above embodiments). In some such embodiments, the introduction of the amide compound allows the use of less fat (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less, or more than 80% less, or more than 90% less) to achieve the level of fat profile of a comparable product with a higher concentration of fat but without the amide compound. In some related embodiments, the use of the amide compound allows the fat to be eliminated from the composition. The fat can be any suitable fat, such as fat derived from animal or vegetable fats. In some embodiments, the fat is an animal fat, such as dairy fat (including the fat in various cheeses), beef tallow, lard, poultry fat, lamb fat, goat fat, fish oil, butter, etc. In some other embodiments, the fat is a non-animal fat, such as olive oil, rapeseed oil, corn oil, safflower oil, nut oil, peanut oil, cashew oil, soybean oil, palm oil, palm kernel oil, coconut oil, cocoa butter, and nut butters (e.g., peanut butter, cashew butter, almond butter, hazelnut butter, etc.). In some embodiments, the fat is cocoa butter. The fat can be present in the ingestible composition in any suitable concentration. In some embodiments, the fat concentration in the ingestible composition ranges from 1 weight percent to 60 weight percent, or from 1 weight percent to 50 weight percent, or from 1 weight percent to 40 weight percent, or from 1 weight percent to 30 weight percent, or from 1 weight percent to 20 weight percent, or from 1 weight percent to 10 weight percent.

[0087] In some embodiments of any of the above-mentioned embodiments, the ingestible composition comprises a kokumi substance and an amide compound (according to any of the above-mentioned embodiments). In some embodiments, the kokumi substance is a yeast extract, a fermented food product, cheese, garlic or an extract thereof, a γ-glutamyl-containing polypeptide, a γ-glutamyl-containing oligopeptide (e.g., a γ-glutamyl-containing tripeptide); an amide compound (e.g., a cinnamic acid amide or a derivative thereof), a nucleotide, an oligonucleotide, a plant extract, a food extract, or any combination thereof. In some embodiments, the kokumi substance is a γ-glutamyl-containing tripeptide. In some embodiments, the ingestible composition comprises a kokumi substance at a lower concentration than a similar kokumi composition that does not include an amide compound (according to any of the above-mentioned embodiments). In some such embodiments, the concentration of the kokumi substance is more than 10% lower, more than 20% lower, more than 30% lower, more than 40% lower, more than 50% lower, more than 60% lower, or more than 70% lower, or more than 80% lower, or more than 90% lower than the concentration of the kokumi substance in a similar kokumi composition that does not include an amide compound (according to any of the above embodiments). In some embodiments, the kokumi substance is present in the ingestible composition at a concentration ranging from 1 ppm to 1000 ppm, or from 1 ppm to 900 ppm, or from 1 ppm to 800 ppm, or from 1 ppm to 700 ppm, or from 1 ppm to 600 ppm, or from 1 ppm to 500 ppm, or from 1 ppm to 400 ppm, or from 1 ppm to 300 ppm, or from 1 ppm to 200 ppm, or from 1 ppm to 100 ppm, or from 1 ppm to 75 ppm, or from 1 ppm to 50 ppm, or from 1 ppm to 25 ppm, or from 1 ppm to 10 ppm, based on the total weight of the ingestible composition.

[0088] In certain embodiments, the ingestible composition comprises alcohol and an amide compound (according to any of the above embodiments). In some such embodiments, the introduction of the amide compound allows the use of less alcohol (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less, or more than 80% less, or more than 90% less) to achieve the level of alcohol profile of a comparable product that uses a higher concentration of alcohol but without the amide compound. In some related embodiments, the use of the amide compound allows the elimination of alcohol from the composition. The alcohol can have any suitable concentration in the ingestible composition. In some embodiments, the alcohol concentration ranges from 1 volume percent to 50 volume percent, or 1 volume percent to 45 volume percent, or 1 volume percent to 40 volume percent, or 1 volume percent to 35 volume percent, or 1 volume percent to 30 volume percent, or 1 volume percent to 25 volume percent, or 1 volume percent to 20 volume percent, or 1 volume percent to 15 volume percent, or 1 volume percent to 10 volume percent, or 1 volume percent to 5 volume percent based on the total volume of the ingestible composition. In some embodiments, the ingestible composition comprises 1 volume percent or less of alcohol based on the total volume of the ingestible composition. Such ingestible compositions can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as a soda (e.g., hard soda), etc. The alcohol can be present in any suitable form, such as alcohol formed from grains, cane sugar, fruit, etc.

[0089] In some cases, it may be possible to reduce the amount of sweetener in a product by enhancing umami or kokumi flavor. Thus, in some embodiments, the ingestible composition comprises one or more sweeteners according to any of the following embodiments.

[0090] Such sweeteners may be present in any suitable amount. For example, in some embodiments, the sweetener is present in a concentration ranging from 0.1% to 12% by weight. In some embodiments, the sweetener is present in an amount of 0.2% to 10% by weight. In some embodiments, the sweetener is present in an amount of 0.3% to 8% by weight. In some embodiments, the sweetener is present in an amount of 0.4% to 6% by weight. In some embodiments, the sweetener is present in an amount of 0.5% to 5% by weight. In some embodiments, the sweetener is present in an amount of 1% to 2% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 5% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 4% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 3% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 2% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 1% by weight. In some embodiments, the sweetener is present in an amount of 0.1% to 0.5% by weight. In some embodiments, the sweetener is present in an amount of 0.5% to 10% by weight. In some embodiments, the sweetener is present in an amount of 2% to 8% by weight. In some further embodiments of the embodiments described in this paragraph, the sweetener is sucrose, fructose, glucose, xylitol, erythritol, or combinations thereof. The above percentages are weight percentages based on the total weight of the ingestible composition.

[0091] In some other embodiments, the sweetener is present in an amount between 10 ppm and 1000 ppm. In some embodiments, the sweetener is present in an amount between 20 ppm and 800 ppm. In some embodiments, the sweetener is present in an amount between 30 ppm and 600 ppm. In some embodiments, the sweetener is present in an amount between 40 ppm and 500 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 400 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 300 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 200 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 150 ppm. In some further embodiments of the embodiments described in this paragraph, the sweetener is a steviol glycoside, a mogroside, a derivative of any of the foregoing, such as a glycoside derivative (e.g., glucosylates), or any combination thereof.

[0092] The composition may include any suitable sweetener or combination of sweeteners. In some embodiments, the sweetener is a common saccharide sweetener such as sucrose, fructose, glucose, and a sweetener composition containing natural sugars, such as corn syrup (including high fructose corn syrup), or other syrups or sweetener concentrates derived from natural fruit and vegetable sources. In some embodiments, the sweetener is sucrose, fructose, or a combination thereof. In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is selected from rare natural sugars, including D-allose, D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-arabinose, D-turanose, and D-leucrose. In some embodiments, the sweetener is selected from semi-synthetic "sugar alcohol" sweeteners, such as erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, maltodextrin, and the like. In some embodiments, the sweetener is selected from artificial sweeteners such as aspartame, saccharin, acesulfame-K, cyclamate, sucralose, and alitame. In some embodiments, the sweetener is selected from the group consisting of cyclamic acid, mogrosides, tagatose, maltose, galactose, mannose, sucrose, fructose, lactose, allulose, neotame and other aspartame derivatives, glucose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), stevioside, rebaudioside A, other sweet stevia-based glycosides, chemically modified steviol glycosides (such as glucosylated steviol glycosides), mogrosides, chemically modified mogrosides (such as glucosylated mogrosides), carrelame, and other guanidine-based sweeteners. In some embodiments, the sweetener is a combination of two or more of the sweeteners described in this paragraph. In some embodiments, the sweetener can be a combination of two, three, four or five sweeteners disclosed herein. In some embodiments, the sweetener can be sugar. In some embodiments, the sweetener can be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is sugar.In some embodiments, the sugar is cane sugar. In some embodiments, the sugar is beet sugar. In some embodiments, the sugar can be sucrose, fructose, glucose or a combination thereof. In some embodiments, the sugar can be sucrose. In some embodiments, the sugar can be a combination of fructose and glucose.

[0093] Sweeteners may include, for example, sweetener compositions containing one or more natural or synthetic carbohydrates, such as corn syrup, high fructose corn syrup, high maltose corn syrup, glucose syrup, sucralose syrup, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), or other syrups or sweetener concentrates derived from natural fruit and vegetable sources, or even semi-synthetic "sugar alcohol" sweeteners such as polyols. Non-limiting examples of polyols in some embodiments include erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerin), threitol, galactitol, palatinose, reduced isomaltooligosaccharides, reduced xylooligosaccharides, reduced gentiooligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, and the like, as well as sugar alcohols, or any other carbohydrates or combinations thereof that can be reduced without adversely affecting the taste.

