WO2011130705A1 - Compounds, compositions, and methods for reducing or eliminating bitter taste - Google Patents

Compounds, compositions, and methods for reducing or eliminating bitter taste Download PDF

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Publication number
WO2011130705A1
WO2011130705A1 PCT/US2011/032780 US2011032780W WO2011130705A1 WO 2011130705 A1 WO2011130705 A1 WO 2011130705A1 US 2011032780 W US2011032780 W US 2011032780W WO 2011130705 A1 WO2011130705 A1 WO 2011130705A1
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WO
WIPO (PCT)
Prior art keywords
formula
group
compound
hydrogen
edible composition
Prior art date
Application number
PCT/US2011/032780
Other languages
French (fr)
Inventor
Kambiz Shekdar
Daniel Lavery
Joseph Gunnet
Jessica Langer
Jane V. Leland
David Hayashi
Peter H. Brown
Louise Slade
William P. Jones
Original Assignee
Chromocell Corporation
Kraft Foods Global Brands Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44799062&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2011130705(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to BR112012025943A priority Critical patent/BR112012025943A2/en
Priority to AU2011239445A priority patent/AU2011239445B2/en
Priority to US13/641,213 priority patent/US8865779B2/en
Priority to NZ602977A priority patent/NZ602977A/en
Priority to JP2013505203A priority patent/JP6068330B2/en
Priority to CN201180027868.5A priority patent/CN103037710B/en
Priority to CA2796072A priority patent/CA2796072A1/en
Application filed by Chromocell Corporation, Kraft Foods Global Brands Llc filed Critical Chromocell Corporation
Priority to MX2012011997A priority patent/MX346673B/en
Priority to RU2012142731/13A priority patent/RU2596989C2/en
Priority to UAA201212838A priority patent/UA112745C2/en
Priority to EP11769724.3A priority patent/EP2557944A4/en
Priority to KR1020127029265A priority patent/KR20130055595A/en
Publication of WO2011130705A1 publication Critical patent/WO2011130705A1/en
Priority to IL222424A priority patent/IL222424A/en
Priority to ZA2012/08490A priority patent/ZA201208490B/en
Priority to US14/480,853 priority patent/US9408407B2/en
Priority to AU2015258252A priority patent/AU2015258252B2/en
Priority to US15/178,149 priority patent/US9872514B2/en
Priority to AU2017245466A priority patent/AU2017245466A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/86—Addition of bitterness inhibitors
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A23L2/56—Flavouring or bittering agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/10—Natural spices, flavouring agents or condiments; Extracts thereof
    • A23L27/14—Dried spices
    • A23L27/16—Onions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/202—Aliphatic compounds
    • A23L27/2024—Aliphatic compounds having oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/203—Alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/204—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/205—Heterocyclic compounds
    • A23L27/2052—Heterocyclic compounds having oxygen or sulfur as the only hetero atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
    • C07C63/04—Monocyclic monocarboxylic acids
    • C07C63/06—Benzoic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/20—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 hydrogenated in the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
    • C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to flavor in edible compositions. Background , of thejiweniion
  • the sense of taste e.g., in human, can detect at least five traditional tastes: sweet, sour, salty, bitter, and umami (savory).
  • Many nutritious substances including vegetables, foods, food ingredients and nutrients comprise bitter tastants and/or have a bitter taste
  • many pharmaceutical substances important to maintain or improve health comprise bitter tastants and/or have a bitter taste.
  • certain food products and consumer products have desirable bitter tastes, including coffee, beer and dark chocolate, in many contexts, consumers dislike such bitter tastes.
  • bitter tastants and/or bitter taste For example, many consumers dislike the perception of certain bitter tastants and/or bitter taste and will avoid food or pharmaceutical products with an undesirable bitter tastant or bitter taste in favor of food and pharmaceutical products that have reduced levels of undesirable bitter tastants or that have reduced or that completely lack bitter taste.
  • This aversion to products containing undesirable bitter tastants and/ or haying undesirable bitter taste may be caused by perception of bitter tastants and/or bitter taste mediated by activation of bitter receptors present in the oral cavity and/or in the gastrointestinal tract.
  • bitter iastants and/or bitter taste prevents or hampers improvement of the nutritive quality and safety of foods as desired levels of nutrients or preservatives comprising bitter tastants and/or having bitter taste cannot be used.
  • dislike of or aversion to the bitter tastants or bitter taste of some pharmaceutical agents negatively impacts compliance with prescribed regimens for their use.
  • additives, preservatives, emulsifiers and foodstuffs used in the production of food products comprise bitter tastants and/or have a bitter taste. While these additives, preservatives, emulsifiers and foodstuffs may affect the taste of a food product, they may also be important for improving the shelf life, nutritive qualisy, or texture of the food product. For example, the increasing trend of hypertension and cardiovascular disease has been attributed, in part, to the high sodium intake of the Western diet. Accordingly, substitution of sodium chloride with another salty tasting compound is desirable.
  • the most common sodium chloride substitute is potassium chloride, which, to a portion of the population, is perceived as possessing a bitter taste in addition to its salty taste.
  • the bitter taste of potassium chloride limits the extent to which, it may be used to replace sodium chloride in foods without causing undesired bitter taste for the portion of the population sensitive to it.
  • sodium lactate has a broad antimicrobial action, is effective at inhibiting spoilage, and growth of pathogenic bacteria, and is commonly used in food products (e.g., meat and poultry products) to extend shelf life and increase food safety. Due to its sodium content, however, sodium lactate, can be undesirable as a preservative. Potassium lactate, which has similar antimicrobial properties, has been used in lieu of sodium lactate. However, potassium lactate is also associated with a bitter taste which limits the extent to which it may be used to replace sodium lactate in foods without causing undesired bitter taste.
  • bitter, sweet, and umami tastants and compounds typically elicit a taste response via G-protein coupled receptors, while salty and sour tastants and compounds are typically hypothesized to elicit a taste response via ion channels.
  • Bitter taste receptors belong to the T2R (also referred to as TAS2R) family of G-protein coupled receptors that induce intracellular calcium concentration changes in response to a bitter tastant.
  • T2R receptors act via gustducin, a taste-specific G-protein. There are at least twenty-five different members of the T2R family, suggesting that the perception of bitter teste is complex, involving several different tastant-receptor interactions.
  • Compounds capable of modulating the activation and/or signaling of bitter taste receptors in the oral cavity and/or the gastrointestinal tract could be effective to allow desired usage levels of bitter tastants or bitter tasting substances in food and pharmaceutical products without resulting in consumer dislike of such products due to perception of the increased le vels of bitter tastants or bitter tastes.
  • blockers or modulators of bitter taste receptors and bitter taste may reduce the perception of bitter tastants and/or bitter taste via the bitter taste receptors and/or taste transduction signaling machinery present in the oral cavity and/or the gastrointestinal tract.
  • bitter taste was masked using sweeteners and other tastants, including salt, in some cases, however, this is undesirable or insufficient because it can alter, mask, or interfere with other tastes/flavors/impressions (e.g., non bitter tastes or desired bitter tastes) in the food product. Additionally, this approach has rarely been able to completely mask the bitter taste present in such food products or pharmaceuticals. For that reason, compounds which reduce bitter taste instead of, or in addition to, masking agents are preferred,
  • compounds thai may be added io food products, consumer products and pharmaceuticals comprising bitter tastants or having a bitter taste to eliminate, modulate or reduce the perception of the bitter tastants or bitter taste or to reduce the corresponding activation of the bitter receptors in the oral cavity and/or the gastrointestin l tract.
  • the present invention provides compounds that modulate bitter taste, edible compositions comprising such compounds, and methods of preparing such edible compositions.
  • the present invention also provides methods of reducing the amount of sodium or sugar in an edible composition and methods of reducing bitter taste of an edible composition.
  • the present invention further provides a method of reducing, modulating or eliminating the bitter taste of a food, consumer or pharmaceutical product in a subject.
  • the present invention also provides a method of modulating, particularly reducing the activation of a bitter taste receptor.
  • the edible composition comprises a terpenoid compound.
  • the terpenoid compound is a compound having a molecular weight less than about 1000, 500, or 300 daltons.
  • the terpenoid compound is a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid).
  • the compound of Formula (I) is selected from the group consisting of damascene compounds (e.g., ⁇ -damascone, trans-a-damascone), ionone compounds (e.g., ⁇ -ionone, a-ionone, ⁇ -ionone, and dihydro-a-ionone, particularly either ⁇ -ionone or a-ionone), nerol, geranyl tsovaterate, geranyl acetone, neryl acetate, geranyl propionate, geranyl butyrate, citroneliyi propionate, citroneliyi isobutyrate, citrai diethyl acetai, geranyl phenylacetate, geranyi formate, DL-citronellol, neryl iso valerate, citronellyl acetate, citrai dimethyl acetai, citrai,
  • the edible composition comprises a chroman compound.
  • the chroman compound is a compound having a molecular weight less than about 1000, 500, or 300 daitons.
  • the chroman compound is a compound of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila) or Compounds 42-53 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
  • the compound of Formula (V) is selected from the group consisting of pentamethyl-6-chromanol, ⁇ -tocopherol, (+)-5-tocopherol, (+)-a-tocopherol acetate, D-a-tocoptierol succinate, DL-a-tocopherol acetate, Vitamin E acetate, 4-cbromanol and dihydrocoumarin.
  • the edible composition comprises a benzo ring-containing compound.
  • the benzo ring-containing compound is a compound having a molecular weight less than about 1000, 500, or 300 daitons.
  • the benzo ring-containing compound is a compound of Formula (Vlil), Formula (IXa), Formula (IXb), Formula (TXc), or Formula (IXd) or Compounds 54-71 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
  • the compound of Formula (VIII) is selected from, the group consisting of benzoic acid, ethyl benzoate, propyl benzoate, phenethyl benzoate, 4-hydroxybenzoic acid, methyl *ara-hydroxybenzoate, ethyl » «ra-hydroxybenzoate, butyl paraben, 4-methoxybenzoic acid, 3-methoxybenzoic acid, 2-methoxybenzoic acid, 4-propoxybenzoic acid,
  • methyl-ori/io-methoxy benzoate methyl-ori/io-methoxy benzoate, ara-hydroxybenzyl alcohol, a-mefhylbenzyl alcohol, and 4-( 1 -hydroxyethyl)-2-methoxyphenol.
  • the edible composition comprises one or more polycyclic compounds.
  • the polycyclic compound is a compound having a molecular weight less than about 1000, 500, 300 or 200 daitons.
  • the polycyclic compound has a bicyclic core with a one-carbon transannular bridge, such as a compound of Formula (XI) or Formula (XII) or Compounds 72-94 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
  • the present invention also includes edible compositions comprising a compound according to any one of Compounds 95-134 or comestibly or biologically acceptable salts or derivatives thereof, or enaniiomers or diasiereomers thereof.
  • the edible composition comprises (a) a compound of the invention; and (b) a bitter tastant.
  • the compound of the invention is a compound having a molecular weight less than about 1000, 500, or 300 daitons.
  • the compound of the invention is a compound of Formula ( ⁇ ), Formula (la).
  • Formula (Ha) is a compound of Formula ( ⁇ ), Formula (la).
  • the edible composition comprises (a) any one of Compounds 1-134, or combinations thereof; and (b) a bitter tastant
  • the edible composition comprises (a) any one of Compounds 1-58, or 61- 134, or combinations thereof; and (b) a bitter tastant.
  • the bitter tastant can be inherent in, e.g., a food product (such as coffee or chocolate) or can be a component of an edible composition (such as a bitter tasting preservative).
  • the bitter tastant present in the edible composition is a bitter tasting salt.
  • the bitter tastant present in the edible composition is a potassium salt, a magnesium salt, or a calcium salt.
  • the bitter tastant is a potassium salt, in some embodiments, the bitter tastant present in the edible compositions is KC1. In other embodiments, the bitter tastant present in the edible composition is potassium lactate.
  • the edible composition further comprises a sodium salt, in some embodiments, the edible composition further comprises NaCl. In other embodiments, the edible composition further comprises sodium lactate. In some embodiments, the edible composition further comprises sugar.
  • the edible composition is a food product comprising at least one compound of the invention.
  • the compound of the invention is a compound of Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib),
  • the compound of the invention is any one of Compounds 1-134, or combinations thereof.
  • the edible composition is a pharmaceutical composition comprising a bitter tasting pharmaceutically active ingredient and a compound of Formula (I), Formul (la ), Formul (Ila), Formula (Ilia), Formula (lib).
  • Formula (Ilib) is a pharmaceutical composition comprising a bitter tasting pharmaceutically active ingredient and a compound of Formula (I), Formul (la ), Formul (Ila), Formula (Ilia), Formula (lib).
  • the pharmaceutical composition comprises a bitter tasting pharmaceutically active ingredient and any one of Compounds 1-134, or combinations thereof.
  • the edible composition is a pharmaceutical composition comprising a pharmaceutically active ingredient, a bitter tastant, and a compound of Formula (I), Formula (la), Formula (11a), Formula (Ilia), Formul (lib), Formula (Illb), Formul (lie),
  • the pharmaceutical composition comprises a pharmaceutically active ingredient, a bitter tastant, and any one of Compounds 1-134, as described herein, or combinations thereof.
  • the edible composition is a consumer product comprising a bitter tastant and a compound of Formula (I), Formula (la), Formula (TIa),
  • the consumer product comprises a bitter tastant and any one of Compounds 1 -134, or combinations thereof.
  • Yet another embodiment of the present invention provides a consumer product for reducing bitter taste of a bitter tastant, wherein said consumer product comprises a compound of Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib).
  • Formula (Illb) comprises a compound of Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib).
  • the consumer product for reducing bitter taste of a bitter tastant comprises any one of Compounds 1-134, as described herein, or combinations thereof.
  • the present invention provides a method of preparing an edible co mposition compris ing ;
  • the method of preparing an edible composition comprises:
  • the edible composition is a food product, a consumer product or a pharmaceutical composition.
  • the comestibiy acceptable carrier is a foodstuff, a food product, or a pharmaceutically acceptable carrier,
  • the comestibiy acceptable earner in (a) is inherently bitter.
  • the comestibiy acceptable carrier may inherently contain a bitter tastant (i.e., the comestibiy acceptable carrier is bitter without addition of a bitter tastant).
  • the inherent bitter tastant is a bitter tasting salt.
  • the inherently bitter foodstuff comprises a potassium salt, a magnesium salt, or a calcium salt.
  • the inherently bitter foodstuff comprises a potassium salt, such as KCl.
  • the method of preparing an edible composition further comprises: (c) adding a bitter tastant.
  • the bitter tastant used in the methods of preparing an edible composition is a bitter tasting salt.
  • the bitter tastant used in the methods of preparing an edible composition is a potassium salt, a magnesium salt, or a calcium salt.
  • the bitter tastant used in the methods of preparing an edible composition is a potassium salt.
  • the bitter tastant used in the methods of preparing an edible composition is KCl.
  • the bitter tastant used in the methods of preparing an edible composition is potassium lactate.
  • the edible composition further comprises a sodium salt. In some embodiments, the edible composition further comprises NaCL In some embodiments, the edible composition further comprises sodium lactate. In some embodiments, the edible composition further comprises sugar.
  • the present invention also provides a method of reducing the amount of sodium in an edible composition.
  • such methods comprise:
  • the method of reducing the amount of sodium in an edible composition comprises:
  • the edible composition is a food product, a consumer product or a pharmaceutical composition
  • the method of reducing the amount of sodium in an edible composition comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25% of the sodium present in an edible composition with potassium, in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sodium present in an edible composition with potassium, in yet other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sodium present in an edible composition with potassium, in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100%i of the sodium present in an edible composition with potassium.
  • the edible composition maintains a salty flavor.
  • the present invention aiso provides a method of reducing the amount of NaCi in an edible composition, in some embodiments, such methods comprise:
  • the method of reducing the amount of NaCi in an edible composition comprises:
  • the method of reducing the amount of sodium in an edible composition comprises incorporating into the edible composition an amount of the compound sufficient to permit repiacement of up to 25% of the NaCi present in an edibie composition with KCl.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the NaCi present in an edible composition with KCl.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the NaCi present in an edible composition with KCl.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the NaCi present in an edibie composition with KCL in some embodiments, the edible composition maintains a. salty flavor.
  • the invention provides a method of reducing the amount of sodium lactate in an edible composition comprising:
  • the edible composition is a food product, a consumer product or a pharmaceutical composition.
  • the method of reducing the amount of sodium lactate in an edible composition comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25%o of the sodium lactate present in an edible composition with potassium lactate.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sodium lactate present in an edible composition with potassium lactate.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sodium lactate present in an edible composition with potassium, lactate.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the sodium lactate present in an edible composition with potassium lactate, in some embodiments, the edible composition has the same shelf life as an edible composition comprising sodium lactate.
  • the invention provides a method of reducing the amount of sugar in an edible composition comprising:
  • the invention provides a method of reducing the amount of sugar in an edible composition comprising:
  • the edible composition is a food product, a consumer product or a pharmaceutical composition.
  • the method of reducing the amount of sugar in an edible composition comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25% of the sugar present in an edible composition with Acesulfame .
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sugar present in an edible composition with Acesulfame K.
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sugar present in an edible composition with Acesulfame .
  • the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the sugar present in an edible composition with Acesulfame .
  • the edible composition maintains a sweet flavor.
  • the present invention also provides a method of reducing the sodium intake of a subject. Such method comprises:
  • the method of reducing the sodium intake of a subject comprises:
  • the method of reducing the sodium intake of a subject comprises:
  • the method of reducing the sodium intake of a subject comprises:
  • the edible composition is a food product, a consumer product or a pharmaceutical composition.
  • the methods of reducing the sodium intake of a subject further comprise (c) identifying a subject in need thereof.
  • ihe methods of reducing the sodium intake of a subject comprise incorporating into ihe edible composition an amount of the compound sufficient to reduce sodium intake by up to 25% using potassium replacement.
  • the amount of compound added in (b) is sufficient to reduce sodium intake by up to 50% using potassium replacement, in yet other embodiments, the amount of compound added in (b) is sufficient to reduce sodium intake by up to 75% using potassium replacement, in other embodiments, the amount of compound added in (b) is sufficient to reduce sodium intake by up to 100% using potassium repiacement,
  • the present invention also provides a method of reducing sugar intake of a subject comprising: (a) replacing an amount of sugar used in preparing an edibie composition with an amount of Acesislfame K; and
  • the method of reducing the sugar intake of a subject comprises:
  • the edibie composition is a food product, a consumer product or a pharmaceutical composition.
  • the methods of reducing the sugar intake of a subject further comprises (c) identifying a subject in need thereof.
  • the methods of reducing the sugar intake of a subject comprise incorporating into the edible composition an amount of the compound sufficient to reduce sugar intake by up to 25% using Acesulfame K replacement.
  • the amount of compound added in (b) is sufficient to reduce sugar intake by up to 50% using Acesulfame K replacement
  • the amount of compound added in (b) is sufficient to reduce sugar intake by up to 75% using Acesulfame replacement.
  • the amount of compound added in (b) is sufficient to reduce sugar intake by up to 100%) using Acesulfame replacement.
  • the present invention also provides a method of reducing the bitter taste attributed to a bitter tastant in an edibie composition comprising adding an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib),
  • the compound added to the edible composition is any one of Compounds 1-134, or combinations thereof.
  • the present invention further provides a method of reducing the bitter taste attributed to a bitter tastant in an edible composition comprising ingesting an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib),
  • the compound ingested with the edible composition is any one of Compounds 1 ⁇ 1 34, or combinations thereof,
  • the edible composition is a food product, a consumer product or a pharmaceutical composition.
  • the method reduces she bitter taste induced by the bitter tastant by up to 25%. In some embodiments, the method reduces the bitter taste induced by the bitter tastant by up to 50%. In other embodiments, the bitter taste induced by the bitter tastant is reduced by up to 75%. In yet other embodiments, the bitter taste induced by the bitter tastant is reduced by up to 100%. In some embodiments, the bitter tastant present in the edible composition is a bitter tasting salt. In some embodiments, the bitter tastant present in the edible composition is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the bitter tastant present in the edible compositions is KC1.
  • the present invention provides a method of preserving an edible composition comprising:
  • the method of preserving an edible composition comprises:
  • the present invention also provides a method of reducing the amount of sodium in an edible composition while preserving the edible composition.
  • such method comprises:
  • the present invention also provides a method of reducing the amount of sodium in an edible composition while preserving the edible composition.
  • such method comprises:
  • the edible composition is a food product.
  • the edible composition is a consumer product in some embodiments, the edible composition is a pharmaceutical composition.
  • the present invention also provides a method of reducing or eliminating bitter taste in a subject utilizing an edible composition
  • an edible composition comprising a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ma), Formula (lib), Formula (Mb), Formula (lie), Formula (IITc), Formula (iVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Me), Formula (iVe), Formula (Hi), Formula (ilg), Formula (ilh).
  • the composition that reduces or eliminates a bitter taste in a subject comprises any one of Compounds 1 -134, or combinations thereof.
  • the bitter taste is inherent, in some embodiments, the bitter taste is due to a bitter tasting salt. In some embodiments, the bitter taste is due to a potassium salt, a magnesium salt, or a calcium salt In some embodiments, the bitter taste is due to KC1. In other embodiments, the bitter taste is due to potassium lactate.
  • the present invention also provides a method of inhibiting or reducing the activation and/or signaling of a bitter taste receptor, wherein the method comprises contacting a bitter taste receptor with a compound of Formula (I), Formula (la).
  • Formula (Ila), Formula (Ilia) comprises contacting a bitter taste receptor with a compound of Formula (I), Formula (la).
  • Formula (Ila), Formula (Ilia) comprises contacting a bitter taste receptor with a compound of Formula (I), Formula (la).
  • the method comprises contacting a bitter taste receptor with any one of Compounds 1-134, or combinations thereof, in some embodiments, the bitter taste receptor is in the oral cavity. In other embodiments, the bitter taste receptor is in the gastrointestinal tract, for example, in the stomach. In other embodiments, the bitter taste receptor is in an in vitro assay.
  • a composition comprising a compound according to Formula (I):
  • R 1 is absent or is selected from the group consisting of hydrogen, Ci-ioalkyl, Ci.iohaloaikyl, C 2 -ioalkenyl, C 2 ..ioalkynyl, hydroxy], C;.i 0 acylamino, Ci.ioacyloxy, Ci-iocarbonate, C;.ioaikoxy, phenyloxy, phenyl-Ci ⁇ alkyloxy, Ci-sheteroaiyloxy, C3.ioalkenyloxy, Cj-ioalkyiryloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi-ioalkylamino,
  • R' is selected from the group consisting of hydrogen, Ci-ioalkyl, Ci.iohaloaikyl, C2-ioalkenyl, Cj.ioalkynyl, halo, hydroxy!, carboxyl, C ⁇ oalkoxycarbonyi,
  • R 3 is selected from the group consisting of hydrogen C]_ioalkyl, C i.iohaloaikyl, C 2 -ioa kenyl, C 2 -ioalkyiiyl, halo, hydroxy!, carboxyl, C uioalkoxycarbonyl,
  • R' f is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C' l -ioal e yl, ⁇ 3 ⁇ 4.ioalkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
  • C3.. 7 carbocyclyl-Ci.. 6 alkyl, Ci. 6 heterocyclyl, phenyl, phenyl-Ci. 6 alky ⁇ , Ci. 5 heteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • R 1 , R 2 , R', and R 4 independently, is optionally substituted with 1-3 substituents selected from the group consisting of Ci .io lkyl, Ci. iohaloalkyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyt, C2. loalkenyloxycarbonyl,
  • Ci. loalkynytoxycarbonyt Ci .ioacyl, Ci.ioaeylamino, C
  • n 0-2;
  • n 0-2;
  • p 0-2;
  • t 0-2;
  • Ci and C ' e in Formula (I) optionally are bonded together to form a 6-membered ring;
  • composition is edible and capable of reducing bitter tasie of a bitter tastant.
  • R 1 is absent or is selected from the group consisting of hydroxyl, C;. 6 alkoxy, and
  • R " is selected from the group consisting of hydrogen, C ⁇ alkyl, CYealkenyl, and Ci-salkynyl;
  • R ! is selected from the group consisting of hydrogen and ⁇ alkoxy
  • R 4 is selected from the group consisting of hydroxyl, C ⁇ alkoxy, and
  • n 0-2;
  • n 0-2;
  • p 0-2;
  • t 0-2;
  • Ci and C ' e in Forniula (I) optionally are bonded together to form a 6-membered ring;
  • R' is absent or is selected from the group cousisiiug of hydroxyl, C;.;alkoxy , and C;.;;acyloxy;
  • R 4 is selected from the group cousisiiug of hydrogen.
  • R " is selected from the group cousisiiug of hydrogen
  • R is selected from the group cousisiiug of hydroxyl, C i_ 3 acyloxy; m is 1 ;
  • n 0;
  • t 1 ;
  • R' is absent or is selected from the group consisting of hydrogen, Ci.ioalkyl, C;.iohaloalkyl, C soalkenyl, hydroxyl, Ci-ioacylamino, Q.ioacyloxy, Ci-iocarbonate, Ci. ioalkoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
  • Ci.5beteroaryl-Ci ⁇ alkyloxy CYioalkenyloxy, C3.ioalkynyioxy, phosphoryl, phosphate, phosphorate, phosphinate, amino, diCi.ioalkylamino, monoiVioalkylamino,
  • Ci .iocarbamate Cuourea, sulfhydryl, Ci .i 0 alkyithio, sulfate, sulfonate, sulfamoyl, sulibnamido, suifonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
  • R " is selected from the group consisting of hydrogen, Ci .ioalkyl, Ci .johaloalkyl, Cj.ioalkenyl, (3 ⁇ 4_ (0 alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
  • Ci-ioirnino Ci-iocarbamate
  • Ci .itrea cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cv;carbocyclyl,
  • R 3 is selected from the group consisting of hydrogen C 1 0 alkyl, Ci.iohaloalkyl, C' l -ioal enyl, ⁇ 3 ⁇ 4.ioalkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
  • R is selected from the group consisting of hydrogen, Cuoalkyl, C-j-ioaBcenyl, ⁇ 3 ⁇ 4. )0 alkynyl, halo, hydroxy!, carboxyl, Ci.ioalkoxycarbonyl,
  • Ci-iocarbonate Cuoafko y, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy, Cs-ioalkenyloxy, Ca-ioalkyoyloxy, phosphoryl, phosphate, ph.osphon.ate, phosphinate, amino, diCi_ioalkylamino, monoCi_ioalkylamirio, C i.i iamido, Ci-ioiroino, Ci.iocarbamate, C MC ,sirea, cyano, nitro, azido, solfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C ⁇ carbocyclyl,
  • R 1 , R 2 , R ' ⁇ and R 4 independently, is optionally substituted with 1-3 substituents selected from the group consisting of CVioalkyl, Ci. i haloalkyl, halo, hydroxy!, carboxyl, Ci.joalkoxycarbortyl, C 2 . 10 alkenyloxycarbon.yl,
  • Ci .iourea cyano, nitro, azido, sulfhydryl, Ci .ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl, CX / carboeyelyi-Ci.ealkyi,
  • Ci.jheteroaryl-C i.ealkyl and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
  • n 0-2;
  • composition according to paragraph 4 wherein as valence and stability permit:
  • R' is absent or is selected from the group consisting of hydroxyl, and C ; . 6 acyloxy;
  • R " is selected from the group consisting of hydrogen. C h alky!, CYealkenyl, and
  • R ! is selected from the group consisting of hydrogen and ⁇ alkoxy;
  • R 4 is selected from the group consisting of hydroxy!, and
  • R 1 , R 2 , R', and R 4 independently, is optionally substituted as noted abo ve;
  • Ci and C ' e in Formula (la) optionally are bonded together to form a 6-membered ring;
  • composition according to paragraph 1 wherein said compound according to Formula (1) is a compound according to Formula (lla):
  • R 2 , 3 , and R 4 are as defined in paragraph 1 .
  • R ⁇ R 5 , and R 4 are as defined in paragraph 1.
  • composition according to paragraph 8 wherein said compound according to Formula (lib) is a compound according to Formul (Tflb):
  • R z is as defined in paragraph 8.
  • composition according to paragraph 1 wherein said compound according to Formula (I) is a compound according to Formula (lie):
  • composition according to paragraph 11 wherein said compound according to Formula (Hie) is a compound according to Formula (IVc);
  • R * is as defined in paragraph 11.
  • composition according to paragraph 13 wherein said compound according to Formula (I) is a compound according to Formula (lid):
  • R 1 , R 2 , R J and R 4 are as defined in paragraph 1.
  • composition according to paragraph 13 wherein said compound according to Formula (lid) is a compound according to Formula (Hid):
  • composition according to paragraph 14 wherein said compound ording to Formula (Hid) is a compound according to Formula (lVd):
  • R 4 is as defined in paragraph 14.
  • composition according to paragraph 1 wherein said compound according to Formula (I) is a compound according to Formula (lie):
  • R 1 , R 2 , R and R-* are as defined in paragraph 1.
  • R '* is as defined in paragraph 17.
  • R , R J , and R 4 are as defined in paragraph 3 .
  • R 1 and R 4 are as defined in paragraph 1 . 21 , The composition according to paragraph 1, wherein said compound according to Formuia (I) is a compound according to Formuia (iih):
  • R 1 , R 3 , and R 4 are as defined in paragraph 1.
  • composition according to paragraph 1, wherein said compound according to Formula (I) is selected from the group consisting of:
  • Palmarosa oil, Rusa oil, and Turkish geranium oil Palmarosa oil, Rusa oil, and Turkish geranium oil
  • R 1 independently for each occurrence, is selected from the group consisting of Ci.ioaik l, Ci.iohaloalkyl, Q M oalkeiiyl, Cj.- ioaikynyl, halo, hydroxy], carboxyl,
  • R z is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, Q.ioafkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
  • R 3 is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, C 2 -ioalkynyl, halo, hydroxy!, carboxyl, C noalkoxycarbonyl,
  • R 4 is selected from the group consisting of hydrogen, C;_ 2 ihaloalkyl, C 2 . 2 i alkenyl, hydroxy!, Ci.io c loxy, Ci.ioalko y, phenyloxy,
  • Ci.ioalkylthio C 3 . 7 carbocycS.yl, Ci-gheterocyclyl,
  • heteroasyl-Ci. 6 alkyl wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
  • R 5 is selected from the group consisting of hydrogen, Cuialkyl,
  • Ci-ioalkylthio, C : ; opposition 7 carbocyciyl, C3. 7 carbocyclyl-C
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1-4 heteroatoras selected from N, O, and S;
  • R 1 , R 2 , R' f , and R 5 independently and independently for each occurrence, is optionally substituted with 1 -3 substiruents selected from the group consisting of Ci.ioalkyl, Ci.iohaloalkyl, halo, hydroxyl, carboxyl, Ci-ioalkoxycarbonyl,
  • iou ea cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulionamido, suifonyl, C 3 . 7 carbocyciyl,
  • Ci. b hetes'ocyclyl-Ci .ealkyl, phenyl, CYsheteroaryl, and
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1 -4 heteroatoms selected from N, O, and S;
  • composition is edible and capable of reducing bitter taste of a bitter tastant.
  • R 1 independently fo each occurrence, is selected from the group consisting of halo, hydroxyl, Cs ⁇ alkyl, Ci-ehaloalkyl, C 2 . 6 alkenyl, C 2 - 6 lkynyl, and Cs ⁇ alkoxy;
  • R' is selected from the group consisting of hydrogen, halo, hydroxyl, C h alky!, C]. 6 haloaikyl, optionally substituted by hydroxy!, amino, mono- or disubstituted Ch lky! amino, or carboxyl;
  • R 3 is selected from the group consisting of hydrogen, hydroxyl, Ci . 6 alkyl, C 2 . 6 alkenyl, C 2 - 6 alkynyl, and Cs ⁇ alkoxy;
  • R * is selected from the group consisting of hydrogen, hydroxyl, Chalky!, C 2- 2ialkenyl, C 2 . 2 iaikynyl, and C ⁇ alkoxy, wherein R 4 is optionally substituted by one or more occurrences of hydroxyl or acetyloxy;
  • R J is selected from the group consisting of hydrogen, hydroxyl, C
  • R 4 and R 5 together form -0; : wherein any of 1 , R 2 , R', R 4 , and R J , independently and independeniiy for each occurrence, is optionally further substituted as in paragraph 1 ;
  • n 0-3
  • R 2 and R 4 are as defined in paragraph 23, wherein the carbon marked with * optionally has R or S stereochemistry or is a mixture of R and S stereochemistry.
  • R* is selected from the group consisting of hydrogen
  • R J , R 'f , and R 5 are as defined in paragraph 23 ,
  • Compound 53 comestibly or biologically acceptable derivatives c thereof, or enantiomers or diastereoiiiers thereof.
  • composition comprising a compound according to Formula (VIII):
  • R 1 independently for each occurrence, is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci .iohaloalkyl, C ;_]oalkenyl, Cj-ioalkynyl, carboxyl,
  • heterocyclyl-C [.. 6 alkyl, phenyl, phenyl-Ci . 6 alkyl, Ci . 5 heteroaryl, and C].
  • R is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl,
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • R 3 is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C 2 .ioalkenyl, d_i 0 alkynyl, hydroxy!, Cuoacyloxy, C i_i 0 alkoxy, phenyloxy,
  • heterocyclic or heteroarom tic rings independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • R 2 and R 3 together form ) or -O-C M0 alkyl-O-;
  • R' is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, d.ioalkynyl, carboxyl, C 1. loalkoxycarbonyl, Cj.- ioaikenyloxycarbonyl, C2-ioalkynyloxycarbonyl, Ci.ioacyl, phosphoryl, phosphonate, phosphinate, cyano, sulfonate, suifamoyl, sulfonyl, C : ; profession 7 carbocyciyl, C w heterocyciyi, Cg-ioai l, Ci.sheteroaryl, and
  • heteroaryl-C L _ 6 alkyl wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoras selected from N, O, and S;
  • any of R 1 , R 2 , R', and R 4 is optionally substituted with 1 -3 substituents selected from the group consisting of Ci-ioalkyl, Ci.iohaloalkyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl, C2-ioalkenyloxycarbonyl, C 2 -ioa3kynyioxycarbonyi, Cnoacyl, Ci.ioacylaroiao, Ci.joacyloxy, Ci-iocarbonate, Cuo-tHcoxy, pbenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diC i.ioalkylamino, monoCi.ioalkylarnino, Ci.ioinxino, C i.iocarbamate, Cuoorea, cyano, nitro, azido, sulfhydryl
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1 -4 heteroatoms selected from N, O, and S;
  • n 0-3;
  • composition is edible and capable of reducing bitter taste of a bitter tastant.
  • R 1 independently for each occurrence, is selected from the group consisting of hydrogen, ( ' ,.:;! CS-ealkynyl, and Cj.eacyl;
  • R z is selected from the group consisting of hydrogen, C ⁇ alkyl, C2-6alkenyl, and C 2 - 6 alk yl;
  • R 3 is selected from the group consisting of hydrogen, C h alky!, C ⁇ alkenyl, and C ⁇ alkynyl;
  • R * is selected from the group consisting of hydrogen, C h alky!, C ⁇ alkenyl,
  • R 4 is as defined in paragraph 29.
  • R 1 and R 4 are as defined in paragraph 29;
  • m 0-2.
  • R ' is C i.galkyl
  • m 0-2.
  • R' , R 3 , and R 4 are as defined in paragraph 29;
  • m 0-2.
  • composition according to paragraph 29, wherein said compo according to Formula (Viil) is selected from the group consisting of:
  • composition comprising a compound according to Formula (Xi):
  • the bond with a dotted line optionally represents a single or double bond
  • R 1 , R , R 3 , R", and R' are independently selected from the group consisting of hydrogen, d.joalkyl, C ioalkenyl, and Cj.-]oalkynyl,
  • each of R 1 , R 2 , R ! , R°, and R 7 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, -O, -SH, -S, - 3 ⁇ 4, -CQ 2 H, -O(C l0 alkyi), -O(C 2-10 alkenyl), -0(C 2 -[oalkynyl), -S(C M .:;aikyl), -S(C 2 _ l0 alkenyl), -S(C 2 possiblyi 0 aikynyl), - NH(C O alkyl), -NH(C 2- [0 alkenyl), -NH(C M oalk.ynyl), -N(Ci.ioalkyI) 2 , - (C 2 .;oalkenyj) 2 , and -N(C 2 _]oalkynyl)
  • R 4 is absent or selected from the group consisting of hydrogen, Ci -i0 alky], C 2 ⁇ 0 alkenyl, C 2 .i 0 alkynyl, Cnoa yl, Ci.joacyloxy, Ci-ioacylamino, C M oacylthioxy, Ci-ioalkylester, Cnoafkenyiester, C M oalkynylester, C ioalkylaroide, Ci-ioalkenylamide, Ci-ioalkyaylainide, C ioalkylthioester, Ci-ioalkeoylthioester, and Ci.ioalkynylthioester;
  • Ci.ioalkynylester C;.ioaikylamide, Ci-ioalkenylamide, Ci-ioalkynylamide, Ci-ioalkylthioester, Ci .ioalkenylthioester, and Ci.ioalkynylthioester,
  • R 5 is absent or selected from the group consisting of hydrogen, Q .. 10 alkyl,
  • each Cuoalkyl, C 2 _;oalkenyl, and C 2 consult 1 oalkynyl may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, ), -SH, ⁇ S, -NH 2 , - C0 2 H, -OCC oalk i), -O(C 2 .
  • X is selected from the group consisting of -C(R )?-, -N(R )-, -0-, and -S-; provided that when the bond with the dotted line represents a double bond, R " is absent, and when the bond with the dotted line represents a single bond, R 4 is present; wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
  • R , R , R " ', R", and R' are independently selected from the group consisting of hydrogen, C h alky],
  • R 4 is absent or selected from the group consisting of hydrogen, C h alky!, C]. fl alkenylester, and Ci-ealkyn l ester;
  • R ' is absent or selected from the group consisting of hydrogen, C h alky 1, CVsalkenyl, and
  • each R a is independently selected from the group consisting of hydrogen.
  • X is selected from the group consisting of— O and S;
  • X is selected from the group consisting of ⁇ C(R il ) 2 -, -N(R a )-, -0-, and -S- ;
  • R 1 , R ⁇ R J , R 6 , and R' are independently selected from the group consisting of hy drogen, C h alky!, and Ci-galkynyl;
  • R is absent or selected from the group consisting of hydrogen, C h alk 1,
  • R 3 is absent or selected from the group consisting of hydrogen, C h alky!, C 2 ⁇ alkenyl, and ⁇ .salkynyl;
  • X is selected from the group consisting of O and S;
  • X is selected from the group consisting of ⁇ C(R il ) 2 -, -N(R a )-, -0-, and -S- ;
  • composition according to paragraph 38 wherein as valence and stability permit: R 1 , R ⁇ , R 3 , R 6 , and R' are independently selected from the group consisting of hydrogen, C h alky!, and Ci-salkynyl;
  • R 4 is absent or selected from the group consisting of hydrogen, C h alky!,
  • Ci-ealkenyl CYealkynyl, and Ci.gacyl
  • R 4 may be optionally substituted with O or ⁇ S;
  • R ⁇ is absent or selected from the group consisting of hydrogen, C h alky!,
  • X is selected from the group consisting of -C(R a ) 2 -, - (R a ) ⁇ , -0-, and -S-;
  • R 3 when the bond with the dotted line represents a double bond, R 3 is absent, and when the bond with the dotted line represents a single bond, R 4 is present.
  • R 1 , R 2 , R J , R 6 , and R' are independently selected from the group consisting of hydrogen, Cijalkyl, C2-3alke yl, and C 2 . 3 alk.ynyl;
  • R 4 is absent or selected from the group consisting of hydrogen, C h alky!,
  • X is selected from the group consisting of O and— S;
  • X is selected from the group consisting of -C(R a ) 2 - and - ⁇ -;
  • composition comprising a compound according to Formula (XII):
  • R 1 and R are independently selected from the group consisting of hydrogen,
  • R J and R 4 are independently selected from the group consisting of hydrogen, C t -ioalkyi, C 2 -ioalkenyl, C 2 _i 0 alkynyl, Ciache l0 acyl, C i_ ! 0 acyloxy, Ci.ioacylamino,
  • each of R 3 and R 4 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, O, -SH, -S, -N3 ⁇ 4, -C0 2 H, -OiCwoalkyl), -O(C 2 . 10 alkenyl), -0(C 2 -joaikynyl), - S(C M O aSkyI), -S(C 2- 10 alkenyl), -S(C 2- ioalkynyl), H(C l- [0 alkyl), NH(C 2 . 10 aikenyl), H(C 2 possibly. oalkynyl), (C l0 alkyi) 2 , N(C 2 _- 0 alkeny 1) 2 ,
  • R a is selected from the group consisting of hydrogen, Ci.ioalkyl, C 2 .; 0 alkenyl, and C 2 _ioalkynyl,
  • composition is edible and capable of reducing bitter taste of a bitter tastant.
  • R 1 and R 2 are independently selected from the group consisting of hydrogen, C h alky], C 2 .. 6 alkenyl, and C 2 _ 6 alkynyl;
  • R 3 and R 4 are independently selected from the group consisting of hydrogen, Ci-ealk i, C 2 .. 6 alkenyl, C 2 .. 6 alkynyl,
  • d is selected from the group consisting of hydrogen, C ⁇ alkyl, and C 2 - 6 alkynyl. 43, The composition according to paragraph 42, wherein as valence and stability permit:
  • R 2 are independently selected from the group consisting of hydrogen, C;. 6 alkyl, C 2 - ⁇ ;aikenyl, and C 2 _ 6 aikynyl;
  • R 4 are independently selected from the group consisting of hydrogen.
  • Ci-galkenylester Ci-galkylfhioester
  • X and Y are independently selected from the group consisting of a direct bond
  • R a is selected from the gs'oup consisting of hydrogen, C h alky!, C 2 . 6 alkenyl, and C 2 . 6 alkynyl, 44, The composition according to paragraph 43, wherein as valence and stability permit:
  • a dotted line optionally represents a single or double bond
  • R 1 and R 2 are independently selected from the group consisting of hydrogen, Ci ⁇ alkyl, C 2 - 4 alk.en.yl, and C 2 _ 4 al.kynyl;
  • R 3 and R 4 are independently selected from the group consisting of hydrogen, C 2 - 4 alk.en.yl, C 2 -4a.ik.ynyl, and
  • a dotted line optionally represents a single or double bond
  • R 1 and R 2 are independently selected from the group consisting of hydrogen, C h alky!, C 2 - 4 alk.en.yl, and C h al y siyl;
  • R 3 and R 4 are independently absent or independently selected from the group consisting of hydrogen, d- 4 alkyl, C 2 - 4 alkenyl, Ci- 4 acyi;
  • composition comprising a compound selected from the group consisting of:
  • composition is edible and capable of reducing bitter taste of a bitter tastant.
  • a composition comprising:
  • composition is edible.
  • composition according to paragraph 49 wherein the bitter tastant is a foodstuff.
  • composition according to paragraph 49 wherein the bitter tastant is a bitter tasting salt.
  • composition according to paragraph 51 wherein the bitter testing sait a magnesium salt, a calcium salt, or a potassium salt.
  • composition according to paragraph 52, wherein the potassium containing salt is KG or potassium lactate.
  • a food product comprising the compositions of any one of paragraphs 1-54, 56.
  • a method of preparing an edible composition comprising:
  • the comestibly acceptable carries' comprises a bitter tasting salt.
  • the bitter tasting salt is a magnesium salt, a calcium salt, or a potassium salt.
  • the potassium salt is KC1 or potassium l ctate.
  • the edible composition further comprises one or more components selected from the group consisting of: NaCl, sodium lactate, and sugar.
  • a method of reducing the amount of NaCl in an edible composition comprising:
  • a method of reducing the amount of sodium lactate in an edible composition comprising:
  • a method of reducing the amount of sugar in an edible composition comprising:
  • a method of reducing the sodium intake of a subject comprising:
  • a method of reducing the sugar intake of a subject comprising:
  • a method of reducing bitter taste attributed to a bitter tastant in an edible co mposition comprising ;
  • a method of reducing bitter taste attributed to a bitter tastant in an edible co mposition comprising ;
  • bitter tasting salt is a magnesium salt, a calcium salt, or a potassium salt. ⁇ 08.
  • the potassium salt is CS or potassium 1 actate ,
  • a method of preserving an edible composition comprising:
  • a method of reducing the amount of sodium in an edible composition while preserving the edible composition comprising:
  • a pharmaceutical composition comprising:
  • a pharmaceutical composition comprising:
  • a consumer product comprising:
  • a consumer product for reducing bitter taste of a bitter tastant comprising:
  • a method of inhibiting a bitter taste receptor comprising:
  • Figures 1A-Q disclose exemplary date for solution and foodstuff tasie testing of the compositions comprising compounds of Formula ( ⁇ ) of the present invention.
  • Figures 2A-E disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (V) of the present invention.
  • Figures 3 ⁇ - ⁇ disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (VIII) of the present invention
  • Figu re 4A-U disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (XI), Formula (XII), and compounds 95 -134 of the present invention. Detailed Description of the invention
  • acyt refers to an alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl or arytcarbonyl substituent, wherein the alkyl, alkenyl, alkynyl or aryl portion may be optionally substituted.
  • alkyl, alkenyl, alkynyl or aryl portion may be optionally substituted.
  • acyi substituents include, but are not limited to, acetyl, propionyl, butyryl and benzoyl.
  • acyloxy refers to an -0-C(0)R substituent, wherein R is alkyl, alkenyl, alkynyl or aryl, and wherein the alkyl, alkenyl, alkynyl or aryl portion may be optionally substituted.
  • acyloxy groups include, but are not limited to, acetoxy, propanoyloxy, butanoyloxy, pentanoyloxy and benzoyloxy.
  • aliphatic refers to straight chain or branched hydrocarbons that are completely saturated or that contain one or more units of unsaturation.
  • aliphatic groups include substituted or unsubstituted linear or branched alkyl, alkenyl and alkynyl groups.
  • alkoxy refers to O-alkyl substituent, wherein the alkyl portion may be optionaliy substituted.
  • alkoxy substituents include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy.
  • alkoxy also explicitly included within the scope of the term "alkoxy" are O-alkenyl or O-alkynyl groups, in all cases, the alkyl, alkene and aikyne portions may be optionally substituted.
  • alkyl refers to both, straight and branched saturated chains containing, for example, 1-3, ! -6, 1-9, or 1- ! 2 carbon atoms. An alkyl group may be optionally substituted.
  • alkylthio refers to an S-alkyl substituent, wherein the alkyl portion may be optionally substituted.
  • alkylthio substituents include, but are not limited to, methylthio, ethylthio and isopropylthio. Also explicitly included within the scope of the term
  • alkylthio are S-alkenyl or S-alkyoyl groups, in all cases, the alkyl, alkene and aikyne portions may be optionally substituted.
  • alkenyl refers to bot straight and branched saturated chains containing, for example, 2-3, 2-6, 2-9, or 2- i 2 carbon atoms, and at least one carbon-carbon double bond.
  • a alkenyl group may be optionally substituted.
  • alkynyl refers to both straight and branched saturated chains containing, for example, 2-3, 2-6, 2-9, or 2-12 carbon atoms, and at least one carbon-carbon triple bond.
  • An alkynyl group may be optionally substituted.
  • araikyl refers to an alkyl group substituted by an aryl. Also explicitly included within the scope of the term “araikyl” are alkenyl or alkynyl groups substituted by an aryl.
  • araikyl groups examples include benzyl and phenethyl.
  • An araikyl group may be optionally substituted.
  • artificial sweetener and “sugar substitute” refer to a food additive that confers a sweet taste but has less caloric energy than sugar. In some instances, the caloric energy of the "artificial sweetener” or “sugar substitute” is negligible.
  • aryl refers to monocyclic or polycyclic aromatic carbon ring systems having five to fourteen members.
  • aryl groups include, but are not limited to, phenyl (Phi, l-naphthyl, 2-naphthyl, 1-anthracyl and 2-anthracyl.
  • An aryl group may be optionally substituted.
  • arylalkoxy refers to a group having the structure -O-R-Ar, where R is alkyl and Ar is an aromatic substituent. Also explicitly included within the scope of the term
  • arylalkoxy are -O-R-Ar groups, wherein R is alkenyl or alkynyl, In all cases, the alkyl, alkene, aikyne and aryl portions may be optionally substituted.
  • bitter or “bitter taste” as used herein refers to the perception or gustatory sensation resulting following the detection of a bitter tastant.
  • the following attributes may contribute to bitter taste: astringent, bitter-astringent, metallic, bitter-metallic, as well as off-tastes, aftertastes and undesirable tastes including but not limited to freezer-burn and card-board taste, and/or any combinations of these.
  • off-taste is often synonymous with “bitter taste.”
  • the diversity of bitter tastes may reflect the large number of bitter receptors and the differential detection of bitter tastants by these receptors.
  • Bitter taste as used herein includes activation of a bitter taste receptor by a bitter tastant.
  • Bitter taste as used herein also includes activation of a bitter taste receptor by a bitter tastoint followed by downstream signaling.
  • Bitter taste as used herein also includes activation of a signaling pathway after stimulation by a bitter tastant.
  • Bitter taste as used herein further includes perception resulting from signaling following the detection of a bitter tastant by a bitter taste receptor.
  • bitter taste as used herein further includes perception resulting from signaling following contacting a bitter taste receptor with a bitter tastant, Bitter taste can be perceived in the brain, [0093]
  • bitter taste receptor refers to a receptor, typically a cell surface receptor, to which a bitter tastant can bind.
  • Bitter taste receptors may be present in the oral cavity, and/or throughout the gastrointestinal tract, including the stomach, intestines, and colon. Bitter receptors can also be present in vitro, such, as in an assay, including but not limited to a cell based assay or a binding assay.
  • bitter tastant refers to a compound that activates or that can be detected by a bitter taste receptor and/or confers the perception of a bitter taste in a subject.
  • bitter tastant also refers to a multiplicity of compounds that combine to activate or be detected by a bitter taste receptor and/or confer the perception of a bitter taste in a subject.
  • bitter tastant further refers to a compound that is enzymatically modified upon ingestion by a subject to activate or be detected by a bitter taste receptor and/or confer the perception of a bitter taste in a subject.
  • bitter tastant a compound which confers a different kind of bitter taste compared to the kind of bitter taste perceived for the same compound by other individuals.
  • bitter tastant also refers to a compound which confers a bitter taste.
  • bitter tastants or substances including foods that comprise a bitter tastant and taste bitter include coffee, unsweetened cocoa, marmalade, bitter melon, beer, bitters, citrus peel, dandelion greens, escarole, quinine, magnesium salts, calcium salts, potassium salts, KG, potassium lactate, Acesulfame K, Brussels sprouts, asparagus, bitter gourd, wild cucumber, celery, hops, kohlrabi, radish leaf, ginseng, pumpkin, collard greens, kale, sparteine, caffeine, atropine, nicotine, urea and strychnine.
  • bitter tastants include pharmaceuticals.
  • pharmaceuticals as bitter tastants include acetaminophen, ampicillin, azithromycin,
  • carbocyl refers to monocyclic or polycyclic non-aromatic carbon ring systems, which may contain a specified number of carbon atoms, preferably from 3 to 12 carbon atoms, which are completely saturated or which contain one or more units of iin saturation.
  • a carbocyciic ring system may be monocyclic, bicyclic or tricyclic.
  • a carbocyclyl ring may be fused to another ring, such as an aryl ring or another carbocyciic ring.
  • carbocyclic rings could include cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, cyclohexenyl, cyclopentenyl, indanyl, tetrahydronaphthyl and the like.
  • carbocyclic or “carbocyclyl,” whether saturated or unsaiuraied, also refers to rings that are optionally substituted unless indicaied.
  • Carbocyclic or “carbocylyi” also encompasses hybrids of aliphatic and carbocyclic groups, such as (cycioa5kyi)alkyl, (cycloalkenyl)alkyl and (cycloalkyl)alkenyl.
  • compositions refers to any comestibly or biologically acceptable salt, ester, or salt of such ester, of a compound of the present invention, which, upon ingestion, is capable of pro viding (directly or indirectly) a compound of the present invention, or a metabolite, residue or portion thereof, characterized by the ability to reduce the perception of a bitter taste attributed to a bitter tastant.
  • the term “comestibly or biologically acceptable derivative” refers to any comestibl or biologically acceptable derivative of a compound of the present invention, which, upon ingestion, is capable of providing (directly or indirectly) a compound of the present invention, or a metabolite, residue or portion thereof, characterized by the ability to reduce the perception of a bitter taste attributed to a bitter tastant.
  • a “comestible product” is a product suitable for oral use, such as eating or drinking. Therefore, a comestibly acceptable compound is an edible compound.
  • consumer product refers to health and beauty products for the personal use and/or consumption by a subject.
  • Consumer products may be present in any form including, but not limited to, liquids, solids, semi-solids, tablets, capsules, lozenges, strips, powders, gels, gums, pastes, slurries, syrups, aerosols and sprays.
