MXPA06001509A - Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof - Google Patents

Abstract

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

Description

FLAVORS NOVEDOSOS, MODIFIERS OF TASTE. DEGUSTING, TASTING IMPROVERS. ACRES OR SWEET DEGUSTANTS, AND / OR IMPROVERS AND USE OF THEM FIELD OF I NVENTION The present invention relates to the discovery of taste modifiers and tasters, such as a flavoring agent or flavoring agents and flavor or taste enhancers, more particularly, modifiers of tasty flavor ("acre") or sweet, - flavorful or sweet flavoring agents and flavor improvers tasteful or ulce, for foods, beverages and other edibles or orally administered med ical products or compositions.

BACKGROUND OF THE INVENTION For centuries, various natural and non-natural compositions and / or compounds have been added to edible (digestible) foods, beverages, and / or orally administered oral compositions to improve their taste. Although it has been known that there are only a few basic types of "flavors", the biological and biochemical basis of flavor perception was misunderstood, and most of the flavor enhancement or taste modification agents have been largely discovered. simple trial and error process. There has been a significant recent prog- ress to identify useful natural flavoring agents, such as, for example, sweeteners such as sucrose, fructose, glucose, erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, certain known natural terpenoids, flavonoids or protein sweeteners. . See for example, a recent article entitled "Noncariogenic Intense Natural Sweeteners" by Kinhorn et al. (Med Res Rev 18 (5) 347-360, 1998), which recently discusses natural materials discovered that are much more intensely sweet than common natural sweeteners such as sucrose, fructose and the like. Similarly, there has been recent progress in identifying and marketing new artificial sweeteners, such as aspartame, saccharin acesulfame-K, cyclamate, sucralose and aiitame, etc., see a recent article by Ager, et al. (Angew Chem Int. Ed. 1998, 37, 1802-1817). The full description of the two references identified above are therefore incorporated herein by reference, for the purpose of describing at least a portion of the knowledge of those of ordinary skill in the art with respect to known sweetening agents. However, there is a need in the art for new and improved flavoring agents. For example, one of the five known basic flavors is the "tasty" or "pungent" taste of monosodium glutamate ("MSG"). MSG is known to produce adverse reactions in some people, but very little progress has been made to identify artificial substitutes for MSG. It is known that few materials of natural origin can increase or improve the effectiveness of MSG as a flavoring flavoring agent, so that less MSG might be necessary for a given flavor application. For example, the nucleotide compounds of inopine monophosphate (I MP) or guanosine monophosphate (GMP) of natural origin are known to have a multiplier effect on the tasty taste of MSG, but IMP and GMP are very difficult and expensive to isolate and purify from natural sources or synthesize, and therefore have only practical application limited to most commercial needs in food or medicinal compositions. Less expensive compounds that would provide the same MSG flavor, or improve the effectiveness of any MSG that is presented, could be of very high value. Similarly, the discovery of compounds that are either novel "High Density" sweeteners (that is, they are often educorants than sucrose) would be of value, or of any compounds, that significantly increase the sweetness of natural or artificial sweeteners. , so that less of those caloric or non-caloric sweeteners would be required, it would be of a very high utility and value. In recent years, substantial progress has been made in biotechnology in general, and in the better understanding of biological and biochemical phenomena underlying taste perception. For example, flavor receptor proteins have recently been identified in mammals that are involved in taste perception. Particularly, two different families of the receptors coupled with the G protein are believed to be involved in taste perception. T2Rs and T1Rs have been identified (See for example, Nelson, et al., Cell (2001) 106 (3): 381-390; Adler, et al., Cell (2000) 100 (6): 693-702; Chandrashekar, et al., Cell (2000) 100: 703-71 1; Matsunami, et al., Number (2000) 404: 601-604; Li, eí al., Proc. Nati Acad. Sci. USA (2002) 99: 4962-4966; Montmayeur, et al., Nature Neuroscience (2001) 4 (S): 492-498: US Patent 6,462, 148; and PCT publications WO 02/06254, WO 00/63166 of the art, WO 02/064631 and WO 03/001876, and US Patent Publication 2003-0232407 A1). The full descriptions of the articles, the patent applications and the issued patents immediately cited in an earlier manner and therefore are hereby incorporated by reference, for all purposes, including their descriptions of the identities and structures of the receptor proteins of mammalian flavor of T2R and T1 R and methods for artificially expressing those receptors in cell lines and using resulting cell lines for selection compounds as "tasty" or "sweet" flavoring agents. While the T2R family includes a family of 25 genes that are involved in the perception of bitter taste, the T1 R only includes three members, T1 R1, T1 R2 and T1 R3 (see Li, et al., Proc. NAtl. Sci. USA (2002) 99: 4962-4966). Recently, it was discovered in WO 02/064631 and / or WO 03/001876 that certain T1 R members, when co-expressed in suitable mammalian cell lines, assemble to form functional flavor receptors. Particularly, it was found that the co-expression of T1 R1 and T1 R3 in a suitable host cell results in a functional taste receptor ("acre") T1 R1 / T1 R3 that responds to the flavorful taste stimulus, including glutamate of monosodium Similarly, it was found that co-expression of T1 R2 and T1 R3 in a suitable host cell results in a functional "sweet" T1 R2 / T1 R3 taste receptor that responds to different flavor stimuli including artificial sweeteners and natural origin (See Li, et al. (Id.) The references cited above also describe assays and / or high-throughput screens that measure the receptor activity T1 R1 / T1 R3 or T1 R2 / T1 R3 by fluorometric imaging in the presence of target compounds Highly selected assays and / or screening methods described above were employed to identify initial "leader" compounds that modulate the activity of the "tasty" taste receptors of T1 R1 / T1 R3 or taste receptors "sweet" of the T1 R2 / T1 R3, then ventured into a repetitive and complex process, long for research, evaluation and optimization, so that it led to various inventions described later entity.

COMPENDIUM OF THE INVENTION The invention has many aspects, all of which are in some way related to certain amide compounds of non-natural origin and / or amide derivative compounds having the generic structure shown below in Formula (I): wherein R1, R2 and R3 can be and are independently further defined in various ways, as further detailed below. In all embodiments of the amide compounds of Formula (I) the group R1 is an organic residue comprising at least three carbon atoms, with a variety of alternative limits in the size and / or chemical characteristics of the R1 group, as well as as will be further described later. In many, but not all embodiments, the ammonium compounds of Formula (I) are "primary" amides, ie one of R2 and R3 is an organic group comprising at least three carbon atoms, although the other of R2 and R3 is hydrogen. The amide compounds of Formula (I) also comprise certain subclasses of amide derivatives or classes of amide-related derivatives, such as, for example, ureas, urethanes, oxalamides, acrylamides, and the like, as will be further described below. Many of the subgenres and species of the "amide" compounds of Formula (I) are shown below to bind to and / or activate one or both of the sweet receptors T1R2 / T1R3"tasty" ("acre") or T1R2 / T1R3 in vitro, in relatively low concentrations in the order of micromolar or low concentrations. The amide compounds are also believed to interact in a similar manner with the sweet or savory taste receptors of animals or humans in vivo, as confirmed by current human taste tests of some of the compounds of Formula (I). Accordingly, many of the sub-genres and species of the "amide" compounds of Formula (I) further described below can, at surprisingly low concentrations, be used as sweet or flavoring flavoring agents, or flavoring or sweet flavoring enhancers. Accordingly, in some embodiments, the invention relates to methods for modulating the palatable flavor of an edible or medicinal product comprising: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the product edible or medicinal or precursor thereof with at least an amount that modulates the flavor tasty, or an amount that modulates the sweet taste, of at least one amide compound of non-natural origin, or an edible acceptable salt thereof, so as to form a modified edible or medicinal product; wherein the amide compound has the formula: wherein R1 comprises an organic or hydrocarbon residue having at least three carbon atoms and optionally one or more heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphorus; and wherein optionally one of R2 and R3 is H, and wherein at least one of the other R2 and R3 comprises an organic or hydrocarbon residue having at least three carbon atoms and optionally one or more heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphorus. The optional additional limitations on the chemical and physical characteristics of the groups R, R2 and R3 will be described later. Some of the amide compounds of Formula (I) have been synthesized by methods known in the prior art for various purposes, but in the knowledge of the invention it has not been previously recognized that such amides can be used at very low concentrations as flavoring agents. tasty or sweet, or flavor enhancers tasty or sweet. In addition, many of the amide compounds of the Formula (I) described herein are novel compounds that have not previously been fully synthesized, and are flavoring or sweet flavoring agents that are effective or flavor enhancers. The invention also relates to edible or medicinal products produced by the processes mentioned above, and edible or medicinal products or ositions, or their precursors containing the amide ounds of Formula (I), which include, but are not necessarily limited to, products and food, beverage and medicinal ositions intended for oral administration, and precursors of same. In many embodiments, one or more of the amide ounds of Formula (I) further identified, described and / or claimed herein, or an edible acceptable salt thereof, may be used in mixtures or in ination with other palatable ounds or known sweets, or used as flavor improvers in food, drink and edible medicine ositions, for human or animal consumption. In some embodiments, the amide ounds of Formula (I), although they have little or perhaps no sweet or savory taste when tested in isolation, can be used at very low concentrations to very significantly improve the effectiveness of other flavorful flavoring agents. or sweet in an edible or medicinal osition or a precursor thereof. The inventions described herein also relate to flavored edible or medicinal products that contain flavor modulation amounts of one or more amide ounds described herein. Many of the amide ounds of Formula (I) and / or their various sub-genders of amide ounds, when used in conjunction with MSG or alone, increase or modulate an in vitro response, and the taste perception is tasty in humans at surprisingly high concentrations. low. In some embodiments, the amide ounds of the invention are T 1 R 1 / T 1 R 3 receptor agonists and can therefore induce or enhance the taste perception of palatability in humans. These ounds can improve, potentiate, modulate or induce other natural and synthetic palatable flavoring agents. In the related embodiments, many of the amide ounds within the scope of Formula (I) are T1 R2 / T1 R3 receptor agonists and therefore may induce the perception of sweet taste in human beings at surprisingly low concentrations. These ounds can improve, potentiate, modulate or induce other synthetic sweet or semi-synthetic flavoring agents, such as, for example, sucrose, fructose, glucose, erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, certain known natural terpenoids, flavonoids, or protein sweeteners, aspartame, saccharin, acelsufame-K, ciciamate, sucralose and alitame and the like or a mixture thereof. Unexpectedly, it has been discovered that in many embodiments of the ounds of Formula (I) there are significant structural similarities and / or overlaps between the amide ounds that can produce or enhance the sweet and flavorful flavors of edible or medicinal ositions, even when it is believed that the relevant biological flavor receptor proteins are significantly different. Even more unexpectedly, it has been found that at least some of the amide ounds of Formula (I) described herein can induce or enhance both sweet and flavorful flavors of edible or medicinal products. Therefore in some aspects the invention relates to ounds of Formula (I) or their various subgenera and species ounds that modulate (e.g., induce, enhance or potentiate) the taste of known natural or synthetic sweetening agents. In some embodiments, the invention relates to novel ounds, flavoring agents, flavor improvers, flavor modification ounds and / or ositions containing the ounds of Formula (I), and their various subgenera and species ounds. In other embodiments, the invention is directed to ounds of Formula (I) or their various ounds of subgenres and species that modulate (e.g., induce, enhance or potentiate) the taste of monosodium glutamate (MSG) or flavoring flavoring agents synthetic In some modalities, the invention relates to edible or medicinal compositions suitable for human or animal consumption, or precursors thereof, which contain at least one compound of the Formula (I), or an edible or pharmaceutically acceptable salt. These compositions will preferably include edible products such as foods or beverages, medicinal products or compositions, intended for oral administration, and oral hygiene products, and additives that when added to these products modulate taste or taste thereof, particularly by improving ( increasing) the tasty flavor and / or ulce of the same. The present invention also relates to novel genera and species of amide compounds within the scope of the compounds of Formula (I), and edible or medicinal derivatives, flavoring agents, products or compositions, including flavoring or sweet flavoring agents and flavor improvers. flavor that they contain. The above discussion simply summarizes certain aspects of the inventions and is not intended, nor should it be construed, as limiting the invention in any way.