[0094] Sweeteners include agave inulin, agave nectar, agave syrup, amazake, brazzein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructans (also called inulin fiber, fructooligosaccharides or oligofructose), green stevia powder, stevia rebaudiana (stevia rebaudiana), rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E, rebaudioside F, rebaudioside I, rebaudioside H, rebaudioside L, rebaudioside K, rebaudioside J, rebaudioside N, rebaudioside O, rebaudioside M and other sweet stevia glycosides, stevioside, stevioside extract, honey, Jerusalem artichoke syrup, licorice root, Monk fruit (fruit, powder or extract), lucuma (fruit, powder or extract), maple sap (e.g., Acer saccharum, Acer nigrum, Acer rubrum, Acer saccharinum), saccharinum, Acer platanoides, Acer negundo, Acer macrophyllum, Acer grandidentatum, Acer glabrum, Acer mono), maple syrup, maple sugar, walnut sap (including sap extracted from, for example, Juglans cinerea, Juglans nigra, Juglans ailatifolia, Juglans regia), birch sap (including sap extracted from, for example, Betula papyrifera, Betula alleghaniensis, Betula alleghaniensis, Betula lenta, Betula nigra, Betula populifolia, Betula pendulapendula), sycamore sap (e.g., sap extracted from Platanus occidentalis), ironwood sap (e.g., sap extracted from Ostrya virginiana), muscovado, molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, cane sugar (also called natural sugar, unrefined cane sugar or sucrose), palm sugar, panocha, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also called tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt flour, beet sugar , cane sugar, crystallized fruit juice crystals, caramel, carbitol, carob syrup, white sugar, hydrogenated starch hydrolysates, hydrolyzed cane juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, arrope, syrup, P-4000, acesulfame potassium (also called acesulfame K or ace-K), alitame (also called aclame), advantame, aspartame, bayuno baiyunoside, neotame, benzamide derivatives, bernadame, canderel, carrelam and other guanidine sweeteners, vegetable fibre, corn sugar, coupling sugar, curculin, cyclamate, cyclocarioside I, demerara, dextran, dextrin, saccharified malt, dulcin, sucrose, vulgin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glucin, gluconic acid, gluconolactone, glucosamine, glucuronic acid, glycerol, glycine, glycyphillin, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, yellow sugarsugar, golden syrup, granulated sugar, Jiaogulan, hernandulcin, isomerized liquid sugar, jallab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro-kynurenine), galactitol, litesse, ligicane, lycasin, lupus, guanidine, falernum, mabinlin I, mabinlin II, maltol, maltisorb, maltodextrin, maltotriol, mannosamine, miraculin, starch syrup, mogrosides (including mogroside IV, mogroside V, and neomogroside), mukuroziosides, nanosugar sugar), naringin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, nigerooligosaccharide, norbu, orgeat syrup, osladin, pekmez, pentazin, periandrin I, perillaldehyde, perillartine, petphyllum, phenylalanine, phlomisoside I, phlorodizin, phyllodulcin, polyglycitol syrup, polypodoside A, pterocaryoside A, pterocaryoside B, rebiana, refiner syrup, rub syrup, rubusoside, serigeain A, shugr, siamenoside I, siraitia grossvenorii grosvenorii), soy oligosaccharides, Splenda, SRI oxime V, steviol glycosides, steviolbioside, stevioside, strogin 1, 2 and 4, sucronate, sucrose, suosan, phloridzin, super aspartame, tetrasaccharides, threitol, treacle, trilobtain, tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, volemitol, birch syrup, aspartame-acesulfame, assugrin, and combinations or blends of any two or more thereof.

[0095] In yet another embodiment, the sweetener may be a chemically or enzymatically modified natural high-potency sweetener. The modified natural high-potency sweetener includes glycosylated natural high-potency sweeteners, such as glucosyl, galactosyl or fructosyl derivatives, containing 1-50 glycoside residues. The glycosylated natural high-potency sweeteners can be prepared by enzymatic transglycosylation reactions catalyzed by various enzymes having transglycosylation activity. In some embodiments, the modified sweetener may be substituted or unsubstituted.

[0096] Additional sweeteners also include combinations of any two or more of any of the sweeteners described above. In some embodiments, the sweetener may include a combination of two, three, four or five sweeteners disclosed herein. In some embodiments, the sweetener may be a sugar. In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or combinations thereof. In some embodiments, the ingestible composition is free (or in some embodiments substantially free) of stevia-derived sweeteners, such as steviol glycosides, glucosylated steviol glycosides, or rebaudiosides. For example, in some embodiments, the ingestible composition does not contain stevia derived sweeteners, or contains stevia derived sweeteners at a concentration of 1000 ppm or less, or 500 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 20 ppm or less, or 10 ppm or less, or 5 ppm or less, or 3 ppm or less, or 1 ppm or less.

[0097] The ingestible composition, in certain embodiments, includes, but is not limited to, Acids including, for example, citric acid, phosphoric acid, ascorbic acid, sodium hydrogen sulfate, lactic acid or tartaric acid; bitter components including, for example, caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol or proteins (such as proteins and protein isolates derived from plants, algae or fungi); Colours containing, for example, caramel colour, Red No. 40, Yellow No. 5, Yellow No. 6, Blue No. 1, Red No. 3, purple carrots, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta carotene, turmeric curcumin or titanium dioxide; Preservatives including, for example, sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfate, sorbic acid or benzoic acid; antioxidants, including, for example, ascorbic acid, calcium disodium EDTA, alpha tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol or sodium hexametaphosphate; For example, resveratrol, Co-Q10, omega-3 fatty acids, theanine, choline chloride (citocoline), fibersol, inulin (chicory root), taurine, ginseng extract, guarana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucoronolactone, inositol, bioflavonoids, echinacea, ginko biloba, yerba mate, flaxseed oil, garcinia cambogia vitamins or functional ingredients including cambogia (spinosa kernel oil) peel extract, white tea extract, ribose, milk thistle extract, grape seed extract, pyridoxine HCl (vitamin B6), cyanocobalamin (vitamin B12), niacinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, copper sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, sodium gluconate, sodium polyphosphate, sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate or zinc sulfate; clouding agents including, for example, ester gum, brominated vegetable oil (BVO) or sucrose acetate isobutyrate (SAIB); Buffers including, for example, sodium citrate, potassium citrate or salts; For example, propylene glycol, ethyl alcohol, glycerin, gum arabic (gum acacia), maltodextrin, modified corn starch, dextrose, natural flavors, natural flavors containing other natural flavors (natural flavors WONF), natural and artificial flavors, artificial flavors, flavors containing silicon dioxide, magnesium carbonate, or tricalcium phosphate; or Starches and stabilizers, such as pectin, xanthan gum, carboxymethylcellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (acacia gum), inulin or carrageenan The composition may include any additional ingredient or combination of ingredients as commonly used in food and beverage products, including

[0098] The ingestible composition may have any suitable pH. In some embodiments, the amide compound enhances the sweetness of the sweetener under a wide range of pH, for example, from lower to neutral pH. Lower and neutral pH include, but are not limited to, pH of 1.5-9.0 or 2.5-8.5; 3.0-8.0; 3.5-7.5; and 4.0-7. In certain embodiments, the compounds disclosed and described herein, individually or in combination, can enhance the perceived sweetness of a certain concentration of sweetener in a taste test at compound concentrations of 50 μM, 40 μM, 30 μM, 20 μM, or 10 μM at both low and neutral pH values. In certain embodiments, the enhancement factor of the compounds disclosed and described herein, individually or in combination, at lower pH is substantially similar to the enhancement factor of the compounds at neutral pH. Such consistent sweetness enhancement properties under a wide range of pH allow for the broad use of the compounds disclosed and described herein, individually or in combination, in a wide range of foods and beverages.

[0099] Ingestible compositions defined according to any of the above embodiments, in certain embodiments, also include one or more additional flavor modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a compound that reduces bitterness, a compound that enhances umami, a compound that reduces sourness or licorice taste, a compound that enhances saltiness, a compound that enhances a cooling effect, or any combination of the above.

[0100] Therefore, in some embodiments, the amide compound of the ingestible composition disclosed herein is combined with one or more sweetness enhancing compounds.Such sweetness enhancing compounds include but are not limited to naturally occurring compounds such as hesperitin, naringenin, rhoifolin, glucosylated steviol glycoside, glucuronate from licorice, aromadendrin-3-O-acetate or other similar flavonol or flavonoid, or synthetic compounds such as any compounds described in US Patent No. 8,541,421; US ​​Patent No. 8,815,956; US Patent No. 9,834,544; US Patent No. 8,592,592; US Patent No. 8,877,922; US Patent No. 9,000,054; and US Patent No. 9,000,051, and US Patent Publication No. 2017 / 0119032. The amide compound may be mixed with such other sweetener enhancers in any suitable ratio (w / w) ranging from 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, e.g., 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12 , 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1. In some embodiments of any of the foregoing embodiments, the amide compound is combined with a glucosylated steviol glycoside in any of the above ratios. As used herein, the term "glucosylated steviol glycoside" refers to the product of enzymatic glucosylation of a natural steviol glycoside compound. Glucosylation generally occurs via glycosidic bonds such as α-1,2, α-1,4, α-1,6, β-1,2, β-1,4, and β-1,6.In some embodiments of any of the foregoing embodiments, the amide compound is combined with 3-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propyl-propanamide, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide, or any combination thereof, in any of the ratios described above.

