Composition for enhancing cooling effect

Abstract

The present disclosure generally relates to cooling modifying compositions that enhance the cooling effect of cooling compounds (e.g., menthol, piper cubeba alcohol, etc.). In certain forms, the present disclosure provides the use of such coolness modifying compositions for the cooling effect of a cooling compound. In certain other forms, the present disclosure provides compositions (e.g., edible compositions or oral care compositions) comprising a cooling compound (e.g., menthol, piper cubeba alcohol, etc.) and a cooling modifying composition of the present disclosure. In certain embodiments, such compositions are in the form of a food product, a beverage product, or an oral care product (e.g., toothpaste, mouthwash, tooth whitening composition, chewing gum, dentifrice, etc.). In certain other embodiments, such compositions are in the form of a body care product (e.g., a cosmetic product, a skin care product, or a hair care product).

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 367,897, filed on July 7, 2022, and European Application No. 22188235.0, filed on August 2, 2022. The entire contents of these applications are expressly incorporated herein by reference. Technical Field

[0003] The present disclosure generally relates to a coolness-modifying composition that enhances the cooling effect of a cooling compound (e.g., menthol, cubebol, etc.). In some forms, the present disclosure provides the use of such a coolness-modifying composition for the cooling effect of a cooling compound. In some other forms, the present disclosure provides a composition (e.g., an edible composition or an oral care composition) comprising a cooling compound (e.g., menthol, cubebol, etc.) and the coolness-modifying composition of the present disclosure. In certain embodiments, such a composition is in the form of a food product, a beverage product, or an oral care product (e.g., a toothpaste, a mouthwash, a tooth whitening composition, a chewing gum, a dentifrice, etc.). Background Art

[0004] Our sensory system is able to detect subtle changes in ambient temperature thanks to the coordinated efforts of certain thermosensory neurons. Temperature-sensitive proteins of the TRP channel family are often found at sites where thermal stimuli are converted into neuronal activity. Remarkably, the temperature range to which these channels respond covers the entire spectrum of perceived temperatures, from warmth to painful heat and from pleasant coolness to unbearable coldness. Furthermore, many of these channels are receptors for ligands that elicit distinct psychophysical sensations, such as the sensation of heat associated with capsaicin and the sensation of coolness associated with menthol.

[0005] Menthol modulates the TRPM8 receptor in a way that produces a cooling sensation in the mouth. This is why natural products containing menthol, such as peppermint extracts, tend to produce a cooling effect in the mouth. For the same reason, menthol is often used as an ingredient in non-extract flavorings for caries where a cooling effect is desired. Even so, menthol can have a bitter or astringent taste that some users may find objectionable. Therefore, it may be desirable to develop strategies that enhance the cooling effect of menthol, thereby allowing for a reduction in the concentration of menthol and a simultaneous reduction in the undesirable astringency or bitterness.

[0006] Certain synthetic compounds can be used to enhance the cooling effect. These compounds can be used alone or in combination with menthol. However, such compounds often impart some off-flavor similar to menthol. Therefore, there is a continuing need to discover new compositions that enhance the cooling effect of menthol in food, beverages, and oral care products without causing a bitter or astringent taste perception. Summary of the invention

[0007] The present disclosure relates to the discovery that certain compositions demonstrate unexpected effectiveness in enhancing cooling sensations, such as that of menthol, in foods, beverages, or oral care products.

[0008] In the first form, the present disclosure provides a coolness modification composition, the composition comprising a coolness enhancing compound selected from the group consisting of (E / Z)-2-methyl-2-butenal, (E / Z)-2-isopropyl-5-methyl-2-hexenal, and any combination thereof. In some embodiments, the coolness modification composition also comprises a high-intensity sweetener. In some embodiments, the high-intensity sweetener is sucralose, saccharin sodium, or a combination thereof. In some embodiments, the composition comprises a flavoring, such as a mint flavoring.

[0009] In a second aspect, the present disclosure provides the use of (E / Z)-2-methyl-2-butenal for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product comprises a cooling compound, such as menthol or cubebol. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0010] In a third aspect, the present disclosure provides the use of (E / Z)-2-isopropyl-5-methyl-2-hexenal for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product comprises a cooling compound, such as menthol or cubebol. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0011] In a fourth aspect, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound in a flavored product, comprising combining a cooling compound (e.g., menthol, cubebol, or a combination thereof) with (E / Z)-2-methyl-2-butenal in a flavored product. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0012] In a fifth aspect, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound in a flavored product, comprising combining a cooling compound (e.g., menthol, cubebol, or a combination thereof) with (E / Z)-2-isopropyl-5-methyl-2-hexenal in a flavored product. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0013] In a sixth aspect, the present disclosure provides a use of the first aspect of the cooling modifier composition for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product comprises a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0014] In a seventh aspect, the present disclosure provides a method of enhancing the cooling sensation of a flavored product, the method comprising combining the first aspect of the cooling modifier composition with a cooling compound (e.g., menthol, cubebol, or a combination thereof) in the flavored product. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening product.

[0015] In an eighth aspect, the present disclosure provides a flavored product comprising the first aspect of the cooling modifier composition and a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening product.

[0016] In a ninth aspect, the present disclosure provides the use of (E / Z)-2-methyl-2-butenal for enhancing the cooling sensation of a body care product. In some embodiments, the body care product comprises a cooling compound, such as menthol or cubebol. In some embodiments, the body care product is a shampoo, a body wash, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a bronzer.

[0017] In a tenth aspect, the present disclosure provides the use of (E / Z)-2-isopropyl-5-methyl-2-hexenal for enhancing the cooling sensation of a body care product. In some embodiments, the body care product comprises a cooling compound, such as menthol or cubebol. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning agent.

[0018] In an eleventh aspect, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound in a body care product, comprising combining a cooling compound (e.g., menthol, cubebol, or a combination thereof) with (E / Z)-2-methyl-2-butenal in a body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning agent.

[0019] In a twelfth aspect, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound in a body care product, comprising combining a cooling compound (e.g., menthol, cubebol, or a combination thereof) with (E / Z)-2-isopropyl-5-methyl-2-hexenal in a body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning agent.

[0020] In a thirteenth aspect, the present disclosure provides a use of the first aspect of the coolness modifying composition for enhancing the cooling sensation of a body care product. In some embodiments, the body care product comprises a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a sunscreen.

[0021] In a fourteenth aspect, the present disclosure provides a method for enhancing the cooling sensation of a body care product, the method comprising combining the first aspect of the coolness modifying composition with a cooling compound (e.g., menthol, cubebol, or a combination thereof) in a body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning aid.

[0022] In a fifteenth aspect, the present disclosure provides a body care product comprising the coolness-modifying composition of the first aspect and a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning aid.

[0023] Further aspects and embodiments thereof are set forth in the following detailed description, drawings, abstract and claims. DETAILED DESCRIPTION

[0024] The following detailed description sets forth various configurations and embodiments provided herein. This description will be read from the perspective of a person of ordinary skill in the relevant art. Therefore, information known to these persons of ordinary skill is not necessarily included.

[0025] Unless otherwise provided herein, the following terms and phrases have the meanings indicated below. The present disclosure may employ other terms and phrases not expressly defined herein. Such other terms and phrases have the meanings they have in the context of the present disclosure for those of ordinary skill in the art. In some cases, a term or phrase may be defined in the singular or in the plural. In this case, it is to be understood that any term in the singular may include its plural form, and vice versa, unless expressly indicated to the contrary.

[0026] As used herein, "sweetener," "sweet flavoring," "sweet flavor entity," or "sweet compound" refers to a compound or an ingestibly acceptable salt thereof that induces a detectable sweet taste in a subject, such as a compound that activates T1R2 / T1R3 receptors in vitro.

[0027] "Cooling sensation" refers to the sensation of a decrease in ambient temperature produced by an ingestible item in the human body, which is usually achieved through the modulation of the TRPM8 receptor.

[0028] "Cooling compound" refers to a compound that modulates the TRPM8 receptor. In some embodiments of any of the embodiments presented herein, the cooling compound is menthol. Note that, as used herein, "menthol" refers to (-)-menthol. In some embodiments of any of the embodiments presented herein, the cooling compound is cubebol. Non-limiting examples of cooling compounds include N-ethyl-p-menthyl-3-carboxamide, isopulegol, 3-(L-menthoxy)propane-1,2-diol, cis / trans-p-menthane-3,8-diol, 3-(L-menthoxy)-2-methylpropane-1,2-diol, 2-[2-(p-menthane-3-yloxy)ethoxy]ethanol, menthoxyethanol, (1R,2R,4R)-1-(2-hydroxy-4-methylcyclohexyl)ene ketone, (1R,2R,5R)-N-ethyl-5-methyl-2-(prop- 1-en-2-yl)-cyclohexanecarboxamide, N-(3-hydroxy-4-methoxyphenyl)-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethyl-cyclohexane-1-carboxamide, L-menthol lactate, (-)-menthol glycol carbonate, (-)-menthone 1,2-glycerol ketal, D / L-menthone 1,2-glycerol ketal, (-) -Menthyl 1-propylene carbonate, (-)-menthyl 2-propylene carbonate, D / L-menthyl 1-propylene carbonate, D / L-menthyl 2-propylene carbonate, (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide, menthyl acetamido oxalate, (E)-3-benzo[1,3]dioxol-5-yl-N,N-diphenyl-2-acrylamide, 3,4-methylenedioxycinnamic acid, N,N-diphenylamide, N,N-dimethyl( -)-menthyl succinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)phenyl)-menthyl carboxamide, (-)-menthyl pyrrolidone formate, L-phenylephrine (L-phenylephrine)-menthane carboxamide, (1R,2S,5R)-N-(4-(cyanomethyl)-phenyl)menthyl carboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthyl carboxamide, 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5] decan-2-one, (1R,2R,4S)-dihydrocymene alcohol, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl-N,2,3-trimethyl-n-butyramide, 3-(p-menthane-3-carboxamido)ethyl acetate, N-ethyl-2,2-diisopropylbutanamide, N-(1,1-dimethyl-2-hydroxyethyl)-2,2-dimethylbutanamide, N-cyclopentane Propyl-5-methyl-2-isopropyl-cyclohexanecarboxamide, (-)-menthyl acetoacetate, (-)-menthyl succinate, (S)-3-hydroxybutyrate (-)-menthyl glutarate, (-)-menthyl glutarate, 1-[2-hydroxyphenyl]-4-[2-nitrophenyl]-1,2,3,6-tetrahydropyrimidin-2-one, di-(-)-menthyl glutarate, and N-(2-hydroxyethyl)-2,3-dimethyl-2-isopropylbutyramide.

[0029] 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" encompasses a single substituent as well as two or more substituents, and so forth.

[0030] As used herein, "for example," "such as," "such as," or "including" are intended to introduce examples that further illustrate a more general subject matter. Unless otherwise expressly noted, such examples are provided merely to aid in understanding the embodiments shown in the present disclosure and are not meant to be limiting in any way. These phrases also do not indicate any kind of preference for the disclosed embodiments.

[0031] As used herein, "include," "comprising," "containing," and "comprised of" refer to an open group, meaning that the group may include other members in addition to those explicitly stated. For example, the phrase "comprising A" means that A must be present, but other members may also be present. The terms "including," "having," and "composed of" and their grammatical variants have the same meaning. In contrast, "consist of" or "composed of" or "composed of" refer to a closed group. For example, the phrase "consisting of A" means that only A is present.

[0032] As used herein, "E / Z" means that a compound having EZ stereochemistry may exist in the form of the E configuration, the Z configuration, or any mixture of E and Z configuration compounds.

[0033] As used herein, "optionally" means that the subsequently described event may or may not occur. In some embodiments, the optional event does not occur. In some other embodiments, the optional event does occur one or more times.

[0034] As used herein, "or" is to be given its broadest reasonable interpretation and is not limited to an "either / or" construction. Thus, the phrase "comprising A or B" means that A may be present and B may not be present, or B may be present and A may not be present, or both A and B may be present. Furthermore, for example, if A defines a group that may have multiple members (e.g., A 1 and A 2 ) of a class, one or more members of the class can exist at the same time.

[0035] Other terms are defined in other parts of this specification even if not included in this section.

[0036] The present disclosure relates to compounds that enhance a cooling sensation. In certain forms, the present disclosure provides the use of (E / Z)-2-methyl-2-butenal for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product comprises a cooling compound, such as menthol or cubebol. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound (e.g., menthol or cubebol) in a flavored product, comprising combining a cooling compound with (E / Z)-2-methyl-2-butenal in a flavored product. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0037] In certain other forms, the present disclosure provides the use of (E / Z) -2-methyl-2-butenal for enhancing the cooling sensation of a body care product. In some embodiments, the body care product comprises a cooling compound, such as menthol or cubebol. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound (e.g., menthol or cubebol) in a body care product, comprising combining the cooling compound with (E / Z) -2-methyl-2-butenal in the body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning aid.

[0038] As used herein, "(E / Z)-2-methyl-2-butenal" refers to the E or Z configuration of 2-methyl-2-butenal, or any mixture thereof. In some embodiments, (E / Z)-2-methyl-2-butenal is (E)-2-methyl-2-butenal. In some other embodiments, (E / Z)-2-methyl-2-butenal is (Z)-2-methyl-2-butenal. In some embodiments, (E / Z)-2-methyl-2-butenal is a mixture of (E)-2-methyl-2-butenal and (Z)-2-methyl-2-butenal. Suitable weight ratios of E- to Z-configurations range from 100:1 to 1:100, or 50:1 to 1:50, or 20:1 to 1:20, or 10:1 to 1:10, or 5:1 to 1:5, or 3:1 to 1:3, or 2:1 to 1:2. In some embodiments, such mixtures contain more E-configurations than Z-configurations. In some such embodiments, the weight ratio of E- to Z-configurations ranges from 3:2 to 100:1, or 3:2 to 50:1, or 3:2 to 25:1, or 3:2 to 10:1, or 3:2 to 5:1, or 3:2 to 4:1, or 3:2 to 3:1, or 3:2 to 2:1.

[0039] In the form of use or incorporation into a flavored product, the flavored product can be any suitable food product, beverage product, or oral care product, each of which is described in further detail below. As described in more detail below, the flavored product can contain any variety of other components, including flavoring agents, natural and artificial sweeteners, etc.

[0040] In the form of use or incorporation into a body care product, the body care product can be any suitable product suitable for use on hair, skin, etc., which will be described in further detail below. As explained in more detail below, the body care product can contain any kind of other components, such as those commonly contained in body care products.

[0041] (E / Z) -2-methyl-2-butenal can be present in the flavored product or body care product at any suitable concentration. In some embodiments, the concentration of (E / Z) -2-methyl-2-butenal in the flavored product or body care product ranges from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm, based on the total weight of the product.

[0042] In some embodiments, the flavored product also includes a high intensity sweetener. In some such embodiments, the high intensity sweetener is saccharin sodium or sucralose. In some embodiments, the high intensity sweetener is saccharin sodium. Saccharin sodium can be present in any suitable concentration. In some embodiments, based on the gross weight of the product, the concentration range of saccharin sodium is 10ppm to 10000ppm, or 50ppm to 5000ppm, or 100ppm to 3000ppm.

[0043] In some embodiments, the flavored product or body care product comprises menthol, i.e. (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, the concentration of menthol ranges from 10 ppm to 20,000 ppm, or from 50 ppm to 10,000 ppm, or from 100 ppm to 7,000 ppm, or from 500 ppm to 5,000 ppm, based on the total weight of the product.