  • Non-limiting examples of consumer products include nutriceutieals, nutritional supplements, lipsticks, lip balms, soaps, shampoos, gums, adhesives (e.g., dental adhesives), toothpastes, oral analgesics, breath fresheners, mouthwashes, tooth whiteners, and other dentifrices.
  • diet collectively refers to the food products and/or beverages consumed by a subject.
  • a subject's “diet” also includes any consumer products or pharmaceutical compositions the subject ingests,
  • ible composition refers to a composition suitable for consumption, typically via the oral cavity (although consumption may occur via non-oral means such as inhalation).
  • Edible compositions may be present in any form including, but not limited to, liquids, solids, semi-solids, tablets, lozenges, powders, gels, gums, pastes, slurries, syrups, aerosols and sprays.
  • edible compositions include food products, pharmaceutical compositions, and consumer products.
  • the term edible compositions also refers to, for example, dietary and nutritional supplements.
  • edible compositions also include compositions that are placed within the oral cavity but not swallowed, including professional dented products, such as dental treatments, fillings, packing materials, molds and polishes.
  • the term "comestible” refers to similar compositions and is generally used as a synonym to the term "edible.”
  • an effective amount of a compound of the present invention is an amount capable of reducing the perception of bitter taste associated with a bitter tastant.
  • effective amount of a compoimd of the invention also refers io an amount which, when added to an edible composition, reduces the bitter taste of, e.g., a NaCl substitute, thereby allowing for the maintenance of the perception of a desired salty flavor of a said edible composition.
  • the term "effective amount of a compoimd” also refers to an amount which, when added to an edible composition, allo ws for the preservation, of a food product, while reducing or eliminating bitter taste associated with a bitter tastant in. the preservative.
  • the term “effective amount” also refers to the amount of a compound of the present invention capable or reducing or eliminating the perception of a bitter taste or aftertaste associated with either a bitter tastant in a food product or an inherently bitter food product.
  • flavor modifi er refers to a compound or a mixture of compounds that, when added to an edible composition, such as a food product, modifies (e.g., masks, eliminates, decreases, reduces, or enhances the perception of) a flavor (e.g., sweet, salty, umami, sour, or bitter taste) present in the edible composition.
  • a flavor e.g., sweet, salty, umami, sour, or bitter taste
  • food product refers to any composition comprising one or more processed foodstuff.
  • Food products include, but are not limited to, confectionaries, bakery products
  • ice creams including but not limited to impulse ice cream, take-home ice cream, frozen yogurt, gelato, sorbet, sherbet and soy, oat, bean and rice-based ice cream
  • dairy products including, but not limited to, drinking milk, cheese, yogurt, and sour milk drinks
  • cheeses including, but not limited to, natural cheeses and processed cheeses
  • butter margarine
  • sweet and savory snacks including but not limited to fruit snacks, chips/crisps, tortilla/com chips, popcorn, pretzels, chocolates, and nuts
  • hot and cold beverages including, but not limited to, beverages, beverage mixes, concentrates, juices, carbonated beverages, non-carbonated beverages, alcoholic beverages, non-alcoholic beverages, soft drinks, sports drinks, isotonic drinks, coffees, teas, bottled waters, and beverages prepared from botanicals and botanical extracts (including cold
  • the food product is animal feed.
  • the food product may be a pet food product, i.e. a food product for consumption by a household pet.
  • the food product is a livestock food product, i.e. a food product for consumption by livestock.
  • foodstuff refers to an unprocessed ingredient or a basic nutrient or flavor containing element used to prepare a food product.
  • foodstuffs include: fruits, vegetables, meats, fishes, grains, milks, eggs, tubers, sugars, sweeteners, oils, herbs, snacks, sauces, spices and salts.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms.
  • heteroaiyi refers to monocyclic or polycyclic aromatic
  • heterooaralkyl alkenyl or alkynyl groups substituted by a heteroaiyi.
  • a heteroaiyi ring may have one to four heteroatoms
  • Heteroaiyi groups include, without limitation, 2-furanyl, 3-furanyl, N-imidazolyl, 2iroidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4isoxazoSyl, 5-isoxazolyl,
  • heteroaryl ring also refers to rings that are optionally substituted.
  • fused polycyclic heteroaryl and aryl ring systems in which a carbocyclic aromatic ring or heteroaiyi ring is fused to one or more other rings include, tetrahydronaphthyl, benzimidazolyl, benzoihienyl, benzoiuranyl, indolyl, quinolinyl, benzothiazolyl, benzoxazolyl, benzimidazoiyl, isoquinolinyl, isoindolyl, acridinyl, benzoisoxazolyl, and the like.
  • heterocyclic or “heterocyclyl” refers to non-aromatic saturated or unsaturated monocyclic or polycyclic ring systems containing one or more heieroatoms and with a ring size of three to fourteen.
  • a heterocyclic ring may have one to four heteroatoms so long as the heterocyclic ring is chemically feasible and stable and may be fused to another ring, such as a carbocyclic, aryl or heteroaryl ring, or to another heterocyclic ring.
  • a heterocyclic ring system may be monocyclic, bicyclic or tricyclic.
  • heterocyclic or “heterocyclyl”, as used herein, is a group in which one or more carbocyclic rings are fused to a heteroaryl.
  • heterocyclic rings include, but are not limited to, 3-l H-benzimidazol-2-one, 3-lH-alkyl ⁇ benzimidazoi-2-one, 2-tetrahydrofuranyl, 3-tetrahydroforariyl, 2-tetrahydrothiophenyl, 3-tetrahydrothiophetryl, 2-morpholino, 3-morpholino, 4-morpholino, 2-thioniorpholino, 3-thiomorpholino, 4-thiomorpbolitK), 1-pyrrolidinyl,
  • ppm parts per million
  • concentration of a solution For example, one gram of solute in 1000 ml of solvent has a concentration of 1000 ppm and one thousandth of a gram (O.OOlg) of solute in 1000 ml of solvent has a concentration of one ppm. Accordingly, a concentration of one milligram per liter (i.e. 1 mg/L) is equal to 1 ppm.
  • pharmaceutically active ingredient refers to a compound in a pharmaceutical composition which is biologically active
  • potassium salt refers to a salt wherein potassium is the cation.
  • Potassium salts in the context of the present invention are preferably edible potassium salts including, but not limited to, Acesuifame K (Ace K), aluminum potassium sulfate, dipotassium guanylate, dipotassium iaosinate, monopotassium glutamate, potassium acetate, potassium acid tartate, potassium acid tartrate, potassium adipate, potassium alginate, potassium aluminum silicate, potassiu!Ti ascorbate, potassium aspartate, potassium benzoate, potassium bicarbonate, potassium bisuifate, potassium bisulfite, potassium bromate, potassium carbonate, potassium chloride, potassium citrate, potassium dihydrogen citrate, potassium dihydrogen phosphate, potassium ferrocyanide, potassium fumarate, potassium gibbereilate, potassium gluconate, potassium hydroxide, potassium hydrogen sulfiie, potassium iodide, potassium lactate, potassium maiate, potassium
  • processed foodstuff refers to a foodstuff has been subjected to any process which alters its original state (excluding, e.g., harvesting, slaughtering, and cleaning).
  • methods of processing foods include, but are not limited to, removal of unwanted outer layers, such as potato peeling or the skinning of peaches; chopping or slicing; mincing or macerating;
  • liquefaction such as to produce fruit juice
  • fermentation e.g. beer
  • emu!sification cooking, such as boiling, broiling, frying, heating, steaming or grilling; deep flying; baking; mixing; addition of gas such as air entrainment for bread or gasification of soft drinks; proofing; seasoning (with, e.g., herbs, spices, salts); spray drying; pasteurization; packaging (e.g., canning or boxing); extrusion; puffing; blending; and preservation (e.g., adding salt, sugar, potassium lactate or other preservatives).
  • replace refers to substituting one compound for another compound in or in the preparation of, for example, an edible composition, such as food product, it includes complete and partial replacements or substitutions.
  • salty flavor refers to the taste elicited by, for example, ions of alkali metals salts (e.g., a f and CI " in sodium chloride).
  • alkali metals salts e.g., a f and CI " in sodium chloride
  • compositions eliciting a salty flavor include table salt (sodium chloride), sea water, sea salt and potassium chloride.
  • the amount of salty flavor or the saltiness of a composition can be determined by, e.g., taste testing.
  • sodium or “sodium salt” refers to the amount of sodium (i.e., sodium salt) ingested or otherwise consumed by a subject.
  • sodium or a “sodium salt” refers to a salt or compound wherein sodium is the cation.
  • Sodium salts in the context of the present invention include, but are not limited to, aluminum sodium sulfate, calcium disodium EDTA, dioctyl sodium sulfosuccinate, disodium 5 '-ribonucleotides, disodium ethylenediaminetetraacetate, disodium guanylate, disodium inosinate sodium acetate, monosodium glutamate (MSG), potassium sodium tartrate, sodium acid pyrophosphate, sodium adipate, sodium alginate, sodium aluminosilicate, sodium aluminum phosphate (acidic), sodium aluminum phosphate (basic), sodium ascorbate, sodium benzoate, sodium bicarbonate, sodium bisulfate, sodium bisulfite, sodium carbonate, sodium carboxymethylcellulose, sodium caseinate, sodium chloride, sodium citrate, sodium cyclamate, sodium dehydroacetate, sodium diacetate, sodium dehydroacetate, sodium dihydrogen citrate, sodium dihydrogen phosphate, sodium
  • hypophosphite sodium tartrate (e.g., sodium L(+) -tartrate), sodium lactate, sodium laur l sulfate, sodium malate, sodium metabisulfite, sodium metaphosphate, sodium methyl parahydroxybenzoate, sodium nitrate, sodium nitrite, sodium O-phenylphenol, sodium phosphate (dibasic), sodium phosphate (monobasic), sodium phosphate (tribasic), sodium polyphosphate, sodium potassium tartrate, sodium propionate, sodium propyl para-hydroxybeozoate, sodium pyrophosphate, sodium saccharin, sodium sesquicarbouate, sodium stearoyl lactylate, sodium stearyl fumarate, sodium succinate, sodium sulfate, and starch sodium octenyisuccinate,
  • sodium tartrate e.g., sodium L(+) -tartrate
  • sodium lactate sodium laur l sulfate
  • sodium malate sodium metabisulfite
  • sodium intake refers to the amount of sodium ingested or otherwise consumed by a subject
  • stable in the context of a chemical structure refers to the chemical state when a system is in its lowest energy state, or in chemical equilibrium with its environment.
  • a stable compound or, e.g., a compound containing a number of atoms or substitutions that are stable
  • a subject refers to a mammal. In preferred embodiments, the subject is human. In some embodiments, a subject is a domestic or laboratory animai, including but not limited to, household pets, such as dogs, cats, pigs, rabbits, rats, mice, gerbils, hamsters, guinea pigs, and ferrets. In some embodiments, a subject is a livestock animal. Non-limiting examples of livestock animals include: alpaca, bison, camel, cattle, deer, pigs, horses, llamas, mules, donkeys, sheep, goats, rabbits, reindeer, and yak.
  • sugar refers to a simple carbohydrate, such as a monosaccharide or a disaccharide, that delivers a primary taste sensation of sweetness.
  • sugar include glucose, fructose, galactose, sucrose, lactose, and maltose.
  • sweet flavor refers to the taste elicited by, for example, sugars.
  • compositions eliciting a sweet flavor include glucose, sucrose, fructose, saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, alitame, and neotame.
  • the amount of sweet flavor or the sweetness of a composition can be determined by, e.g., taste testing.
  • terpenes refers to compounds comprising repeating units of isoprene.
  • the basic molecular formula of a terpene is (CsHs),, where n is the number of linked isoprene units.
  • terpeneoids refers to compounds comprising terpenes and derivatives thereof.
  • terpenoids have at least one C 5 H 8 hydrocarbon unit with one or more points of unsaturation.
  • terpenoids comprise saturated terpene unites and derivatives thereof and have no points of unsaturation.
  • An aryl, aralkyl, heteroaryl, or heteroaralkyl group may contain one or more
  • substituents on the unsaturated carbon atom of an aryl or heteroaryl group include, but are not limited to, halogen, -CF 3 , -R', -OR', -OH, -SH, -SR', protected OH (such as acyloxy), -N0 2 , -CN, -NH 2 , -NHR, -N(R') 2 , -NHCOR', -NHCONH 2 , -NHCONHR', -NHCON(R') 2 , -NRCOR', -NHC0 2 H, - ⁇ ! tU ) R ' .
  • 11' is selected from H, aliphatic, carbocyciyi, heterocyclyl, aryl, aralkyl, heteroar l, or heteroaralkyl and each R' is optionally substituted with one or more halogen, niiro, cyano, amino, -NH-(imsubstituted aliphatic), -N-( «nsubstituted aliphatic);., carboxy, carbamoyl, hydroxy, -0-(unsubstiruted aliphatic), -SH, -S-(unsubstituted aliphatic), CF 3 , -S(0) 2 NH 2 ' unsubstituted aliphatic, unsubstituted carbocyciyi, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted aralkyl, unsubstituted heteroaryl, or unsubstituted heteroa
  • An aliphatic group, a carbocyclic ring or a heterocyclic ring may contain one or snore substituents.
  • the compounds of the invention are intended to include all stereochemical forms of the compound, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S). Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the invention.
  • formulas depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present formulas except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by a I J C- or l C-enriched carbon are within the scope of this invention.
  • the present invention provides edible compositions comprising a compound of the present invention, including food products, consumer products, and pharmaceutical compositions comprising said compounds, and methods of preparing a such compositions.
  • the present invention also provides methods of reducing the amount of sodium (e.g., NaCl or sodium lactate) or sugar in a food product, a method of reducing the sodium or sugar intake in a diet, a method of reducing bitter taste, and a method of reducing the activity of a bitter taste receptor.
  • the present invention also includes reducing the amount of sodium in a edible composition or diet by replacing a sodium containing compound or composition with a potassium containing compound or composition.
  • the present invention also includes reducing the amount of sugar in a edible composition or diet by replacing sugar with a pot sium containing sweetener, such as Acesulfame K.
  • the invention provides an edible composition comprising a compound of the invention for reducing bitter taste of a bitter tastant.
  • Edible .comB ⁇ Edible .comB ⁇
  • R 1 , R2, R3, R4, m, n, p and t refer to compounds of Formula (i), Formula (la), Formula (Ila), Formula ( ITa), Formula (Tib),
  • the present invention provides an edible composition for reducing bitter taste of a bitter tastant, wherein the composition comprises a terpenoid compound.
  • the terpenoid compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant.
  • the terpenoid compound has a molecular weight less than about 1000, 500, or 300 daltons.
  • the terpenoid compound is a compound of Formula (I):
  • R 1 is absent or is selected from the group consisting of hydrogen, Ci .ioaikyl, C;.[i;.haioaikyl, C ;.]oalkenyl, C ? ..joalkynyl, hydroxy!, Cj.ioacyl amino, Cj.ioacyloxy, Ci-iocarbonate, Cuoaikoxy, phenyloxy, phenyl-Cj ⁇ alkyloxy, Ci.sheteroaryloxy, C ; . 5 heteroaryl-C [. 6 alkyloxy, C 3-!
  • R 3 is selected from the group consisting of hydrogen C 1 0 alkyl, Ci.iohaloalkyl, C2-ioalkenyl, Q.ioalkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
  • 6 lkyl, Ci. 6 heterocycly!, phenyl, Ci.sheteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • R' is selected from the group consisting of hydrogen, Cj.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, Ci-ioaikynyi, halo, hydroxy!, carboxyl, C i.soalkoxycarbonyi,
  • R 1 , R 2 , R', and R 4 independently, is optionally substituted wish 1-3 substituents selected from ihe group consisting of C[.i 0 alkyl, C i.iohaloalkyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl, C2- loalkenyloxycarbonyl,
  • n 0-2;
  • n 0-2;
  • p 0-2;
  • t 0-2;
  • Ci and C ' e in Formula (I) optionally are bonded together to form a 6-membered ring;
  • R 1 is absent or is selected from the group consisting of hydroxy!, Ciache 6 aikoxy, and C]. 6 aeyloxy;
  • R' is selected from the group consisting of hydrogen, C h alky!, C2-6alkenyl, and
  • R 3 is selected from the group consisting of hydrogen and Ci . 6 alkoxy
  • R * is selected from the group consisting of hydroxy!, C ; .. fi a1koxy, and
  • n 0-2;
  • n 0-2;
  • p 0-2;
  • t 0-2;
  • R ! is absent or is selected from the group consisting of hydroxy!, C,_ 6 a]koxy, and C;. 6 acyloxy;
  • R z is selected from the group consisting of hydrogen, C h alky!, C 2 - 6 alkenyl, and C 2 - 6 alkynyl;
  • R J is selected from the group consisting of hydrogen and Ci. 6 a!koxy
  • R 4 is selected from the group consisting ofhydroxyl, C;. 6 a!koxy, and
  • n 0-2;
  • p 0-2;
  • t 0-2;
  • R 1 is absent or is selected from the group consisting of hydroxy!, Q ⁇ alkoxy, and
  • R z is selected from the group consisting of hydrogen.
  • C h alky C 2-3 alkenyl, and C 2 . 3 lkynyl;
  • R 3 is selected from the group consisting of hydrogen and jalkoxy
  • R '* is selected from the group consisting of hydroxy!, Qjalkoxy, and m is 1 ;
  • n 0;
  • t 1 ;
  • R ! is absent or is selected from the group consisting of hydroxy!, C ⁇ alkoxy, and
  • R ⁇ is selected from the group consisting of hydrogen, C h alky!, Cksalkenyl, and C2- 3 alkynyl;
  • R 3 is selected from the group consisting of hydrogen and
  • R 4 is selected from the group consisting of hydroxy!, C,_ 3 alkoxy, and Cuacyloxy; m is 1 ;
  • n 0;
  • p 1 ;
  • t 1 ;
  • R 1 is absent.
  • R 1 is absent and C. is past of a double bond
  • R' is present and is hydrogen, hydroxyl, d ⁇ aikoxy, or Cj-gacyloxy.
  • R l is present and is hydrogen or hydroxvl.
  • the compound of Formuia (I) includes a £ " -double bond between C ' s and C fi .
  • the compound of Formuia ( ⁇ ) includes a Z-double bond between C ' s and Ce.
  • the compound of Formula (I) includes a mixture of is Z-double bonds between C 5 and C 6 , in yet additional embodiments, the compound of Formula (I) does not include a double bond between C $ and C 6 .
  • the compound of Formula (I) includes a Z-double in one or more "t” segments.
  • the compound of Formula (I) includes a v-double bond in one or more "t” segments.
  • the compound of Formula (I) includes a mixture of 7/Z-double bonds in one or more "t” segments.
  • the compound of Formuia (I) includes no carbon-carbon double bonds, one carbon -carbon double bond, two carbon -carbon double bonds, three carbon-carbon double bonds, four carbon-carbon double bonds, five carbon -carbon double bonds, or six carbon-carbon double bonds.
  • the compound of Formula (I) includes no carbon-carbon double bonds, one carbon-carbon double bond, two carbon-carbon double bonds, three carbon-carbon double bonds or four carbon-carbon double bonds.
  • the compound of Formula (I) includes no carbon-carbon double bonds, one carbon-carbon double bond, or two carbon-carbon double bonds.
  • R is hydrogen, in other embodiments, R " is
  • Ci.. 6 alkyl such as methyl, or C 2 ⁇ alkenyl, such as isoallyl (e.g., 1-propenyl).
  • R ! is hydrogen
  • R' is C [. ⁇ alkoxy, such as methoxy or ethoxy
  • R 4 is hydroxyl. in other embodiments, R 4 is
  • R 4 is C i .ieacyloxy, such as C [,.»acyioxy, e.g., formyloxy, acetyioxy, proptonyloxy, butanoyloxy, phenyiacetyioxy, etc.
  • R is C ⁇ acyloxy or Cijacyloxy. in other embodiments, R 4 is acetyioxy.
  • R 3 and R 4 together form ).
  • m is 0, in other embodiments, m is 1 , In yet further embodiments, m is 2.
  • n is 0. In other embodiments, n is 1. in yet further embodiments, n is 2.
  • p is 0. In other embodiments, p is 1. in yet further embodiments, p is 2.
  • t is 0. In other embodiments, t is 1 , In yet further embodiments, t is 2.
  • m is 1, n is 0, p is 1, and t is 1.
  • the terpenoid compound is a compound of Formula (ia);
  • R' is absent or is selected from the group consisting of hydrogen, Ci.ioalkyl, C;.iohaloalkyl, C soalkenyl, hydroxyl, Ci-ioacylamino, Q.ioacyloxy, Ci-iocarbonate, Ci. ioalkoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
  • Ci .iocarbamate Cuourea, sulfhydryl, Ci .i 0 alkyithio, sulfate, sulfonate, sulfamoyl, sulibnamido, suifonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
  • R " is selected from the group consisting of hydrogen, C i .ioalkyl, Ci .johaloalkyl, Cj.ioalkenyl, (3 ⁇ 4_ (0 alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
  • Ci-ioirnino Ci-iocarbamate
  • Ci.ir.itrea cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cv;carbocyclyl,
  • R 3 is selected from the group consisting of hydrogen C 1 0 alkyl, Ci.iohaloalkyl, C' l -ioal enyl, ⁇ 3 ⁇ 4.ioalkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
  • R is selected from the group consisting of hydrogen, Cuoalkyl, Ci.johaloalkyl, C-j-ioaBcenyl, ⁇ 3 ⁇ 4. )0 alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
  • Ci-iocarbonate Cuoafko y, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy, Cs-ioalkenyloxy, Cj-ioalkynyloxy, phosphoryl, phosphate, ph.osphon.ate, phosphinate, amino, di.Ci_ioalkylamino, monoCi_ioalkylamirio, C i.i iamido, Ci-ioiroino, Ci.iocaibamate, C MC ,iirea, cyano, nitro, azido, solfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C ⁇ carbocyclyl,
  • R 1 , R 2 , R', and R 4 independently, is optionally substituted with 1-3 substituents selected from the group consisting of CVioalkyl, Ci. i haloalkyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl, (.3 ⁇ 4. l oalkenyloxycarbonyl,
  • Ci.ioacyl Ci.ioacylaraioo
  • Ci.ioacyloxy Ci.ioacyloxy
  • CYiocarbonate Cj.ioalkoxy
  • phenyloxy phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi. joalkylamino, Ci.i 3 amido, Ci..
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • n 0-2;
  • R 1 is absent or is selected from the group consisting of hydroxyl, and C;. 6 acyloxy:
  • R 3 is selected from the group consisting of hydrogen and Ci-galkoxy
  • R' f is selected from the group consisting of hydroxyl
  • Ci-ieacyloxy; or R 3 and R 4 together form 0;
  • n 0-2;
  • R 1 is absent.
  • R 1 is absent and Ci is part of a double bond.
  • R 1 is present and is hydroxy!, Ci-galkoxy, or C i-eacyloxy, particularly hydroxy!.
  • the compound of Formula (ia) includes a E-double bond between C 5 and C 6 .
  • the compound of Formula (la) includes a Z-doub e bond between C 5 and C 6 .
  • the compound of Formula (la) includes a mixture of is/Z-double bonds between C5 and C ⁇ .
  • Formula (ia) does not include a double bond between C5 and CY
  • the compound of Formula (la) includes no carbon-carbon double bonds, one carbon-carbon double bond, two carbon-carbon double bonds, three carbon-carbon double bonds, or four carbon-carbon double bonds. In particular embodiments, the compound of Formula (la) includes no carbon-carbon double bonds, one carbon-carbon double bond, or two carbon-carbon double bonds.
  • R 2 is hydrogen. In other embodiments, R 2 is
  • CYealkenyl such as isoallyl (e.g., 1-propenyl).
  • R 3 is hydrogen. In other embodiments, R 3 is C [. ⁇ alkoxy, such as methoxy or ethoxy,
  • R 4 is hy droxyi. In other embodiments, R 4 is
  • R* is Cngacyloxy, such as C [ normally s acyloxy, e.g., formyloxy, acetyloxy, propionyloxy, botanoyloxy, phenylacetyloxy, etc.
  • R J and R 4 iogeiher form— O.
  • m is 0. In other embodiments, m is 1. In yet further embodiments, m is 2.
  • Q and C 6 are bonded together to form a 6-membered ring.
  • C i and C 6 are bonded together to form a 6-membered ring, and m is 0.
  • the compound of Formula (I) is a compound of Formul (Ha):
  • the compound of Formula (lla) is a compound of Formula (Ilia):
  • R 2 is as defined above.
  • C] and C are bonded together to form a 6-membered ring.
  • C i and C 3 ⁇ 4 are bonded together to form a 6-membered ring, and m is 1.
  • the compound of Formula ( ⁇ ) is a compound of Formula (lib):
  • the exo-cyciic dashed bond is a double bond, in other embodiments, the exo-cyclic dashed bond is a single bond.
  • the compound of Formula (lib) is a compound of Formula (111b) :
  • the exo-cyclic dashed bond is a. double bond. In other embodiments, the exo-cyclic dashed bond is a single bond,
  • the compound of Formula (I) does not include a double bond between C 5 and C 6 .
  • the compound of Formula (i) does not include a double bond between C 5 and C 6 , and C . and C 6 are not bonded together to form a 6-membered ring.
  • the compound of Formula (i) is a compound of Formula (lie):
  • R 1 is absent and C
  • the compound of Formula (lie) is a compound of Formula (Mb):
  • R 2 , R', and R 4 are as defined above.
  • R 4 is hydroxy! or C fl acyloxy, such as
  • Ci-gacyioxy e.g., formyloxy, acetyloxy, propionyloxy, butanoyloxy, phenyiacetyioxv, etc.
  • R 2 and R 3 are hydrogen and R 4 is hydroxy! or C ' igacyloxy, such as C 6 .ioaryl-C ( . 6 acyl, e.g., phenylacetyloxy.
  • R 2 and R J are bydrogen and R 4 is hydroxy!
  • the compound of Formula (IHc ) is a compound of Formula (IVc):
  • R 4 is as defined above.
  • the compound of Formula (I) includes a ii-double bond between C$ and Q.
  • the compound of Formula (I) includes a IT-double bond between and C & and C; and Cg are not bonded together to form a 6-membered ring.
  • the compound of Formula (I) is a compound of Formula (lid):
  • R a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R", R 1 , R 3 , and R 4 are as defined above.
  • R 1 is absent and Ci is part of a double bond.
  • the compound of Formula (lid) is a compound of Formula (Hid):
  • R 2 , , and R 4 are as defined above.
  • R 'f is hydroxy! or d-ieacyloxy, such as e.g., phenylacetyloxy.
  • R 4 is hydroxy! or Ci-ieacyloxy such as e.g., formyloxy, acetyloxy, propionyloxy, butanoy!oxy, phenylacetyloxy, etc.
  • R 2 and R" are hydrogen and R 'f is hydroxy! or C M6 acyloxy, suc as ( ⁇ !0 aryl-d. ⁇ sac l, e.g., phenylacetyloxy.
  • R' ' and R* are hydrogen and R 4 is hydroxy! or d-i 6 acyioxy, such as e.g., fomiyloxy, aceiyloxy, propionyioxy, butanoyloxy, phenylacetyloxy, etc.
  • the compound of Formula (Hid) is a compound of Formula (IVd):
  • R 4 is as defined above.
  • the compound of Formula (I) includes a Z-double bond between C5 and Cg.
  • the compound of Formula (I) includes a Z-double bond between C ⁇ and C & and C> and Ce are not bonded together to form a 6-membered ring.
  • the compound of Formula (I) is a compound of Formula (He):
  • R ! , R , R " , and R are as defined above.
  • R 1 is absent and there is a double bond between Ci and C2.
  • the compound of Formula (He) is a compound of Formula (Hie):
  • R 4 is hydroxy! or C i_ ! 6 acyioxy, such as e.g., phenylacetyioxy.
  • R 4 is hydroxyl or C ' i.; 6 acyloxy, such as C t -gacyloxy, e.g., formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc.
  • R:' are hydrogen and R 4 is hydroxyl or C M6 acyloxy, such as C 6 _; 0 aryFCi_ 6 acyl, e.g., phenylacetyioxy.
  • R 2 and R J are hydrogen and R 4 is hydroxyl or Ci.iKacyloxy, such, as Cj.gacyloxy, e.g., formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc.
  • the comp of Formula (IVe) is hydroxyl or C M6 acyloxy, such as C 6 _; 0 aryFCi_ 6 acyl, e.g., phenylacetyioxy.
  • R 2 and R J are hydrogen and R 4 is hydroxyl or Ci.iKacyloxy, such, as Cj.gacyloxy, e.g., formyioxy, acetyloxy, propionyloxy, butanoy
  • R 4 is as defined abo ve.
  • R 1 is present and is hydroxyl, C ' l ⁇ aikoxy, or Ci-gacyloxy, particularly hydroxyl.
  • the compound of Formula (I) is a compound of Formula (lifj:
  • R 2 , R', and R 4 are as defined above.
  • R " and R ' are hydrogen and R 4 is hydroxyl or Ci.ieacytoxy, such as e.g., phenylacetyioxy.
  • R 2 and R 3 are hydrogen and R 4 is hydroxyl or Cueacylo y, such as Ci.gacyloxy, e.g. formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc.
  • the compound of Formula (I) is a compound of Formula (ilg):
  • R is hydrogen and R " and R 4 are both C[- lko y, such as methoxy or ethoxy.
  • the compound of Formula ( ⁇ ) is a compound of Formula (lih):
  • the compound of Formula (I) is selected from the group consisting of damascene compounds (e.g., ⁇ -damascone, trans-a-damascone), ionone compounds (e.g., ⁇ -ionone, a-ionone, y-ionone, and dihydro- -ionone, particularly either ⁇ -ionone or a-ionone), nerol, geranyi isovalerate, geranyi acetone, neiyl acetate, geranyi propionate, geranyi butyrate, citronellyl propionate, citronellyl isobutyrate, citral diethyl acetal, geranyi phenyi
  • damascene compounds e.g., ⁇ -damascone, trans-a-damascone
  • ionone compounds e.g., ⁇ -ionone, a-ionone, y-ionone, and
  • the compound of Formula (I) is:
  • Palmarosa oil, Rusa oil, and Turkish, geranium oil 40 Palmarosa oil, Rusa oil, and Turkish, geranium oil
  • R 1 , R 2 , R 3 , R 4 , R ⁇ R° and n refer to compounds of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila).
  • the present invention provides an edible composition for reducing bitter taste of a bitter tastant, wherein the composition comprises a cbrosnan compound.
  • the chroman compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant.
  • the chroman compound has a molecular weight less than about 1000, 500, or 300 daltons.
  • the cbrosnan compound is a compound of Formul (V):
  • R 1 independently for each occurrence, is selected from the group consisting of C : _[oalkyl, C i.iohaloalkyl, Cj,ioalkenyl, .ioalkynyl, halo, hydroxy!, carboxyl,
  • Ci.ioalkoxycarbonyl CVioalkenyloxycarbonyl, i ioa!kynyloxycarbonyl, Ci.ioacyl, Ci-ioacylamino, Ci.ioacyioxy, CViocarbonate, Ci.ioalkox , phenyioxv,
  • R 3 is selected from the group consisting of hydrogen, Cuoalkyl, Ci.iohaloalkyl,
  • R 'f is selected from the group consisting of hydrogen
  • Ci_ioacyloxy Ci_ioacyloxy, Cuoalkoxy, phenyloxy,
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1-4 heteroatoms selected from. N, O, and S;
  • R 5 is selected from the group consisting of hydrogen, Ci.Tiaikyi,
  • phenyl-C j. 6 alkyloxy Ci.sheteroarytoxy, C3.1 oalkenyloxy, C;i..]i)alkynyioxy, amino, diCi.ioalkylamino, monoCj-ioalkylamino, sulihydryi,
  • heterocyclic or heteroaromatic rings independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
  • R 4 and R 5 together form or - -Ci -!0 alkyl-O-;
  • any of R 1 , R , R J , R 4 , and R ' is optionally substituted with 1-3 substituents selected from the group consisting of C ( -ioalkyl, C ' l .iohaloalkyl, halo, hydroxyl, carboxyl, C i. i0 alkoxycarbonyl, C 2 -ioalkenyioxycarbonyl, CVioalkynyloxycarbonyl, Ci.ioac l, Ci. K iacylamino, Ci.
  • Ci-sheteroaryl-C ealkyl and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from , O, and S; and
  • n 0-3.
  • R 1 independently for each occurrence, is selected from the group consisting of halo, hydroxy!, C h alky 1, Ci.ghaloalkyl, C 2 _,;alkenyl, C ⁇ lk n l, and Cusalkoxy;
  • R is selected from the group consisting of hydrogen, halo, hydro xyl. C h alky!, C ; _ 6 haS o Iky 1, C 2 -,;alkenyl, C 2 - 6 alkyn l, C;_ 6 a!koxy, C l-6 acyloxy optionally substituted by hydroxy!, amino, mono- or disubstituted C h alky! amino, or carboxyl;
  • R 3 is selected from the group consisting of hydrogen, hydroxy!, C h lk !,
  • R* is selected from the group consisting of hydrogen, hydroxy!, C h lky!, C 2-2 iaBcenyl, C 2 - 2 ;aikyny!, and Ci-ealkoxy, wherein R 4 is optionally substituted by one or more occurrences of hydroxy! or acetyloxy;
  • R ⁇ is selected from the group consisting of hydrogen, hydroxy!, C h lky!, C 2 - 2 ialkeny], C 2 . 2! alkynyi, and C ⁇ alkoxy, wherein R 5 is optional] ⁇ ? substituted by one or more occurrences of hydroxy! or acetyloxy;
  • n 0-3.
  • one or more occurrences of R' is C h alky!, such as methyl; R J is hydrogen; and R s is such as methyl.
  • the compound of Formula (V) is a compound of

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Abstract

The present invention provides edible compositions comprising a compound of the present invention, food products comprising such edible compositions and methods of preparing such food products. The present invention also provides methods of reducing the amount of NaC1 in a food product, methods of reducing the sodium intake in a diet, and methods of reducing bitter taste in a food product.

Description

COMPOUNDS, COMPOSITIONS, AND METHODS
FOR REDUCING OR ELIMINATING BITTER TASTE
[0001] The present invention relates to flavor in edible compositions. Background, of thejiweniion
[0002] The sense of taste, e.g., in human, can detect at least five traditional tastes: sweet, sour, salty, bitter, and umami (savory). Many nutritious substances including vegetables, foods, food ingredients and nutrients comprise bitter tastants and/or have a bitter taste, in addition, many pharmaceutical substances important to maintain or improve health comprise bitter tastants and/or have a bitter taste. While certain food products and consumer products have desirable bitter tastes, including coffee, beer and dark chocolate, in many contexts, consumers dislike such bitter tastes. For example, many consumers dislike the perception of certain bitter tastants and/or bitter taste and will avoid food or pharmaceutical products with an undesirable bitter tastant or bitter taste in favor of food and pharmaceutical products that have reduced levels of undesirable bitter tastants or that have reduced or that completely lack bitter taste. This aversion to products containing undesirable bitter tastants and/ or haying undesirable bitter taste may be caused by perception of bitter tastants and/or bitter taste mediated by activation of bitter receptors present in the oral cavity and/or in the gastrointestinal tract. In many cases, consumer dislike of bitter iastants and/or bitter taste prevents or hampers improvement of the nutritive quality and safety of foods as desired levels of nutrients or preservatives comprising bitter tastants and/or having bitter taste cannot be used. Also, dislike of or aversion to the bitter tastants or bitter taste of some pharmaceutical agents negatively impacts compliance with prescribed regimens for their use.
[0003] For instance, several additives, preservatives, emulsifiers and foodstuffs used in the production of food products comprise bitter tastants and/or have a bitter taste. While these additives, preservatives, emulsifiers and foodstuffs may affect the taste of a food product, they may also be important for improving the shelf life, nutritive qualisy, or texture of the food product. For example, the increasing trend of hypertension and cardiovascular disease has been attributed, in part, to the high sodium intake of the Western diet. Accordingly, substitution of sodium chloride with another salty tasting compound is desirable. The most common sodium chloride substitute is potassium chloride, which, to a portion of the population, is perceived as possessing a bitter taste in addition to its salty taste. The bitter taste of potassium chloride limits the extent to which, it may be used to replace sodium chloride in foods without causing undesired bitter taste for the portion of the population sensitive to it.
[0004] Another common food additive, sodium lactate, has a broad antimicrobial action, is effective at inhibiting spoilage, and growth of pathogenic bacteria, and is commonly used in food products (e.g., meat and poultry products) to extend shelf life and increase food safety. Due to its sodium content, however, sodium lactate, can be undesirable as a preservative. Potassium lactate, which has similar antimicrobial properties, has been used in lieu of sodium lactate. However, potassium lactate is also associated with a bitter taste which limits the extent to which it may be used to replace sodium lactate in foods without causing undesired bitter taste.
[0005] in addition, the increasing incidence of obesity and diabetes has been attributed, in past, to the high sugar intake of many diets. Accordingly, substitutio of sugar with another sweet tasting compound is desirable. Artificial and natural sugar substitutes that may be used to reduce sugar in foods are often associated with bitter taste which again limit the extent to which these may be used to replace sugar in foods without causing adverse bitter taste. For example, a common sugar substitute is Acesulfame K, which also has a bitter taste in addition to its sweet taste.
[0006] Without being limited by theory, bitter, sweet, and umami tastants and compounds typically elicit a taste response via G-protein coupled receptors, while salty and sour tastants and compounds are typically hypothesized to elicit a taste response via ion channels. Bitter taste receptors belong to the T2R (also referred to as TAS2R) family of G-protein coupled receptors that induce intracellular calcium concentration changes in response to a bitter tastant. T2R receptors act via gustducin, a taste-specific G-protein. There are at least twenty-five different members of the T2R family, suggesting that the perception of bitter teste is complex, involving several different tastant-receptor interactions. Compounds capable of modulating the activation and/or signaling of bitter taste receptors in the oral cavity and/or the gastrointestinal tract could be effective to allow desired usage levels of bitter tastants or bitter tasting substances in food and pharmaceutical products without resulting in consumer dislike of such products due to perception of the increased le vels of bitter tastants or bitter tastes. In some instances, blockers or modulators of bitter taste receptors and bitter taste may reduce the perception of bitter tastants and/or bitter taste via the bitter taste receptors and/or taste transduction signaling machinery present in the oral cavity and/or the gastrointestinal tract.
[0007] Traditionally in food preparation and pharmaceuticals, bitter taste was masked using sweeteners and other tastants, including salt, in some cases, however, this is undesirable or insufficient because it can alter, mask, or interfere with other tastes/flavors/impressions (e.g., non bitter tastes or desired bitter tastes) in the food product. Additionally, this approach has rarely been able to completely mask the bitter taste present in such food products or pharmaceuticals. For that reason, compounds which reduce bitter taste instead of, or in addition to, masking agents are preferred,
[0008] it is, therefore, desirable to provide compounds thai may be added io food products, consumer products and pharmaceuticals comprising bitter tastants or having a bitter taste to eliminate, modulate or reduce the perception of the bitter tastants or bitter taste or to reduce the corresponding activation of the bitter receptors in the oral cavity and/or the gastrointestin l tract. Similarly, it is desirable to provide food products, consumer products, and pharmaceutical compositions comprising such compounds. It is also desirable to decrease the sodium intake of a subject using such, compounds to eliminate, modulate or reduce the perception of bitter taste associated with salt substitutes. It is further desirable to decrease the sugar intake of a subject using such compounds to eliminate, modulate or reduce the perception of bitter taste associated with sugar substitutes.
[0009] The present invention provides compounds that modulate bitter taste, edible compositions comprising such compounds, and methods of preparing such edible compositions. The present invention also provides methods of reducing the amount of sodium or sugar in an edible composition and methods of reducing bitter taste of an edible composition. The present invention further provides a method of reducing, modulating or eliminating the bitter taste of a food, consumer or pharmaceutical product in a subject. The present invention also provides a method of modulating, particularly reducing the activation of a bitter taste receptor.
Edible .comflos^
[0010] One aspect of the present invention provides edible compositions for reducing bitter taste of a bitter tastant. In some embodiments, the edible composition comprises a terpenoid compound. In some embodiments, the terpenoid compound is a compound having a molecular weight less than about 1000, 500, or 300 daltons. In certain embodiments, the terpenoid compound is a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid). Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (IVe), Formula (Ιίί), Formula (Ilg), and Formula (lih) or Compounds 1-41 or a comestsbly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0011] in certain embodiments, the compound of Formula (I) is selected from the group consisting of damascene compounds (e.g., β-damascone, trans-a-damascone), ionone compounds (e.g., β-ionone, a-ionone, γ-ionone, and dihydro-a-ionone, particularly either β-ionone or a-ionone), nerol, geranyl tsovaterate, geranyl acetone, neryl acetate, geranyl propionate, geranyl butyrate, citroneliyi propionate, citroneliyi isobutyrate, citrai diethyl acetai, geranyl phenylacetate, geranyi formate, DL-citronellol, neryl iso valerate, citronellyl acetate, citrai dimethyl acetai, citrai, geranial, neral, neryl bistyrate, citroneiial, hydroxycitronellal, citronellyl valerate, geraniol, neryl isobutyrate, geranyi acetate, citronellyl formate, and hydroxycitronellal dimethyl acetal or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0012] in some embodiments, the edible composition comprises a chroman compound. In some embodiments, the chroman compound is a compound having a molecular weight less than about 1000, 500, or 300 daitons. in certain embodiments, the chroman compound is a compound of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila) or Compounds 42-53 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0013] In certain embodiments, the compound of Formula (V) is selected from the group consisting of pentamethyl-6-chromanol, α-tocopherol, (+)-5-tocopherol, (+)-a-tocopherol acetate, D-a-tocoptierol succinate, DL-a-tocopherol acetate, Vitamin E acetate, 4-cbromanol and dihydrocoumarin.
[001 ] in some embodiments, the edible composition comprises a benzo ring-containing compound. In some embodiments, the benzo ring-containing compound is a compound having a molecular weight less than about 1000, 500, or 300 daitons. In certain embodiments, the benzo ring-containing compound is a compound of Formula (Vlil), Formula (IXa), Formula (IXb), Formula (TXc), or Formula (IXd) or Compounds 54-71 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0015] in certain embodiments, the compound of Formula (VIII) is selected from, the group consisting of benzoic acid, ethyl benzoate, propyl benzoate, phenethyl benzoate, 4-hydroxybenzoic acid, methyl *ara-hydroxybenzoate, ethyl »«ra-hydroxybenzoate, butyl paraben, 4-methoxybenzoic acid, 3-methoxybenzoic acid, 2-methoxybenzoic acid, 4-propoxybenzoic acid,
methyl-ori/io-methoxy benzoate, ara-hydroxybenzyl alcohol, a-mefhylbenzyl alcohol, and 4-( 1 -hydroxyethyl)-2-methoxyphenol.
[0016] In some embodiments, the edible composition comprises one or more polycyclic compounds. In some embodiments, the polycyclic compound is a compound having a molecular weight less than about 1000, 500, 300 or 200 daitons. In certain embodiments, the polycyclic compound has a bicyclic core with a one-carbon transannular bridge, such as a compound of Formula (XI) or Formula (XII) or Compounds 72-94 or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0017] The present invention also includes edible compositions comprising a compound according to any one of Compounds 95-134 or comestibly or biologically acceptable salts or derivatives thereof, or enaniiomers or diasiereomers thereof.
[0018] In some embodiments, the edible composition comprises (a) a compound of the invention; and (b) a bitter tastant. in some embodiments, the compound of the invention is a compound having a molecular weight less than about 1000, 500, or 300 daitons. In certain embodiments, the compound of the invention is a compound of Formula (Ϊ), Formula (la). Formula (Ha),
Formula (ilia), Formula (lib). Formula (IHb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IVe), Formula (Πί), Formula (Hg), Formula (iih), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formul (IXb), Formula (IXc), Formula. (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof.
[0019] In another embodiment, the edible composition comprises (a) any one of Compounds 1-134, or combinations thereof; and (b) a bitter tastant
[0020] In another embodiment, the edible composition comprises (a) any one of Compounds 1-58, or 61- 134, or combinations thereof; and (b) a bitter tastant.
[0021] According to the invention, the bitter tastant can be inherent in, e.g., a food product (such as coffee or chocolate) or can be a component of an edible composition (such as a bitter tasting preservative). In some embodiments, the bitter tastant present in the edible composition is a bitter tasting salt. In some embodiments, the bitter tastant present in the edible composition is a potassium salt, a magnesium salt, or a calcium salt. In some esnbodiments, the bitter tastant is a potassium salt, in some embodiments, the bitter tastant present in the edible compositions is KC1. In other embodiments, the bitter tastant present in the edible composition is potassium lactate.
[0022] In some embodiments, the edible composition further comprises a sodium salt, in some embodiments, the edible composition further comprises NaCl. In other embodiments, the edible composition further comprises sodium lactate. In some embodiments, the edible composition further comprises sugar.
[0023] In another aspect of the invention, the edible composition is a food product comprising at least one compound of the invention. In certain embodiments, the compound of the invention is a compound of Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib),
Formula (nib), Formula (lie), Formula (IIIc), Formula (I Vc), Formula (lid). Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (IVe), Formula (Ilf), Formula (Hg), Formula (iih). Formula (V ), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (Did), Formula (Xi) or Formula (XII), as described herein, or combinations (hereof. In another embodiment, the compound of the invention is any one of Compounds 1-134, or combinations thereof.
[0024] In another aspect of the present invention, the edible composition is a pharmaceutical composition comprising a bitter tasting pharmaceutically active ingredient and a compound of Formula (I), Formul (la ), Formul (Ila), Formula (Ilia), Formula (lib). Formula (Ilib),
Formula (lie), Formul (IIIc), Formula (IVc), Formula (lid). Formula (Hid), Formula (IVd), Formula (lie), Formul (Me), Formula (IVe), Formula (Ilf), Formula (lig), Formula (Iih),
Formula ( V), Formul (Via), Formula (VIb), Formula (Vila), Formula (Viii), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formul (XII), as described herein, or combinations thereof. In another embodiments, the pharmaceutical composition comprises a bitter tasting pharmaceutically active ingredient and any one of Compounds 1-134, or combinations thereof.
[0025] in yet other embodiments, the edible composition is a pharmaceutical composition comprising a pharmaceutically active ingredient, a bitter tastant, and a compound of Formula (I), Formula (la), Formula (11a), Formula (Ilia), Formul (lib), Formula (Illb), Formul (lie),
Formula (IIIc), Formula (Wc), Formul (lid), Formula (Hid), Formula (Wd), Formul (lie), Formula (Hie), Formula (We), Formul (Ilf), Formula (Ti ), Formula (llh), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (ΓΧΌ), Formula (IXc), Formula (IXd), Fonnula (XI) or Formula (Xil), as described herein, or combinations thereof. In yet other embodiments, the pharmaceutical composition comprises a pharmaceutically active ingredient, a bitter tastant, and any one of Compounds 1-134, as described herein, or combinations thereof.
[Θ026] In another aspect of the present invention, the edible composition is a consumer product comprising a bitter tastant and a compound of Formula (I), Formula (la), Formula (TIa),
Formula (Ilia), Formula (Tib), Formula (Tllb), Formula (Tic), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ITIe), Formula (We), Formula (Ilf), Formula (Hg), Formula (llh), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Fonnula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. In another embodiments, the consumer product comprises a bitter tastant and any one of Compounds 1 -134, or combinations thereof.
[0027] Yet another embodiment of the present invention provides a consumer product for reducing bitter taste of a bitter tastant, wherein said consumer product comprises a compound of Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib). Formula (Illb),
Formula ( ie), Formula (IIIc), Formula (TVc), Formula (lid). Formula (lild). Formula (IVd), Formula (Tie), Formula (Hie), Fonnula (We), Formula (Ilf), Formula (Tig), Formula (llh), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. In yet other embodiments, the consumer product for reducing bitter taste of a bitter tastant comprises any one of Compounds 1-134, as described herein, or combinations thereof.
[0028] In a further aspect, the present invention provides a method of preparing an edible co mposition compris ing ;
(a) providing a comestibly acceptable carrier ; and
(b) adding to the comestibly acceptable carrier of (a) a compound of Formula (I),
Formula (la), Formula (Ila), Formul (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (TVc), Formula (ITd), Fonnula (Hid), Formula (IVd), Formula (lie), Formula (Tile), Formula (We), Formula (Ilf), Formula (Ilg), Formula (lib), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VT.TI), Formula (IXa), Formula (IXb), Formula (IXc), Formiila (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof,
[0029] in another embodiment, the method of preparing an edible composition comprises:
(a) providing a comestibiy acceptable carrier ; and
(b) adding to the comestibiy acceptable carrier of (a) any one of Compounds !■■ ί 34, or combinations thereof,
[0030] In some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition. In some embodiments, the comestibiy acceptable carrier is a foodstuff, a food product, or a pharmaceutically acceptable carrier,
[0031] In some embodiments, the comestibiy acceptable earner in (a) is inherently bitter. In such embodiments, the comestibiy acceptable carrier may inherently contain a bitter tastant (i.e., the comestibiy acceptable carrier is bitter without addition of a bitter tastant). In some embodiments, the inherent bitter tastant is a bitter tasting salt. In some embodiments, the inherently bitter foodstuff comprises a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the inherently bitter foodstuff comprises a potassium salt, such as KCl.
[0032] In other embodiments, the method of preparing an edible composition further comprises: (c) adding a bitter tastant. In some embodiments, the bitter tastant used in the methods of preparing an edible composition is a bitter tasting salt. In some embodiments, the bitter tastant used in the methods of preparing an edible composition is a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the bitter tastant used in the methods of preparing an edible composition is a potassium salt. In some embodiments, the bitter tastant used in the methods of preparing an edible composition is KCl. In other embodiments, the bitter tastant used in the methods of preparing an edible composition is potassium lactate.
[0033] In some embodiments, the edible composition further comprises a sodium salt. In some embodiments, the edible composition further comprises NaCL In some embodiments, the edible composition further comprises sodium lactate. In some embodiments, the edible composition further comprises sugar.
[0034] The present invention also provides a method of reducing the amount of sodium in an edible composition. In some embodiments, such methods comprise:
(a) replacing an amount of one or more sodium salts used in preparing an edible composition with an amount of one or more potassium salts; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie). Formula (lilc), Formula (IVc), Formula (lid ),
Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (TVe),
Formula (Ilf), Formula (Ilg), Formula (Ilh), Formula (V), Formul (Via), Formula (Vlb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (iXb), Formula (IXc),
Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. [0035] in another embodiment, the method of reducing the amount of sodium in an edible composition comprises:
(a) replacing an amount of one or more sodium salts used in preparing an edible composition with an amount of one or more potassium salts; and
(b) incorporating into the edible composition an effective amount of any one of
Compounds 1-134, or combinations thereof.
[0036] in some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition,
[0037] in some embodiments of the present invention, the method of reducing the amount of sodium in an edible composition, comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25% of the sodium present in an edible composition with potassium, in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sodium present in an edible composition with potassium, in yet other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sodium present in an edible composition with potassium, in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100%i of the sodium present in an edible composition with potassium. In some embodiments, the edible composition maintains a salty flavor.
[0038] The present invention aiso provides a method of reducing the amount of NaCi in an edible composition, in some embodiments, such methods comprise:
(a) replacing an amount of NaCi used in preparing an edible composition with an amount of KC1; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formuia (la), Formuia (Ha), Formula (Ilia), Formula (lib),
Formuia (Illb), Formula (lie), Formula (Ilic), Formuia ( TVc), Formuia (lid),
Formuia (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IV e),
Formuia (Ilf), Formuia (ilg), Formula (iih). Formula ( V), Formuia (Via), Formula (VIb), Formuia (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc),
Formuia (Did), Formula (XI) or Formuia (XII), as described herein, or combinations thereof,
[0039] In another embodiment, the method of reducing the amount of NaCi in an edible composition comprises:
(a) replacing an amount of NaCi used in preparing an edible composition with an amount of KC1; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1 - 134, or combinations thereof.
[0040] In some embodiments of the present invention, the method of reducing the amount of sodium in an edible composition, comprises incorporating into the edible composition an amount of the compound sufficient to permit repiacement of up to 25% of the NaCi present in an edibie composition with KCl. in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the NaCi present in an edible composition with KCl. in yet other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the NaCi present in an edible composition with KCl. in other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the NaCi present in an edibie composition with KCL in some embodiments, the edible composition maintains a. salty flavor.
[0041] in another embodiment, the present invention pro vides a method of reducing the amount of sodium lactate in an edible composition comprises:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (iia), Formula (ilia), Formula (lib),
Formula (iilb), Formula (Tic), Formula (IIIc), Formula (iVc), Formula (iid),
Formula (Hid), Formula (TVd), Formula (He), Formula (Tlie), Formula (IV e),
Formula (lit), Formula (ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (VTb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (iXb), Formula (IXc),
Formula (IXd), Formula (XT) or Formula (XII), as described herein, or combinations thereof.