DETAILED DESCRIPTION OF THE INVENTION The present invention can be more readily understood by reference to the following detailed description of various embodiments of the invention and the Examples included herein and to the drawings and chemical tables and their prior and following description. Prior to the present compounds, the compositions, and / or methods are described and manifested, it will be understood that unless otherwise specifically stated by the claims, the invention is not limited to specific foods or food preparation methods, carriers or edible or pharmaceutical formulations, or to particular modes for formulating the compounds of the invention in edible or medicinal products or compositions intended for oral administration, because someone of ordinary experience in the relevant techniques is well aware, such things can course, vary. It will also be understood that the terminology used herein is for purposes of describing particular modalities only and is not intended to be limiting.

DEFINITIONS As used herein, the term "medicinal product" includes both solid and liquid compositions that are non-toxic ingestible materials that have a medicinal value or comprise medicinally active agents such as cough syrups, cough drops, aspirins and chewable medicinal tablets. An oral hygiene product includes solids and liquids such as toothpaste or mouthwash. An "edible, biologically or medicinally acceptable carrier or excipient" is a solid or liquid medium and / or composition that is used to prepare a desired dosage form of the inventive compound, to administer the inventive compound in a dispersed / diluted form, so that the biological effectiveness of the inventive compound is maximized. An edible carrier, biologically or medicinally, includes many common food ingredients, such as waters in neutral, acidic or basic pH juices, fruit or vegetable juices, vinegar, marinades, beers, wine, natural water / fat emulsions such as milk or condensed milk, edible oil and fatty matter, fatty acids, low molecular weight oligomers of propylene glycol, glyceryl esters of fatty acids and dispersions or emulsions of such hydrophobic substances in aqueous media, salts such as sodium chloride, wheat flours, solvents such as ethanol, solid edible diluents such as vegetable powders or flours, or other liquid carriers; dispersion or suspension aids; surface active agents; isotonic agents; Thickeners or emulsifiers; conservatives; solid binders; lubricants and the like.

A "flavor" in the present refers to the perception of taste and / or smell in a subject, which includes sweet, sour, bitter, acrid and others. The subject can be a human being or an animal. A "flavoring agent" herein refers to a compound or a biologically acceptable salt thereof that induces a taste or flavor in an animal or a human being. A "flavor modifier" herein refers to a biologically acceptable compound or salt that modulates, including enhancing or potentiating, and inducing the flavors and / or odors of a natural or synthetic flavoring agent in an animal or a human being. A "flavor improver" herein refers to a compound or a biologically acceptable salt thereof that enhances the flavors or odors of a natural or synthetic flavoring agent. The "savory flavor" herein refers to the tasty "pungent" flavor normally induced by MSG (monosodium glutamate) in an animal or a human being. The "flavoring flavoring agent", "flavoring compound" or "compound that activates the flavoring receptor" herein refers to a compound or biologically acceptable salt thereof that produces a tasty taste detectable in a subject, e.g., MSG (glutamate of monosodium) or a compound that activates a T1 R 1 / T1 R3 receptor in vitro. The subject can be a human being or an animal.

The "sweet flavoring agent", "sweet compound" or "sweet receptor activating compound" herein refers to a compound or a biologically acceptable salt thereof that produces a detectable sweet taste in a subject, e.g., sucrose, fructose, glucose and other known natural saccharide-based sweeteners, or known artificial sweeteners such as saccharin, cyclamate, aspartame and the like as discussed herein further, or a compound that activates a T1R2 / T1R3 receptor in vitro. The subject can be a human being or an animal. A "flavor modifier" herein refers to a compound or a biologically acceptable salt thereof that modulates, which includes improving or potentiating, inducing and blocking the savory flavor of flavoring natural or synthetic flavoring agents, for example, glutamate. monosodium (MSG) in an animal or a human being. A "sweet taste modifier" herein refers to a compound or a biologically acceptable salt thereof that modulates, which includes enhancing or potentizing, inducing and blocking the sweet taste of natural or synthetic sweet flavoring agents, for example, sucrose, fructose, glucose and other sweeteners based on known natural saccharides, or known artificial sweeteners such as saccharin, cyclamate, aspartame, and the like in an animal or a human being. A "savory flavor improver" herein refers to a compound or a biologically acceptable salt thereof that enhances or potentiates the savory flavor of natural or synthetic savory flavoring agents, for example, monosodium glutamate (MSG) in an animal or a human being. A "sweet taste improver" herein refers to a compound or a biologically acceptable salt thereof that enhances or potentiates the sweet taste of natural or synthetic sweet flavoring agents, for example, sucrose, fructose, glucose and other sweeteners based on known natural saccharides, or known artificial sweeteners such as saccharin, cyclamate, aspartame and the like as also discussed herein in an animal or a human being. A "compound activating the acre receptor" herein refers to a compound that activates an acrid receptor, such as a T1R1 / T1R3 receptor. A "compound that activates a sweet receptor" herein refers to a compound that activates a sweet receptor, such as a T1R2 / T1R3 receptor. A "compound that modulates the acre receptor" herein refers to a compound that modulates (activates, enhances or blocks) an acrid receptor. A "compound that modulates the sweet receptor" herein refers to a compound that modulates (activates, enhances or blocks) a sweet receptor. A "compound enhancing acrid receptor" herein refers to a compound that enhances or potentiates the effect of a natural or synthetic accrete receptor that activates the compound, e.g., monosodium glutamate (MSG). A "sweet receptor enhancing compound" herein refers to a compound that enhances or potentiates the effect of a natural or synthetic sweet receptor that activates a compound, for example, sucrose, fructose, glucose and other sweeteners based on natural saccharides known, or known artificial sweeteners such as saccharin, cyclamate, aspartame, and the like as discussed further herein. An "amount of flavoring flavoring agent" herein refers to an amount of a compound that is sufficient to induce flavor taste in an edible or medicinal product or composition or a precursor thereof. A moderately broad range of a quantity of flavoring flavoring agent can be from about 0.001 ppm to 100 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. The alternative ranges of the amounts of flavoring flavoring agent can vary from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm., from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. An "amount of the sweet flavoring agent" herein refers to an amount of a compound that is sufficient to induce the taste of the product in an edible or medicinal product or composition or a precursor thereof. A moderately broad range of an amount of the sweet flavoring agent can be from about 0.001 ppm to 100 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. The alternative ranges of the amounts of the sweet flavoring agent can be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. An "amount that modulates the flavor tasty" herein refers to an amount of a compound of the Formula (I) that is sufficient to alter (either increase or decrease) the flavor tasty in an edible or medicinal product or composition, or a precursor thereof, sufficiently to be perceived by a human subject. A moderately broad range of an amount that modulates the flavor taste can be from about 0.001 ppm to 100 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. Alternative ranges of amounts that modulate the flavor taste can be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm.