[0044] In some embodiments, the flavored product or body care product comprises menthol. Menthol can be present in the flavored product or body care product in any suitable ratio and relative concentration (w / w) to (E / Z)-2-methyl-2-butenal. In some embodiments, the w / w ratio of menthol to (E / Z)-2-methyl-2-butenal in the flavored product ranges from 1:1 to 200:1, or from 5:1 to 100:1.

[0045] In some embodiments, the flavored product or body care product comprises cubebol, which is also known as (3S,3aR,3bR,4S,7R,7aR)-octahydro-3,7-dimethyl-4-(1-methylethyl)-1H-cyclopenta[1.3]cyclopropa[1.2]benzene-3-ol. Cubebol can be present in the flavored product or body care product at any suitable concentration. In some embodiments, the concentration of cubebol in the flavored product or body care product ranges from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm, based on the total weight of the product.

[0046] Other compounds and additives can be included in the flavored product or body care product, as described in more detail below. For example, in some embodiments, the flavored product or body care product includes one or both of (E / Z)-2-isopropyl-5-methyl-2-hexenal or any other cooling compound, such as any of the above.

[0047] In certain forms, the present disclosure provides the use of (E / Z)-2-isopropyl-5-methyl-2-hexenal for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product comprises a cooling compound, such as menthol or cubebol. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound (e.g., menthol or cubebol) in a flavored product, comprising combining the cooling compound with (E / Z)-2-isopropyl-5-methyl-2-hexenal in the flavored product. In some embodiments, the flavored product is a food product or a beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, a dentifrice, a chewing gum, or a tooth whitening composition.

[0048] In certain other forms, the present disclosure provides the use of (E / Z) -2-isopropyl-5-methyl-2-hexenal for enhancing the cooling sensation of a body care product. In some embodiments, the body care product comprises a cooling compound, such as menthol or cubebol. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound (e.g., menthol or cubebol) in a body care product, comprising combining a cooling compound with (E / Z) -2-isopropyl-5-methyl-2-hexenal in a body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a sunscreen.

[0049] As used herein, "(E / Z) -2-isopropyl-5-methyl-2-hexenal " refers to the E or Z configuration of 2-isopropyl-5-methyl-2-hexenal, or any mixture thereof. In some embodiments, (E / Z) -2-isopropyl-5-methyl-2-hexenal is (E) -2-isopropyl-5-methyl-2-hexenal. In some other embodiments, (E / Z) -2-isopropyl-5-methyl-2-hexenal is (Z) -2-isopropyl-5-methyl-2-hexenal. In some embodiments, (E / Z) -2-isopropyl-5-methyl-2-hexenal is a mixture of (E) -2-isopropyl-5-methyl-2-hexenal and (Z) -2-isopropyl-5-methyl-2-hexenal. Suitable weight ratios of the E configuration to the Z configuration range from 100:1 to 1:100, or 50:1 to 1:50, or 20:1 to 1:20, or 10:1 to 1:10, or 5:1 to 1:5, or 3:1 to 1:3, or 2:1 to 1:2. In some embodiments, such mixtures contain a greater amount of the E configuration than the Z configuration. In some such embodiments, the weight ratio of the E configuration to the Z configuration ranges from 3:2 to 100:1, or 3:2 to 50:1, or 3:2 to 25:1, or 3:2 to 10:1, or 3:2 to 5:1, or 3:2 to 4:1, or 3:2 to 3:1, or 3:2 to 2:1.

[0050] In the form of use or incorporation into a flavored product, the flavored product can be any suitable food product, beverage product, or oral care product, each of which is described in further detail below. As described in more detail below, the flavored product can contain any variety of other components, including flavoring agents, natural and artificial sweeteners, etc.

[0051] In the form of use or incorporation into a body care product, the body care product can be any suitable product suitable for use on hair, skin, etc., which will be described in further detail below. As explained in more detail below, the body care product can contain any kind of other components, such as those commonly contained in body care products.

[0052] (E / Z) -2-isopropyl-5-methyl-2-hexenal can be present in the flavored product or body care product in any suitable concentration. In some embodiments, the concentration of (E / Z) -2-isopropyl-5-methyl-2-hexenal in the flavored product ranges from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm, based on the total weight of the product.

[0053] In some embodiments, the flavored product comprises a high intensity sweetener. In some such embodiments, the high intensity sweetener is saccharin sodium or sucralose. In some embodiments, the high intensity sweetener is saccharin sodium. Saccharin sodium can be present in any suitable concentration. In some embodiments, based on the gross weight of the product, the concentration range of saccharin sodium is 10ppm to 10000ppm, or 50ppm to 5000ppm, or 100ppm to 3000ppm.

[0054] In some embodiments, the flavored product comprises menthol, i.e. (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, the concentration of menthol ranges from 10 ppm to 20,000 ppm, or from 50 ppm to 10,000 ppm, or from 100 ppm to 7,000 ppm, or from 500 ppm to 5,000 ppm, based on the total weight of the product.

[0055] In some embodiments, the flavored product or body care product comprises menthol. In such embodiments, menthol can be present in the flavored product or body care product in any suitable ratio in a relative concentration (w / w) relative to (E / Z)-2-isopropyl-5-methyl-2-hexenal. In some embodiments, the w / w ratio of menthol to (E / Z)-2-isopropyl-5-methyl-2-hexenal in the flavored product ranges from 1:1 to 200:1, or from 5:1 to 100:1.

[0056] In some embodiments, the flavored product or body care product comprises cubebol, which is also known as (3S,3aR,3bR,4S,7R,7aR)-octahydro-3,7-dimethyl-4-(1-methylethyl)-1H-cyclopenta[1.3]cyclopropa[1.2]benzene-3-ol. Cubebol may be present in the flavored product at any suitable concentration. In some embodiments, the concentration of cubebol in the flavored product ranges from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm, based on the total weight of the product.

[0057] Other compounds and additives can be included in the flavored product or body care product, as described in more detail below. For example, in some embodiments, the flavored product includes one or both of (E / Z)-2-methyl-2-butenal or any other cooling compound, such as any of the above.

[0058] The present disclosure relates to coolness modifying compositions.For the purpose of delivery to or incorporation into a flavored product or body care product, the coolness enhancing compound (according to any of the above embodiments) may be included in any suitable composition, typically a coolness modifying composition.

[0059] In at least a first aspect, the present disclosure provides a coolness-modifying composition comprising a coolness-enhancing compound selected from the group consisting of (E / Z)-2-methyl-2-butenal, (E / Z)-2-isopropyl-5-methyl-2-hexenal, and any combination thereof.

[0060] The coolness modifying composition may comprise any combination of coolness enhancing compounds. In some further such embodiments, the coolness enhancing composition comprises a combination of (E / Z)-2-methyl-2-butenal (according to any of the above embodiments) and (E / Z)-2-isopropyl-5-methyl-2-hexenal (according to any of the above embodiments).

[0061] The coolness modification composition may include any combination of coolness enhancing compounds. In some embodiments, the coolness enhancing composition includes (E / Z) -2-methyl-2-butenal (according to any of the above embodiments). In some other such embodiments, the coolness enhancing composition includes a combination of (E / Z) -2-isopropyl-5-methyl-2-hexenal (according to any of the above embodiments). In some other such embodiments, the coolness enhancing composition includes a combination of (E / Z) -2-methyl-2-butenal (according to any of the above embodiments) and (E / Z) -2-isopropyl-5-methyl-2-hexenal (according to any of the above embodiments).

[0062] In the foregoing embodiments, when the coolness modifying composition comprises a combination of coolness enhancing compounds, the coolness enhancing compounds may be present in any suitable relative amounts. In some embodiments, when the coolness modifying composition comprises a combination of coolness enhancing compounds, the ratio (w / w) of any two coolness enhancing compounds ranges from 1:20 to 20:1, or from 1:10 to 10:1, or from 1:5 to 5:1, or from 1:3 to 3:1, or from 1:2 to 2:1, or from 2:3 to 3:2.

[0063] In addition, the coolness enhancing compound can be present in the coolness modifying composition at any suitable concentration. In embodiments where the coolness modifying composition is a flavored product suitable for human ingestion, the coolness enhancing compound is present at a concentration ranging from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm.

[0064] The coolness-modifying composition may include any number of additional ingredients, such as ingredients commonly used as additives and excipients in food products, beverage products, oral care products (eg, toothpaste, mouthwash, and chewing gum), and body care products.

[0065] In some embodiments, the coolness modification composition includes menthol, i.e. (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, when the coolness modification composition is a flavored product suitable for human intake, menthol is present in a concentration of 10ppm to 20000ppm, or 50ppm to 10000ppm, or 100ppm to 7000ppm, or 500ppm to 5000ppm. In some embodiments, when the coolness modification composition is a body care product suitable for application to human skin or hair, based on the gross weight of the composition, menthol is present in a concentration of 10ppm to 20000ppm, or 50ppm to 10000ppm, or 100ppm to 7000ppm, or 500ppm to 5000ppm. Menthol can be present in any suitable ratio relative to the relative concentration (w / w) of the coolness enhancing compound. In some embodiments, the w / w ratio of menthol to the coolness enhancing compound in the coolness-modifying composition is from 1:1 to 200:1, or from 5:1 to 100:1.

[0066] In some embodiments, the coolness-modifying composition comprises cubebol. Cubebol can be present in the flavored product or body care product at any suitable concentration. In some embodiments, the concentration of cubebol in the flavored product or body care product ranges from 1 ppm to 1000 ppm, or from 5 ppm to 500 ppm, or from 10 ppm to 300 ppm, or from 20 ppm to 200 ppm, based on the total weight of the composition.

[0067] In some embodiments, the coolness modification composition includes other coolants, such as N-ethyl-p-menthyl-3-carboxamide. N-ethyl-p-menthyl-3-carboxamide can be present in any suitable concentration. In some embodiments, when the coolness modification composition is a flavored product suitable for human ingestion, based on the total weight of the composition, N-ethyl-p-menthyl-3-carboxamide is present in a concentration of 1ppm to 20000ppm, or 5ppm to 10000ppm, or 10ppm to 7000ppm, or 50ppm to 5000ppm. In some embodiments, when the coolness modification composition is a body care product suitable for application to human skin or hair, based on the total weight of the composition, N-ethyl-p-menthyl-3-carboxamide is present in a concentration of 1ppm to 20000ppm, or 5ppm to 10000ppm, or 10ppm to 7000ppm, or 50ppm to 5000ppm. N-ethyl-p-menthyl-3-carboxamide can be present in any suitable ratio relative to the relative concentration (w / w) of the coolness enhancing compound. In some embodiments, the w / w ratio of menthol to the coolness enhancing compound in the coolness modifying composition is from 1:1 to 200:1, or from 5:1 to 100:1.

[0068] In some embodiments, the coolness modification composition comprises a cooling compound. In some embodiments, the cooling compound is menthol. In some embodiments, the cooling compound is cubebol. In some embodiments, the cooling compound is N-ethyl-p-menthyl-3-carboxamide. In some embodiments, the cooling compounds are: menthol, cubebol, N-ethyl-p-menthyl-3-carboxamide, isopulegol, 3-(L-menthoxy)propane-1,2-diol, cis / trans-p-menthane-3,8-diol, 3-(L-menthoxy)-2-methylpropane-1,2-diol, 2-[2-(p-menthane-3-yloxy)ethoxy]ethanol, menthoxyethanol, (1R,2R,4R)-1-(2-hydroxy-4-methylcyclohexyl)ethylene ketone, (1R,2R,5R)-N-ethyl cyclohexanecarboxamide, N-(3-hydroxy-4-methoxyphenyl)-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethyl-cyclohexane-1-carboxamide, L-menthol lactate, (-)-menthol glycol carbonate, (-)-menthone 1,2-glycerol ketal, D / L-menthone Menthyl 1,2-glycerol ketal, (-)-menthol 1-propylene carbonate, (-)-menthyl 2-propylene carbonate, D / L-menthyl 1-propylene carbonate, D / L-menthyl 2-propylene carbonate, (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(L-methylethyl)cyclohexanecarboxamide, menthyl acetamido oxalate, (E)-3-benzo[1,3]dioxol-5-yl-N,N-diphenyl-2-acrylamide, 3,4-methylenedioxycinnamic acid, N, N-diphenylamide, N,N-dimethyl (-)-menthyl succinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)phenyl)-menthyl carboxamide, (-)-menthyl pyrrolidone formate, L-phenylephrine p-menthane carboxamide, (1R,2S,5R)-N-(4-(cyanomethyl)-phenyl)menthyl carboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthyl carboxamide, 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5] decan-2-one, (1R,2R,4S)-dihydrocymene alcohol, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl-N,2,3-trimethyl-n-butyramide, ethyl 3-(p-menthane-3-carboxamido)acetate, N-ethyl-2,2-diisopropylbutyramide, N-(1,1-dimethyl-2-hydroxyethyl)-2,2-dimethylbutyramide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexane Alkanecarbonamide, (-)-menthyl acetoacetate, (-)-menthyl succinate, (S)-3-hydroxybutyrate (-)-menthyl glutarate, (-)-menthyl glutarate, 1-[2-hydroxyphenyl]-4-[2-nitrophenyl]-1,2,3,6-tetrahydropyrimidin-2-one, di-(-)-menthyl glutarate, N-(2-hydroxyethyl)-2,3-dimethyl-2-isopropylbutanamide, or any combination thereof.

[0069] In some embodiments, the cooling compound can be a cooling compound described in WO 2021 / 074281, for example, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (propyl) (2-(4-phenyl-1H-imidazol-2-yl) piperidin-1-yl) ketone, (2S)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl) piperidin-1-yl) butan-1-one, (5-methyltetrahydrofuran-3-yl) (2-(4-phenyl-1H-imidazol-2-yl) piperidin-1-yl) ketone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl) piperidin-1-yl)-2-methyl but-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl) piperidin-1-yl) but-2-en-1-one, (E)- 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-((R)-2-(5-p-tolyl)- 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(2,3-dihydrobenzofuran-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-2-yl)-2-(methylthio)propan-1-one -yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-chloro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(4-cyclobutylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one -1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(Benzo[b]thiophene-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(Methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-3-en-1-one, 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H- imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2 -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio) propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one 1-(2-(5-(benzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1-(2-(methylthio)propanoyl) 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)piperidin-1-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(4-phenyl ...2-(Ethylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-3-yl)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylamino)-N-(4-( 2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1, 2-(methylthio)-1-(2-(4-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one -1-one, 2-(methylthio)-1-(2-(4-(5-methylthiophene-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(methylthio)-1-(2-(4-(pyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one )piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2 -yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)isoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-p-tolyl)- 1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2,3-trimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin- 1-yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 2-amino-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, -1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-ethoxy-1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile,2-Mercapto-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, -1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl) 2-Methyl-2-(methylthio)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4 ,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile,4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, 4-(2-(1-(2 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)-1-(piperidin-2-yl)-1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, -2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl 1-((2-(methylthio)propane-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine,1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(4-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(4-hydroxy-2-(5-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-( 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(3-hydroxy-2- 1-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one,1-(2-Hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-Hydroxy-6-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one , 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)methanone 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one,2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H -imidazol-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, or any combination thereof.