[0042] In another embodiment, the invention provides a method of reducing the amount of sodium lactate in an edible composition comprising:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1-134, or combinations thereof.
[0043] In some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition.
[0044] In some embodiments of the present invention, the method of reducing the amount of sodium lactate in an edible composition, comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25%o of the sodium lactate present in an edible composition with potassium lactate. In other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sodium lactate present in an edible composition with potassium lactate. In yet other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sodium lactate present in an edible composition with potassium, lactate. In other esnbodiiTients, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the sodium lactate present in an edible composition with potassium lactate, in some embodiments, the edible composition has the same shelf life as an edible composition comprising sodium lactate.
[0045] in another embodiment, the invention provides a method of reducing the amount of sugar in an edible composition comprising:
(a) replacing an amount of sugar used in preparing an edible composition with an amount of Acesulfame K; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formul (IIIc), Formula (IVc), Formula (lid),
Formula (Hid), Formula (iVd), Formula (He), Formula (Tile), Formula (FVe),
Formula (Ilf), Formula (lig), Formula (Ills), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations t ereof.
[0046] In another embodiment, the invention provides a method of reducing the amount of sugar in an edible composition comprising:
(a) replacing an amount of sugar used in preparing an edible composition with an amount of Acesulfame K; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1-134, or combinations thereof.
[0047] In some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition.
[0048] In some embodiments of the present invention, the method of reducing the amount of sugar in an edible composition, comprises incorporating into the edible composition an amount of the compound sufficient to permit replacement of up to 25% of the sugar present in an edible composition with Acesulfame . In other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 50% of the sugar present in an edible composition with Acesulfame K. in yet other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 75% of the sugar present in an edible composition with Acesulfame . In other embodiments, the amount of the compound incorporated into the edible composition is sufficient to permit replacement of up to 100% of the sugar present in an edible composition with Acesulfame . in some embodiments, the edible composition maintains a sweet flavor.
[0049] The present invention also provides a method of reducing the sodium intake of a subject. Such method comprises:
(a) replacing an amount of NaCl used in preparing an edible composition with an amount of KCl; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Die), Formula (We), Formula (Hi), Formula ( Ilg), Formula (IIli), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula ( VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, thereby reducing the sodium intake of the subject,
[0050] In another embodiment, the method of reducing the sodium intake of a subject comprises:
(a) replacing an amount ofNaCl used in preparing an edible composition with an amount of KC1; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1 - 134, or combinations thereof, thereby reducing the sodium intake of the subject.
[0051] In another embodiment, the method of reducing the sodium intake of a subject comprises:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (iia), Formula (Ilia), Formula (lib),
Formula (iiib), Formula (He), Formula (IIIc), Formula (I c), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ille), Formula (IVe), Formula (Hi), Formula (ilg), Formula (iih), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, thereby reducing the sodium intake of the subject.
[0052] in another embodiment, the method of reducing the sodium intake of a subject comprises:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1-134, or combinations thereof, thereby reducing the sodium intake of the subject.
[0053] In some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition.
[0054] In some embodiments of the present invention, the methods of reducing the sodium intake of a subject further comprise (c) identifying a subject in need thereof. In some embodiments, ihe methods of reducing the sodium intake of a subject comprise incorporating into ihe edible composition an amount of the compound sufficient to reduce sodium intake by up to 25% using potassium replacement. In other embodiments, the amount of compound added in (b) is sufficient to reduce sodium intake by up to 50% using potassium replacement, in yet other embodiments, the amount of compound added in (b) is sufficient to reduce sodium intake by up to 75% using potassium replacement, in other embodiments, the amount of compound added in (b) is sufficient to reduce sodium intake by up to 100% using potassium repiacement,
[0055] The present invention also provides a method of reducing sugar intake of a subject comprising: (a) replacing an amount of sugar used in preparing an edibie composition with an amount of Acesislfame K; and
(b) incorporating into the edibie composition an effective amount of a compound according to Formula (i), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib),
Formula (Illb), Formula (He), Formula (TIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IVe), Formula (Ilf), Formula (Tig), Formula (Ills), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formul (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, thereby reducing the sugar intake of the subject,
[0056] In another embodiment, the method of reducing the sugar intake of a subject comprises:
(a) replacing an amount of sugar used in preparing an edibie composition with an amount of Acesulfame K; and
(b) incorporating into the edibie composition an effective amount of any one of Compounds 1- 134, or combinations thereof, thereby reducing the sugar intake of the subject.
[0057] In some embodiments, the edibie composition is a food product, a consumer product or a pharmaceutical composition.
[0058] In some embodiments of the present invention, the methods of reducing the sugar intake of a subject further comprises (c) identifying a subject in need thereof. In some embodiments, the methods of reducing the sugar intake of a subject comprise incorporating into the edible composition an amount of the compound sufficient to reduce sugar intake by up to 25% using Acesulfame K replacement. In other embodiments, the amount of compound added in (b) is sufficient to reduce sugar intake by up to 50% using Acesulfame K replacement, in yet other embodiments, the amount of compound added in (b) is sufficient to reduce sugar intake by up to 75% using Acesulfame replacement. In other embodiments, the amount of compound added in (b) is sufficient to reduce sugar intake by up to 100%) using Acesulfame replacement.
[0059] The present invention also provides a method of reducing the bitter taste attributed to a bitter tastant in an edibie composition comprising adding an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib),
Formula (Illb), Formula (lie), Formula (IIIc), Formula (I Vc), Formula (lid). Formula (Hid), Formula (IVd), Formula (He), Formula (ille), Formula (IVe), Formula (Hi), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (VIb), Formul (Vila), Formula (VIII), Formula (IXa), Formul (IXb), Formula (IXc), Formula (IXd), Formul (XI) or Formula (XII), as described herein, or combinations thereof, to the edible composition such that any bitter taste induced by the bitter tastant is reduced. In other embodiments, the compound added to the edible composition is any one of Compounds 1-134, or combinations thereof.
[0060] The present invention further provides a method of reducing the bitter taste attributed to a bitter tastant in an edible composition comprising ingesting an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib),
Formula (Il b), Formula (lie), Formula (IITc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Die), Formula ( e), Formula (Hi), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula ί V i l l i. Formula (IXa), Formula (iXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, before, along with, or after the edible composition such that any bitter taste induced by the bitter tastant is reduced. In other embodiments, the compound ingested with the edible composition is any one of Compounds 1■ 1 34, or combinations thereof,
[0061] in some embodiments, the edible composition is a food product, a consumer product or a pharmaceutical composition.
[0062] in some embodiments, the method reduces she bitter taste induced by the bitter tastant by up to 25%. In some embodiments, the method reduces the bitter taste induced by the bitter tastant by up to 50%. In other embodiments, the bitter taste induced by the bitter tastant is reduced by up to 75%. In yet other embodiments, the bitter taste induced by the bitter tastant is reduced by up to 100%. In some embodiments, the bitter tastant present in the edible composition is a bitter tasting salt. In some embodiments, the bitter tastant present in the edible composition is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the bitter tastant present in the edible compositions is KC1.
[0063] in furth er aspect, the present invention provides a method of preserving an edible composition comprising:
(a) providing an edible composition; and
(b) adding to the edible composition of (a) potassium lactate and an effective amount of a compound of Formula (i), Formula (ia), Formula (Ila), Formula (Ilia), Formula (lib), Formula (ilib), Formula (lie), Formula (IIlc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (iVe), Formula (Ilf), Formula (ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations (hereof.
[0064] In another embodiment, the method of preserving an edible composition comprises:
(a) providing an edible composition; and
(b) adding to the edible composition of (a) potassium lactate and an effective amount of any one of Compounds 1-134, or combinations thereof.
[0065] The present invention also provides a method of reducing the amount of sodium in an edible composition while preserving the edible composition. In some embodiments, such method comprises:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ila), Formul (Ilia), Formula (lib),
Formula (Ilib), Formula (lie), Formula (IITc), Formula (IVc), Formula (TId), Formula (Tlld), Formula (IVd), Formula (Tie), Formula (Tile), Formula (IVe), Formula (lit), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formisla (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (iXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof.
[0066] The present invention also provides a method of reducing the amount of sodium in an edible composition while preserving the edible composition. In. some embodiments, such method comprises:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of any one of Compounds 1 - 134, or combinations thereof,
[0067] in some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a consumer product in some embodiments, the edible composition is a pharmaceutical composition.
[0068] The present invention also provides a method of reducing or eliminating bitter taste in a subject utilizing an edible composition comprising a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ma), Formula (lib), Formula (Mb), Formula (lie), Formula (IITc), Formula (iVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Me), Formula (iVe), Formula (Hi), Formula (ilg), Formula (ilh). Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. In other embodiments, the composition that reduces or eliminates a bitter taste in a subject comprises any one of Compounds 1 -134, or combinations thereof.
[0069] In some embodiments the bitter taste is inherent, in some embodiments, the bitter taste is due to a bitter tasting salt. In some embodiments, the bitter taste is due to a potassium salt, a magnesium salt, or a calcium salt In some embodiments, the bitter taste is due to KC1. In other embodiments, the bitter taste is due to potassium lactate.
[0070] The present invention also provides a method of inhibiting or reducing the activation and/or signaling of a bitter taste receptor, wherein the method comprises contacting a bitter taste receptor with a compound of Formula (I), Formula (la). Formula (Ila), Formula (Ilia),
Formula (lib). Formula (Mb ), Formula (lie), Formula (ilic). Formula (IVc), Formula (lid), Formula (illd ), Formul (IVd), Formula (lie), Formula (Me), Formula (IVe), Formula (ilf), Formula (Tig), Formula (ilh), Formula (V), Formula (Via), Formula (Vib), Formul (Vila), Formula (Vili), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. In other embodiments, the method comprises contacting a bitter taste receptor with any one of Compounds 1-134, or combinations thereof, in some embodiments, the bitter taste receptor is in the oral cavity. In other embodiments, the bitter taste receptor is in the gastrointestinal tract, for example, in the stomach. In other embodiments, the bitter taste receptor is in an in vitro assay. [0071] Particular embodiments of the invention are set forth in the following numbered paragraphs:
1. A composition comprising a compound according to Formula (I):
Figure imgf000016_0001
Formula (1);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereom er thereo f,
wherein, as valence and stability permit;
R1 is absent or is selected from the group consisting of hydrogen, Ci-ioalkyl, Ci.iohaloaikyl, C2-ioalkenyl, C2..ioalkynyl, hydroxy], C;.i0acylamino, Ci.ioacyloxy, Ci-iocarbonate, C;.ioaikoxy, phenyloxy, phenyl-Ci ^alkyloxy, Ci-sheteroaiyloxy,
Figure imgf000016_0002
C3.ioalkenyloxy, Cj-ioalkyiryloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi-ioalkylamino,
Ci. iocarbamate, Ci.i0urea, sulfliydryl, CMoaikylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R' is selected from the group consisting of hydrogen, Ci-ioalkyl, Ci.iohaloaikyl, C2-ioalkenyl, Cj.ioalkynyl, halo, hydroxy!, carboxyl, C ^oalkoxycarbonyi,
C2-ioalkenyloxycarbonyl, Cj.ioalkynyloxycarbonyl, Ci.i acyl, Ci.ioacylamino, Ci .ioacyloxy, Cj-iocarbonate, C;.i alkoxy, phenyloxy, i-5heteroaryloxy,
Ci_5heteroaryl-C].6alkyloxy, C3.ioalkeny
Figure imgf000016_0003
phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi.ioalkylamino, Ci-oamido, Ct.toimmo, Ci.iocarbamate, C ^ourea, cyano, nitro, azido, sulfliydryl, Ci_;0a!kylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl,
Figure imgf000016_0004
C i_6heierocyclyl-Ci_6alkyl, phenyl,
Figure imgf000016_0005
Cj.sheteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen C]_ioalkyl, C i.iohaloaikyl, C2-ioa kenyl, C2-ioalkyiiyl, halo, hydroxy!, carboxyl, C uioalkoxycarbonyl,
C2.10alke11yloxycarbon.yl, C2-ioalkynyloxycarbonyl, Ci.ioacyl, Ci-ioacylarnino, Ci.ioacyloxy, Ci-iocarbonate, Ci.ioalkoxy, phenyloxy,
Figure imgf000016_0006
C usheteroaryloxy,
C;.5heteroas l-Ci.6alkyloxy, C3„ioalkenyloxy, C3.i0aikynylox>r, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoC loaikylamino, Ci.i3amido, Ci.icimino, Ci.iocarbamaie, Ci .itrea, cyano, nitro, azido, sulfliydryl, Ci-ioalkyltbio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C _7earbocycryl,
C3.7cai'bocyclyl-C;.6alkyl, C^heterocyclyl, Ci.6heterocyciyl-C i_6alkyl, phenyl, pheny] -Ci_6aikyl, Ci.sheteroaryi, and
Figure imgf000017_0001
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R'f is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C'l-ioal e yl, <¾.ioalkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, C2-ioalkynyioxycarbonyi, Cnoa yl, Ci.ieacylamino, Ci.je cyloxy Ci-iocarbonate, Cuo-tHcoxy, phenyloxy, phenyl-Ci.ealkyloxy, Ci-sheteroaryloxy, C;.5heteroa:ryl-Ci.6alky]oxy, Ci.ioalkenyloxy,
Figure imgf000017_0002
phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCMOalkylamino, C i.i iamido, Ci. ioimino, Ci .iocarbamate, Ci-iourea, cyano, tiitro, azido, sulfbydryl, Ci.;oalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, Cs^carbocyclyl,
C3..7carbocyclyl-Ci..6alkyl, Ci.6heterocyclyl,
Figure imgf000017_0003
phenyl, phenyl-Ci.6alky{, Ci.5heteroaryl, and
Figure imgf000017_0004
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R3 and R4 together form =0 or -0-C alkvl-O-;
& 1-10 ' '
wherein any of R1, R2, R', and R4, independently, is optionally substituted with 1-3 substituents selected from the group consisting of Ci .io lkyl, Ci. iohaloalkyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyt, C2. loalkenyloxycarbonyl,
Cj. loalkynytoxycarbonyt, Ci .ioacyl, Ci.ioaeylamino, C|.|<acyloxy, Ci_iocarbonate, C;.ioaikoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoC oalkylamino, Ci.namido, C i.ioimino, Ci.iocarbamate, C;.i(;,urea, cyano, nitro, azido, sulfliydryl, Cwoaikyltbio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl,
Figure imgf000017_0005
Ci.6heterocyclyi, C;.6heterocyclyl-Ci.6alkyi, phenyl,
Figure imgf000017_0006
Ci.jheteroaryl, and
Ci-sheteroaryl-C
Figure imgf000017_0007
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein Ci and C'e in Formula (I) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds; herein the composition is edible and capable of reducing bitter tasie of a bitter tastant.
2. The composition according to paragraph 1, wherein as valence and stability permit:
R1 is absent or is selected from the group consisting of hydroxyl, C;.6alkoxy, and
Cj-eacyloxy;
R" is selected from the group consisting of hydrogen, C^alkyl, CYealkenyl, and Ci-salkynyl;
R! is selected from the group consisting of hydrogen and ^alkoxy;
R4 is selected from the group consisting of hydroxyl, C^alkoxy, and
CM6acyioxy;
or RJ and R4 together form =0;
wherein any of R1, R2, R', and R4, independently, is optionally substituted as in paragraph 1 ; and
m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein Ci and C'e in Forniula (I) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
3. The composition according to paragraph 1, wherein as valence and stability permit:
R' is absent or is selected from the group cousisiiug of hydroxyl, C;.;alkoxy , and C;.;;acyloxy;
R4 is selected from the group cousisiiug of hydrogen. Chalky!, CYsalkeuyl, and C2-;;alkynyl;
R"" is selected from the group cousisiiug of hydrogen
R is selected from the group cousisiiug of hydroxyl,
Figure imgf000018_0001
C i_3acyloxy; m is 1 ;
n is 0;
p i 1 ; and
t is 1 ;
wherein all dotted bonds indicate optional carbon-carbon double bonds. 4. The composition according to paragraph 1 , wherein said compound according to Formula (I) is a compound according to Formula (la):
Figure imgf000019_0001
Formula (la);
or a comestibly or biologically acceptable salt or derivative thereof, or an enansiorner or diastereomer thereof,
wherein, as valence and stability permit:
R' is absent or is selected from the group consisting of hydrogen, Ci.ioalkyl, C;.iohaloalkyl, C soalkenyl,
Figure imgf000019_0002
hydroxyl, Ci-ioacylamino, Q.ioacyloxy, Ci-iocarbonate, Ci. ioalkoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
Ci.5beteroaryl-Ci ^alkyloxy, CYioalkenyloxy, C3.ioalkynyioxy, phosphoryl, phosphate, phosphorate, phosphinate, amino, diCi.ioalkylamino, monoiVioalkylamino,
Ci .iocarbamate, Cuourea, sulfhydryl, Ci .i0alkyithio, sulfate, sulfonate, sulfamoyl, sulibnamido, suifonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
R" is selected from the group consisting of hydrogen, Ci .ioalkyl, Ci .johaloalkyl, Cj.ioalkenyl, (¾_(0alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
Cj. loalkenyloxycarbonyl,€2-! oalkynyloxycarbonyl, Cnoae l, .ioacykmino, Cj.ioacyloxy, Ci-iocarbonate, Cuoalkoxy, phenyloxy, pheriyl-C i ^alkyloxy, Ci.sheteroaryioxy,
C;.5heteroaryl-C [.6alkyloxy, CYioalkenyloxy, C3.[.::.aikynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCj.ioalkylamino, monoC 1. loalkylamino, C|-!3amido, Ci-ioirnino, Ci-iocarbamate, Ci .itrea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cv;carbocyclyl,
C3.7carbocyclyl-C;.6alkyl, C;.6heterocyclyl,
Figure imgf000019_0003
phenyl, pheny] -Ci_6aikyl, Cusheteroaryl, and
Figure imgf000019_0004
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen C 1 0alkyl, Ci.iohaloalkyl, C'l-ioal enyl, <¾.ioalkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
C2- loalkenyloxycarbonyl, C2.ioalkynyloxycarbonyl, Cnoacyl, Ci-ioacylaroiao, Ci.ioacyloxy, Ci-iocarbonate, Cuo-tHcoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
Figure imgf000019_0005
Cs-ioalkenyloxy, Ca-ioalkyoyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi.ioalkylamino, C i_i 3amido, Ci-ioiroioo, C .. ^carbamate, Ci.iourea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cs^carbocyclyl,
Figure imgf000019_0006
Ci.6heterocyelyl, Ci .6heterocyclyl-Ci.6aikyl, phenyl,
Figure imgf000019_0007
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R is selected from the group consisting of hydrogen, Cuoalkyl,
Figure imgf000020_0001
C-j-ioaBcenyl, <¾.)0alkynyl, halo, hydroxy!, carboxyl, Ci.ioalkoxycarbonyl,
C-2- loalkenyloxycarbonyl, C2-i oalkynyloxycarbonyl, C ,„i0acyl, Cj.ieacylaroiao, Ci„i6acyloxy,
Ci-iocarbonate, Cuoafko y, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy,
Figure imgf000020_0002
Cs-ioalkenyloxy, Ca-ioalkyoyloxy, phosphoryl, phosphate, ph.osphon.ate, phosphinate, amino, diCi_ioalkylamino, monoCi_ioalkylamirio, C i.i iamido, Ci-ioiroino, Ci.iocarbamate, CMC,sirea, cyano, nitro, azido, solfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C^carbocyclyl,
Figure imgf000020_0003
phenyl,
Figure imgf000020_0004
Ci-5heteroaryls and wherein heterocyclic or heteroaromatic rings, independently for eac occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R 5 and R4 together form =0 or -O-C a1kyl-0-;
wherein any of R1 , R2, R'\ and R4, independently, is optionally substituted with 1-3 substituents selected from the group consisting of CVioalkyl, Ci. i haloalkyl, halo, hydroxy!, carboxyl, Ci.joalkoxycarbortyl, C2.10alkenyloxycarbon.yl,
C2-ioalkynyloxycarbonyl, Ci .ioacyl, Ci.ioacylaraioo, CVioacyloxy, CYiocarbonate, Cj.ioalkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCj_ic.alkylamirio, monoCi. joalkylamino, Ci.i3amido, Ci..!0imino, C;. ^carbamate, Ci .iourea, cyano, nitro, azido, sulfhydryl, Ci .ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl, CX/carboeyelyi-Ci.ealkyi,
Figure imgf000020_0005
Figure imgf000020_0006
Ci.sheteroaryl, and
Ci.jheteroaryl-C i.ealkyl; and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
m is 0-2;
wherein Q and C6 in Formula (la) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
5. The composition according to paragraph 4, wherein as valence and stability permit:
R' is absent or is selected from the group consisting of hydroxyl,
Figure imgf000020_0007
and C;.6acyloxy;
R" is selected from the group consisting of hydrogen. Chalky!, CYealkenyl, and
Ci-salkynyl;
R! is selected from the group consisting of hydrogen and ^alkoxy; R4 is selected from the group consisting of hydroxy!,
Figure imgf000021_0001
and
Ci.ifiiic lo y;
or R3 and R4 together form =0;
wherein any of R1, R2, R', and R4, independently, is optionally substituted as noted abo ve; and
in is 0-2;
wherein Ci and C'e in Formula (la) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
6. The composition according to paragraph 1, wherein said compound according to Formula (1) is a compound according to Formula (lla):
Figure imgf000021_0002
Formula (lla);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, 3, and R4 are as defined in paragraph 1 .
7. The composition according to paragraph 6, wherein said compound according to Formula (31a) is a compound according to Formula (ilia):
Figure imgf000021_0003
Formula (ilia);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R is as defined in paragraph 6. 8. The composition according to paragraph 1, wherein said compound according to Formula (I) is a compound according to Formula (lib):
Figure imgf000022_0001
Formula (lib);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as vaience and stability permit, R\ R5, and R4 are as defined in paragraph 1.
9, The composition according to paragraph 8, wherein said compound according to Formula (lib) is a compound according to Formul (Tflb):
Figure imgf000022_0002
Formula (Bib);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, Rz is as defined in paragraph 8.
10. The composition according to paragraph 1, wherein said compound according to Formula (I) is a compound according to Formula (lie):
Figure imgf000022_0003
Formula (lie);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit R', 3, and R4 are as defined in paragraph 1. [ 1 , The compositio according to paragraph 10, wherein said compound according to Formula (lie) is a compound according to Formula (TIIc):
Figure imgf000023_0001
Formula (IITc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as vaience and stability permit, R\ R5, and R4 are as defined in paragraph 10,
12. The composition according to paragraph 11 , wherein said compound according to Formula (Hie) is a compound according to Formula (IVc);
Me Me
Formula (IVc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R* is as defined in paragraph 11.
13. The composition according to paragraph 1, wherein said compound according to Formula (I) is a compound according to Formula (lid):
Figure imgf000023_0002
Formula (lid);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as vaience and stability permit, R1, R2, RJ and R4 are as defined in paragraph 1.
14. The composition according to paragraph 13, wherein said compound according to Formula (lid) is a compound according to Formula (Hid):
Figure imgf000023_0003
Formula (Hid); or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherem, as valence and stability permit, R~, W, and R4 are as defined in paragraph 13 ,
15. The composition according to paragraph 14, wherein said compound ording to Formula (Hid) is a compound according to Formula (lVd):
Me Me
Formula (TVd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined in paragraph 14.
16. The composition according to paragraph 1, wherein said compound according to Formula (I) is a compound according to Formula (lie):
Figure imgf000024_0001
Formula (lie);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R1, R2, R and R-* are as defined in paragraph 1.
1 7. The composition according to paragraph 16, wherein said compound according to Formula (lie) is a compound according to Formula (Hie):
Figure imgf000024_0002
Formula (Hie); or a comestibly or biologically acceptable salt or derivative thereof, or an enaiitiomer or diastereomer thereof, wherein, as valence and stability permit, R~, W, and R4 are as defined in paragraph 16,
18. The composition according to paragraph 17, wherein said compound ording to Formula (Hie) is a compound according to Formula (IVe):
Figure imgf000025_0001
Formula (IV e);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R'* is as defined in paragraph 17.
19. The composition according to paragraph 1, wherein said compound according to Formula (1) is a compound according to Formula (Πί):
Figure imgf000025_0002
Formula (lit);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wiierein, as valence and stability permit, R , RJ, and R4 are as defined in paragraph 3 .
20, The compositio according to paragraph 1, wherein said compound according to Formula (I) is a compound according to Formula (Tig);
Figure imgf000025_0003
Formula (Ilg);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wiierein, as valence and stability permit, R1 and R4 are as defined in paragraph 1 . 21 , The composition according to paragraph 1, wherein said compound according to Formuia (I) is a compound according to Formuia (iih):
Figure imgf000026_0001
Formula (Iih);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereosner thereof, wherein, as valence and stability permit, R1, R3, and R4 are as defined in paragraph 1.
22. The composition according to paragraph 1, wherein said compound according to Formula (I) is selected from the group consisting of:
Figure imgf000026_0002
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Compound
38 itronelia oii.
(Mixture)
Compound Geranium oil
39 (also referred to as Geranium oil Algerian, oil of Geranium, oil of pelargonium, oil of
(Mixture) rose geranium, Pelargonium oil, and Rose geranium oil Algerian),
Geranium East Indian oil
Compound
(also referred to as palroarosa oil, Indian grass oil, oil of Geranium (East Indian), 40
Palmarosa oil, Rusa oil, and Turkish geranium oil),
(Mixture)
Compound
41
comestibly or biologically acceptable derivatives thereof, or an enantiomer or diastereomer thereof.
Figure imgf000030_0001
Formula (V);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1 , independently for each occurrence, is selected from the group consisting of Ci.ioaik l, Ci.iohaloalkyl, QMoalkeiiyl, Cj.- ioaikynyl, halo, hydroxy], carboxyl,
Cj-ioalkoxycarbonyl, Cj.ioalkenyloxycarbonyl, C2-!oalkyiiyloxycarbonyl, C ,.10acyi, C ,„ioacylamino, C-Moacyioxy, C'l.iocarbonate, C [„l0alkoxy, phenyloxy, phenyl-C
Figure imgf000030_0002
C i-sheteroaryloxy, Ci-sheteroaryl-C Ci.ioalkenyloxy, C3.ioalkynyloxy, phosphoryl, phosphate, phosphonate, phosphinaie, amino,
Figure imgf000030_0003
monoCi-ioalkyiarnino, Ci-uamido, Cj.ioimino, C [-l0carbamate, C).io«rea, cyano, niiro, azido, suifhydryl, Cuioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl,
Figure imgf000031_0001
walkyl, phenyl, phenyl-C
Figure imgf000031_0002
C i.Jieieroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1 -4 heteroatoms selected from N, O, and S;
Rz is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, Q.ioafkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyls C2-ioa3kynyloxycarbonyl, Cnoacyl, Ci.ioacykroino, Ci.ioacyloxy, Ci-iocarbonate, CuoaHcoxy, phenyloxy, phenyl-Ci.ealkyloxy, Ci-sheteroaryloxy,
Figure imgf000031_0003
Cs-ioalkenyloxy, Cj-ioalkynyloxy, phosphoryl, phosphate, pb.osphon.ate, phosphinate, amino, diCi-ioalkylamino, monoCi.ioalkylamino,
Figure imgf000031_0004
Ci.ioimino, Ci.iocarbamate, CMC,urea, cyano, nitro, azido, suifhydryl, C i.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C^carbocyc!y!,
C3.7ca!'boc}¾lyl-C].6 lkyl, Ci.6heterocycryl,
Figure imgf000031_0005
phenyl, phenyl-Cs.6alkyl, Ci.sheteroaryl, and
Figure imgf000031_0006
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, C2-ioalkynyl, halo, hydroxy!, carboxyl, C noalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, Cj-ioalkynyloxycarbonyl, Ci.ioacy!, Ci .ic.acylamino, Ci .ioacyloxy, Ci-iocarbonate, Ci.ioalkoxy, phenyloxy, phenyl-C i
Figure imgf000031_0007
C]..5heteroar}'l-Ci.flalkyloxy, C ioalkenyloxy, Cj.ioalkynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi-ioalkylamino, monoCj.ioalkyiamino, Ci.iiamido, C;..ii)imino, Ci.iocarbamate, ^o rea, cyano, nitro, azido, suifhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl,
C:!_7carbocyclyl-C ,^alkyl, C ^heterocyclyl, C i_6heierocyclyl-Ci_6alkyl, phenyl,
Figure imgf000031_0008
Ci.sheteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R4 is selected from the group consisting of hydrogen,
Figure imgf000031_0009
C;_2ihaloalkyl, C2.2i alkenyl,
Figure imgf000031_0010
hydroxy!, Ci.io c loxy, Ci.ioalko y, phenyloxy,
Figure imgf000031_0011
Cs-ioaikynyloxy, amino, diCi-ioalkylamino, monoCnoa!kylamino, suifhydryl,
Ci.ioalkylthio, C3.7carbocycS.yl,
Figure imgf000031_0012
Ci-gheterocyclyl,
Figure imgf000031_0013
Ci.sheteroaryl, and
C;.5heteroasyl-Ci.6alkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
R5 is selected from the group consisting of hydrogen, Cuialkyl,
C2-2! ikenyl, C2..2; lkynyl, hydroxy!, Ci .ioacyloxy, Cnoalkoxy, phenyloxy, phenyl-C
Figure imgf000032_0001
Cs-ioalkenyioxy, C3.10alkyny.oxy, amino, diCi.ioalkylamino, monoC i. loaikylamino, solfhydryl,
Ci-ioalkylthio, C:;„7carbocyciyl, C3.7carbocyclyl-C
Figure imgf000032_0002
C;.6heteiOcyciyi-Ci„6ajky{, phenyl,
Figure imgf000032_0003
Ci.5heteroaryl, and
C!-5heteroaryl-C
Figure imgf000032_0004
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoras selected from N, O, and S;
or R and R together form
Figure imgf000032_0005
wherein any of R1, R2, R'f, and R5, independently and independently for each occurrence, is optionally substituted with 1 -3 substiruents selected from the group consisting of Ci.ioalkyl, Ci.iohaloalkyl, halo, hydroxyl, carboxyl, Ci-ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, C2-ioa3kynyioxycarbonyi, Cnoacyl, Ci.ioacylaniino, CVioacyloxy, CMOcarbonate, C;_] 0aikoxy, pheoyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diC |.i0alkylamino, monoC Oalkylamino, C 3amido, CMOimino, C |.i0carbamate, Ci. iou ea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulionamido, suifonyl, C3.7carbocyciyl,
Figure imgf000032_0006
Ci.bhetes'ocyclyl-Ci .ealkyl, phenyl,
Figure imgf000032_0007
CYsheteroaryl, and
C!-5heteroaryl-Ci.6alkyl; and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1 -4 heteroatoms selected from N, O, and S; and
is 0-3;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
24. The composition according to paragraph 23, wherein as valence and stability permit:
R1, independently fo each occurrence, is selected from the group consisting of halo, hydroxyl, Cs^alkyl, Ci-ehaloalkyl, C2.6alkenyl, C2-6 lkynyl, and Cs^alkoxy;
R' is selected from the group consisting of hydrogen, halo, hydroxyl, Chalky!, C].6haloaikyl,
Figure imgf000032_0008
optionally substituted by hydroxy!, amino, mono- or disubstituted Ch lky! amino, or carboxyl;
R3 is selected from the group consisting of hydrogen, hydroxyl, Ci .6alkyl, C2.6alkenyl, C2-6alkynyl, and Cs^alkoxy;
R* is selected from the group consisting of hydrogen, hydroxyl, Chalky!, C2-2ialkenyl, C2.2iaikynyl, and C^alkoxy, wherein R4 is optionally substituted by one or more occurrences of hydroxyl or acetyloxy;
RJ is selected from the group consisting of hydrogen, hydroxyl, C|.2]alkyl, C2..2ialkenyi,
Figure imgf000032_0009
wherein R5 is optionally substituted by one or more occurrences of hydroxyl or acetyloxy;
or R4 and R5 together form -0; : wherein any of 1, R2, R', R4, and RJ, independently and independeniiy for each occurrence, is optionally further substituted as in paragraph 1 ;
and
n is 0-3,
25. The composition according to paragraph 23, wherein said compound according to Formula (V) is a compound according to Formula (Via):
Figure imgf000033_0001
Formula (Via);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2 and R4 are as defined in paragraph 23, wherein the carbon marked with * optionally has R or S stereochemistry or is a mixture of R and S stereochemistry.
26. The composition according to paragraph 25, wherein said compound according to Formula (Via) is a compound according to Formula (Vila):
Figure imgf000033_0002
Formula (Vila);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R* is selected from the group consisting of hydrogen,
Figure imgf000033_0003
optionally substituted by hydroxy 1, amino, mono- or disubsiituted Chalky! amino, or carboxyl; and
wherein the carbon marked with * optionally has R or S stereochemistry or is a mixture of R and S stereochemistry. 27. The composition accoi'ding to paragraph 23, wherein said compound according to Formula (V) is a compound accoi'ding to Formula (VIb):
Figure imgf000034_0001
Formula (VIb);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantioroer or diastereomer thereof, wherein, as valence and stability permit, RJ, R'f, and R5 are as defined in paragraph 23 ,
28. The composition according to paragraph 23, wherein said compound according to Formisla (V) is selected from the groisp consisting of:
Figure imgf000034_0002
Figure imgf000035_0001
Compound 53 comestibly or biologically acceptable derivatives c thereof, or enantiomers or diastereoiiiers thereof.
29. A composition comprising a compound according to Formula (VIII):
Figure imgf000036_0001
Formul (VIII);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1, independently for each occurrence, is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci .iohaloalkyl, C ;_]oalkenyl, Cj-ioalkynyl, carboxyl,
C;.[i;.alkoxycarbonyl, CVioalkenyloxycarboiiyl, Cj.ioalkynyloxycarbonyl, Ci.ioac l, phosphoryl, phosphonate, phosphinate, sulfonate, sulfamoyl, sulfonyl,
Figure imgf000036_0002
Figure imgf000036_0003
C'|.6heterocyclyl-C [..6alkyl, phenyl, phenyl-Ci .6alkyl, Ci .5heteroaryl, and C].5heteroaryl-C'i.6alkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl,
Ci-ioiilkenyl, <¾.)0alkynyi, hydroxy!, Cueacyloxy, C i_! 0allvoxy, phenyloxy, phenyl-C
Figure imgf000036_0004
d-ioalkenyioxy, C3.10alkyny.Qxy, amino, diCi.ioalkylamino, monoC \. loaikylamino, sulfliydryl,
CMOalky3thio, C:;„7carbocycly3, d^carbocyclyl-C i-salkyl, C |„6heterocyclyL
Figure imgf000036_0005
Ci.sheteroaryl, and
Figure imgf000036_0006
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2.ioalkenyl, d_i0alkynyl, hydroxy!, Cuoacyloxy, C i_i0alkoxy, phenyloxy,
phenyl-Ci.6alkyloxy, C i.5heteroaryloxy,
Figure imgf000036_0007
C3.i0alkenyloxy,
Ci. loalkynyloxy, amino, diCi .ioalkylamino, monoCi.ioalkyiamino, sulfnydryi,
Ci. ioalkylthio, C3.7carbocyclyl,
Figure imgf000036_0008
Ci.bhetei'ocyclyl-Ci .ealkyl, phenyl,
Figure imgf000036_0009
Ci .sheteroaryl, and
Figure imgf000036_0010
wherein heterocyclic or heteroarom tic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R2 and R3 together form ) or -O-CM0alkyl-O-;
R' is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, d.ioalkynyl, carboxyl, C 1. loalkoxycarbonyl, Cj.- ioaikenyloxycarbonyl, C2-ioalkynyloxycarbonyl, Ci.ioacyl, phosphoryl, phosphonate, phosphinate, cyano, sulfonate, suifamoyl, sulfonyl, C:;„7carbocyciyl,
Figure imgf000037_0001
C wheterocyciyi,
Figure imgf000037_0002
Cg-ioai l, Ci.sheteroaryl, and
Ci.5heteroaryl-C L_6alkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoras selected from N, O, and S;
wherein any of R1, R2, R', and R4, independently and independently for each occurrence, is optionally substituted with 1 -3 substituents selected from the group consisting of Ci-ioalkyl, Ci.iohaloalkyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl, C2-ioalkenyloxycarbonyl, C2-ioa3kynyioxycarbonyi, Cnoacyl, Ci.ioacylaroiao, Ci.joacyloxy, Ci-iocarbonate, Cuo-tHcoxy, pbenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diC i.ioalkylamino, monoCi.ioalkylarnino,
Figure imgf000037_0003
Ci.ioinxino, C i.iocarbamate, Cuoorea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, suifamoyl, sulfonamido, sulfonyl, C3-7carbocyclyl, C3-7carbocyclyl-Cwalkyl, C^heterocyclyl,
Figure imgf000037_0004
Ci.sheteroaryl, and
Figure imgf000037_0005
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1 -4 heteroatoms selected from N, O, and S; and
n is 0-3;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
30, The composition according to paragraph 29, wherein as valence and stability permit:
R1, independently for each occurrence, is selected from the group consisting of hydrogen, ( ' ,.:;!
Figure imgf000037_0006
CS-ealkynyl, and Cj.eacyl;
Rz is selected from the group consisting of hydrogen, C^alkyl, C2-6alkenyl, and C2-6alk yl;
R3 is selected from the group consisting of hydrogen, Chalky!, C^alkenyl, and C^alkynyl;
or R2 and R3 together form =0;
R* is selected from the group consisting of hydrogen, Chalky!, C^alkenyl,
Figure imgf000037_0007
wherein any of R1, R , R3, and R4, independently' and independently for each occurrence, is optionally further substituted as in paragraph 29; and
is 0-3.
.31 , The composition according to paragraph 29, wherein said compound according to Formula (Vlii) is a compound according to Formula (IXa);
Figure imgf000038_0001
Formula (IXa);
or a comestibly or biologically acceptable salt or derivative thereof, or an euautiomer or diastereomer thereof, wherein, as valence and stoibility permit, R4 is as defined in paragraph 29.
32. The composition accoi'ding to paragraph 29, wherein said compound according to Formula (VTII) is a compound according to Formula (IXb):
Figure imgf000038_0002
Formula (IXb);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1 and R4 are as defined in paragraph 29; and
m is 0-2.
33. The composition accoi'ding to paragraph 29, wherein said compound according to Formula (VTII) is a compound according to Formula (IXc):
Figure imgf000038_0003
Formula (IXc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability oermit: 1 and R4 are as defined in paragraph 29;
R' is C i.galkyl; and
m is 0-2.
34. The composition according to paragraph 29, wherein said compound ording to Formula (VIII) is a compound according to Formula (IXd):
Figure imgf000039_0001
Formula (IXd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R' , R3, and R4 are as defined in paragraph 29; and
m is 0-2.
35, The composition according to paragraph 29, wherein said compo according to Formula (Viil) is selected from the group consisting of:
Figure imgf000039_0002
Figure imgf000040_0001
Figure imgf000041_0001
comestibly or biologically acceptable derivatives thereof, or enantioraers or diastereomers thereof.
36. A composition comprising a compound according to Formula (Xi):
Figure imgf000041_0002
Formula (Xi);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond,
R1, R , R3, R", and R' are independently selected from the group consisting of hydrogen, d.joalkyl, C ioalkenyl, and Cj.-]oalkynyl,
wherein each of R1, R2, R!, R°, and R7 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, -O, -SH, -S, - ¾, -CQ2H, -O(C l0alkyi), -O(C2-10alkenyl), -0(C2-[oalkynyl), -S(CM.:;aikyl), -S(C2_l0alkenyl), -S(C2„i0aikynyl), - NH(C Oalkyl), -NH(C2- [0alkenyl), -NH(CMoalk.ynyl), -N(Ci.ioalkyI)2, - (C2.;oalkenyj)2, and -N(C2_]oalkynyl)2, and
R4 is absent or selected from the group consisting of hydrogen, Ci-i0alky], C2^0alkenyl, C2.i0alkynyl, Cnoa yl, Ci.joacyloxy, Ci-ioacylamino, CMoacylthioxy, Ci-ioalkylester, Cnoafkenyiester, CMoalkynylester, C ioalkylaroide, Ci-ioalkenylamide, Ci-ioalkyaylainide, C ioalkylthioester, Ci-ioalkeoylthioester, and Ci.ioalkynylthioester;
wherein R4 may be optionally substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, =5, -NH2, -C02H, - O(Ci-!0alkyl), -0(C2-ioalkenyi),
Figure imgf000042_0001
-S(Ci.10alkyl), -S(C2-!0alkeay]), -S(C2„10alkynyl), -NH(C,.ioalkyl), -NH(C2.10alkenyl), -NH(C2.i0alkynyl), - N(Ci.!0alkyl)2, -N(C2.i0a]kenyl)2, - (C2.10allcynyi)2, Cnoac l, Cuoacyioxy, Ci-ioacylamino, Ci.ioacylthioxy, Ci. ioalkyl ester, C;.ioalkenylester,
Ci.ioalkynylester, C;.ioaikylamide, Ci-ioalkenylamide, Ci-ioalkynylamide, Ci-ioalkylthioester, Ci .ioalkenylthioester, and Ci.ioalkynylthioester,
R5 is absent or selected from the group consisting of hydrogen, Q ..10alkyl,
C2. lo lken l, and C2.i0aikynyl,
wherein R5 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, =S, -M i -. -C02H, -O(CM alkyl), -O(C2..!0alkenyl), -O(C2.i0alkynyl), -Sl C . alkyi !. - Si t ■ ..aikc-iyi ). -S(C2_) 0alkynyl), -Ni ii C . aiky! i. -\ H( t ■ ..aikc-iyi ). - l 'H(C2.10alkynyl), -N(C,.i0alkyl)2, -N(C2.lc.alkenyi)2, and ~N(C2.;0alkynyl)2; wherein R° and R' are optionally taken together to form— O, =S or ^R^; wherein each Ra is independentiy selected from the group consisting of hydrogen, C ,„i0alltyl, C2_;oalkenyl, and C2_! 0alkynyl,
wherein each Cuoalkyl, C2_;oalkenyl, and C2„1oalkynyl may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, ), -SH, ~S, -NH2, - C02H, -OCC oalk i), -O(C2.10alkenyl), -O(C2„l0alkynyl), -S(C l0alkyi), -S(C2-] 0alken.yl), -S(C2-10alkynyl), Η(0Μ03¾ν1), -NH(C2- [0alkenyl), - NH(C2.10alkynyl), »NiC 0alkyl)2, -N(C2_l0alkenyl)2, and ■
N(C2.10alkynyl)2;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of =C(Ra)- and -N-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(R )?-, -N(R )-, -0-, and -S-; provided that when the bond with the dotted line represents a double bond, R" is absent, and when the bond with the dotted line represents a single bond, R4 is present; wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
37. The composition according to paragraph 36, wherein as valence and stability permit:
R , R , R"', R", and R' are independently selected from the group consisting of hydrogen, Chalky],
Figure imgf000043_0001
R4 is absent or selected from the group consisting of hydrogen, Chalky!,
Figure imgf000043_0002
C].flalkenylester, and Ci-ealkyn l ester;
R' is absent or selected from the group consisting of hydrogen, Chalky 1, CVsalkenyl, and
Figure imgf000043_0003
wherein R6 and R' are optionally taken together to form
Figure imgf000043_0004
wherein each Ra is independently selected from the group consisting of hydrogen. Chalky!, Ci-ealkenyl, and C2^alkyn l;
wherein any of R1, R2, R3, R4, R5, R6, R', and Ra are independently optionally substituted as in paragraph 36;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of -C(Ra')- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of— O and S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of■C(Ril)2-, -N(Ra)-, -0-, and -S- ;
provided that when the bond with the dotted line represents a double bond, 3 is absent, and when the bond with the dotted line represents a single bond, R4 is present.
38. The composition according to paragraph 37, wherein as valence and stability permit: R1, R\ RJ, R6, and R' are independently selected from the group consisting of hy drogen, Chalky!,
Figure imgf000043_0005
and Ci-galkynyl;
R is absent or selected from the group consisting of hydrogen, Chalk 1,
Ci-salkenyl,
Figure imgf000043_0006
C)-6acyloxy, C)-6alkenylester, and
Ci.6alkynylester;
wherein R4 may be optionally substituted with one or more substituents selected from the group consisting of -OH, ==0, -SH, and =S;
R3 is absent or selected from the group consisting of hydrogen, Chalky!, C2^alkenyl, and ^.salkynyl;
wherein Rb and R' are optionally taken together to form =0, =S or = (Ra)2; wherein each Ra is independently selected from the group consisting of hydrogen. Chalky!, C-j-ealkenyL and C2-6alk.yn.yI;
wherein when the bond with the dotted line represents a double bond and R4 is present, X. is selected from the group consisting of -C(Ra')- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of O and S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of■C(Ril)2-, -N(Ra)-, -0-, and -S- ;
provided that when the bond with the dotted line represents a double bond, R? is absent, and when the bond with the dotted line represents a single bond, R4 is present.
39. The composition according to paragraph 38, wherein as valence and stability permit: R1, R~, R3, R6, and R' are independently selected from the group consisting of hydrogen, Chalky!,
Figure imgf000044_0001
and Ci-salkynyl;
R4 is absent or selected from the group consisting of hydrogen, Chalky!,
Ci-ealkenyl, CYealkynyl, and Ci.gacyl;
wherein R4 may be optionally substituted with O or ^S;
R~ is absent or selected from the group consisting of hydrogen, Chalky!,
C2.3alkeo.yl, and C2.3alkyo.yl;
wherein Rb and R' are optionally taken together to form ==0, ==:S or ==C(Ra)2; wherein each Ra is independently selected from the group consisting of hydrogen, Chalky!, C2.3alk.enyl, and C2-3alkyn.yl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X. is selected from the group consisting of -C(Ra')- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2-, - (Ra)~, -0-, and -S-;
provided that when the bond with the dotted line represents a double bond, R3 is absent, and when the bond with the dotted line represents a single bond, R4 is present.
40, The composition according to paragraph 39, wherein as valence and stability permit: R1, R2, RJ, R6, and R' are independently selected from the group consisting of hydrogen, Cijalkyl, C2-3alke yl, and C2.3alk.ynyl;
R4 is absent or selected from the group consisting of hydrogen, Chalky!,
C2-6alk.en.yl, C2-6alkynyl, Ci-6acyl;
wherein R4 may be optionally substituted with— Ό or :==S;
R~ is absent or selected from the group consisting of hydrogen, C^alkyl, C2-3alkenyl, and C2-3alkynyl; wherein R6 and R' are optionally taken together to form ·= ), or ^C(Ra)2; wherein each Ra is independently selected from the group consisting of hydrogen. Chalky!, C -salkenyL and C2_:ialkynyl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is ==€(Ra}-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of O and— S; and
wherein when the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2- and -Ό-;
provided that when the dotted line represents a double bond, RJ is absent, and when the bond with the dotted line represents a single bond, R4 is present.
41. A composition comprising a compound according to Formula (XII):
Figure imgf000045_0001
Formula (XII);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond, R1 and R are independently selected from the group consisting of hydrogen,
C )aikyl, Cj-ioalkenyl, and C2..joalkynyl;
wherein 1 and R" may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -8H, -S, -NH2, -C O ! i . -OiCj.joalkyl), -O(C2.10alkenyl), -O(C2..!0alkynyi), - S(C, .|0alkyi), -S(C2..! 0alkenyl), -SCQno lk nyl), -NH(C, .10alkyl), - FI(C2.ioalltenyl), -NH(C2_i0alkynyl), - (Ci„l0alkyl)2, -N(C2„10aikenyl)2, and - N(C2„l0alkynyl)2;
RJ and R4 are independently selected from the group consisting of hydrogen, Ct-ioalkyi, C2-ioalkenyl, C2_i0alkynyl, Ci„l0acyl, C i_! 0acyloxy, Ci.ioacylamino,
C ,„ioacylthioxy, C [„l0alkylester, Ci.ioalkenylester, C ,0alkynylester, Cj.ioaikylamide,
Ci.ioalkenylamide, Cuioalkyoylatnide, Ci.ioalkylthioester, Ci-ioalkenyltbioester, and C ; . i oalkynylthi o e ster ;
wherein each of R3 and R4 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, O, -SH, -S, -N¾, -C02H, -OiCwoalkyl), -O(C2.10alkenyl), -0(C2-joaikynyl), - S(CM OaSkyI), -S(C2- 10alkenyl), -S(C2-ioalkynyl), H(C l- [0alkyl), NH(C2.10aikenyl), H(C2„. oalkynyl), (C l0alkyi)2, N(C2_- 0alkeny 1)2,
(C2.;oaikynyl)2, C ,_i0acy{, C ,„i0acy{oxy, Ci.ioacylamino, Ci-!0acylthioxy, Ci„l0alky{ester, Ci.ioalkeoylester, C[_.oalkynylester, Cj.ioalk lamide,
C i-ioalkenylaroide, Ci-ioalkynylarnide, C i.ioalkylt ioester, Ci-ioalkeoylthioester, and Ci.ioalkynylt ioester; and
X and Y are independently selected from the group consisting of a direct bond, Ci-ioalkyl, C2_i0alkenyl, C2_ioalkynyl, N(R°), -0-, -S-, =0, and =S, provided that when either X or Y is =0 or ~S, then RJ and R\ respectively, are absent,
wherein Ra is selected from the group consisting of hydrogen, Ci.ioalkyl, C2.;0alkenyl, and C2_ioalkynyl,
wherein each C i_i0alkyl, C2_io lkenyl, and C2.;0alkynyl may be optionally independent!}? substitiUed with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, S. - Ni l -. -C02H, -O(CM0alkyl), -O(C2..!0alkenyl),
-O(C2..!0alkynyl), -S(C Oalkyl), -S(C2-ioalketiyl), -S(C2.i0a1kynyl), NH(Ci.ioa1kyl), - NH(C2..,0alkenyl), -NH(C2.,0alkynyl), -N(C 0alkyi)2, - (C2.,„aikenyl)2, and - (C2.10alkynyl)2;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
42, The composition according to paragraph 41, wherein as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond, R1 and R2 are independently selected from the group consisting of hydrogen, Chalky], C2..6alkenyl, and C2_6alkynyl;
R3 and R4 are independently selected from the group consisting of hydrogen, Ci-ealk i, C2..6alkenyl, C2..6alkynyl,
Figure imgf000046_0001
and Ci.6alkynylester;X and Y are independently selected from the group consisting of a direct bond, Ci..6aikyl, C2..6alkenyl, C2..6alkynyl, N(Ra), -0-, -S-, =0, and =S, provided that when either X or Y is =0 or =S, then R3 and R4, respectively, are absent,
wherein any of R1, R , R3, R", and Ra are independently optionally substituted as noted in paragraph 41 ; and
wherein d is selected from the group consisting of hydrogen, C^alkyl,
Figure imgf000046_0002
and C2-6alkynyl. 43, The composition according to paragraph 42, wherein as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond, 1 and R2 are independently selected from the group consisting of hydrogen, C;.6alkyl, C2-<;aikenyl, and C2_6aikynyl;
3 and R4 are independently selected from the group consisting of hydrogen. Chalky!, C2-6alk.en.yl,
Figure imgf000047_0001
and C |.6aikynylester;
wherein each, of RJ and R4 may be optionally independently substituted with one or snore substituents selected from the group consisting of -OH, =0, -SH,
Figure imgf000047_0002
Figure imgf000047_0003
Ci-galkenylester, Ci-galkylfhioester,
Figure imgf000047_0004
X and Y are independently selected from the group consisting of a direct bond,
Chalky!, C2-6alk.en.yl, C^alkynyl, N(R°), -0-, -S-, =0, and =S, provided that when either X or Y is =0 or -$, then RJ and R4, respectively, are absent, and
wherein Ra is selected from the gs'oup consisting of hydrogen, Chalky!, C2.6alkenyl, and C2.6alkynyl, 44, The composition according to paragraph 43, wherein as valence and stability permit:
the bond with, a dotted line optionally represents a single or double bond,
R 1 and R2 are independently selected from the group consisting of hydrogen, Ci ^alkyl, C2-4alk.en.yl, and C2_4al.kynyl;
R3 and R4 are independently selected from the group consisting of hydrogen,
Figure imgf000047_0005
C2-4alk.en.yl, C2-4a.ik.ynyl, and
wherein each, of RJ and R4 may be optionally independently substituted with one or snore substituents selected frosn the group consisting of -OH, =0, -SH, ==S, C^acyloxy, Ci-4acylthioxy, C;_4a5kyiester,
Figure imgf000047_0006
Figure imgf000047_0007
X and Y are independently selected from the group consisting of a direct bond, Ci.ealkyl, C^alkenyl, C2-.6alk.ynyl, -0-, -S-, =0, and =S, provided that when either X or Y is =0 or -S, then RJ and R4, respectively, are absent.