An "amount that modulates sweet taste" herein refers to an amount of a compound of Formula (I) that is sufficient to alter (either increase or decrease in) the sweet taste in an edible product or composition or medicinal, or a precursor thereof, sufficiently to be perceived by a human subject. A moderately broad range of a quantity that modifies the d u lce flavor may be from about 0.001 ppm to 100 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. The alternative ranges of the amounts modulating the sweet taste can be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. . A "flavor enhancing amount" herein refers to an amount of a compound that is sufficient to enhance the taste of natural or synthetic flavoring agents, for example, monosodium glutamate (MSG) in an edible product or composition. or medicinal. A moderately broad range of a flavor enhancing amount can be from about 0.001 ppm to 100 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. Alternative ranges of flavor enhancing amounts may be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. A "sweet taste enhancing amount" herein refers to an amount of a compound that is sufficient to improve the taste of natural or synthetic flavoring agents, (e.g., sucrose, fructose, glucose and other saccharide-based sweeteners). known natural, or known artificial sweeteners such as saccharin, cyclamate, aspartame, and the like as herein further denoted) in an edible or medicinal product or composition. A moderately broad range of an amount that improves sweet taste can be from about 0.001 ppm to 1000 ppm, or a narrow range from about 0.1 ppm to about 10 ppm. The alternative ranges of sweet taste improving amounts can be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. An "amount modulating the acre receptor" herein refers to an amount of a compound that is sufficient to modulate (activate, improve or block) an acrid receptor. A preferable range of an amount that modulates the acre receptor is 1 pM to 100 mM and more preferably 1 nM to 100 pM and more preferably 1 nM to 30 pM. A moderately broad range of an amount that improves the pungent taste can be from about 0.001 ppm to 100 ppm, a narrow range from about 0.01 ppm to about 10 ppm. The alternative ranges of the acrylic flavor improving amounts can be from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm or from about 0.1 ppm to about 3 ppm. An "amount that modulates or activates a receiver T1 R1 / T1 R3"is an amount of the compound that is sufficient to modulate or activate a T1R1 / T1R3 receptor.These amounts are preferably the same as the amounts that modulate the accrete receptor. a flavor receptor that can be modulated by a tasty compound.Preferably, an acrid receptor is a coupled G protein receptor, and more preferably the acre receptor is a T1 R1 / T1 R3 receptor.The compounds of the invention modulate a pungent receptor and preferably they are agonists of the T1 R1 / T1 R3 receptor.An agonist of this receptor has the effect to activate the G protein signaling cascade., this agonist effect of the compound in the receptor also produces a tasty taste perceived in the taste test. It is desirable, therefore, that such inventive compounds serve as a replacement for MSG, which is not tolerated by some edible products, for example. In addition, this agonist effect is also responsible for the tasty synergistic flavor effect, which occurs when a compound of the invention is combined with another flavoring flavoring agent such as MSG. The nucleotides, IMP or GMP, are conventionally added to the MSG, to enhance the palatability of the MSG, so that the relatively smaller MSG is necessary to provide the same flavor tasty as compared to the MSG alone. Therefore, it is desirable that combining the compounds of the invention with another flavoring flavoring agent such as MSG advantageously eliminates the need to add expensive nucleotides, such as I MP, as a flavor enhancer, although reducing or eliminating the At the same time the amount of a tasty compound such as MSG necessary to provide the same tasty flavor as compared to the tasty compound or MSG alone. An "amount that modulates the sweet receptor" in the present refers to an amount of a compound that is sufficient to modulate (activate, improve or block) a sweet receptor. A preferable range of an amount that modulates the sweet receptor is 1 pM to 100 mM and more preferably 1 nM to 100 pM and more preferably 1 nM to 30 pM. An "amount that modulates or activates the receiver T1 R2 / T1 R3" is an amount of the compound that is sufficient to modulate or activate a T1 R2 / T1 R3 receptor. These amounts are preferably the same as the amounts that modulate the sweet receptor. A "sweet receptor" is a flavor receptor that can be modulated by a sweet compound. Preferably, a sweet receptor is a receptor coupled to the G protein, and more preferably the acre receptor is a T1 R2 / T1 R3 receptor. Many compounds of Formula (I) can modulate a sweet receptor and preferably are T1 R2 / T1 R3 receptor agonists. An agonist of this receptor has the effect of activating the protein G signaling cascade. In many cases, this agonist effect of the compound on the receptor also produces a sweet taste perceived in a taste test. It is desirable, therefore, that such inventive compounds serve as a replacement for sucrose, fructose, glucose and other sweeteners based on natural saccharides, or known artificial sweeteners such as saccharin, cyclamate, aspartame and the like, or mixtures thereof as discussed. also in the present. A "synergistic effect" is related to the improved flavor and / or sweet taste of a combination of tasty and / or sweet compounds or compounds that activate the receptor, as compared to the sum of the associated flavor effects or effects associated with flavor. with each individual compound. In the case of flavor improving compounds, a synergistic effect on MSG effectiveness can be indicated for a compound of Formula (I) having an EC50 ratio (defined below) of 2.0 or more, or preferably 5.0 or more, or 10.0 or more, or 15.0 or more. An E50 assay for a sweet improvement has not been developed yet, but in the case of both sweet and sweet improver compounds, a synergistic effect can be confirmed by human taste tests, as described elsewhere herein. When the compounds described herein include one or more chiral centers, the stereochemistry of such chiral centers can independently be in the R or S configuration or a mixture of the two. The chiral centers can also be designed as R or S or R, S or D, I, L or D, I, D, L. Correspondingly, the amide compounds of the invention, if they can be present in an optically active form can really presented in the form of a racemic mixture of enantiomers, or in the form of any of the separated enantiomers in isolated and substantially purified form, or as a mixture comprising any relative proportions of the enantiomers. With respect to the compounds described herein, the suffix "ene" added to any of the terms described above means that the substituent is connected to two other parts in the compound. For example, "alkylene" is (CH2) n, "alkylene" is such a portion that it contains a double bond, and "alkynylene" is such a portion that contains a triple bond. As used herein, "hydrocarbon residue" refers to a chemical subgroup within a larger chemical compound, which has only carbon and hydrogen atoms. The hydrocarbon residue can be aliphatic or aromatic, straight chain, cyclic, branched, saturated or unsaturated. The hydrocarbon residue, when established however, may contain or be substituted with heteroatoms such as O, S or N, or the halogens (fluorine, chlorine, bromine and iodine), or substituent groups containing heteroatoms (OH, NH2, NO2 , SO3H and the like) on and above the carbon and hydrogen atoms of the substituent residue. Thus, when specifically observed as containing such heteroatoms, or designed as "substituted", the hydrocarbon residue may also contain carbonyl groups, amino groups, hydroxyl groups and the like, or contain heteroatoms inserted in the "main structure" of the hydrocarbon residue . As used herein, "inorganic waste" refers to a residue that does not contain carbon, but contains at least some heteroatoms, including O, N, S, one or more halogens, alkali metal or alkaline earth metal ions. Examples include, but are not limited to H, Na +, Ca ++ and K +, halo, hydroxy, NO2 or NH2. As used herein, the term "alkyl", "alkenyl" and "alkynyl" includes cyclic and straight-chain and branched monovalent substituents that are respectively saturated, do not saturate with at least one double bond, and are not saturated with at least one triple union. "Alkyl" refers to a hydrocarbon group that can be conceptually formed from an alkane by removing hydrogen from the structure of a hydrocarbon compound having straight or branched carbon chains, and replacing the hydrogen atom with another atom or group substituent In some embodiments of the invention, the alkyl groups are "C1 to C6 alkyl" such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, amyl, ter-amyl. , hexyl and the like. In some embodiments of the invention, the "C 1 to C 4 alkyl groups (alternatively called" lower alkyl "groups) are methyl, ethyl, propyl, iso-butyl, sec-butyl, t-butyl and iso-propyl. Preferred alkyl groups of the invention have three or more carbon atoms preferably 3 to 16 carbon atoms, 4 to 14 carbon atoms, or 6 to 12 carbon atoms Preferred alkenyl groups are "C2 to C7 alkenyl" such as vinyl, allyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-heptenyl, 3-heptenyl, 4- heptenyl, 5-heptenyl, 6-heptenyl, as well as linear and branched chain dienes and thienines The preferred alkynyl groups are "C2 to C7 alkynyl" such as ethynyl, propynyl, 2-butynyl, 2-pentynyl, 3-pentynyl , 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl as well as di and tri-inos of branched and linear chains incl. undo eno-inos. The hydrocarbon waste can be optionally replaced. Two such optional substituents at adjacent positions can be joined to form a saturated or unsaturated, aromatic or optionally substituted non-aromatic fused ring containing 3-8 members. The substituents optionally are generally hydrocarbon residues which may contain one or more heteroatoms or an inorganic residue such as H, Na +, Ca 2+ or K +. The terms "substituted alkyl""substituted alkenyl", "substituted alkynyl" and "substituted alkylene" indicate that the alkyl, alkenyl, alkynyl and alkylene groups are substituted by one or more, and preferably one or two substituents, preferably halogen, hydroxy, C1-alkoxy to C7, alkoxy-alkyl, oxo, C3 to C7 cycloalkyl, naphthyl, amino, (monosubstituted) amino, (disubstituted) amino, guanidino, heterocycle, substituted heterocycle, imidazolyl, indolyl, pyrrolidinyl, acyl of C1 to C7, acyloxy of C1 to C7, nitro, carboxy, carbamoyl, carboxamide, N- (C1 to C6 alkyl) carboxamide, N, N-di (C1 to C6 alkyl) carboxamide, cyano, methylsulfonylamino, thiol, alkylthio of C1 to C4 or groups C1 to C4 alkylsulfonyl. The substituted alkyl groups can be substituted once or more, and preferably once or twice, with the same or with different substituents. In many embodiments of the invention, a preferred group of substituent groups include hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, S Et ", SCH3 (methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy) groups. , ethoxy, isopropoxy and trifluoromethoxy In many embodiments of the invention comprising the foregoing lists of substituent groups, an even more preferred group of substituent groups include hydroxy, SEt, SCH3, methyl, ethyl, isopropyl, methoxy, and ethoxy groups Examples of the above substituted alkyl groups include 2-oxo-prop-1-yl, 3-oxo-but-1-yl, cyanomethyl, nitromethyl, chloromethyl, hydroxymethyl, tetrahydropyranyloxymethyl, trityloxymethyl, propionyloxymethyl, ammonomethyl, carboxymethyl, allyloxycarbonylmethyl. , allyloxycarbonylaminomethyl, methoxymethyl, ethoxymethyl, t-butoxymethyl, acetoxymethyl, chloromethyl, trifluoromethyl, 6-hydroxyhexyl, 2,4-dichloro (n-butyl), 2-aminopropyl, 1-chloroethyl, 2-chloroethyl, 1-bromoethyl, 2- c paroethyl, 1-fluoroethyl, 2-fluoroethyl, 1-iodoethyl, 2-iodoethyl, 1-chloropropyl, 2-chloropropyl, 3-chloropropyl, 1-bromopropyl, 2-bromopropyl, 3-bromopropyl, 1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 2-aminoethyl, 1-aminoethyl, N-benzoyl-2-aminoethyl, N-acetyl-2-aminoethyl, N-benzoyl-1-aminoethyl, N-acetyl-1-aminoethyl and the like. Examples of the above substituted alkenyl groups include styrenyl, 3-chloropropen-1-yl, 3-chloro-buten-1-yl, 3-methoxy-propen-2-yl, 3-phenyl-buten-2-yl, -cyano-buten-3-yl and the like. Geometric isomerism is not critical, and all geometric isomers for a given substituted alkenyl can be used. Examples of the previously substituted alkynyl groups include phenylacetylene-1-yl, 1-phenyl-2-propyn-1-yl and the like. The term "oxo" denotes a carbon atom bonded to two additional carbon atoms substituted with an oxygen atom doubly bonded to the carbon atom, whereby a ketone moiety is formed. "Alkoxy" refers to an OR group, wherein R is an alkyl or substituted alkyl. "Alkoxy-alkyl" refers to an alkyl group containing an alkoxy. Preferred alkoxy groups are "C1 to C7 alkoxy" such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, t-butoxy and similar groups. The term "C1 to C7 substituted alkoxy" means that the alkyl portion of the alkoxy can be substituted in the same manner as in relation to substituted alkyl of C1 to C6.

Similarly, the term "C1 to C7 phenylalkoxy" as used herein means "C1 to C7 alkoxy" attached to a phenyl radical. "Acyloxy" refers to an OR group wherein R is an acyl group. Preferred acyloxy groups are "C1 to C7 acyloxy" such as formyloxy, acetoxy, propionyloxy, butyryloxy, pivaloyloxy, pentanoyloxy, hexanoyloxy, heptanoyloxy and the like. As used herein, "acyl" encompasses the definitions of alkyl, alkenyl, alkynyl, and the related hetero forms that are coupled to an additional residue through a carbonyl group. Preferred acyl groups are "C1 to C7 acyl" such as formyl, acetyl, propionyl, butyryl, pentanoyl, pivaloyl, hexanoyl, heptanoyl, benzoium and the like. The most preferred acyl groups are acetyl and benzoyl. The term "substituted acyl" denotes the acyl group substituted by one or more, and preferably one or two groups of halogen, hydroxy, oxo, alkyl, cycloalkyl, naphthyl, amino, (monosubstituted) amino, (disubstituted) amino, guanidino, heterocyclic ring, substituted heterocyclic ring, imidazolyl, indolyl, pyrrolidinyl, C1 to C7 alkoxy, alkoxy-alkyl, C1 to C7 acyl, C1 to C7 acyloxy, nitro, C1 to C6 alkyl ester, carboxy, alkoxycarbonyl, carbamoyl, carboxamide , N- (C 1 to C 6 alkyl) carboxamide, N, N-di (C 1 to C 6 alkyl) carboxamide, cyano, methylsulfonylamino, thioi, C 1 to C 4 alkylthio or C 1 to C 4 alkylsulfonyl. The substituted acyl groups can be substituted once or more, and preferably once or twice, with the same or with different substituents. Examples of substituted acyl groups of C1 to C7 include 4-phenylbutyroyl, 3-phenylbutyroyl, 3-phenylpropanoyl, 2-cyclohexanilacetyl, cyclohexanecarbonyl, 2-furanyl and 3-dimethylaminobenzoyl. Cycloalkyl residues are hydrocarbon groups within a molecule comprising at least one ring having 3 to 8 carbon atoms linked to a ring. Examples of such cycloalkyl residues include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and fused polycyclic or saturated bicyclic cycloalkanes such as decalin groups, norbornyl groups, and the like. Preferred cycloalkyl groups include "C3 to C7 cycloalkyl" such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl rings. Similarly, the term "C5 to C7 cycloalkyl" includes cyclopentyl, cyclohexyl or cycloheptyl rings. The "substituted cycloalkyl" denotes the above cycloalkyl rings which are preferably substituted by one or two halogens, hydroxy, C1 to C4 alkylthio, C1 to C4 alkylsulfoxide, C1 to C4 alkylsulfonyl, C1 to C4 substituted alkylthio, substituted alkylsulfoxide from C1 to C4, substituted alkylsulfonyl of C1 to C4, alkyl of C1 to C6, alkoxy of C1 to C7, substituted alkyl of C1 to C6, alkoxy-C1 to C7 alkyl, oxo, (monosubstituted) amino, (disubstituted) amino , trifluoromethyl, carboxy, phenyl, substituted phenyl, phenylthio, phenylsulfoxide, phenylsulfonyl, amino. In many embodiments of the substituted cycloalkyl groups, the substituted cycloalkyl group will have 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH, methyl groups , ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy.