[0070] In one embodiment, the cooling compound is (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, )piperidin-1-yl)methanone, (5-methyltetrahydrofuran-3-yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pent-3-en-1-one, (S)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazole -2-yl)piperidin-1-yl)propan-1-one, (tetrahydrofuran-3-yl)(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one 1-(2-(4-(3-chloro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3- 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclobutylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, -(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b]thiophen-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)hexa-3,5-dien-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)pent-4-en-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)pent-4-en-1-one, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, -methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-3-en-1-one,1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, )-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophene-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(benzo[d][1,3]dioxol-5-yl) )-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H 2-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-carbonyl)cyclopropane-1-carbonitrile, 2-(5-methylfuran-2-yl)-1-( 2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(allylthio)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one -1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one,2-(Methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, -(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl) Propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (Methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin- 1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolylisoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolylthiazol-2-yl)piperidin-1-yl)propan-1-one, (2-(5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, )piperidin-1-yl)but-3-en-1-one, 2,2,3-trimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile,2-amino-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin 2-Ethoxy-1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-mercapto-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl) -imidazol-2-yl)piperidin-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one,3-(2-(1-(2-methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2- (5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, methyl 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoate, N-(2-hydroxyethyl)-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, N -(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine,1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5- 1-(2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-1- 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2- 1-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(4-hydroxy-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one,1-(2-Hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinylpropan-1-one -1-one, 1-(4-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl) 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid,4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio) )propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H -imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, or any combination thereof.

[0071] In some embodiments, the coolness modifying composition may include a cooling compound selected from the group consisting of: 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, or a combination thereof.

[0072] In some embodiments, the coolness modifying composition can include a cooling compound selected from the group consisting of: 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, or any combination thereof.

[0073] However, in some embodiments, the coolness-modifying composition may not contain a cooling compound selected from the group consisting of 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, or any combination thereof.

[0074] The present disclosure relates to the coolness modification composition applicable to flavored products.In some embodiments of any of the aforementioned embodiments, the coolness modification composition comprises a sweetener, such as low-calorie, zero-calorie or high-intensity sweetener.Term " high-intensity sweetener " refers to a sweetener sweeter than sucrose, such as at least 10 times sweeter than sucrose, or at least 20 times, or at least 50 times, or at least 100 times, or at least 250 times, or at least 500 times, or at least 750 times, or at least 1000 times, or at least 2500 times, or at least 5000 times, or at least 7500 times, or at least 10000 times.In this article, saying that sweetener is sweeter than sucrose x times refers to the concentration of sucrose weight 1 / x in the aqueous solution of the sweetener to produce a sweetness suitable with sucrose.The example of suitable sweetener is described in more detail below. In some embodiments, the sweetener is sucralose, which refers to 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-pyranogalactoside. In some embodiments, the sweetener is saccharin sodium. Saccharin sodium can be present in any suitable concentration. In some embodiments, the concentration range of saccharin sodium is 10ppm to 10000ppm, or 50ppm to 5000ppm, or 100ppm to 3000ppm. Saccharin sodium can have any suitable relative concentration relative to the coolness enhancing compound. In some embodiments, the ratio (w / w) of saccharin sodium relative to the coolness enhancing compound in the coolness modification composition is 1: 1 to 1000: 1, or 5: 1 to 500: 1.

[0075] In some embodiments, the coolness modification composition comprises glucosylated natural steviol glycosides. As used herein, the term "natural steviol glycosides" refers to steviol glycosides naturally present in plant species Stevia rebaudiana, Stevia phlebophylla or Rubus chingii. Such compounds are glycosides of diterpene steviol. Some non-limiting examples include stevioside, rebaudioside A, rebaudioside C, dulcoside A, etc. As used herein, the term "glucosylated natural steviol glycosides" refers to compounds obtained by enzymatic glucosylation of natural steviol glycosides to increase the degree of glucosylation. As used herein, the term "GSG" can be used interchangeably with "glucosylated natural steviol glycosides".

[0076] In the embodiment where GSG is present, any suitable GSG can be used. Therefore, GSG can have any suitable degree of additional glucosylation, and suitable type of glucosylation. In some embodiments, the GSG used for the coolness modification composition has a glucosylation degree of at least 1.0, which means that at least one mole of glucose has been enzymatically added to the natural steviol glycosides for each mole of natural steviol glycosides. In some other embodiments, the GSG used for the coolness modification composition has a glucosylation degree of at least 1.1, or at least 1.2, or at least 1.3, or at least 1.4, or at least 1.5, or at least 1.6, or at least 1.7, or at least 1.8, or at least 1.9, or at least 2.0, or at least 2.1, or at least 2.2, or at least 2.3, or at least 2.4, or at least 2.5. Glucosylation can be of any suitable type. For example, in some embodiments, the glucose enzymatically added to the natural steviol glycosides is alpha-glucose, beta-glucose, or a combination thereof. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is α-glucose. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is β-glucose. In some embodiments, the glucose enzymatically added to the natural steviol glycoside is a combination of α-glucose and β-glucose. Glucose added by enzymatic glucosylation can be incorporated by any suitable connection. Typically, the added glucose unit is connected to other glucose units already present on the natural steviol glycoside. In some embodiments, the enzymatically added glucose unit is added through a 1,6 bond, meaning that the glucose unit is added through the 1-position of the added glucose unit and the 6-position of the glucose unit already present on the natural steviol glycoside. In some other embodiments, the enzymatically added glucose unit is added through a 1,4 bond. In some other embodiments, the enzymatically added glucose unit is added through a 1,2 bond.

[0077] In embodiments where GSG is present, GSG may be present at any suitable concentration. In some embodiments, GSG is present in the coolness modifying composition at a concentration ranging from 1 ppm to 100 ppm, or from 1 ppm to 50 ppm, or from 1 ppm to 30 ppm, or from 1 ppm to 20 ppm, or from 1 ppm to 10 ppm.

[0078] In some embodiments, the coolness modifying composition comprises 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one, or any suitable salt thereof may be used. In some embodiments, the coolness modifying composition disclosed herein comprises the hydrochloride salt of 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one.

[0079] In some embodiments of any of the foregoing embodiments, the coolness modification composition further comprises a lactone. Any suitable lactone or a combination of multiple lactones can be used. In some embodiments, the lactone is included in a lactone ring having 3 to 8 members in the ring, such as a 3-membered lactone ring, a 4-membered lactone ring, a 5-membered lactone ring, a 6-membered lactone ring, a 7-membered lactone ring, or an 8-membered lactone ring.

[0080] In some embodiments, lactone comprises a 5-membered lactone ring with or without an unsaturated bond (excluding the unsaturation in the oxo substituent on the ring), such as a carbon-carbon double bond. In some embodiments, lactone comprises a 5-membered lactone ring with at least one unsaturated bond (e.g., one carbon-carbon double bond). Non-limiting examples of lactones comprising a 5-membered lactone ring with at least one unsaturated bond include angelica lactone α, angelica lactone β, mentha lactone, 5,5-dimethyl-2 (5H)-furanone, 5-ethyl-2 (5H)-furanone, 5-pentyl-2 (5H)-furanone, 5-hexyl-2 (5H)-furanone, 5-pentyl-2 (3H)-furanone, 4-methyl-3-pentyl-2 (5H)-furanone and 2 (5H)-furanone. In some embodiments, lactone comprises a 5-membered lactone ring without any unsaturated bonds. Non-limiting examples of such lactones include gamma butyrolactone, gamma valerolactone, gamma caprolactone, gamma enantholactone, gamma octalactone, gamma undecalactone, gamma decanolactone, dihydrojasmone lactone, and dihydromentholactone (3,6-dimethyl-hexahydro-2(3H)-benzofuranone). In some embodiments, the lactone is dihydromentholactone.

[0081] In some embodiments, lactone comprises a 6-membered lactone ring with or without unsaturated bonds. In some embodiments, lactone comprises a 6-membered lactone ring with at least one unsaturated bond. Non-limiting examples of lactones comprising a 6-membered lactone ring with at least one unsaturated bond include delta-2-decene lactone, coumarin and 6-methylcoumarin. In some other embodiments, lactone comprises a 6-membered lactone ring without any unsaturated bonds. Non-limiting examples of lactones comprising a 6-membered lactone ring without any unsaturated bonds include decanolactone delta, dodecanolactone delta and cyclohexyl lactone.

[0082] For example, in some embodiments, the coolness modification composition includes caloric sugars, such as sucrose, glucose, fructose (e.g., in the form of high fructose corn syrup), or any combination thereof. In some embodiments, the coolness modification composition includes one or more rebaudioside (e.g., rebaudioside A, rebaudioside D, rebaudioside E, rebaudioside M, or any combination thereof). In general, the concentration of rebaudioside (e.g., rebaudioside A) is about 20 to 50 times higher than the concentration of the above-mentioned sucralose. In some embodiments, the coolness modification composition includes one or more high-intensity artificial sweeteners, such as acesulfame potassium, aspartame, cyclamate, neotame, etc. When any such artificial high-intensity sweeteners are present in the coolness modification composition, their concentrations will be approximately the same as those described for the above-mentioned sucralose. In some other embodiments, the coolness modification composition includes one or more low-calorie carbohydrates or sugar alcohols, such as allulose, xylitol, erythritol, etc. In some other embodiments, the coolness-modifying composition comprises mogroside, for example, as mogroside juice or extract, or as mogroside III, mogroside IV, mogroside V, simoneoside I, isomogroside V, mogroside IV E , Isogroside IV E , isomogroside IV, mogroside III E , 11-oxomogroside V, one or more of the 1,6-α isomer of simonoside I, and any combination thereof. Other mogroside compounds that may be appropriately included in the coolness modifying composition are described in U.S. Patent Application Publication No. 2017 / 0119032.

[0083] Various other sweeteners may also be included in the coolness-modifying composition. Non-limiting examples include D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-arabinose, D-turanose, D-leucrose, isomalt, lactitol, mannitol, sorbitol, maltodextrin, saccharin, alitame, cyclamic acid, tagatose, maltose, galactose, mannose, lactose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated starch hydrolysate (HSH), chemically modified mogrosides (such as glucosylated mogrosides), carrelame and other guanidine-based sweeteners, honey, Jerusalem artichoke syrup, licorice root, monk fruit (fruit, powder or extract), lucuma (fruit, powder or extract), maple sap (including, for example, from sugar maple (Acer syrup)), saccharum, black maple (Acer nigrum), American red maple (Acer rubrum), silver maple (Acersaccharinum), Norway maple (Acer platanoides), ash maple (Acer negundo), bigleaf maple (Acer macrophyllum), roughtooth maple (Acer grandidentatum), Rocky Mountain maple (Acer glabrum), monochromatic maple (Acer mono), maple syrup, maple sugar, walnut sap (including, for example, sap extracted from white walnut (Juglans cinerea), black walnut (Juglans nigra), ghost walnut (Juglans ailatifolia), walnut (Juglans regia), birch sap (including, for example, sap extracted from paper birch (Betula papyrifera), Canada yellow birch (Betula alleghaniensis), mountain birch (Betula lenta), river birch (Betula nigra), gray birch (Betula populifolia), weeping birch (Betula pendula), sycamore sap (e.g., sap extracted from Platanus occidentalis), ironwood sap (e.g., sap extracted from Ostrya virginiana), unrefined cane sugar (mascobado), molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, cane sugar (e.g.,sugar (also known as natural sugar, unrefined sucrose or table sugar), palm sugar, panocha, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, tapioca syrup (also known as tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt powder, beet sugar, cane sugar (cane sugar) sugar), crystallized fruit juice crystals, caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrolates, hydrolyzed canned fruit juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, concentrated grape juice (arrope), syrup, P-4000, acesulfame potassium (also known as acesulfame potassium or ace-K), alitame (also known as aclame), advantame, aspartame, baiyunosdie, neotame, benzamide derivatives, bernadame, canderel, guanidine sweeteners (carrelame) and other guanidine sweeteners, plant fiber, corn sugar, coupling sugar, curculin, cyclamates, cyclocaryoside I, demerara, dextran, dextrin, diastatic malt (diastatic maltmalt), dulcin, sucrol, valzin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glucin, gluconic acid, gluconic acid lactone, glucosamine, glucuronic acid, glycerol, glycine, glycyphillin, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, brown sugar, golden syrup, granulated sugar, gynostemma pentaphyllum, hernandulcin, isomerized liquid sugar, jallab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, amino acid, 6-chloro-kynurenine), galactitol, litesse, ligicane, lycasin, lugduname, guanidine, falernum, mabinin I, mabinin II, maltol, maltisorb, maltodextrin, maltotriol, mannosamine, micraculin, mizuame, mogrosides (including, for example, mogroside IV, mogroside V and neomogroside), mukurozioside, nanosaccharides, sugar), naringin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, nib oligosaccharide, norbu, almond syrup, osladin, pekmez, pentadin, periandrin I, perillaldehyde, perillartine, petphyllum, phenylalanine, phloisosideside I, phlorodizin, phyllodulcin, polyglycitol syrup, polypodoside A, pterocaryoside A, pterocaryoside B, rebiana, refined syrup, rub syrup, rubusoside, selligueain A), shugr, simenoside I, siraitia grosvenorii, soy oligosaccharides, Splenda, SRIoximeV, steviol glycosides, steviol biosides, stevioside, strogins 1, 2 and 4, sucrose, sucrononate, sugar, sodium p-nitrophenylureidopropionate (suosan), phloridzin, super aspartame, tetrasaccharide, threitol, treacle, trilobtain, tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, heptyl heptol, birch syrup, aspartame-acesulfame, assugrin, and combinations or blends of any two or more thereof.

[0084] In certain embodiments, the coolness-modifying composition may include any additional ingredients or combinations of ingredients commonly used in food and beverage products, including but not limited to:

[0085] Acids, including, for example, citric acid, phosphoric acid, ascorbic acid, sodium bisulfate, lactic acid, or tartaric acid;

[0086] bitter ingredients, including, for example, caffeine, quinine, green tea, catechins, polyphenols, robusta green coffee bean extract, green coffee bean extract, potassium chloride, menthol, or proteins (e.g., proteins and protein isolates from plants, algae, or fungi);

[0087] Coloring agents, including, for example, caramel, red #40, yellow #5, yellow #6, blue #1, red #3, purple carrot, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta-carotene, turmeric curcumin, or titanium dioxide;

[0088] preservatives, including, for example, sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfite, sorbic acid, or benzoic acid;

[0089] Antioxidants including, for example, ascorbic acid, calcium disodium EDTA, alpha-tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate;

[0090] Vitamins or functional ingredients, including, for example, resveratrol, Co-Q10, omega 3 fatty acids, theanine, choline chloride (Citcoline), inositol, inulin (chicory root), taurine, ginseng extract, guarana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucuronolactone, inositol, bioflavonoids, echinacea, Ginkgo Biloba, yerba mate, flaxseed oil, Garcinia cambogia peel extract, white tea extract, ribose, milk thistle, thistle extract, grape seed extract, pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), niacinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, cupric 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;

[0091] Clouding agents, including, for example, ester gums, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB);

[0092] buffers, including, for example, sodium citrate, potassium citrate, or saline;

[0093] Flavors, including, for example, propylene glycol, ethanol, glycerin, gum arabic (acacia), maltodextrin, modified corn starch, dextrose, natural flavorings, natural flavorings with other natural flavorings (natural flavoring WONF), natural and artificial flavorings, artificial flavorings, silicon dioxide, magnesium carbonate, or tricalcium phosphate; or

[0094] Starches and stabilizers, including, for example, pectin, xanthan gum, carboxymethyl cellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (acacia gum), inulin, or carrageenan.

[0095] When dissolved or suspended in an aqueous medium, the coolness-modifying composition can have any suitable pH value, such as from a lower pH value to a neutral pH value. Lower and neutral pH values ​​include, but are not limited to, pH values ​​of 1.5 to 9.0, or 2.5 to 8.5; 3.0 to 8.0; 3.5 to 7.5, and 4.0 to 7.