[0101] In some further embodiments, the amide compounds of the ingestible compositions disclosed herein are combined with one or more other umami or kokumi enhancing compounds. Such umami enhancing compounds include, but are not limited to, naturally occurring compounds such as erucamide, or synthetic compounds such as any of the compounds described in U.S. Patent Nos. 8,735,081; 8,124,121; and 8,968,708. The amide compound may be mixed with such a umami enhancer in any suitable ratio (w / w) in the range of 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, for example, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:16, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:51, 1:52, 1:53, 1:54, 1:55, 1:56, 1:57, 1:58, 1:59, 1:60, 1:61, 1:62, 1:63, 1:64, 1:65, 1:66, 1:67, 1:68, 1:69, 1:70, 1 They can be used in combinations of 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0102] In some further embodiments, the amide compound of the ingestible composition disclosed herein is combined with one or more cooling enhancing compounds. Such cooling enhancing compounds include, but are not limited to, naturally occurring compounds, such as menthol or its analogs, or synthetic compounds, such as any of the compounds described in U.S. Pat. Nos. 9,394,287 and 10,421,727. The amide compound may be combined with such cooling enhancing agents in any suitable ratio (w / w) ranging from 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:16, 1:17, 1:18, 1:19 ... They can be used in combinations of 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0103] In some further embodiments, the amide compound of the ingestible composition disclosed herein is combined with one or more bitter taste suppressing compounds, including but not limited to naturally occurring compounds such as menthol or its analogs, or synthetic compounds such as any of the compounds described in U.S. Patent Nos. 8,076,491; 8,445,692; and 9,247,759. The amide compound may be mixed with such a bitterness suppressing agent in any suitable ratio (w / w) in the range of 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, for example, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:16, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:51, 1:52, 1:53, 1:54, 1:55, 1:56, 1:57, 1:58, 1:59, 1:60, 1:61, 1:62, 1:63, 1:64, 1:65, 1:66, 1:67, 1:68, 1:69, 1:70, 1 They can be used in combinations of 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0104] In some further embodiments, the amide compounds of the ingestible compositions disclosed herein are combined with one or more acidity regulating compounds. The amide compounds may be combined with such acidity regulating compounds in any suitable ratio (w / w) ranging from 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, They can be used in the following combinations: 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0105] In some further embodiments, the amide compounds of the ingestible compositions disclosed herein are combined with one or more texture-modifying compounds, including, but not limited to, tannins, cellulosic materials, bamboo powder, and the like. The amide compounds may be combined with such texture enhancers in any suitable ratio (w / w) ranging from 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:16, 1:18, 1:19, 1:19, 1:20 ... They can be used in combinations of 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0106] In some further embodiments, the amide compounds of the ingestible compositions disclosed herein are combined with one or more flavor-masking compounds, including, but not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonate salts), and the like. The amide compounds may be combined with such texture enhancers in any suitable ratio (w / w) ranging from 1:1000 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:16, 1:17, 1:18, 1:19, 1:19, 1:20 ... They can be used in combinations of 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0107] In some aspects related to the above aspects and embodiments, the present disclosure provides the use of amide compounds to enhance the flavor of a flavored composition, such as a flavored article. Any suitable flavor can be used in such a flavored composition, such as fruit flavors, meat flavors, vegetable flavors, etc. In some embodiments, the flavored composition is a soup or broth, or chips, or a beverage.

[0108] Flavoured products In certain aspects, the present disclosure provides a flavored product comprising any of the compositions of the aforementioned aspects or embodiments thereof. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt, soup, meat analogs, dairy analogs, etc.

[0109] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of fortified sparkling beverages, cola, lemon-lime flavored sparkling beverages, orange flavored sparkling beverages, grape flavored sparkling beverages, strawberry flavored sparkling beverages, pineapple flavored sparkling beverages, ginger ale, root beer, fruit juice, fruit flavored juice, juice beverages, nectar, vegetable juice, vegetable flavored juice, sports drinks, energy drinks, fortified water beverages, fortified water with vitamins, near water beverages, coconut water, tea-based beverages, coffee, cocoa beverages, dairy beverages, cereal extract beverages, and smoothies. In some embodiments, the beverage may be a soft drink.

[0110] In certain embodiments of any of the aspects and embodiments described herein that refer to a flavored product, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

[0111] Further non-limiting examples of food and beverage products or formulations include sweet coatings, frostings or glazes for such products or any entities within the soup category, the dried prepared foods category, the beverage category, the ready meal category, the canned or preserved foods category, the frozen prepared foods category, the refrigerated prepared foods category, the snack foods category, the baked goods category, the confectionery category, the dairy category, the ice cream category, the meal replacements category, the pasta and noodle category, and the sauces, dressings, condiments category, the baby food category, and / or the spreads category.

[0112] Broadly, the soup category refers to canned / preserved, dried, instant, refrigerated, UHT and frozen soups. For the purposes of this definition, soup means a food prepared from meat, poultry, fish, vegetables, grains, fruits and other ingredients, cooked in a liquid that may contain visible pieces of some or all of these ingredients. Soups may be clear (as in a broth) or thick (as in a chowder), smooth, pureed or chunky, ready-to-serve, semi-concentrated or concentrated, and can be served hot or cold, as a first or main dish of a meal, or as a snack (to be consumed like a beverage). Soups can be used as an ingredient to prepare other meal components and can vary from broths (consomme) to sauces (cream or cheese-based soups).

[0113] The dry and culinary food category generally refers to: (i) cooking aid products such as powders, granules, pastes, concentrated liquid products, including concentrated bouillons, bouillons and bouillon-like products in compressed cubes, tablets or powders, or granules form, sold separately as finished products or as ingredients in products, sauces and recipe mixes (regardless of technology); (ii) meal solution products such as dried soup mixes, dried and freeze-dried soups, including dried instant soups, dried ready-to-cook soups, ready-to-eat meals, meals and a la carte dishes, dried or ambient preparations; and (iii) meal garnish products such as seasonings, marinades, salad dressings, salad toppings, dips, bread crumbs, batter mixes, shelf-stable spreads, barbecue sauces, liquid recipe mixes, including recipe mixes for salads, concentrates, sauces or sauce mixes, whether dried, liquid or frozen, sold as finished products or as an ingredient in products.

[0114] The beverage category generally refers to beverages, beverage mixes and concentrates, including but not limited to carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrated formulations for the preparation of beverages such as sodas, and dry powdered beverage precursor mixes. The beverage category also includes alcoholic beverages, soft drinks, sports drinks, isotonic drinks and hot drinks. Alcoholic beverages include but are not limited to beer, cider / paired wines, FABs, wines and spirits. Soft drinks include but are not limited to carbonated beverages such as cola and non-cola carbonated beverages; fruit juices such as juices, nectars, juice drinks and fruit-flavored beverages; bottled waters including sparkling waters, spring waters and purified / table waters; functional beverages, including sports, nutritional or elixir drinks, which may be carbonated or non-carbonated; concentrates such as ready-to-drink liquid and powder concentrates. Hot or cold beverages include, but are not limited to, coffee or iced coffee, such as brewed, instant and compounded coffee; tea or iced tea, such as black tea, green tea, white tea, oolong tea and flavored tea; and other beverages, including flavored, malted or plant-based powders, granules, blocks or tablets mixed with milk or water.

[0115] The snack food category generally refers to any food that can be a light snack, including, but not limited to, sweet and savory snacks and snack bars. Examples of snack foods include, but are not limited to, fruit snacks, chips / crisps, extruded snacks, tortilla / corn chips, popcorn, pretzels, nuts, and other sweet and savory snacks. Examples of snack bars include, but are not limited to, granola / muesli bars, breakfast bars, energy bars, fruit bars, and other snack bars.

[0116] The baked goods category generally refers to any edible product whose preparation process involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, any baked food product, and any combination thereof.

[0117] The ice cream category generally refers to frozen desserts that contain cream and sugar and flavorings. Examples of ice cream include, but are not limited to, impulse ice cream; takeaway ice cream; frozen yogurt and artisan ice cream; soy, oat, bean (e.g., red and mung bean) and rice-based ice cream.

[0118] The confectionery category generally refers to sweet edible products. Examples of confectionery include, but are not limited to, candy, gelatin, chocolate confectionery, sugar confectionery, gum, etc., and any combination products.