The term "cycloalkylene" means a cycloalkyl, as defined above, wherein the cycloalkyl radical is attached to two positions which are connected together to two additional separate groups. Similarly, the term "substituted cycloalkylene" means a cycloalkylene wherein the cycloalkyl radical is attached to two positions which are connected together to two additional separate groups and which also support at least one additional substituent. The term "cycloalkenyl" preferably denotes a 1,2 or 3-cyclopentenyl ring, a 1,2,3 or 4-cyclohexenyl ring or a 1,2,3,4 or 5-cycloheptenyl ring, although the term "substituted cycloalkenyl" "denotes the above cycloalkenyl rings substituted with a substituent, preferably by a C 1 to C 6 alkyl, halogen, hydroxy, C 1 to C 7 alkoxy, alkoxy-alkyl, trifluoromethyl, carboxy, alkoxycarbonyl, oxo, (monosubstituted) amino, (disubstituted) amino, phenyl, substituted phenyl, amino or protected amino. The term "cycloalkenylene" is a cycloalkenyl ring, as defined above, wherein the cycloalkenyl radical is attached to two positions that are connected together to two separate additional groups. Similarly, the term "substituted cycloalkenylene" means a cycloalkenylene substituted, more preferably, by halogen, hydroxy, alkylthio of C1 to C4, alkylsulfoxide of C1 to C4, alkylsulfonyl of C1 to C4, alkylthio substituted of C1 to C4, alkylsulfoxide substituted of C1 to C4, substituted alkylsulfonyl of C1 to C4, alkyl of C1 to C6, alkoxy of C1 to C7, substituted alkyl of C1 to C6, alkoxy-C1 to C7 alkyl, oxo, (monosubstituted) amino, (disubstituted) amino, trifluoromethyl, carboxy, alkoxycarbonyl, phenyl, substituted phenyl, phenylthio, phenylsulfoxide, phenylsulfonyl, amino, or substituted amino group. The term "heterocycle" or "heterocyclic ring" optionally means rings of 3 to 8 members, optionally substituted having one or more carbon atoms connected in a ring that also has 1 to 5 heteroatoms, such as oxygen, sulfur and / or nitrogen inserted inside the ring. These rings of 3 to 8 members can be saturated, restored or partially restored, but are preferably saturated. An "amino-substituted heterocyclic ring" means any of the heterocyclic rings described above is substituted with at least one amino group. Preferred heterocyclic rings include furanyl, thiofuranyl, piperidyl, pyridyl, morpholino, aziridinyl, piperidinyl, piperazinyl, tetrahydrofuran, pyrrolo and tetrahydrothiophenyl. The term "substituted heterocyclic" or "substituted heterocyclic ring" means the heterocyclic ring described above is substituted with, for example, one or more, and preferably one or two, substituents which are the same or different substituents of which may preferably be groups halogen, hydroxy, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, C1 to C7 alkoxy, C1 to C7 substituted alkoxy, alkoxy alkyl, C to C7 acyl, C to C7 acyloxy, carboxy , alkoxycarbonyl, carboxymethyl, hydroxymethyl, alkoxy-alkylamino, (monosubstituted) amino, (disubstituted) amino carboxamide, N- (C 1 to C 6 alkyl) carboxamide, N, N-di (C 1 to C 6 alkyl) carboxamide, trifluoromethyl, N - ((C 1 to C 6 alkyl) ) sulfonyl) amino, N (phenylsulfonyl) amino, or substituted with a fused ring, such as benzo-ring. In many embodiments of the substituted heterocyclic groups, the substituted cycloalkyl group will have 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, N H2, NHC H3, N (CH3) 2 l CO2CH3, SEt groups , SCH 3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. An "aryl" group refers to a combined monocyclic, aromatic bicyclic aromatic or bicyclic aromatic moiety comprising at least one aromatic six-membered benzene ring, preferably comprising between 6 and 12 ring carbon atoms, such as phenyl, biphenyl or naphthyl groups, which may be optionally substituted with various organic and / or inorganic substituent groups, wherein the substituted aryl group and its substituents comprise between 6 and 1 8, or preferably 6 and 16 total carbon atoms. Preferred optional substituent groups include 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl groups , trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. The term "heteroaryl" means a heterocyclic aryl derivative that preferably contains a five-membered or six-membered aromatic ring and conjugate system having from 1 to 4 heteroatoms, such as oxygen, sulfur and / or nitrogen, inserted within the ring conjugated and unsaturated heterocyclic. Heteroaryl groups include monocyclic heteroaromatic portions, linked bicyclic heteroaromatics or combined bicyclic heteroaromatics. Examples of heteroaryls include pyridinyl, pyrimidinyl and pyrazinyl, pyridazinyl, pyrrolyl, furanyl, thiofuranyl, oxazolyl, isoxazolyl, phthalimido, thiazolyl, quinolinyl, isoquinolinyl, indolyl or a furan or thiofuran directly attached to a phenyl, pyridyl or pyrrolyl ring and the rings similar conjugated and unsaturated heteroaromatics. Any monocyclic, bicyclic linked or fused bicyclic heteroaryl ring system having the characteristics of aromaticity in terms of electron distribution through the ring system is included in this definition. Normally, the aromatic ring systems contain 3-12 carbon atoms in the ring and 1 to 5 heteroatoms in the ring independently selected from oxygen, nitrogen and sulfur atoms. The term "substituted heteroaryl" means that the heteroaryl described above is substituted with, for example, one or more, and preferably one or two, substituents which are the same or different, which substituents may preferably be halogen, hydroxy, hydroxy groups protected, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, substituted alkyl of C1 to C7, alkoxy of C1 to C7, substituted alkoxy of C1 to C7, alkoxy-alkyl, acyl of C1 to C7, substituted acyl of C1 to C7, C1 to C7 acyloxy, carboxy, alkoxycarbonyl, carboxymethyl, hydroxymethyl, amino, (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (C1 to C6 alkyl) carboxamide, N, N-di (alkyl) C1 to C6) carboxamide, trifluoromethyl, N - ((C1 to C6 alkyl) sulfonyl) amino or N- (phenylsulfonyl) amino. In many embodiments of the substituted heteroaryl groups, the substituted cycloalkyl group will have 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3l SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. Similarly, "arylalkyl" and "heteroarylalkyl" refer to aromatic and heteroaromatic systems that are coupled to another residue through a carbon chain, including substituted or unsubstituted, saturated or unsaturated carbon chains, typically 1-6C . These carbon chains can also include a carbonyl group, thereby making them capable of providing substituents as an acyl moiety. Preferably, the arylalkyl or heteroarylalkyl is an alkyl group substituted at any position by an aryl, substituted aryl, heteroaryl or substituted heteroaryl group. Preferred groups also include benzyl, 2-phenylethyl, 3-phenyl-propyl, 4-phenyl-n-butyl, 3-phenyl-n-amyl, 3-phenyl-2-butyl, 2-pyridinylmethyl, 2- (2- pyridinyl) ethyl and the like. The term "substituted arylalkyl" denotes an arylalkyl group substituted on the alkyl portion with one or more, and preferably one or two groups preferably chosen from halogen, hydroxy, oxo, amino, (monosubstituted) amino, (disubstituted) amino , guanidino, heterocyclic ring, substituted heterocyclic ring, C1 to C6 alkyl, substituted alkyl of C1 to C6, alkoxy of C1 to C7, substituted alkoxy of C1 to C7, alkoxy-alkyl, acyl of C1 to C7, substituted acyl of C1 to C7, C1 to C7 acyloxy, nitro, carboxy, alkoxycarbonyl, carbamoyl, carboxamide, N- (C1 to C6 alkyl) carboxamide, N, N- (dialkyl of C1 to C6) carboxamide, cyano, N- (alkylsulfonyl of C1 to C6) amino, thiol, alkylthio of C1 to C4, alkylsulfonyl groups of C1 to C4; and / or the phenyl group can be substituted with one or more, and preferably one or two, substituents preferably chosen from halogen, hydroxy, protected hydroxy, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, substituted alkyl from C1 to C6, C1 to C7 alkoxy, C1 to C7 alkoxy, alkoxy alkyl, C1 to C7 acyl, C1 to C7 substituted acyl, C1 to C7 acyloxy, carboxy, alkoxycarbonyl, carboxymethyl, hydroxymethyl, amino , (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (C 1 to C 6 alkyl) carboxamide, N, N-di (C 1 to C 6 alkyl) carboxamide, trifluoromethyl, N - ((C 1 to C 6 alkyl) sulfonyl) amino, N- (phenylsulfonyl) amino, cyclic C2 to C7 alkylene or a phenyl group, substituted or unsubstituted, for a resulting biphenyl group. The substituted alkyl or phenyl groups may be substituted with one or more, and preferably one or two, substituents which may be the same or different. Examples of the term "substituted arylalkyl" include groups such as 2-phenyl-1-chloroethyl, 2- (4-methoxyphenyl) ethyl, 4- (2,6-dihydroxyphenyl) -n-hexyl, 2- (5-cyano- 3-methoxyphen-yl) -n -pentyl, 3- (2,6-dimethylphenii) propyl, 4-chloro-3-aminobenzyl, 6- (4-methoxyphenyl) -3-carboxy-n-hexyl, 5- (4- aminomethylphenyl) -3- (aminomethyl) -n-pentyl, 5-phenyl-3-oxo-n-pent-1-yl and the like. The term "arylalkylene" specifies an arylalkyl, as defined above, wherein the arylalkyl radical is attached to two positions that are connected together to two separate additional groups. The definition includes groups of the formula: -phenylalkyl and alkyl-phenya-alkyio-. Substitutions in the phenyl ring may be 1, 2, 1, 3, or 1, 4. The term "substituted arylalkylene" is an arylalkylene as defined above which is further substituted preferably by halogen, hydroxy, protected hydroxy, alkylthio C1 to C4, alkylsulfoxide of C1 to C4, alkylsulfonyl of C1 to C4, alkylthio substituted of C1 to C4, alkylsulfoxide substituted of C1 to C4, alkylsulfonyl substituted of C1 to C4, alkyl of C1 to C6, alkoxy of C1 to C7, alkyl substituted from C1 to C6, alkoxyC1 to C7 alkyl, oxo, (monosubstituted) amino, (disubstituted) amino, trifluoromethyl, carboxy, alkoxycarbonyl, phenyl, substituted phenyl, phenylthio, phenylsulfoxide, phenylsulfonyl, amino or protected amino group in the phenyl ring or in the alkyl group. The term "substituted phenyl" specifies a phenyl group substituted with one or more, and preferably one or two, portions preferably chosen from the groups consisting of halogen, hydroxy, protected hydroxy, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, C1 to C6 substituted alkyl, C1 to C7 alkoxy, C1 to C7 substituted alkoxy, alkoxy alkyl, C1 to C7 acyl, C1 to C7 substituted acyl, C1 to C7 acyloxy, carboxy , alkoxycarbonyl, carboxymethyl, hydroxymethyl, amino, (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (C1 to C6 alkyl) carboxamide, N, N-di (C1 to C6 alkyl) carboxamide, trifluoromethyl, N - ((C1 to C6 alkyl) sulfonyl ) amino, N- (phenylsulfonyl) amino or phenyl, wherein the phenyl is substituted or not substituted, so that for example, a biphenyl results. In many embodiments of the substituted phenyl groups, the substituted cycloalkyl group will have 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, 'groups. SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. The term "phenoxy" denotes a phenyl linked to an oxygen atom. The term "substituted phenoxy" specifies a phenoxy group substituted with one or more, and preferably one or two, portions preferably chosen from the groups consisting of halogen, hydroxy, protected hydroxy, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, C1 to C7 alkoxy, C1 to C7 substituted alkoxy, alkoxy alkyl, C1 to C7 acyl, C1 to C7 acyloxy, carboxy, alkoxycarbonyl, carboxymethyl, hydroxymethyl, amino, (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (C1 to C6 alkyl) carboxamide, N, N-di (C1 to C6 alkyl) carboxamide, trifluoromethyl, N - ((C1 to C6 alkyl) sulfonyl ) amino and N-phenylsulfonyl) amino. The term "substituted phenylalkoxy" denotes a phenylalkoxy group wherein the alkyl portion is substituted with one or more, and preferably one or two groups selected preferably from halogen, hydroxy, protected hydroxy, oxo, amino, (monosubstituted) amino , (disubstituted) amino, guanidino, heterocyclic ring, substituted heterocyclic ring, C1 to C7 alkoxy, alkoxy-alkyl, C1 to C7 acyl, C1 to C7 acyloxy, nitro, carboxy, alkoxycarbonyl, caryl, carboxamide, N- ( C 1 to C 6 alkyl) carboxamide, N, N (C 1 to C 6 dialkyl) carboxamide, cyano, N- (C 1 to C 6 alkylsulfonyl) amino, thiol, C 1 to C 4 alkylthio, C 1 to C 4 alkylsulfonyl groups; and / or the phenyl group can be substituted with one or more, and preferably one or two, substituents preferably chosen from halogen, hydroxy, protected hydroxy, thio, alkylthio, cyano, nitro, C1 to C6 alkyl, alkoxy C1 to C7, alkoxy-alkyl, acyl of C1 to C7, acyloxy of C1 to C7, carboxy, alkoxycarbonyl carboxymethyl, hydroxymethyl, amino, (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (alkyl of C1 to C6) carboxamide, N, N-di (C1 to C6 alkyl) carboxamide, trifluoromethyl, N ((C1 to C6 alkyl) sulfonyl) amino, N- (phenylsulfonyl) amino or a phenyl group, substituted or unsubstituted, for a group resulting biphenyl. The substituted alkyl or phenyl groups may be substituted with one or more, and preferably one or two, substituents which may be the same or different. The term "substituted naphthyl" specifies a naphthyl group substituted with one or more, and preferably one or two, portions either in the same ring or in different rings chosen from groups consisting of halogen, hydroxy, protected hydroxy, thio , alkylthio, cyano, nitro, C1 to C6 alkyl, C1 to C7 alkoxy, alkoxy alkyl, C1 to C7 acyl, C1 to C7 acyloxy, carboxy, alkoxycarbonyl, carboxymethyl, hydroxymethyl, amino, (monosubstituted) amino, (disubstituted) amino, carboxamide, N- (C 1 to C 6 alkyl) carboxamide, N, N-di (C 1 to C 6 alkyl) carboxamide, trifluoromethyl, N - ((C 1 to C 6 alkyl) sulfonyl ) amino or N (phenylsulfonyl) amino. The terms "halo" and "halogen" refer to fluorine, chlorine, bromine or iodine atoms. There may be one or more halogens, which are the same or different. The preferred halogens are chlorine and fluorine. Although many of the compounds of the invention having halogen atoms as substituents are very effective in binding to the relevant flavor receptors, such as halogenated organic compounds can often have undesirable toxicological properties when administered to an animal in vivo. Thus, in many embodiments of the compounds of Formula (I), if a halogen atom (including a fluorine or chlorine atom) is listed as a possible substituent atom, an alternative preferred group of substituents would NOT include the halogen, fluorine or chlorine. The term "(monosubstituted) amino" refers to an amino group with a substituent preferably chosen from the group consisting of phenyl, substituted phenyl, C1 to C6 alkyl, substituted alkyl of C1 to C6, acyl of C1 to C7 , substituted acyl of C1 to C7, alkenyl of C2 to C7, substituted alkenyl of C2 to C7, alkynyl of C2 to C7, alkynyl substituted of C2 to C7, phenylalkyl of C7 to C12, phenylalkyl substituted of C7 to C12 and a heterocyclic ring . The (monosubstituted) amino may additionally have an amino protecting group as encompassed by the term "(monosubstituted) protected amino". The term "(disubstituted) amino" refers to an amino group preferably substituted with two substituents chosen from the group consisting of phenyl, substituted phenyl, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 1 acyl C7, C2 to C7 alkenyl, C2 to C7 alkynyl, C7 to C12 phenylalkyl, and C7 to C12 substituted phenylalkyl. The two substituents can be the same or different.