[0096] In certain embodiments, the coolingness modifying composition according to any of the preceding embodiments further comprises one or more additional flavor modifying compounds, such as compounds that enhance sweetness (e.g., hesperidin, naringenin, etc.), compounds that block bitterness, compounds that enhance umami, compounds that reduce sourness or licorice taste, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing compounds.

[0097] In some embodiments, the coolness modification composition disclosed herein comprises one or more sweetness enhancing compounds. Such sweetness enhancing compounds include, but are not limited to, naturally derived compounds, such as hesperidin, naringenin, wild sumac glycosides, glucosylated steviol glycosides, glucuronic acid derived from licorice, aromandin (aromadendrin) -3-O-acetate or other similar flavonols or flavonoids, or synthetic compounds, such as U.S. Patent Nos. 8,541,421; 8,815,956; 9,834,544; 8,592,592; 8,877,922; 9,000,054; and 9,000,051, and any compound described in U.S. Patent Application Publication No. 2017 / 0119032. Some suitable examples include 3-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propyl-propionamide, 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.

[0098] In some further embodiments, the coolness modification composition disclosed herein comprises one or more other umami or kokumi enhancing compounds. Such umami enhancing compounds include, but are not limited to, naturally derived compounds, such as (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl) acrylamide (ericamide), or synthetic compounds, such as any of the compounds described in U.S. Pat. Nos. 8,735,081; 8,124,121; and 8,968,708.

[0099] In some further embodiments, the coolness modification composition disclosed herein comprises one or more coolness enhancing compounds. Such coolness enhancing compounds include, but are not limited to, naturally derived 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. Examples include N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; 2-(4-fluorophenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; 2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 2-((2,3-dihydro-1H-indene-5-yl)- )oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 5-methoxy-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)benzofuran-2-carboxamide; 2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; and any combination thereof.

[0100] In some further embodiments, the coolingness modifying compositions disclosed herein include one or more bitter blocking compounds. Such bitter blocking compounds include, but are not limited to, naturally derived compounds, such as menthol or its analogs, or synthetic compounds, such as any of the compounds described in U.S. Pat. Nos. 8,076,491; 8,445,692; and 9,247,759.

[0101] In some further embodiments, the mouthfeel-modifying compositions disclosed herein comprise one or more mouthfeel-modifying compounds. Such mouthfeel-modifying compounds include, but are not limited to, tannins, cellulosic materials, bamboo powder, and the like.

[0102] In some further embodiments, the coolness modification composition disclosed herein comprises one or more flavor masking compounds. Such flavor masking compounds include, but are not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

[0103] In certain embodiments, the coolness-modifying compositions disclosed herein may include cyclosal. When cyclosal is present, its relative concentration is similar to that of the lactone.

[0104] The coolness modifying composition can be in any suitable form. For example, in some embodiments, the composition is in solid form, such as a solid powder. In some such embodiments, the composition further comprises a solid carrier, such as a carbohydrate. In some other embodiments, the coolness modifying composition is in the form of a liquid solution or suspension. This liquid form can be aqueous or non-aqueous, or it can also be an emulsion, such as an oil-in-water or water-in-oil emulsion. In some embodiments, the coolness modifying composition is incorporated into a flavor product such as a food or beverage product, or an oral care product such as a toothpaste or a mouthwash.

[0105] In some embodiments, the coolness modification composition includes one or more flavorings, or any other additives described in H. Mitchell, SWEETENERS AND SUGAR ALTERNATIVES IN FOOD TECHNOLOGY, Backwell Publishing Ltd., 2006. As used herein, the term "flavoring" includes those flavors known to the technician, such as natural and artificial flavors. These flavorings can be selected from synthetic flavoring oils and flavoring aromatic substances or oils from plants, leaves, flowers, fruits, etc., oleoresins and extracts, and combinations thereof. Non-restrictive representative flavoring oils include spearmint oil, cinnamon oil, sedge oil (methyl salicylate), peppermint oil, Japanese mint oil, clove oil, laurel oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace, bitter almond oil and cassia oil. Also useful flavoring agents are artificial, natural and synthetic fruit flavors, such as vanilla, and citrus oils, including lemon, orange, lime, grapefruit, yazu, 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, papaya, etc. Other potential flavors include milk flavors, butter flavors, cheese flavors, cream flavors and yogurt flavors; vanilla flavors; tea or coffee flavors, such as green tea flavors, oolong tea flavors, tea flavors, cocoa flavors, chocolate flavors and coffee flavors; mint flavors, such as peppermint flavors, spearmint flavors and Japanese mint flavors; spice flavors, such as asafoetida flavors, ajwain flavors, anise flavors, angelica flavors, fennel flavors, allspice flavors, cinnamon flavors, chamomile flavors, mustard flavors, cardamom flavors, coriander flavors, cumin flavors, clove flavors, pepper flavors, cilantro flavors, sassafras flavors Flavors, savory flavors, Sichuan pepper flavors, basil flavors, juniper berry flavors, ginger flavors, star anise flavors, horseradish flavors, thyme flavors, tarragon flavors, dill flavors, green pepper flavors, nutmeg flavors, basil flavors, marjoram flavors, rosemary flavors, bay leaf flavors and mustard (Japanese horseradish) flavors; wine flavors, such as red wine flavors, whiskey flavors, brandy flavors, rum flavors, gin flavors and liqueur flavors; floral flavors; and vegetable flavors, such as onion flavors, garlic flavors, cabbage flavors, carrot flavors, celery flavors, mushroom flavors, and tomato flavors.These flavoring agents can be used in liquid or solid form and can be used alone or in combination. Commonly used flavoring agents include mints, such as peppermint, menthol, spearmint, artificial vanilla, cinnamon derivatives, and various fruit flavors, whether used alone or in combination. Flavoring agents can also provide breath freshening properties, especially mint flavors when used in conjunction with cooling agents.

[0106] Flavoring agents can also provide breath freshening properties, particularly mint flavoring agents when used in combination with cooling agents. These flavoring agents can be used in liquid or solid form and can be used alone or in combination. Other useful flavoring agents include aldehydes and esters, such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarvyl acetate, eugenyl formate, p-methylanisole, etc. Generally, any flavoring agent or food additive can be used, such as those described in Chemicals Used in Food Processing, publication 1274, pages 63-258 by the National Academy of Sciences.

[0107] Other examples of aldehyde flavoring agents include, but are not limited to, acetaldehyde (apple), benzaldehyde (cherry, almond), anisaldehyde (licorice, fennel), cinnamaldehyde (cinnamon), citral, i.e., α-citral (lemon, lime), neral, i.e., β-citral (lemon, lime), decanal (orange, lemon), ethyl vanillin (vanilla, cream), heliotropin, i.e., piperonal (vanilla, cream), vanillin (vanilla, cream), α-amylcinnamaldehyde (spicy fruity flavor), butyraldehyde (butter, cheese), valeraldehyde (butter, cheese), citronella (citronella, lemon), ethyl vanillin (vanilla, cream ... Aldehydes (modified products, various types), decanal (citrus fruits), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), 2-ethylbutyraldehyde (berries), hexenal, i.e., trans-2 (berries), toluylcarboxaldehyde (cherries, almonds), veratraldehyde (vanilla), 2,6-dimethyl-5-heptene, i.e., melonal (melon), 2,6-dimethyloctanal (green fruits), and 2-dodecenal (citrus, oranges), cherry, grape, strawberry shortcake, and mixtures thereof. This list of flavoring agents is exemplary only and is not meant to generally limit the scope of the term "flavoring agent" or the general disclosure.

[0108] In certain embodiments, mint flavoring agents, including menthol and related compounds, or other breath freshening compounds, can be combined with a cooling agent, such as those described in U.S. Pat. Nos. 9,394,287 and 9,732,071. Other examples of cooling agents include 5-methyl-2-(propan-2-yl)cyclohexyl-N-ethyloxamate, N-ethyl-p-menthanecarboxamide (WS-3, also known as menthane-3-carboxylic acid-N-acetamide), N-2,3-trimethyl-2-isopropylbutanamide (WS-23), menthyl lactate ( ML), Menthone Glyceryl Acetal ( MGA), monomenthyl succinate Monomenthyl glutarate, O-menthyl-glycerol, menthyl-N,N-dimethyl succinamate, N-(4-cyanomethylphenyl)-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)-3-p-menthanecarboxamide, menthol and menthol derivatives (e.g. L-menthol, D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol), menthyl ethers (e.g. (1-menthoxy)-1,2-propanediol, (1-menthoxy)-2-methyl-1,2-propanediol, 1-menthyl-methyl ether), menthyl esters (e.g. menthyl formate, menthyl acetate , menthyl isobutyrate, menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthyl pyroglutamate), N-(4-cyanomethylphenyl)-p-menthanecarboxamide, N-(2-(pyridin-2)-yl)ethyl)-3-p-menthanecarboxamide, menthyl carbonate (e.g. menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate, menthyl glycerol carbonate or mixtures thereof), menthanecarboxylic acid amides (e.g. menthanecarboxylic acid-N-ethylamide [WS3], N-α.-(menthane-carbonyl)glycine ethyl ester [WS5], menthanecarboxylic acid-N-(4-cyanophenyl)amide, menthanecarboxylic acid-N-(alkoxyalkyl)amide), menthone and menthone derivatives (e.g. L-menthone glycerol ketal), 2,3-dimethyl-2-(2-propyl)-butyric acid derivatives (e.g. 2,3-dimethyl-2-(2-propyl)-butyric acid-N-methylamide [WS23]), isopulegol or its esters (1-(-)-isopulegol, 1-(-)-isopulegol acetate), menthane derivatives (e.g. p-menthane-3,8-diol), N-(4-cyanomethylphenyl)-p- menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)-3-p-menthanecarboxamide, cubebol or a synthetic or natural mixture containing cubebol, a pyrrolidone derivative of a cycloalkyldione derivative (e.g. 3-methyl-2(1-pyrrolidinyl)-2-cyclopenten-1-one) or a tetrahydropyrimidin-2-one (e.g. icilin or related compounds, such as those described in WO2004 / 026840), N-(4-cyanomethylphenyl)-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)-3-p-menthanecarboxamide, menthyl ethers (e.g. (1-menthoxy) -1,2-propanediol, (1-menthyloxy)-2-methyl-1,2-propanediol), more polar menthyl esters (e.g., menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthyl pyroglutamate), menthyl carbonates (e.g., menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate, menthyl glycerol carbonate), half esters of menthol with dicarboxylic acids or their derivatives (e.g., monomenthyl succinate, monomenthyl glutarate, monomenthyl malonate, O-menthyl succinate-N,N-(dimethyl) acyl amine, O-menthyl succinate amide), 3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridine amide, isopropyl-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine, 3,4,6,7,11b,12-hexahydro-3,3-dimethyl-spiro[13H-dibenzo[a,f]quinolizin-1-3,2'-[1,3]dithiolane]-1(2H)-one, 5,6,10b,11-tetrahydro-3-methyl-spiro[12H-benzo[a]furo[3,4-f]quinolizin-1-2,2'-[1,3]dithiolane]-1(3H)-one. The most preferred cooling compounds are compounds selected from the group consisting of 5-methyl-2-(propan-2-yl)cyclohexyl-N-ethyloxamate, N-ethyl-p-menthanecarboxamide (WS-3, also known as menthane-3-carboxylic acid-N-ethylamide), menthyl lactate (. ML), Menthone Glyceryl Acetal ( MGA), N-(4-cyanomethylphenyl)-p-menthanecarboxamide and (1-menthoxy)-1,2-propanediol.

[0109] In some embodiments of any of the foregoing embodiments, the coolness modifying composition comprises any compound, material, or combination thereof typically included in body care products, such as products suitable for application to human hair or skin.

[0110] In some embodiments, the composition includes one or more fragrances (fragrance). In some embodiments, at least a portion of the fragrance can be encapsulated. Suitable fragrances include complex mixtures of fragrance compounds, which are selected to provide any desired odor. In the context of the present disclosure, the term "fragrance / fragrance" is used synonymously with "spice". Fragrance compounds commonly used in the field of fragrances and suitable for the purpose of the present disclosure are more fully described in S. Arctander's PERFUME FLAVORS AND CHEMICALS, Vols. I and II (1969) and THE MERCK INDEX, 8th edition, Merck & Co., Inc. Rahway, NJ. The term "fragrance compound" covers naturally occurring and synthetic materials known to be used in fragrances, and animal oils. Fragrance compounds can also be any natural oil or extract or chemical compound used in fragrance compositions. Natural oils and extracts are described in Guenther's THE ESSENTIAL OILS 1949, and may include extracts, pressed materials, collected exudates and distillates from any of the following parts of suitable plants: roots, rhizomes, bulbs, corms, stems, bark, heartwood, leaves, flowers, seeds and fruits. Examples of such extracts and distillates include citrus oils such as oils of orange, mandarin, grapefruit, lime or lemon, tree oils such as pine or cedar, herbal oils such as peppermint, thyme, lavender, basil, rosemary, cloves, or flower extracts such as oils of rose, jasmine, lily of the valley or geranium.

[0111] In some embodiments, the body care composition may include one or more ingredients that provide active benefits for hair or skin care, such as compounds with antioxidant activity. For example, in some embodiments, the body care product includes ascorbic acid, also known as vitamin C, which is an essential nutrient with antioxidant activity. In some embodiments, the body care composition includes vitamin E, which refers to eight structurally related antioxidant compounds that exhibit free radical scavenging activity. These compounds include four tocopherol compounds and four tocotrienol compounds. In some embodiments, the body care composition includes resveratrol, which is an antioxidant compound naturally present in grape skin. In some embodiments, the body care composition includes certain oligopeptides, such as acetyl hexapeptide-8 (also known as acetyl hexapeptide-3), which is a synthetic peptide that relaxes wrinkles. A variety of other such compounds may also be included, such as retinol, niacinamide, coenzyme Q10, and various polyphenols, such as flavonoids such as catechins. The amount of these active ingredients can be the same as the typical amount in other body care products.

[0112] The body care compositions disclosed herein may include or be incorporated into any suitable type of vehicle and carrier. Generally speaking, the vehicle or carrier will be a dermatologically acceptable vehicle or carrier. Non-limiting examples of vehicles or carriers include water, glycerol, alcohol, oil, silicon-containing compounds, organosilicon compounds, and waxes. Variations and other suitable carriers will be apparent to those skilled in the art and are suitable for use in the body care compositions disclosed herein. In certain embodiments, the concentrations and combinations of compounds, ingredients, and agents may be selected so that these combinations are chemically compatible and do not form a complex precipitated from a finished body care product.

[0113] The body care compositions disclosed herein can be constructed or formulated into a variety of different forms. Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil-in-water, oil-in-water, silicone-in-water, water-in-silicone, oil-in-water-in-oil, silicone-in-water-in-oil emulsions, etc.), creams, lotions, solutions (e.g., aqueous or hydroalcoholic), anhydrous bases (e.g., lipsticks and powders), gels, facial masks, scrubs, body butters, exfoliating creams, and ointments. Variations and other structures will be apparent to those skilled in the art and are suitable for use in the body care compositions disclosed herein.