[0119] The meal replacement category generally refers to any food product intended to replace a regular meal, especially for people who are health or fitness conscious. Examples of meal replacements include, but are not limited to, diet and recovery products.

[0120] The ready meal category generally refers to any food that can be served as a meal without extensive preparation or processing. Ready meals include products to which the manufacturer has added recipe "skill" to provide a high degree of readiness, perfection, and convenience. Examples of ready meals include, but are not limited to, canned / preserved, frozen, dried, and refrigerated ready meals; dinner mixes; frozen pizza; refrigerated pizza; and pre-prepared salads.

[0121] The pasta and noodles category includes any pasta and / or noodles, including but not limited to canned, dried and refrigerated / fresh pasta; and plain, instant, refrigerated, frozen and snack noodles.

[0122] The canned / preserved food category includes, but is not limited to, canned / preserved meat and meat products, fish / seafood, vegetables, tomatoes, beans, fruit, ready meals, soups, pasta, and other canned / preserved foods.

[0123] The frozen processed foods category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish / seafood, processed vegetables, meat alternatives, processed potatoes, bakery products, desserts, ready meals, pizza, soups, noodles and other frozen foods.

[0124] The dry packaged food category includes, but is not limited to, cooked rice, dessert mixes, dry ready meals, dry soups, instant soups, dry pasta, plain noodles and instant noodles. The refrigerated packaged food category includes, but is not limited to, refrigerated processed meats, processed fish / seafood products, lunch kits, fresh cut fruit, ready meals, pizza, prepared salads, soups, fresh pasta and noodles.

[0125] The sauces, dressings and condiments category includes, but is not limited to, tomato paste and puree, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickles, and other sauces, dressings and condiments.

[0126] Baby food categories include, but are not limited to, milk or soy-based formulas; as well as prepared, dry and other baby foods.

[0127] Spread categories include, but are not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads and yeast-based spreads.

[0128] The dairy category generally refers to edible products made from mammalian milk. Examples of dairy products include, but are not limited to, drinking dairy products, cheese, yogurt and sour milk drinks, and other dairy products.

[0129] Additional examples of flavored products, particularly food and beverage products or formulations, are provided below. Exemplary ingestible compositions include one or more of confectionery, chocolate confectionery, tablets, count lines, self-lined / soft lines in bags, boxed assortments, standard boxed assortments, twist wrapped miniatures, seasonal chocolates, chocolates with toys, alfafores, other chocolate confectionery, mints, standard mints, power mints, hard candies (boiled sweets), pastilles, gum, jellies and chews, toffee, caramel and nougat, medicated confectionery, lollipops, liquorice, other sugar confectionery, bread, packaged / industrially produced bread, non-packaged / hand-made bread, pastries, cakes, packaged / industrially produced cakes, non-packaged / hand-made cakes, cookies, chocolate coated biscuits, sandwich biscuits, filled biscuits, dry biscuits and crackers, bread substitutes, breakfast cereals, rte cereals, home breakfast cereals, flakes, muesli, other cereals, children's breakfast cereals, hot cereals, ice cream, impulse ice cream, single dairy ice cream, single ice cream, multipack dairy ice cream, multipack ice cream, takeaway ice cream, takeaway dairy ice cream, ice cream desserts, bulk ice cream, takeaway Ices for desserts, Frozen yogurt, Handcrafted ice cream, Dairy products, Milk, Raw / pasteurized milk, Whole raw / pasteurized milk, Semi-skimmed raw / pasteurized milk, Long life / uht milk, Whole fat long life / uht milk, Semi-skimmed long life / uht milk, Fat free long life / uht milk, Goat's milk, Condensed / evaporated milk, Plain condensed / evaporated milk, Flavoured, functional and other condensed milk, Flavoured milk beverages, Dairy only flavoured milk beverages, Flavoured milk beverages with fruit juice, Soy milk, Sour milk beverages, Fermented milk beverages, Coffee cream, Milk powder, Flavoured milk powder beverages, Cream, Cheese, Processed cheese, Spreadable processed cheese, Non spreadable processed cheese, Raw cheese, Spreadable raw cheese, Hard cheese, Packaged hard cheese, Non packaged hard cheese, Yogurt, Plain / natural yogurt, Flavoured yogurt, Yogurt with fruit,Probiotic yoghurt, Drinkable yoghurt, Regular drinking yoghurt, Probiotic drinking yoghurt, Refrigerated and shelf stable desserts, Dairy based desserts, Soy based desserts, Refrigerated snacks, Fromagee frais and quark, Plain Fromagee frais and quark, Flavoured Fromagee frais and quark, Dry Fromagee frais and quark, Sweet and dry snacks, Fruit snacks, Chips / crisps, Extruded snacks, Tortilla / corn chips, Popcorn, Pretzels, Nuts, Other sweet snacks Savory and dry snacks, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, diet products, recovery drinks, ready meals, canned ready meals, frozen ready meals, dried ready meals, refrigerated ready meals, dinner mixes, frozen pizza, refrigerated pizza, soups, canned soups, dried soups, instant soups, refrigerated soups, hot soups, frozen soups, pasta, canned pasta, dried pasta, refrigerated / fresh pasta, noodles, plain noodles, instant noodles, cup / bowl instant noodles, pouch instant noodles, cold Stored noodles, Snack noodles, Canned foods, Canned meat and meat products, Canned fish / seafood, Canned vegetables, Canned tomatoes, Canned beans, Canned fruit, Canned ready meals, Canned soups, Canned pasta, Other canned foods, Frozen foods, Frozen processed red meat, Frozen processed chicken, Frozen processed fish / seafood, Frozen processed vegetables, Frozen meat substitutes, Frozen potatoes, Oven baked potato chips, Other oven baked potato products, Non oven frozen potatoes, Frozen bakery products, Frozen desserts, Frozen ready meals, Frozen pizza, Frozen soups, Frozen noodles, Other frozen foods, Dessert mixes, Dessert ready meals, Dessert mixes Dried Soup, Instant Soup, Dried Pasta, Plain Noodles, Instant Noodles, Cup / Bowl Instant Noodles, Pouch Instant Noodles, Refrigerated Food, Refrigerated Processed Meat, Refrigerated Fish / Seafood Products, Refrigerated Processed Fish, Refrigerated Coated Fish, Refrigerated Smoked Fish, Refrigerated Lunch Kits, Refrigerated Ready Meals, Refrigerated Pizza, Refrigerated Soup, Refrigerated / Fresh Pasta, Refrigerated Noodles, Oils & Fats, Olive Oil, Vegetable & Seed Oils, Cooking Oils, Butter, Margarine, Spreadable Oils & Fats, Functional Spreadable Oils & Fats, Sauces, Dressings & Condiments, Tomato Paste & Puree, Bouillon / Stock Cubes,Included are stock cubes, gravy granules, liquid stocks and fonds, herbs and spices, fermented sauces, soy-based sauces, pasta sauces, wet sauces, dry sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular salad dressings, low-fat salad dressings, vinaigrettes, dips, pickles, other sauces, dressings and condiments, baby foods, milk powders, standard milk powders, follow-on milk powders, infant milk powders, hypoallergenic milk powders, prepared baby foods, dry baby foods, other baby foods, spreads, jams and preserves, honey, chocolate spreads, nut-based spreads and yeast-based spreads. Exemplary ingestible compositions also include confectionery, bakery products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacements, ready meals, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, fats and oils, baby foods or spreads, or mixtures thereof. Exemplary ingestible compositions also include solid or liquid concentrate compositions for preparing breakfast cereals, sweetened drinks, or beverages, ideally allowing for reduced concentrations of traditionally known saccharide or artificial sweeteners.

[0130] Some embodiments provide chewable compositions that may or may not be intended to be swallowed. In some embodiments, the chewable compositions may be gums, chewing gums, sweetened gums, sugarless gums, functional gums, bubble gums, which contain the compounds disclosed and described herein, individually or in combination.

[0131] In some embodiments, the amide compounds disclosed and described herein may be provided individually or in combination in a flavor concentrate formulation suitable for subsequent processing, for example, to produce a ready-to-use (i.e., immediately available) product. By "flavor concentrate formulation" is meant a formulation that needs to be reconstituted with one or more dilution media to become a ready-to-use composition. The term "ready-to-use composition" is used interchangeably herein with "ingestible composition" and refers to any substance that can be taken orally, alone or with another substance, whether or not intended for consumption. In one embodiment, a ready-to-use composition includes a composition that can be directly consumed by a human or animal. A flavor concentrate formulation is typically used by mixing with or diluting with one or more dilution media, such as any consumable or ingestible ingredient or product, to impart or modify one or more flavors to the dilution media. Such a process of use is often referred to as reconstitution. Reconstitution can be carried out in a domestic or industrial environment. For example, a consumer can reconstitute a frozen fruit juice concentrate with water or other aqueous medium in the kitchen to obtain a ready-to-use fruit juice drink. In another example, manufacturers can reconstitute soft drink syrup concentrates with water or other aqueous media on an industrial scale to produce ready-to-use soft drinks.Flavor concentrate formulations have higher concentrations of flavorings or flavor modifiers than ready-to-use compositions, so flavor concentrate formulations are usually not suitable for direct consumption without reconstitution.The use and manufacture of flavor concentrate formulations have many advantages.For example, one advantage is that flavor concentrate formulations can be reconstituted by adding suitable solvents, solids or liquids when used, which reduces weight and volume for transportation.