The term "amino protecting group" as used herein, refers to substituents of the amino group commonly employed to block or protect the amino functionality while reacting other functional groups of the molecule. The term "(monosubstituted) amino protected" means that there is an amino protecting group on the monosubstituted amino nitrogen atom. In addition, the term "protected carboxamide" means that there is an amino protecting group on the carboxamide nitrogen. Similarly, the term "N- (C 1 to C 6 alkyl) protected carboxamide" means that there is an amino protecting group on the carboxamide nitrogen. The term "alkylthio" refers to sulphide groups such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, t-butylthio and similar groups. The term "alkylsulfoxide" denotes sulfoxide groups such as methylsulfoxide, ethylsulfoxide, n-propylsulfoxide, isopropylsulfoxide, n-butylsulfoxide, sec-butylsulfoxide and the like. The term "alkylsulfonyl" embraces groups such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, t-butylsulfonyl and the like. The terms "substituted alkylthio", "substituted alkylsulfoxide" and "substituted alkylsulfonyl" indicate the alkyl portion of these groups which can be substituted as described above in relation to "substituted alkyl". The terms "phenylthio", "phenylsulfoxide" and "phenylsulfonyl" specify a thiol, sulfoxide, or sulfone, respectively, containing a phenyl group. The terms "substituted phenylthio", "substituted phenylsulfoxide", and "substituted phenylsulfonyl" means that the phenyl of these groups can be substituted as described above in relation to "substituted phenyl". The term "alkoxycarbonyl" means an "alkoxy" group attached to a carbonyl group. The term "substituted alkoxycarbonyl" denotes a substituted alkoxy linked to the carbonyl group, which alkoxy can be substituted as described above in relation to the substituted alkyl. The term "phenylene" means a phenyl group in which the phenyl radical is attached to two positions that connect together to two separate additional groups. Examples of "phenylene" include 1,2-phenylene, 1,3-phenylene and 1,4-phenylene. The term "substituted alkylene" means an alkyl group wherein the alkyl radical is attached to two positions that connect together to two separate additional groups and also support an additional substituent. Examples of "substituted alkylene" include aminomethylene, 1- (amino) -1,2-ethyl, 2- (amino) -1,2-ethyl, 1- (acetamido) -1,2-ethyl, 2- (acetamido) -1, 2-ethyl, 2-h id roxy-1,1-ethyl, 1- (amino) -1,3-propyl. The term "substituted phenylene" means a phenyl group in which the phenyl radical is attached to two positions which are connected together to two separate additional groups, wherein the phenyl is substituted as described above with respect to the "substituted phenyl". The terms "cyclic alkylene", "substituted cyclic alkylene", "cyclic heteroalkylene" and "substituted cyclic heteroalkylene", define such a cyclic group bonded ("molten") to the phenyl radical resulting in a bicyclic ring system. The cyclic group may be saturated or contain one or two double bonds. In addition, the cyclic group may have one or two methylene or methine groups replaced by one or two oxygen, nitrogen or sulfur atoms which are the cyclic heteroalkylene. The alkylene or cyclic heteroalkylene group can be replaced once or twice by the same or different substituents preferably selected from the group consisting of the following portions: hydroxy, protected hydroxy, carboxy, protected carboxy, oxo, protected oxo, acyloxy C1 to C4, formyl, acyl of C1 to C7, alkyl of C1 to C6, alkoxy of C1 to C7, alkylthio of C1 to C4, alkylsulfoxide of C1 to C4, alkylsulfonyl of C1 to C4, halo, amino, protected amino, ( monosubstituted) amino, (monosubstituted) amino protected, (disubstituted) amino, hydroxymethyl or a protected hydroxymethyl. The fused alkylene or cyclic heteroalkylene group on the benzene radical may contain two to ten members in the ring, but preferably contains three to six members. Examples of such saturated cyclic groups are when the resulting bicyclic ring system is 2,3-dihydro-indanyl and a tetralin ring. When the cyclic groups are not saturated, examples occur when the resulting bicyclic ring system is a naphthyl or indolyl ring. Examples of fused cyclic groups each containing a nitrogen atom and one or more double bonds, preferably one or two double bonds, are when the benzene radical is fused to a pyridino, pyran, pyrrolo, pyridinyl, dihydripyrrolo or dihydropyridinyl ring . Examples of fused cyclic groups each containing an oxygen atom and one or two double bonds are when the benzene ring radical is fused to a furo, pyran, dihydrofuran or dihydropyran ring. Examples of fused cyclic groups that each have a sulfur atom and contains one or two double bonds are when the benzene radical is fused to a thieno, thiopyran, dihydrothien or dihydrothiopyran ring. Examples of cyclic groups containing two heteroatoms selected from sulfur and nitrogen and one or two double bonds are when the benzene radical ring is fused to a thiazole, isothiazole, dihydrothiazole or dihydroisothiazole ring. Examples of cyclic groups containing two heteroatoms selected from oxygen and nitrogen and one or two double bonds are when the benzene ring is fused to an oxazolo, isoxazolo, dihydroxazolo or dihydroisoxazolo ring. Examples of cyclic groups containing two nitrogen heteroatoms and one or two double bonds occur when the benzene ring is fused to a pyrazolo, imidazole, dihydropyrazolo or dihydroimidazole or pyrazinyl ring. The term "carbamoyl" means a group -NCO- wherein the radical is attached to two positions that connect two separate additional groups. One or more of the compounds of the invention may be presented as a salt. The term "salt" embraces those salts that form with the carboxylate anions and nitrogens amine and include salts formed with the anions and organic and inorganic cations discussed below. In addition, the term includes salts that are formed by standard acid base reactions with basic groups (such as amino groups) and organic and inorganic acids. Such acids include hydrochloric, hydrofluoric, trifluoroacetic, sulfuric, phosphoric, acetic, succinic, citric, lactic, maleic, fumaric, palmitic, colic, pamoic, musician, D-glutamic, D-canphoric, glutaric, phthalic, tartaric, lauric, stearic, salicyclic, methanesulfonic, benzenesulfonic, sorbic, picric, benzoic, cinnamic and the like. The term "organic and inorganic cation" refers to counter-ions for the carboxylate anion of a carboxylate salt. The counter-ions are chosen from alkali and alkaline earth metals (such as lithium, sodium, potassium, barium, aluminum and calcium); ammonium and mono, di and trialkylamines such as trimethylamine, cyclohexylamine; and organic cations, such as dibenzylammonium, benzylammonium, 2-hydroxyethylammonium, bis (2-hydroxyethyl) ammonium, phenylethylbenzylammonium, dibenzylethylene diammonium, and similar cations. See for example, "Pharmaceutical Salts", Berge et al., J. Pharm. Sci. (1977) 66: 1-19, which is incorporated herein by reference. Other cations encompassed by the above term include the protonated form of procaine, quinine and N-methylglucosamine, and the protonated forms of basic amino acids such as glycine, ornithine, histidine, phenylglycine, lysine and arginine. In addition, any zwitterionic form of the present compounds formed by a carboxylic acid and an amino group is referred to by this term. For example, a cation for a carboxylate anion will exist when R2 or R3 is replaced with a group (quaternary ammonium) methyl. A preferred cation for the carboxylate anion is the sodium cation. The compounds of the invention can also exist as solvates and hydrates. Thus, these compounds can be crystallized with, for example, hydration waters, or one, a number of, or any fraction thereof of solvent molecules mother liquor. The solvates and hydrates of such compounds are included within the scope of this invention. The term "amino acid" includes any of the twenty naturally occurring amino acids or the D form of any of the naturally occurring amino acids. In addition, the term "amino acid" also includes other amino acids of non-natural origin in addition to amino acids D, which are functional equivalents of naturally occurring amino acids. Such amino acids of non-natural origin include for example, norleucine ("Nle"), norvaline ("Nva"), L- or D-naphthalanine, ornithine ("Orn"), homoarginine (homoArg) and others well known in the art of peptide, such as those described in M. Bodanzsky, "Principies of Peptide Synthesis", 1st and 2nd revised ed. , Springer-Verlag, New York, NY, 1884 and 1993, and Stewart and Young, "Solid Phase Peptide Synthesis" 2nd. Ed., Pierce Chemical Co., Rockford, I L, 1984, both of which are incorporated herein by reference. The amino acids and amino acid analogs can be purchased commercially (Sigma Chemical Co.; Advanced Chemtech) or synthesized using methods known in the art. The "amino acid backbone" refers to any secondary chain from the "amino acids" described above. "Substituted" herein refers to a substituted portion, such as hydrocarbon, for example, alkyl or substituted benzyl wherein at least one element or radical, eg, a hydrogen is replaced by another, eg, a hydrogen replaced by a halogen as a chlorobenzyl. A residue of a chemical species, as used in the specification and final claims, refers to a structural fragment, or to a portion that is the resulting product of the chemical species in a particular reaction scheme or subsequent formulation or chemical product, regardless of whether the fragment or the structural portion is actually obtained from the chemical species. Thus, a residue of ethylene glycol in a polyester refers to one or more repeating units -OCH2CH2O-, regardless of whether the ethylene glycol is used to prepare the polyester. Similarly, a residue of 2,4-t'-azolidindione in a chemical compound refers to one or more 2,4-thiazolidinedione portions of the compound, regardless of whether the residue was obtained by reacting 2,4-thiazolidinedione to obtain the compound. The term "organic waste" defines a carbon containing a residue, that is, a residue comprising at least one carbon atom, and includes, but is not limited to, groups, residues or carbon-containing radicals, defined above. . Organic residues may contain several heteroatoms, or be linked to another molecule through a heteroatom, including oxygen, nitrogen, sulfur, phosphorus or the like. Examples of organic residues include, but are not limited to, alkyl or substituted alkyl, alkoxy or substituted alkoxy, mono mono or disubstituted amino, amide, etc. groups. The organic residues may preferably comprise 1 to 18 carbon atoms, 1 to 15 carbon atoms, 1 to 12 carbon atoms, 1 to 8 carbon atoms or 1 to 4 carbon atoms. By the term "effective amount" of a compound as provided herein is meant a sufficient amount of the compound to provide the desired regulation of a desired function, such as gene expression, protein function, or a condition of disease . As will be indicated later, the exact amount required will vary from subject to subject, depending on the species, age, general condition of the subject, specific identity and formulation of the drug, etc. In this way, it is not possible to specify an exact "effective amount". However, an appropriate effective amount can be determined by someone of ordinary skill in the art i using only routine experimentation. It should be noted that, as used in the specification and the appended claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to an "aromatic compound" includes mixtures of aromatic compounds. Frequently, the ranges are expressed herein as "approximately" a particular value, and / or "approximately" another particular value. When such a range is expressed, another modality includes from a particular value and / or the other particular value. Similarly, when the values are expressed as approximations, by the use of the "approximately" antecedent, it will be understood that the particular value forms another modality. It will also be understood that the endpoints of each of the ranges are significant in relation to the other endpoint and independently of the other endpoint. "Optional" or "optionally" means that the episode or circumstance subsequently described may or may not occur, and that the description includes instances where such an episode or circumstance occurs and examples where they do not. For example, the phrase "optionally substituted lower alkyl" means that the lower alkyl group may or may not be substituted and that the description includes unsubstituted lower alkyl and lower alkyls where substitution exists.