[0114] A variety of other ingredients, such as those commonly used in cosmetics, skin care products, or hair care products, can be used. CTFA INTERNATIONAL COSMETIC INGREDIENT DICTIONARY AND HANDBOOK (2004 and 2008) describes a variety of non-limiting ingredients that can be used in the compositions disclosed herein. Examples of these ingredient categories include: fragrances (artificial and natural; such as gluconic acid, phenoxyethanol, and triethanolamine), dyes and pigment ingredients (such as Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C Blue No. 4, D&C Green No. 5, D&C Orange No. 4, D&C Red No. 17, D&C Red No. 33, D&C Violet No. 2, D&C Yellow No. 10, and D&C Yellow No. 11), flavorings or fragrances (such as Stevia, rebaudiana) (sweet leaf) extract and menthol), adsorbents, lubricants, solvents, humectants (including, for example, emollients, humectants, film formers, occlusives and agents that affect the skin's natural moisturizing mechanisms), water-reppelants, UV absorbers (physical and chemical absorbers, such as para-aminobenzoic acid ("PABA") and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (such as B, D, E and K), trace metals (such as zinc, calcium and selenium), anti-irritants (such as steroids and non-steroidal anti-inflammatory drugs), plant extracts (such as aloe vera, Chamomile, cucumber extract, ginkgo biloba, ginseng and rosemary), antimicrobials, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum starch octenylsuccinate, kaolin, corn starch, oat starch, cyclodextrins, talc and zeolite), skin bleaching and whitening agents (e.g., hydroquinone and niacinamide lactate), humectants (e.g., sorbitol, urea, methyl gluceth-20, saccharide isomers isomerate and mannitol), exfoliants, water repellents (e.g., magnesium hydroxide / aluminum hydroxide stearate), skin conditioning agents (e.g., aloe extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyldodecyl oleate, and dipotassium glycyrrhizinate). Further non-limiting examples of some of these ingredients are provided in the following subsections.

[0115] In some embodiments, the body care composition comprises one or more UV absorbers or reflectors. Suitable UV absorbers or reflectors include chemical and physical sunscreen substances. Non-limiting examples of chemical sunscreens include para-aminobenzoic acid (PABA), PABA esters (PABA glyceride, PABA amyl dimethyl ester and PABA octyl dimethyl ester), PABA butyl ester, PABA ethyl ester, PABA ethyl dihydroxypropyl ester, benzophenones (oxybenzone, sulfoisobenzone, benzophenone and benzophenone 1 to 12), cinnamate salts / esters (oxtinoxate, isoamyl p-methoxycinnamate, octyl methoxycinnamate, cinoxate, methyl diisopropyl cinnamate, DEA methoxycinnamate, ethyl diisopropyl cinnamate, glyceryl caprylate dimethoxycinnamate and ethyl methoxycinnamate), cinnamate esters, salicylates / esters (homomethyl salicylate, benzyl salicylate, glycol salicylate, isopropyl benzyl salicylate, etc.), anthranilic acid salts / esters, ethyl urocanate, homosalate, octisalate, dibenzoylmethane derivatives (e.g., avobenzone), octocrylene, octyl triazone, digallocetate, aminobenzoic acid glyceryl ester, 2-hydroxy-1,4-naphthoquinone (lawsone) and dihydroxyacetone, ethylhexyl triazone, dioctyl butyramido triazone, benzalmalonate polysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, diethylamino hydroxybenzoyl hexyl benzoate, bis diethylamino hydroxybenzoyl benzoate, bisbenzoxazolyl phenyl ethylhexyl imino triazine, formotriazole trisiloxane, methylene bisbenzotriazolyl tetramethylbutylphenol, and bis-ethylhexyloxyphenol methoxyphenyl triazine, 4-methylbenzylidene camphor and isopentyl 4-methoxycinnamate. Non-limiting examples of physical sunscreens include kaolin, talc, petrolatum, and metal oxides (eg, titanium dioxide and zinc oxide).

[0116] In some embodiments, the body care composition comprises one or more moisturizing agents. Non-limiting examples of moisturizing agents that can be used include amino acids, chondroitin sulfate, diglycerol, erythritol, fructose, glucose, glycerol, glycerol polymers, ethylene glycol, 1,2,6-hexanetriol, honey, hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolysate, inositol, lactitol, maltitol, maltose, mannitol, natural moisturizing factor, PEG-15 butylene glycol, polyglyceryl sorbitol, salts of pyrrolidone carboxylic acid, PCA potassium, propylene glycol, sugar isomers, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose, urea and xylitol. Other non-limiting examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extract, Aloe barbadensis, aloe barbadensis extract, aloe barbadensis gel, Althaea officinalis extract, Prunus armeniaca kernel oil, arginine, arginine aspartate, Arnica montana extract, aspartic acid, avocado oil, barrier sphingolipids, butanol, beeswax, behenyl alcohol, beta-sitosterol, Betula alba bark extract, Borago officinalis extract, Ruscus aculeatus extract, butylene glycol, Calendula officinalis extract, calendula oil, Euphorbia cernua cerifera wax, canola oil, caprylic / capric triglyceride, elettaria cardamomum oil, copernicia cerifera wax, daucus carota sativa oil, ricinus communis oil, ceramides, ozokerite, ceteareth-5, ceteareth-12, ceteareth-20, cetearyl caprylate, ceteth-20, ceteth-24, cetyl acetate, cetyl caprylate, cetyl palmitate, anthemis nobilis oil, cholesterol, cholesterol esters, cholesteryl hydroxystearate, citric acid, salvia sclarea oil, theobroma cacao butter, coco caprylate / caprate, coconut oil nucifera oil, collagen, collagen amino acids, corn (Zeamays oil, fatty acids, decyl oleate, dimethicone copolyol, dimethiconol, dioctyl adipate, dioctyl succinate, dipentaerythrityl hexacaprylate / hexacaprate, DNA, erythritol, ethoxydiglycol, ethyl linoleate, Eucalyptus globulus oil, Oenothera biennis oil, fatty acids, Geranium maculatum oil, glucosamine, glucosyl glutamate, glutamic acid, glycereth-26, glycerin, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, linoleate, glyceryl myristate, oleate, glyceryl stearate, glyceryl stearate SE, glycine, glycol stearate, glycol stearate SE, glycosaminoglycan, grape (Vitis vinifera) seed oil, hazelnut (Corylus americana (American hazelnut) nut oil, hazelnut (Corylus avellana, European filbert) nut oil, hexylene glycol, hyaluronic acid, mixed safflower (Carthamus tinctorius) oil, hydrogenated castor oil, hydrogenated coconut glycerides, hydrogenated coconut oil, hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm glycerides, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glycerides, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin, hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocetyl stearate, isocetyl stearoyl stearate, isodecyl oleate, isopropyl isostearate, isopropyl lanolin, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl neopentanoate, jasmine (Jasminum officinale oil, jojoba (Buxuschinensis) oil, kelp, Aleurites moluccana nut oil, lactamide MEA, lanolin alcohol polyether-16, lanolin alcohol polyether-10 acetate, lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax, lavender (Lavandula angustifolia, narrow-leaved lavender) oil, lecithin, lemon (Citrus medica limonum) oil, linoleic acid, linolenic acid, macadamia (Macadamiaternifolia oil, maltitol, chamomillarecutita oil, methyl glucose sesquistearate, methylsilanol PCA, mineral oil, mink oil, mortierella oil, myristyl lactate, myristyl myristate, myristyl propionate, neopentyl glycol dicaprylate / dicaprate, octyldodecanol, octyldodecyl myristate, octyldodecyl stearoyl stearate, octyl hydroxystearate, octyl palmitate, octyl salicylate, octyl stearate, oleic acid, olive (Olea europaea) oil, orange (Citrus aurantiumdulcis) oil, palm (Elaeis guineensis) oil, palmitic acid, panthenol, panthenyl ethyl ether, paraffin, PCA, peach (Prunus persica) kernel oil, peanut (Arachis hypogaea) oil, PEG-8C12-18 esters, PEG-15 coconut alkylamine, PEG-150 distearate, PEG-60 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-20 methyl glucose sesquistearate, PEG-40 sorbitan full oleate, PEG-5 soy sterol, PEG-10 soy sterol, PEG-2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate, PEG-100 stearate, PEG-150 stearate, pentadecalactone, peppermint (Mentha piperita oil, Petrolatum, phospholipids, plankton extract, polyamino acid polysaccharide condensate, polyglyceryl-3 diisostearate, polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, potassium myristate, potassium palmitate, propylene glycol, propylene glycol dicaprylate / dicaprate, propylene glycol dicaprylate, propylene glycol dipelargonate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (Oryza sativa) bran oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil, safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) oil officinalis oil, sandalwood (Santalumalbum) oil, serine, serum albumin, sesame (Sesamumindicum) oil, shea butter (Butyrospermumparkii) oil, silk powder, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, sodium palmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan stearate, sorbitol, soybean (Glycine soja) oil, sphingolipids, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxy polydimethylsiloxane, stearoxy trimethylsilane, stearyl alcohol, glycyrrhetinic acid stearyl alcohol, heptanoic acid stearyl alcohol, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond (Prunus amygdalus dulcis oil, synthetic beeswax, tocopheryl acetate, tocopheryl linoleate, tribehenin, tridecyl neopentanoate, tridecyl stearate, triethanolamine, tristearin, urea, vegetable oil, water, wax, wheat (Triticum vulgare) germ oil and ylang-ylang (Canangaodorata) oil.

[0117] In some embodiments, the body care compositions disclosed herein include one or more antioxidants, e.g., in addition to or in combination with those disclosed above. For example, in some embodiments, one or more of these additional antioxidants can be used in combination with ascorbic acid, vitamin E, or a combination thereof. Non-limiting examples of antioxidants that can be used include acetylcysteine, ascorbic acid derivatives such as ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, cysteine, cysteine ​​HCl, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, isoascorbic acid, ascorbic acid esters, ethyl ferulate, ferulic acid, gallic acid esters, hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural plant antioxidants activators such as green tea or grape seed extract, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, quinone, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbitan furfural, thiodiglycol, thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50, tocophersolan, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate, and tris(nonylphenyl) phosphite.

[0118] In some embodiments, the body care composition comprises one or more structurants. In certain embodiments, the structurant helps to provide rheological properties that contribute to stability to the composition. In some embodiments, the structurant can also serve as an emulsifier or surfactant. The non-limiting example of a structurant includes stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, a polyethylene glycol ether of stearyl alcohol with an average of about 1 to about 21 ethylene oxide units, a polyethylene glycol ether of cetyl alcohol with an average of about 1 to about 5 ethylene oxide units, and mixtures thereof.

[0119] In some embodiments, the body care composition comprises one or more emulsifiers. Emulsifiers can reduce the interfacial tension between phases and improve the formulation and stability of the emulsion. Emulsifiers can be nonionic, cationic, anionic and zwitterionic emulsifiers. Non-limiting examples include esters of glycerol, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitan, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, TEA stearate, DEA oleth-3 phosphate, polyethylene glycol 20 sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soya sterol, steareth-2, steareth-20, steareth-20, stearic acid, steareth-3 phosphate ... Ceteth-21, Ceteareth-20, Cetearyl Glucoside, Cetearyl Alcohol, C12-13 Pareth-3, PPG-2 Methyl Glucose Ether Distearate, PPG-5-Ceteth-20, Bis-PEG / PPG-20 / 20 Dimethicone, Ceteth-10, Polysorbate 80, Cetyl Phosphate, Potassium Cetyl Phosphate, Diethanolamine Cetyl Phosphate, Polysorbate 60, Glyceryl Stearate, PEG-100 Stearate, Arachidyl Alcohol, Arachidyl Glucoside, and mixtures thereof.

[0120] In some embodiments, the body care composition comprises one or more silicone-containing compounds. Non-limiting examples of silicone-containing compounds include any member of a polymer product family in which the main chain of the molecule is composed of alternating silicon and oxygen atoms and side groups connected to silicon atoms. By changing the -Si-O- chain length, side groups and crosslinking, silicone can be synthesized into a variety of materials. Their consistency can change from liquid to gel and then to solid. The silicone-containing compounds suitable for use in the body care compositions disclosed herein include but are not limited to those commonly known to those of ordinary skill in the art. Non-limiting examples include silicone oils (e.g., volatile oils and non-volatile oils), gels and solids. In certain embodiments, the silicon-containing compound includes silicone oils, such as polyorganosiloxanes. Non-limiting examples of polyorganosiloxanes include dimethicone, cyclomethicone, polyorganosiloxane-11, phenyl trimethicone, trimethylsilylamino dimethicone, stearoxy trimethylsilane, or mixtures of these materials with other organosiloxane materials in any given ratio to achieve the desired consistency and application characteristics according to the intended application (e.g., for specific areas such as skin, hair or eyes). "Volatile silicone oils" include silicone oils with low heat of vaporization, such as less than about 50 cal / g silicone oil. Non-limiting examples of volatile silicone oils include cyclomethicone; low viscosity dimethicone, such as dimethicone with a viscosity of about 50 cst or less. Other non-limiting volatile silicone oils that can be used in the context of the present invention include those available from manufacturers such as Dow Corning, General Electric and SWS Silicones.

[0121] In some embodiments, the body care composition comprises one or more exfoliants. Exfoliants comprise ingredients that remove dead skin cells from the outer surface of the skin. These agents may act mechanically, chemically, or otherwise. Non-limiting examples of mechanical exfoliants include abrasives, such as pumice, silica, cloth, paper, shells, beads, solid crystals, solid polymers, and the like. Non-limiting examples of chemical exfoliants include acid and enzyme exfoliants. Acids that may be used as exfoliants include, but are not limited to, glycolic acid, lactic acid, citric acid, alpha hydroxy acids, beta hydroxy acids, and the like. Other exfoliants known to those skilled in the art may also be considered for use in the context of the body care composition of the present disclosure.

[0122] In some embodiments, the body care composition comprises one or more essential oils. Essential oils include oils extracted from herbs, flowers, trees and other plants. Such oils are usually present as tiny droplets between plant cells and can be extracted by several methods known to those skilled in the art (e.g., steam distillation, enfleurage, for example, by using fat extraction, maceration, solvent extraction, or mechanical pressing). When these types of oils are exposed to air, they tend to evaporate (e.g., volatile oils). Essential oils are generally insoluble in water, but are soluble in ethanol, ether, fixed oils (plants) and other organic solvents. Essential oils are usually named after the plants from which they are extracted. Non-limiting examples of essential oils that can be used in the body care compositions of the present disclosure include sesame oil, macadamia oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, pimento oil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cedarwood oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper berry oil, lavender oil, lemon oil, lemongrass oil, lime oil, tangerine oil, marjoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, rose otto oil, thyme ... Other essential oils known to those skilled in the art are also contemplated for use in the context of the present invention.

[0123] In some embodiments, the body care composition comprises one or more thickening agents. Thickening agents including thickeners or gelling agents include materials that increase the viscosity of the composition. Thickeners include those that increase the viscosity of the composition without substantially modifying the efficacy of the active ingredient in the composition. Thickeners can also increase the stability of the composition. Commonly used thickeners include hydrogenated polyisobutylene, trihydroxystearin, ammonium acryloyldimethyltaurate / vp copolymers, or combinations thereof. Other non-limiting examples of other thickeners that can be used include carboxylic acid polymers, cross-linked polyacrylate polymers, polyacrylamide polymers, polysaccharides and gums. The example of carboxylic acid polymers includes cross-linked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of these acrylic acid and substituted acrylic acid, wherein the cross-linking agent contains two or more carbon-carbon double bonds and is derived from polyols. The example of commercially available carboxylic acid polymers includes carbomer, which is an acrylic acid homopolymer cross-linked with the allyl ether of sucrose or pentaerythritol.