45, The composition according to paragraph 44, wherein as valence and stability permit:
the bond with, a dotted line optionally represents a single or double bond,
R 1 and R2 are independently selected from the group consisting of hydrogen, Chalky!, C2-4alk.en.yl, and Chal y siyl;
R3 and R4 are independently absent or independently selected from the group consisting of hydrogen, d-4alkyl, C2-4alkenyl,
Figure imgf000047_0008
Ci-4acyi;
wherein each of RJ and R4 may be optionally' independent!}? substituted with one or snore substituents selected frosn the group consisting of -OH, =0, -SH, =S, Ci-4acyloxy, C].4alkylester,
Figure imgf000047_0009
and X and Y are independently selected from the groisp consisting of a direct bond, _4alkyl, C2-4alke yl, C2.4alk.ynyl, -0-, -S-, =0, and ~S, provided thai when either X or Y =0 or -S, then R3 and R4, respectively, are absent.
46. The composition according to paragraph 36, wherein said compound according to F
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
or comesiib!y or biologically acceptoibie denvaiives thereof, or enaniiomers or diastereomer thereof.
Figure imgf000051_0001
or comestibly or biologically accepiabk derivatives thereof, or enautiomers or diastereomers thereof.
48. A composition comprising a compound selected from the group consisting of:
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diass ereorn er thereo f ;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
49. A composition comprising:
(a) a compound according to Formula (I), Formula (la), Formula (11a), Formula (ilia), Formula (lib), Formida (liib), Formuia (lie), Formuia (Ilic), Formula (IVc), Formula (lid), Formula (Hid), Formuia (IVd), Formula (lie), Formula (Hie), Formuia (IVe), Formula (Πί , Formula (Hg), Formuia (illi), Formuia (V), Formula (Via), Formuia (Vib),
Formula (Viia), Formida ( Vlii), Formula (IXa), Formuia (Kb), Formula (IXc), Formuia (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof; and
(b) a bitter tastant,
wherein the composition is edible.
50. The composition according to paragraph 49, wherein the bitter tastant is a foodstuff.
51 . The composition according to paragraph 49, wherein the bitter tastant is a bitter tasting salt.
52. The composition according to paragraph 51 , wherein the bitter testing sait a magnesium salt, a calcium salt, or a potassium salt.
53. The composition according to paragraph 52, wherein the potassium containing salt is KG or potassium lactate.
54. The composition of any one of paragraphs 1-53, wherein the edible composition further comprises one or more components selected from the group consisting of: aCl, sodium lactate, and sugar.
55. A food product comprising the compositions of any one of paragraphs 1-54, 56. A method of preparing an edible composition comprising:
(a) providing a comestibly acceptable carrier; and
(b) adding to the comestibly acceptable carrier of (a) a compound according to Formula (Ϊ), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (illb),
Formula (lie), Formula (Iile), Formul (IVc), Forsnula (lid), Formula (Hid), Forsnula (IVd), Forsnula (lie). Formula (iile), Forsnul (IVe), Forsnula (Ilf), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Forsnula (VIII), Forsnula (IXa), Formula (iXb), Forsnula (IXc), Formula (IXd), Formula (XI) or Formula (Xii), as described herein, or combinations thereof, or any one of Compounds 1 -134, as described herein, or combinations thereof.
57. The method according to paragraph 56, wherein said comestibly acceptable carrier is inherently bitter.
58. The method according to paragraph 57, wherein the comestibly acceptable carries' comprises a bitter tasting salt. 59. The method according to paragraph 58, wherein the bitter tasting salt is a magnesium salt, a calcium salt, or a potassium salt.
60. The method according to paragraph 59, wherein the potassium salt is C1 or potassium lactate.
61. The method according to any one of paragraphs 56-60, wherein the edible composition further comprises one or snore components selected from she group consisting of:
NaCl, sodium lactate, and sugar.
62. The method according to paragraph 56, wherein the method further comprises:
(c) adding a bitter tastant.
63. The method according to paragraph 62, wherein the bitter tastant is a bitter tasting salt.
64. The method according to paragraph 63, wherein the bitter tasting magnesium salt, a calcium salt, or a potassium salt.
65. The method according to paragraph 64, wherein the potassium salt is KC1 or potassium l ctate. 66. The method according to any one of paragraphs 62-65, wherein the edible composition further comprises one or more components selected from the group consisting of: NaCl, sodium lactate, and sugar.
67. A method of reducing the amount of NaCl in an edible composition comprising:
(a) replacing an amount of NaCl used in preparing an edible composition with an amount of KC1; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib).
Formula (Ilib), Formula (lie), Formula (lile), Formula (IVc), Fonmila (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Me), Formula (IVe), Formula (ilf), Formula (llg), Formula (Ilk), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof.
68. The method according to paragraph 67, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of NaCl typically present in the edible composition by up to 25%.
69. The method according to paragraph 67, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of NaCl typically present in the edible composition by up to 50%.
70. The method according to paragraph 67, wherein the amount of compound added in (b) is sufficient to pemiit replacement of the amount of NaCl typically present in the edible composition by up to 75%.
71. The method according to paragraph 67, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of NaCl typically present in the edible composition by up to 100%.
72. The method according to any one of paragraphs 67-71, wherein the edible composition maintains a salty flavor.
73. A method of reducing the amount of sodium lactate in an edible composition comprising:
(a) replacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (iia), Formula (Ilia), Formula (lib),
Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Fonnula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Die), Formula (We), Formula (Ilf , Formula ( Ilg), Formula (Ilk), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula ( VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 134 as described herein, or combinations thereof.
74. The method according to paragraph 73, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sodium lactate typically present in the edible composition by up to 25%.
75. The method according to paragraph 73, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sodium lactate typically present in the edible composition by up to 50%.
76. The method according to paragraph 73, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sodium lactate typically present in the edible composition by up to 75%.
77. The method according to paragraph 73, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sodium lactate typically present in the edible composition by up to 100%.
78. The method according to any one of paragraphs 73 -77, wherein the edible composition has the same shelf life as an edible composition comprising sodium lactate.
79. A method of reducing the amount of sugar in an edible composition comprising:
(a) replacing an amount of sugar present an edible composition with an amount of Acesulfame K; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ha), Fonnula (Ilia), Formula (lib). Formula (llib), Formula (lie). Formula (IIIc), Formula (IVc), Fonnula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (We), Formula (Hi), Formula (Ilg), Formula (Ilk), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 1 34, as described herein, or combinations thereof. 80. The method according to paragraph 79, wherein ihe amount of compound added in (b) is sufficient to pemiit replacement of the amount of sugar typically present in the edible composition by up to 25%.
81. The method according to paragraph 79, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sugar typically present in the edible composition by up to 50%.
82. The method according to paragraph 79, wherein the amount of compound added in (b) is sufficient to permit replacement of the amount of sugar typically present in she edible composition by up to 75%. 83. The method according to paragraph 79, wherein the amount of compound added in (b) is sufficient to pemiit replacement of the amount of sugar typically present in the edible composition by up to 100%.
84. The method according to any one of paragraphs 79-83, wherein the edible composition maintains a sweet flavor,
85. A method of reducing the sodium intake of a subject, the method comprising:
(a) replacing an amount of a sodium salt used in preparing an edible composition with an amount of a pota ssium salt; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (Ha), Formula (ilia), Formula (lib). Formula (fflb), Formula (lie), Formula (TIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Ille), Formula (iVe), Formula (Ilf), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formul (Vlli), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (Xi) or Formula (ΧΠ), as described herein, or combinations thereof, or any one of Compounds 1 - 134, as described herein, or combinations thereof.
86. The method according to paragraph 85, wherein the sodium salt is aC'l and the potassium salt is KC1,
87. The method according to paragraph 85, wherein the sodium salt is sodium lactate, and the potassium salt is potassium lactate. 88. The method according to any one of paragraphs 85-87, wherein the method further comprises (c) identifying a subject in need thereof. 89. The method according to any one of paragraphs 85-88, wherein the amount of compound added in (b) is sufficient to reduce sodium intake by up to 25% by replacement with potassium,
90. The method according to any one of paragraphs 85-88, wherein the amount of compound added in (b) is sufficient to reduce sodium intake by up to 50% by replacement with potassium,
91 . The method according to any one of paragraphs 85-88, wherein the amount o compound added in (b) is sufficient to reduce sodium intake by up to 75% by replacement, with potassium. 92. The method according to any one of paragraphs 85-88, wherein the amount of compound added in (b) is sufficient to reduce sodium intake by up to 100% by replacement with potassium.
93. A method of reducing the sugar intake of a subject, the method comprising:
(a) replacing an amount of sugar used in preparing an edible composition with an amount of a Acesulfame K; and
(b) incorporating into the edibl e composition an effective amount of a compound according to Formula (Ϊ), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (ilib), Formula (ilc), Formula (IIlc), Formula (IV c), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ille), Formula (IVe), Formula (Ilf), Formula (Ilg), Formula (ilh), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VIII),
Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -134, as described herein, or combinations thereof.
94. The method according to paragraph 93, wherein the method further comprises (c) identifying a subject in need thereof.
95. The method according to paragraph 93 or 94, wherein the amount of compound added in (b) is sufficient to reduce sugar intake by up to 25% by replacement with Acesulfame .
96. The method according to paragraph 93 or 94, wherein the amount of compound added in (b) is sufficient to reduce sugar intake by up to 50% by replacement with Acesulfame . 97, The method according to paragraph 93 or 94, wherein the amount of compound added in (b) is sufficient to reduce sugar intake by up to 75% by replacement with Acesulfame .
98, The method according to paragraph 93 or 94, wherein the amount of compound added in (b) is sufficient to reduce sugar intake by up to 100% by replacement with Acesulfame .
99, A method of reducing bitter taste attributed to a bitter tastant in an edible co mposition compris ing ;
(a) adding an effective amount of a compound according to Formula (I), Formula (la), Formula (Tla), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie),
Formula (Illc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IV e), Formula (ITf), Formula ( lg), Formula (lib), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VITI), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 134, as described herein, or combinations thereof, to the edible composition such that any bitter taste induced by the bitter tastant is reduced.
100, A method of reducing bitter taste attributed to a bitter tastant in an edible co mposition compris ing ;
(a) ingesting an effective amount of a compound according to Formula (I), Formula (la), Formula (ila), Formula (Ilia), Formula (lib), Formula (iilb), Formula (lie),
Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (iVd), Formula (lie), Formula (Hie), Formula (FVe), Formula (ITf), Formula (Ilg), Formula (lib), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (Vlil), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 134, as described herein, or combinations thereof, along with the edible composition such that any bitter taste induced by the bitter tastant is reduced.
101 , The method according to any one of paragraphs 56-100 or 102-111 , wherein the edible composition is a food product, a consumer product, or a pharmaceutical composition. 102. The method according to any one of paragraphs 99- 101, wherein the bitter taste induced by the bitter tastant is reduced by up to 25%
103. The method according to any one of paragraphs 99- 101, wherein the bitter taste induced by the bitter tastant is reduced by up to 50% 104. The method according to any one of paragraphs 99-101, wherein the bitier taste induced by the bitier ta stent is reduced by up to 75%
105. The method according to any one of paragraphs 99-101 , wherein the bitter taste induced by the bitter tastant is reduced by up to 100% 106, The method according to any one of paragraphs 99-105, wherein the bitter tastant is a bitter tasting salt.
107. The method according to paragraph 106, wherein the bitter tasting salt is a magnesium salt, a calcium salt, or a potassium salt. ί 08. The method according to paragraph. 107, wherein the potassium salt is CS or potassium 1 actate ,
109. The method according to any one of paragraphs 99-108, wherein the edible composition further comprises aC'l, sodium lactate, or sugar.
1 10. A method of preserving an edible composition comprising:
(a) providing an edible composition; and
(b) combining with the edible composition of (a) potassium lactate and a compound according to Formula (1), Formula (la), Formula (lia), Formula (ilia), Formula (lib), Formula (ilib), Formula (lie), Formula (lilc), Formula (IVc), Fonmila (ild), Formula (Hid), Formula (iVd), Formula (lie), Formula (file), Formula (IV e), Formula (Hi), Formula (llg),
Formula (illi), Formula (V), Formula (Via), Formula (Vlb), Fonmila (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof,
1 1 1. A method of reducing the amount of sodium in an edible composition while preserving the edible composition, the method comprising:
(a) replacing an amount of sodium lactate used in preparing an edible composition with a amount of potassium lactate; and
(b) incorporating into the edible compositio an effective amount of a compound according to Formula (1), Formula (la), Formula (lia), Formula (ilia), Formula (lib), Formula (Ilib), Formula (lie), Formula (Hie), Formula (IVc), Fonmila (Ild), Formula (Hid), Formula (IVd), Formula (He), Formula (Tile), Formula (iVe), Formula (lit), Formula (ilg), Formula (Till), Formula (V), Formula (Via), Formula (Vlb), Fonmila (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof. 112. A method of inhibiting, reducing, or eliminating a bitter taste in a subject comprising:
(a) placing a compound according to Formuia (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formuia (lie), Formuia (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (ITIe), Formuia (IVe), Formula (Iif), Formula (Ilg), Formula (lib), Formuia (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formuia (ΓΧΌ), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1- 134, as described herein, or combinations thereof in the oral cavity of the subject. 1 33. The method according to paragraph 112, wherein the bitter taste is due to a bitter tasting salt.
1 14. The method according to paragraph 113, wherein the bitter taste is due to a magnesium salt, a calcium salt, or a potassium salt.
115. The method according to paragraph 114, wherein the bitter taste is due to KCI or potassium lactate.
1 16. A pharmaceutical composition comprising:
(a) a bitter tasting pharmaceutical active ingredient; and
(b) a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (He), Formula (Ilic), Formuia (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formuia (Hie), Formula (IVe), Formula (iif). Formula (Ilg), Formula (lih), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (iXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof. 1 17. A pharmaceutical composition comprising:
(a) a pharmaceutical active ingredient;
(b) a bitter tastant; and
(c) a compound according to Formula (I), Formuia (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (illb), Formuia (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ITIe), Formula (IVe), Formula (iif). Formula (Ilg), Formula (lih), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof. 118. A consumer product comprising:
(a) a bitter testing ingredient; and
(b) a compound according to Formula (I), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib), Formula (Mb), Formula (lie), Formuia (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (Me), Formui (IVe), Formula (II f), Formula (Ilg), Formula (lib ), Formui (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formui (ΓΧΌ), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1- 134, as described herein, or combinations thereof. 1 39. A consumer product for reducing bitter taste of a bitter tastant, wherein said consumer product comprises:
(a) a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Mb), Formuia (lie), Formuia (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Me), Formuia (IVe), Formula (III), Formula (Hg), Formuia (IIIi), Formuia (V), Formula (Via), Formula (Vib),
Formula (Vila), Formula ( VIII), Formula (IXa), Formuia (Kb), Formula (IXc), Formuia (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1- 134, as described herein, or combinations thereof.
120. A method of inhibiting a bitter taste receptor comprising:
(a) contacting the bitter taste receptor with a compound according to Formuia (I),
Formula (la), Formula (Ila), Formula (Ilia), Formuia (lib), Formula (Mb), Formula (lie), Formula (Ilic), Formula (IVc), Formuia (lid), Fomiuia (Hid), Formuia (IVd), Formula (He), Formula (Me), Formula (I e), Formuia (lit), Formula (llg). Formula (lib.), Formula (Vj, Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formuia (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described herein, or combinations thereof.
121. The method according to paragraph 120, wherein the bitter taste receptor is in the oral cavity of a subject. 122. The method according to paragraph 120, wherein the bitter taste receptor is in the gastrointestinal tract of a subject.
123. The method according to paragraph 120, wherein the bitter taste receptor is present in an in vitro assay.
Brief Description of the Drawings [0072] Figures 1A-Q disclose exemplary date for solution and foodstuff tasie testing of the compositions comprising compounds of Formula (Γ) of the present invention.
[0073] Figures 2A-E disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (V) of the present invention.
[0074] Figures 3Α-Ϊ disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (VIII) of the present invention,
[0075] Figu re 4A-U disclose exemplary data for solution and foodstuff taste testing of the compositions comprising compounds of Formula (XI), Formula (XII), and compounds 95 -134 of the present invention. Detailed Description of the invention
[0076] In order that the invention described herein may be fully understood, the following detailed description is set forth.
[0077] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as those commonly understood by one of ordinal}' skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. The materials, methods and exampies are illustrative only, and are not intended to be limiting. All publications, patents and other documents mentioned herein are incorporated by reference in their entirety.
[0078] Throughout this specification, the word "comprise" or variations such as "comprises" or "comprising" will be understood to imply the inclusion of a stated integer or groups of integers but not the exclusion of any other integer or group of integers.
[0079] The term "acyt" refers to an alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl or arytcarbonyl substituent, wherein the alkyl, alkenyl, alkynyl or aryl portion may be optionally substituted. Examples of acyi substituents include, but are not limited to, acetyl, propionyl, butyryl and benzoyl.
[0080] The term "acyloxy" refers to an -0-C(0)R substituent, wherein R is alkyl, alkenyl, alkynyl or aryl, and wherein the alkyl, alkenyl, alkynyl or aryl portion may be optionally substituted. Examples of acyloxy groups include, but are not limited to, acetoxy, propanoyloxy, butanoyloxy, pentanoyloxy and benzoyloxy.
[0081] The term "aliphatic" refers to straight chain or branched hydrocarbons that are completely saturated or that contain one or more units of unsaturation. For example, aliphatic groups include substituted or unsubstituted linear or branched alkyl, alkenyl and alkynyl groups. Unless indicated otherwise, the term "aliphatic" encompasses both substituted and unsubstituted hydrocarbons, [0082] The terms "alkylamide," "alkenylamide and "alkynylamide" refer to amides of the structures alkyl-NR-C(=0)-, alkenyl -NR-C(=0)-, and alkyayl-NR-C(=0)-, wherein R may be separately defined, or R is also alkyl, alkenyl or alkynyl. [0083] The term "alkoxy" refers to O-alkyl substituent, wherein the alkyl portion may be optionaliy substituted. Examples of alkoxy substituents include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy. Also explicitly included within the scope of the term "alkoxy" are O-alkenyl or O-alkynyl groups, in all cases, the alkyl, alkene and aikyne portions may be optionally substituted.
[0084] The term "alkyl" refers to both, straight and branched saturated chains containing, for example, 1-3, ! -6, 1-9, or 1- ! 2 carbon atoms. An alkyl group may be optionally substituted.
[0085] The term "alkylthio" refers to an S-alkyl substituent, wherein the alkyl portion may be optionally substituted. Examples of alkylthio substituents include, but are not limited to, methylthio, ethylthio and isopropylthio. Also explicitly included within the scope of the term
"alkylthio" are S-alkenyl or S-alkyoyl groups, in all cases, the alkyl, alkene and aikyne portions may be optionally substituted.
[0086] The term "alkenyl" refers to bot straight and branched saturated chains containing, for example, 2-3, 2-6, 2-9, or 2- i 2 carbon atoms, and at least one carbon-carbon double bond. A alkenyl group may be optionally substituted.
[0087] The term "alkynyl" refers to both straight and branched saturated chains containing, for example, 2-3, 2-6, 2-9, or 2-12 carbon atoms, and at least one carbon-carbon triple bond. An alkynyl group may be optionally substituted.
[ Θ88] The term "araikyl" refers to an alkyl group substituted by an aryl. Also explicitly included within the scope of the term "araikyl" are alkenyl or alkynyl groups substituted by an aryl.
Examples of araikyl groups include benzyl and phenethyl. An araikyl group may be optionally substituted.
[ Θ89] The terms "artificial sweetener" and "sugar substitute" refer to a food additive that confers a sweet taste but has less caloric energy than sugar. In some instances, the caloric energy of the "artificial sweetener" or "sugar substitute" is negligible.
[0090] The term "aryl" refers to monocyclic or polycyclic aromatic carbon ring systems having five to fourteen members. Examples of aryl groups include, but are not limited to, phenyl (Phi, l-naphthyl, 2-naphthyl, 1-anthracyl and 2-anthracyl. An aryl group may be optionally substituted.
[0091] The term "arylalkoxy" refers to a group having the structure -O-R-Ar, where R is alkyl and Ar is an aromatic substituent. Also explicitly included within the scope of the term
"arylalkoxy" are -O-R-Ar groups, wherein R is alkenyl or alkynyl, In all cases, the alkyl, alkene, aikyne and aryl portions may be optionally substituted.
[0092] The term "bitter" or "bitter taste" as used herein refers to the perception or gustatory sensation resulting following the detection of a bitter tastant. The following attributes may contribute to bitter taste: astringent, bitter-astringent, metallic, bitter-metallic, as well as off-tastes, aftertastes and undesirable tastes including but not limited to freezer-burn and card-board taste, and/or any combinations of these. It is noted that, in the art, the term "off-taste" is often synonymous with "bitter taste." Without being limited by theory, the diversity of bitter tastes may reflect the large number of bitter receptors and the differential detection of bitter tastants by these receptors. Bitter taste as used herein includes activation of a bitter taste receptor by a bitter tastant. Bitter taste as used herein also includes activation of a bitter taste receptor by a bitter tastoint followed by downstream signaling. Bitter taste as used herein also includes activation of a signaling pathway after stimulation by a bitter tastant. Bitter taste as used herein further includes perception resulting from signaling following the detection of a bitter tastant by a bitter taste receptor. Bitter taste as used herein further includes perception resulting from signaling following contacting a bitter taste receptor with a bitter tastant, Bitter taste can be perceived in the brain, [0093] The term "bitter taste receptor" refers to a receptor, typically a cell surface receptor, to which a bitter tastant can bind. Bitter taste receptors may be present in the oral cavity, and/or throughout the gastrointestinal tract, including the stomach, intestines, and colon. Bitter receptors can also be present in vitro, such, as in an assay, including but not limited to a cell based assay or a binding assay.
[Θ094] The term "bitter tastant," "bitter ligand," or "bitter compound" refers to a compound that activates or that can be detected by a bitter taste receptor and/or confers the perception of a bitter taste in a subject. A "bitter tastant" also refers to a multiplicity of compounds that combine to activate or be detected by a bitter taste receptor and/or confer the perception of a bitter taste in a subject. A "bitter tastant" further refers to a compound that is enzymatically modified upon ingestion by a subject to activate or be detected by a bitter taste receptor and/or confer the perception of a bitter taste in a subject. Because the perception of bitter taste may vary from individual to individual, some individuals may describe a "bitter tastant" as a compound which confers a different kind of bitter taste compared to the kind of bitter taste perceived for the same compound by other individuals. The term bitter tastant also refers to a compound which confers a bitter taste. Those of skill in the art can readily identify and understand what is meant by a bitter tastant, Non-limiting examples of bitter tastants or substances including foods that comprise a bitter tastant and taste bitter include coffee, unsweetened cocoa, marmalade, bitter melon, beer, bitters, citrus peel, dandelion greens, escarole, quinine, magnesium salts, calcium salts, potassium salts, KG, potassium lactate, Acesulfame K, Brussels sprouts, asparagus, bitter gourd, wild cucumber, celery, hops, kohlrabi, radish leaf, ginseng, pumpkin, collard greens, kale, sparteine, caffeine, atropine, nicotine, urea and strychnine.
[0095] Further examples of bitter tastants include pharmaceuticals. Non-limiting examples of pharmaceuticals as bitter tastants include acetaminophen, ampicillin, azithromycin,
chlorpheniramine, cimetidine, dextromethorphan, diphenhydramine, erythromycin, ibuprofen, penicillin, phenylbutazone, psuedoephedrine, ranitidine, spironolactone and theophylline all of which have been associated with bitter taste.
[0096] The term "carbocyclyl" or "carbocyciic," refers to monocyclic or polycyclic non-aromatic carbon ring systems, which may contain a specified number of carbon atoms, preferably from 3 to 12 carbon atoms, which are completely saturated or which contain one or more units of iin saturation. A carbocyciic ring system, may be monocyclic, bicyclic or tricyclic. A carbocyclyl ring may be fused to another ring, such as an aryl ring or another carbocyciic ring. Examples of carbocyclic rings could include cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, cyclohexenyl, cyclopentenyl, indanyl, tetrahydronaphthyl and the like. The term "carbocyclic" or "carbocyclyl," whether saturated or unsaiuraied, also refers to rings that are optionally substituted unless indicaied. The term "carbocyclic" or "carbocylyi" also encompasses hybrids of aliphatic and carbocyclic groups, such as (cycioa5kyi)alkyl, (cycloalkenyl)alkyl and (cycloalkyl)alkenyl.
[0097] The term "comestibly or biologically acceptable salt" refers to any comestibly or biologically acceptable salt, ester, or salt of such ester, of a compound of the present invention, which, upon ingestion, is capable of pro viding (directly or indirectly) a compound of the present invention, or a metabolite, residue or portion thereof, characterized by the ability to reduce the perception of a bitter taste attributed to a bitter tastant. Similarly, the term "comestibly or biologically acceptable derivative" refers to any comestibl or biologically acceptable derivative of a compound of the present invention, which, upon ingestion, is capable of providing (directly or indirectly) a compound of the present invention, or a metabolite, residue or portion thereof, characterized by the ability to reduce the perception of a bitter taste attributed to a bitter tastant. A "comestible product" is a product suitable for oral use, such as eating or drinking. Therefore, a comestibly acceptable compound is an edible compound.
[0098] The term "consumer product" refers to health and beauty products for the personal use and/or consumption by a subject. Consumer products may be present in any form including, but not limited to, liquids, solids, semi-solids, tablets, capsules, lozenges, strips, powders, gels, gums, pastes, slurries, syrups, aerosols and sprays. Non-limiting examples of consumer products include nutriceutieals, nutritional supplements, lipsticks, lip balms, soaps, shampoos, gums, adhesives (e.g., dental adhesives), toothpastes, oral analgesics, breath fresheners, mouthwashes, tooth whiteners, and other dentifrices.
[0099] The term "diet" collectively refers to the food products and/or beverages consumed by a subject. A subject's "diet" also includes any consumer products or pharmaceutical compositions the subject ingests,
[0100] The term "edible composition" refers to a composition suitable for consumption, typically via the oral cavity (although consumption may occur via non-oral means such as inhalation).
Edible compositions may be present in any form including, but not limited to, liquids, solids, semi-solids, tablets, lozenges, powders, gels, gums, pastes, slurries, syrups, aerosols and sprays. As used herein, edible compositions include food products, pharmaceutical compositions, and consumer products. The term edible compositions also refers to, for example, dietary and nutritional supplements. As used herein, edible compositions also include compositions that are placed within the oral cavity but not swallowed, including professional dented products, such as dental treatments, fillings, packing materials, molds and polishes. The term "comestible" refers to similar compositions and is generally used as a synonym to the term "edible."
[0101] The term "effective amount" refers to an amount sufficient to produce a desired property or result. For example, an effective amount of a compound of the present invention is an amount capable of reducing the perception of bitter taste associated with a bitter tastant. The term " effective amount" of a compoimd of the invention also refers io an amount which, when added to an edible composition, reduces the bitter taste of, e.g., a NaCl substitute, thereby allowing for the maintenance of the perception of a desired salty flavor of a said edible composition. The term "effective amount of a compoimd" also refers to an amount which, when added to an edible composition, allo ws for the preservation, of a food product, while reducing or eliminating bitter taste associated with a bitter tastant in. the preservative. The term "effective amount" also refers to the amount of a compound of the present invention capable or reducing or eliminating the perception of a bitter taste or aftertaste associated with either a bitter tastant in a food product or an inherently bitter food product.
[0102] The term "flavor modifi er" refers to a compound or a mixture of compounds that, when added to an edible composition, such as a food product, modifies (e.g., masks, eliminates, decreases, reduces, or enhances the perception of) a flavor (e.g., sweet, salty, umami, sour, or bitter taste) present in the edible composition.
[0103] The term "food product" refers to any composition comprising one or more processed foodstuff. Food products include, but are not limited to, confectionaries, bakery products
(including, but not limited to, doughs, breads, biscuits, crackers, cakes, pastries, pies, tarts, quiches, and cookies), ice creams (including but not limited to impulse ice cream, take-home ice cream, frozen yogurt, gelato, sorbet, sherbet and soy, oat, bean and rice-based ice cream), dairy products (including, but not limited to, drinking milk, cheese, yogurt, and sour milk drinks), cheeses (including, but not limited to, natural cheeses and processed cheeses), butter, margarine, sweet and savory snacks (including but not limited to fruit snacks, chips/crisps, tortilla/com chips, popcorn, pretzels, chocolates, and nuts), hot and cold beverages (including, but not limited to, beverages, beverage mixes, concentrates, juices, carbonated beverages, non-carbonated beverages, alcoholic beverages, non-alcoholic beverages, soft drinks, sports drinks, isotonic drinks, coffees, teas, bottled waters, and beverages prepared from botanicals and botanical extracts (including cold beverages that are prepared with botanical or fungi extracts as ingredients, and drinks that are prepared in various ways, such as infusions, decoctions, or other means of extraction or distillation of various plant parts, including, but not limited to leaves, flowers, stems, fruits, roots, rhizomes, stems, bark, volatile oils, or even the whole plant)), snack bars (including, but not limited to granola bars, muesli bars, protein bars, breakfast bars, energy bars, and fruit bars), meal replacement products, ready meals (including, but not limited to canned meals, preserved meals, frozen meals, dried meals, chilled meals, dinner mixes, frozen pizza, chilled pizza, and prepared salads), soups (including but not limited to broth-like soups and cream-based soups), broth, gravy, soy sauce, meats and fish (including raw, cooked, and dried meats), deli products (including but not limited to meats and cheeses suitable for slicing or pre-sliced meats and cheeses, e.g., turkey, chicken, ham, bologna, salami, bierwurst, capicola, chorizo, corned beef, dutch loaf, Serrano, prosciutto, head cheese, liverwurst, meatloaf (including olive loaf, pepper loaf, pimento loaf, and ham and cheese loaf), mortadella, pastrami, peppetoni, roast beef, roast pork, saucisson, smoked meat, summer sausage, tongue, American cheese, blue cheese, cheddar cheese, Colby cheese, Colby-Jack cheese, gouda, Monterey Jack cheese, muenster cheese mozzarelia, parmigiano cheese, pepper jack cheese, provoione, romano cheese, siring cheese, spray cheese, and swiss cheese), vegetables (including, but not limited to, raw, pickled, cooked, and dried vegetables, such as trench fries), fruits (including raw, cooked, and dried fruits), grains (including, but not limited to, dried cereals and breads), prepared foods (including, but not limited to, dried, canned, or jarred sauces and soups), snack foods, pasteis (including, but not limited to, fresh pasta, chilled pasta, frozen pastel, dried pasta), noodles (including, but not limited to, egg noodles, wheat noodles, rice noodles, mung bean noodles, potato noodles, buckwheat noodles, corn noodles, cellophane noodles, cho w mein, fettuccini, fusilli, gnocchi, lasagna, lioguini, lo mein, macaroni, manicotti, pad thai, penne, ramen, rice vermicelli, rigatoni, soba, spaghetti, spatzle, udon, and ziti), canned foods, frozen foods, dried foods, chilled foods, oils and fats, baby food, spreads, salads, cereals (including, but not limited to, hot and cold cereals), sauces (including, but not l imited to, tomato pastes, tomato purees, bouillon cubes, stock cubes, table sauces, boys bases sauces, pasta sauces, cooking sauces, marinades, dry sauces, powder mixes, ketchups, mayonnaises, salad dressings, vinegrettes, mustards, and dips), jellies, jams, preserves, honey, puddings, recipe mixes, syrups, icings, fillings, infused foods, salt-preserved food, marinated foods and condiments (suc as ketchup, mustard and steak sauce). In some embodiments, the food product is animal feed. For example, the food product may be a pet food product, i.e. a food product for consumption by a household pet. In other embodiments, the food product is a livestock food product, i.e. a food product for consumption by livestock.
[0104] The term "foodstuff refers to an unprocessed ingredient or a basic nutrient or flavor containing element used to prepare a food product. Non-limiting examples of foodstuffs include: fruits, vegetables, meats, fishes, grains, milks, eggs, tubers, sugars, sweeteners, oils, herbs, snacks, sauces, spices and salts.
[0105] The term "halo" or "halogen" refers to a fluorine, chlorine, bromine or iodine substituent [0106] The term "heteroaiyi" refers to monocyclic or polycyclic aromatic ring systems having five to fourteen members and one or more heteroatoms. One having ordinary skill in the art will recognize that the maximum number of heteroaioms in a stable, chemically feasible heteroaiyi ring is determined by the size of the ring and valence. The term "heieroaralkyl" refers to an a kyl group substituted by a heieroaryl. Also explicitly included within the scope of the term "heieroaralkyl" are alkenyl or alkynyl groups substituted by a heteroaiyi. In general, a heteroaiyi ring may have one to four heteroatoms, Heteroaiyi groups include, without limitation, 2-furanyl, 3-furanyl, N-imidazolyl, 2iroidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4isoxazoSyl, 5-isoxazolyl,
2- oxadiazolyl, 5-oxadiazolyl, 2-oxazolyl, 4-oxazoSyl, 5-oxazolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl,
3- pyiidyl, 4-pyiidyl, 2-pyiimidyl, 4-pyrimidyl, 5-pyrimidyl, 3-pyridazinyl, 2-thiazolyl, 4thiazolyl, 5-thiazolyl, 5-tetrazolyl, 2-triazolyl, 5-triazolyl, 2-thienyl, and 3-thienyl. The term "heteroaryl ring", "heteroaryl group", or "heteroaralkyl" also refers to rings that are optionally substituted. Examples of fused polycyclic heteroaryl and aryl ring systems in which a carbocyclic aromatic ring or heteroaiyi ring is fused to one or more other rings include, tetrahydronaphthyl, benzimidazolyl, benzoihienyl, benzoiuranyl, indolyl, quinolinyl, benzothiazolyl, benzoxazolyl, benzimidazoiyl, isoquinolinyl, isoindolyl, acridinyl, benzoisoxazolyl, and the like.
[0107] The term "heterocyclic" or "heterocyclyl" refers to non-aromatic saturated or unsaturated monocyclic or polycyclic ring systems containing one or more heieroatoms and with a ring size of three to fourteen. One having ordinary skill in the art will recognize that the maximum number of heteroatoms in a stable, chemically fea sible heterocyclic ring is determined by the size of the ring, degree of unsaturation, and valence, in general, a heterocyclic ring may have one to four heteroatoms so long as the heterocyclic ring is chemically feasible and stable and may be fused to another ring, such as a carbocyclic, aryl or heteroaryl ring, or to another heterocyclic ring. A heterocyclic ring system may be monocyclic, bicyclic or tricyclic. Also included within the scope of within the scope of the term "heterocyclic" or "heterocyclyl", as used herein, is a group in which one or more carbocyclic rings are fused to a heteroaryl. Examples of heterocyclic rings include, but are not limited to, 3-l H-benzimidazol-2-one, 3-lH-alkyl~benzimidazoi-2-one, 2-tetrahydrofuranyl, 3-tetrahydroforariyl, 2-tetrahydrothiophenyl, 3-tetrahydrothiophetryl, 2-morpholino, 3-morpholino, 4-morpholino, 2-thioniorpholino, 3-thiomorpholino, 4-thiomorpbolitK), 1-pyrrolidinyl,
2- pyrrolidinyl, 3-py!xolidinyl, 1 -piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,
3- piperidinyl, 4-piperidinyl, 4-thiazolidinyl, dsazoionyl, N-substitiited dsazoionyl, 1-phthalimidinyl, benzoxane, benzotriazol-l-yl, benzopyrrolidine, benzopiperidine, benzoxolane, benzothioiane, benzothiane, aziranyl, oxiranyl, azetidinyl, pyrrolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, pyranyl, dioxanyl, dithianyl, trithianyl, quinuclidinyl, oxepanyl, succinimidyl asid thiepanyl.
[0108] The term "isoprene" (also referred to as "isoterpene") refers to 2-methyl- 1 ,3 -butadiene and is represented by the formula CH2 XCH3)CH=<¾.
[0109] The terms "parts per million" and "ppm" are used in the food industry to refer to a low concentration of a solution. For example, one gram of solute in 1000 ml of solvent has a concentration of 1000 ppm and one thousandth of a gram (O.OOlg) of solute in 1000 ml of solvent has a concentration of one ppm. Accordingly, a concentration of one milligram per liter (i.e. 1 mg/L) is equal to 1 ppm.
[0110] The terms "perception of a bitter taste," "perception of saltiness," "perception of a flavor" and similar terms, refer to the awareness of a subject of a particular taste or flavor.
[0111] The term "pharmaceutically active ingredient" refers to a compound in a pharmaceutical composition which is biologically active,
[0112] The term "potassium salt" refers to a salt wherein potassium is the cation. Potassium salts in the context of the present invention are preferably edible potassium salts including, but not limited to, Acesuifame K (Ace K), aluminum potassium sulfate, dipotassium guanylate, dipotassium iaosinate, monopotassium glutamate, potassium acetate, potassium acid tartate, potassium acid tartrate, potassium adipate, potassium alginate, potassium aluminum silicate, potassiu!Ti ascorbate, potassium aspartate, potassium benzoate, potassium bicarbonate, potassium bisuifate, potassium bisulfite, potassium bromate, potassium carbonate, potassium chloride, potassium citrate, potassium dihydrogen citrate, potassium dihydrogen phosphate, potassium ferrocyanide, potassium fumarate, potassium gibbereilate, potassium gluconate, potassium hydroxide, potassium hydrogen sulfiie, potassium iodide, potassium lactate, potassium maiate, potassium metabisulfite, potassium nitrate, potassium nitrite, potassium persulfate, potassium phosphate (dibasic), potassium phosphate (monobasic), potassium phosphate (tribasic), potassium polymetaphosphate, potassium polyphosphates, potassium pyrophosphate, potassium propionate, potassium saccharin, potassium sodium tartrate (e.g., potassium sodium L(+) -tartrate), potassium sorbate, potassium sulfate, potassium sulfite, and potassium tripolyphosphate.
[0113] The term "processed foodstuff refers to a foodstuff has been subjected to any process which alters its original state (excluding, e.g., harvesting, slaughtering, and cleaning). Examples of methods of processing foods include, but are not limited to, removal of unwanted outer layers, such as potato peeling or the skinning of peaches; chopping or slicing; mincing or macerating;
liquefaction, such as to produce fruit juice; fermentation (e.g. beer); emu!sification; cooking, such as boiling, broiling, frying, heating, steaming or grilling; deep flying; baking; mixing; addition of gas such as air entrainment for bread or gasification of soft drinks; proofing; seasoning (with, e.g., herbs, spices, salts); spray drying; pasteurization; packaging (e.g., canning or boxing); extrusion; puffing; blending; and preservation (e.g., adding salt, sugar, potassium lactate or other preservatives).
[0114] The term "replace" or "replacing" refers to substituting one compound for another compound in or in the preparation of, for example, an edible composition, such as food product, it includes complete and partial replacements or substitutions.
[0115] The term "salty flavor" refers to the taste elicited by, for example, ions of alkali metals salts (e.g., af and CI" in sodium chloride). Non-limiting examples of compositions eliciting a salty flavor include table salt (sodium chloride), sea water, sea salt and potassium chloride. The amount of salty flavor or the saltiness of a composition can be determined by, e.g., taste testing.
[0116] The term "sodium" or "sodium salt" refers to the amount of sodium (i.e., sodium salt) ingested or otherwise consumed by a subject. In general, "sodium" or a "sodium salt" refers to a salt or compound wherein sodium is the cation. Sodium salts in the context of the present invention include, but are not limited to, aluminum sodium sulfate, calcium disodium EDTA, dioctyl sodium sulfosuccinate, disodium 5 '-ribonucleotides, disodium ethylenediaminetetraacetate, disodium guanylate, disodium inosinate sodium acetate, monosodium glutamate (MSG), potassium sodium tartrate, sodium acid pyrophosphate, sodium adipate, sodium alginate, sodium aluminosilicate, sodium aluminum phosphate (acidic), sodium aluminum phosphate (basic), sodium ascorbate, sodium benzoate, sodium bicarbonate, sodium bisulfate, sodium bisulfite, sodium carbonate, sodium carboxymethylcellulose, sodium caseinate, sodium chloride, sodium citrate, sodium cyclamate, sodium dehydroacetate, sodium diacetate, sodium dehydroacetate, sodium dihydrogen citrate, sodium dihydrogen phosphate, sodium DL-malate, sodium, erythorbate, sodium erythorbin, odium ethyl para-hydroxybenzoate, sodium ferric pyrophosph te, sodium ferrocyanide, sodium formate, sodium, fumarate, sodium gluconate, sodium hydrogen carbonate, sodium hydrogen DL- malate, sodium hydrogen acetate, sodium hydrogen sulfite, sodium hydroxide, sodium
hypophosphite, sodium tartrate (e.g., sodium L(+) -tartrate), sodium lactate, sodium laur l sulfate, sodium malate, sodium metabisulfite, sodium metaphosphate, sodium methyl parahydroxybenzoate, sodium nitrate, sodium nitrite, sodium O-phenylphenol, sodium phosphate (dibasic), sodium phosphate (monobasic), sodium phosphate (tribasic), sodium polyphosphate, sodium potassium tartrate, sodium propionate, sodium propyl para-hydroxybeozoate, sodium pyrophosphate, sodium saccharin, sodium sesquicarbouate, sodium stearoyl lactylate, sodium stearyl fumarate, sodium succinate, sodium sulfate, and starch sodium octenyisuccinate,
[0117] The term "sodium intake" refers to the amount of sodium ingested or otherwise consumed by a subject,
[0118] The term "stability" or "stable" in the context of a chemical structure refers to the chemical state when a system is in its lowest energy state, or in chemical equilibrium with its environment. Thus, a stable compound (or, e.g., a compound containing a number of atoms or substitutions that are stable) is not particularly reactive in the environment or during normal use, and retains its useful properties on the timescaie of its expected usefulness.
[0119] The term "subject" refers to a mammal. In preferred embodiments, the subject is human. In some embodiments, a subject is a domestic or laboratory animai, including but not limited to, household pets, such as dogs, cats, pigs, rabbits, rats, mice, gerbils, hamsters, guinea pigs, and ferrets.. In some embodiments, a subject is a livestock animal. Non-limiting examples of livestock animals include: alpaca, bison, camel, cattle, deer, pigs, horses, llamas, mules, donkeys, sheep, goats, rabbits, reindeer, and yak.
[0120] The term "sugar" refers to a simple carbohydrate, such as a monosaccharide or a disaccharide, that delivers a primary taste sensation of sweetness. Non-limiting examples of sugar include glucose, fructose, galactose, sucrose, lactose, and maltose.
[0121] The term "sweet flavor" refers to the taste elicited by, for example, sugars. Non-limiting examples of compositions eliciting a sweet flavor include glucose, sucrose, fructose, saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, alitame, and neotame. The amount of sweet flavor or the sweetness of a composition can be determined by, e.g., taste testing.
[0122] The term "terpenes" refers to compounds comprising repeating units of isoprene. The basic molecular formula of a terpene is (CsHs),, where n is the number of linked isoprene units.
[0123] The term "terpeneoids" refers to compounds comprising terpenes and derivatives thereof. Thus, in some embodiments, terpenoids have at least one C5H8 hydrocarbon unit with one or more points of unsaturation. In other embodiments, terpenoids comprise saturated terpene unites and derivatives thereof and have no points of unsaturation.
[8124] An aryl, aralkyl, heteroaryl, or heteroaralkyl group may contain one or more
independently selected substituents. Examples of suitable substituents on the unsaturated carbon atom of an aryl or heteroaryl group include, but are not limited to, halogen, -CF3 , -R', -OR', -OH, -SH, -SR', protected OH (such as acyloxy), -N02, -CN, -NH2, -NHR, -N(R')2, -NHCOR', -NHCONH2, -NHCONHR', -NHCON(R')2, -NRCOR', -NHC02H, -\ ! tU ) R'. -C02R', -C02H, -CO ', -CON¾, -CONHR', -CON(R')2, -S(0)2H, -S« ) !■} ' -8(0)3H, -S(0)3R', -S(0)2NH2' -S(0)H, -S(0)R', -S(0)2NHR', -S(0)2N(R')2, - HS(0)2H, or N i SS« ) !■} ' where 11' is selected from H, aliphatic, carbocyciyi, heterocyclyl, aryl, aralkyl, heteroar l, or heteroaralkyl and each R' is optionally substituted with one or more halogen, niiro, cyano, amino, -NH-(imsubstituted aliphatic), -N-(«nsubstituted aliphatic);., carboxy, carbamoyl, hydroxy, -0-(unsubstiruted aliphatic), -SH, -S-(unsubstituted aliphatic), CF3, -S(0)2NH2' unsubstituted aliphatic, unsubstituted carbocyciyi, unsubstituted heterocyclyl, unsubstituted aryl, unsubstituted aralkyl, unsubstituted heteroaryl, or unsubstituted heteroaralkyl.
[0125] An aliphatic group, a carbocyclic ring or a heterocyclic ring may contain one or snore substituents. Examples of suitable substltuents on a saturated or unsaturated carbon of an aliphatic group, a carbocyclic ring or a heterocyclic ring include, but are not limited to, those listed above for the unsaturated carbon as well as the following: =0, =S, =NNHR', =NN(R')2, =N-OR', =NNHCOR', =NNHC02R', =N HS02R', HN-GN, or = R', wherein R' is as defined above. Guided by this specification, the selection of suitable substituents is within the knowledge of one skilled in the art.
[0126] As defined herein, the compounds of the invention are intended to include all stereochemical forms of the compound, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S). Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, formulas depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present formulas except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by a I JC- or l C-enriched carbon are within the scope of this invention.
[0127] The present invention provides edible compositions comprising a compound of the present invention, including food products, consumer products, and pharmaceutical compositions comprising said compounds, and methods of preparing a such compositions. The present invention also provides methods of reducing the amount of sodium (e.g., NaCl or sodium lactate) or sugar in a food product, a method of reducing the sodium or sugar intake in a diet, a method of reducing bitter taste, and a method of reducing the activity of a bitter taste receptor. The present invention also includes reducing the amount of sodium in a edible composition or diet by replacing a sodium containing compound or composition with a potassium containing compound or composition. The present invention also includes reducing the amount of sugar in a edible composition or diet by replacing sugar with a pot sium containing sweetener, such as Acesulfame K.
EdJ g _c_omgosjtions
[0128] According to one aspect, the invention provides an edible composition comprising a compound of the invention for reducing bitter taste of a bitter tastant. Edible .comB^
[0164] The substituent definitions in this section (i.e., R 1 , R2, R3, R4, m, n, p and t) refer to compounds of Formula (i), Formula (la), Formula (Ila), Formula ( ITa), Formula (Tib),
Formula (Tlib), Formula (lie), Formula (lITc), Formula (IVc), Formula (lid), Formula (Tlid), Formula (TVd), Formula (Tie), Formula (Tile), Formula (iVe), Formula (ITf), Formula (ilg), and Formul (Tlh).
[ 129] All stereochemical forms of the compounds discl osed in this and any section herein are specifically contemplated, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S). Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the compounds disclosed in this and any section herein are also specifically contemplated.
[0130] in some embodiments, the present invention provides an edible composition for reducing bitter taste of a bitter tastant, wherein the composition comprises a terpenoid compound. The terpenoid compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant. in some embodiments, the terpenoid compound has a molecular weight less than about 1000, 500, or 300 daltons. In certain embodiments, the terpenoid compound is a compound of Formula (I):
Figure imgf000079_0001
Formula (1);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1 is absent or is selected from the group consisting of hydrogen, Ci .ioaikyl, C;.[i;.haioaikyl, C ;.]oalkenyl, C?..joalkynyl, hydroxy!, Cj.ioacyl amino, Cj.ioacyloxy, Ci-iocarbonate, Cuoaikoxy, phenyloxy, phenyl-Cj ^alkyloxy, Ci.sheteroaryloxy, C;.5heteroaryl-C [.6alkyloxy, C3-!oalkenyloxy, C3.[0aikynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCj.ioalkylamino, monoC i . ((^Ikylamino,
Ci-iocarbamate, C iourea, sulfhydryl, Ci-ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from , O, and S;
is selected from the group consisting of hydrogen, d-ioalkyl,
Figure imgf000079_0002
Ci-ioal enyl, <¾.)0alkynyl, halo, hydroxy!, carboxyl, Ci.ioalkoxycarbonyl,
C-2- loalkenytoxycarbonyl, C2-i oalkynyloxycarbonyl, C ,.) 0acyl, Ci„i0acy!amino, C).)0acylo3 Ci-iocarbonate, Cuo-tikoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy,
Figure imgf000079_0003
Cs-ioalkenyloxy, Cj.ioalkynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi-ioalkylamino, monoCi.ioalkyiamino, C i.i iamido, Ci-ioimino, Ci.iocarbamaie, .itrea, cyano, nitro, azido, sulfliydryl, C
Figure imgf000080_0001
sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, C;_7carbocycryl,
C3.7carbocyclyi-C;.6alkyl, C;.6heterocyclyl,
Figure imgf000080_0002
phenyl, pheoy]-C1-6alkyl,
Figure imgf000080_0003
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen C 1 0alkyl, Ci.iohaloalkyl, C2-ioalkenyl, Q.ioalkynyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, C2-ioa3kynyloxycarbonyl, Cnoacyl, Ci.ioacylaroioo, Ci.ioacyloxy, Ci-iocarbonate, Cuo-tikoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy, Cs-ioalkenyloxy, Cj-ioalkyoyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCMOalkylamino, C i.i iamido, .ioimino, Ci.iocarbamate, CMC,urea, cyano, nitro, azido, sulfbydryl, C i.;0alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, Cs^carbocyclyl,
C3.7ca!'boc}¾iyi-C].6 lkyl, Ci.6heterocycly!,
Figure imgf000080_0005
phenyl,
Figure imgf000080_0006
Ci.sheteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R' is selected from the group consisting of hydrogen, Cj.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, Ci-ioaikynyi, halo, hydroxy!, carboxyl, C i.soalkoxycarbonyi,
C2-] oalkenyloxycarbonyl, C?.. loalkynyloxycarbonyl, C ;. [ cy!, C .16acy!amino, C i . |6acyloxy, C]..]i)Carbonate, Ci.ioalkoxy, phenyloxy, phenyl-C^alkyloxy, C i-5heteroaryioxy,
C]..5heteroar}'l-C].flalkyloxy, C ioalkenyloxy, Cj.ioalkynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi.ioalkylamino, Ci.iiamido, C ,_ioimino, Ci.iocarbamate, Ct-iourea, cyano, nitro, azido, sulfliydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, Crf.ycarbocyclyl,
C:!_7carbocyclyl-C ^alkyl, C ,.6heterocyclyl, C i_6heierocycly!-Ci_6aikyl, phenyl,
Figure imgf000080_0007
Ci.sheteroaryl, and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R3 and R4 together form =0 or -O-C alkvl-O-:
° l-!0
wherein any of R1, R2, R', and R4, independently, is optionally substituted wish 1-3 substituents selected from ihe group consisting of C[.i0alkyl, C i.iohaloalkyl, halo, hydroxy!, carboxyl, Ci-ioalkoxycarbonyl, C2- loalkenyloxycarbonyl,
C2-10alkyn.yloxycarbon.yl, Ci.ioacyl, Cuioacylamino, Ci.ioacyloxy, Ci.iocarbonate, Ci.ioalkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoC ioalkylamiao, Ci.namido, C i.ioi ino, Ci.iocarbamate, Ci.iourea, cyano, nitro, azido, sulfliydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocycl.yl,
Figure imgf000080_0008
C i_6heterocyclyl,
Figure imgf000081_0001
Ci.jheteroaiyl, and
Ci-sheteroaryl-C
Figure imgf000081_0002
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroaioms selected from N, O, and S; and
m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein Ci and C'e in Formula (I) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
[0131] According to some embodiments of compounds of Formula (I),
as valence and stability permit:
R1 is absent or is selected from the group consisting of hydroxy!, Ci„6aikoxy, and C].6aeyloxy;
R' is selected from the group consisting of hydrogen, Chalky!, C2-6alkenyl, and
C^alkynyl;
R3 is selected from the group consisting of hydrogen and Ci .6alkoxy;
R* is selected from the group consisting of hydroxy!, C; ..fia1koxy, and
C,,.]6acyioxy;
or R' and Έ7 together form— O;
wherein any of R1, R , R3, and R4, independently, is optionally substituted as noted above; and
m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein C] and in Formula (1) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds,
[0132] According to some embodiments of compounds of Formula (i),
as valence and stability permit:
R! is absent or is selected from the group consisting of hydroxy!, C,_6a]koxy, and C;.6acyloxy;
Rz is selected from the group consisting of hydrogen, Chalky!, C2-6alkenyl, and C2-6alkynyl;
RJ is selected from the group consisting of hydrogen and Ci.6a!koxy;
R4 is selected from the group consisting ofhydroxyl, C;.6a!koxy, and
C;.i6acyloxy;
or RJ and R4 together form =0; m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein C [ and C6 in Formula (I) optionally are bonded together to form a
6-membe ed ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
[0133] According to some embodiments of compounds of Formula (I),
as valence and stability permit:
R1 is absent or is selected from the group consisting of hydroxy!, Q^alkoxy, and
Figure imgf000082_0001
Rz is selected from the group consisting of hydrogen. Chalky], C2-3alkenyl, and C2.3 lkynyl;
R3 is selected from the group consisting of hydrogen and jalkoxy;
R'* is selected from the group consisting of hydroxy!, Qjalkoxy, and
Figure imgf000082_0002
m is 1 ;
n is 0;
P is 1 ;
t is 1 ;
wherein C] and Ce in Formula (I) optionally are bonded together to form a
6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds,
[0134] According to some embodiments of compounds of Formula (1),
as valence and stability permit:
R! is absent or is selected from the group consisting of hydroxy!, C^alkoxy, and
C ,„3acyloxy;
R~ is selected from the group consisting of hydrogen, Chalky!, Cksalkenyl, and C2-3alkynyl;
R3 is selected from the group consisting of hydrogen and
Figure imgf000082_0003
R4 is selected from the group consisting of hydroxy!, C,_3alkoxy, and Cuacyloxy; m is 1 ;
n is 0;
p is 1 ; and
t is 1 ;
wherein all dotted bonds indicate optional carbon -carbon double bonds.