The Amide Compounds of the Invention The compounds of the invention are all organic compounds (containing carbon) since all have at least one "amide" group thereon, have the following general structure, which will be referred to below as the compounds amide having the Formula (I) shown below: (I) The amide compounds of Formula (I) do not include any amide compounds that are known to occur naturally in biological systems or foods, such as peptides, proteins, nucleic acids, glycopeptides or glycoproteins or the like. The amide compounds of the Formula (I) of the invention are manufactured and artificial synthetic amide compounds, although the Applicants do not exclude the possibility that the compounds of the Formula (I) could conceivably be prepared purposely, either in their specific form or in the form of a peptide or "prodrug" form modified with proteins by humans using one or more of the methods of modern biotechnology. For the various modalities of the compounds of Formula (I), the groups R1, R2 and R3 can be and are further independently defined in various ways, as will be further detailed, so as to form and / or include a substantial number of subgenres and / or species of the compounds of Formula (I). It is therefore contemplated specifically that any of the sub-genres and / or species of the compounds of Formula (I) described below can, either in their specific form or as an edible acceptable salt, be combined in an effective amount with a product or edible or medial precursor thereof by the processes and / or methods described elsewhere herein, or by any such other process as would be apparent to those of ordinary experience to prepare edible or medicinal products or precursors of the same. , to form a modified edible or medicinal product with tasty or sweet flavor, or a precursor thereof. In some embodiments of the compounds of Formula (I), R 1 is a hydrocarbon residue which may contain one or more heteroatoms or an inorganic residue, and R 2 and R 3 are each independently H or * a hydrocarbon residue which may contain one or more heteroatoms; more preferably, R1, R2 and R3 are independently selected from the group consisting of arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyl, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, -R4OH, -R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4CONR5R6, -R4NR5R6, -R4N (R5) COR6, -R4SR5, -R4SOR5, -R4SO2R5, -R4SO2NR5R6 and -R4N (R5) SO2R6, or optionally substituted groups thereof and preferably one of R2 or R3 is H; wherein each R4 is independently a hydrocarbon residue which may contain one or more hetero-axons, preferably independently selected from a (C1-C6) alkylene or small (C1-C6) alkoxyalkylene; and wherein each R5 and R6 are independently H or hydrocarbon residue which may contain one or more heteroatoms, preferably selected independently of a (C1-C6) alkyl or small (C1-C6) alkoxyalkyl. In many embodiments of the compounds of the Formula (I), R1 comprises an organic residue based on hydrocarbons having at least three carbon atoms and optionally one at 20, 15, 10, 8, 7, 6 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or matches. In many embodiments of the compounds of Formula (I), one of R2 and R3 is optionally H, and one or both of R2 and R3 comprises an organic or hydrocarbon-based residue having at least three carbon atoms and optionally one at ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphors. The compounds of Formula (I) are relatively "small molecules" when compared to many biological molecules, and can often have a variety of limitations on their total absolute physical size, molecular weight and physical characteristics, so that they can be at least a little soluble in aqueous media, and are of appropriate size to effectively bind to the Relevant heterodimeric T1 R1 / T1 R3 or T1 R2 / T1 R3 taste receptors that share a common T1 R3 protein subunit. Although not wishing to be bound by any theory, it is believed that MSG binds to the T1 R1 subunit of the "tasty" taste receptors T1 R1 / T1 R3, and several known sweeteners bind to the T1 subunit of the receptors. sweet T1 R2 / T1 R3. Accordingly, our unexpected and surprising discovery that the amyloid compounds of Formula (I) can share many overlapping physical and chemical characteristics, and can sometimes bind to either or both of the tasty and sweet receptors, is perhaps in reasonable retrospect. and / or rotational from a chemical / biochemical / biological point of view. As an example of the overlapping physical and chemical properties and / or the physical / chemical limitations on the tasty and / or sweet amides of the Formula (I), in most embodiments of the compounds of the Formula (I), the Molecular weight of the compounds of Formula (I) should be less than about 800 grams per mole, or in additional related embodiments less than or equal to about 700 grams per mole, 600 grams per mole, 500 grams per mole, 459 grams per mole mol, 400 grams per mole, 350 grams per mole or 300 grams per mole. Similarly, the compounds of Formula (I) may have preferred ranges of molecular weight, such as, for example, from about 1 75 to about 500 grams per mole, from about 200 to about 450 grams per mole, from about 225 to about about 400 grams per mole, from about 250 to about 350 grams per mole. In a freed-up series, R1 has between 3 and 16 carbon atoms or 4 and 14 carbon atoms or 5 and 12 carbon atoms, and 0, 1, 2, 3, 4 or 5 heteroatoms selected from oxygen, nitrogen, sulfur, fluorine or chlorine and / or at least one of R2 or R3 has been 3 and 16 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur, fluorine or chlorine; or preferably at least one of R2 or R3 has between 4 and 14 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur, fluorine; or even more preferably, at least one of R2 or R3 has between 5 and 12 carbon atoms and 0, 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur. In addition to the foregoing general physical and chemical characteristics and / or limitations, which may be shared by the various sub-genres of the sweet and savory compounds of Formula (I), the compounds of Formula (I) may also share chemical structural characteristics specifically definable or groups or chemical residues, as also described below. For example, in some embodiments, R1, R2 and R3 can be independently selected from the group consisting of an arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyl, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, -R4OH, -R4OR5 , -R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5 and -R4SO2R5, and an optionally substituted derivative thereof comprising 1, 2, 3 or 4 carbonyl, amino, hydroxyl or halogen groups, and wherein R4 and R5 are Ci-Cβ hydrocarbon residues. In further related embodiments of the amide compounds of Formula (I), R1, R2 and R3 can be independently selected from the group consisting of arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyl, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, and optionally substituted derivatives thereof, comprising 1, 2, 3 or 4 carbonyl, amino, or hydroxyl or chloro or fluoro groups. In both of the aforementioned embodiments, an alternative and preferred group of optional substituent groups would be substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl , isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy substituent groups. In many embodiments of the compounds of Formula (I), one of R2 and R3 is hydrogen and the other group R2 or R3 is a residue or organic group. For example, in many embodiments of the compounds of Formula (I), at least one or R2 and R3 is a branched or cyclic organic residue having a carbon atom directly attached to both (a) the amide nitrogen atom and (b) ) two additional carbon atoms from other organic residues, which are branched or cyclic organic residues comprising additional hydrogen atoms and up to 10 additional optional carbon atoms and optionally from zero to five heteroatoms independently selected from oxygen, nitrogen, sulfur, fluorine and chlorine. Such branched groups R2 and R3 include organic radicals having the formula: Where na and nb are independently selected from 1, 2, and 3, and each of the substituent residues R2a or R2b is independently selected from hydrogen, a halogen, a hydroxy or a carbon-containing residue optionally having from zero to five heteroatoms independently selected from oxygen, nitrogen, sulfur and a halogen. In some embodiments, R2a or R2b are independent substituent groups, but in other embodiments one or more of the radicals R2a or R2b may be joined together to form ring structures. In some embodiments of the compounds of the Formula (I), at least one of R 2 and R 3 is a branched alkyl radical having 5 to 12 carbon atoms, or at least one of R 2 and R 3 is a cycloalkyl or cycloalkenyl ring comprising 5 to 12 carbon atoms in the ring. In such embodiments of R2 and R3 the branched alkyl radical or the cycloalkyl or cycloalkenyl ring can be optionally substituted with 1, 2, 3 or 4 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3 , SEt, SCH3l methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In other embodiments of the amide compounds of Formula (I), at least one of R2 and R3 is a "benzylic" radical having the structure wherein Ar is an aromatic or heteroaromatic ring such as phenyl, pyridyl, furanyl, thiofuranyl, pyrrolyl or similar aromatic ring systems, m is 0, 1, 2 or 3, and each R2 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, and each substituent group R2a can be independently selected from the group consisting of the alkyl, alkoxy-alkyl, alkenyl, cycloalkenyl, cycloalkyl, -R4OH, -R4OR5, -R4CN group , -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5 and -R4SO2R5. In many embodiments of the compounds of the Formula (I), at least one of R2 or R3 is a C3-C10 branched alkyl. These branched C3-C10 alkyls have been found to be highly effective R2 groups for both tasty and sweet amide compounds. In the further embodiments, the branched C3-C10 alkyl may be optionally substituted with one or two substituents independently selected from the group hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In the further embodiments of the compounds of Formula (I), at least one of R2 or R3 is a lower alkyl ester of the a-substituted carboxylic acid or an a-substituted carboxylic acid. Preferably, at least one of R2 or R3 is an alkyl ester (especially methyl) lower than the a-substituted carboxylic acid. In some preferred embodiments, the ester residue of the α-substituted carboxylic acid or α-substituted carboxylic acid corresponds to that of an optically active α-amino acid or an ester thereof, or its opposite enantiomer. In many embodiments of the compounds of Formula (I), at least one of R2 or R3 is a 5- or 6-membered aryl or heteroaryl ring, optionally substituted with 1, 2, 3 or 4 substituent groups selected from the group which consists of alkyl, alkoxy, alkoxy-alkyl, OH, CN, CO2H, CHO, COR6, CO2R6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl; and R6 is Ci-Ce alkyl. Preferably the aryl or heteroaryl ring is substituted with 1, 2, 3 or 4 substituent groups selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3l SCH3, SEt, methyl groups , ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some embodiments of the compounds of Formula (I), at least one of R2 or R3 is a phenyl, pyridyl, furanyl, thiofuranyl or pyrrolyl ring optionally substituted with one or two substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. In many embodiments of the compounds of Formula (I), at least one of R 2 or R 3 is a cycloaicyl, cycloalkenyl or a saturated heterocyclic ring having 3 to 10 carbon atoms in the ring, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3 >; C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, hydroxy and halogen. In some additional embodiments, at least one of R2 or R3 is a cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or a piperidyl ring optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2 , NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some preferred embodiments, at least one of R2 or R3 is a cyclohexyl, optionally substituted with 1, 2 or 3 methyl groups. Examples of such methyl substituted cyclohexyl rings have the formula In many embodiments of the compounds of Formula (I), compounds especially have activity for sweet receptors, at least one of R2 or R3 is a 1- (1,2,3,4) tetrahydronaphthalene ring or a ring 2,3 -d ihydro-1 H-indene that has the formula: wherein m is 0, 1, 2 or 3 and each R2 'can be attached to either an aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2l CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. It will be understood that optical and / or diastereomeric isomerism can occur in the cyclohexyl or cyclopentyl rings of this substituent, and deferring optics and / or diastereomers can often have at least some different biological activities. In some embodiments, at least one of R2 or R3 is a 1- (1,2,3,4) tetrahydronaphthalene ring with certain preferred substitution patterns. In particular, at least one of R2 or R3 may have the formula: wherein each R2 is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, groups. methoxy, ethoxy, isopropoxy and trifluoromethoxy. Similarly, in some preferred embodiments, at least one of R2 or R3 may have the formula: In some embodiments, at least one of R2 or R3 is a 1- (1, 2,3,4) tetrahydronaphthalene ring unsubstituted in racemic or optically active form, as shown below: Aromatic or Heteroaromatic Compounds In many preferred embodiments of the amide compounds of Formula (I) having one or both of the sweet and savory receptor agonist activity, there is a preferred subgenus of the amide compounds having the following formula (II): (H) wherein A comprises a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 3 or 4; each R1 'is independently selected from alkyl, alkoxy, alkoxy-alkyl, hydroxyalkyl, OH, CN, CO2H, CO2R6, CHO, COR6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl; and R6 is C6-C6 alkyl, and R2 can be any of the embodiments contemplated herein above, or the like. In some embodiments, the group A of the Formula (II) comprises an aryl ring, that is, it contains at least one aromatic benzene ring of six members. The aryls include at least benzene and naphthalene rings, which can not, but in many embodiments are further substituted with at least 1, 2, or 3 substituent groups R1 'independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. In some preferred embodiments, one or two of the substituent groups R1 are joined together to form a saturated alkylene dioxy ring or a phenyl ring, as exemplified by the following preferred structures (lia) and (IIb); wherein R a and R-? D are independently hydrogen or a lower alkyl, or alternatively R a and R y are independently hydrogen or methyl, or alternatively both R 1 a and R-ib are hydrogen. In many embodiments of the amide compounds of Formula (II), A is a heteroaryl ring, and usually a monocyclic or bicyclic fused heteroaryl ring. The bicyclic fused heteroaryls are typified by the following benzofurans (Formula lie) and benzothiofurans (Formula lid): wherein m is 0, 1, 2 or 3 and each R1 'can be attached to any phenyl or heteroaryl ring and each R1' is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. Additional examples of fused bicyclic heteroaryls as groups A are typified by the following compounds benzoxazole (Formula Me) and (Formula llf): (lie) (Ilf) wherein R-? a or R? b is independently hydrogen or a lower alkyl. In many embodiments of the amide compounds of Formula (II), A is a monocyclic heteroaryl ring. Monocyclic heteroaryls can be used as a group A in formula (II) are typified by the following structures: Where m is 0, 1, 2 or 3 and each R1 'is independently selected from hydroxy, fluoro, chloro, N H2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy.