[0124] Non-limiting examples of cross-linked polyacrylate polymers include cationic and non-ionic polymers. Non-limiting examples are described in U.S. Pat. Nos. 5,100,660; 4,849,484; 4,835,206; 4,628,078; 4,599,379. Non-limiting examples of polyacrylamide polymers (including nonionic polyacrylamide polymers, including substituted branched or unbranched polymers) include polyacrylamide, isoparaffin and laureth-7, acrylamide and substituted acrylamide with acrylic acid and substituted acrylic acid multi-block copolymers. Non-limiting examples of polysaccharides include cellulose, carboxymethyl hydroxyethyl cellulose, cellulose acetate propionate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl hydroxyethyl cellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Another example is an alkyl-substituted cellulose, in which the hydroxyl groups of the cellulose polymer are hydroxyalkylated (e.g., hydroxyethylated or hydroxypropylated) to form a hydroxyalkylated cellulose, which is then substituted with C 10 -C 30 The straight or branched alkyl groups are further modified by ether linkages. Typically these polymers are C 10 -C 30 Ethers of linear or branched alcohols and hydroxyalkyl cellulose. Other useful polysaccharides include scleroglucans, which contain linear chains of (1-3) linked glucose units, wherein every three units have (1-6) linked glucoses. Non-limiting examples of gums that can be used include acacia gum, agar, algin, alginic acid, ammonium alginate, pullulan, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar gum, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

[0125] In some embodiments, the body care composition comprises one or more preservatives. Non-limiting examples of preservatives that can be used in the context of the present invention include quaternary ammonium preservatives such as polyquaternium-1 and benzalkonium halides (e.g., benzalkonium chloride and benzalkonium bromide), parabens (e.g., methylparaben and propylparaben), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof.

[0126] In some embodiments, the body care composition comprises one or more emollients. Non-limiting examples of suitable emollients include the following: (a) silicone oils and modifications thereof, such as linear and cyclic polydimethylsiloxanes; amino, alkyl, alkylaryl and aryl silicone oils; (b) fats and oils, including natural fats and oils, such as jojoba oil, soybean oil, sunflower oil, rice bran oil, avocado oil, almond oil, olive oil, sesame oil, persic oil, castor oil, coconut oil, mink oil; cocoa butter; tallow, lard; hardened oils obtained by hydrogenating the above oils; and synthetic mono-, di- and tri-glycerides, such as myristic acid glyceryl and 2-ethylhexanoic acid glyceryl; (c) (i) waxes such as carnauba wax, spermaceti, beeswax, lanolin and their derivatives; (ii) hydrophobic plant extracts; (iii) hydrocarbons such as liquid paraffin, petrolatum, microcrystalline wax, ozokerite, squalene, pristan and mineral oil; (iv) higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid, isostearic acid, arachidonic acid and polyunsaturated fatty acids (PUFA); (v) higher alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cholesterol and 2-hexyldecanol; (v) esters such as cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, alkyl lactates, alkyl citrates and alkyl tartaric acid esters; (i) essential oils and extracts thereof, for example, mint oil, jasmine oil, camphor oil, white cedar oil, bitter orange peel oil, rye (ryu) oil, turpentine oil, cinnamon oil, bergamot oil, satsuma oil, calamus oil, pine oil, lavender oil, laurel oil, clove oil, hiba oil, eucalyptus oil, lemon oil, lemon oil, borage (starflower) oil, thyme oil, peppermint oil, rose oil, sage oil, sesame oil, ginger oil, basil oil, juniper oil, lemongrass oil, rosemary oil, rosewood oil, avocado oil, grape oil, grapeseed oil, myrrh oil, cucumber oil, watercress oil, calendula oil, elderflower oil, geranium oil, linden flower oil, amaranth oil, algae oil, ginkgo oil, ginseng oil, carrot oil, guarana oil, tea tree oil, jojoba oil, comfrey oil, oatmeal oil, cocoa butter, neroli oil, vanilla oil, green tea oil, pennyroyal oil royal) oil, aloe oil, menthol, eugenol, citral, citronella oil, borneol, linalool, geraniol, evening primrose oil, camphor oil, thymol, spirantol oil, penene oil, limonene oil and terpenoid oils; (j) lipids such as cholesterol, ceramides, sucrose esters and pseudoceramides;(k) vitamins, minerals and skin nutrients, such as vitamin A, E and K; vitamin alkyl esters, including vitamin C alkyl esters; magnesium, calcium and milk; (l) sunscreens, such as octyl methoxycinnamate and butyl methoxybenzoylmethane; (l) phospholipids; (m) polyhydroxy alcohols, such as glycerol, propylene glycol, etc.; and polyols, such as polyethylene glycol; (n) anti-aging compounds, such as alpha hydroxy acids, beta hydroxy acids; and (o) mixtures of any of the foregoing components, etc.;

[0127] In some embodiments, the body care composition comprises one or more tackifiers. The non-limiting example of suitable tackifier comprises aliphatic hydrocarbon resin, aromatic modified aliphatic hydrocarbon resin, hydrogenated polycyclopentadiene resin, polycyclopentadiene resin, rosin, rosin ester, wood rosin, wood rosin ester, tall oil rosin, tall oil rosin ester, polyterpenes, aromatic modified polyterpenes, terpene phenolic resin, aromatic modified hydrogenated polycyclopentadiene resin, hydrogenated aliphatic resin, hydrogenated aliphatic aromatic resin, hydrogenated terpenes and modified terpenes, hydrogenated rosin acid, hydrogenated rosin ester, polyisoprene, partially or completely hydrogenated polyisoprene, polybutene diene, partially or completely hydrogenated polybutene diene etc. Tackifier can be completely or partially hydrogenated. Tackifier can also be non-polar, and non-polar means that tackifier does not contain the monomer with polar group substantially. In some embodiments, there is no polar group. In some embodiments, the polar group is present in an amount of up to about 5 weight percent, preferably up to about 2 weight percent, and more preferably up to about 0.5 weight percent.

[0128] In some embodiments, the body care composition comprises one or more colorants, such as pigments or dyes. Examples of suitable pigments include, but are not limited to, inorganic pigments, organic pigments, lakes, pearlescent pigments, iridescent or optically variable pigments, and mixtures thereof. The term "pigment" is understood to refer to inorganic or organic, white or colored particles. Within the scope of the present invention, the pigment may be optionally surface treated, but is not limited to, treatments such as silicones, perfluorinated compounds, lecithin, and amino acids.

[0129] In some embodiments, the body care compositions include one or more surfactants.Surfactants useful as the surfactant component in the compositions disclosed herein include nonionic, anionic, cationic, and amphoteric (zwitterionic) surfactants and may be used in combination with one another.

[0130] In some embodiments, the body care composition comprises one or more pH adjusting agents. pH adjusting agents include inorganic and organic acids and bases, particularly ammonia, citric acid, phosphoric acid, acetic acid, sodium hydroxide, lactic acid, levulinic acid, glycolic acid, tartaric acid, malic acid, pyrrolidonecarboxylic acid (PCA), succinic acid, citric acid, glutamic acid, 2-amino-2-methyl-1-propanol (AMP) and triethanolamine (TEA).

[0131] In some embodiments, the body care composition comprises one or more reducing agents. Suitable reducing agents include, but are not limited to, thiourea, salts (e.g., sodium salts) of thiosulfates, sulfites, bisulfites, metabisulfites, borohydrides, and hypophosphites, ascorbic acid and its salts, esters, and derivatives (e.g., ascorbyl palmitate and ascorbic acid polypeptides), and tocopherol and its salts, esters, and derivatives (e.g., tocopherol acetate). Other well-known reducing agents, such as those listed in the INCI manual, may also be used.

[0132] In some embodiments, the body care composition comprises one or more fragrances. Non-limiting examples of suitable fragrances include natural oils or naturally derived materials, and synthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones, esters, lactones, ethers, nitriles, and polyfunctional compounds. Non-limiting examples of natural oils include the following: basil oil (Ocimum basilicum), bay oil (Pimento acris), bee balm (Monarda didyma, American peppermint) oil, bergamot oil (Citrus aurantium bergamia), cardamom oil (Elettaria cardamomum), cedarwood oil (Cedrus atlantica), chamomile oil (Anthemis nobilis), cinnamon (Cinnamomum cassia), lemongrass oil (Cymbopogon nardus), clary sage oil (Salvia sclarea), clove oil (Eugenia caryophyllus), clove leaf (Eufenia caryophyllus), sedge oil (Cyperus esculentus), cypress (Cupressus sempervirens, Mediterranean cypress) oil, lemon eucalyptus (Eucalyptus sempervirens, Mediterranean cypress) oil. citriodora oil, Geranium maculatum oil, Ginger (Zingiber officinale) oil, Grapefruit (Citrus grandis) oil, Hazelnut (Corylus avellana) nut oil, Jasmine (Jasminum officinale) oil, Juniper (Juniperus communis) oil, Juniper oxycedrus tar, Juniperus virginiana oil, Kiwi (Actinidia chinensis) water, Lavandin (Lavandula hybrida, lavender) oil, Lavandula angustifolia oil, Lavandula angustifolia water, Lemon (Citrusmedica limonum) oil, Lemongrass (Cymbopogon schoenanthus (Cymbopogon schoenanthus) oil, Citrus aurantifolia (Citrus aurantifolia) oil, Tilia cordata (Tilia linden) oil, Tilia cordata (Tilia cordata) water, Citrus nobilis (Citrus nobilisGuangxi Shagan (Orange) Oil, Nutmeg (Myristica fragrans) Oil, Orange (Citrus aurantiumdulcis) Flower Oil, Orange (Citrus aurantium dulcis) Oil, Orange (Citrus aurantium dulcis) Water, Patchouli (Pogostemon cablin) Oil, Peppermint (Menthe piperita) Oil, Peppermint (Menthe peperita) Water, Rosemary (Rosmarinus officinalis) Oil, Rose Oil, Rose (Rosa damascena, Damascus Rose) Extract, Rose (Rosa multiflora, Rose) Extract, Rosewood (Aniba rosaeodora) Extract, Sage (Salvia officinalis) Oil, Sandalwood (Santalum album) Oil, Spearmint (Menthe viridis) Oil, Tea Tree (Melaleuca alternifolia) Oil and Ylang-ylang (Cananga odorata) Oil. Some non-limiting examples of synthetic hydrocarbon fragrances include caryophyllene, β-farnesene, limonene, α-pinene and β-pinene. Some non-limiting examples of synthetic alcohol fragrances include bacdanol, citronellol, linalool, phenylethyl alcohol and α-terpineol (R.dbd.H). Some non-limiting examples of synthetic aldehyde fragrances include 2-methylundecane, citral, hexylcinnamaldehyde, isocitral, lily of the valley aldehyde and 10-undecene aldehyde. Some non-limiting examples of synthetic ketone fragrances include cashmeran, α-ionone, isocyclemone E, koavone, musk ketone and tonafol. Some non-limiting examples of synthetic ester fragrances include benzyl acetate, 4-tert-butylcyclohexyl acetate (cis and trans), cedryl acetate, cyclacet acetate, isobornyl acetate, and alpha-terpinyl acetate (R = acetyl). Some non-limiting examples of synthetic lactone fragrances include coumarin, jasmine lactone, musk lactone, and peach aldehyde. Some non-limiting examples of synthetic ether fragrances include ambroxan, anther, and galaxol. Some non-limiting examples of synthetic nitrile fragrances include cinnamonitrile and geranyl nitrile. Finally, some non-limiting examples of synthetic multifunctional fragrances include amyl salicylate, isoeugenol, hedione, heliotropine, lyral, and vanillin. ,

[0133] In some embodiments, the body care composition comprises one or more foaming agents. Foaming agents include, for example, sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglycerol sulfonate, sodium α-olefin sulfonate, N-acyl amino acid salts such as N-acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerol fatty acid ester, fatty acid diethanolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, and polyoxyethylene fatty acid ester. These foaming agents can be used alone or in combination of two or more.

[0134] In some embodiments, the body care composition comprises one or more tanning agents. Suitable tanning agents include, but are not limited to, α-hydroxyaldehydes and ketones, glyceraldehyde and related alcohol aldehydes, various indoles, imidazoles and their derivatives, and various approved pigmentation agents. Other suitable tanning agents include, but are not limited to, methylglyoxal, glyceraldehyde, erythrulose, alloxan, 2,3-dihydroxysuccinic dialdehyde, 2,3-dimethoxysuccinic dialdehyde, 2-amino-3-hydroxy-succinic dialdehyde, and 2-benzylamino-3-hydroxysuccinic dialdehyde.

[0135] In some embodiments, the body care composition comprises one or more astringents. Suitable astringents include, but are not limited to, aluminum citrate, aluminum lactate, birch extract, coffee extract, evening primrose extract, grape extract, henna extract, ivy extract, lemon extract, witch hazel extract, ammonium and potassium alum, aluminum triphosphate, aluminum glycinate and aluminum phenol sulfate, alcloxa, aldioxa, aluminum stearate, aluminum sulfate and aluminum citrate, sodium aluminum phosphate, sodium alum, sodium aluminum chlorohydroxy lactate, calcium lactate, calcium chloride, calcium sulfate hydrate, sodium aluminum lactate, zinc acetate, zinc chloride, zinc sulfate, zinc lactate, zeolite zinc, zinc phenolsulfonate, and combinations thereof.

[0136] In some embodiments, the body care composition comprises one or more antiseptics. Suitable antiseptics include, but are not limited to, methyl, ethyl, propyl or butyl parabens, phenoxyethanol, o-phenylphenol, dehydroacetic acid or its salts, p-cresol, m-cresol, o-chloro-m-xylenol, peppermint oil, Echinacea, bloodroot, cayenne, tea tree oil, wild bergamot, chaparral, stinging nettle, laurel, myrrh, garcinia bark, toothache tree, calendula, chamomile, mupirocin, neomycin sulfate, bacitracin, polymyxin B, 1-ofloxacin, tetracyclines (chlortetracycline hydrochloride, oxytetracycline hydrochloride and tetrachcycline hydrochloride) hydrochoride), clindamycin phosphate, gentamicin sulfate, benzalkonium chloride, benzethonium chloride, hexylresorcinol, methylbenzethonium chloride, phenol, quaternary ammonium compounds, triclocarban, triclosan, and tea tree oil.

[0137] In some embodiments, the body care composition comprises one or more deodorants or antiperspirants. Suitable antiperspirants and deodorants include, but are not limited to, zinc salts such as zinc sulfate and zinc chloride, glycinates such as aluminum zirconium glycinate, aluminum chlorohydrate, aluminum zirconium tetrachloride hydrate, zinc carbonate, o-phenylphenol, and quaternary ammonium compounds such as dimethylbenzylammonium chloride and hexamethonium chloride.

[0138] In some embodiments, the body care composition comprises one or more lightening agents. Examples of lightening agents include, but are not limited to, hydroquinone, kojic acid, licorice or its derivatives, ascorbic acid or its derivatives, arbutin, bearberry extract, Glycyrrhiza glabra and its derivatives, Chlorella vulgaris extract, Perilla extract, coconut extract, and / or other decolorizing agents.

[0139] In some embodiments, the body care composition comprises one or more biocides. Examples of biocides include, but are not limited to, triclosan, 3,4,4'-triclocarbanilide (triclocarban); 3,4,4'-trifluoromethyl-4,4'-diclocarbanilide (chloroflocarban); 5-chloro-2-methyl-4-isothiazolin-3-one; iodopropynyl butylcarbamate; 8-hydroxyquinoline; 8-hydroxyquinoline citrate; 8-hydroxyquinoline sulfate; 4-chloro-3,5-dimethylphenol (chloroxylenol); 2-bromo-2-nitropropane-1,3-diol; diazolidinyl urea; butoconazole; nystatin; terconazole; nitrofurantoin; phenazopyridine; acyclovir; clotrimazole; imazole); chloroxylenol; chlorhexidine; miconazole; terconazole; butyl paraben; ethyl paraben; methyl paraben; methylchloroisothiazoline; methylisothiazoline; a mixture of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 3-iodo-2-propynylbutylcarbamate; hydroxyquinoline; EDTA (ethylenediaminetetraacetic acid); tetrasodium EDTA; parabens; alkylpyridine compounds; cocophosphatidyl PG-dimethylammonium chloride; chlorhexidine gluconate; chlorhexidine digluconate; chlorhexidine acetate; chlorhexidine isethionate; chlorhexidine hydrochloride; benzalkonium chloride; benzethonium chloride; polyhexamethylene biguanide; and mixtures thereof.