[0135] in some embodiments of Formula (I), R1 is absent. For example, in certain embodiments, R1 is absent and C. is past of a double bond, in other embodiments, R' is present and is hydrogen, hydroxyl, d^aikoxy, or Cj-gacyloxy. In other embodiments, Rl is present and is hydrogen or hydroxvl. [0136] in certain embodiments, the compound of Formuia (I) includes a £"-double bond between C's and Cfi. in other embodiments, the compound of Formuia (Ϊ) includes a Z-double bond between C's and Ce. in further embodiments, the compound of Formula (I) includes a mixture of is Z-double bonds between C5 and C6, in yet additional embodiments, the compound of Formula (I) does not include a double bond between C$ and C6. In some embodiments, the compound of Formula (I) includes a Z-double in one or more "t" segments. In other embodiments, the compound of Formula (I) includes a v-double bond in one or more "t" segments. In further embodiments, the compound of Formula (I) includes a mixture of 7/Z-double bonds in one or more "t" segments.
[0137] in some embodiments, the compound of Formuia (I) includes no carbon-carbon double bonds, one carbon -carbon double bond, two carbon -carbon double bonds, three carbon-carbon double bonds, four carbon-carbon double bonds, five carbon -carbon double bonds, or six carbon-carbon double bonds. In some embodiments, the compound of Formula (I) includes no carbon-carbon double bonds, one carbon-carbon double bond, two carbon-carbon double bonds, three carbon-carbon double bonds or four carbon-carbon double bonds. In particular embodiments, the compound of Formula (I) includes no carbon-carbon double bonds, one carbon-carbon double bond, or two carbon-carbon double bonds.
[0138] In some embodiments of Formula (i), R is hydrogen, in other embodiments, R" is
Ci..6alkyl, such as methyl, or C2^alkenyl, such as isoallyl (e.g., 1-propenyl).
[0139] In certain embodiments of Formuia (I), R! is hydrogen, in other embodiments, R' is C [.^alkoxy, such as methoxy or ethoxy,
[0140] In some embodiments of Formula (i), R4 is hydroxyl. in other embodiments, R4 is
such as methoxy or ethoxy. In yet further embodiments, R4 is C i .ieacyloxy, such as C [,.»acyioxy, e.g., formyloxy, acetyioxy, proptonyloxy, butanoyloxy, phenyiacetyioxy, etc. In some embodiments, R is C^acyloxy or Cijacyloxy. in other embodiments, R4 is acetyioxy.
[0141] In some embodiments of Formula (I), R3 and R4 together form ).
[0142] In certain embodiments of Formula (I), m is 0, in other embodiments, m is 1 , In yet further embodiments, m is 2.
[0143] In certain embodiments of Formula (I), n is 0. In other embodiments, n is 1. in yet further embodiments, n is 2.
[0144] In certain embodiments of Formula (I), p is 0. In other embodiments, p is 1. in yet further embodiments, p is 2.
[0145] In certain embodiments of Formula (I), t is 0. In other embodiments, t is 1 , In yet further embodiments, t is 2.
[0146] In some embodiments of Formula (I), m is 1, n is 0, p is 1, and t is 1.
[0147] In certain embodiments, the terpenoid compound is a compound of Formula (ia);
Figure imgf000084_0001
Formula (la);
or a comestibly or biologically acceptable salt or derivative thereof, or an enansiorner or diastereomer thereof,
wherein, as valence and stability permit:
R' is absent or is selected from the group consisting of hydrogen, Ci.ioalkyl, C;.iohaloalkyl, C soalkenyl,
Figure imgf000084_0002
hydroxyl, Ci-ioacylamino, Q.ioacyloxy, Ci-iocarbonate, Ci. ioalkoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
Ci.5beteroaryl-Ci ^alkyloxy, CYioalkenyloxy, C3.ioalkynyioxy, phosphoryl, phosphate, phosphorate, phosphinate, amino, diCi.ioalkylamino, monoiVioalkylamino,
Ci .iocarbamate, Cuourea, sulfhydryl, Ci .i0alkyithio, sulfate, sulfonate, sulfamoyl, sulibnamido, suifonyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 3 -4 heteroatoms selected from , O, and S;
R" is selected from the group consisting of hydrogen, C i .ioalkyl, Ci .johaloalkyl, Cj.ioalkenyl, (¾_(0alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
Cj. loalkenyloxycarbonyl,€2-! oalkynyloxycarbonyl, Cnoae l, .ioacykmino, Cj.ioacyloxy, Ci-iocarbonate, Cuoalkoxy, phenyloxy, pheriyl-C i ^alkyloxy, Ci.sheteroaryioxy,
C;.5heteroaryl-C [.6alkyloxy, CYioalkenyloxy, C3.[.::.aikynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCj.ioalkylamino, monoC 1. loalkylamino, C|-!3amido, Ci-ioirnino, Ci-iocarbamate, Ci.ir.itrea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cv;carbocyclyl,
C3.7carbocyclyl-C;.6alkyl, C;.6heterocyclyl,
Figure imgf000084_0003
phenyl, pheny] -Ci_6aikyl, Cusheteroaryl, and
Figure imgf000084_0004
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen C 1 0alkyl, Ci.iohaloalkyl, C'l-ioal enyl, <¾.ioalkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
C2- loalkenyloxycarbonyl, C2.ioalkynyloxycarbonyl, Cnoacyl, Ci-ioacylaroiao, Ci.ioacyloxy, Ci-iocarbonate, Cuo-tHcoxy, phenyloxy, phenyl-Ci-ealkyloxy, Ci.sheteroaryioxy,
Figure imgf000084_0005
Cs-ioalkenyloxy, Ca-ioalkyoyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi.ioalkylamino, C i_i 3amido, Ci-ioiroioo, C .. ^carbamate, Ci.iourea, cyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, suifonyl, Cs^carbocyclyl,
Figure imgf000084_0006
Ci.6heterocyelyl, Ci .6heterocyclyl-Ci.6aikyl, phenyl,
Figure imgf000084_0007
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R is selected from the group consisting of hydrogen, Cuoalkyl, Ci.johaloalkyl, C-j-ioaBcenyl, <¾.)0alkynyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl,
C-2- loalkenyloxycarbonyl, C2-i oalkynyloxycarbonyl, C ,„i 0acyl, Ci_i6acyiamino, Ci„i6acyloxy,
Ci-iocarbonate, Cuoafko y, phenyloxy, phenyl-Ci-ealkyloxy, Ci-sheteroaryloxy,
Figure imgf000085_0001
Cs-ioalkenyloxy, Cj-ioalkynyloxy, phosphoryl, phosphate, ph.osphon.ate, phosphinate, amino, di.Ci_ioalkylamino, monoCi_ioalkylamirio, C i.i iamido, Ci-ioiroino, Ci.iocaibamate, CMC,iirea, cyano, nitro, azido, solfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C^carbocyclyl,
Ca^carbocyclyl -C ; _6alkyl , C _6heterocyclyl, C i _6heterocyclyl-C ^alkyl, phenyl, pheny]-Ci.6alkyl, Ci-5heteroaryls and
Figure imgf000085_0002
wherein heterocyclic or heteroaromatic rings, independently for eac occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
o R and B." together form =0 or -O-C, a1kyl-0-;
wherein any of R 1, R2, R', and R4, independently, is optionally substituted with 1-3 substituents selected from the group consisting of CVioalkyl, Ci. i haloalkyl, halo, hydroxyl, carboxyl, Ci.ioalkoxycarbonyl, (.¾. loalkenyloxycarbonyl,
C2-ioalkynyloxycarbonyl, Ci.ioacyl, Ci.ioacylaraioo, Ci.ioacyloxy, CYiocarbonate, Cj.ioalkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi. joalkylamino, Ci.i3amido, Ci..!0imino, Cj.iocarbamate, Ci .iourea, cyano, nitro, azido, sulfhydryl, Ci .ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl, Cj./carbocyclyl-Ci.ealkyl,
Figure imgf000085_0003
Figure imgf000085_0004
Ci.sheteroaryl, and
Figure imgf000085_0005
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
m is 0-2;
wherein Q and C6 in Formula (la) optionally are bonded together to form a 6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
According io some embodiments of compounds of Formula (la),
as valence and stability permit :
R1 is absent or is selected from the group consisting of hydroxyl,
Figure imgf000085_0006
and C;.6acyloxy:
If is selected from the group consisting of hydrogen, C^alkyl, C2-6al em , and
C'l-ealkynyl;
R3 is selected from the group consisting of hydrogen and Ci-galkoxy;
R'f is selected from the group consisting of hydroxyl,
Figure imgf000085_0007
and
Ci-ieacyloxy; or R3 and R4 together form =0;
wherein any of R1, R2, R', and R4, independently, is optionally substituted as noted above; and
m is 0-2;
wherein C [ and C6 in Formula (ia) optionally are bonded together to form a
6-membered ring; and
wherein all dotted bonds indicate optional carbon-carbon double bonds.
[0149] in some embodiments of Formula (la), R1 is absent. For example, in certain embodiments. R1 is absent and Ci is part of a double bond. In other embodiments, R1 is present and is hydroxy!, Ci-galkoxy, or C i-eacyloxy, particularly hydroxy!.
[0150] in certain embodiments, the compound of Formula (ia) includes a E-double bond between C5 and C6. In other embodiments, the compound of Formula (la) includes a Z-doub e bond between C5 and C6. In further embodiments, the compound of Formula (la) includes a mixture of is/Z-double bonds between C5 and C^. In yet additional embodiments, the compound of
Formula (ia) does not include a double bond between C5 and CY
[0151] In some embodiments, the compound of Formula (la) includes no carbon-carbon double bonds, one carbon-carbon double bond, two carbon-carbon double bonds, three carbon-carbon double bonds, or four carbon-carbon double bonds. In particular embodiments, the compound of Formula (la) includes no carbon-carbon double bonds, one carbon-carbon double bond, or two carbon-carbon double bonds.
[0152] in some embodiments of Formula (ia), R2 is hydrogen. In other embodiments, R2 is
such as methyl, or CYealkenyl, such as isoallyl (e.g., 1-propenyl).
[0153] In certain embodiments of Formula (la), R3 is hydrogen. In other embodiments, R3 is C [.^alkoxy, such as methoxy or ethoxy,
[0154] In some embodiments of Formula (la), R4 is hy droxyi. In other embodiments, R4 is
such as methoxy or ethoxy. In yet further embodiments, R* is Cngacyloxy, such as C [„sacyloxy, e.g., formyloxy, acetyloxy, propionyloxy, botanoyloxy, phenylacetyloxy, etc.
[0155] In some embodiments of Formula (la), RJ and R4 iogeiher form— O.
[0156] In certain embodiments of Formula (la), m is 0. In other embodiments, m is 1. In yet further embodiments, m is 2.
[0157] In some embodiments of the compound of Formula (I), Q and C6 are bonded together to form a 6-membered ring. For example, in certain embodiments, C i and C6 are bonded together to form a 6-membered ring, and m is 0. For instance, in some embodiments, the compound of Formula (I) is a compound of Formul (Ha):
Figure imgf000087_0001
Formula (lla);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R4 are as defined above, [0158] As noted above, in some eiTibodiments, R! and R4 together form =0. For example, in certain embodiments, the compound of Formula (lla) is a compound of Formula (Ilia):
Figure imgf000087_0002
Formula (III a);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof, wherein, as valence and stability permit, R2 is as defined above.
[ 159] As noted above, in some embodiments of the compound of Formula (I), C] and C( are bonded together to form a 6-membered ring. For example, in certain embodiments, C i and C¾ are bonded together to form a 6-membered ring, and m is 1. For instance, in some embodiments, the compound of Formula (Ϊ) is a compound of Formula (lib):
Figure imgf000087_0003
Formula (lib);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R4 are as defined abov In some embodiments, the exo-cyciic dashed bond is a double bond, in other embodiments, the exo-cyclic dashed bond is a single bond.
[0160] As noted above, in some embodiments, RJ and R4 together form =0. For example, in certain embodiments, the compound of Formula (lib) is a compound of Formula (111b) :
Figure imgf000088_0001
Formula (lllb)
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2 is as defined abo ve. In some embodiments, the exo-cyclic dashed bond is a. double bond. In other embodiments, the exo-cyclic dashed bond is a single bond,
[0161] According so other embodiments of the compound of Formul (I), d and C6 are not bonded together to form a 6-membered ring and the compound is a substantially linear compound.
[0162] As noted above, in certain embodiments, the compound of Formula (I) does not include a double bond between C5 and C6. For example, in certain embodiments, the compound of Formula (i) does not include a double bond between C5 and C6, and C . and C6 are not bonded together to form a 6-membered ring. For instance, in some embodiments, the compound of Formula (i) is a compound of Formula (lie):
Figure imgf000088_0002
Formula (He);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R!, I , R", and R4 are as defined above.
[0163] As rioted above, in some embodiments, R1 is absent and C| is part of a double bond. For example, in certain embodiments, the compound of Formula (lie) is a compound of Formula (Mb):
Figure imgf000088_0003
Formula (Me);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R4 are as defined above.
[ 164] As noted above, in some embodiments, R4 is hydroxy! or C flacyloxy, such as
Ci-gacyioxy, e.g., formyloxy, acetyloxy, propionyloxy, butanoyloxy, phenyiacetyioxv, etc. For example, in certain embodiments, R2 and R3 are hydrogen and R4 is hydroxy! or C' igacyloxy, such as C6.ioaryl-C(.6acyl, e.g., phenylacetyloxy. For example, in some embodiments, R2 and RJ are bydrogen and R4 is hydroxy! or such as d-gacyioxy, e.g., fonnyloxy, acetyloxy, propionyloxy, botanoyloxy, phenylacetyloxy, etc. For instance, in some embodiments, the compound of Formula (IHc ) is a compound of Formula (IVc):
Figure imgf000089_0001
Formula (IVc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined above.
[0165] As noted above, in certain embodiments, the compound of Formula (I) includes a ii-double bond between C$ and Q. For example, in certain embodiments, the compound of Formula (I) includes a IT-double bond between and C& and C; and Cg are not bonded together to form a 6-membered ring. For instance, in some embodiments, the compound of Formula (I) is a compound of Formula (lid):
Figure imgf000089_0002
Formula (lid);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R", R1, R3, and R4 are as defined above.
[0166] As noted above, in some embodiments, R1 is absent and Ci is part of a double bond. For example, in certain embodiments, the compound of Formula (lid) is a compound of Formula (Hid):
Figure imgf000089_0003
Formula (Hid);
or a comestibly or biologically acceptable sals or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, , and R4 are as defined above.
[0167] As nosed above, in some embodiments, R'f is hydroxy! or d-ieacyloxy, such as
Figure imgf000089_0004
e.g., phenylacetyloxy. For example, in some embodiments, R4 is hydroxy! or Ci-ieacyloxy such as
Figure imgf000089_0005
e.g., formyloxy, acetyloxy, propionyloxy, butanoy!oxy, phenylacetyloxy, etc. For example, in certain embodiments, R2 and R" are hydrogen and R'f is hydroxy! or CM6acyloxy, suc as (^!0aryl-d.<sac l, e.g., phenylacetyloxy. For example, in some embodiments, R'' and R* are hydrogen and R4 is hydroxy! or d-i6acyioxy, such as e.g., fomiyloxy, aceiyloxy, propionyioxy, butanoyloxy, phenylacetyloxy, etc. For instance, in some embodiments, the compound of Formula (Hid) is a compound of Formula (IVd):
Figure imgf000090_0001
Formula (IVd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined above.
[0168] As noted above, in certain embodiments, the compound of Formula (I) includes a Z-double bond between C5 and Cg. For example, in certain embodiments, the compound of Formula (I) includes a Z-double bond between C< and C& and C> and Ce are not bonded together to form a 6-membered ring. For instance, in some embodiments, the compound of Formula (I) is a compound of Formula (He):
Figure imgf000090_0002
Formula (He);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit. R!, R , R", and R are as defined above.
[0169] As noted above, in some embodiments, R1 is absent and there is a double bond between Ci and C2. For example, in certain embodiments, the compound of Formula (He) is a compound of Formula (Hie):
Figure imgf000090_0003
Formula (Hie);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R4 are as defined above. [0170] As noted above, in some embodiments, R4 is hydroxy! or C i_! 6acyioxy, such as
Figure imgf000091_0001
e.g., phenylacetyioxy. For example, in some embodiments, R4 is hydroxyl or C'i.;6acyloxy, such as Ct-gacyloxy, e.g., formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc. For example, in certain embodiments, " and R:' are hydrogen and R4 is hydroxyl or CM6acyloxy, such as C6_;0aryFCi_6acyl, e.g., phenylacetyioxy. For example, in some embodiments, R2 and RJ are hydrogen and R4 is hydroxyl or Ci.iKacyloxy, such, as Cj.gacyloxy, e.g., formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc. For instance, in some embodiments, the comp of Formula (IVe);
Figure imgf000091_0002
Formula (TVe);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined abo ve.
[0171] As noted above, in some embodiments, R1 is present and is hydroxyl, C' l^aikoxy, or Ci-gacyloxy, particularly hydroxyl. For instance, in some embodiments, the compound of Formula (I) is a compound of Formula (lifj:
Figure imgf000091_0003
Formula (Hi);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R4 are as defined above.
[0172] in some embodiments of the compound of Formula (i), R" and R ' are hydrogen and R4 is hydroxyl or Ci.ieacytoxy, such as
Figure imgf000091_0004
e.g., phenylacetyioxy. For example, in some embodiments, R2 and R3 are hydrogen and R4 is hydroxyl or Cueacylo y, such as Ci.gacyloxy, e.g. formyioxy, acetyloxy, propionyloxy, butanoyloxy, phenylacetyioxy, etc. For instance, in some embodiments, the compound of Formula (I) is a compound of Formula (ilg):
Figure imgf000091_0005
Formula (iig);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R! and R4 are as defined above. [0173] in some embodiments of the compound of Formula (I), R is hydrogen and R" and R4 are both C[- lko y, such as methoxy or ethoxy. For instance, in some embodiments, the compound of Formula (Ϊ) is a compound of Formula (lih):
Figure imgf000092_0001
Formula (iih);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereorner thereof, wherein, as valence and stability permit, R:, R', and R4 are as defined above, [0174] in certain embodiments, the compound of Formula (I) is selected from the group consisting of damascene compounds (e.g., β-damascone, trans-a-damascone), ionone compounds (e.g., β-ionone, a-ionone, y-ionone, and dihydro- -ionone, particularly either β-ionone or a-ionone), nerol, geranyi isovalerate, geranyi acetone, neiyl acetate, geranyi propionate, geranyi butyrate, citronellyl propionate, citronellyl isobutyrate, citral diethyl acetal, geranyi phenyiacetate, geranyi formate, DL-citronellol, neryl isovalerate, citronellyl acetate, citral dimethyl acetal, citral, gerartial, neral, neryl butyrate, citronelial, hydroxycitroneliai, citronellyl valerate, geraniol, neryl isobutyrate, geranyi acetate, citronellyl forsnate, hydroxycitroneliai dimethyl acetal, and phytyl acetate.
[0175] in certain embodiments, the compound of Formula (I) is:
Figure imgf000092_0002
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Compound Citron ella oil
38
(Sigma Cat. No. W230840),
(Mixture)
Geranium oil
Compound
39 (also referred to as Geranium oil Algerian, oil of Geranium, oil of pelargonium, oil of
(Mixture) rose geranium, Pelargonium oil, and Rose geranium oil Algerian)
(Sigma Cat. No. W250813),
Geranium East Indian oil
(also referred to as palmarosa oil, Indian grass oil, oil of Geranium (East Indian),
Compound
40 Palmarosa oil, Rusa oil, and Turkish, geranium oil)
(Mixture) (Sigma Cat No. W283109),
Compound
41
(Vigon Cat. No. P-00698), or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diasiereomer thereof.
Edible compositions comprising chroman compounds
[0164] The substituent definitions in this section (i.e., R1, R2, R3, R4, R\ R° and n) refer to compounds of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila).
[0176] All stereochemical forms of the compounds disclosed in this and any section herein are specifically contemplated, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, 8), Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the compounds disclosed in this and any section herein are also specifically contemplated.
[0177] In some embodiments, the present invention provides an edible composition for reducing bitter taste of a bitter tastant, wherein the composition comprises a cbrosnan compound. The chroman compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant. In some embodiments, the chroman compound has a molecular weight less than about 1000, 500, or 300 daltons. I certain embodisnents, the cbrosnan compound is a compound of Formul (V):
Figure imgf000098_0001
Formula (V);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1, independently for each occurrence, is selected from the group consisting of C:_[oalkyl, C i.iohaloalkyl, Cj,ioalkenyl, .ioalkynyl, halo, hydroxy!, carboxyl,
Ci.ioalkoxycarbonyl, CVioalkenyloxycarbonyl, i ioa!kynyloxycarbonyl, Ci.ioacyl, Ci-ioacylamino, Ci.ioacyioxy, CViocarbonate, Ci.ioalkox , phenyioxv,
Figure imgf000098_0002
C;.5heteroaryloxy, Ci.5heteroary!-Ci.6alkyloxy, C3.ioalkenyloxy, Q.joalkynyloxy, phosphoryi, phosphate, phosphonate, phosphinate, amino, diC aikylamino, monoC |. loalkylainino, C^n mido, Ci.ioimino, Ci.iocarbamate, Ci.ioorea, cyano, nitro, azido, sulfhydryl, Cuioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocyclyl, Cv/carbocyclyl-C nsalkyl, C i-6heterocyclyl, C'i
Figure imgf000098_0003
phenyl,
Figure imgf000098_0004
C sheteroaryl, and wherein heterocyclic or heteroaromaiic rings, independently for each occurrence, comprise 1-4 heteroaioms selected from N, O, and S;
If is selected from the group consisting of hydrogen, Cuoalkyl, C,..johaloalkyl, C2-ioalkenyl, Q.ioalkynyl, halo, hydroxy!, carboxyl, Ci.ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, C2-ioalkynyloxycarbonyl, Cnoacyl, Ci-ioacylamino, Ci.ioacyioxy,
Ci.iocarbonate, Cnoafkoxy, pbenyloxy, pheny!-Ci.6a]kyloxy, Ci-sheteroaryloxy,
Figure imgf000098_0005
Cs-ioalkenyloxy, Cj.ioalkynyloxy, phosphoryi, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoCi.ioalkyiamino, C i_i3amido, Ci.ioimino, Ci_i0carbamate, Ci„i0urea, cyano, nitro, azido, sulfhydryl, C i_10a1kylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C^carbocyclyl,
Ci. cas'bocj'clyl-Ci.o lkyl, Ci.6heterocycly!, Ci .6heterocycly!-Ci.6alkyl, phenyl,
Figure imgf000098_0006
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen, Cuoalkyl, Ci.iohaloalkyl,
C2-ioalkenyl, C2.10alk.ynyl, halo, hydroxy!, carboxyl, C i.ioalkoxycarbonyl,
C2-ioalkenyloxycarbonyl, C .ioalkynyloxycarbonyl, Ci.i acyl, Ci-ioacylamino, Ci .ioacyioxy, Ci.iocarbonate, Ci.ioalkoxy, phenyioxv,
Figure imgf000098_0007
C i-5heteroaryloxy, Ci-sheteroaiyl-C
Figure imgf000099_0001
Ci.ioalkenyloxy, C3_[.:;aIkynyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCj.ioalkylamino, monoC \. loalkylamino, Ci.i3amido, Ci.iciniino, Cj.iocarbamaie, Ci.ir.itrea, cyano, nitro, azido, sulihydryi, C ,oalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C^carbocyclyl,
C3.7cai'bocyc]yl-C;.6alkyl, C^heterocyclyl, Ci.6heterocycly3-C |„6alkyl, phenyl,
Figure imgf000099_0002
Ci-sheteroaryl, and Ci-sheteroaryl-Ci-ealkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R'f is selected from the group consisting of hydrogen,
Figure imgf000099_0003
Figure imgf000099_0004
hydroxy!, Ci_ioacyloxy, Cuoalkoxy, phenyloxy,
phenyl-Ci-ealkyloxy, C i-sheteroaryloxy,
Figure imgf000099_0005
Cj.ioalkenyloxy, Cj.io lkynyl xy, amino, diCi_ioalkylarnino, monoCMOalkylamino, sulihydryi,
CMOalkylthio, C3-7carbocyclyl, C3-7carbocyclyl-C i.6alkyl, C ^heterocyclyl,
Ci.bhetei'ocyclyl-Ci .ealkyl, phenyl,
Figure imgf000099_0006
CYsheteroaryl, and
Figure imgf000099_0007
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from. N, O, and S;
R5 is selected from the group consisting of hydrogen, Ci.Tiaikyi,
Figure imgf000099_0008
C2-2ialkenyl, C2-2ialkynyl, hydroxyl, Cuo-tcyloxy, Ci.i0alkoxy, phenyloxy,
phenyl-C j.6alkyloxy, Ci.sheteroarytoxy,
Figure imgf000099_0009
C3.1 oalkenyloxy, C;i..]i)alkynyioxy, amino, diCi.ioalkylamino, monoCj-ioalkylamino, sulihydryi,
C s-ioalkylthio, C3. ?carbocyelyl, C3. ycarboeyelyl-C 1
Figure imgf000099_0010
Figure imgf000099_0011
Ci-sheteroaryl, and
C]..5heteroar}'l-C].flalkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R4 and R5 together form or - -Ci-!0alkyl-O-;
wherein any of R1, R , RJ, R4, and R', independently and independently for each occurrence, is optionally substituted with 1-3 substituents selected from the group consisting of C(-ioalkyl, C' l.iohaloalkyl, halo, hydroxyl, carboxyl, C i. i0alkoxycarbonyl, C2-ioalkenyioxycarbonyl, CVioalkynyloxycarbonyl, Ci.ioac l, Ci.Kiacylamino, Ci.Kiacyloxy, C ,„iocarbonate, C;.[.:;alkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylarnino, monoC [_l0alkylamino,
Figure imgf000099_0012
C|-i0imino, Ci_!0carbamate, C ,„iourea, cyano, nitro, azido, sulihydryi, C oalky3thio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, C3.7carbocydyl,
Figure imgf000099_0013
Figure imgf000099_0014
C i_5heieroaryl, and
Ci-sheteroaryl-C ealkyl; and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from , O, and S; and
n is 0-3.
According to some embodiments of compounds of Formula V,
as valence and stability' permit: R1, independently for each occurrence, is selected from the group consisting of halo, hydroxy!, Chalky 1, Ci.ghaloalkyl, C2_,;alkenyl, C^lk n l, and Cusalkoxy;
R is selected from the group consisting of hydrogen, halo, hydro xyl. Chalky!, C ; _6haS o Iky 1, C2-,;alkenyl, C2-6alkyn l, C;_6a!koxy, Cl-6acyloxy optionally substituted by hydroxy!, amino, mono- or disubstituted Chalky! amino, or carboxyl;
R3 is selected from the group consisting of hydrogen, hydroxy!, Ch lk !,
Figure imgf000100_0001
R* is selected from the group consisting of hydrogen, hydroxy!, Ch lky!, C2-2iaBcenyl, C2-2;aikyny!, and Ci-ealkoxy, wherein R4 is optionally substituted by one or more occurrences of hydroxy! or acetyloxy;
R~ is selected from the group consisting of hydrogen, hydroxy!, Ch lky!, C2-2ialkeny], C2.2!alkynyi, and C^alkoxy, wherein R5 is optional]}? substituted by one or more occurrences of hydroxy! or acetyloxy;
or R4 and 5 together form =0;
wherein any of R1, R , R3, R", and R5, independently and independently for each occurrence, is optionally further substituted as noted above; and
n is 0-3.
[0179] According to some embodiments of the compound of Formula (V), one or more occurrences of R' is C halky!, such as methyl; RJ is hydrogen; and Rs is
Figure imgf000100_0002
such as methyl. For example, in certain embodiments, the compound of Formula (V) is a compound of
Formula (Via):
Figure imgf000100_0003
Formula (Via);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, and R4 are as defined above, wherein the carbon marked with * optionally has R or 5 stereochemistry or is a mixture of R and S stereochemistry.
[0180] According to some embodiments, R2 is hydroxy!;
Figure imgf000100_0004
optionally substituted by hydroxy!, amino, mono- or disubstituted Chalky! amino, or carboxyl; and R" is Ci.2ialkyl, such as methyl or -CH2-ISP wherein ISP represents 1 to 4 saturated isoprene units (particular!}? 3 isoprene units), or C2-2ialkenyl, such as -CH2-ISP wherein ISP represents 1 to 4 isoprene units wherein one or more isoprene unit optionally includes a carbon-carbon double bond. For example, in certain embodiments, the compound of Formuia (Via) is a compound
Formula (Vila):
Figure imgf000101_0001
Formula (Vila);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R6 is selected from the group consisting of hydrogen, Chalky!; or Cj ^acyl optionally substituted by hydroxyl, amino, mono- or disubstituted C]. alk l amino, or carboxyl; and
wherein the carbon marked with * optionally has R or S stereochemistry or is i mixture oiR and S stereochemistry.
[ 18 IJ in certain embodiments, R6 is hydrogen, in other embodiments, R6 is
Figure imgf000101_0002
such as acetyl or propionyl, optionally substituted by hydroxyl, amino, mono- or disubstituted C
Figure imgf000101_0003
amino, or carboxyl. For example, in certain embodiments, R6 is carboxyl-substituted propionyl. such as 3-carboxylpropionyl. in some embodiments, RO- is succinate.
[0182] In certain embodiments, the compound of Formuia ( V) is:
Figure imgf000101_0004
Figure imgf000102_0001
10;
Figure imgf000103_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0183] in certain embodiments, the compound of Formula (V) is selected from the group consisting of pentametbyl-6-chromanol, a-tocopherol, (+)-6-tocopherol, (+)-a-tocopherol acetate, D-a-toeopherol succinate, DL-ct-tocopherol acetate, and Vitamin E acetate.
[0184] According to some embodiments of the compound of Formula (V), n is 0 and R2 is hydrogen. For example, in certain embodiments, the compound of Formula (V) is a compound of Formula (VIb):
Figure imgf000103_0002
Formuia (VIb);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, RJ, R4, and R5 are as defined abov [0185] in some embodiments, RJ is hydrogen. In other embodiments, RJ is hydroxyl.
[0186] According so certai embodiments, one or both of R'f and R3 is hydrogen, for example, both R4 and R5 are hydrogen. In other embodiments, R4 and R5 together form ==:0.
[0187] in certain embodiments, the compound of Formula (V) or Formula (VIb) is:
OH
Compound 52
(Sigma Cat No. 303895),
Compound 53
(Sigma CatC No. W238104), or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diasiereomer thereof
[0188] in certain embodiments, the compound of Formula ( V) or Formula ( VIb) is selected from the group consisting of 4-chromanol and dihydrocoismarin.
Edible compositions cosTiprisiiig benzo ring-coiitaiaing compounds
[0164] The subsiituent definitions in this section (i.e., R1, R2, R3, R4, R", m, and n) refer io compounds of Formula i V U ! s. Formuia (IXa), Formuia (IXb), Formuia (IXc), or Formula (IXd).
[0189] All stereochemical forms of the compounds disclosed in this and any section herein are specifically contemplated, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S), Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the compounds disclosed in this and any section herein are also specifically contemplated.
[0190] its some embodiments, the present invention provides an edible composition for reducing bitter taste of a bitter ta stant, wherein the composition comprises a benzo ring-containing compound. The benzo ring-containing compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant. In some embodiments, the benzo ring-containing compound has a molecular weight less than about 1000, 500, or 300 daltons. in certain embodiments, the benzo ring-containing compound is a compound of Formula (VIII):
Figure imgf000104_0001
Formula (VIII);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R , independently for each occurrence, is selected from the group consisting of hydrogen, Ci_;0alkyi, Ci.iohaloalkyi, Ci-ioaikenyl, C2-;oalkynyi, carboxyl,
Ci-ioalkoxycarbonyl, Ci-ioalkenyksxycarbonyl, C2-ioalkynyloxycarbonyl, C i_;0acyi, phosphoryl, phosphonate, phosphinate, sulfonate, sulfamoyl, sulfonyl,
Figure imgf000104_0002
C3-7carbocyclyl-C ;-6alkyi, Ci-ebeterocyclyl ,
Figure imgf000104_0003
phenyl,
Figure imgf000104_0004
CVsheteroaryl, and wherein heterocyclic or beteroaromatic rings, independent!}? for each occurrence, comprise 1 -4 heteroatoms selected from , O, and S;
R is selected from the group consisting of hydrogen, Ci.ioalkyl, CYiohaloalkyl, C2-ioalkenyi, CYioalkynyl, hydroxy!, Ci .ioacyloxy, Ci..ioalkoxy, phenyloxy, phenyl-Ci .ealkyloxy, Ci-sheteroaryloxy,
Figure imgf000104_0005
C3.ioalkeuyloxy, C3.10alkyny.oxy, amino, diCi.ioalkylamino, monoC i. loalkylamino, solfhydryl,
Ci-ioalkylthio, C:;„7carbocyciyl, C3.7carbocyclyl-C
Figure imgf000105_0001
Figure imgf000105_0002
Ci.jheteroaryl, and
Figure imgf000105_0003
wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
R3 is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl, C2-ioalkenyl, Q-ioalkynyl, hydroxy], Cuoacyloxy, Cnoalkoxy, phenyloxy,
C i.sheteroaryloxy, C3.ioalkeny!oxy,
Figure imgf000105_0004
no, diCi.ioalkylamino, monoCi.ioalkylamino, sulfhydryl,
Ci-ioalkylthio, C3.7carbocycK ,
Figure imgf000105_0005
Figure imgf000105_0006
phenyl, phenyl-Ci-ealkyl, Ci-sheteroaryl, and
C;.5heteroa:ry!-Ci.6alkyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
or R2 and R3 together form =0 or -O-Ci.ioalkyl-O;
R~ is selected from the group consisting of hydrogen, Ci.ioalkyl, Ci.iohaloalkyl,
Figure imgf000105_0007
ioalkenyloxycarbonyl, C2. loaikynyioxycarbonyi, Ci. ioacyl, phosphoryl, phosphonate, phosphinate, cyano, sulfonate, sulfamoyl, sulfonyl, C3.7carbocyclyl,
Figure imgf000105_0008
Figure imgf000105_0009
Ce-ioaryl, Ci-sheteroaryl, and
C]..5heteroar}'l-Ci.fla[kyl, wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S;
wherein any of R1, R , R3, and R4, independently and independently for each occurrence, is optionally substituted with 1-3 substituents selected from the group consisting of Ci.io lkyl, Ci.iohaloalkyl, halo, hydroxy!, carboxyl, Ci.ioalkoxycarbonyl, C2-ioalkenyioxycarbonyl, Ci.ioalkynyloxycarbonyl, Ci.ioacyl, Ci.ioacylamino, Ci.ioacyloxy,
Ci-iocarbonate, Ci.ioalkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylamino, monoC i. i(^lkylamino, Cj.namido, Ci.u>imino, Ci-iocarbamate, C ,.iourea, cyano, nitro, azido, sulfhydryl, C;_ioalkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, C Carbocyclyl,
Figure imgf000105_0010
Cwheterocyclyl, C.eheterocyclyl-Ci.galkyl, phenyl, phenyl-C
Figure imgf000105_0011
C i.jheteroaryl, and
Figure imgf000105_0012
and wherein heterocyclic or heteroaromatic rings, independently for each, occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
n is 0-3.
According to some embodiments of compounds of Formula (VIII),
as valence and stability permit:
R1, independent!}? for each occurrence, is selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl, C2.,;alkynyl, and Ci_6acyl;
R is selected from the group consisting of hydrogen, Chalky!, CVea!keny!, and C2.6alkynyl; R" is selected from the group consisting of hydrogen. Chalky!, Q^ealkenyl, and
Ci-ealkynyl;
or R2 and " together form =0;
R is selected from the group consisting of hydrogen, Chalky!, C2-(¾alkeay], C2_6alkynyl, C]_6acyl, and C6.;oary3-C |„6alkyj;
wherein any of R1, R2, R: and R4, independently and independently for each occurrence, is optionally further substituted as noted above; and
is 0-3 ,
[0192] According so sosne embodiments of the compound of Formula (VIII), n is 0, and and R together form :==0. For example, in certain embodiments, the compound of Formula (VIII) is benzoic acid or a benzoic acid ester. For instance, in some embodiments, the compound of Formula (VIII) is a compound of Formula (IXa):
Figure imgf000106_0001
Formula (IXa);
or a comestihly or biologically acceptable salt or derivative thereof, or an eoaotiomer or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined above.
[0193] In certain embodiments, R4 is hydrogen. In other embodiments, R4 is Chalky!, such as methyl, ethyl, propyl, or butyl, or C6.ioaryl-C;.6a5kyi, such as
Figure imgf000106_0002
e.g., benzyl or dihydroc i nnamyl .
[0194] In certain embodiments, the compound of Fonmila (VIII) or Formula (IXa) is:
Compound 54
(Sigma Cat No. 12349),
Compound 55
(Sigma Cat No. W24221 7), 0
Compound 56
(Sigma Cat No. 307009),
Compound 57
(Sigma Cat No. W286001), or a comestibiy or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0195J In certain embodiments, the compound of Formuia (VIII) or Formula (IXa) is selected from the group consisting of benzoic acid, ethyl benzoate, propyl benzoate, and phenethyl benzoate.
[0196] According io some embodiments of the compound of Formula ( VIII), n is 1-3, and R2 and RJ together form =0. For example, in certain embodiments, the compound of Formula (VIII) is a hydroxybenzoic acid or a hydroxybenzoic acid ester. For instance, in some embodiments, the compound of Formula (VIII) is a compound of Formula (IXb):
Figure imgf000107_0001
or a comestibiy or biologically acceptable salt or derivative thereof, or an enantiomer or diass ereom er thereo f,
wherein, as valence and stability permit:
R1 and R4 are as defined above; and
m is 0-2.
[0197] In certain eiiibodiraents, the compound of Formuia (VIII) or Formula (IXb) includes a hydroxy! group on the 4-position of the benzo ring. In other embodiments, the compound of Formula (VIII) or Formula (IXb) includes a hydroxy! group on 2-position of the benzo ring.
[0198] In certain embodiments, R4 is hydrogen. In other embodiments, R4 is Chalky!, such as methyl, ethyl, propyl, or butyl.
[0199] In certain embodiments, the compound of Formula (Vlli) or Formula (IXb) is:
Figure imgf000108_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0200] in certain embodiments, ihe compound of Formula (Viii) or Formula (IXb) is selected from the group consisting of 4-hydroxybenzoic acid, methyl ?ara-hydroxybenzoate, ethyl parahydroxybenzoate, and butyl paraben.
[0201] According to some embodiments of the compound of Formula (VIII), n is 1-3, and Rr and R"' together form =0. For example, in certain embodiments, the compound of Formula (VIII) is a C [„6alkyjoxybenzoic acid or a C walkyloxybenzoic acid ester. For instance, in some embodiments, the compound of Formula (Viii) is a compound of Formula (IXc):
Figure imgf000109_0001
Formula (IXc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diass ereom er thereo f,
wherein, as valence and stability permit;
R1 and R4 are as defined above;
Figure imgf000109_0002
in is 0-2.
[0202] In certain embodiments, R4 is hydrogen, in other embodiments, R4 is Chalky!, such as methyl.
[0203] In certain embodiments, R5 is methyl, ethyl, or propyl, in some embodiments, the compound of Formula (Vill) or Formula (IXc) includes a rnethoxy group on the 4-position, the 3-position, or the 2-position of the benzo ring.
[0204] In certain embodiments, the compound of Formula (Vlli) or Formula (IXc) is:
Figure imgf000109_0003
Figure imgf000110_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enaniiomer or diastereomer thereof.
[0205] in certain embodiments, the compound of Formula (Viii) or Fonnula (Die) is selected from the group consisting of 4-!rtethoxybenzoic acid, 3 -methoxybenzoic acid, 2-methoxybetizoic acid, 4-propoxybenzoic acid, and methyl-o/ ¾o-methoxy benzoate.
[0206] According to some embodiments of the compound of Formula (VIII), R2 is hydrogen, and at least one occurrence of R1 is H, For example, in certain embodiments, the compound of Formula ( Viii) is a compound of Formula (iXd);
Figure imgf000110_0002
Formula (IXd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enaniiomer or diastereom er thereo f,
wherein, as valence and stability permit;
R1, R3, and R4 are as defined above; and
m is 0-2.
[Θ207] In certain embodiments, RJ is hydrogen. I other embodiments, R! is Ch lky!, such as methyl.
[Θ208] In some embodiments, R4 is hydrogen.
[Θ209] In certain embodiments, m is 0. In other embodiments, m is 1 or 2, and R1 is Chalk !, such as methyl.
[0210] In certain embodiments, the compound of Formula (VIII) or Formula (IXd) is:
Figure imgf000110_0003
Figure imgf000111_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof.
[0211] in certain embodisnents, the compound of Fonnula (Viil) or Formula (IXd) is selected from the group consisting of para-hydroxybenzyl alcohol, a-methylbenzyl alcohol, and
4-(l-bydroxyethyl)-2-met oxyphenol.
Edible compositions comprising polycvclic compounds
[0164] The substituent definitions in this section (i.e., R1, R2, R3, R4, R5, R6, R7, and Ra, X and Y) refer to compounds of Formula (Xi) or Formula (XII).
[0212] All stereochemical forms of the compounds disclosed in this and any section herein are specifically contemplated, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S), Single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the compounds disclosed in this and any section herein are also specifically contemplated.
[0213] In some embodiments, the present invention provides an edible composition for reducing bitter taste of a bitter tastant, wherein the composition comprises a polycyclic compound. The polycvclic compounds of this invention are capable of reducing or eliminating bitter taste of a bitter tastant. In some embodiments, the polycyclic compound has a molecular weight less than about 1000, 500, 300 or 200 daltons. In certain embodiments, the polycyclic compound has a bicyclic core with a one-carbon transannular bridge, such as a compound of Formula
Figure imgf000111_0002
Formula (XI); or a comestibly or biologically acceptable salt or derivaiive thereof, or an enantiomer or diasiereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond,
R1, R , RJ, R6, and R' are independently selected from the group consisting of hydrogen, Cj.ioalkyl, C2_ioalkenyl, and C2-ioalk n l,
wherein each of R", R R3, R6, and R' may be optionally independently substituted with one or snore substituents selected from the group consisting of halo, -OH, -Q, -SH, -S, -NH2, -C02H, -O(Ci.10alkyl), -Q(C2.i0alkenyl), -0(C2-i(>alkyQyl), -S(C;.ioalkyl), -S(C2.;oalkenyl), -S(C2_ioalkynyl),■■
H(CMOalkyl), -NH(C2.i0alkenyl), ΛΠΚ . . a!kyn l i -N(C Oalkyl)2, - N(C2_!0alk.enyl)2, and -N(C2.i0alkynyi)2, and
R'f is absent or selected from the group consisting of hydrogen, Ci.ioalkyl, C2. ioalkenyi, C2.ioalkynyl, Ci.ic. cyl, Ci .ioacyloxy, Ci .ioaeylamino, CYioacylthioxy, Ci. io lkyl ester, Ci.ioalkenylester, Ci-ioaikynyl ester, Ci.ioalkylaroide, CVioalkenylamide, Ci-ioaB yiiyiamide, Ci.ioalkylthioester, Ci-ioalkenylthioester, and Ci.ioalkynylthioester;
wherein R4 may be optionally substituted with one or more substituents selected from the group consisting of halo, -OH, = , -SH, =S, -NH2, -C02H, - O(C|-!0a!kyl), -0(C2.ioalkenyl), -O(C2.10alkynyl), -S(Ci.|0alkyl), -S(C2.10alkenyl), -S(C2..] 0alkynyl), -Ni ii C . alkyi !. -NH(C2.,i:.alkenyl), -Ni ii . alkynyi i. - ] (C [..]oalkyi)2, -N(C2.i()alkenyl)2, -N(C2_]oalkynyi)2, Ci.ioacyi, Ci .ioacyloxy, Ci-ioacylamino, Ci.ioacylthioxy, Cj.joalkylester, Ci.ioalkenylester, Ci.ioalkynylester, Ci.ioalkylamide, Cj.ioalkenylamide, C ioalkynylamide, Ci.ioalkylthioester, Ci .ioalkenyithioester, and Ci.ioalkynylthioester,
RJ is absent or selected from the group consisting of hydrogen, Cuoalkyl, Ca-ioalkenyl, and C2.10alkyn.yl,
wherein RJ may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, ), -SH, ^S, Al l , - H. M l -O(Ci.ioaikyl), -O(C2.l0alkenyl), -O(C2.10alkynyl), -S(C].10alkyl), - S(C2.10alkenyl), -S(C2-) 0alkynyl), Al li C .. iky! i. -NH(C2.10alkenyl), - NH(C2.ioaikynyl), -N(Ci.i0aiky'l.)2, -N(C2.l0alkenyl)2, and -N(C2-!oalkyQyl)2; wherein R6 and R' are optionally taken together to form =0,— S or =C(Ra)2;
wherein each Ra is independently selected from the group consisting of hydrogen, Ci.io lkyl, C2.;oaikenyl, and C 0alkynyi,
wherein each. C i.io lkyl, C2.;oalkenyl, and C2.;oalkynyi may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, =S, -NH2, - C02H, -O(Ci.ioalkyl), -O(C2..!0alkenyl), -O(C2.i0alkynyl), -S(Ci.i0alkyl), -S(C2.i0alkenyl), -S(C2..!0alkynyl), NH(C Oalky1), -NH(C2.i0a1kenyl), - H(C2„l0aikynyl), -N(C U! 0aikyl)2, -N(C' 2.!0alkeiiyl)2, and - N(C2.10aikynyl)2;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of=C(Ra)- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of ==€> and :==S; and
wherein when the bond with the dotted line represents a. single bond, X is selected from the group consisting of -C(Ra)2-, -N(Ra)-, -O, and -S-;
provided that when the bond with the dotted line represents a double bond, R? is absent, and when the bond with the dotted line represents a single bond, R4 is present,
[0214] According to some embodiments of Formula (XI),
as valence and stability permit:
R1, RJ, R6, and R ' are independently selected from the group consisting of hydrogen, Ci..6aikyl, C^ealkenyl, and C2.6alkynyl;
R½ is absent or selected from the group consisting of hydrogen, d..6alkyl,
C2.6alkenyl, C2.6alkynyl, Ci..fiacyl, C..6acyioxy, Ci .6alkylester, Ci .ealkenyiester, and Ci.6alkynylester;
R5 is absent or selected from the group consisting of hydrogen, Q .6aikyl, C2_6alkenyl, and C^alkynyl;
wherein R6 and R7 are optionally taken together to form =0, =S or =C(Ra)2; wherein each Ra is independently selected from the group consisting of hydrogen, Chalky!, C2..6alkenyi, and C^alkynyl;
wherein any of R1, R2, R3, R* R5, R6, R7, and R' are independently optionally substituted as noted above;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of =C(Ra)- and ^N-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and HS; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2-, -N(Ra)-, -0-, and -S-;
provided that when the bond with the dotted line represents a double bond, RJ is absent, and when the bond with the dotted line represents a single bond, R4 is present.
[0215] According to some embodiments of Formula (XI),
as valence and stability permit:
R1, R2, R3, R6, and R7 are independently selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl, and C2_6alkynyl;
R4 is absent or selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl, C2.6alkynyi,
Figure imgf000113_0001
Ci.ealkenyiester, and C;.6alkynyl ester; wherein R4 may be optionally substituted with one or more substituents selected from the group consisting of -OH, ^O, -SH, and ^S;
R' is absent or selected from the group consisting of hydrogen, Chalk 1,
Figure imgf000114_0001
and C2.6alkyn.yl;
wherein R6 and R' are optionally taken together so form =0, =S or ==:C(RA)2; wherei each RA is independently selected from the group consisting of hydrogen, Ci.6alkyl, C2-6alk.en.yl, and C2.6all yn.yl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of -C(RA')- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of— O and S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(RA)2-, - (RA)-, -0-, and -S-;
provided that when the bond with the dotted line represents a double bond, 3 is absent, and when the bond with the dotted line represents a single bond, R4 is present,
[0216] According to other embodiments of compounds of Formula (XT),
as valence and stability permit:
R1, R2, R', R6, and R' are independently selected from the group consisting of hydrogen,
Figure imgf000114_0002
C2.3alk.enyl, and C2-3 lk nyl;
R" is absent or selected from the group consisting of hydrogen, Cwalkyl,
C2..t,alkenyl, (¾6alkynyL, and Ci-gaeyl;
wherein R4 may be optionally substituted with =0 or HS;
RJ is absent or selected from the group consisting of hydrogen, Chalky!, C2-3 lkenyl, and
Figure imgf000114_0003
wherein R6 and R' are optionally taken together to form =0, or ^C(RA)2; wherein each RA is independently selected from the group consisting of hydrogen, C ,.3alkyl, C2.3alkenyl, and C'2-3alkyny{;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of =C(RA)- and ^N-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(RA)2-, -N(RA)- , -0-, and -S-;
provided that when the bond with the dotted line represents a double bond, R5 is absent, and when the bond with the dotted line represents a single bond, R4 is present.
[0217] in yet other embodiments of compounds of Formula (XT),
as valence and stability permit:
R', R , R3, R6, and R' are independently selected from the group consisting of hydrogen, Chalky!, C2-3aikenyl, and C2-3alkyny1; R4 is absent or selected from the group consisting of hydrogen, Chalky!, C^alkenyl, C2.6alkynyl, C,_6acyl;
wherein R4 may be optionally substituted with or ^S;
R:' is absent or selected from the group consisting of hydrogen, Chalky!, C2.3alkeo.yl, and C^alkyoyl;
wherein Rb and R' are optionally taken together so form ==0, ==:S or ==:C(Ril)2; wherein each Ra is independently selected from the group consisting of hydrogen, C1.3alk.yl, C2.3alk.enyl, and C-2.3alkyo.yl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is ==€(Ri1}-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S; and
wherein when the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2- and -0-;
provided that when the dotted line represents a double bond, " is absent, and when the bond with the dotted line represents a single bond, R4 is present.
[0218] in some embodiments of Formula (XI), R1 is selected from the group consisting of hydrogen, Chalky!, C2.3alkenyL and C2.3alk.ynyt. in other embodiments, R! is methyl, ethyl or propyl, particularly methyl.
[0219] in some embodiments of Formula (Xi), R~ is selected from the group consisting of hydrogen, Ch lky!, C2.3alkenyL and CVsalkynyt. in other embodiments, R is methyl, ethyl or propyl, particularly methyl.
[0220] in some embodiments of Formula (Xi), R3 is selected from the group consisting of hydrogen, Chalky!, C2.3alkenyL and CVsalkynyt. in other embodiments, R! is methyl, ethyl or propyl, particularly methyl.
[0221] In some embodiments of Formula (XI), R4 is absent or selected from the group consisting of hydrogen, C^alkyl, C^alkenyl, Q-ealkynyl, and C^acyl, wherein R4 may be optionally substituted with or
Figure imgf000115_0001
In yet other embodiments, R4 is absent or Ci.sacyi.
[0222] In some embodiments of Formula (XI), RJ is absent or selected from the group consisting of hydrogen, C |.3alky3, C2-3alkenyl, and C2-3alkynyl. In other embodiments, RJ is absent, methyl, ethyl or propyl, particularly, absent, methyl or ethyl.
[0223] In some embodiments of Formula (XI), R6 is selected from the group consisting of hydrogen, C1.3alk.yl, C2.3alk.enyl, and C^alkynyl, In other embodiments, R6 is methyl, ethyl or propyl, particularly methyl.