[0132] A flavored product defined according to any of the above embodiments, in certain embodiments, also includes one or more additional flavor modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a compound that reduces bitterness, a compound that enhances umami, a compound that reduces sourness, a compound that enhances saltiness, a compound that enhances a cooling effect, or any combination of the above.

[0133] In certain embodiments of any aspect and embodiment described herein that refers to a sweetener or flavor concentrate, the sweetener or flavor concentrate is a composition that is specially manufactured for the production of a non-naturally occurring product, e.g., a flavored product, such as a food or beverage product.

[0134] In one embodiment, the flavor concentrate formulation comprises i) the compounds disclosed and described herein, either individually or in combination, ii) a carrier, and iii) optionally at least one adjuvant. The term "carrier" refers to a normally inert accessory substance, such as a solvent, binder, or other inert medium, that is used in combination with the compound and one or more optional adjuvants to form a formulation. For example, water or starch can be the carrier of the flavor concentrate formulation. In some embodiments, the carrier is the same as the dilution medium for reconstituting the flavor concentrate formulation, and in other embodiments, the carrier is different from the dilution medium. The term "carrier" as used herein includes, but is not limited to, ingestible acceptable carriers.

[0135] The term "adjuvant" refers to an additive that complements, stabilizes, maintains or enhances the intended function or effectiveness of an active ingredient, such as a compound of the present invention. In one embodiment, the at least one adjuvant includes one or more flavoring agents. The flavoring agents can be any flavor known to those skilled in the art or consumers, such as the flavors of chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or combinations thereof. In another embodiment, the at least one adjuvant includes one or more sweeteners. The one or more sweeteners can be any of the sweeteners described herein. In another embodiment, the at least one adjuvant includes one or more ingredients selected from the group consisting of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, salts, and combinations thereof. Examples of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, and salts are described in U.S. Pat. No. 6,468,576, the entire contents of which are incorporated herein by reference for all purposes.

[0136] In one embodiment, the flavor concentrate formulation may be in a form selected from the group consisting of liquids, including solutions and suspensions, solids, foams, pastes, gels, creams, and combinations thereof, such as liquids containing a certain amount of solids. In one embodiment, the flavor concentrate formulation is in the form of a liquid, including aqueous and non-aqueous. In some embodiments, the flavor concentrate formulation may be carbonated or non-carbonated.

[0137] The flavor concentrate formulation may further include a freezing point depressant, a nucleating agent, or both as at least one adjuvant. A freezing point depressant is a consumably acceptable compound or agent that can depress the freezing point of a liquid or solvent to which the compound or agent is added. That is, a liquid or solution containing a freezing point depressant has a lower freezing point than a liquid or solvent without the freezing point depressant. A freezing point depressant can not only depress the freezing onset point, but also reduce the water activity of the flavor concentrate formulation. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethyl alcohol, polyols such as glycerol, and combinations thereof. A nucleating agent refers to a consumably acceptable compound or agent that can promote nucleation. The presence of a nucleating agent in the flavor concentrate formulation can improve the texture of the frozen blushes of the frozen slushes by increasing the number of desirable ice crystallization centers, and helps maintain the physical properties and performance of the slushes at freezing temperatures. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

[0138] In one embodiment, the flavor concentrate formulation is formulated to have a low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water in the formulation to the vapor pressure of pure water at the same temperature. In one embodiment, the flavor concentrate formulation has a water activity of less than about 0.85. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.80. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.75.

[0139] In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 2 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 5 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 10 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 15 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 20 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 30 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 40 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 50 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 60 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration up to 100 times the concentration of the compound in the ready-to-use composition.

[0140] The sweetener or flavor concentrate defined according to any of the above-described embodiments may, in certain embodiments, also comprise one or more additional flavor modifying compounds, such as compounds that enhance sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), compounds that reduce bitterness (e.g., eriodictyol, homoeriodictyol, sterubin, and their salts or glycoside derivatives, as well as vanillyl lignans such as matairesinol, and other compounds described in WO 2012 / 146584), compounds that enhance umami (e.g., rubemamine, rubesenamine, (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide, etc.), compounds that reduce sourness and / or licorice flavor, compounds that enhance saltiness, compounds that enhance the cooling effect, or any combination of the above.

[0141] Packaged flavor composition In some further aspects, the present disclosure provides packaged flavoring compositions comprising: (a) an amide compound (according to any of the above embodiments); and (b) at least one bulking agent.

[0142] The packaged flavoring composition can be in any suitable form, including, but not limited to, an amorphous solid, a crystal, a powder, a tablet, a liquid, a cube, a glace or coating, a granular product, an encapsulated form bound to or coated on a carrier / particle, wet or dried, or a combination thereof.

[0143] The packaged flavoring composition may contain further additives known to those skilled in the art. These additives include, but are not limited to, air-forming agents, bulking agents, carriers, fibers, sugar alcohols, oligosaccharides, sugars, intense sweeteners, nutritive sweeteners, flavors, flavor enhancers, flavor stabilizers, acidulants, anti-caking agents, and free-flow agents. Such additives are described by H. Mitchell (H. Mitchell, "Sweeteners and Sugar Alternatives in Food Technology", Blackwell Publishing Ltd, 2006, which is incorporated herein by reference in its entirety). As used herein, the term "flavoring agent" may include flavors known to those skilled in the art, such as natural and artificial flavors. These flavoring agents may be selected from synthetic flavor oils and flavoring aromatics and / or aromatic oils, oleoresins and extracts derived from plants, leaves, flowers, fruits, etc., and combinations thereof. Non-limiting representative flavor oils include spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, mentha oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar oil, nutmeg oil, allspice, sage oil, mace, almond oil, and cassia oil.Also useful flavors are artificial, natural, and synthetic fruit flavors such as vanilla, and citrus oils including lemon, orange, lime, grapefruit, yuzu, and sudachi, and fruit essences including apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, watermelon, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruits, mango, mangosteen, pomegranate, and papaya.Other possible flavours include milk flavours, butter flavours, cheese flavours, cream flavours and yogurt flavours; vanilla flavours; tea or coffee flavours such as green tea flavours, oolong tea flavours, black tea flavours, cocoa flavours, chocolate flavours and coffee flavours; mint flavours such as peppermint flavours, spearmint flavours and peppermint flavours; asafoetida flavours, ajowan flavours, anise flavours, angelica flavours, fennel flavours, allspice flavours, cinnamon flavours, chamomile flavours, mustard flavours, cardamom flavours, caraway flavours, cumin flavours, clove flavours, pepper flavours, coriander flavours, sassafras flavours, savoury flavours, Zanthoxyli Fructus flavor, perilla flavor, juniper berry flavor, ginger flavor, star anise flavor, horseradish flavor, thyme flavor, tarragon flavor, dill flavor, chili flavor, nutmeg flavor, basil flavor, marjoram flavor, rosemary flavor, bay leaf flavor and wasabi flavor; alcohol flavors such as wine flavor, whiskey flavor, brandy flavor, rum flavor, gin flavor and liqueur flavor; floral flavor; and vegetable flavors such as onion flavor, garlic flavor, cabbage flavor, carrot flavor, celery flavor, mushroom flavor and tomato flavor. These flavoring agents can be used in liquid or solid form and can be used individually or mixed. Commonly used flavors include mints, such as peppermint, menthol, spearmint, artificial vanilla, cinnamon derivatives and various fruit flavors, whether used individually or mixed. Flavors, especially mint flavors when used in combination with cooling agents, can also provide breath freshening properties.

[0144] Flavors, especially mint flavors when used in combination with cooling agents, can also provide breath freshening properties. These flavors can be used in liquid or solid form and can be used individually or in admixture. Other useful flavors include aldehydes and esters, such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarbyl acetate, eugenyl formate, p-methylanisole, and the like, can be used. In general, any flavor or food additive can be used, as described in Chemicals Used in Food Processing, publication 1274, pages 63-258, by the National Academy of Sciences. This publication is incorporated herein by reference.