[0140] Other ingredients commonly used in body care compositions such as skin care or hair care products may also be included.

[0141] The present disclosure relates to flavored products and related uses. In at least another form, the present disclosure provides the use of the coolness modifying composition of the aforementioned form and its embodiment to enhance the cooling sensation of the flavored product, such as enhancing the coolingness of a cooling compound (e.g., menthol, cubebol, or other cooling compounds described above) in the flavored product. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a flavored product, the method comprising introducing the coolness modifying composition of the aforementioned form and its embodiment into the flavored product.

[0142] In connection with these forms, the flavored product can be any flavored product according to the forms and embodiments set forth below. In some embodiments, the flavored product is a beverage product, such as an enhanced sparkling beverage, cola, lemon-lime flavored sparkling beverage, orange flavored sparkling beverage, grape flavored sparkling beverage, strawberry flavored sparkling beverage, pineapple flavored sparkling beverage, ginger ale, root beer, juice, fruit-flavored juice, juice beverage, honeydew beverage, vegetable juice, vegetable flavored juice, sports drink, energy drink, fortified water beverage, vitamin-fortified water, near water beverage, coconut water, tea beverage, coffee, cocoa beverage, beverage containing milk ingredients, beverage containing cereal extract and smoothie. In some other embodiments, the flavored product is a food product, such as packaged food, canned food, meal replacement product, etc. In some embodiments, the flavored product is an oral care product, such as a toothpaste, a mouthwash, or a tooth whitening composition, such as a composition disclosed in U.S. Patent Application Publication No. 2019 / 0167545, which is incorporated herein by reference.

[0143] The flavored product can be in any suitable physical form. For example, in some embodiments, the flavored composition can be in solid form, such as a powder. In further embodiments of this type, the flavored product is a tooth powder, such as a tooth powder for whitening teeth, removing stains (such as tobacco stains), etc. In some other embodiments, the flavored product can be a paste or slurry, such as a toothpaste. In some other embodiments, the flavored product can be in the form of a cream or gel, such as a tooth gel, a skin cream, or a tooth cream. In some other embodiments, the flavored product can be a liquid suspension or solution, such as with an aqueous carrier. In some embodiments, the flavored product can be in the form of an emulsion, such as a microemulsion or a nanoemulsion, in which a surfactant, an emulsifier, etc. can be present. In some embodiments, the flavored product is a personal care product, such as a product for application to skin, face, lips, gums, oral cavity, etc. Such personal products can be used for any suitable purposes, such as skin whitening, tooth whitening, etc.

[0144] In certain forms, the present disclosure provides a flavored product comprising any composition of the foregoing forms 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.

[0145] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of enhanced 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, juice, fruit-flavored juice, fruit drinks, nectar drinks, vegetable juice, vegetable-flavored juice, sports drinks, energy drinks, fortified water drinks, vitamin-fortified water, near water drinks, coconut water, tea drinks, coffee, cocoa drinks, beverages containing milk ingredients, beverages containing cereal extracts, and smoothies. In some embodiments, the beverage may be a soft drink.

[0146] In some embodiments, the flavored product is an oral care product. By "oral care product," it is meant a personal care product or other product that is not intentionally swallowed for the purpose of systemic administration of a particular therapeutic agent during normal use, but is retained in the oral cavity long enough to contact substantially all tooth surfaces and / or oral tissues for oral activities. Oral care compositions can be in a variety of forms, including toothpaste, dentifrice, tooth gel, subgingival gel, mouthwash, mousse, foam, oral spray, lozenge, chewable tablet, chewing gum, or denture products. Oral care compositions can also be incorporated into strips or films for direct application or attachment to oral surfaces.

[0147] In some embodiments, the flavored product is a pharmaceutical product, such as a product designed to carry or deliver certain active pharmaceutical ingredients (APIs). Such APIs can be over-the-counter (OTC) drugs, such as acetaminophen, and other OTC cough and cold medicines. In some embodiments, the API is a prescription-based drug.

[0148] In certain embodiments of any of the configurations and embodiments described herein involving a flavored product, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

[0149] Other non-limiting examples of food and beverage products or preparations include sweetened coatings, frostings or icings of such products, or any entity included in the following: soups, dry processed foods, beverages, ready-to-eat foods, canned or preserved foods, frozen processed foods, refrigerated processed foods, snack foods, baked foods, confectionery, dairy products, ice cream, meal replacements, pasta and noodles, as well as sauces, dressings, condiments, baby foods and / or spreads.

[0150] In general, soups refer to canned / preserved, dehydrated, instant, refrigerated, UHT and frozen soups. For the purpose of this definition, soup means a food made from meat, poultry, fish, vegetables, grains, fruit and other ingredients, cooked in a liquid, which may contain visible fragments of some or all of these ingredients. It may be clear (as a stock) or thick (as a chowder), smooth, pureed or chunky, ready-to-eat, semi-concentrated or concentrated, and served hot or cold, as a first or main course or as a snack (sipping beverage) between meals. Soup may be used as a raw material for the preparation of other meal ingredients, ranging from stocks (consommé) to sauces (cream- or cheese-based soups).

[0151] The Dehydrated and Cooking Foods category generally refers to: (i) cooking aid products, such as powdered, granulated, paste-like, concentrated liquid products, including concentrated bouillon, bouillon, and bouillon-like products in pressed blocks, tablets, or powdered or granulated form, sold individually as finished products or as ingredients in products, sauces, and recipe mixes (regardless of technology); (ii) dietary solution products, such as dehydrated soups and freeze-dried soups, including dehydrated soup mixes, dehydrated instant soups, dehydrated instant soups, dehydrated ready-to-eat soups, dehydrated or self-heating preparations of ready-made dishes, meals, and single-serving entrees, including pasta, potatoes, and rice; and (iii) dietary garnish products, such as condiments, marinades, salad dressings, salad toppings, dips, mixes, batter mixes, shelf-stable sauces, barbecue sauces, liquid recipe mixes, concentrates, sauces or sauce mixes, including salad recipe mixes, sold as finished products or as ingredients in products, whether dehydrated, liquid, or frozen.

[0152] Beverages generally refer 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 concentrate formulations for preparing beverages (e.g., soda), and dry powder beverage precursor mixtures. Beverages also include alcoholic beverages, soft drinks, sports drinks, isotonic beverages and hot drinks. Alcoholic beverages include but are not limited to beer, cider / perry, FABs, wine and spirits. Soft drinks include but are not limited to carbonated beverages, such as cola and non-cola carbonated beverages; fruit juices, such as fruit juices, honey drinks, fruit drinks and fruit-flavored drinks; bottled water, including soda water, spring water and purified / table water; functional beverages, which can be carbonated or still beverages, including sports drinks, energy drinks or elixir drinks; concentrates, such as ready-to-drink liquids and powder concentrates. Beverages, whether hot or cold, include, but are not limited to, coffee or iced coffee, such as fresh, instant and blended coffee; tea or iced tea, such as black, green, white, oolong and flavored teas; and other beverages, including flavored, malt-based or plant-based powders, granules, blocks or tablets mixed with milk or water.

[0153] Snacks generally refer to any food that is a simple, informal meal, including but not limited to sweet and savory snacks and snack bars. Examples of snacks include but are not limited to fruit snacks, potato chips / crisps, extruded snacks, tortillas / corn chips, popcorn, pretzels, nuts and other sweet and savory snacks. Examples of snack bars include but are not limited to granola / cereal bars, breakfast bars, energy bars, fruit bars and other snack bars.

[0154] The baked goods category generally refers to any edible product that is prepared during a process that involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, cakes, waffles, tortillas, soft cookies, pies, bagels, tarts, quiches, cakes, any baked goods, and any combination thereof.

[0155] Ice cream generally refers to frozen desserts containing cream, sugar and flavorings. Examples of ice cream include, but are not limited to: impulse ice cream; family-packed ice cream; frozen yogurt and handmade ice cream; soy, oat, bean (such as red bean and mung bean) and rice-based ice cream.

[0156] Candy generally refers to edible products with a sweet taste. Examples of candy include, but are not limited to, hard candy, gelatin, chocolate candy, granulated candy, chewing gum, etc., and any combination of products.

[0157] The meal replacement category generally refers to any food that is intended to replace a normal meal, especially for those who are concerned with health or fitness. Examples of meal replacements include, but are not limited to, weight loss products and recovery products.

[0158] The ready-to-eat food category generally refers to any food that can be consumed as a meal without extensive preparation or processing. Ready-to-eat foods include products to which the manufacturer has added recipe "skills" so that they have a high degree of readiness, completeness, and convenience. Examples of ready-to-eat foods include, but are not limited to, canned / preserved, frozen, dried, refrigerated ready meals; dinner mixes; frozen pizza; refrigerated pizza; and prepared salads.

[0159] 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.

[0160] The canned / preserved foods category includes, but is not limited to, canned / preserved meats and meat products, fish / seafood, vegetables, tomatoes, beans, fruits, ready meals, soups, pasta, and other canned / preserved foods.

[0161] The frozen processed food category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish / seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizza, soups, noodles, and other frozen foods.

[0162] The dry processed food category includes, but is not limited to, rice, dessert mixes, dry ready meals, dehydrated soups, instant soups, dry pasta, plain noodles, and instant noodles. The refrigerated processed food category includes, but is not limited to, refrigerated processed meats, processed fish / seafood products, lunch boxes, fresh-cut fruit, ready meals, pizza, prepared salads, soups, fresh pasta, and noodles.

[0163] The Sauces, Dressings and Condiments category includes, but is not limited to, tomato sauces and purees, 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.

[0164] The baby food category includes, but is not limited to, milk- or soy-based formulas; and prepared, dry, and other baby foods.

[0165] Spreads include, but are not limited to, jams and preserves, honey, chocolate spreads, nut spreads and yeast spreads.

[0166] Dairy products generally refer to edible products produced from the milk of mammals. Examples of dairy products include, but are not limited to, drinking milk products, cheese, yogurt and sour milk drinks, and other dairy products.

[0167] Additional examples of flavored products, particularly food and beverage products or formulations, are provided below. Exemplary ingestible compositions include one or more candies, chocolates, chocolate chips, chocolate countlines, selflines / softlines, boxed varieties, standard boxed varieties, twist-wrapped miniature chocolates, flavored chocolates, chocolates with toys, sandwiches, other chocolate candies, mints, standard mints, strong mints, hard candies, pastilles, gums, jellies and chews, toffees, caramels and nougats, medicated candies, lollipops, licorice, other candies, breads, packaged / industrial breads, bulk / artisan breads, pastries, cakes, packaged / industrial cakes, bulk / artisan cakes, cookies, chocolate coatings Biscuits, biscuits, sandwich cookies, crackers and crackers, bread substitutes, breakfast cereals, ready-to-eat cereals, family breakfast cereals, corn flakes (flakes), muesli, other cereals, children's breakfast cereals, hot cereals, ice cream, ready-to-eat ice cream, single-serve dairy ice cream, single-serve water ice cream, multi-pack dairy ice cream, multi-pack water ice cream, family-pack ice cream, family-pack dairy ice cream, ice cream desserts, loose ice cream, family-pack water ice cream, frozen yogurt, artisanal ice cream, dairy products, milk, fresh / pasteurized milk, whole fat fresh / pasteurized milk, semi-skimmed fresh / pasteurized milk, extended shelf life / ultra-high temperature milk, whole fat extended shelf life / ultra-high temperature milk , semi-skimmed extended shelf life / UTH milk, fat-free extended shelf life / UTH milk, goat's milk, condensed milk / evaporated milk, plain condensed milk / evaporated milk, flavoured, functional and other condensed milk, flavoured milk drinks, flavoured dairy milk drinks, flavoured milk drinks with fruit juice, soy milk, yoghurt drinks, fermented milk drinks, coffee creamer, milk powder, flavoured milk powder drinks, cream, cheese, processed cheese, spreadable cheese, unspreadable processed cheese, unprocessed cheese, spreadable unprocessed cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, yoghurt, plain / natural yoghurt, flavoured yoghurt, fruit yoghurt, probiotic yoghurt, drinkable yoghurt, regular drinkable yoghurt, probiotic drinkable yoghurt, frozen and shelf-stable snacks, dairy-based snacks, dairy-based snacks bean desserts, frozen snacks, fresh cheese and quark cheese, original fresh cheese and quark cheese, flavored fresh cheese and quark cheese, salty fresh cheese and quark cheese, sweet and salty snacks, fruit snacks, chips / potato chips, puffed snacks, tortilla chips / corn chips, popcorn, pretzels, nuts, other sweet and savory snacks, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, weight loss products, recovery drinks, ready meals, canned ready meals, frozen ready meals, dried ready meals, frozen ready meals, dinner mixes, frozen pizza, refrigerated pizza, soups, canned soups, dehydrated soups, instant soups, cold soups, hot soups, frozen soups, pasta, canned pasta, dry pasta,Frozen / fresh pasta, noodles, plain noodles, instant noodles, instant noodles in cups / bowls, instant noodles in bags, frozen noodles, snack noodles, canned food, canned meat and meat products, canned fish / seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready-to-eat food, canned soup, canned pasta, other canned food, frozen food, frozen processed red meat, frozen processed poultry, 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 baked goods, frozen desserts, frozen ready-to-eat food, frozen pizza, frozen soup, frozen noodles, other frozen food, dried food, dessert mixes, dried ready-to-eat food, dehydrated soup, instant soup, dried pasta, plain noodles, instant noodles, instant noodles in cups / bowls, instant noodles in bags, refrigerated food, refrigerated processed meat, refrigerated fish / seafood products, refrigerated processed fish, refrigerated coated fish , refrigerated smoked fish, refrigerated lunch packs, refrigerated ready meals, refrigerated pizza, refrigerated soups, refrigerated / fresh pasta, refrigerated noodles, oils and fats, olive oil, vegetable and seed oils, cooking fats, butter, margarine, spreads and fats, functional spreads and fats, sauces, seasonings and condiments, tomato pastes and purees, bouillon / stock cubes, stock cubes, gravy granules, liquid stocks and stocks, 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, reduced fat salad dressings, balsamic vinegar, dips, pickles, other sauces, seasonings and condiments, baby food, formula, standard formula, growing-up formula, toddler formula, hypoallergenic formula, prepared baby food, dried baby food, other baby food, spreads, jams and preserves, honey, chocolate spreads, nut-based spreads and yeast-based spreads. Exemplary ingestible compositions also include candies, baked products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready-to-eat foods, soups, pasta, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods or spreads, or mixtures thereof. Exemplary ingestible compositions also include breakfast cereals, sweetened beverages, or solid or liquid concentrate compositions for preparing beverages, ideally enabling the reduction of previously known sugar sweeteners or artificial sweeteners.

[0168] Some embodiments provide chewable compositions that may or may not be swallowed. In some embodiments, the chewable composition may be gum, chewing gum, saccharified gum, sugarless gum, functional gum, bubble gum, which contain the compounds disclosed and described herein, alone or in combination.