[0224] In some embodiments of Formula (XI), R7 is selected from the group consisting of hydrogen, Ci„3alkyl, C2.3alkenyl, and ^.salkynyl. In other embodiments, R7 is methyl, ethyl or propyl, particularly methyl. [0225] in some embodiments of Formula (XI), R6 and R ' are optionally taken together io form ), or = '(Ra)2, wherein each Ra is independently selected from the group consisting of hydrogen, C ^alkyl, C^.aalkenyl, and C'2-3alkynyl. In other embodiments, R6 and R' are optionally taken together to form =0 or =C(Ra)2, wherein each Ra is independently selected from the group consisting of hydrogen, C1-3alkyl, C2-3alkenyl, and
Figure imgf000116_0001
In yet other embodiments, R6 and R7 are optionally taken together to form
Figure imgf000116_0002
Ra is hydrogen, in a particular embodiment, R" and R' are taken together to form
Figure imgf000116_0003
Ra is hydrogen.
[0226] in some embodiments of Formula (XI), wherein the bond with the dotted line represents a double bond and R-* is present, X is ( \ ■■.
[0227] in some embodiments of Formula (XI), wherein when the bond with the dotted line represents a double bond and R-* is absent, X is selected from the group consisting of =0 and =S. in other embodiments of Formula (XI), wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S. In yet other embodiments of Formula (XI), wherein when the bond with the dotted line represents a double bond and R" is absent, X is =0.
[0228] In some embodiments of Formula (XI), wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2- and -0-.
[0229] In certain embodiments, the compound of Formula (XI) is one or more of the following compounds:
Figure imgf000116_0004
Figure imgf000117_0001
Figure imgf000118_0001
[0230] in cestain embodiments, the polycyclic compound is a compound of Formula (XII):
Figure imgf000119_0002
Formula (XII): or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond, R1 and are independently selected from the group consisting of hydrogen,
C io ikyl, C2-!oalketiy], and Q-ioalkynyl;
wherein R* and R2 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, =S, -NH2, ·( < )■! !. -O(Ci.10alkyl), -O(C2„10alkenyl), -O(C2.i0alkynyl), - S(Ci.ioalkyl), -S(C2.i0alkenyl), -S(C2.i0alkynyl), - H(Cs. ioalkyl), - NH(C2.i0alkenyi), - H(C2.i0a]kyny]), -N(CM0alkyl)2, -N(C2.ioalkenyl)2, and - N(C2.i0alkynyl)2;
R! and R4 are independently selected from the group consisting of hydrogen, C;.i0alkyl, C2..i0alkenyl, C2.i0alkynyl, C Oacyl, CMOacyloxy,€i .i0acylamino,
C;.i0acyithioxy, Ci.i0alkyiester, CVioalkenylester, Ci.i0alk nylester, Ci .i0aikylamide, C:.[(;.alkenylamide, C] . loalkynylamide, Ci.ioalkyithioester, Q-ioalkenyltbioester, and C ; . [ (vaikyny Ithio e ster ;
wherein each of R3 and R" may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, O, -SH, -S, -NH2, -C02H, -O(C,.10alkyl), -O(C2.10alkenyi), -O(C2..10alkynyi), - S(C,-10alkyl), -S(C2.[0alkeiryl), -S(C2.10alkynyl), H(C l- [0alkyl), NH(C2. l0alkenyl), NI-I(C2-) oalkynyl), (C l0alkyl)2, N(C2_- 0alkenyl)2,
N(C' 2.;oa'lkynyl)2, C(.)oacyi, C ,„i0acyioxy, C' l.ioacylamino, C'l-ioacylthioxy, Ci„l0alkylester, Ci.ioalkerrylesier, Cuoalkynyiester, Cj.ioaikylamide, C i- ,oalkenylamide, Ci.ioalkynylamide, C ^alkylthioester, Cj.ioalkenylthioester, and C ,_!oaikynyithioester; and
X and Y are independently selected from the group consisting of a direct bond, CMOalky3, C2-i 0alkenyl, C,.10alkynyl, (Ra), -0-, -S-, =0, and =S, provided that when either X or Y is =0 or :==S, then RJ and R4, respectively, are absent,
wherein Ra is selected from the group consisting of hydrogen, C;.i 0alkyl, C2-;oa3kenyl, and C2„i 0aikynyl,
wherein each Ci-ioalkyl, C2_;0alkenyl, and C2„ioaikynyl may be optionally independently substituted with one or snore substituents selected from the group consisting of halo, -OH, ===0, -SH, =S, -NH2,■■
C02H, - Of ( . alky! ;. -O(C2.i0a3kenyl), -O(C2„!0aikynyl), -S(CMOaikyl), -S(C2.10alkenyl), -S(C2_i0aikynyl), NH(C,.10alkyl), -NH(C2-!0alkeoyl), - NH(C2.i0alkynyl),
Figure imgf000120_0001
-N(C2„,0alkenyl)2, and - N(C2.10alkynyl)2.
[0231] According to other embodiments of Formula (XTI),
as valence and stability permit,
the bond with a dotted line optionally represents a single or double bond,
R1 and R are independently selected from the group consisting of hydrogen, Chalky!, Qwalkenyl, and C2.6alkynyl;
R3 and R4 are independently selected from the group consisting of hydrogen,
Chalky!, Qwalkenyl, C2-6alkynyl, C U6acyl, C^acyloxy, C^alkylester, C^alkenylester, and C].6alkynylester;
X and Y are independently selected from the group consisting of a direct bond, Chalky!, C2..6alkenyl, C2..6alkynyl, N(Ra), -0-, -S-, -0, and -S, provided that when either X or Y is -O or -8, then R3 and R4, respectively, are absent,
wherein any of R1, R , RJ, R4, and R are independently optionally substituted as noted above; and
wherein R" is selected from the group consisting of hydrogen, Chalky!, C^alkenyl, and C2.6alkynyl.
[0232] According to other embodiments of Formula (XII),
as valence and stability permit,
the bond with a dotted line optionally represents a single or double bond,
R1 and are independently selected from the group consisting of hydrogen, Chalky!, C2_6alkenyl, and C2„6aikynyl;
R3 and R4 are independently selected from the group consisting of hydrogen,
C;_6alkyl, C2.6alkenyl, C2_6alkynyi,
Figure imgf000120_0002
and C].6alkynylester;
wherein each of R3 and R'* may be optionally independently substituted with one or more substituents selected from the group consisting of -OH, =0, - SH, =S, C).«acyloxy, C^acylthioxy, C^alkylester, Cwalkenylester,
Figure imgf000121_0001
X and Y are independently selected from the groisp consisting of a direct bond, Chalky!, C2-6alk.en.yl, C2-6alkynyl, N(R ), -0-, -S-, =0, and =S, provided that when either X or Y is ==:0 or S, then RJ and R4, respectively, are absent, and
wherein Ra i s selected from the group consisting of hydrogen,
Figure imgf000121_0002
C2-6<i keny , and C2-6 lkynyl.
[0233] According so other embodiments of Formula (ΧΠ),
as valence and stability permit,
the bond with a dotted line optionally represents a single or double bond,
R1 and R2 are independently selected from the group consisting of hydrogen, Ci ^alkyl, C2-4alkenyl, arsd C2-4aIkynyl;
R3 and R4 are independently selected from the group consisting of hydrogen, Ci..alkyl,
Figure imgf000121_0003
C2.4alk.ynyl, and
wherein each of RJ and R"* may be optionally independently substituted with one or more substituents selected from the group consisting of -OH, =0, - SH, -S, Ci .4acyloxy, C;.4acylthioxy, C^alkylester, C^alkenylester,
Ci.4alkynyiester, Ci.4alkylthioester, C^alkenylthioester, and Ci .4alkynylthioester; and
X and Y are independently selected from the group consisting of a direct bond,
Chalky!,
Figure imgf000121_0004
-0-, -S-, O, and HS, provided that when either X or Y is =0 or =S, then R! and R4, respectively, are absent.
[0234] According to other embodiments of Formula (XII),
as valence and stability permit,
the bond with a dotted line optionally represents a single or double bond,
R! and R are indepeudenily selected from the group consisting of hydrogen, C ,„4alkyl, C2.4alkenyl, and C2_ alkynyi;
R3 and R4 are independently absent or independently selected from the group consisting of hydrogen, C[_4aikyl, C2-4alkenyl, C2.4alk.ynyi, Ci-4acyl;
wherein each of R3 and R4 may be optionally independently substituted with one or more substituents selected from she group consisting of -OH,— O,■■ SH, =S, Ci.iacyloxy, C:.4alk.ylester, C^alkenylester, and C^alkynylester; and X and Y are independently selected from the group consisting of a direct bond, C;.4alkyl, Q^alkenyl, C2-4alkynyl, -0-, -S-, =0, and =S, provided that when either X or Y is— O or =S, then R3 and R4, respectively, are absent.
[0235] in some embodiments of Formula (XII), R* is selected from the group consisting of hydrogen, Chalky!, C2-4alkenyl, and C2.4alkynyl. In other embodiments, R1 is hydrogen or Ci.4alkyl, preferably methyl. [0236] in some embodiments of Formula (XII), R is selected from the group consisting of hydrogen, C ^alkyl, C^^aikenyi, and C^alkynyi. In other embodiments, R2 is hydrogen or
C i_4alkyl, preferably methyl,
[0237] In some embodiments of Formula (XII), R3 is selected from the group consisting of hydrogen, C^alkyl, C2.4ajkenyl, C2-»alkynyl, and C^acyl, wherein R:' may be optionally substituted with one or more substituents selected from the group consisting of -OH, =0, -SH, ===S,
Figure imgf000122_0001
In other embodiments of Formula (XII), R3 is hydrogen or Chalky!, wherein R3 may be optionally substituted with one or more substituents selected from the group consisting of -OH, =0, -SH, =5, or Ci„4acyloxy. In yet other embodiments of Formula (Π), R" is hydrogen or
Figure imgf000122_0002
such as methyl, wherein RJ may be optionally substituted with one or snore substituents selected from the group consisting of -OH or in some embodiments, RJ is methyl, methyl substituted with -OH or methyl substituted with acetate.
[0238] In some embodiments of Formula (XII), R4 is selected from the group consisting of hydrogen, Chalky!,
Figure imgf000122_0003
and Ci .4acyl, wherein R'* may be optionally substituted with one or more substituents selected from the group consisting of -OH, =0, -SH, =S, Ci..4acyioxy, Cy4alkylester, Cwalkenylester, and CMalkynylester. In other embodiments of Formula (XII), R4 is hydrogen or C1.4alk.yl, wherein R4 may be optionaily substituted with one or more substituents selected from the group consisting of -OH, =0, -SH, =S, or C^acyloxy. In yet other embodiments of Formula (XII), R4 is hydrogen or
Figure imgf000122_0004
such as methyl, wherein R4 may be optionaily substituted with one or more substituents seiected from the group consisting of -OH or Cj.4acyloxy. In yet other embodiments, R4 is hydrogen.
[0239] In some embodiments of Formula (XII), X is selected from the group consisting of a direct bond,
Figure imgf000122_0005
-0-, -S-, K), and =S, provided that when either X or Y is =0 or =S, then RJ and R4 respectively, are absent. In other embodiments, X is selected from the group consisting of a direct bond, -0-, -S-, =0, and ~S, provided thai when X is =0 or =S, then RJ is absent. In yet other embodiments, X is a direct bond or =0, particularly a direct bond.
[0240] In some embodiments of Formula (XII), Y is selected from the group consisting of a direct bond, C [.4alkyl, C2-4aikenyl, C2.4alk.ynyl, -0-, -S-, =0, and =S, provided that when either X or Y is =0 or =S, then RJ and R4 respectively, are absent. In other embodiments, Y is selected from the group consisting of a direct bond, -0-, -S-, =0, and =5, provided that when Y is =0 or =S, then RJ is absent. In yet other embodiments, Y is a direct bond, Ό- or =0, particularly -0-,
[0241] In certain embodiments, the compound of Formula (XII) is one or more of the following compounds:
(Sigma Cat. No. W3765Q7) 12;
[0242] in certain embodiments, the compound of Formuia (XI) or Formuia (ΧΪΓ is selected from the group consisting of isopinocampheol, Myrtanol, Isobomyi acetate, D-camphor, (+) Camphene, Myrtenyl acetate, Bornyi isovaierate, Bornyi acetate, 1,3,3 Trimethyl-2-Norbornanyl acetate, Isobomyi propionate, 2 Ethyl 1 ,3,3 Trimethyl 2 Norbomanoi and L-Bomyl acetate. Ed jhje coigposM
[0243J The present invention includes edible compositions comprising the following compounds or comestibly or biologically acceptable salts or derivatives thereof, or enantiomers or diastereomers thereof. The structural similarity between some of the compounds below would be evident to one of skill in the art. Accordingly, the present invention also includes compounds which are structurally related to those described below. To the extent that the compounds below can be grouped according to structure, the present invention includes such groupings. For example, compounds 95-112 define a genus of compounds with a 2-pheny!chromene or 2-pheny!chroman core; compounds 113-118 define a genus of benzo-l,3-dioxole compounds; compounds 120, 122, 123, 125, and 126 define a genus of azulene-based compounds; and compounds 132 and 133 define a genus of dihydrofuran-2-one compounds.
[0244] AH stereochemical forms of the compounds disclosed in this and any section herein are specifically contemplated, including geometric isomers (i.e., E, Z) and optical isomers (i.e., R, S). Single stereochemical isomers as well as enantiomeric and diastereorneric mixtures of the compounds disclosed in this and any section herein are also specifically contemplated.
[0245] in other embodiments, the compound of the present invention is one or more of the following compounds :
Figure imgf000124_0001
Figure imgf000125_0001
(Sigma Cat. No. G6657)
OH O
ilndofme Cat. No. 020082)
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof.
[0246] in certain embodiments, ihe compound of the invention is selected from the group consisting of 7-rnethoxyilavone, Pinocembrin, Peonidin chloride, Scurellarein tetramethyl ether, Chrysin dimethyl ether, 7-hydroxyflavone, Isorhamnetin, Catechin, Gailocatechm, Epicatechin gallate, Epigallocatechin gallate, Datiscetin, Diosmetin, Querceiin, Kaempferol, Pipeline, Piperonai, Black pepper oil, Piperonvi acetate, Piperonyl isobutyrate, Isosafrole, Camphor oil, Guaiol, Car ophyllene oxide, Guaiazulene, Azulene, Guaiacol, Guaiene, Shogaol, Ginger oil, Ginger oleoresin, Harmine, Pongamol, and isocitric acid lactone.
[0247] in some embodiments, the edible compositions of this invention comprise terpenoid compounds, chroman compounds, benzo-ring containing compounds, polycyclic compounds, or compounds 95-134 as described herein, or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, or mixtures thereof,
[0248] If a comestibly or biologically acceptable salt of a compound of the present invention is used, such salt is preferably derived from inorganic or organic acids and bases. Examples of such salts include, but are not limited to, acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide,
2-bydroxyethanesulfonate, lactate, maleate, malonate, methaiiesuifonate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, tosylate and undecanoate. Salts derived from appropriate bases include alkali metal (e.g., sodium and potassium), alkaline earth metal (e.g., magnesium), ammonium and N+(C [.4 alkyl) salts. This invention also envisions the quaternization of any basic nitrogen-containing groups of the compounds disclosed herein. Water or oil-soluble or dispersible products may be obtained by such quaternization. In some embodiments, the compounds of the present invention are present as sodium, potassium or citrate salts.
[0249] Another aspect of the present invention provides edible compositions comprising a) a compound of ihe invention; and b) a bitter tastant. in some embodiments, the compound is a compound having a molecular weight less than about 1000, 500, or 300 daltons, in certain embodiments, the compound is a compound of Formula (I), Formula (la), Formula (iia),
Formula (Ilia), Formula (lib), Formula (illb), Formula (lie), Formula (Hie), Formula (IVc), Formula (lid). Formula (Hid), Formula (iVd), Formula (lie), Formula (iile), Formula (IVe), Formula (iif). Formula (Hg), Formula (lih), Formula (V), Formula (Via), Formula (Vib),
Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof. In some embodiments, the compound of the invention is a compound selected from Compounds 1-134 or combinations thereof. In other embodiments, the compound of the invention is a compound selected from Compounds 1 -58 or 61 - 134, or combinations thereof.
[0250] In some embodiments, the bitter tastant present in the edible composition is a bitter tasting salt. In some embodiments, the bitter tastant present in the edible composition is a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the bitter tastant present in the edible composition is a potassium salt. In some embodiments, the bitter tastant present in the edible compositions is KC1. in other embodiments, the bitter tasiant present in the edible composition is potassium lactate.
[0251] in another embodiment, the edible compositions comprise a) a compound of the invention; and b) a potassium salt. In some embodiments, the potassium sait is KC1 or potassium lactate, in specific embodiments, the potassium salt is KC1. In certain embodiments, the compound is a compound of Formula (I), Formula (la), Formula (iia), Formula (Ilia), Formula (lib),
Formula (Ilib), Formula (lie), Formula (TIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (iVe), Formula (Ilf), Formula (Tig), Formula (Ilh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XT') or Formula (XII), as described herein, or cosnbinasions thereof. In some embodiments, the compound of the invention is a compound seiected from Compounds 1 -134 or combinations thereof.
[ [0252] In some embodiments, the edible composition further comprises a sodium salt, in some embodiments, the edible compositions further comprise NaCl. In some embodiments, the edible compositions further comprise sodium lactate. In some embodiments, the edible compositions further comprise sugar.
[0253] In some embodiments, the edible composition further comprises one or more additionai components seiected from the group consisting of preservatives, nutritives, flavorants or additional flavor modifiers, which may lack an inherent flavor,
[0254] In some embodiments, the edible composition further comprises one or more emulsifiers. Sodium and potassium based emulsifiers are commonly used as emulsifiers in the food art.
Sodium-based emulsifiers include, e.g., sodium salts of fatty acids, sodium alginate, sodium aluminum phosphate, sodium casemate, sodium metaphosphate, sodium phosphate (dibasic), sodium phosphate (monobasic), sodium phosphate (tribasic), sodium polyphosphate, sodium pyrophosphate, and sodium stearoyl lactyiate. Potassium-based emulsifiers include, e.g., potassium salts of fatty acids, potassium alginate, potassium citrate, potassium phosphate (dibasic), potassium phosphate (monobasic), potassium phosphate (tribasic), potassium polyphosphate, potassium polymetaphosphate, and potassium pyrophosphate. Accordingly, some embodiments of the present invention include replacing a sodium-based emulsifier with a potassium based emulsifier and adding a compound of the present invention.
[0255] In some embodiments, the edible composition further comprises a surfactant to increase or decrease the effectiveness of the compounds of the present invention. Suitable surfactants include, but are not limited to, non-ionic surfactants (e.g., mono and diglycerides, fatty acid esters, sorbitan esters, propylene glycol esters, and lactyiate esters) anionic surfactants (e.g., sulfosuccinates and lecithin) and cationic surfactants (e.g., quaternary ammonium salts),
[0256] in some embodiments wherein the edible compositions further comprises a preservative, the preservative improves the shelf life of the edible composition . Suitable preservatives include, but are not limited to, ascorbic acid, benzoic acid, butyl p-hydroxybenzoate, calcium benzoate, calcium disodium EDTA, calcium hydrogen sulfite, calcium propionate, calcium sorbate, chitosan, cupric sulfate, dehydroacetic acid, diethyl pyrocarbonaie, dimethyl dicarbonate, disodium EDTA, E-poiyiysine glycine, erythorbic acid, ethyl p-hydroxybenzoate, formic acid, gum gisaiac, heptylparaben, hinokitiol, isobutyl paiaoxybenzoate, Japanese styrax benzoin extract,
methylparaben, mil protein extract, natamycin, nisin, peptin extract, 2-phenylpbenol, piirtaricin, potassium acetate, potassium benzoate, potassium lactate, potassium metabisulfite, potassium nitrate, potassium nitrite, potassium p rosolfite, potassium sorbate, potassium sulfite, propionic acid, propyl p-hydroxybenzoate, propyl p-oxybenzoate. propylene oxide, propylparaben, sodium benzoate, sodium bisulfite, sodium dehydroacetate, sodium diacetate, sodium erythorbate, sodium hydrogen sulfite, sodium bypopbosphite, sodium hyposulfite, sodium metabisulfite, sodium nitrate, sodium nitrite, sodium o-pbeoylphenol, sodium propionate, sodium pyrosulfite, sodium sulfite, sodium thiocyanate, sorbic acid and sulfur dioxide. In some embodiments, the preservative has a bitter flavor,
[Θ257] In some embodiments, the composition may further comprise one or more additional components selected from the group consisting of flow agents, processing agents, sugars, amino acids, other nucleotides, and sodium or potassium salts of orga ic acids such as citrate and tartarate. Such additional ingredients may add flavor, or aid in blending, processing or flow properties of the edible composition.
[0258] In some embodiments, the rate of release of the compound of the present invention is regulated. The release rate of the compound of the present invention can be altered by, for example, varying its solubility in water. Rapid release can be achieved by encapsulating the compound of the present invention with a material with high water solubility. Delayed release of the compound of the present invention can be achieved by encapsulating the compound of the present invention with a material with low water solubility. The compound of the present invention can be co-encapsulated with carbohydrates or masking tastants such as sweeteners. The rate of release of the compound of the present invention can also be regulated by the degree of encapsulation, in some embodiments, the compound of the present: invention is fully encapsulated. In other embodiments, the compounds of the present invention are partially encapsulated. In some embodiments, the rate of release is regulated so as to release with the bitter tastant.
[0259] The edible compositions of this invention are prepared according to techniques well-known in the art. In general, an edible composition of the invention is prepared by mixing a component or ingredient of the edible composition with a compound of the invention.
Alternatively, a compound of the invention can be added directly to the edible composition, In some embodiments, a bitter tastant is added simultaneously or sequentially with a compound of the invention. If sequentially, the bitter tastant may be added before or after the compound of the invention. In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a ph rmaceutical composition. In some embodiments, the edible composition is a consumer product. [0260] The amount of both a compound of the present invention and a bitter tastant used in an edible composition depends upon a variety of factors, including the puroose of the composition and the desired or acceptable perception of bitterness, saltiness, or sweetness. The amount may depend on the nature of the edible composition, the particular compound added, the bitter tastant, other compounds present in the composition, the method of preparation (including amount of eat used), and the pH of the edible composition, it will be understood that those of skill in the art will know how to determine the amounts needed to produce the desired taste(s).
[0261] in general, a compound of the present invention in an edible composition may be present at a concentration between about 0.001 ppm and 1000 ppm. in some embodiments, the edible composition comprises between about 0.005 to 500 ppm; 0,01 to 100 ppm; 0,05 to 50 ppm; 0.1 to 5 ppm; 0.1 to 10 ppm; 1 to 10 ppm; 1 to 30 ppm; 1 to 50 ppm; 10 to 30 ppm; 10 to 50 ppm; or 30 to 50 ppm of a compound of the present invention. In yet other embodiments, the edible composition comprises about 0.1 to 30 ppm, 1 to 30 ppm or 1 to 50 ppm of a compound of the present invention. In additional embodiments, the edible composition comprises about 0.1 to 5 ppm; 0.1 to 4 ppm; 0.1 to 3 ppm; 0.1 to 2 ppm; 0.1 to 1 ppm; 0.5 to 5 ppm; 0.5 to 4 ppm; 0.5 to 3 ppm; 0.5 to 2 ppm; 0.5 to 1.5 ppm; 0.5 to 1 ppm; 5 to 15 ppm; 6 to 14 ppm; 7 to 13 ppm; 8 to 12 ppm; 9 to 1 1 ppm; 25 to 35 ppm; 26 to 34 ppm; 27 to 33 ppm; 28 to 32 ppm; or 29 to 31 ppm.
[0262] in yet other embodiments, the edible composition comprises about 0.1 pm, about 0.5 ppm, about I ppm, about 2 ppm, about 3 ppm, about 4 ppm, about 5 ppm, about 6 ppm, about 7 ppm, about 8 ppm, about 9 ppm, or about 10 ppm of a compound of the present invention, in other embodiments, the edible composition comprises about 1 1 ppm, about 32 ppm, about 13 ppm, about 14 ppm, about 15 ppm, about 16 ppm, about 17 ppm, about 18 ppm, about 19 ppm, about 20 ppm, about 21 ppm, about 22 ppm, about 23 ppm, about 24 ppm, about 25 ppm, about 26 ppm, about 27 ppm, about 28 ppm about, 29 ppm, or about 30 ppm of a compound of the present invention.
[0263] in still other embodiments, the edible composition comprises about 31 ppm, about 32 ppm, about 33 ppm, about 34 ppm, about 35 ppm, about 36 ppm, about 37 ppm, about 38 ppm, about 39 ppm, about 40 ppm, about 41 ppm, about 42 ppm, about 43 ppm, about 44 ppm, about 45 ppm, about 46 ppm, about 47 ppm, about 48 ppm, about 49 ppm, or about 50 ppm of a compound of the present invention.
[0264] In other embodiments, the edible composition comprises more than about 0.5 ppm, 1 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, or 30 ppm of a compound of the present invention, up to, for example, about 30 ppm or 50 ppm. In additional embodiments, the edible composition comprises less than about 50 ppm, 30 ppm, 25 ppm, 20 ppm, 15 ppm, 10 ppm, 5 ppm, 1 ppm, or 0.5 ppm of a compound of the present invention. In yet additional embodiments, the edible composition comprises less than about 30 ppm, 10 ppm, or 1 ppm of a compound of the present invention.
[0265] When the edible composition comprises KCI, the amount of KCi will vary depending on the nature of the edible composition, the amount of perceived saltiness desired and the presence of other compounds in the composition, in some embodiments, KCi is present at a concentration between about 0.001-5% w/w; 0.01-5% w/w; 0.1-5% w/w; 1-5% w/w; 0.5-4.8% w/w; 0.5-4% w/w; 0.5-3% w/w; 0.75-3% w/w; 1-2.5% w/w; or 1-2% w/w. in some embodiments, KC1 is present at a concentration of about 0.5% w/w, about 1% w/w, about 1,5% w/w, about 2% w/w, about 2.5% w/w, about 3% w/w, about 3.5% w/w, about 4% w/w, about 4.5% w/w, or about 5% w/w. in some embodiments, KC1 is present at a concentration of up to about 0.5% w/w, up to about 1% w/w, up to about 1.5% w/w, up to about 2% w/w, up to about 2.5% w/w, up to about 3% w/w, up to about 3.5% w/w, up to about 4% w/w, up to about 4.5% w/w, or up to about 5% w/w. in some embodiments, KC1 is present at a concentration of about 2% w/w.
[0266] in some embodiments, KC1 is added to the edible composition as a salt substitute in an amount sufficient to replace NaCl. For example, the amount of CS in the edible compositions may range from about 0,5 to about 1 ,5 times the replaced NaCl depending upon the application, e.g., if about 0.5 mg of NaCl is replaced, about 0.25 to about 0.75 mg of KC1 is added. Typically, KC1 is added in the same weight amount as the NaCl being replaced.
[0267] Similarly, when the edible composition comprises potassium lactate, the amount of potassium lactate added vari es depending on the nature of the edible composition, the amount of preservation required and the presence of other compounds in the composition. Potassium, lactate may be present at a concentration between about 0.001-5% w/w; 0.01 -5% w/w; 0.1 -5% w/w; 0.5-4.8% w/w; 0.5-4% w/w; 0.5-3% w/w; 0.75-3% w/w; 1-2.5% w/w; or 1-2% w/w.
[0268] in some embodiments, potassium lactate is added to the edible composition in an amount sufficient to replace sodium lactate. For example, the amount of potassium lactate in the food or beverage after the sodium lactate substitute is added may range from about 0.5 to about 1.5 times the replaced sodium lactate depending upon the application, e.g., if about 0.5 mg of sodium lactate is replaced, about 0.25 to about 0.75 mg of potassium lactate is added. Typically, potassium lactate will be added in the same weight amount as the sodium lactate being replaced.
[0269] Further, when the edible composition comprises an artificial sweetener, such as
Acesulfame K, the amount of the sweetener added varies depending on the nature of the edible composition, the amount of sweetness required and the presence of other compounds in the composition. Acesulfame , for example, may be present at a concentration between about 1-200 ppm, 10-200 ppm, 50-150 ppm, 50-125 ppm, 75-125 ppm, and 75-100 ppm, preferably about 75 ppm.
[0270] In some embodiments, an artificial sweetener is added to the edible composition in an amount sufficient to replace sugar, in some embodiments, the artificial sweetener has a bitter taste or aftertaste, in some embodiments, the artificial sweetener is Acesulfame K. For example, the amount of Acesulfame K in the edible composition snay range from about 0.001 to about 0.01 times the replaced sugar depending upon the application, e.g., if about 100 mg of sugar is replaced, about 0.1 to about 1 mg of Acesulfame K is added. Typically, Acesulfame K will be added in about 0.005 times the amount of sugar being replaced.
[0271] in some embodiments, the edible compositions are included in a package, in some embodiments, the edible composition is packaged in bulk, in which the package contains more of the compositions than would typically be used for a single dish or serving of food or beverage. Such bulk packages can be in the form of paper, plastic, or cloth bags or cardboard boxes or drums. Such bulk packages may be fitted with plastic or metal spouts to facilitate the dispensing of the edible composition.
[0272] In some embodiments, the package contains an edible composition comprising a compound of the present invention and a bitter tastant, in some embodiments, the package contains an edible composition comprising a compound of the present invention and bitter ta sting salt. In some embodiments, the package contains an edible composition comprising a compound of the present invention and a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the package contains an edible composition comprising a compound of the present invention and a potassium salt. In some embodiments, the package contains an edible composition comprising a compound of the present invention and KC1. In other embodiments, the package contains an edible composition comprising a compound of the present invention and potassium lactate. In some embodiments, the package contains an edible composition comprising a compound of the present invention a potassium salt, and a sodium salt. In other embodiments, the package contains an edible composition comprising a compound of the present invention, KC1 and NaCl. In yet other embodiments, the package contains an edible composition comprising a compound of the present invention, potassium lactate and sodium lactate. In other embodiments, the package contains an edible composition comprising a compound of the present invention and Acesulfame K and sugar. in other embodiments, the package contains an edible composition comprising a compound of the present invention, potassium lactate, KC1 and NaCl,
[0273] in some embodiments, the edible compositions of the present invention are compositions suitable to be used as seasonings, as ingredients in food products or as condiments. In such embodiments, the edible composition may or may not contain a bitter tastant. For example, the edible composition may be used in, e.g., a seasoning which comprises a bitter tastant such as, e.g., KC1. Such seasonings can be used in the place of table salt (i.e., NaCl) to season prepared food products. Alternatively, the edible composition may be used in, e.g., a seasoning which does not contain a bitter tastant. Such seasonings can be used to season prepared food products which contain a bitter tastant (either inherently present or added during preparation) in order to reduce the bitter taste associated with the bitter tastant. In some embodiments, the edible composition is a seasoning comprising KC1 and a compound of the invention, in some embodiments, the edible composition is a seasoning comprising KG, NaCl and a compound of the invention, in some embodiments the seasoning further comprises a spice or a blend of spices,
[0274] Alternatively, the edible compositions may be used for medicinal or hygienic purposes, for example, in soaps, shampoos, mouthwash, medicines, pharmaceuticals, cough syrup, nasal sprays, toothpaste, dental adhesives, tooth whitenets, glues (e.g., on stamps and envelopes), and toxins used in insect and rodent control. Food^roduct
[0275J in some embodiments, the edible composition is a food product. According to such embodiments, the food product compi'ises (a) a food stuff; and (b) a compound of Formula (1), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib), Formula (ilib), Formula (lie), Formula (Hie), Formula (IV c), Formula (lid), Formula (Hid), Formula (iVd), Formula (He), Formula (Hie), Formula (IV e), Formula (ilfj, Formula (lig). Formula (lih). Formula (Yj, Formula (Via), Formula (Vib), Formula (Vila), Formula (VIH), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1- 334, as described above, or combinations thereof.
[0276] in some embodiments, the food product further comprises a bitter tastant, as described herein. In some embodiments, the bitter tastant is a potassium salt, such as KG or potassium lactate. In specific embodiments, the potassium salt is KC1.
[0277] in some embodiments, the food product further comprises one or more additional flavor modifiers.
[0278] in some embodiments, the food product further comprises one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or additional flavor modifiers, which may lack an inherent flavor.
[0279] In some embodiments, the edible composition is a pharmaceutical composition.
According to such embodiments, the pharmaceutical composition comprises (a) a bitter tasting pharmaceutically active ingredient; and (b) a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Ilib), Formula (lie), Formula (TIIc), Forsnula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IVe), Formula (TIf), Formula (lie). Formula (lih). Formula (V), Formula (Via), Formula (Vib),
Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -134, as described above, or combinations thereof.
[0280] According to some embodiments, the pharmaceutical composition can comprise any bitter tasting pharmaceutically active ingredient. Non-limiting examples of bitter pharmaceutical compounds include: acetaminophen, ampicillin, azithromycin, chlorpheniramine, cimetidine, dextromethorphan, diphenhydramine, erythromycin, ibuprofen, penicillin, phenylbutazone, psuedoephedrine, ranitidine, spironolactone statins (including, but not limited to, atorvastatin, ceirvastatin, fluvastatin, louvastatin, mevastatin, pravastatin, pravastatin, rosuvastatin, and simvastatin) and theophylline.
[0281] in other embodiments, the invention provides a pharmaceutical composition comprising (a) a pharmaceutically active ingredient; (b) a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formuia (lib), Formula (Illb), Formuia (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formuia (IVe), Formula (Ilf), Formula (Hg), Formuia (IIIi), Formuia (V), Formula (Via), Formula (VIb), Formula (Viia), Formula (VIII), Formula (IXa), Formuia (IXb ), Formula (IXc), Formuia (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of
Compounds 1- ! 34, as described above, or combinations thereof; and (c) a bitter tastant, In such, embodiments, the pharmaceutical compositions may comprise any pharmaceutically active ingredient,
[0282] In other embodiments, the invention provides a pharmaceutical composition comprising (a) a pharmaceutically active ingredient; (b) a compound of Formui (I), Formula (la), Formula (Ila), Formula (Ilia), Formuia (lib), Formuia (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ITIe), Formula (IVe), Formula (ilf), Formula (llg), Formula (lib.), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (iXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (ΧΪΙ), as described herein, or combinations thereof, or any one of
Compounds 1- 134, as described above, or combinations thereof; and (c) a potassium salt. In some embodiments, the potassium salt is KC1 or potassium lactate, in some embodiments, the potassium salt is KC1.
[0283] In some embodiments, the pharmaceutical composition further comprises one or more additional flavor modifiers.
[0284] In some embodiments, the pharmaceutical composition further comprises one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor.
Consumer product
[0285] in some embodiments, the edible compositions is a consumer product. According to such embodiments, the consumer product comprises (a) a bitter tastant; and (b) a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formuia (Illb), Formula (He), Formula (IIIc), Formula (IVc), Formuia (lid), Formuia (Hid), Formuia (IVd), Formuia (He), Formula (Hie), Formula (IVe), Formuia (Ilf), Formula (Hg), Formula (Dh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formuia (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof.
[0286] In another embodiment, the invention provides a consumer product comprising (a) a potassium salt; and (b) a compound of Formula (I), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (ille), Formula (IVe), Formula (Ilf), Formula (lig), Formula (Ills), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formu!a (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof. In some embodiments, the potassium salt is KCi or potassium lactate. In some embodiments, the potassium salt is KCI.
[0287] In other embodiments, the invention provides a consumer product for reducing bitter taste of a bitter tastant, wherein said consumer product comprises a compound of Forsnuia (I), Formula (la), Forsnuia (Ila), Formula (ilia), Formula (lib), Formula (Illb), Formula (He), Forsnuia (IIIc), Forsnuia (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Tile), Formula (IVe), Formula (Hi), Formula (Ilg), Forsnuia (lib), Forsnuia (V), Formula (Via), Formula (Wo), Forsnuia (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc),
Formula (IXd), Forsnuia (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -134, as described above, or combinations thereof. In some embodiments, the bitter tastant is a potassium salt. In some embodiments, the potassium salt is KCI or potassium lactate. In some embodiments, the bitter tastant is KCI.
[0288] In some embodiments, the consumer product further comprises one or snore additional flavor modifiers.
[0289] In some embodiments, the consumer product further comprises one or more additionai components selected from the group consisting of preservatives, nutritives, flavorants or additional flavor modifiers, which may lack an inherent flavor, Μ¾ί¾ __^
[0290] According to anoth er aspect, th e invention provides a method of preparing an edible composition. The method comprises: (a) providing a comestibly acceptable carrier; and (b) adding to the comestibly acceptable carrier of (a) a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (lllb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (llie), Formula (IVe), Formula (Hi), Formula (Hg), Formuia (lib), Formuia (V), Formuia (Via), Formula (Vlb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb ), Formula (IXc), Formuia (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof, with the comestibly acceptable carrier. In some embodiments, the compound of the invention has been dissolved in a solvent prior to the addition step (b),
[0291] in some embodiments, the comestibly acceptable carrier in (a) is inherently bitter, in such embodiments, the comestibly acceptable carrier may inherently contain a bitter tastant. In some embodiments, the inherent bitter tastant is a bitter tasting salt. In some embodiments, the inherent bitter tastant is a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the inherent bitter tastant is a potassium salt. In some embodiments, the inherent bitter tastant is KCI. In other embodiments, the inherent bitter tastant is potassium lactate. [0292] in some embodiments, the method of preparing a edible composition further comprises: (c) adding a bitter tastant. In some embodiments, the bitter tastant is a potassium sait. In some embodiments, the potassium salt is KCi or potassium lactate, in specific embodiments, the potassium sait is KCl. In some embodiments, the bitter tastant is added before the compound of the present invention. In other embodiments, the bitter tastant is added after the compound of the present invention. In some embodiments, the compounds of the present invention are combined with the bitter tastant and then combined with the comestibly acceptable carrier, in other embodiments, the compound of the present invention is combined sequentially with the comestibly acceptable carrier and then the bitter tastant. In yet other embodiments, the compounds of the present invention are combined with a mixture of the bitter tastant and the comestibly acceptable carrier.
[0293] in some embodiments, a compound of the invention and the bitter tastant, if present, are mixed with the comestibly acceptable carrier. In other embodiments, the compound and the bitter tastant, if present, are sprayed onto or coat the comestibly acceptable carrier. In some embodiments, the compound of the invention is plated on a carbohydrate or salt, encapsulated on a salt or a carbohydrate (spray dried), or co-crystallized with a potassium salt to create a "topping" salt.
[0294] in some embodiments, the bitter tastant is a bitter tasting salt, in some embodiments, the bitter tastant is a potassium salt, a magnesium sait, or a calcium salt. In some embodiments, the bitter tastant is a potassium salt, in some embodiments, the bitter tastant is KCl. In other embodiments, the bitter tastant is potassium lactate.
[0295] in some embodiments, the edible composition further comprises a sodium salt, in some embodiments, the edible composition further comprises NaCi. In other embodiments, the edible composition further comprises sodium lactate, in further embodiments, the edible composition further comprises sugar.
[0296] In some embodiments, the methods of preparing an edible composition further comprise adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor. In some embodiments, the methods of preparing an edible composition further comprise adding one or more additional flavor modifiers.
[0297] In some embodiments, the edible composition is a consumer product,
[0298] According io another aspect, the invention provides a method of preparing an edible composition, wherein the edible composition is a food product. The method comprises: (a) providing a foodstuff; and (b) adding to the foodstuff of (a) a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (ΠΓο), Formula (He), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Tile), Formula (IVe), Formula (Hi), Formula (lig), Formula (lib), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (Viil), Formula (IXa), Formula (IXb), Formula (Die), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof. In some embodiments, the compound of the invention is added in ihe form of an edible composition comprising the compound of the invention,
[0299] In some embodiments, the foodstuff in (a) is inherently bitter, in such embodiments, the food stuff may inherently contain a bitter tastant. in some embodiments, the inherent bitter tastant is a bitter tasting salt. In some embodiments, the inherent bitter tastant is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the inherent bitter tastant is a potassium salt. In some embodiments, the inherent bitter tastant is KCl. in other embodiments, the inherent bitter tastant is potassium lactate,
[0300] In some embodiments, the method comprises: (a) providing a food product; and (b) adding to the food product of (a) a compound of Formula (I), Formula ( a), Formula (Ila), Formula (Ilia), Formula (lib), Formula (IITb), Formula (lie), Formula (illc), Formula (IVc), Formula (lid), Formula (iild), Formula (IVd), Formula (He), Formula (ITIe), Formula (IVe), Formula (Ilf), Formula (ilg), Formula (lib), Formula (V), Formula (Via), Formula (VTb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof. In some embodiments, the compound of the invention is added in th e form of an edible composition comprising the compound of the in vention.
[0301] In some embodiments, the food product in (a) comprises a bitter tastant. In some embodiments, the bitter tastant is a bitter tasting salt. In some embodiments, the bitter tastant is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the bitter tastant is a potassium salt. In some embodiments, the bitter tastant is KCl. In other embodiments, the bitter tastant is potassium lactate.
[0302] in some embodiments, the method of preparing a food product further comprises: (c) adding a bitter tastant. In some embodiments, the bitter tastant is a potassium salt, such as KCl or potassium lactoite. in specific embodiments, the potassium salt is KCl. In some embodiments, the bitter tastant is added before the compound of the present invention, in other embodiments, the bitter tastant is added after the compound of the present invention. In some embodiments, the compound of the invention is added with the bitter tastant, in some embodiments, the compound of the present invention is combined with the bitter tastant and then combined with the foodstuff or food product, in other embodiments, the compound of the present invention is combined sequentially with the foodstuff or food product and then the bitter tastant. In y et other embodiments, the compound of the present invention is combined with a mixture of the bitter tastant and the foodstuff or food product.
[0303] In some embodiments, the compound and the bitter tastant, if present, are mixed with the foodstuff. In other embodiments, the compound and the bitter tastant, if present, are sprayed onto or coat the foodstuff. In some embodiments, the compound of the invention is plated on a carbohydrate or salt, encapsulated on a salt or a carbohydrate (spray dried), or co-crystallized with a potassium salt to create a "topping" salt.
[0304] in some embodiments, the bitter tastant is a bitter tasting salt, in some embodiments, the bitter tastant is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the bitter tastant is a potassium salt, in some embodiments, the bitter tastant is KC1, in other embodiments, the bitter tastant is potassium lactate.
[0305] in some embodiments, the food product further comprises a sodium salt, in some e bodiments, the food product further comprises NaCl. in other embodiments, the food product further comprises sodium lactate. In further embodiments, the food product further comprises sugar.
[0306] in some embodiments, the methods of preparing a food product further comprise adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor.
[8307] According to another aspect, the invention provides a method of preparing an edible composition, wherein the edible composition is a pharmaceutical composition. The method comprises: (a) providing a pharmaceutically active ingredient; and (b) adding to the
pharmaceutically active ingredient of (a) a compound of Formula (I), Formula (la), Formula (ITa), Formula (ilia), Formula (iib), Formula (llib), Formula (lie), Formula (ITIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (iVd), Formula (He), Formula (Hie), Formula (IVe), Formula (ilf), Formula (Ilg), Formula (lih), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (iXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 3 -134, as described above, or combinations thereof, with the pharmaceutically active ingredient, in some embodiments, the compound of the invention is added in the form of an edible composition comprising the compound of the invention.
[0308] in some embodiments, the pharmaceutically active ingredient in (a) is inherently bitter, in such embodiments, the pharmaceutically active ingredient may inherently contain a bitter tastant. In some embodiments, the inherent bitter tastant is a bitter tasting salt. In some embodiments, the inherent bitter tastant is a potassium salt, a magnesium salt, or a calcium salt, in some embodiments, the inherent bitter tastant is a potassium salt.
[0309] in some embodiments, the method of preparing a pharmaceutical composition further comprises: (c) adding a bitter tastant. in some embodiments, the bitter tastant is a potassium salt. In some embodiments, the potassium salt is Ci or potassium lactate, in specific embodiments, the potassium salt is KCI. In some embodiments, the bitter tastant is added before the compound of the present invention, in other embodiments, the bitter tastant is added after the compound of the present invention, in some embodiments, the bitter tastant is added with the compound of the invention. In some embodiments, the compound of the present invention is combined with the bitter tastant and then combined with the pharmaceutically active ingredient, in other embodiments, the compound of the present invention is combined sequentially with the pharmaceuticaily active ingredient and then the bitter tastani. in yet other embodiments, the compound of the present invention is combined with a mixture of the bitter tastant and the pharmaceutically active ingredient,
[0310] in some embodiments, the compound and the bitter tastant, if present, are mixed with the pharmaceutically active ingredient. In other embodiments, the compound and the bitter tastant, if present, are sprayed onto or coat the pharmaceutical composition, in some embodiments, the compound of the invention is encapsulated with the pharmaceutically active ingredient. In some embodiments, the compound of the invention is in a form such that the rate of release is regulated vis a vis the rate of release of the bitter tastant, which in some embodiments is the pharmaceutically active ingredient.
[0311] In some embodiments, the bitter tastant is a bitter tasting salt. In some embodiments, the bitter tastant is a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the bitter tastant is a potassium salt. In some embodiments, the bitter tastant is KG. In other embodiments, the bitter tastant is potassium lactate.
[0312] In some embodiments, the pharmaceutical composition further comprises a sodium salt. In some embodiments, the pharmaceutical composition further comprises NaCl. In other embodiments, the pharmaceutical composition further comprises sodium lactate. In further embodiments, the pharmaceutical composition further comprises sugar,
[0313] In some embodiments, the pharmaceutical composition further comprises a
pharmaceutically acceptable earner. Pharmaceutically acceptable carriers that may be used in these compositions include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisi!icaie, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, poiyethyiene-polyoxypropylene -block polymers, polyethylene glycol and wool fat.
[0314] In some embodiments, the methods of preparing a pharmaceutical composition further comprise adding one or more additional components selected from the group consisting of preservatives, nutritives, fiavorants or flavor modifiers, which may lack an inherent flavor.
Method of reducing or eliminating the perception of bitter taste in a subject
[0315] According to another aspect, the invention provides a method of reducing or eliminating the perception of bitter taste in a subject. The method comprises the use of an edible composition comprising a compound according to Formula (I), Formula (ia), Formula (Ha), Formul (Ilia), Formula (lib), Forsnuia (IITb), Fonnula (lie), Formula (iiic), Formul (FVc), Formula (lid), Formula (Hid), Formisla (IVd), Formula (lie), Formisla (Hie), Formula (iVe), Formula (ilf), Formula (Ilg), Fonnula (llli), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (Viii), Formula (iXa), Formula (iXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (Xli), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof,
[0316] The method can be used to reduce or eliminate bitter taste in. any edible composition, including a foodstuff, food product, pharmaceutical composition or consumer product. The edible composition may be ixs any form. In some embodiments, the composition is in the form of, for example, a gum, lozenge, sauce, condiment, meat matrix, meat slurry, paste, suspension, spread, coating, a liquid, a gel, an emulsion, granules, or seasoning.
[0317] In some embodiments the edible composition is utilized by, for example, placement in the oral cavity or by ingestion. In some embodiments, the edible composition is placed in the oral cavity or ingested before a bitter food stuff, food product, pharmaceutical composition or consumes' product. In some embodiments, the edible composition is placed in the oral cavity or ingested concurrently with a bitter food stuff food product, pharmaceutical composition or consumer product, either as a separate edible composition or by incorporation in the bitter food stuff, food product, pharmaceutical composition or consumer product. In some embodiments, the edible composition is placed in the oral cavity or ingested after a bitter food stuff, food product, pharmaceutical composition or consumer product. For example, a compound of the invention can be combined with foodstuffs or food products to reduce the bitter taste of a food product.
Alternatively, a compound of the invention can be used, for example, in a lozenge or gum for use after exposure to a bitter food stuff, food product, pharmaceutical composition or consumer product (e.g., to reduce or eliminate a bitter aftertaste).
Method of reducing the amount of sodium in an edible composition
[0318] According to another embodiment, the invention provides a method of reducing the amount of sodium in an edible composition, such as a food product, a pharmaceutical composition or a consumer product, in some embodiments, the invention provides a method of reducing the amount of a sodium containing compound in an edible composition, such as a food product, a pharmaceutical composition or a consumer product, in another embodiment, the invention provides a method of reducing the amount ofNaCl in an edible composition, such as a food product, a pharmaceutical composition or a consumer product, in another embodiment, the invention provides a method of reducing the amount of sodium lactate in an edible composition, such as a food product, a pharmaceutical composition or a consumer product. In some embodiments, the sodium salt is replaced with a non-sodium salt. In some embodiments, the non-sodium salt is a calcium salt, a magnesium salt, or a potassium salt, in some embodiments, the non-sodium salt, is a potassium salt.
[0319] In some embodiments, the method comprises: (a) replacing an amount of a. sodium salt, used in preparing an edible composition with an amount, of a potassium salt; and (b) incorporating into the edible composition an effective amount of a compound of Formula (I), Formula (ia), Formula (Ha), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (iVd), Formula (lie). Formula (Hie), Formula (IVe), Formula (Ilf), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via),
Formula (Vib), Forsnuia (Vila), Formula (VIII), Formula (iXa), Formula (IXb), Formula (iXc),
Formula (IXd), Forsnuia (XI) or Forsnuia (XII), as described herein, or combinations thereof, or any one of Compounds 1 -134, as described abo ve, or combinations thereof. In some embodiments, the compound of the invention is added in the form of an edible composition comprising the compound of the invention.
[0320] In some embodiments, the method of reducing the amount of sodium in an edible composition comprises the steps of: (a) ingesting a first edible composition, in which an amount of a sodium salt has been replaced with an amount of a potassium salt; and (b) ingesting a second edible compound, which comprises a compound of the invention. In some embodiments, the first edible composition is ingested before the second edible composition. In some embodiments, the first edible composition is ingested after the second edible composition. In some embodiments, the first edible composition is ingested concurrently with the second edible composition.
[0321] In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0322] In some embodiments, the potassium salt is added to the edible composition prior to addition of an effective amount of a compound of the invention. In some embodiments, the potassium salt is added to the edible composition subsequent to addition of an effective amount of a compound of the invention. In some embodiments, the potassium salt is added to the edible composition concurrent with addition of an effective amount of a compound of the invention.
[0323] In some embodiments, the amount of sodium replaced in the edible composition in step (a) is an amount sufficient to maintain or restore she health of a subject. In some embodiments, the amount of sodium replaced in the edible composition is an amount sufficient to decrease hypertension in a subject. In some embodiments, the amount of sodium replaced by potassium in the edible composition is an amount to sufficient to change the texture or freezing point of the edible composition. In some embodiments, the amount of sodium replaced is up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention.
Figure imgf000146_0001
[0325] In some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100% of the amount of sodium present in the edible composition with potassium. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention, in some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 25% of the amount of sodium present in the edible composition with potassium. In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 50% of the amount of sodium present in the edible composition with potassium. In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 75% of the amount of sodium present in the edible composition with potassium. In yet other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 100% of the amount of sodium present in the edible composition with potassium.
[Θ326] in some embodiments, the method of reducing the amount of sodium in an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor.
[Θ327] In some embodiments, the method comprises: (a) replacing an amount of NaCi used in preparing an edible composition with an amount of KC1; and (b) incorporating into the edible composition an effective amount of a compound of Formula (1), Formula (la), Formula (iia), Formula (ilia), Formula (lib), Formula (iiib), Fonmila (lie), Formula (Illc), Formuia (IVe), Formula (lid), Formula (iiid), Formula (IVd), Formula (lie), Formuia (Ille), Formula (IVe), Formula (lit). Formula (lig). Formula (lih), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Fonmila (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof.
[0328] In some embodiments, the method of reducing the amount of sodium in an edible composition comprises the steps of: (a) ingesting a first edible composition, in which an amount of NaCl has been replaced with an amount of KC1; and (b) ingesting a second edible compound, which comprises a compound of the invention. In some embodiments, the first edible composition is ingested before the second edible composition. In some embodiments, the first edible composition is ingested after the second edible composition. In some embodiments, the first edible composition is ingested concurrently with the second edible composition.
[0329] In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0330] In some embodiments, the KC1 is added to the edible composition prior to addition of an effective amount of a compound of the invention. In some embodiments, the KC1 is added to the edible composition subsequent to addition of an effective amount of a compound of the invention. In some embodiments, the KC1 is added to the edible composition concurrent with addition of an effective amount of a compound of the invention. [0331] in some embodiments, the amount ofNaCl replaced by KCI in the edible composition in step (a) is an amount sufficient to maintain or restore the health of a subject, in some embodiments, the amount of NaCl replaced by KCi in the edible composition is an amount sufficient to decrease hypertension in a subject, in some embodiments, the amount of NaCi replaced by KCI in the edible composition is an amount to sufficient to change the texture or freezing point of the edible composition. In. some embodiments, the amount of NaCi replaced by KCI is up to 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%, These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention.
[0332] in some embodiments, the amount of compound added in step (b) reduces the perception of bitter taste in the subject. The bitter taste is completely reduced or partially reduced. In some embodiments, the perception of salty taste is maintained.