In some preferred embodiments of the compounds of Formula (II), A is a substituted furan ring, thiofuran or oxazole, so that compounds having Formulas (Ng) are formed. (Hh) and (lli): (? Í) wherein m is 0, 1, 2 or 3 and each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl , methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some of these embodiments, m is 1 or 2. In many embodiments of the compounds of the various subgenres of Formula (II) immediately described above, at least one of R2 or R3 may be a C3-C10 branched alkyl; an a-substituted carboxylic acid or a lower aikylester of the a-substituted carboxylic acid; a 5 or 6 membered aryl or heteroaryl ring, optionally substituted with 1, 2, 3 or 4 substituent groups selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy; a cyclohexyl, optionally substituted with 1, 2 or 3 methyl groups; or a 1- (1, 2,3,4) tetrahydronaphthalene ring or a 2,3-dihydro-1 H-indene ring having the formula: wherein m is 0, 1, 2 or 3, and each R2 'can be attached to any aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy; as will be described above with respect to the general amide compounds of Formula (I). The subgenus of the aromatic or heteroaromatic amide compounds of the Formula (II) immediately described above contain many excellent agonists of the taste receptors ("acre") T1R1 / T1R3 and / or sweet taste receptors T1R2 / T1R3, a very low concentrations of the amide compound in the order of micromolar or lower concentrations, and can induce a remarkable sensation of a tasty acrid flavor in humans, and / or can serve as flavor enhancers of the tasty acrid flavor of MSG, or significantly improve the effectiveness of a variety of known sweeteners, especially sweeteners based on saccharides. Accordingly, many of the aromatic or heteroaromatic amide compounds of Formula (II) can be used as flavoring or sweet flavoring agents or flavoring enhancers when they are contacted with a wide variety of edible products and / or compositions, or its predecessors, as described somewhere in the present. In another subgenus of the compounds of Formula (I), the amide compound has Formula (III): (111) wherein A comprises a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 3 or 4; each R1 is independently selected from alkyl, alkoxy, alkoxy alkyl, hydroxyalkyl, OH, CN, CO2H, CHO, COR6, CO2R6, SH, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl and R6 is C? alkyl? -C6; B is a 5 or 6 membered aryl or heteroaryl ring; m 'is 0, 1, 2, 3 or 4; R2 'is selected from the group consisting of alkyl, alkoxy, alkoxy-alkyl, OH, CN, CO2H, CHO, COR6, CO2R6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl; and R6 is C6-C6 alkyl. In the compounds of Formula (III), optional substituent groups R1 and R2 can also be independently selected from hydroxy, fluoro, chloro, NH3, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy groups , isopropoxy and trifluoromethoxy. In the compounds of Formula (III), both rings A and B comprise a five or six membered aryl or heteroaryl ring. For ring A, any of the various embodiments of the A rings listed above for the compounds of Formula (II) include phenyl and the monocyclic and bicyclic heteroaryls may be suitable. In some bicyclic embodiments, the A ring of the compounds of Formula (III) have the following structures: wherein R1a and R-ib are independently hydrogen or a lower alkyl. In the compounds of Formula (III), the B-rings are an optionally substituted monocyclic or five or six membered aryl or heteroaryl ring, such as phenyl, pyridyl, furanyl, thiofuranyl, pyrrolyl and the like monocycles. In some embodiments, the compounds of Formula (III) wherein b is phenyl, ie wherein the amide compound is easily derived from a substituted aniline precursor, may in many cases be previously known chemical compounds, but it is believed that this has previously been unknown that such compounds can be used as very effective pungent flavoring compounds, lower than molar or lower concentrations, see for example compound A1 in Table 1 below.