[0169] In some embodiments, the coolness modification composition disclosed and described herein can be provided in the form of a flavoring concentrate preparation alone or in combination, such as being suitable for subsequent processing to produce a ready-to-use (i.e., instant) product." flavoring concentrate preparation" refers to a preparation that should be reconstituted with one or more dilution media to become a ready-to-use composition. The term "ready-to-use composition" is used interchangeably with "ingestible composition" herein, and it means that no matter it is intended to be used for or not for consumption, any substance that can be taken orally either alone or together with another substance. In one embodiment, the ready-to-use composition includes a composition that can be directly eaten by a human or animal. The flavoring concentrate preparation is usually used by mixing or diluting with one or more dilution media, such as any edible or ingestible ingredient or product, to impart or change the dilution medium with one or more flavorings. Such a use process is generally referred to as recovery. Recovery can be carried out in a home environment or an industrial environment. For example, a consumer can recover a frozen fruit juice concentrate in a kitchen with water or other aqueous media to obtain a ready-to-use fruit juice beverage. In another example, soft drink syrup concentrate can be reconstituted with water or other aqueous media on a large-scale industrial scale by manufacturers to produce instant soft drinks. Since the concentration of the flavoring or seasoning that the flavoring concentrate preparation has is higher than the instant composition, the flavoring concentrate preparation is usually not suitable for direct consumption without reconstitution. There are many benefits to using and producing the flavoring concentrate preparation. For example, one benefit is to reduce the weight and volume of transportation, because the flavoring concentrate preparation can be reconstituted by adding a suitable solvent, solid or liquid when using.

[0170] The flavored product according to any of the preceding embodiments further comprises, in certain embodiments, one or more additional flavor-modifying compounds, such as compounds that enhance sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), compounds that block bitterness, compounds that enhance umami, compounds that enhance kokumi, compounds that reduce sourness, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing.

[0171] In certain embodiments of any of the forms and embodiments described herein involving a sweetening or flavoring concentrate, the sweetening or flavoring concentrate is a non-naturally occurring product, such as a composition specifically manufactured for the production of a flavored product, such as a food or beverage product.

[0172] In one embodiment, the flavoring concentrate formulation comprises i) a compound disclosed and described herein, either alone or in combination; ii) a carrier; and iii) optionally at least one adjuvant. The term "carrier" refers to a generally inactive auxiliary substance, such as a solvent, adhesive, or other inert medium, which is used in combination with the compound of the present invention and one or more optional adjuvants to form a formulation. For example, water or starch can be a carrier for the flavoring concentrate formulation. In some embodiments, the carrier is the same as the dilution medium used to reconstitute the flavoring concentrate formulation; in other embodiments, the carrier is different from the dilution medium. As used herein, the term "carrier" includes, but is not limited to, an acceptable carrier for ingestion.

[0173] The term "adjuvant" means an additive that supplements, stabilizes, maintains or enhances the expected function or efficacy of an active ingredient such as the compounds of the present invention. In one embodiment, at least one adjuvant comprises one or more flavoring agents. Flavoring agents can have any flavor known to those skilled in the art or consumers, such as chocolate, coffee, tea, mocha, French vanilla, peanut butter, Indian milk tea (chai), or the flavor of a combination thereof. In another embodiment, at least one adjuvant comprises one or more sweeteners. One or more sweeteners can be any sweetener described in the present application. In another embodiment, the at least one adjuvant comprises 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. Patent No. 6,468,576, the entire contents of which are incorporated herein by reference for all purposes.

[0174] In one embodiment, the flavoring concentrate formulation of the present invention can be in the form of a liquid, solid, foam, paste, gel, emulsion and a combination thereof selected from solutions and suspensions, such as a liquid containing a certain amount of solid content. In one embodiment, the flavoring concentrate formulation is in the form of a liquid including water-based and non-aqueous. In some embodiments, the flavoring concentrate formulation of the present invention can be carbonated or non-carbonated.

[0175] The flavoring concentrate formulation may further include a freezing point depression agent, a nucleating agent or both as the at least one adjuvant. A freezing point depression agent is an acceptable compound or agent for ingestion, which can reduce the freezing point of a liquid or solvent to which the compound or agent has been added. That is, the freezing point of a liquid or solution containing a freezing point depression agent is lower than the freezing point of a liquid or solvent without a freezing point depression agent. In addition to reducing the initial freezing point, a freezing point depression agent can also reduce the water activity of the flavoring concentrate formulation. Examples of freezing point depression agents include, but are not limited to, carbohydrates, oils, ethanol, polyols such as glycerol and combinations thereof. A nucleating agent represents an acceptable compound or agent for ingestion that can promote nucleation. The presence of a nucleating agent in the flavoring concentrate formulation can improve the mouthfeel of slush, and helps maintain the physical properties and performance of slush at freezing temperatures by increasing the number of required ice crystal centers. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide and combinations thereof.

[0176] In one embodiment, the flavoring 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 water activity of the flavoring concentrate formulation is less than about 0.85. In another embodiment, the water activity of the flavoring concentrate formulation is less than about 0.80. In another embodiment, the water activity of the flavoring concentrate formulation is less than about 0.75.

[0177] The present application relates to body care products and related uses. In at least another form, the present disclosure provides the use of the above-mentioned coolness modification composition for enhancing the cooling sensation of body care products. In some embodiments, the body care product comprises a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a body deodorant, a body lotion, a body oil, a sunscreen, or a sunscreen.

[0178] In at least another form, the present disclosure provides a method for enhancing the cooling sensation of a body care product, the method comprising combining the above-described coolness modifying composition with a cooling compound (e.g., menthol, cubebol, or a combination thereof) in a body care product. In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning aid.

[0179] In at least another form, the present disclosure provides a body care product comprising the above-described coolness-modifying composition and a cooling compound (e.g., menthol, cubebol, or a combination thereof). In some embodiments, the body care product is a shampoo, a shower gel, a soap, an exfoliating scrub, a moisturizer, a facial serum, an antiperspirant, a deodorant, a body lotion, a body oil, a sunscreen, or a tanning aid.

[0180] In some embodiments, the body care product is a personal care or beauty product. Personal care and beauty products include products that can be applied to the skin, hair, and nails, and can be either leave-on or rinse-off products. In the context of the present disclosure, "rinse-off" means that the intended use of the product includes application to the skin and / or hair, and then the product is rinsed or wiped off the skin or hair within a few seconds to a few minutes of the application step. Personal care and beauty products include powders, creams, emulsions, lotions, gels and oils for application to the skin (face, hands, feet, etc.), color bases (liquids and pastes) and tissues impregnated with liquids; products for applying and removing makeup on the face and eyes; hair care products, including hair tints and hair bleaches; products for perming, straightening, styling and setting hair; shaving products, including creams, foams, mousses and hair removal products; tanning products and products for sunless tanning; deodorant and antiperspirant products.

[0181] In some embodiments, the personal care or beauty product is selected from the group consisting of: shaving aids, shampoos, hair care products, leave-on skin care products, skin cleansing or washing products (e.g., rinse-off skin cleansing or washing products), wet wipes, and body sprays, deodorants, or antiperspirants. Shaving aids specifically include foams, gels, creams, and soap bars (see, e.g., U.S. Pat. No. 7,069,658, U.S. Pat. No. 6,944,952, U.S. Pat. No. 6,594,904, U.S. Pat. No. 6,182,365, U.S. Pat. No. 6,185,822, U.S. Pat. No. 6,298,558, and U.S. Pat. No. 5,113,585). Shampoos and hair care products specifically include two-in-one shampoos and shampoos specifically formulated for dry or oily hair, or shampoos containing additives such as anti-dandruff agents. Hair care products can be either rinse-off or disposable hair care products, and also include hair tonics, bleaching agents, colorants, setting and styling products. Reference can be made to, for example, U.S. Patent No. 6,162,423, U.S. Patent No. 5,968,286, U.S. Patent No. 5,935,561, U.S. Patent No. 5,932,203, U.S. Patent No. 5,837,661, U.S. Patent No. 5,776,443, U.S. Patent No. 5,756,436, U.S. Patent No. 5,661,118, U.S. Patent No. 5,618,523. Disposable skin care products include eau de parfum, eau de toilette, cologne, wet wipes, body spray, deodorant and antiperspirant. Skin washing products specifically include beauty and hygiene soap bars, shower gels, liquid soaps, bath liquids, exfoliating gels and creams (see, for example, U.S. Pat. No. 3,697,644; U.S. Pat. No. 4,065,398; U.S. Pat. No. 4,387,040). Wet wipes (wipes) specifically include skin cleansing wipes, baby wipes, makeup removal wipes and skin refreshing wipes (see, for example, U.S. Pat. No. 4,775,582; WO 02 / 07701; WO 2007 / 069214 and WO 95 / 16474). Body sprays, deodorants and antiperspirants specifically include sticks, liquid roll-on applicators and pressurized sprays.

Claims

1. A coolness modification composition, comprising: a) a coolness enhancing compound selected from the group consisting of: (E / Z)-2-methyl-2-butenal, (E / Z)-2-isopropyl-5-methyl-2-hexenal, and any combination thereof; and b) a cooling compound selected from the group consisting of: (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, oxazol-2-yl)piperidin-1-yl)butan-1-one, (5-methyltetrahydrofuran-3-yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-2-en-1-one piperidin-1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-((R)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (tetrahydrofuran-3-yl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1 -yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H -imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(methylthio)propan-1-one, 1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b ]thiophene-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)hexa-3,5-diene-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)pent-4-ene-1-one -1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- methylbut-3-en-1-one, 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5 -(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one 2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(ethylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(Furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(Furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one 1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one ketone, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan-1-one, -imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)isoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2,3-trimethyl-1-(2- 1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2- 1-yl)-1H-imidazol-4-yl)benzonitrile, 2-amino-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-( 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2-methyl 2-Methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butane-1,3-dione, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-Methyl-3-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3,3 -difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde,4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, methyl 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoate, N-(2-hydroxyethyl)- 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, )-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine,1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(4- 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(4-hydroxy-2-(5-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(4-hydroxy-2-(5-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one -1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)-propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one,1-(3-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one 1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one,1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2 -yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, and any combination thereof; or A cooling compound selected from the group consisting of 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, and any combination thereof; or A cooling compound selected from the group consisting of 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, or any combination thereof.

2. The coolness-modifying composition of claim 1, wherein the coolness-enhancing compound is (E / Z)-2-methyl-2-butenal.

3. The coolness-modifying composition of claim 1, wherein the coolness-enhancing compound is (E / Z)-2-isopropyl-5-methyl-2-hexenal.

4. The coolness modifying composition according to any one of claims 1 to 3, wherein the coolant compound is selected from the group consisting of: (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2S)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (5-methyltetrahydrofuran-3-yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one 2-en-1-one, (E)-2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-((R)-2-(5-( 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(2,3-dihydrobenzofuran-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-2-yl)-2-(methylthio)propan-1-one -yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-chloro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(4-cyclobutylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one -1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(Benzo[b]thiophene-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(Methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-3-en-1-one, 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H- imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2 -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio) propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-1-yl)- -3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(benzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1-(2-(methylthio)propanoyl) 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(5-methylfuran-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-1-(2-(5-piperidin-2-yl)piperidin-1-yl)-1-(2-(4-phenyl-1H-imidazol ...2-(Ethylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylamino)-N-(4-( 2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1 ,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one -1-one, 2-(methylthio)-1-(2-(4-(5-methylthiophene-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(methylthio)-1-(2-(4-(pyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2- (Methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolylisoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolylisoxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-p-tolylthiazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-(p-tolyl) 2,2,3-trimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)but-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1 -yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 2-amino-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-ethoxy-1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile,2-Mercapto-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, -1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl) 1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4, 4-Pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-Fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile,4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butanone, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, methyl 4-(2-(1-(2- 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)-1-(2-(methylthio)-1-(piperidin-2-yl)-1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)- 2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl )-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propane-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine,1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(4-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(4-hydroxy-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(5 -Hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinylpropan-1-one, 1-(4-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinylpropan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinylpropan-1-one,1-(2-Hydroxy-6-(5-(p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-Hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(5-Hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(4-Hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one 1-keto, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4-(2-(1-(2-methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)methanone 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one,2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H -imidazol-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, and any combination thereof.

5. The coolness modifying composition according to any one of claims 1 to 3, wherein the coolant compound is selected from the group consisting of: 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, and any combination thereof.

6. The coolness modifying composition according to any one of claims 1 to 3, wherein the cooling compound is selected from the group consisting of: 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, or any combination thereof.

7. A flavored product comprising the coolness modifying composition according to any one of claims 1 to 6.

8. The flavored product according to claim 7, further comprising a high intensity sweetener.

9. The flavored product according to claim 8, wherein the high intensity sweetener is sodium saccharin, sucralose or any combination thereof.

10. The flavored product according to any one of claims 7 to 9, further comprising 4-amino-5,6-dimethyl-thieno[2,3-d]pyrimidin-2(1H)-one or a salt thereof.

11. A flavoured product according to any one of claims 7 to 10, further comprising a flavouring agent, such as a mint flavouring agent.

12. The flavored product according to any one of claims 7 to 11, further comprising one or more cooling enhancing compounds selected from the group consisting of: N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; 2-(4-Fluorophenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; 2-(2-Hydroxy-4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiazol-5-ylmethyl)-acetamide; 5-methoxy-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)benzofuran-2-carboxamide; 2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; and Any combination of them.

13. The flavored product according to any one of claims 7 to 12, further comprising 2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide.

14. The flavored product according to any one of claims 7 to 13, wherein the flavored product is a food product, a beverage product, an oral care product or a pharmaceutical product.

15. A body care product comprising the coolness modifying composition according to any one of claims 1 to 6.

16. The body care product according to claim 15, wherein the body care product is a cosmetic product, a skin care product or a hair care product.

17. A method of enhancing the cooling sensation of a cooling compound in a flavored product or a body care product, the method comprising combining the cooling compound with a coolness enhancing compound in the flavored product or the body care product, wherein the coolness enhancing compound is selected from the group consisting of: (E / Z)-2-methyl-2-butenal, (E / Z)-2-isopropyl-5-methyl-2-hexenal, and any combination thereof; and in, The cooling compound is selected from the group consisting of: (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, -2-yl)piperidin-1-yl)methanone, (2S)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (5-methyltetrahydrofuran-3-yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, (E)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-2-en-1-one, 1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((R)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((S)-2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-((R)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (tetrahydrofuran-3-yl)(2-(5-(p-tolyl) 1-(2-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzofuran-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(2,3-dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1 -yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-((1,1-dioxythiomorpholine)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H -imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(methylthio)propan-1-one, 1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b ]thiophene-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)hexa-3,5-diene-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)pent-4-ene-1-one -1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- methylbut-3-en-1-one, 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5 -(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one,1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1 -carbonyl) cyclopropane-1-carbonyl) cyclopropane-1-carbonitrile, 2-(5-methylfuran-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(allylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(ethylthio)-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(Furan-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(Furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(Furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetamide, 1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one 1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one , 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophene-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)isoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-(Methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2,3-trimethyl-1-(2- 1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl) -1H-imidazol-4-yl)benzonitrile, 2-amino-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-mercapto-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one,2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-p-tolyl)-1H- imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propanoyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3,3 -difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde,4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo[1.1.1]pentan-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, methyl 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoate, N-(2-hydroxyethyl)- 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, )-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine,1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(4- 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(4-hydroxy-2-(5-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(4-hydroxy-2-(5-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthiopropan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-p-tolyl-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonyl)propan-1-one -1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfonylpropan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)-propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one,1-(3-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(5-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(4-hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylthio)propan-1-one 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one 1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one,1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2 -yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, and any combination thereof; or The cooling compound is selected from the group consisting of: 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, and any combination thereof; or The cooling compound is selected from the group consisting of: 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, or any combination thereof.