[0145] Further examples of aldehyde flavourings are acetaldehyde (apple), benzaldehyde (cherry, almond), anisaldehyde (licorice, anise), cinnamaldehyde (cinnamon), citral, i.e. α-citral (lemon, lime), neral, i.e. β-citral (lemon, lime), decanal (orange, lemon), ethyl vanillin (vanilla, cream), heliotrope, i.e. piperonal (vanilla, cream), vanillin (vanilla, cream), α-amylcinnamaldehyde (spicy fruity flavours), butyraldehyde (butter, cheese), valeraldehyde (butter, Cheese), citronellal (modified, many varieties), decanal (citrus), aldehyde C-8 (citrus), aldehyde C-9 (citrus), aldehyde C-12 (citrus), 2-ethylbutyraldehyde (berries), hexenal, i.e., trans-2 (berries), tolylaldehyde (cherries, almonds), veratraldehyde (vanilla), 2,6-dimethyl-5-heptenal, i.e., melonal (melon), 2,6-dimethyloctanal (unripe fruits), and 2-dodecenal (citrus, mandarin), cherry, grape, strawberry shortcake, and mixtures thereof. This list of flavorings is merely illustrative and is not intended to limit either the term "flavoring" generally or the scope of the present disclosure.

[0146] In some embodiments, the flavoring agent may be used either in liquid form and / or in dry form. When used in the latter form, suitable drying means such as spray drying of oils may be used. Alternatively, the flavoring agent may be adsorbed on water-soluble substances such as cellulose, starch, sugar, maltodextrin, gum arabic, or may be encapsulated. The actual techniques for preparing such dry forms are well known.

[0147] In some embodiments, the table sweetener can be made to taste like brown sugar, in which case compounds that impart brown notes can be added to the composition to make it taste more similar to brown sugar.

[0148] In some embodiments, flavorants can be used in many different physical forms known in the art to provide an initial burst of flavor and / or a prolonged sensation of flavor, including, but not limited to, free forms such as spray dried, powders, bead forms, encapsulated forms, and mixtures thereof.

[0149] Suitable bulking agents include, but are not limited to, maltodextrin (10DE, 18DE or 5DE), corn syrup solids (20 or 36DE), sucrose, fructose, glucose, invert sugar, sorbitol, xylose, ribulose, mannose, xylitol, mannitol, galactitol, erythritol, maltitol, lactitol, isomalt, maltose, tagatose, lactose, inulin, glycerol, propylene glycol, polyols, polydextrose, fructooligosaccharides, cellulose and cellulose derivatives, and the like, and mixtures thereof. Additionally, granulated sugar (sucrose) or other caloric sweeteners such as crystalline fructose, other carbohydrates, or sugar alcohols can be used as bulking agents since they provide good content uniformity without adding significant calories.

[0150] In one embodiment, the at least one bulking agent can be a bulking agent described in US Pat. No. 8,993,027.

[0151] In one embodiment, the at least one bulking agent can be a bulking agent described in US Pat. No. 6,607,771.

[0152] In one embodiment, the at least one bulking agent can be a bulking agent described in US Pat. No. 6,932,982.

[0153] In some embodiments, the tabletop sweetener composition may further comprise at least one anti-caking agent. As used herein, the terms "anti-caking agent" and "flow agent" refer to any composition that prevents, reduces, inhibits or inhibits at least one sweetener from attaching, binding or contacting another sweetener molecule. Alternatively, an anti-caking agent may refer to any composition that aids in content uniformity and uniform dissolution. Non-limiting examples of anti-caking agents include cream of tartar, calcium silicate, silicon dioxide, microcrystalline cellulose (Avicel, FMC BioPolymer, Philadelphia, Pa.) and tricalcium phosphate. In one embodiment, the anti-caking agent is present in the tabletop sweetener composition in an amount of about 0.001 to about 3% by weight of the tabletop sweetener composition.

[0154] In some embodiments, the sweetener composition of any of the foregoing aspects and embodiments thereof is encapsulated using typical means for encapsulating flavor or fragrance compounds. Non-limiting examples of such techniques include U.S. Patent Application Publication No. 2016 / 0235102, U.S. Patent Application Publication No. 2019 / 0082727, U.S. Patent Application Publication No. 2018 / 0369777, U.S. Patent Application Publication No. 2018 / 0103667, U.S. Patent Application Publication No. 2016 / 0346752, U.S. Patent Application Publication No. 2015 / 0164117, U.S. Patent Application Publication No. 2014 / 0056836, U.S. Patent Application Publication No. 2012 / 0027866, U.S. Patent Application Publication No. 2010 / 0172 No. 945 and U.S. Patent Application Publication No. 2007 / 0128234, as well as U.S. Patent Nos. 7,488,503, 6,416,799, 5,897,897, 5,786,017, 5,603,971, 4,689,235, 4,610,890, 3,704,137, 3,041,180, and 2,809,895. All of the foregoing patent publications and patents are incorporated herein by reference as if set forth in their entirety herein.

[0155] Non-animal protein materials and products made therefrom Products intended to replace or substitute meat or dairy products often rely on a variety of non-animal ingredients, such as fibers and proteins derived from plants, algae or fungi, to mimic the texture and flavor of meat or dairy products. Non-limiting examples of such plant proteins include soy protein, pea protein, kidney bean protein, grain protein, etc. Due to compositional differences between such plant-derived and animal-derived ingredients, such as the lack of glutamate-containing proteins and glutathione, these products may lack the umami or kokumi flavor that consumers traditionally associate with meat or dairy products.

[0156] Thus, in certain aspects, the present disclosure provides a flavored product comprising a plant-derived material (such as a plant-derived starch, a plant-derived protein, or a combination thereof) and an amide compound (according to any of the aspects and embodiments described above). In some further embodiments, the flavored product may comprise any of the combinations of features described above for ingestible compositions containing an amide compound. In some embodiments, the flavored product is a beverage, such as soy milk, almond milk, rice milk, oat milk, a protein drink, a meal replacement beverage, or other similar products. In some other embodiments, the flavored product is a meal replacement, such as a plant-based chicken product (such as a plant-based chicken nugget), a plant-based beef product (such as a plant-based burger), and the like. In some other embodiments, the flavored product is a protein powder, a meal replacement powder, a plant-based creamer for coffee or tea, and the like. In certain further embodiments, any such flavored product contains additional ingredients and has additional features as are typically used in the preparation and / or manufacture of such products. For example, such amide compounds (according to any of the above embodiments) may be combined with other flavors and taste modifiers according to techniques known in the relevant art, and may even be encapsulated in certain materials. Suitable concentrations of the amide compounds are described above.

[0157] In some further embodiments similar to those described above, proteins or starches derived from algal or fungal sources can be used in place of or in combination with vegetable starches or proteins.

[0158] Non-meat protein materials and products made therefrom Certain non-meat animal proteins, such as milk proteins and proteins derived from bone broth, are commonly used in food products and are also sold as the main ingredient of certain protein powders. Such proteins may impart flavors that lack the full umami or richness that consumers may desire. This is particularly true for protein isolates, such as whey protein, collagen protein, casein protein, and the like. For this reason, the present disclosure provides ingestible compositions comprising a non-meat animal protein and an amide compound (according to any of the above aspects and embodiments). The amide compound may be present in any suitable combination according to the embodiments described in the previous section of the present disclosure. In some embodiments, the non-meat animal protein is bone protein, such as collagen protein derived from the bones of animals, such as cows, pigs, donkeys, horses, chickens, ducks, goats, geese, rabbits, lambs, sheep, buffaloes, ostriches, camels, and the like. In some embodiments, the non-meat animal protein is a milk protein, such as whey protein, casein protein, or any combination thereof. The milk may be from any suitable animal, such as cow, donkey, horse, sheep, buffalo, camel, etc.

[0159] The amide compounds may be included in certain food or beverage products that contain animal milk or materials derived from animal milk, including cheese, cheese spread, yogurt, kefir, milk, processed dairy products, cottage cheese, sour cream, butter, etc.

[0160] Preparation method The compounds disclosed herein can be synthesized by the methods described below or modifications of these methods. Modifications of the methodology include, among others, temperatures, solvents, reagents, etc. known to those skilled in the art. Generally, in any of the processes for preparing the compounds disclosed herein, it may be necessary or desirable to protect sensitive or reactive groups on any of the molecules concerned.

[0161] Working Example The following examples are included to further illustrate the present invention. The examples should not be interpreted as specifically limiting the present invention. Variations of these examples within the scope of the claims are within the expertise of those skilled in the art and are considered to be included within the scope of the invention described and claimed herein. The reader will recognize that those skilled in the art, armed with this disclosure and the skills in the art, can prepare and use the present invention without the exhaustive examples.