[0333] In some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100% of the amount of
NaCJ present in the edible composition with KCI. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 25% of the amount of NaCi present in the edible composition with KCI. In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 50% of the amount of NaCi present in the edible composition with KCI. In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 75% of the amount of NaCl present in the edible composition with KCI. in yet other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 100% of the amount of NaCl present in the edible composition with KCI.
[0334] In some embodiments, the method of reducing the amount of NaCl in an edible composition or food product comprises maintaining a salty flavor.
[0335] In some embodiments, the method of reducing the amount of NaCl in an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor,
[0336] In other embodiments, the method of reducing the amount of sodium in an edible composition comprises: (a) replacing an amount of sodium lactase present in the edible composition with an amount of potassium lactate; and (b) incorporating into the edible composition an effective amount of a compound of Formula (I), Formula (la), Formula (ila), Forsnuia (ilia), Formula (lib), Formula (ilib), Formul (He), Forsnuia (Ilic), Formula (iVc), Formula (lid), Formula (illd), Formula (iVd), Formula (He), Formula (ille), Forsnuia (IVe), Formula (lif), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Forsnuia (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Forsnuia (IXb), Formula (IXc), Forsnuia (IXd), Forsnuia (XI) or Forsnuia (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof,
[0337] in some embodiments, the method of reducing the amount of sodium in an edible composition comprises the steps of: (a) ingesting a first edible composition, in which an amount of sodium lactate has been replaced with an amount of potassium lactate; and (b) ingesting a second edible compound, which comprises a compound of the invention, in some embodiments, the first edible composition is ingested before the second edible composition, in some embodiments, the first edible composition is ingested after the second edible composition, in some embodiments, the first edible composition is ingested concurrently with the second edible composition.
[0338] in some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition, in some embodiments, the edible composition is a consumer product.
[0339] in some embodiments, the potassium iactate is added to the edible composition prior to addition of an effective amount of a compound of the invention, in some embodiments, the potassium lactate is added to the edible composition subsequent to addition of an effective amount of a compound of the invention, in some embodiments, the potassium iactate is added to the edible composition concurrent with addition of an effective amount of a compound of the invention.
[0340] in some embodiments, the amount of sodium lactate replaced by potassium iactate in the edible composition in step (a) is an amount sufficient to maintain or restore the health of a subject. in some embodiments, the amount of sodium lactate replaced by potassium lactate in the edible composition is an amount sufficient to decrease hypertension in a subject, in some embodiments, the amount of sodium iactate replaced by potassium iactate in the edible composition is an amount to sufficient to change the texture or freezing point of the edible composition, in some embodiments, the amount of sodium lactate replaced by potassium lactate is up to 3 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%s, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention,
[0341] in some embodiments, the amount of compound added in step (b) reduces the perception of bitter taste in the subject, 'The bitter taste is completely reduced or partially reduced, in some embodiments, the perception of salty teste is maintained.
[0342] in some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100% of the amount of sodium lactate present in the edible composition with potassium lactate. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 25% of the amount of sodium iactate present in the edible composition with potassium lactate, in other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 50% of the amount of sodium lactate present in the edible composition with potassium lactate, in other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 75% of the amount of sodium lactate present in the edible composition with potassium lactate, in yet other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 100% of the amount of sodium lactate present its the edible composition with potassium lactate.
[0343] in some embodiments, the method of reducing the amount of sodium lactate in an edible composition or food product comprises maintaining the preservatio n of the food product.
[0344] in some embodiments, the method of reducing the amount of sodium lactate in an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which, may Sack an inherent flavor.
Method jf redjm
[0345] According to another embodiment, the invention provides a method of reducing the amount of sugar in an edible composition. In some embodiments, the method comprises: (a) replacing an amount of sugar used in preparing an edible composition with an amount of
Acesulfame K; and (b) incorporating into the edible composition an effective amount of a compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib),
Formula (Illb), Formula (lie), Formula ( ITc), Formula (IVc), Formula (TId), Formula (illd), Formula (TVd), Formula (Tie), Formula (Tile), Formula (IVe), Formula (ITf), Formula (Ilg), Formula (Till), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VIII),
Formula (iXa), Formula (iXb), Formula (iXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof,
[0346] In some embodiments, the edible composition is a food product, in some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0347] In some embodiments, the Acesulfame K is added to the edible composition prior to addition of an effective amount of a compound of the invention, in some embodiments, the Acesulfame is added to the edible composition subsequent to addition of an effective amount of a compound of the invention. In some embodiments, the Acesulfame is added to the edible composition concurrent with addition of an effective amount of a compound of the invention.
[0348] in some embodiments, the amount of sugar replaced in the edible composition in (a) is an amount sufficient to maintain or restore the health of a subject, in some embodiments, the amount of sugar replaced in the edible composition is an amount sufficient to result in weight loss in a subject. In some embodiments, the amount of sugar replaced by Acesulfame K in the edible composition is an amount to sufficient to alleviate the effects of, or treat, a disease associated with sugar consumption or excessive weight of the subject (e.g., diabetes), in some embodiments, the amount of sugar replaced by Acesulfame K is up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%:., 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%), These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention.
[0349] in some embodiments, the amount of compound added in (b) reduces the perception of bitter taste in the subject. The bitter taste is completely reduced or partially reduced. In some embodiments, the perception of sweet taste is maintained.
[0350] in some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100% of the amount of sugar present in the edible composition with Acesulfame K. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention, in some embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 25% of the amount of sugar present in the edible composition with
Acesulfame K... In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 50% of the amount of sugar present in the edible composition with Acesulfame K... In other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 75% of the amount of sugar present in the edible composition with Acesulfame K.. In yet other embodiments, the amount of compound added in step (b) is sufficient to permit replacement of up to 100% of the amount of sugar present in the edible composition with Acesulfame K..
[0351] In some embodiments, the method of reducing the amount of sugar in an edible composition comprises maintaining a sweet flavor.
[0352] In some embodiments, the method of reducing the amount of sugar in an edibie composition or food product further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, fiavorants or flavor modifiers, which may lack an inherent flavor.
Method of reducing sodium intake of a subject
[0353] According to another embodiment, the invention provides a method of reducing sodium intake of a subject. In some embodiments, the method comprises the step of providing an edibie composition of the present invention to the subject, wherein all or a portion of the sodium salts in the edible composition is replaced with one or more non-sodium salts, and wherein the edible composition comprises a compound of the present invention. In some embodiments, the non- sodium salt is a calcium salt, a magnesium salt, or a potassium salt, in some embodiments, the non- sodium salt is a potassium salt, in some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product. In some embodiments the sodium salt is NaCl and the potassium salt is KC1, In some embodiments, the sodium salt is sodium lactate and the potassium salt is potassium lactate. [0354] in some embodiments, the methods of reducing sodium intake of a subject further comprise she step of identifying a subject in need thereof. The skilled worker would be able to identify a subject in need of reducing sodium intake. Non-limiting examples of such subjects include subjects that suffer from any one or more of the following disorders: Hypernatremia, hypertension, cardiovascular disease, edema, seizures due to cerebral edema, dehydration (due to excess sweating, diarrhea, urinary tract disorders or diuretics), diabetes insipidus, Conn's syndrome, and Cushing's syndrome.
[0355] in some embodiments, the amount of the sodium salt replaced by a potassium salt in the edible composition is an amount sufficient to maintain or restore the health of a subject. In. some embodiments, the amount of the sodium salt replaced by a potassium salt in the edible composition is an amount sufficient to decrease hypertension in a subject, in some embodiments, the amount of the sodium salt replaced by a potassium salt in the edibie composition is up to 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some embodiments, a subject's daily sodium intake is less than 2500 mg day, less than 2000 mg/day, less than 1500 mg day, less than 1000 mg/day, or less than 500 mg/day, where desirable.
[0356] in some embodiments, the amount of the compound of the invention added to the edible composition is sufficient to permit reduction of a subject's sodium intake by up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 35%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some embodiments, the amount of compound of the invention added to the edibie composition is sufficient to permit reduction of the subject's sodium intake by up to 25%. in other embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of the subject's sodium intake by up to 50%. in other embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of the subject's sodium intake by up to 75%. In yet other embodiments, the amount of compound of the invention added to the edibie composition is sufficient to permit reduction of the subject's sodium intake by up to 100%.
[0357] in some embodiments, the method of reducing sodium intake of a subject further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor.
[0358] According to another embodiment, the invention provides a method of reducing sugar intake of a subject. In some embodiments, the method comprises the step of providing an edible composition of the present invention to the subject, wherein all or a portion of the sugar in the edible composition is replaced with Acesulfame K, and wherein the edible composition comprises a compound of the present invention. In some embodiments, the edible composition is a food product, in some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edibie composition is a consumer product.
[0359] in some embodiments, the methods of reducing sugar intake of a subject further comprise the step of identifying a subject in need thereof. The skilled worker would be able to identify a subject in need of reducing sugar intake. No n - limiting examples of such subjects include subjects that suffer from any one or more of the following disorders: diabetes, pre-diabetes, insulin resistance, obesity, excessive weight, and hyperglycemia.
[0360] In some embodiments, the amount of sugar replaced by Acesulfame K in the edible composition is an amount sufficient to maintain or restore the health of a subject. In some embodiments, the amount of sugar replaced by Acesulfame K in the edible composition is an amount sufficient to result in weight loss in a subject. In some embodiments, the amount of sugar replaced by Acesulfame K in the edible composition is an amount to sufficient to alleviate the effects of, or treat, a disease associated with sugar consumption or excessive weight of the subject (e.g., diabetes). In some embodiments, the amount of sugar replaced by Acesulfame K in the edible composition is up to ! %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 300%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some embodiments, the subject's daily sugar intake is less than 250 g/day, less than 200 g/day, less than 175 g/day, less than 150 g/day, less than 125 g day, less than 100 g/day, less than 75 g/day, less than 50 g/day or less than 25 g/day.
[0361] In some embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of a subject's sugar intake by up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 35%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention, in some embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of a subject's sugar intake by up to 25%. In other embodiments, the amount of compound of the invention added to the edibie composition is sufficient to permit reduction of a subject's sugar intake by up to 50%. In other embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of a subject's sugar intake by up to 75%. In yet other embodiments, the amount of compound of the invention added to the edible composition is sufficient to permit reduction of a subject's sugar intake by up to 100%.
[0362] In some embodiments, the method of method of reducing sugar intake of a subject further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which may lack an inherent flavor. Meth^
[0363] According to another embodiment, the invention provides methods of reducing the bitter taste in an edibie composition, in some embodiments, the edible composition is a food product. In some embodiments, the edibie composition is a pharmaceutical composition. In some
embodiments, the edibie composition is a consumer product.
[0364] in one embodiment, the method comprises: (a) adding an effective amount of a compound of Formuia (I), Formuia (la), Formuia (ila), Formuia (ilia), Formuia (lib), Formuia (iiib).
Formula (He), Formuia (Me), Formuia (IVe), Formula (lid), Formuia (Hid), Formula (IVd), Formula (He), Formuia (lile), Formuia (IVe), Formula (Πί), Formula (ilg), Formula (llh), Formula (V), Formuia (Via), Formula (Vib), Formuia (Vila), Formuia (Vlli), Formuia (IXa),
Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof, to an edible composition such that bitter taste is reduced.
[0365] in alternate embodiments, the method comprises: (a) ingesting an effective amount of a compound of Formula (Ϊ), Formula (la). Formula (31a), Formula (Ilia), Formula (lib),
Formula (Iiib), Formula (lie). Formula (IIIc), Formula (IVe), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Die), Formuia (IVe), Formuia (lif), Formula (Ilg), Formula (Ills), Formula (V), Formula (Via), Formula (Vib). Formula (Vila), Formuia (VIII'), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XT') or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 134, as described above, or combinations thereof, before, along with, or after the edible composition such, that bitter taste is reduced.
[0366] In some embodiments, the bitter tastant is a bitter tasting salt. In some embodiments, the bitter tastant is a potassium salt, a magnesium salt, or a calcium salt. In some embodiments, the bitter tastant is a potassium salt. In some embodiments, the bitter tastant is KC1. In other embodiments, the bitter tastant is potassium lactate. In some embodiments, the bitter tastant is inherent in the edible composition, such as in an inherently bitter foodstuff.
[Θ367] In some embodiments, the bitter taste is reduced by up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 1 00%. These amounts are not meant to be limiting, and increments between the recited percentages are specifical ly envisioned as part of the invention. In some embodiments, the bitter taste is reduced by up to 25%, in other embodiments, the bitter taste is reduced by up to 50%. In other embodiments, the bitter taste is reduced by up to 75%. in other embodiments, the bitter taste is reduced by up to 100%.
[0368] In some embodiments, the method of reducing the bitter taste attributed to a bitter tastant in an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers (which lack an inherent flavor). Method. o j^
[0369] According to another embodiment, the invention provides a method of preserving an edible composition an edibie composition comprising:
(a) providing an edibie composition; and
(b) combining with the edibie composition of (a) a preservative and an effective amount of compound of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib). Formula (Illb), Formula (11c), Formula (lile), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Me), Formula (lVe), Formula (Hi), Formula (llg), Formula (Mi), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof.
[0370] in another embodiment, the method of preserving an edible composition comprises:
(a) providing an edibie composition; and
(b) combining with the edible composition of (a) a preservative and an effective amount of any one of Compounds 1-134, or combinations thereof.
[0371] According to the invention, the preservative can be any bitter- Easting preservative, in some embodiments, the preservative in (a) is a potassium salt, in some embodiments, the preservative in (a) is potassium lactate.
[0372] In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0373] In some embodiments, the method of preserving an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, flavorants or flavor modifiers, which, may lack an inherent flavor. Method^o re^
edible^comij sit oB
[0374] According to another embodiment, the invention provides a method of reducing the amount of sodium in an edible composition while preserving the edible composition. In some embodiments, the method comprises replacing an amount of sodium containing preservative used in preparing an edible composition with an amount of potassium containing preservative and adding an effective amount of a compound of Formula (I), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib), Formula (Mb), Formula (He), Formula (Hie), Formula (IVc), Formula (Hd), Formula (Hid), Formula (IVd), Formula (He), Formula (Hie), Formula (IVe), Formula (Hi), Formula (llg), Formula (Hh), Formula (V), Formula (Via), Formula (Vlb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof. [0375] in some embodiments, the method comprises repiacing an amount of sodium lactate used in preparing an edible composition with an amount of potassium lactate and adding an effective amount of a compound of Formula (I), Formula (la), Formula (lia). Formula (Ilia), Formula (lib), Formula (llib), Formula (lie). Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (lile), Formula (We), Formula (Ilf), Formula (Tig), Formula (Ills), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formul (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 - 134, as described above, or combinations thereof.
[0376] In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0377] In some embodiments, the effective amount of the compound is sufficient to permit reduction of the amount of sodium lactate typically used in preparing an edible composition by up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% 75%, 80%, 85%, 90%, 95% or 100%. These amounts are not meant to be limiting, and increments between the recited percentages are specifically envisioned as part of the invention. In some em bodiments, the effective amount of the compound is sufficient to permit reduction of the amount of sodium lactate typically present in an edible composition by up to 25%. In other embodiments, the effective amount of the compound is sufficient to permit reduction of the amount of sodium lactate typically present in an edible composition by up to 50%. In other embodiments, the effective amount of the compound is sufficient to permit reduction of the amount of sodium lactate typically present in an edible composition by up to 75%, in yet other embodiments, the effective amount of the compound is sufficient to permit reduction of the amount of sodium lactate typically present in an edible composition by up to 100%.
[0378] In some embodiments, the method of reducing the bitter taste attributed to a bitter tastant in an edible composition further comprises adding one or more additional components selected from the group consisting of preservatives, nutritives, fiavorants or flavor modifiers, which may lack an inherent flavor. In some embodiments, the method of reducing the amount of sodium lactate in an edible composition while preserving the food product further comprises adding one or more additional flavor modifiers.
[0379] According to another embodiment, the invention provides a method of inhibiting or reducing activation and/or signaling of a bitter taste receptor. In some embodiments, the method comprises contacting a bitter taste receptor with a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (ΙΠΌ), Formula (He), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (Tile), Formula (We), Formula (Ilf), Formula (Ilg), Formula (lib), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-134, as described above, or combinations thereof. In some embodiments, the method comprises contacting a bitter taste receptor with any one of Compounds 1-58, or 61-134, or combinations thereof.
[0380] In some embodiments, the method comprises contacting a bitter taste receptor with an edible composition comprising a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (ΪΠΌ), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (ITIe), Formula (IVe), Formula (II f), Formula (Ilg), Formula (lib). Formula (V), Formula (Via), Formula (Vib),
Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1- 134, as described above, or combinations thereof.
[0381] In some embodiments, the edible composition is a food product. In some embodiments, the edible composition is a pharmaceutical composition. In some embodiments, the edible composition is a consumer product.
[0382] In some embodiments, the bitter taste receptor is an ex vivo receptor present in, for example, an assay. In some embodiments, the bitter taste receptor is an in vitro receptor present in, for example, an assay. In other embodiments, the bitter taste receptor is an in vivo receptor present in a subject. In some embodiments, the bitter taste receptor is present in the oral cavity or gastrointestinal tract of a subject. In some embodiments, the bitter receptor is in the oral cavity of a human. In some embodiments, the bitter receptor is in the oral cavity of a non-human animal. In some embodiments, the bitter receptor is in the oral cavity of an animal model.
[0383] In some embodiments, inhibition of a bitter taste receptor will affect a physiological process or condition. Non-limiting examples of physiological processes and conditions affected by inhibition of bitter taste receptors include bitter taste, hypertension, nausea, emesis, effects on the gastrointestinal tract, appetite, nutrition, nutrient absorption, satiety, hunger, diabetes, obesity, blood glucose levels, blood glucose regulation, metabolism, diet, and eating disorders.
Terrj enojd. Compound s
[0384] in some embodiments, one or more of the compounds of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (iilb), Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (Hie), Formula (IVe), Formula (lif , Formula (Ilg), or Formula (Ilh), as described herein, is commercially available, for example from commercial sources such as Sigma-Aldrich® of St. Louis, Missouri, USA; TCI America, Portland, Oregon, LISA; and Acros Orga.ni.cs, Geel, Belgium; among others.
[0385] In other embodiments, one or more of the compounds of Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb), Formula (lie), Formula (IIIc), Formula (IVc), Formisla (lid), Formula (Hid), Formula (IVd), Formula (lie). Formula (Hie), Formula (IVe), Formula (III), Formula (Ilg), or Formula (lih) is prepared from commercially available reagents by routine methods in synthetic organic chemistry.
[0386] in one embodiment, one or more compounds of Formula (I), Formula (la), Formula (Ha), Formula (Ilia), Formula (lib), or Formula (Illb) is prepared by in a multi-step sequence beginning with epoxidation of diene Ai to afford epoxide Pi, which then undergoes Bronsted acid or Lewis acid catalyzed cyciization to afford cyclohexene P2 a fter quenching of the cation by deprotonation. Reduction of the olefin of P2 followed by elimination of the hydroxy group affords olefin product P3 (Scheme I):
Figure imgf000158_0001
P2 P3
Scheme I
[0387] Suitable epoxidation conditions include those known in the art for epoxidizing olefins, such as use of hydrogen peroxide, peroxycarboxylic acids (e.g., perbenzoic acids, such as wj-CPBA), aikyl hydroperoxides (e.g., fert-butylperoxide), acetone peroxide, or transition mesa! reagents, such as osmium tetroxide, manganese with sodium hypochlorite (Jacobsen epoxidation), or titanium with tartrate ester (Sharpless epoxidation). In one embodiment, selective epoxidation of the internal olefin of Ai is achieved by the use of a directing group on the -C(R2)(K )(R4) moiety, such as a hydroxy group. Moreover, epoxidation of A 1 can also be stereoselective through the use of chiral reagents and/or catalysts, such as those used in the Jacobsen epoxidation or the Sharpless epoxidation. Stereoselective epoxidation can afford an enantiomerically enriched cyciization product P3 as the stereochemistsy of the epoxide can be transferred during the cyciization step.
[0388] In some instances, the cyciization step in Scheme I is promoted by the presence of Bronsted acids, such as inorganic acids (e.g., HQ, H„SO , etc.) or organic acids (acetic acid, trifluoroacetie acid, triflic acid, etc.). In certain embodiments, the cyciization step in Scheme I is promoted by the use of Lewis acids, such as boron compounds (e.g., Bu2BOTf or BF3*Et20), titanium compounds (e.g., TiCl4 or titanium alkoxides), aluminum compounds (e.g., A1C13 or aluminum alkoxides), silicon compounds (e.g., trialkylsilyl triflates, such as TMS-O'T'f, tria!kylsilyl halides, etc.), and the like.
[0389] Suitable reducing conditions include those known in the art for reducing olefins, such as hydrogenolysis with hydrogen and palladium, such as palladium on carbon. [0390] During the final elimination step of Scheme Ϊ, the hydroxy group may be converted to a leaving group to facilitate the elimination. Suitable leaving groups include those recognized in the art for elimination reactions, such as halide (e.g., chloro, bromo, iodo), alkoxy, aryloxy, activated leaving groups, and the like, in some embodiments, elimination conditions also employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOH, LiOH, etc), carbonates (such as a2C03, K2C03, CaC03, etc) and bicarbonaf.es (such, as NaHCOj, KHCO3, etc). Other suitable bases include aprotic amine bases, such, as triethylamine, pyridine, 2,6-hxtidine, ! ,8-diazabicycloimdec-7-ene (DBU), 4-(dimetbylamino)-pyridine, etc. in some instances, suitable bases include strong bases such as a!koxides (such as sodium or potassium ferf-butoxide), lithium diisopropyl amide (LDA), lithium bis(trimetbylsilyl)araide (LiHMDS), sodium bis(trimethylsilyl)amide (NaHMDS), and the like, in other instances, the elimination employs acidic conditions. Suitable acids include inorganic acids (e.g., HC1, H SO , etc.) or organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc),
[03 1] Although in Scheme 1 the cation formed during the cycHzation step is quenched by deprotonation resulting in an olefin, in other embodiments, the catio is quenched by addition of water. The resulting hydroxy group can also be eliminated and the resulting olefin reduced.
[0392] in one embodiment, one or more compounds of Formula (1), Formula (la), Formula (lia), Formula (ilia), Formula (lib), or Formula (TTib) is prepared by nucleophilic attack by nucleophile A2 on aldehyde P3, wherein RJ and R4 together form =0, followed by oxidatio n of the resulting alcohol P4 to afford product P5 (Scheme ii):
Figure imgf000159_0001
P3 P4 P5
Scheme ii
[0003] Oxidation can be carried out using routine methods known in the art, such as Swern oxidation, PCC, TPAP/ MO, Dess-Martin periodinane, IBX, TEMPO, etc.
[0393] in another embodiment, one or more compounds of Formula (Γ), Formula (la), Formula (11a), Formula (lila), Formul (lib), or Formula (liib) is prepared by nucleophilic attack by nucleophile A2 on acyi compound P3, wherein R3 and R4 together form =0, to displace leaving group LG to afford product P5 (Scheme III):
Figure imgf000159_0002
P3 P5
Scheme Til [0004] Suitable leaving groups include those recognized in the art for acylation reactions, such as halide (e.g., chloro, bromo, io lo), alkoxy, aryloxy, leaving groups associated with activated esters (e.g., N-succinamide or thai associated with dicyclohexylcarbodiimide), and the like, in some embodiments, acylation conditions also employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such, as NaOH, LiOH, etc.), carbonates (such as Na CO,, K CO.,,
CaCO,, etc. ), and bicarbonates (such as NaHCO , KHC'O , etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethyiamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU), 4-(dimethylamino)-pyridine, etc.
[0394] in one particular embodimeni, compound P3 is an acid halide, such as an acid chloride or bromide, and the acylation reaction proceeds in the presence of an aprotic amine base, such as triethyiamine, pyridine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU),
4-(dimethylamin.o)-pyridine. When P3 is an acid halide, compound P3 can be prepared from the corresponding carboxylic acid using routine methods known in the art.
[0395] in one embodiment, one or more compounds of Formula (T), Formula (lie), Formula (IITc), Formula (lid), Formula (Hid), Formula (lie), Formula · 111·.: ·. or Formula (Iif) is prepared by oxidation of alcohol A 3 to aldehyde P6 (Scheme IV):
Figure imgf000160_0001
A3 P6
Scheme IV
[0003] Oxidation can be carried out using routine methods known in the ari, such as Swern oxidation, PCC, TPAP/NMO, Bess-Martin perioditiatie, IBX, TEMPO, etc.
[0396] in another embodiment, one or more compounds of Formula (I), Formula (lie),
Formula (Hie), Formula (lid), Formula (Hid), Formula (lie), Formula (Hie), or Formula (iif) is prepared by nucleophilic attack by nucleophile A2 on aldehyde P6 followed by oxidation of the resulting alcohol P7 to afford product P8 (Scheme V):
Figure imgf000160_0002
P8
Scheme V
[0397] In some embodiments, one or more compounds of Formula (I), Formula (lie),
Formula (iilc), Formula (lid), Formula (Hid), Formula (He), Formula (Die), or Formula (Iif) is prepared by nucleophilic attack by niscleopbile A2 on acyl compound A4 to displace leaving group LG to afford product P8 (Scheme VI):
Figure imgf000161_0001
A4 P8
Scheme VI
[0004] Suitable leaving groups include those recognized in the art for acylaiion reactions, such as halide (e.g., chloro, bromo, iodo), alkoxy, aryloxy, leaving groups associated with activated esters (e.g., N-succinamide or that associated with dicyclohexylcarbodiimide), and the like. In some embodiments, acylation conditions also employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOH, LiOH, etc.), carbonates (such, as Na^CO , CO^,
CaCO , etc.), and bicarbonaies (such as NaHCO , KHCO , etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU), 4-(dimethylamino)-pyridine, etc.
[0398] In one particular embodiment, compound A4 is an acid halide, such as an acid chloride or bromide, and the acylation reaction proceeds in the presence of an a rotic amine base, such as triethylamine, pyridine, 2,6-lutidine, 1 ,8-diazabicycloundec-7-ene (DBU),
4-(dimethylamino)-pyridine. When A4 is an acid halide, compound A4 can be prepared from the corresponding carboxylic acid using routine methods known in the art.
[0399] In some embodiments, compound A4 is prepared from the corresponding carboxylic acid using routine methods known in the art. In other embodiments, compound A4 is prepared from alcohol A3 by oxidation using methods known in the art,
[0400] in one embodiment, one or more compounds of Formula (1), Formula (ITc), Formula (TIIc), Formula (TId), Formula (TIM), Formuia (Tie), Formula (lile), Formula (ITf), or Formula (Tlh) is prepared by acetal formation under acidic conditions between aldehyde P6 and nucleophile A2, when R" represents alkoxy, to afford acetal product P9 (Scheme VII):
Figure imgf000161_0002
Scheme VII
[0401] Suitable acids for acetal formation include inorganic acids (e.g., HQ, H SO , etc.) and organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc.).
[0402] In one embodiment, one or more compounds of Formula (T), Formul (lie), Formula (IITc), Formula (IVc), Formula (ITd), Formuia (ITId), Formula (IVd), Formula (He), Formula (Tile), Formula (IVe), Formula (ITf), Formula (ilg), or Formula (ITh), wherein R4 is -OC(0)-R, is prepared by acylation of alcohol A3 with acyl compound A5 bearing leaving group LG to afford product P10 (Scheme VIII):
Figure imgf000162_0001
A3 A5 P10
Scheme VIII
[ 403J Suitable leaving groups include those recognized in the art for acylation reactions, such as halide (e.g., chloro, bromo, iodo), aryioxy, leaving groups associated with activated esters (e.g., iV-succinamide or that associated with dicyclohexyicarbodiimide), and the like. In certain embodiments, acyl compound A5 is an acid anhydride; that is LG is -OC(0)R. In some embodiments, acylation conditions also employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal carbonates (such as NaiCQ;, K2CO3, CaC<¾, etc.) and bicarbonates (such as NaHCO;, KliCO;, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triefhylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine,
l,8-diazabicycloundec-7-ene (DBU), 4-(dimethyIamino)-pyridine, etc.
[0404] in one particular embodiment, compound A5 is an acid halide, such as an acid chloride or bromide, and the acylation reaction proceeds in the presence of an amine base, such as triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU), 4-(dimethyiamino)-pyridine, etc.
[0405] in another embodiment, compound A2 is an activated ester and acylation proceeds under mild conditions that do not result in the generation of strong acids.
[0406] Compound A5 can be prepared from the corresponding carboxylic acid using routine methods known in the art, Chroman Compounds
[Θ407] In some embodiments, one or more of the compounds of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila), as described herein, is commercial!}? available, for example from commercial sources such as Sigma-Aldrich® of St. Louis, Missouri, USA; TCI America, Portland, Oregon, USA; and Acr s Organics, Geel, Belgium; among others,
[Θ408] In other embodiments, one or more of the compounds of Formula (V), Formula (Via), Formula (VIb), or Formula (Vila), is prepared from commercially available reagents by routine methods in synthetic organic chemistry.
[0409] In one embodiment, one or more compounds of Formula (V), Formula (Via),
Formula ( VIb), or Formula (Vila) is prepared by cyclization of phenol A21 by intramolecular displacement of leaving group LG (Scheme IX):
Figure imgf000163_0001
P21
Scheme IX
[0410] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, a'lkoxy, acyloxy, and she like, in some instances, she displacement reaction employs an inorganic or organic base in order to deproionaie the phenol. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth mesa! hydroxides (such as NaOH, LiOH, etc.), carbonates (such as Na2C<¾, K2C<¾, CaCO:i, etc.), and bicarboaates (such as NaHC<¾, KHC03, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, trietbylatnine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, 1 ,8-diazabicycloimdec-7-eiie (DBU),
4-(dimethylamino)-pyridine, etc. In some embodiments, LG is hydroxy and the cyclization is promoted by acidic conditions, such as with, inorganic acids (e.g., HC1, H2SO4, etc.) or organic acids (acetic acid, trifiuoroacetic acid, triflic acid, etc.).
[041 1 j in certain embodiments, phenol A21 is prepared in two steps, first by nucleophilic attack on ketone A22 with nucleophile A23 to give alcohol P22, second by conversion of the tertiary alcohol of P22 to leaving group LG (Scheme X):
Figure imgf000163_0002
A22 A23 P22 A21
Scheme X
[0412] Conversion of the tertiary alcohol of P22 to leaving group LG can be performed by routine methods known in the art, such as conversion to a halide, mesylate, tosylate, or triflate, acylation, or treatment with inorganic acids (e.g., HQ, H2SO4, etc.) or organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc.),
[0413] In certain embodiments, phenoi A21, wherein R4 or R5 is H, is prepared in two steps, first by nucleophilic attack on aldehyde A24 with nucleophile A23 to give alcohol P23, second by conversion of the secondary alcohol of P23 to leaving group LG (Scheme XI):
Figure imgf000163_0003
A24 A23 P23 A21
Scheme XI [0414] Conversion of the secondary alcohol of P23 to leaving group LG can be performed by routine methods known in the art, such as conversion to a halide, mesylate, tosylate, or triflate, acyiation, or treatment with inorganic acids (e.g., HC1, H2SO4, etc.) or organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc.).
[0415] in some embodiments, aldehyde A24 is prepared by oxidation of primary alcohol A25 (Scheme XII):
Figure imgf000164_0001
A25 A24
Scheme ΧΠ
[0416] Oxidation can be carried out using routine methods known in the art, such as Swern oxidation, PCC, TPAP/NMO, Dess-Martin periodinane, ΪΒΧ, TEMPO, etc,
[0417] in another embodiment, one or more compounds of Formula (V) or Formula (VTb) is prepared by lactonization between the phenol and activated carboxyl group -C(0)-LG of A26 resulting in loss of leaving group LG to afford lactone P24 (Scheme ΧΠί):
Figure imgf000164_0002
A26 P24
Scheme XITI
[0418] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo), alkoxy, acyloxy, activated groups (e.g., -O-N-succinamide, or that generated by use of dicyclobexylcarbodiimide, DCC), and the like. When LG is halide, suitable lactonization conditions often employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal carbonates (such as Na2C03, K2C03, CaC03, etc.) and bicarbonates (such as aHC03, KHCO3, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU), 4-(dimethylarnino)-pyridine, etc.
[0419] in another embodiment, compound A22 is prepared by nucleophilic attack of nucleophile A23 on lactone P24 (Scheme XIV);
Figure imgf000165_0001
P23 A22
Scheme XV
[0421] Oxidation can be carried out using routine methods known in the art, sisch as Swern oxidation, PCC, TPAP/NMO, Dess-Mariin periodinane, IBX, TEMPO, etc,
[0422] in another embodiment, one or more compounds of Formula (V) or Formula (Vib), wherein R and R" are H, is prepared by reduction of lactone P24 to the corresponding cyclic ether P25 (Scheme XVI);
Figure imgf000165_0002
P24 P25
Scheme XVI
[0423] Suitable reduction conditions include those known in the art for reducing esters, such as treatment with hydride sources, such as lithium aluminum hydride (LiAlH4), diisobutylaluminum hydride (DIBAL), and various borane compounds.
[0424] The skilled artisan will appreciate that any of the above reactions in which, a stereogenic center is formed can be performed under enantioselective conditions that produce a product enriched in one enantiomer, for example, with greater than about 25, 50, 70, 80, 90, 95, 97, 98, or 99% ee. Such stereoselectivity can be induced throug the use of chiral auxiliaries, reagents, and catalysts as known in the art.
Benzo Ring-containing Compounds
[0425] in some embodiments, one or more of the compounds of Formula (VIIT), Formula (TXa), Formula (IXb), Formula (IXc), or Formula (FXd), as described herein, is commercially available, for example from commercial sources such as Sigma-Aldrich® of St. Louis, Missouri, USA; TCI America, Portland, Oregon, USA; and Acros Organics, Geel, Belgium; among others. [0426] in other embodiments, one or more of the compounds of Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), or Formula (IXd) is prepared from commercially available reagents by routine methods in synthetic organic chemistry.
[0427] in one embodiment, one or more compounds of Formula ( VIII), Formula (IXa), Formula (IXb), or Formula (IXc) is prepared by esterification of benzoic acid A31 (when X is OH) or of acid balide A31 (when X is halide) with alcohol A32 to afford ester P31 (Scheme XVII):
Figure imgf000166_0001
A31 A32 P31
Scheme XVII
[0428] Suitable esierification conditions when X is OH include those known in the art, such as Fischer esterification, Steglich esterification (i.e., using dicyclohexylcarbodiimide, DCC), as well as others involving activated esters (when X is an activated group, such as -O-N-succinamide).
When X is halide, suitable esterification conditions often employ an inorganic or organic base.
Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal carbonates (such as Na2C03, K2C03, CaC03, etc.) and bicarbonates (such as NaHC03, HC03, etc.). Other suitable bases include amine bases, such, as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine,
1 ,8 -diazabicycloundec-7-ene (DBU), 4-(dimethylamino)-pyridine, etc.
[0429] Compound A31 (when X is halide) can be prepared from the corresponding carboxylic acid using routine methods known in the art,
[0430] Although not pictured, in some instances, one or more compounds of Formula (VIII),
Formula (IXa), Formula (IXb), or Formula (IXc) is prepared by esterification of the acid anhydride of benzoic acid A31 (when X is OH) with alcohol A32 to afford ester P31. Whe utilizing an acid anhydride, suitable esterification conditions often employ an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal carbonates (such as Na2C03, 2C03, CaC03, etc.) and bicarbonates (such as aHC03, KHCO3, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8~diazabicycloundec-7-ene (DBU), 4-(dimetbylamino)-pyridine, etc. In some instances, reaction with acid anhydrides also includes use of a reagent that reacts with the acid anhydride to generate an activated ester in situ.
[0431] In another embodiment, one or more compounds of Formula (VIII), Formula (IXa), Formula (IXb), or Formula (IXc) is prepared by alkylation of benzoate A31 (when X is O") with compound A33 by displacement of the leaving group LG of A33 to afford ester P3 I (Scheme XVIII):
Figure imgf000167_0001
A31 A33 P31
Scheme XVIII
[0432] In some instances, the benzoate is generated by deprotonating benzoic acid A31 (when X is OH) with an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal carbonates (such as Na2CO;, K2CO;, CaC03, etc.) and bicarbonates (such as NaHCCK, HCCK, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l ,8-diazabicycloundec-7-ene (DBU),
4-(dimethylamino)-pyridine, etc. Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like.
[0433] In certain embodiments, one or more compounds of Formula (VIII) or Formula (IXd) is prepared by nucleophilic addition of one or more nucleophiles A34 to ester P31 to afford alcohol P32, which can optionally under go etherification with compound A33 by displacement of leaving group LG to afford ether P33 (Scheme XIX):
Figure imgf000167_0002
P31 A34 P32 P33
Scheme XIX
[0434] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like. In some instances, the displacement reaction employs an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as aOFI, LiOFI, etc.), carbonates (such as Na2C<¼, K2C<¼, CaC(¾, etc.), and bicarbonates (such as NaHCO;, HCO3, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine,
1 ,8-diazabicycloundec-7-ene (DBU), 4-(dimethylammo)-pyridine, etc. In some instances, suitable bases include strong bases such as aikoxides (such, as sodium or potassium feri-butoxide), lithium diisopropyl amide (LDA), lithium bis(trimethylsilyl)amide (LiHMDS), sodium
bis(trimethylsilyl)arnide (NaHMDS), and the like,
[0435] In another embodiment, one or more compounds of Formula (VIII) or Formula (IXd) is prepared by nucleophilic addition of nucleophile A34 to aldehyde A35 to afford alcohol P34 (Scheme XX):
Figure imgf000168_0001
A35
Scheme XX
[0436] in certain embodiments, alcohol P34 is oxidized to a carbonyl (e.g., using routine methods known in the art, such as Swem oxidation, PCC, TPAP NMO, Dess-Martin periodiiiaiie, IBX, TEMPO, etc.), which is then subjected to nucieophiiic attack by nucieophiie A34 (which can be the same or different from A 4 in Scheme XX) to afford alcohoi P32, which, as noted above, can optionally undergo etherification with compound A33 to afford ether P33 (Scheme XXI):
Figure imgf000168_0002
Scheme XXI
in some embodiments, one or more compounds of Formula (VIII) or Formula (IXd) is prepared by etherification of alcohol P34 with compound A33 by displacement of the leaving group LG to afford ether P35 (Scheme XXII):
Figure imgf000168_0003
P34 P35
Scheme XXII
[0438] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like. In some instances, the displacement reaction employs an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOH, LiOH, etc.), carbonates (such as Na2C03, K2C03, CaC03, etc.), and bicarbonates (such as NaHC03, KHCO3, etc). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6- iutidine,
1 ,8-diazabicycloundec-7-ene (DBU), 4-(dimethylamino)-pyridine, etc. In some instances, suitable bases include strong bases such as alkoxides (such as sodium or potassium fert-butoxide), lithium diisopropyl amide (LDA), lithium bis(trimethylsilyl)amide (Li IMDS), sodium
bis(trimethylsilyl)amide (NaHMDS), and the like.
[0439] in some embodiments, one or more compounds of Formula (VIII) or Formula (IXd), wherein R' and/or RJ is hydrogen, is prepared by reduction of ester P31 to ether P36 (Scheme XXIII):
Figure imgf000169_0001
P31 P36
Scheme XXIII
[0440] Suitable reduction conditions include those known in. the art for reducing esters, such as treatment with hydride sources, such as lithium aluminum hydride (LiAlH4), diisobut laluminum hydride (DIBAL), and various taorane compounds.
[0441] In certain, embodiments, one or snore compounds of Formula (VIII) or Formula (IXd), wherein R2 and/or R3 is hydrogen, is prepared by etherification of benzyl alcohol A36 with compound A 3 by displacement of the leaving group LG to afford to ether P36 (Scheme XXIV):
Figure imgf000169_0002
A36 A33 P36
Scheme XXIV
[0442] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like. In some instances, the displacement reaction employs an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOH, LiOH, etc.), carbonates (such as ajCOj, K2CO3, CaCOi, etc.), and bicarbonates (such as NaHCO ;, HCO3, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, ptperidine, pyrrolidine, 2,6-lutidine,
l,8-diazabicycloundec-7-ene (DBU), 4-(dimethylamino)-pyridine, etc. In some instances, suitable bases include strong bases such as alkoxides (such as sodium or potassium ferr-butoxide), lithium diisopropyl amide (LDA), lithium bis(trimethylsilyl)amide (LillMDS), sodium
bis(trimethylsilyl)amide ( aHMDS), and the like.
[0443] in alternate embodiments, one or more compounds of Formula (VIII) or Formuia (IXd ), wherein R" and /or is hydrogen, is prepared by etherification of alcohol A32 with compound A37 by displacement of the leaving group LG to afford to ether P36 (Scheme XXV):
( 10)n Q LG + HO-R4 » (Ri O)n Q °R4
A37 A32 P36
Scheme XXV
Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like. In some instances, the displacement reaction employs an inorganic or organic base. Suitable bases include those recognized in the art for such. reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOH, LiOH, etc.), carbonates (such as Na2C<¾, K2C03, CaC03, etc.), and bicarbonates (such as aHCO;;, KliCO;, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethyiamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine,
l,8-diazabicycloundec-7-ene (DBU), 4-(dimethyiamino)-pyridine, etc. in some instances, suitable bases include strong bases such as alkoxides (such as sodium or potassium fer.'-butoxide), lithium diisopropyl amide (LDA), lithium bisftrimethylsilyrjamide (LiHMDS), sodium
bis(trimethylsilyl)amide (NaHMDS), and the like,
Polycyclic Compounds
[0445] in some embodiments, one or more of the compounds of Formula (XI) or Formula (XII) as described herein, is commercially available, for example from commercial sources such as Sigma- Aldrich® of St. Louis, Missouri, USA; TCI America, Portland, Oregon, USA; and Acres Orgaoics, Geel, Belgium; among others.
[Θ446] In other embodiments, one or more of the compounds of Formula (XI) or Formula (XII) is prepared from commercially available reagents by routine methods in synthetic organic chemistry, [Θ447] In one embodiment, one or more compounds of Formula (XI) is prepared by reduction of a commercially available ketone A41 , such as camphor (e.g., where R1, R', and R' are methyl and R6 and R' are hydrogen) to afford alcohol P41 (i.e., wherein R4 is hydrogen) (Scheme XVI). Ketones such as A43 are commercially available in racemic and enantiomerically enriched forms. The alcohol product P41 is optionally etherified or acyiated with compound A42 by displacement of the leaving group LG to afford to ether or acyl compound P42 (Scheme XXVI):
Figure imgf000170_0001
A41 P41 P42
Scheme XXVI
[0448] Suitable reduction conditions include those known in the art for reducing ketones, such as treatment with hydride sources, such as lithium aluminum hydride (LiAlH4), diisobutylaluminum hydride (DIRAL), and various borane compounds. In some instances, reduction of the ketone is diastereoselective such that an excess of one diastereomeric product is prepared, such as an excess of the endo alcohol or the exo alcohol.
[0449] Suitable leaving groups include those recognized in the art, such as halide (e.g., chloro, bromo, iodo), triflate, mesylate, tosylate, and the like. In some instances, the displacement reaction employs an inorganic or organic base. Suitable bases include those recognized in the art for such reactions, and include but are not limited to alkaline and alkaline earth metal hydroxides (such as NaOFi, LiOH, etc.), carbonates (such as Na2C03, K2C03, CaC(¾, etc.), and bicarbonates (such as NaHCO ;, KliCO;, etc.). Other suitable bases include amine bases, such as ammonia, ammonium hydroxide, triethyiamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycIoundec-7- ene (DBU), 4-(dimethy¼mino)-pyridine, etc. in some instances, suitable bases include strong bases such as alkoxides (such as sodium or potassium fert-butoxide), lithium diisopropyi amide (LDA), lithium bisi trimethylsilyljamide (LiHMDS), sodium bisi trimethylsilyliamide (NaHMDS), and the like.
[0450] in some embodiments, when alcohol P41 is acylated, compound A42 is a acylhalide or an acid anhydride, in one particular embodiment, compound A42 is an acid halide, such as an acid chloride or bromide, and the acylation reaction proceeds in the presence of an aprotic amine base, such as triethylamine, pyridine, 2,6-lutidine, l,8 -diazabicycloundec-7 -ene (DBU), 4- (dimethylammo)-pyridine. When A42 is an acid halide, compound A42 can be prepared from the corresponding carboxylic acid using routine methods known in the art.
[0451] in another embodiment, one or more compounds of Formula (XT) is prepared by nueleophilic addition of nucleophile A43 (e.g., Grignard reagent, alkyilitiiiurn reagent) to ketone A41 to afford alcohol P43 (Scheme XXVIT). As noted above for the alcohol product P41 , the alcohol product P43 is optionally etherified or acylated with compound A42, by displacement of the leaving group LG to afford to ether or acyl compound P44 (Scheme XXVII):
Figure imgf000171_0001
Scheme XXVII
[0452] In another embodiment, one or more compounds of Formula (XT), is prepared by enolizing commercially available ketone Α4 Γ (e.g., wherein one or both of R6 and R7 is hydrogen) with a strong base, optionally in the presence of a Lewis acid. The resulting enolate intermediate can then be reacted with electrophile A44 to afford product P45 (Scheme XXVIli).
Figure imgf000171_0002
A41 ' P45
Scheme XXVIli
[0453] Examples of suitable bases for enolizing ketone A4 [ ' include strong bases such as alkoxides (such as sodium or potassium fert-butoxkle), lithium diisopropyi amide (LDA), lithium bis(trimethylsilyl)amide (LiHMDS), sodium bis(trimethylsilyl)amide (NaHMDS), and the like.
[0454] Examples of suitable Lewis acids for promoting the enolization of ketone A41 include boron compounds (e.g., Bu2BOTf or BF3*Et20), titanium compounds (e.g., TiCl4 or titanium alkoxi les), aluminum compounds (e.g., AICI3 or aluminum alkoxides), silicon compounds (e.g., trialkylsilyl triflaies, such as TMS-OTf, trialkylsilyl hahdes, etc.), and the like,
[0455] With product ketone P45 in hand, the ketone can be reduced and optionally etherated or acyiated as in Scheme XVI above or subject to nocleophilic attack and optionally etherated or acyiated as i Scheme XVII above to give products P4 i , P42, P43, and P44.
[0456] in another embodiment, one or more compounds of Formula (XI), is prepared by enolizing product P45, as with alcohol A41 above, e.g., wish a strong base, optionally in she presence of a Lewis acid. The resulting enolate intermediate is then be reacted with electrophile A45 to afford product P46, which has the structure of A41 (Scheme XXIX).
Figure imgf000172_0001
[0457] in another embodiment, one or more compounds of Formula (XI) are prepared by imine formation between compounds A41, P45, or P46 and amine A46 to afford imine product P47 (Scheme XXX). Imine P47 is optionally reduced to afford amine product P48 (Scheme XXX):
Figure imgf000172_0002
Scheme XXX
[0458] in some embodiments, imine formation conditions employ dehydrating agents, such as molecular sieves, heat, and/or the use of an azeotrope to remove water.
[0459] Suitable imine reducing conditions include those known in the art for reducing imines and iminimum ions, such as hydrogenolysis with hydrogen and palladium, such as palladium on carbon. Another suitable source of hydrogen includes formic acid.
[0460] in one embodiment, one or more compounds of Formula (XII) is prepared by hydroboration of a commercially available olefin A48, such as β-pinene (e.g., where R4is hydrogen and Y is a direct bond, and R1 and R^ are methyl) to give product organoborane P49, which is optionally oxidative!}' cleaved to afford alcohol P410 (Scheme XXXI).
Figure imgf000173_0001
Scheme XXXI
[0461] Suitable inline hydroboration conditions include the use of reagents such as borane, diborane, 9-BBN, among others. Oxidative cleavage of the organoborane P49 is carried out by standard methods, e.g., with hydrogen peroxide. The organoborane P9 is also optionally used i a Suzuki coupling with a suitable organohalide.
[0462] Olefins such as A48 are commercially available in racemic and enantiomerically enriched forms. Examples include -pinene and β-pinene, pinenone, and pinenol.
[Θ463] In some embodiments, and in similar fashion as described above for Scheme XXVI, compounds of Formula (XVII) are prepared by etherifying or acylating the alcohol product P410 with electrophilic compound A49 by displacement of the leaving group LG to afford to ether or acyl compound P41 1 (Scheme XXXII):
Figure imgf000173_0002
P410 P411
Scheme ΧΧΧΠ
[0464] in other embodiments, one or more compounds of Formula (XII) is prepared by oxidative cleavage of a commercially available olefin A48 to give product ketone P412 (Scheme XXXIII). Ketone P412 is then able to under go reactions similar to those described for the ketones in Schemes XXVi-XXX above, such as enolate formation with base followed by nueleophilic attack on eiectrophile A410 to give product ketone P413, followed by reduction of the ketone P413 to give product alcohol P4I4, which is optionally etherified or acviation with eiectrophile A411 (Scheme XXXIII):
Figure imgf000174_0001
P414 P415
Scheme XXXIII
[0465] Suitable oxidative cleavage conditions include the use of catalytic ruthenium or osmium in combination with excess oxidants, such as oxone, sodium periodate, sodium perchlorate, bleach, and the like.
[0466] in other embodiments, one or more compounds of Formula (XII), wherein the bond with a dotted line is a double bond is prepared by elimination of the leaving group LG in compound A432 under basic or acidic conditions (Scheme XXXIV). Compound A412 is prepared from the corresponding alcohol P415 by conversion of the hydroxy group into the leaving group LG (Scheme XXXIV);
Figure imgf000174_0002
Scheme XXXIV
[0009] Conversion of the hydroxy group of P415 to leaving group LG can be performed by routine methods known in the art, such as conversion to a halide, mesylate, tosylate, or triflate, acylation, or treatment with inorganic acids (e.g., HC1, H2SO , etc.) or organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc.).
[0009] Suitable bases for elimination of leaving group LG of A432 to afford olefin P416 include strong bases such as alkaline and alkaline earth metal hydroxides (such as iNaOH, LiOH, etc.), alkoxides (such as sodium or potassium ieri-butoxide), lithium diisopropyl amide (LDA), lithium bis(trimethylsilyl)amide (LiHMDS), sodium bis(himethylsilyi)amide (NaHMDS), and the like. Depending on the leaving group, suitable bases also include milder bases, such as alkaline and alkaline earth metal carbonates (such as NaiCO;, K2CO3, CaC<¾, etc.), and bicarbonates (such as aHCO;;, KHCO3, etc.), as well as amine bases, such as ammonia, ammonium hydroxide, triethylamine, pyridine, piperidine, pyrrolidine, 2,6-lutidine, l,8-diazabicycloundec-7-ene (DBU), 4-(dimeihylamino)-pyridine, etc. [0009] in some instances elimination of leaving group LG of A412 to afford olefin P416 occurs by treatment with inorganic acids (e.g., HCi, H2SO4, etc.) or organic acids (acetic acid, trifluoroacetic acid, triflic acid, etc.). in some embodiments, olefin P416 can be obtained directly from alcohol P41S by treatment with an inorganic or organic acid.
[0009] The alcohol P415 is obtained by nucleophilic attack of a nucleopbile R3-X" on the ketone P413, which is described above.
[0467] Regarding each of the synthetic schemes above, the skilled artisan will appreciate that aryl and/or heteroaryl, alkenyi, aSkynyl, araikyl, heteroaralkyl, allyl, and propargyl moieties herein may be readily coupled directly using Stille, Suzuki, Heck, Negishi, Sonongashira, Kumad , Glaser, or other related reactions, such as palladium-mediated cross -coupling reactions. Aryl and/or heteroaryl moieties herein may also be readily coupled through a heteroatom, e.g., using reactions such as the UHmann reaction, any of various palladium-mediated reactions developed by S.
Buchwald and others, by nucleophilic aromatic substitution, or other such reactions. Similarly, amines, alcohols, thiols, and other such beteroatom-hearing compounds herein may be coupled to aryl and/or heteroaryl moieties using palladium-mediated reactions developed by S. Buchwald and others, nucleophilic aromatic substitution, etc. Aryl and/or heteroaryl moieties linked by substituted or unsubstituted hydrocarbon chains herein may also be prepared by Stille, Suzuki, Heck, Friedel-Crafts, and other reactions as will be apparent to those of skill in the art.
[0468] it will be understood that the various substituents on the compounds in the above syntheses can be protected from the reaction conditions as necessary using the proper protecting groups, such as those disclosed in Greene, T. W.; Wilts, P.G.M. Greene's Protective Groups in Organic Synthesis, 4th ed.; Wiley-interscience: New York, 2006.
[0469] in order that this invention be more fully understood, the following examples are set forth, These examples are for the purpose of illustration only and are not to be construed as limiting the scope of the invention in any way.
[0470] The test compounds used in the following examples were obtained from commercial vendors for synthetic and natural compounds, including VitasM, ChemDiv, ChemBridge, Chromadex, Sigma Aldrich, Penta, Spectrum Chemical, Vigon, and indofine.