[0162] Example 1: Synthesis of N,N'-(butane-1,4-diyl)dibenzamide [ka]

[0163] To a solution of 1,4-diaminobutane di-HCl salt (506 mg, 3.141 mmol) in dry DCM (25 mL) was added TEA (1.752 mL, 12.566 mmol) and the solution was cooled in an ice bath. Benzoyl chloride (730 uL, 6.283 mmol) was added and the solution was stirred and allowed to warm to room temperature overnight. The resulting precipitate was collected by vacuum filtration and washed with DCM. The precipitate was recrystallized from EtOH and water. The resulting crystals were collected by vacuum filtration and washed with water. The crystals were dried overnight on a lyophilizer to give N,N'-(butane-1,4-diyl)-dibenzamide as a crystalline white solid (412 mg, 44% yield). 1 H NMR (400MHz, d6-DMSO) δ1.57(m,4H), 3.33(m,4H), 7.43~7.52(m,6H), 7.84(d,J=7.2Hz,4H), 8.47(t,J=5.6Hz,2H). MS 297(MH + ).

[0164] Example 2: Synthesis of (E)-N-(4-(2-methylbut-2-enamido)butyl)benzo[d][1,3]dioxole-5-carboxamide [ka]

[0165] To a solution of (E)-N-(4-aminobutyl)-2-methylbut-2-enamide HCl salt (Example 2a, 154 mg, 0.747 mmol) in anhydrous DCM (5 mL) was added TEA (208 uL, 1.494 mmol) and piperonyl chloride (138 mg, 0.747 mmol). The solution was stirred at room temperature for 16 h and then purified twice by preparative HPLC (ACN / water). The cleanest fractions were concentrated by rotary evaporation. This material was dissolved in EtOH and water and lyophilized overnight to give (E)-N-(4-(2-methylbut-2-enamido)butyl)benzo[d][1,3]dioxole-5-carboxamide as a fluffy white powder (148 mg, 62% yield). 1 H NMR (400MHz, d6-DMSO) δ1.46(br.s,4H), 1.68(dt,J=6.8,1.2Hz,3H), 1.71~1.76(m,3H), 3.10(q,J=6.3Hz,2H), 3.21(q,J=6.3Hz,2H), 6.08(s, 2H), 6.23~6.34(m,1H), 6.97(d,J=8.1Hz,1H), 7.37(d,J=1.7Hz,1H), 7.42(dd,J=8.2,1.8Hz,1H), 7.72(t,J=5.6Hz,1H), 8.28(t,J=8.0Hz,1H). MS 319(MH + ).

[0166] Example 2a: Synthesis of (E)-N-(4-aminobutyl)-2-methylbut-2-enamide HCl salt [ka]

[0167] To a solution of tert-butyl (E)-(4-(2-methylbut-2-enamido)butyl)carbamate (Example 2b, 2.65 g, 9.803 mmol) in MeOH (5 mL) was added 4N HCl in dioxane (6 mL) and the solution was stirred at room temperature for 16 h. The solution was concentrated by rotary evaporation to give (E)-N-(4-aminobutyl)-2-methylbut-2-enamide HCl salt as a yellow oil (2.702 g, quantitative yield). MS 171 (MH + ).

[0168] Example 2b: Synthesis of tert-butyl (E)-(4-(2-methylbut-2-enamido)butyl)carbamate [ka]

[0169] To a solution of tiglic acid (1.595 g, 15.934 mmol) in dry DCM (30 mL) was added TBTU (6.651 g, 20.714 mmol), N-(tert-butoxycarbonyl)-1,4-diaminobutane (2.20 g, 11.685 mmol) and DIEA (5.55 mL, 31.868 mmol). The solution was stirred at room temperature for 16 h and purified by silica gel column chromatography with a 0-100% EtOAc / Hexane gradient. The clean fractions were concentrated by evaporation to give tert-butyl (E)-(4-(2-methylbut-2-enamido)butyl)carbamate as a white powder (2.702 g, 86% yield). 1 H NMR (400MHz, d6-DMSO) δ1.37(s,13H), 1.68(dd,J=6.9,1.2Hz,3H), 1.72(t,J=1.3Hz,3H), 2.89(q,J=6.3 Hz,2H), 3.06(q,J=6.3Hz,2H), 6.27(dq,J=6.9,1.4Hz,1H), 6.78(t,J=5.6Hz,1H), 7.69(t,J=5.7Hz,1H). MS 171(MH + -Boc).

[0170] Example 3: Synthesis of (E)-N-(4-cinnamamidobutyl)-2-methylbut-2-enamide [ka]

[0171] To a solution of tiglic acid (SID 113253, 139 mg, 1.39 mmol) in anhydrous DMF (5 mL) was added TBTU (578 mg, 1.80 mmol), N-(4-aminobutyl)cinnamamide HCl salt (Example 3a, 353 mg, 1.39 mmol) and DIEA (483 uL, 2.77 mmol). The solution was stirred at room temperature for 16 h and then purified by preparative HPLC (ACN / water). The cleanest fractions were concentrated by rotary evaporation. This material was dissolved in EtOH and water and lyophilized overnight to give (E)-N-(4-cinnamamidobutyl)-2-methylbut-2-enamide (SID 28870163) as a fluffy white powder (238 mg, 57% yield). 1 H NMR (400MHz, d6-DMSO) δ1.44(t,J=3.2Hz,4H), 1.69(d,J=6.8Hz,3H), 1.73(s,3H), 3.11(q,J=5.6Hz,2H), 3.19(q,J=6.4Hz,2H), 6. 28(q,J=5.6Hz,1H), 6.63(d,J=16.0Hz,1H), 7.36~7.42(m,4H), 7.56(d,J=6.8Hz,2H), 7.73(t,J=5.2Hz,1H), 8.10(t,J=5.2Hz,1H). MS 301(MH + ).

[0172] Example 3a: Synthesis of N-(4-aminobutyl)cinnamamide HCl salt [ka]

[0173] To a solution of tert-butyl (4-cinnamamidobutyl)carbamate (Example 3b, 1.01 g, 3.18 mmol) in MeOH (5 mL) was added 1.25 M HCl in MeOH (5 mL) and the solution was stirred at room temperature for 16 h. The solution was concentrated by rotary evaporation to give N-(4-aminobutyl)cinnamamide HCl salt (SID 62731519) as a white powder (1.01 g, quantitative yield). 1H NMR (400MHz, d6-DMSO) δ1.48~1.59(m,4H), 2.76~2.81(m,2H), 3.20(q,J=6.4Hz,2H), 6.28(br.s, 1H), 6.67(d,J=16.0Hz,1H), 7.37~7.56(m,4H), 7.56(d,J=6.8Hz,2H), 7.90(m,2H), 8.28(m,1H). MS 219(MH + ).

[0174] Example 3b: Synthesis of tert-butyl (4-cinnamamidobutyl)carbamate [ka]

[0175] To a solution of trans-cinnamic acid (SID 850255, 500 mg, 3.38 mmol) in dry DCM (9 mL) was added TBTU (1.41 g, 4.39 mmol), N-(tert-butoxycarbonyl)-1,4-diaminobutane (635 mg, 3.38 mmol) and DIEA (1.176 mL, 6.75 mmol). The solution was stirred at room temperature for 16 h and purified by silica gel column chromatography with a 0-25% EtOAc / hexanes gradient. The clean fractions were concentrated by rotary evaporation to give tert-butyl (4-cinnamamidobutyl)carbamate as a white powder (1.01 g, 94% yield). 1 H NMR (400MHz, d6-DMSO) δ1.37(s,9H), 1.38~1.43(m,4H), 2.91(q,J=6.0Hz,2H), 3.16(q,J=5.6Hz,2H), 6. 63(d,J=15.6Hz,1H), 6.82(t,J=6.0Hz,1H), 7.35~7.43(m,4H), 7.53~7.56(m,2H), 8.10(t,J=5.6Hz,1H). MS 319(MH + ).

[0176] Example 4: Synthesis of (E)-4-((4-cinnamamidobutyl)amino)-3-methyl-4-oxobut-2-en-1-yl acetate [ka]

[0177] To a solution of (E)-N-(4-cinnamamidobutyl)-4-hydroxy-2-methylbut-2-enamide (32 mg, 0.103 mmol) in dry DCM (4 mL) was added triethylamine (16 uL, 0.114 mmol) and a catalytic amount of DMAP (0.6 mg, 0.005 mmol). The solution was cooled in an ice bath and acetic anhydride (11 uL, 0.114 mmol) was added. The solution was stirred cold for 1.5 hours. The reaction was incomplete by LCMS so additional acetic anhydride (11 uL, 0.114 mmol) was added to the cold solution. The solution was stirred and allowed to warm to room temperature overnight after which LCMS confirmed the disappearance of starting material. The solution was diluted with DCM and washed with saturated NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The crude residue was dissolved in MeOH and purified by preparative HPLC (ACN / water). The cleanest fractions were concentrated by rotary evaporation to give (E)-4-((4-cinnamamidobutyl)amino)-3-methyl-4-oxobut-2-en-1-yl acetate (168) as a white solid (27 mg, 73% yield). 1 H NMR (500MHz, d6-DMSO) δ1.45(m,4H), 1.79(s,3H), 2.03(s,3H), 3.14(dq,J=27.5,6.3Hz,4H), 4.67(d,J=6.4Hz,2H), 6.20(td, J=6.4,1.6Hz,1H), 6.61(d,J=15.8Hz,1H), 7.31~7.46(m,4H), 7.52~7.58(m,2H), 7.95(t,J=5.8Hz,1H), 8.10(t,J=5.7Hz,1H). MS 359(MH + ).

[0178] Example 5 - Compound testing Each of compounds 101-135, as well as compounds 168 and 169 (listed in Table 1), was synthesized according to one of the general procedures described in Examples 1-4 above. The compounds were then tested in an in vitro cell-based assay with cells expressing the T1R umami receptor. Dose-binding curves were recorded and EC50s were determined for enhancement of MSG binding. Calculated EC50 values ​​for certain test compounds are listed in Table 2.

[0179]

Table 2-1

Table 2-2

Claims

1. 1. Use of a flavor modifying compound to enhance the saltiness, umami, or kokumi taste of an ingestible composition, the flavor modifying compound having formula (I): 【Chemistry 1】 [In the formula, R １ is C ６～１４ Aryl or C ４～１２ heteroaryl, each of which is R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: R ２ is C １～１０ Alkyl, C ２～２０ Alkenyl, C ６～１４ Aryl or C １～１２ heteroaryl, and the alkyl and alkenyl groups are each R Ｘ and each of the aryl and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: X １ is a direct bond, C １～６ Alkylene or C ２～６ alkenylene, each of the alkylene and alkenylene groups being R Ｘ and optionally substituted with one or more substituents independently selected from the group consisting of: X ２ and X ３ One of the groups is -NH- or -N(C １～６ alkyl)-, and the other is -O-, -NH- or -N(C １～６ alkyl)-, R Ｘ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ Alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, —O—C(O)—(C ６～１０ aryl), -O-C(O)-(C ６～１０ hydroxyaryl) and —O—C(O)—((C １～６ Alkoxy)-C ６～１０ aryl), R Ｙ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, C １～６ Alkyl and C ２～６ alkenyl, and any adjacent substituents on the aryl or heteroaryl rings can be optionally joined to form a fused carbocyclic or heterocyclic ring having from 5 to 7 members. or a edible acceptable salt thereof.

2. X １ C such as -CH=CH- in E configuration ２～６ The use according to claim 1, which is an alkenylene.

3. X ２ and X ３ The use according to claim 1 or 2, wherein both are -NH-.

4. R １ is -OH, -O-(C １～６ Alkyl) and C １～６ 3. The use according to claim 1 or 2, wherein the phenyl is substituted with one or more substituents independently selected from the group consisting of alkyl, and any two of the substituents on adjacent carbons of the phenyl ring can be optionally joined to form a methylenedioxy fused ring.

5. R １ is -OH, -O-CH ３ , —O—CH ２ -CH ３ The use according to claim 4, wherein the phenyl is substituted 1 to 3 times with any combination thereof.

6. R １ The use according to claim 1 or 2, wherein is unsubstituted phenyl.

7. R ２ C １～１０ Alkyl or C ２～１０ 3. The use according to claim 1 or 2, wherein said alkyl group is alkenyl, each of which is optionally substituted one or two times by -OH.

8. R ２ is unsubstituted C ２～１０ The use according to claim 7, wherein the alkyl group is alkenyl.

9. R ２ The use according to claim 8, wherein is 2-buten-2-yl in either the E or Z configuration.

10. R ２ is substituted with one or two -OH groups such as 4-hydroxybut-2-en-2-yl; ２～１０ 3. The use according to claim 1 or 2, wherein the alkyl group is alkenyl.

11. The use according to claim 1, wherein the taste modifying compound is any one of compounds 101 to 189, or a edible acceptable salt thereof.

12. 12. The use according to claim 11, wherein the flavor modifying compound is any one of compound 102, compound 103, compound 104, compound 105, compound 106, compound 115, compound 119, compound 127, compound 128, compound 129, compound 130, compound 131, compound 132, compound 133, compound 134, compound 135, compound 168, or a edible acceptable salt thereof.

13. 2. The use according to claim 1, for enhancing the saltiness of an ingestible composition.

14. 2. The use according to claim 1, for enhancing the palatability of an ingestible composition.

15. 2. The use according to claim 1, which is for enhancing the kokumi flavor of an ingestible composition.

16. 16. The use of any one of claims 13 to 15, wherein the ingestible composition comprises a salty substance, an umami substance, a kokumi substance, or any combination thereof.

17. 1. A method for enhancing the saltiness, umami, or kokumi taste of an ingestible composition, comprising introducing a flavor modifying compound to the ingestible composition, the flavor modifying compound having formula (I): 【Chemistry 2】 [In the formula, R １ is C ６～１４ Aryl or C ４～１２ heteroaryl, each of which is R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: R ２ is C １～１０ Alkyl, C ２～２０ Alkenyl, C ６～１４ Aryl or C １～１２ heteroaryl, and the alkyl and alkenyl groups are each R Ｘ and each of the aryl and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: X １ is a direct bond, C １～６ Alkylene or C ２～６ alkenylene, each of the alkylene and alkenylene groups being R Ｘ and optionally substituted with one or more substituents independently selected from the group consisting of: X ２ and X ３ One of the groups is -NH- or -N(C １～６ alkyl)-, and the other is -O-, -NH- or -N(C １～６ alkyl)-, R Ｘ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, —O—C(O)—(C ６～１０ aryl), -O-C(O)-(C ６～１０ hydroxyaryl) and —O—C(O)—((C １～６ Alkoxy)-C ６～１０ aryl), R Ｙ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ Alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, C １～６ Alkyl and C ２～６ alkenyl, and any adjacent substituents on the aryl or heteroaryl rings can be optionally joined to form a fused carbocyclic or heterocyclic ring having from 5 to 7 members. or a edible acceptable salt thereof.

18. 1. An ingestible composition comprising: (a) a flavor modifying compound; and (b) a salty tastant, an umami tastant, a kokumi tastant, or any combination thereof, wherein the flavor modifying compound has formula (I): 【Chemistry 3】 [In the formula, R １ is C ６～１４ Aryl or C ４～１２ heteroaryl, each of which is R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: R ２ is C １～１０ Alkyl, C ２～２０ Alkenyl, C ６～１４ Aryl or C １～１２ heteroaryl, and the alkyl and alkenyl groups are each R Ｘ and each of the aryl and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R Ｙ and optionally substituted with one or more substituents independently selected from the group consisting of: X １ is a direct bond, C １～６ Alkylene or C ２～６ alkenylene, each of the alkylene and alkenylene groups being R Ｘ and optionally substituted with one or more substituents independently selected from the group consisting of: X ２ and X ３ One of the groups is -NH- or -N(C １～６ alkyl)-, and the other is -O-, -NH- or -N(C １～６ alkyl)-, R Ｘ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, —O—C(O)—(C ６～１０ aryl), -O-C(O)-(C ６～１０ hydroxyaryl) and —O—C(O)—((C １～６ Alkoxy)-C ６～１０ aryl), R Ｙ is a halogen atom, oxo, -CN, nitro, -OH, -NH ２ , -C(O)H, -OC(O)H, -C(O)-OH, -NH-C(O)H, -C(O)-NH ２ , -O-(C １～６ alkyl), -NH-(C １～６ Alkyl), -N(C １～６ Alkyl) ２ , -C(O)-(C １～６ alkyl), -O-C(O)-(C １～６ alkyl), -NH-C(O)-(C １～６ alkyl), -C(O)-O-(C １～６ alkyl), -C(O)-NH-(C １～６ alkyl), -C(O)-N(C １～６ Alkyl) ２ , -S(O) ２ - (C １～６ alkyl), -O-S(O) ２ - (C １～６ alkyl), -NH-S(O) ２ - (C １～６ alkyl), -S(O) ２ -O-(C １～６ alkyl), -S(O) ２ -NH-(C １～６ alkyl), -S(O) ２ -N(C １～６ Alkyl) ２ , C ３～１０ Cycloalkyl, C ２～１４ Heterocyclyl, C ６～１４ Aryl, C ２～１４ Heteroaryl, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Haloalkyl, C ２～６ Haloalkenyl, C １～６ Haloalkoxy, C ２～６ Haloalkenyloxy, (C １～６ Alkoxy)-C １～６ Alkyl, C １～６ Alkyl and C ２～６ alkenyl, and any adjacent substituents on the aryl or heteroaryl rings can be optionally joined to form a fused carbocyclic or heterocyclic ring having from 5 to 7 members. or a edible acceptable salt thereof.

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