[0471] The taste test panelists used in the following examples were screened based upon and selected for their ability to perceive the bitter taste associated with potassium chloride. Only panelists capable of perceiving bitter taste participated in the following taste tests.
[0472] Due to the complex nature of taste perception in subjects and the inherently subjective nature of the following experiments, individual taste test trials may yield different results for a given compound. The data presented in the following Examples is illustrative of the taste testing results observed. It is noted that the data presented in the Figures represents a subset of the data presented in the Examples below. [0473] The taste testing experiments below were conducted with panels of varying siz panels comprising varying numbers of panelists).
Ex mpje ί Generation of KG Test Solutions.
[8474] Edible KG solution compositions ("KG test solutions") were prepared by first dissolving varying amounts of the test compounds in an amount of ethanoi or water (depending on the solubility of the compound) to create a 5mg/mL stock compound solution. An amount of this stock compound solution is then added to an aqueous KG solution. Enough EtOH is then added to the resulting stock compound/KCl solution so that the final KG test solution contains 1% EtOH. KG solution standards were similarly prepared by dissolving various amounts of KG in water and ethanoi without adding any test compound. NaCi solution standards were similarly prepared by dissolving various amounts of aCl in water and ethanoi without adding any test compound (NaCi solution standards did not contain any KG).
Table L KCI Taste Tesi Solution
Figure imgf000176_0001
Figure imgf000177_0001
Figure imgf000178_0001
Example 2 Effect of test compounds on the perception of bitter taste of aqueous KCl
solutions in humans.
[0475] The effect of the test compounds on the perception of the bitter taste of an aqueous solution of KCl in humans was evaluated using a "sip and spit" test as follows.
[0476] A set of KCl solution standards was developed and each standard solution was assigned a bitterness taste score of 0-15 (corresponding to aqueous KCl concentrations of 0 mM-120 mM). Panelists were trained to recognize these standards. In addition, before each day of testing, panelists were tested to see if they could determine differences in taste between the standard solutions, if a panelist was unable to recognize a change in KCl concentration, they were excluded from the panel for that day.
[0477] in a blind teste test, panelists were asked to compare the bitter taste of a small quantity (e.g., 8 ml) of each of the KCl Test Solutions to the taste of a KCl solution standard, without swallowing (see. e.g., Table 1). Specifically, panelists were asked to rate the bitterness of each KCl Test Solution on a scale of 0-15 using the same scale developed for the KCl solution standards. Each sample was tested in 2-4 discrete taste test experiments. Panelists were asked to rinse with water, eat a cracker, and wait approximately 10 minutes between samples.
[0478] Illustrative results of the aqueous solution testing are presented in Figures 1-4 and Table 1. Example 3 Generation of Potassium Lactate Test Solutions.
[0479] Edible potassium lactate solution compositions ("potassium lactate test solutions") were prepared by first dissolving varying amounts of the test compounds in an amount of ethanol or water (depending on the solubility of the compound) to create a 5mg mL stock compound solution. An amount of this stock compound solution is then added to an aqueous potassium lactate solution. Enough EtOH is then added to the resulting stock compound/potassium lactate solution so that the final potassium lactate test solution contains 1% EtOH. Potassium lactate solution standards were similarly prepared by dissolving various amounts of potassium lactate in water and ethanol without adding any test compound. Sodium lactate solution standards were similarly prepared by dissolving various amounts of sodium lactate in water and ethanol without adding any test compound (sodium lactate solution standards did not contain any potassium lactate).
Table 2. Potassium Lactate Taste Test Solutions
Figure imgf000179_0001
Figure imgf000180_0001
Standard 41 g/L : Π?Βί -4 Effect of test compounds cm the perception of bitter taste of aqueous potassium lactate solutions in humans.
[0480] The effect of the test compounds on the perception of the bitter taste of an aqueous solution of potassium lactate in humans was evaluated using the "sip and spit" test described in Example 2.
[0481] Illustrative results of the aqueous solution testing are presented in Figures 1 -4 and in
E mple s Generation of KCi 'T est Foodstuff Slurries.
[0482] Edible KCI food compositions ("KCI test foodstuff slurries") were prepared as follows. Dehydrated, salt-free turkey powder was weighed and mixed with various amounts of KCI and/or NaCl and then solubilized with boiling water to create a homogenized solubilized turkey slurry. Varying amounts of the test compounds were dissolved in an amount of ethanoi or water
(depending on the solubility of the compound) to create a 5mg/mL stock compound solution. An amount of this stock compound solution was then added to the turkey slurry . Enough EtOH is then added to the resulting stock compound/turkey slurry so that the slurry contains 1% EtOH. The slurry was again homogenized by boiling and mixing and allowed to cool to yield the final KCi test foodstuff slurry for taste testing. KC'I foodstuff slurry standards were similarly prepared without any test compound. NaCl foodstuff slurry standards were similarly prepared without adding any test compound (NaCl foodstuff slurry standards did not contain any KCi).
Table 3, KCI Foodstuff Slurry Compositions
Figure imgf000180_0002
Figure imgf000181_0001
Example 6 Effect of test compounds on the perception of bitter iaste of KCl foodstuff slurries in humans using a two- alternative forced choice method (2AFC),
[0483 J The effect of th e test compounds on th e perception of the bitter taste of KCi foodstuff slurries in humans was evaluated using a tvvo-aitemative -forced-choice "sip and spit" test as follows.
[0484] in a blind iaste test, panelists received two portions of turkey slurry - one portion being the KCl foodstuff slurry siaudard and the other being one of the KCl test foodstuff slurries ( each prepared as described in Example 5). The panelists tasted each of the portions by sipping and spitting. Each sample was tested in 2-4 discrete taste test experiments. Panelists were asked io rinse with water, eat a cracker, and wait about 10 minutes between samples, in each case, the panelists were asked to compare the bitter taste of the two turkey samples to each other (i.e.
panelists were asked to indicate which sample was less bitter).
[0485] illustrative results of the foodstuff testing are presented in Figures 1 -4 and in Table 3.
Example 7 Generation of Potassium Lactate Test Foodstuff Slurries.
[0486] Edible potassium lactate food compositions ("potassium lactate test foodstuff slurries") were prepared as follows. Dehydrated, salt-free turkey powder was weighed and mixed with various amounts of potassium lactate and/or sodium lactate and then solubilized with boiling water to create a homogenized sohsbilized turkey slurry. Varying amounts of the test compounds were dissolved in an amount of eihanol or water (depending on the solubility of the compound) to create a 5mg/'mL stock compound solution. An amount of this stock compound solution was then added to the turkey slurry. Enough EtOH is then added to the resulting stock compound/turkey slurry so that the final slurry contains 1% EtOH. The final slurry was again homogenized by boiling and mixing and allowed to cool to yield the final slurry for taste testing. Potassium lactate foodstuff slurry standards were similarly prepared without any test compound. Sodium lactate foodstuff slurry standards were similarly prepared without adding any test compound (sodium lactate foodstuff slurry standards did not contain any potassium lactate).
Table 4. Potassium Lactate Foodstuff Slurr Compositions
Figure imgf000182_0001
E¾jjmpje_8 Effect of test compounds on the perception of bitter taste of potassium lactate r2AFC\
[ 487J The effect of th e test compounds on th e perception of the bitter taste of potassium lactate foodstuffs in humans was evaluated using the two-alternative-forced-choice "sip and spit" test described in Example 6.
[0488] illustrative results of the foodstuff testing are presented in Figures 1-4 and in Table 4,
Ejyamph; 9 Effect of test compounds on the perception of bitter taste of aqueous KC1
solutions in humans using a Latin Square two-alternative forced choice method ("Latin Square-2AFC).
[0489] The effect of the test compounds on the perception of the bitter taste of an aqueous solution of KC1 in humans was evaluated using a "sip and spit" test using a Latin Square-2AFC testing method as follows.
[0490] in a blind taste test, panelists were asked to compare the bitter taste of a small quantity (e.g., 8 mi) of a KG Test Solution to the taste of a KG solution standard (prepared as described in Example 1), without swallowing, NaCl solution standards were prepared as described in Example 1.
[0491] in order to eliminate any effects of sample order, a complete Latin Square design was employed so that each possible order of sample presentation was utilized across subjects. Each sample was tested in several discrete taste test experiments. Panelists were asked to rinse with water, eat a cracker, and wait about 10 minutes between samples, in each case, the panelists were asked to choose the sample which tasted "less bitter," Illustrative results of the aqueous solution Latin Sq«are-2AFC testing are presented in Table 5,
Table s. KC1 Latiii Square-2AFC Taste Test Solution
Figure imgf000183_0001
ExaiaBleJ Effect of test compounds on the perception of bitter taste of KCl foodstuff slurries
Figure imgf000184_0001
Square-2AFC),
[0492] The effect of the test compounds on the perception of the bitter taste of KCl foodstuff slurries in humans was evaluated using a "sip and spit" test using a Latin Square -2 AFC testing method as follows,
[0493 J in a blind taste test, panelists received two portions of turkey slurry - one portion being the KCl foodstuff slurry standard and the other being one of the KCl test foodstuff slurries (prepared as described in Example 5). NaCl foodstuff slurry standards were prepared as described in Example 1.
[0494J The panelists tasted each of the portions by sipping and spitting. In order to eliminate any effects of sample order, a complete Latin Square design was employed so that each possible order of sample presentation was utilized across subjects. Each sample was tested in several discrete taste test experiments. Panelists were asked to rinse with water, eat a cracker, and wait about 10 minutes between samples. In each case, the panelists were asked to choose the sample that tasted less bitter.
[0495] illustrative results of the foodstuff Latin Sqoare-2AFC testing are presented in Table 6.
Table 6. KCl Latin Square-2AFC Taste Test Turkey Slurry
Figure imgf000184_0002
Example 11 Effect of test compounds on the perception of bitter taste of KCl solid-matrix foodstuffs in humans using a Latin Square two- alternative forced choice method (Latin Square-2AFC'¾.
[0496] The effect of the test compounds on the perception of the bitter taste of KCl in solid-matrix foodstuffs in humans was evaluated using a "chew and spit" test using a Latin Square -2 AFC testing method as follows.
[0497] Two types of marinades containing Prague powder, sugar, Evian™ water, KCl and/or NaCl in water were prepared. One marinade contained 80% KC1:20% NaCl (by weight) (i.e. , marinade concentration of 1.6% KCI). A second marinade contained 60% KC1:40% NaCl (by weight) (i.e. , marinade concentration of 1.2% KCi). Compound stock solutions were prepared by dissolving an amount of test compound in ethanol or water (depending on the solubility of the compound) to create a 5mg/'mL stock compound solution. Enough ethanol was added to each stock compound solution to generate a final stock compound solution containing 1% ethanol. The marinade, the stock compound solution and ground turkey were added to a mixing bowl, mixed at low-speed for about 2 minutes, and then mixed at high-speed for about 5 minutes. The marinated turkey mixture was divided into one pound aliquots, vacuum sealed into food saver bags, and allowed to marinate for about 2 hours in a refrigerator. The vacuum-sealed turkey was then cooked in an about 86°C water bath for about 30 minutes, if after about 30 minutes, the internal turkey temperature had not reached about 170°F, the vacuum-sealed turkey was cooked for about an additional 5 minutes. The vacuum-sealed turkey was then refrigerated for about two weeks before taste testing, KCi standards were similarly prepared by dissolving KCi in the marinade without adding any test compound during the turkey preparation. NaCl standards were similarly prepared by dissolving NaCl in the marinade without adding any test compound during the turkey preparation (NaCl standards did not contain any KCI).
[0498] The panelists tasted portions by chewing and spitting, in order to eliminate any effects of sample order, a complete Latin Square design was employed so that each possible order of sample presentation was utilized across subjects. Each sample was tested in several discrete taste test experiments. Panelists were asked to rinse with water, eat a cracker, and wait about 10 minutes between samples. In each case, the panelists were asked to choose the sample that tasted less bitter, illustrative results presented in Table 7.
Table 7. KCI Latin Sq»are~2AFC Taste Solid Tiirkey
Figure imgf000185_0001
Figure imgf000186_0001

Claims

We claim:
1. A composition comprising a compound according to a formula selected from the group consisting of:
(a) Formula (I):
Figure imgf000187_0001
Formula (I);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1 is absent or is selected from the group consisting of hydroxyi, Q^alkoxy, and
Figure imgf000187_0002
R' is selected from the group consisting of hydrogen, Cj.flalkyl,
Figure imgf000187_0003
and C2-t,alkynyl;
R3 is selected from the group consisting of hydrogen and Ci .6alkoxy;
R4 is selected from the group consisting of hydroxyi, C, _6alkoxy, and
C ;„i6acyioxy;
or IV and R4 iogeiher form H3;
wherein any of R1, R , RJ, and R4, independenily, is optionally substituted with 1-3 substituents selected from the group consisting of Cj.ioalkyl, Ci.iobaloalkyl, halo, hydroxy!, carboxyl, C l0alkoxycarbonyl, C2-i oalkenyloxycarbonyl,
C2-ioalkynyloxycarbonyl, C).)0acyl, Ci.ioacylamiao, Ci.ioac loxy, C .:;carbo«ate, Cj-ioalkoxy, pbenyloxy, phosphoryl, phosphate, phosphonate, phospb.in.ate, amino, diCi-ioalkylamiao, monoCi-ioalkylamino, Cuuamido, Ci-ioimino, Ci.iocarbamate, C;-iourea, cyano, nitro, azido, sulfhydryl, CMoal.kyltbio, sulfate, sulfonate, sulfarooyl, siilfonamido, sulfonyl, C3.7carbocyciyl,
Figure imgf000187_0004
Figure imgf000187_0005
phenyl, phertyl-C i_6alkyl, C sheteroaryl, and
C;.5beteroas l-C],6alkyl; and wherein heterocyclic or heteroaro malic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
m is 0-2;
n is 0-2;
p is 0-2;
t is 0-2;
wherein Q and C6 in Formula (I) optionally are bonded together to form a 6-membered ring; and wherein all doited bonds indicate optional carbon-carbon double bonds;
wherein the composition is edible and capable of reducing bitter tasie of a tastant:
Figure imgf000188_0001
Formula (V);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1, independently for each occurrence, is selected from the group consisting of halo, hydroxy!,
Figure imgf000188_0002
R" is selected from the group consisting of hydrogen, halo, hydroxy!, Chalky!, Ci-ebaloalkyl,
Figure imgf000188_0003
optionally substituted by hydroxyl, amino, mono- or disubstituted
Figure imgf000188_0004
amino, or carboxyl;
R'! is selected from the group consisting of hydrogen, hydroxyl, C].6alkyl,
Figure imgf000188_0005
R4 is selected from the group consisting of hydrogen, hydroxyl,
Figure imgf000188_0006
Ci-jj lkenyl, C2-2;alkynyl, and
Figure imgf000188_0007
wherein R4 is optionally substituted by one or more occurrences of hydroxyl or acetyloxy;
R' is selected from the group consisting of hydrogen, hydroxyl, C^ lky'l, C2_2)alkenyl, C2-2i ikynyl, and C] -6alkoxy, wherein RJ is optionally substituted by one or more occurrences of hydroxyl or acetyloxy;
or R4 and R3 together form =0;
wherein any of R1, R2, R4, and R5, independently and independently for each occurrence, is optionally substituted with 1 -3 substiiuenis selected from the group consisting of Ci-ioalkyl, Ci.iohaloalkyl, halo, hydroxyl, carboxyl, Ci-ioalkoxycarbonyl, C2-ioalkenyloxycarbonyl, C2-ioalkynyloxycarbonyl, C;_]0aeyl, Ci.]0acylamino, Ci_]0acyloxy, Ci.iocarbonate, C;.]0alkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diCi.ioalkylaroioo, monoCi-ioalkyiainino, Ci.i3amido, Ci-ioitntno, Ci.iocarbamate, Ci. iou ea, eyano, nitro, azido, sulfhydryl, Ci.ioalkylthio, sulfate, sulfonate, sulfamoyl, su!fonamido, sulfonyl, C3
Figure imgf000188_0008
Ci^heterocyclyl,
Figure imgf000189_0001
Ci.jheteroaiyl, and
Ci-sheteroaryl-C
Figure imgf000189_0002
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroaioms selected from N, O, and S; and
is 0-3;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant;
(c) Formula (VIIF):
Figure imgf000189_0003
Formula (Viii);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit;
R1, independently for each occurrence, is selected from the group consisting of hydrogen, ( ' ,.:;!
Figure imgf000189_0004
CS-ealkynyl, and
Rz is selected from the group consisting of hydrogen, C^alkyl, C2-6alkeoyl, and
Figure imgf000189_0005
R3 is selected from the group consisting of hydrogen, C^alkyl, C2-6alkenyj, and C2..6alkynyl;
or R2 and R3 together form =0;
R* is selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl, C2-6alkynyl, Cj
Figure imgf000189_0006
wherein any of R1, R , R3, and R4, independently and independently for each occurrence, is optionally substituted with 1 -3 substituents selected from the group consisting of€i.;0alkyi, Ci.iohaioalkyi, halo, hydroxy!, earhoxyl,
Ci.i0alkoxycar onyl, C2.ioaikenyioxycarbo yi, C^. ioaikynyioxycarbonyi, Ci-io c l, Ci.ioacylamino, Ci.ioacyloxy, C i .iocarbonate, Cj.ioalkoxy, phenyloxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, diC].ioalkyiamino, monoCi.i alkylamino, CVnamido, Ci_i»imino, C]..]ocarbamate, Ci.iourea, cyano, nitro, azido, sulfhydryl, Ci .joaikylthio, sulfate, sulfonate, sulfamoyi, sulfonamido, sulfonyl, C:;.7carbocyclyl, C3-7carbocyclyl-C [..6alkyl, C
Figure imgf000189_0007
C'i.6heterocyclyi-C|..6aIkyl, phenyl, phenyl-Ci.6alkyi, Ci.s'iieteroaryl, and
Figure imgf000189_0008
and wherein heterocyclic or heteroaromatic rings, independently for each occurrence, comprise 1-4 heteroatoms selected from N, O, and S; and
n is 0-3; and
wherein the composition is edible and capable of reducing bitter tasie of a bitter tastant;
(d) Formula (XI):
Figure imgf000190_0001
Formula (XI);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond,
R1, R , R3, R", and R' are independently selected from the group consisting of hydrogen, Chalky],
Figure imgf000190_0002
wherein each of R1, R2, R!, R°, and R7 may be optionally independently substituted with one or more substitiients selected from the group consisting of halo, -OH, -0, -SH, -S, -NH2, -CQ2H, -O(C !0alkyi), -Q(C2.10alkenyl), -0(C2-ioalkynyl), -S(C Oalkyl), -S(C2„l0alkenyl), -S(C2„10aikynyl),
-NH(C ,„ [0alkyl), - H(C2„10aikenyl), - H(C2- l0alkynyl), - (C U! 0alkyl)2, -N(C2. ic.alkenyl)2, and -N(C2. i .:;alkynyl)2;
R4 is absent or selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl,
Figure imgf000190_0003
and C^alkyny tester;
wherein R4 may be optionally substituted with one or more substitiients selected from the group consisting of halo, -OH, =0, -SH, =5, - H2, -C02IT, •OK . alkyi !. -O(C 0a3kenyl), -0(C2-ioalkyrryl), -S(CMOalkyj),
Figure imgf000190_0004
•Si ( . ..niky.K l j.
Figure imgf000190_0005
-M-I(C2.10alkenyl), - H(C2.10alkynyl), -N(CMOalky3)2, -N(C 0a3kenyl)2, -N(C2.ioalkynyl)2, CMOa yl, Ci-ioacyloxy,
Ci-ioacylamino, Ci.ioacylthioxy, CMOalky3ester, Cnoafkenylester,
Ci.;0alkynylester, Cwoalkylamide, C Oalkenyiamide, Ci.ioalkynylamide, Ci.;0alkylthioester, Ci_ioalkenylthioester, and Ci_;0alkynyithioester; R' is absent or selected from the group consisting of hydrogen, Chalk 1, Ci-ealkenyl, and C2-6aIk.yn.yI;
wherein R5 may be optionally independently substituted with one or more substttuents selected from the group consisting of halo, -OH, =0, -SH, =5, -NH2, -C02H, -O(C1-i0alkyl), "O(C2.!0alkenyj), -O(C2„l0alkyny3), -S(C ,„l0ajkyl), - K: ( . ..nii -nyi ;.
Figure imgf000191_0001
-NH(Ci.10alkyl), -NH{C2„10alkenyj), -NH(C2-;oa]kyny3), -N(C oalkyl)2, -N(C2-!oalkeHyl)2, and " (C2-i0alkynyl)2; wherein Rb and R' are optionally taken together so form ==0, ==:S or ==:C(Ril)2; wherei each Ra is independently selected from the group consisting of hydrogen,
Figure imgf000191_0002
C2-6alk.en.yl, and C2_6al.kynyl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is selected from the group consisting of =C(Ra)- and =N-;
wherein when the bond with the dotted line represents a double bond and R4 is absent, X is selected from the group consisting of =0 and =S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2-, -N(R*>, -0-, and -S-;
provided that when the bond with the dotted line represents a double bond, R3 is absent, and when the bond with the dotted line represents a single bond, R* is present; and
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant; and
(e) Formula (XII):
Figure imgf000191_0003
Formula (XII);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof,
wherein, as valence and stability permit:
the bond with a dotted line optionally represents a single or double bond,
R1 and R2 are independently selected from the group consisting of hydrogen, Ci.galkyl, C2_,;alkenyl, and C2_6alkynyl;
wherein R1 and R2 may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH,— O, -SH, S. -NH2, - O H i. -O(CM0alky3), -O(C2„! 0a3kenyl), ~O(C2.!0alkynyi), -S(C,.[0alkyi), -S(C2.10alkenyi), -S(C2-,0alkynyi), Al li C -lik l i.
-NH(C2.l0alkenyl), -NH(C oalkynyl),
Figure imgf000192_0001
-N(<¾.)0alkenyl)2, and -N(C2_[0alkynyl)2;
R" and R4 are independently selected from the group consisting of hydrogen, C;.6alkyl, C2_6a.lken.yl, C2_6alkynyl, Ci_6acyl, C) -6acyloxy,
Figure imgf000192_0002
Figure imgf000192_0003
wherein each of RJ and R"* may be optionally independently substituted with one or more substituents selected from the group consisting of halo, -OH, =0, -SH, =5, -NH2, -C02H, -O(Cl -!0alkyl), -0(C2-ioalkenyl), -O(C2-l 0alkynyl), -S{CMOaikyl), -S(C2-ioalkenyl), -S(C2_i0alkynyl), NH(Ci.l 0alkyl), H(C2.ioalkenyl), NH(C2_<0alkynyl), (Ci.10alkyl)2, N(C2..0alkenyl)2,
(C2_!oalkynyl)2, Ci.io cyl, C;_]0aeyloxy, Ci.ioacylamino, Ci.ioacylthioxy, Ci_;0alkylester, Ci.ioalkenylester, Ci_;0alkynylester, Ci_ioalkylamide,
Ci.ioalkenylamide, C^soalkynylamide, Ci.ioalkylthioester, Ci .ioalkenylthioester, and Ci .ioalkynylthioester; and
X and Y are independently selected from the group consisting of a direct bond, C].6alkyl, C2.6alkenyl,€2.6alkynyl, N(R*), -0-, -S-, =0, and =$, provided that when either X or Y is— O or =S, then RJ and R4, respectively, are absent,
wherein R" is selected from the group consisting of hydrogen, C].flalkyl,
Figure imgf000192_0004
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant.
2. The composition according to claim 1, wherein said compound is a compound according to Formula (I), wherein as valence and stability permit:
R1 is absent or is selected from the group consisting of hydroxy!, CY^alkoxy, and
C].3aeyloxy;
R' is selected from the group consisting of hydrogen, Chalky!, C2.3alkenyl, and C2..3alkynyl;
R3 is selected from the group consisting of hydrogen and Ci .ialkoxy;
R'* is selected from the group consisting of hydroxy!, Qjalkoxy, and Cuacyloxy; m is 1 ;
n is 0;
p is 1 ; and
t is 1 ;
wherein all dotted bonds indicate optional carbon-carbon double bonds,
3. The composition according to claim 1, wherein said compound according to Formula (!) is a compound selected from the group consisting of: compound ac
Figure imgf000193_0001
Formula ( la); or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R , RJ, and
R4 are as defined for the compound of Formula (I) in claim 1 ; or
(b) a compound according to Formula (lib):
Figure imgf000193_0002
Formula (lib);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomei' thereof, wherein, as valence and stabiiity permit, R2, RJ, and R4 ar defined for the compound of Formula (I) in claim 1 ; compound according to Formula (He):
Figure imgf000193_0003
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R' , R\ R}, and R4 are as defined for the compound of Formula (1) in claim 1 ;
(d) a. compound according to Formula (lid):
Figure imgf000194_0001
Formula (lid);
or a comestibiy or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R', R\ R}, and R4 are as defined for the compound of Formula ( ) in claim 1 ;
(e) a compound according to Formula (lie):
Figure imgf000194_0002
Formula (lie);
or a comestibiy or biologically acceptable salt or derivative thereof, or an enaniiomer or diastereomer thereof, wherein, as valence and stability permit, R1, R , R3, and R4 as defined for the compound of Formula (Ϊ) in claim 1 ;
(f) a compound according to Formula (ilf):
Figure imgf000194_0003
Formula (Ilf);
or a comestibiy or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, R'!, and R* are as defined for the compound of Formula (I) in claim 1 ;
(g) a compound according to Formula (ilg):
Figure imgf000194_0004
Formula (ilg);
or a comestibiy or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R' and R"* are as defined for the compound of Formula (I) in claim 1 ; and
(h) a compound according to Formula (Till): 94 -
Figure imgf000195_0001
Formula (Ilh);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R' , R3, and R4 are as defined for the compound of Formula (Ϊ) i claim 1 ,
4, The composition according to claim 1 , wherein said compound according to
Formula (I) is a compound selected from the group consisting of; compound according to Formula (Ilia):
Figure imgf000195_0002
Formula (Ilia);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R" is as defined for the compound of Formula (I) in claim 1 ; compound according to Formula (iilb):
Figure imgf000195_0003
Formula (Ilib);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomei' thereof, wherein, as valence and stabiiity permit, R2 is as defined for the compound of Formula (I) in claim 1 ;
(c) a compound according to Formula (IIIc): 95 -
Figure imgf000196_0001
Formula (Me);
or a comestibly or biologically acceptable salt or derivative thereof, or enantiomer or diastereomer thereof, wherein, as valence and stability permit, R", R3, and defined for the compound of Formula (I) in claim 1 :
(d) a compound according to Formula (Hid):
Figure imgf000196_0002
Formula (Hid);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R'', 3, and R"* are defined for the compound of Formula (I) in claim 1 ; and
(e) a compound according to Formula (Me):
Formula (Me);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof, wherein, as valence and stability permit, R2, R', and R* are as defined for the compound of Formula (i) in claim 1.
5. The composition according to claim 1, wherein said compound according to
Formula (I) is a compound selected from the group consisting of: compound according to Formula (iVc):
Me Me or a comestibly or biologically acceptable salt or derivative thereof, or an euautiomer or diastereomer thereof, wherein, as valence and stoibility permit, R4 is as defined for the compound of Formula (I) in claim 1 ;
(b) a compound according to Formula (IVd):
Figure imgf000197_0001
Formula (IVd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined for th compound of Formula (I) in claim 1 ; and
(c) a compound according to Formula (IVe):
Figure imgf000197_0002
Formula (IV e);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiorner or diastereomer thereof, wherein, as valence and stability permit, R4 is as defined for the compound of Formula (I) i claim 1.
6. The composition according to claim i, wherein said compound according to
Formula (V) is a compound selected from the group consisting of;
(a) a compound of Formula (Via):
Figure imgf000197_0003
Formula (Via);
or a comestibly or biologically acceptable salt or derivative thereof, wherein, as valence and stability permit, and R4 are as defined for the compound of Formula ( V) in claim 1, wherein the carbon marked with * optionally has R or S stereochemistry mixture of R and S stereochemistry ; and
(b) a compound of Formula (VIb):
R3
R5
Formula (VIb);
or a comestibly or biologically acceptable salt or derivative thereof, wherein, as valence and stability permit, ', R4, and RJ are as defined for the compound of Formula (V) in claim 1.
7. The composition according to claim 1, wiierein said compound according to
Formula (V) is a compound selected from:
(a) a compound of Formula (Vila);
Figure imgf000198_0001
Formula (Vila);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diasiereomer thereof,
wherein, as valence and stability permit:
R" is selected from the group consisting of hydrogen. Chalky!; or
Figure imgf000198_0002
optionally substituted by hydroxy 1, amino, mono- or disubstituted Chalky! amino, or carboxyl; and
wherein the carbon marked with * optionally has R or 5 stereochemistry or is mixture of R and S stereochemistry .
8. The composition according to claim 3 , wherein said compound according to
Formula (VIII) is a compound selected from the group consisting of: (a) a compound of Formula (IXa):
Figure imgf000199_0001
Formula (IXa);
or a comestibly or biologically acceptable salt or derivative thereof, or an euautiomer or diastereomer thereof, wherein, as valence and stoibility permit, R4 is as defined for the compound of Formula (Viil) in claim 1 ;
(b) a compound of Formula (IXb):
Figure imgf000199_0002
Formula (IXb);
or a comestibly or biologically acceptable salt or derivative thereof, or an euautiomer or diasiereomer thereof,
wherein, as valence and stability permit;
R1 and R4 are as defined for the compound of Formula (Vlii) in claim m is 0-2;
(c) a compound of Formula (IXc):
Figure imgf000199_0003
Formula (IXc);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R1 and R4 are as defined for the compound of Formula (Vlii) in claim 1 ; R' is Ci.galk l; and
m is 0-2; and
(d) a compound of Formula (IXd):
Figure imgf000200_0001
Formula (IXd);
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or diastereomer thereof,
wherein, as valence and stability permit:
R!, RJ, and R are as defined for ihe compound of Formula (VIII) in claim 1 ; and m is 0-2,
9. The composition according to claim 1, wherein said compound is a compound according to Formula (XI), wherein as valence and stability permit:
(a) R1, R3, R6, and R' are independently selected from the group consisting of hydrogen, ( ' ,.:;!
Figure imgf000200_0002
R4 is absent or selected from the group consisting of hydrogen,
Figure imgf000200_0003
C2-6alkeny3, C2-«alkyQy], Ci-eacyl,
Figure imgf000200_0004
Ci-ealkeoylester, and Ci-ealkynylester;
wherein R4 may be optionally substituted with one or more substituents selected from the group consisting of -OH, =0, -SH, and =S;
R5 is absent or selected from the group consisting of hydrogen, Chalky!, C^alkenyl, and ( ealkynyl;
wherein R6 and R' are optionally taken together to form =0, =S or
= (Ra)2;
wherein each Ra is independently selected from the group consisting of hydrogen, C!-6alkyl, C2-6alkenyl, and C2.6alkynyl;
wherein when the bond with the dotted line represents a double bond and R' is present, X is selected from the group consisting of C(Ra)- and =N-;
wherein when the bond with the dotted line represents a double bond and R' is absent, X is selected from the group consisting of =0 and -S; and wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Rd)2-, -N(Rd)-, -0-, and -S-;
provided that when the bond with the doited line represents a double bond, RJ is absent, and when the bond with the dotted line represents a single bond, R4 is present;
(b) R', R', R'\ R*, and R' are independently seiected from the group consisting of hydrogen, Chalky],
Figure imgf000201_0001
R4 is absent or seiected from the group consisting of hydrogen. Chalky!, CVealkenyl, C2-«alkynyl, and
Figure imgf000201_0002
wherein R" may be optionally substituted with =0 or =S;
R1 is absent or seiected from the group consisting of hydrogen, Ci jalkyl, C2.3alkenyl, and
Figure imgf000201_0003
wherein Rft and R7 are optionally taken together to form =0, or
-C(Ra)2;
wherein each Ra is independently selected from the group consisting of hydrogen. Chalky!, Cj-salkenyl, and C2.3alk.ynyl;
wherein when the bond with the dotted line represents a double bond and R is present, X is selected from the group consisting of =C(R")- and =Ν·;
wherein when the bond with the dotted line represents a double bond and R'f is absent, X is selected from the group consisting of— Ό and =S; and
wherein when the bond with the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2-, -N(Ra)-, -0-, and -S-;
pro vided that, when the bond with the dotted line represents a double bond, ? is absent, and when the bond with the dotted line represents a single bond, R'* is present; or
(c) R!, R^, R", R°, and R' are independently selected from the group consisting of hydrogen, Chalky!, C^alkenyl, and C2.3alky. nyl;
R4 is absent or seiected from the group consisting of hydrogen. Chalky!,
Figure imgf000201_0004
wherein R4 may be optionally substituted with =0 or =S;
R5 is absent or selected from the group consisting of hydrogen, C1-3alkyl, C2-3alk nyl, and C2.3alkynyl;
wherein R6 and R' are optionally taken together to form :==0, ==:S or
Figure imgf000201_0005
wherein each Ra is independently selected from the group consisting of hydrogen, Chalky!, C2.3alkenyl, and C2.3alk)rnyl;
wherein when the bond with the dotted line represents a double bond and R4 is present, X is =C(R*)s wherein when the bond with the dotted line represents a double bond and R is absent, X is selected from the group consisting of ~0 and ~S; and
wherein when the dotted line represents a single bond, X is selected from the group consisting of -C(Ra)2- and -Q-;
provided that when the doited line represents a double bond, R5 is absent, and when the bond with the doited line represents a single bond, R'F is present.
The composition according to claim 3 , wherein said compound is a cording to Formula (XII), wherein as valence and stability permit:
(a) the bond with a dotted line optionally represents a single or double bond,
R1 and R are independently selected from the group consisting of hydrogen, Chalky!, C2.6alkenyl, and C^alkynyl;
R3 and R4 are independently selected from the group consisting of hydrogen,
Figure imgf000202_0001
acyl,
Figure imgf000202_0002
wherein each of R' and R4 may be optionally independently substituted with one or more substiruents selected from the group consisting of -OH, ==€>, -SH, =S, C] -6acyloxy, C]_6acylthioxy, Ci.6a]kylester, Ci-ealkenylester, Q-ealkynylester, Ci-ealkylthioester, Ci _6alkenylthioester, and
Figure imgf000202_0003
X and Y are independently selected from the group consisting of a direct bond, C^alkyl, C2^alkeayl, C2.6alkynyl, N(RA), -0-, -S-, ===0, and ~S, provided that when either X or Y is =0 or =S, then RJ and R4, respectively, are absent, and
wherein Ra is selected from the group consisting of hydrogen, Chalky], C2.6alkenyl, and C .6alkynyl;
(b) the bond with a dotted line optionally represents a single or double bond,
R' and R2 are independently selected from the group consisting of hydrogen, Ci ^alkyl, C2.4.alkenyl, and C^alkynyl;
R! and R4 are independently selected from the group consisting of hydrogen, Ci .4alkyl, C2.4alkenyl, C2..4alkynyi, and CV+acyl; wherein each of R3 and R4 may be optionally independently substituted with one or more substituents selected from the group consisting of -OH, =0, -SH,
Figure imgf000202_0004
Figure imgf000202_0005
Ci .4alkenylthioesier, and C Malkynylthioesier; and
X and Y are independently selected from the group consisting of a direct bond. Chalky!, Q^alkenyl, C2„6alkynyl, -0-, -S-, ), and =S, provided that when either X or Y is or ~S, then R" and R4, respectively, are absent; or
(c) the bond with a dotted line optionally represents a single or double bond,
R! and R are independently selected from the group consisting of hydrogen, Chalky!, C2^alkenyl, and C2_4alkynyl;
RJ and R4 are independently absent or independently selected from the group consisting of hydrogen, Chalky!, C2-4 lken l, C2-4alkyny3, C i.4acyl;
wherein each of R" and R4 may be optionally independently substituted with one or more substituents selected from the group consisting of -OH,
Figure imgf000203_0001
Ci.4alkenylester, and Ci„4alkynylester; and
X and Y are independently selected from the group consisting of a direct bond, Chalky!, C2.4alk.enyl, C2.4aBcyn.yl, -0-, -S-, =0, and =S, provided that when either X or Y is =0 or =S, then R5 and R4, respectively, are absent.
! 1 , The composition according to claim 1, wherein said compound is selected from the group consisting of Compounds 1-94 and having the structure:
Me Me 0
Compound
1
Me Me 0
Compound
2
Me Me 0
Compound <X r- 3
Me Me 0
Compound
4
Me Me 0
Compound
5
Figure imgf000204_0001
Figure imgf000205_0001
Figure imgf000206_0001
Figure imgf000207_0001
Figure imgf000208_0001
Figure imgf000209_0001
Figure imgf000210_0001
Figure imgf000211_0001
Figure imgf000212_0001
Figure imgf000213_0001
Figure imgf000214_0001
or comestibly or biologically acceptable derivatives thereof, or eoaotiorners or diastereomers thereof ,
12. A composition comprising a compound selected from the group consisting of
Compounds 95- 333 and having the structure:
Figure imgf000214_0002
Figure imgf000215_0001
Figure imgf000216_0001
Figure imgf000217_0001
Figure imgf000218_0001
Figure imgf000219_0001
Figure imgf000220_0001
or a comestibly or biologically acceptable salt or derivative thereof, or an enantiomer or
diastereomer thereof;
wherein the composition is edible and capable of reducing bitter taste of a bitter tastant
13. The composition according to any one of claims 1-12 further comprising a bitter tastani.
The composition according to claim 13, wherein the bitter tastant is KG or potassium lactate.
15. The composition of any one of claims 1 - 14, wherein the composition further comprises one or snore component selected from the group consisting of: NaCl, sodium lactate, and sugar,
16. A food product comprising the composition of any one of claims 1-15. i 7, A method of preparing an edible composition comprising:
(a) providing a comestibly acceptable carrier; and
(b) adding to said comestibly acceptable carrier a compound according to Formula (I), Formula (la), Fosmula (lia), Formula (Ilia), Formula (lib), Formula (liib),
Formula (lie). Formula (life), Formula (IVc), Formula (lid). Formula (liid), Formula (IVd), Formula (lie), Formula (lile), Formula (TVe), Formula (Hi), Formula (Tig), Formula (Till), Formula (V), Formula (Via), Formula (VTb), Formula (Vila), Formula (VTII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (iXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof
18. The method according to claim 17, wherein said comestibly acceptable carrier is inherently bitter, 19. The method according to claim 18, wherein the comestibly acceptable carrier comprises a bitter tasting potassium salt.
20. The method according to claim 1 , wherein the potassium salt is KCi or potassium lactate.
21. The method according to any one of claims 17-20, wherein the edible composition further comprises one or snore component selected from the group consisting of:
NaCl, sodium lactate, and sugar.
22. The method according to claim 17, wherein the method further comprises:
(c) adding a bitter tastant to said comestibly acceptable carrier, wherein said bitter tastant is a potassium salt.
23. The method according to claim 22, wherein the potassium salt is KCI or potassium lactate.
24. The method according to claim 22 or 23, wherein the edible composition further comprises one or more component selected from the group consisting of: NaCl, sodium lactate, and sugar, 25. A method of reducing the amount of NaCl in an edible composition comprising:
(a) replacing an amount of NaCl used in preparing said edible composition with an amount of KCI; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (lia), Formuia (Ilia), Formula (lib),
Formula (liib), Formuia (lie), Formula (IIIc), Formula (IVc), Formula (lid). Formula (lild ), Formula (IVd), Formula (lie), Formuia (ille), Formula (IVe), Formula (Hi), Formula (Ilg), Formula (iih). Formula (V ), Formuia (Via), Formula (Vib), Formuia (Vila), Formuia (VIII), Formula (IXa), Formuia (IXb ), Formula (IXc), Formuia (Did), Formuia (XI) or Formuia (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof, to produce an edible composition with reduced NaCl.
26. The method according to claim 25, wherein the amount of compound incorporated into the edible composition is sufficient to permit replacement of the amount of NaCl present in the edible composition by up to 25%, 50%, 75% or 100%.
27. The method according to claim 25 or 26, wherein the edible composition with reduced NaCl maintains a salty flavor.
28. A. method of reducing the amount of sodium lactate in an edible composition comprising;
(a) replacing an amount of sodium lactate used in preparing said edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (lla), Formula (Ilia), Formula (lib),
Formula (Tllb), Formula (lie), Formula (lllc), Formula (iVc), Formula (lid), Formula (Hid), Formula (TVd), Formula (He), Formula (Tile), Formula (IVe), Formula (lit), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -58 and 61- 134, as described herein, or combinations thereof to produce an edible composition with reduced sodium lactate.
29. The method according to claim 28, wherein the amount of compound incorporated into the edible composition is sufficient to permit replacement of the amount of sodium lactate present in the edible composition by up to 25%, 50%, 75% or 100%,
30. The method according to claim 28 or 29, wherein the edible composition with reduced sodium lactate has the same shelf life as an edible composition comprising the full amount sodium lactate.
.31 , A method of reducing the amount of sugar in an edible composition comprising:
(a) replacing an amount of sugar used in preparing an edible composition with an amount of Acesulfame K; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (lla), Formula (Ilia), Formula (Tib), Formula (illb), Formula (ITc), Formula (Tile), Formula (IVc), Formula (lid), Formula (liid), Formula (IVd), Formula (lie), Formula (Hie), Formula (IVe), Formula (Hi), Formula (Ilg), Formula (ilh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -58 and 63 -134, as described herein, or combinations thereof, to produce an edible composition with reduced sugar.
32. The method according to claim 31 , wherein the amount of compound incorporated into the edible composition is sufficient to permit replacement of the amount of sugar present in the edible composition by up to 25%, 50%, 75% or 100%.
33. The method according to claim 31 or 32, wherein the edible composition with reduced sugar maintains a sweet flavor.
34. A. method of reducing the sodium intake of a subject, the method comprising:
(a) replacing an amount of a sodium salt used in preparing an edible composition with an amount of a potassium salt; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (lla), Formula (ilia), Forsnula (lib), Formula (Tflb), Formul (lie), Forsnula (IIlc), Formula (IVc), Formula (lid), Formula (Hid), Formula (TVd), Formula (lie), Formula (Tile), Formula (iVe), Formula (ITf), Formula (ilg), Formula (Tlh), Formula (V), Formula (Via), Forsnula (Vib), Forsnula (Vila), Formula (VIII), Formula (TXa), Forsnula (TXb), ForsTiula (TXc), Forsnula (IXd), Forsnula (XI) or Forsnula (XII), as described herein, or combinations thereof, or any one of Compounds 1 -58 and 61- 134, as described herein, or combinations thereof.
35. The method according to claim 34, wherein the sodium salt is NaCi and the potassium salt is KG.
36. The method according to claim 34, wherein the sodium salt is sodium lactate, and the potassium salt is potassium lactate.
37. The method according to any one of claims 34-36, wherein the method further comprises: (c) identifying a subject in need thereof.
38. The method according to any one of claims 34-37, wherein the amount of compound incorporated into the edible composition is sufficient to reduce sodium intake by up to 25%, 50%, 75% or 100%.
39. A method of reducing the sugar intake of a subject, the method comprising:
(a) replacing an amount of sugar used in preparing an edible composition with an amount of a Acesulfame K; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formula (la), Formula (ITa), Formula (Ilia), Forsnula (lib),
Formula (Illb), Formula (Tic), Formula (lilc), Formula (IVc), Formula (lid), Formula (Hid), Formula (TVd), Formula (He), Formula (Hie), Formula (IVe), Formula (ilf), Formula (Ilg), Formula (Tlh), Formula (V), Formula (Via), Formula (Vib), Formula (Vila), Formula (VIII), Formula (TXa), Forsnula (TXb), Formula (TXc), Forsnula (IXd), Formula (XI) or Forsnula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof.
40. The method according to claim 39, wherein the method further comprises (c) identifying a subject in need thereof. 41 . The method according to claim 39 or 40, wherein the amount of compound incorporated into the edible composition is sufficient to reduce sugar intake by up to 25%, 50%, 75% or 100%,
42. A method of reducing bitter taste attributed to a bitter tastant in an edible composition, wherein said bitter tastant is a potassium salt, said method comprising: (a.) providing an edible composition comprising a bitter tastant; and
(b) adding an effective amount of a compound according to Formula (I), Formula (la), Formula (lla), Formula (Ilia), Formula (lib), Formula (Tllb), Formula (lie),
Formula (liic), Formula (TVc), Formula (lid), Formula (Hid), Formula (IV d), Formula (Tie), Formula (IITe), Formula (TVe), Formula (Ilf), Formula (Tig), Formula (I!h), Formula (V),
Formula (Via), Formula (VTb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof, to the edible composition generated in (a) such that any bitter taste induced by the bitter tastant is reduced, 43, A method of reducing bitter taste attributed to a bitter tastant in an edible composition, wherein said bitter tastant is a potassium salt, said method comprising;
(a) ingesting an effective amount of compound according to Formula (I), Formula (la), Formula (lla), Formula (Ilia), Formul (lib), Formula (Tllb), Formul (lie),
Formula (IITc), Formula (TVc), Formula (lid), Formula (Tlid), Formula (IV d), Formula (He), Formula (IITe), Formula (TVe), Formula (ilfj, Formula (Tig), Formula (i!h), Formula (V),
Formula (Via), Formula (VTb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61- 134, as described herein, or combinations thereof, before, along with, or after the edible composition such that any bitter taste induced by the bitter tastant is reduced.
44, The method according to claim 42 or 43, wherein the bitter taste induced by the bitter tastant is reduced by up to 25%, 50%, 75% or 100%
45. The method according to any one of claims 42-44, wherein the potassium salt is KC1 or potassium lactate. 46, The method according to any one of claims 42-45, wherein ihe edible composition further comprises aC'l, sodium lactate, or sugar.
47. A method of preserving an edible composition comprising:
(a) providing an edible composition; and
(b) incorporating into the edible composition potassium lactate and an effective amount of a compound according to Formula (I), Formula (la), Formula (Ha),
Formula (Ilia), Formula (lib), Formula (Mb), Fomiuia (lie), Formuia (illc), Formula (IVc), Formula (lid), Formula (Hid), Formula (iVd), Formula (He), Formula (Hie), Formula (iVe), Formula (Hi), Formula (Hg), Formuia (Ilh), Formula (V), Formula (Via), Formula (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof.
48. A method of reducing the amount of sodium in an edible composition while preserving the edible composition, the method comprising:
(a) replacing an amount of sodium lactate used in preparing said edible composition with an amount of potassium lactate; and
(b) incorporating into the edible composition an effective amount of a compound according to Formula (I), Formuia (ia), Formuia (Ha), Formula (Ilia), Formula (lib). Formula (Hib), Formula (lie), Formula (Illc), Formula (IVc), Fonmila (lid), Formula (Hid), Formula (IVd), Formula (He), Formula (Me), Fomiuia (IV e), Formuia (Hi), Formula (Ilg), Formula (Ilh), Formula (V), Formula (Via), Formula (VIb), Fonmila (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof. 49. The method according to any one of claims 17-48, wherein the edible composition is selected from the group consisting of a food product, a consumer product, and a pharmaceutical composition.
50. A method of inhibiting, reducing, or eliminating ihe perception of a bitter taste in a subject, wherein said bitter tastant is a potassium salt, said method comprising:
(a) placing a compound according to Formula (I), Formula (la). Formula (Ha),
Formula (Ilia), Formula (lib), Formula (Mb), Formula (lie), Formuia (Illc), Formula (IVc), Formula (lid), Formula (Hid), Formuia (IVd), Formula (lie), Formuia (Me), Formula (IVe), Formula (TIf), Formula (ilg). Formula (Ilh), Formula (V), Formula (Via), Formuia (VIb), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formuia (XII), as described herein, or combinations thereof, or any one of Compounds 1-58 and 61-134, as described herein, or combinations thereof in the oral cavity of the subject.
51 . The method according to claim 50, wherein the bitter taste is due to Ci or potassium lactate. 52. A pharmaceutical composition comprising:
(a) a bitter tasting pharmaceutical acti ve ingredient, wherein said pharmaceutical active ingredient is a potassium salt; and
(b) a compound according to Formula (I), Formula (Ta), Formula (iia), Formula (ilia), Formula (Tib), Formula (Ilib), Formula (lie), Formula (liic), Formula (TVc), Formula (iid), Formula (illd), Formuia (TVd), Formula (Tie), Formul (lile), Formula (IVe), Formula (Til), Formula (lie). Formula (lih), Formula (V), Formula (Via), Formuia (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (TXe), Formula (IXd), Formula (XI) or Formula (XII), as described herein, or combinations thereof, or any one of Compounds 3 -58 and 61-134, as described herein, or combinations thereof. 53. A pharmaceutical composition comprising:
(a) a pharmaceutical active ingredient;
(b) a bitter tastant, wherein said bitter tastant is a potassium salt; and
(c) a compound according to Formula (Ϊ), Formula (la), Formula (Iia), Formula (Ilia), Formula (Tib), Formula (Ilib), Formula (He), Formula (liic), Formul (TVc), Formula (lid), Formula (illd), Formuia (TVd), Formula (Tie), Formul (Hie), Formula (IVe), Formula (Til), Formula (lig), Formula (lih), Formula (V), Formula (Via), Formuia (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formui (XII), as described herein, or combinations thereof, or any one of Compounds 1 -58 and 61-134, as described herein, or combinations thereof. 54. A consumer product comprising:
(a) a bitter tasting ingredient, wherein said bitter tasting ingredient is a potassium salt; and
(b) a compound according to Formula (I), Formula (la). Formula (Ha), Formula (Ilia), Formula (lib), Formula (Ilib), Formula (He), Formula (IIIc), Formuia (IVe), Formula (iid). Formula (Illd), Formuia (IVd), Formula (lie), Formuia (lile), Formuia (IVe), Formula (Til), Formula (Tig), Formula (iih), Formula (V), Formula (Via), Formuia (Vib), Formula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Formula (IXd), Formula (XI) or Formui (XII), as described herein, or combinations thereof, or any one of Compounds 1 -58 and 61-134, as described herein, or combinations thereof. 55, A consumer product for reducing bitter taste of a bitter tastant, wherein said bitter iastani is a potassium salt, and wherein said consumer product comprises:
(a) a compound according to Formula (I), Formula (la), Formula (Ila), Formula (Ilia), Formula (lib), Formula (Illb , Formula (lie), Formula (IIIc), Formula (IVc), Formula (lid), Formula (Hid), Formula (IVd), Formula (lie), Formula (lile), Formul (IVe), Formula (lif), Forsnula (Ilg), Formula (lib). Formula (V), Forsnula (Via), Formula (Vib), Forsnula (Vila), Formula (VIII), Formula (IXa), Formula (IXb), Formula (IXc), Forsnula (IXd), Fos'snula (XI) or Formula (Xil), as described herein, or combinations thereof, or any one of Compounds 1-58 and 6 i -134, as described herein, or combinations thereof.
PCT/US2011/032780 2010-04-15 2011-04-15 Compounds, compositions, and methods for reducing or eliminating bitter taste WO2011130705A1 (en)

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MX2012011997A MX346673B (en) 2010-04-15 2011-04-15 Compounds, compositions, and methods for reducing or eliminating bitter taste.
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US13/641,213 US8865779B2 (en) 2010-04-15 2011-04-15 Compounds, compositions, and methods for reducing or eliminating bitter taste
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JP2013505203A JP6068330B2 (en) 2010-04-15 2011-04-15 Compounds, compositions and methods for reducing or eliminating bitterness
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UAA201212838A UA112745C2 (en) 2010-04-15 2011-04-15 COMPOUNDS, COMPOSITIONS, AND METHODS TO REDUCE OR REMOVE BITTER TASTE
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US15/178,149 US9872514B2 (en) 2010-04-15 2016-06-09 Compounds, compositions, and methods for reducing or eliminating bitter taste
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JP2013518850A (en) * 2010-02-04 2013-05-23 ジボダン エス エー Oxalamide derivatives as umami flavoring agents
US20130064781A1 (en) * 2011-09-09 2013-03-14 Lvmh Recherche Method for masking the bitterness of a uv-screening agent
US9750673B2 (en) 2011-09-09 2017-09-05 Lvmh Recherche Cosmetic composition comprising a bitter compound, a fragrance, an extract of Stevia and a salt
WO2013058758A3 (en) * 2011-10-20 2014-04-03 Chromocell Corporation Compounds, compositions, and methods for reducing or eliminating bitter taste
AU2011379360B2 (en) * 2011-10-20 2016-08-11 Chromocell Corporation Compounds, compositions, and methods for reducing or eliminating bitter taste
US9706790B2 (en) 2011-10-20 2017-07-18 Chromocell Corporation Compounds, compositions, and methods for reducing or eliminating bitter taste
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US11540539B2 (en) 2013-02-08 2023-01-03 General Mills, Inc. Reduced sodium food products
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WO2020025693A1 (en) 2018-08-02 2020-02-06 Firmenich Sa Monoester sugar derivatives as flavor modifiers
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WO2021219725A1 (en) 2020-04-29 2021-11-04 Bunge Loders Croklaan B.V. Composition, confectionery product and process

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