Urea Compounds In another subgenre of the amide compounds of Formula (I), the urea compound is a urea compound having the Formula (IV): wherein R7, R8 and R9 are each a hydrocarbon residue which may contain one or more heteroatoms or an inorganic residue, and are preferably independently selected from arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyal, alkyl, alkoxyalkyl, alkenyl, cycloalkyl groups , cycloalkenyl, aryl and heteroaryl, each of which can be optionally substituted, or one of R7 or R8 can be and often is H. In some embodiments of the urea compounds of Formula (IV), R7 and R8 together form a heterocyclic or heteroaryl ring having 5, 6 or 7 ring atoms which may be optionally substituted with 1, 2 or 3 substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. Examples of such a urea compound may have the Formulas (IVa) and (IVb): (IVa) (IVb) wherein m and n are independently 0, 1, 2 or 3, and each R1 'and R2 is independently selected from fluoro, chloro, NH2, NHCH3) N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl , trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In such embodiments, n is preferably 0. In further embodiments of the urea compounds of Formula (IV), R9 and one of R7 and R8 are independently selected from arylalkenyls, heteroarylalkenyls, arylalkys, heteroarylalkys, alkyls, alkykylaryls, alkenyls, cycloalkyls, cycloalkenyls, aryls and heteroaryls, each of which carbon-containing groups can be optionally substituted with 1, 2, or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2 groups , COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In further embodiments of the urea compounds of Formula (IV), R9 and one of R7 and R8 are independently selected from arylalkyl, heteroarylalkyl, alkyl, cycloalkyl, aryl, heterocycle and heteroaryl, each of which may optionally comprise one a five heteroatoms independently selected from oxygen, nitrogen, sulfur, chlorine and fluorine. In further embodiments of the urea compounds of Formula (IV), R9 and one of R7 and R8 are independently selected from alkyl, phenyl, cyclohexyl or pyridyl, each of which may optionally comprise one to four substituents independently selected from of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In the further embodiments of the urea compounds of Formula (IV), at least one of R7 and R8 has one of the heteroaromatic formulas: wherein m is 0, 1, 2 or 3 and each R1 'independently selected from hydrogen groups, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In such embodiments, R9 is preferably a C3-C10 branched alkyl, arylalkyl or a cycloalkyl which may be optionally substituted with 1, 2 or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N ( CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In further embodiments of the urea compounds of Formula (IV), at least one of R7 and R8 is a phenyl ring optionally substituted with 1, 2 or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3 groups , N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. In such embodiments, R9 is preferably a branched C3-C10 alkyl, arylalkyl or a cycloalkyl which may be optionally substituted with 1, 2 or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N groups (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In further embodiments of the urea compounds of Formula (IV), R 9 is a branched C 3 -C 10 alkyl. In the additional embodiments of the urea compounds of Formula (IV), R9 has the structure wherein B is a phenyl, pyridyl, furanyl, thiofuranyl, pyrrole, cyclopentyl, cyclohexyl or piperidyl ring, m is 0, 1, 2 or 3, and each R 2 is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, and R9a is selected from the group consisting of an alkyl, alkoxyalkyl, alkenyl, cycloalkenyl, cycloalkyl, -R4OH, -R4OR5, -R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5 and -R4SO2R5 comprises 1 to 12 carbon atoms or preferably Oxalamide Compounds In another subgenre of the amide compounds of Formula (I), the amide compound is an oxalamide compound having Formula (V): (V) wherein R 10 and R 30 are each independently selected from a hydrocarbon residue which may contain one or more heteroatoms, or preferably R 10 and R 30 are independently selected from the group consisting of arylalkyl, heteroarylalkyl, heterocyclealkyl, or groups optionally substituted therefrom, and R20 and R40 are each independently H or a hydrocarbon residue which may contain one or more heteroatoms; preferably R20 and R40 are H or C1-C3 alkyl, or optionally substituted groups thereof. More preferably R20 and R40 are H. In addition, they may be 0, 1, 2, 3 or 4 optional substituent groups for R10 and R30 independently selected from hydroxy, fluoro, chloro, NH2, NHCH3l N (CH3) 2, CO2CH3 groups , SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In the preferred embodiment of the oxalamide compounds of Formula (V), R 10 and R 30 are independently selected from hydrocarbon residues having at least three carbon atoms and optionally one to ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphors , and wherein R20 and R40 are independently selected from hydrogen and a hydrocarbon residue having at least three carbon atoms and optionally one to ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphors. In many preferred embodiments of the oxalamide compounds of Formula (V), R20 and R40 are hydrogen. In such embodiments, R 10 and R 30 may be independently selected from the group consisting of arylalkyl, heteroarylalkyl, cycloalkylaryl, and heterocyclealkyls comprising five to 15 carbon atoms, wherein each of R 10 and R 30 may optionally comprise one a one to four substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy groups. In many embodiments of the oxalamide compounds of Formula (V), the oxalamide compound has the Formula (Va): (Va) wherein A and B are independently aryl, heteroaryl, cycloalkyl or a heterocycle comprising from 5 to 12 ring atoms; m and n are independently 0, 1, 2, 3 or 4-8; R 20 and R 40 are hydrogen, R 50 is hydrogen or an alkyl or substituted alkyl residue comprising one to four carbon atoms; R60 is absent or a C1-C5 alkylene or a substituted C1-C5 alkylene; R70 and R80 are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxy-alkyl, OH, SR9, halogen, CN, NO2, CO2R9, COR9, CONR9R10, NR9R10, NR9COR10, SOR9, SO2R9, SO2NR9R10, NR9SO2R10 , alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle; R9 and R10 are independently selected from H, C? -C6 alkyl, C3-C6 cycloalkyl and C? -C6 alkenyl.

In the preferred embodiments of the oxalamide compounds of Formula (Va), R60 is a group -CH2CH2-, A and B are independently selected from phenyl, pyridyl, furanyl, thiofuranyl pyrrolyl rings R 70 R 80 are independently selected from hydroxy groups, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some embodiments of the oxalamide compounds of Formula (Va), A and B are independently a phenyl, pyridyl, furanyl, benzofuranyl, pyrrole, benzothiophene, piperidyl, cyclopentyl, cyclohexyl or cycloheptyl ring.; m and n are independently 0, 1, 2 or 3; R20 and R40 are hydrogen; R50 is hydrogen or methyl; R60 is a C1-C5 or preferably alkylene of C2; R70 and R80 are independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy groups. In many embodiments of the oxalamide compounds of Formula (V), the oxalamide compound has Formula (Vb): wherein A is a phenyl, pyridyl, furanyl, pyrrole, piperidyl, cyclopentyl, cyclohexyl or cycloheptyl ring; m and n are independently 0, 1, 2 or 3; R50 is hydrogen or methyl; P is 1 or 2; and R70 and R80 are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, or two of R 70 together form a methylenedioxy ring. In some embodiments of the oxalamide compounds of Formula (Vb), the pyridyl-R80 radical has the structure: In certain preferred embodiments of the amide compounds of Formula (V), the oxalamide compound has the Formula (Vc): wherein Ar 1 is a substituted aryl or heteroaryl ring comprising five to 12 carbon atoms; R50 is hydrogen or methyl; n is 0, 1, 2 or 3; each R80 is independently selected from the group consisting of hydroxy, fluoro, chloro, NH2 > NHCH3, N (CH3) 2l CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some embodiments of the oxalamide compounds of the Formula (Vc), Ar 1 is a 2-, 3-, or 4-monosubstituted phenyl, phenyl 2,4-, 2,3-, 2,5, 2,6,3, 5- or 3,6-disubstituted, 3-alkyl-4-substituted phenyl, a trisubstituted phenyl wherein the substituent groups are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH 2, NHCH 3, N (C H 3 ) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, or two adjacent substituents together form a methylenedioxy ring on the phenyl ring. In some embodiments of the oxalamide compounds of the Formula (Vc), Ar 1 is a substituted heteroaryl ring comprising from 5 to 12 carbon atoms and wherein the substituent groups are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, N HCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In certain preferred embodiments of the amide compounds of Formula (V), the oxalamide compound has the Formula (You): (Vd) wherein A is a substituted aryl or heteroaryl ring comprising five to 12 carbon atoms; R50 is hydrogen or methyl; n is 0.1 each R 80 is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) 2, COOCH 3, SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. Preferably, A is a phenyl, pyridyl, furanyl, pyrrole, piperidyl, cyclopentyl, cyclohexyl or cycloheptyl ring optionally substituted with 1, 3 or 3 substituent groups independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2 groups , NHCH 3, N (CH 3) 2, COOCH 3, SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. In certain preferred embodiments of the amide compounds of Formula (V), the oxalamide compound has the formula (Ve): (Vc) where m and n are independently 0, 1, 2 or 3; R 70 and R80 are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxy-alkyl, OH, SR9, halogen, CN, NO2, C02R9, COR9, CONR9R10, NR9R10, NR9COR10, SOR9, SO2R9, SO2NR9R10, NR9SO2R10, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocycle; and R9 and R10 are independently selected from H, C-t-C6 alkyl, C3-C6 cycloalkyl, and C? -C6 alkenyl groups. Preferably, R7o and R8o are independently separated from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl groups , trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. Preferably, the pyridyl-R80 radical of the oxalamide compound of the Formula (Ve) has the structure: As can be seen from the inspection of the Examples attached below, the oxalamide compounds of the Formulas (Va) - (Ve) are excellent agonists of the taste receptors ("acre") T1 R 1 / T1 R3 at very low concentrations in the order of micromolar or lower concentrations, it induces a remarkable sensation of a tasty acrid flavor in humans and / or can serve as flavor enhancers of the tasty acrid flavor of MSG. Accordingly, the oxalamide compounds of Formulas (Vc), (Vd) and (Ve) can be used as flavoring flavoring agents or flavor enhancers when they are in contact with a wide variety of products and / or edible compositions or their precursors, as described somre in the present.

Compounds Acrylamide In another subgenre of the amide compounds of Formula (I), the amide compound is an acrylamide compound having Formula (VI): (SAW) wherein A is a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 3 or 4; each R1 'is independently selected from alkyl, alkoxy, alkoxy-alkyl, OH, CN, CO2H, CO2R6, CHO, COR6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl, and R2 can be any of the various embodiments of R2 described above with respect to the amides of Formula (I). In some of the acrylamide compounds of Formula (VI), A is a phenyl ring and m is 1, 2, 3 or 4, or preferably m is 1 or 2, and R 1 can be independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. In some of the acrylamide compounds of Formula (VI), R2 is a C3-C10 alkyl, or a lower alkyl ester of the a-substituted carboxylic acid.

Edible or Pharmaceutically Acceptable Compounds Many of the amide compounds of the Formula (I) or their various subgenres listed comprise acidic or basic groups, so that they depend on the acidic or basic ("pH") character of the edible or medicinal compositions wherein they formulate, these may be presented as salts, which are preferably edible acceptable (i.e., designated as generally recognized as safe, or GRAS) or pharmaceutically acceptable salts (many of which have been recognized by the Federal Food and Drug Administration). Amide compounds of Formula (I) having acidic groups, such as carboxylic acids, will tend (at an almost physiological neutral pH) to be present in solution in the form of anionic carboxylates, and will therefore have a cation in the preferred embodiments. edible and / or pharmaceutically acceptable, many of which are known to those of ordinary skill in the art. Such edible and / or pharmaceutically acceptable cations include alkali metal cations (lithium, sodium and potassium cations), alkaline earth metal (magnesium, calcium and the like) or ammonium (NH4) + cations or organically substituted ammonium cations such as cations.

(R-N H3) +. Amide compounds of Formula (I) having basic substituent groups, such as heterocyclic groups containing amino or nitrogen, will tend (at near neutral physiological pH, or at common acidic pH in many foods) to be presented in solution in the form of groups cationic ammonium, and will therefore have in the preferred embodiments an associated edible and / or pharmaceutically acceptable anion, many of which are known to those of ordinary skill in the art. Such edible and / or pharmaceutically acceptable anionic groups include the anionic form of a variety of carboxylic acids (acetates, citrates, tartrates, anionic salts or fatty acids, etc.), halides (especially fluorides or chlorides), nitrates and the like. The amide compounds of Formula (I) and their various sub-genres should preferably be edible acceptable, that is, appear adequate for consumption in foods or beverages, and must also be pharmaceutically acceptable. The typical method to demonstrate that a fring compound is edible is to have the compound tested and / or evaluated by a Panel of Experts in the Association of Fr and Extracts Manufacturers and declared as to be "Generally Recognized as Safe" ("GRAS" ). The FEMA / G RAS evaluation process for fring compounds is complex, but well known to those of ordinary experience in food preparation techniques, as discussed by Smith et al. In an article entitled "GRAS Fring Substances 21", Food Technology, 57 (5), pp. 46-59, May 2003, the complete contents of which are incorporated herein by reference. When evaluated in the FEMA / GRAS process, a new fr compound is normally tested for any adverse toxic effects in laboratory rats when such rats are fed for at least about 90 days at a concentration 100 times, or 1000 times, or even concentrations higher than the proposed maximum allowable concentration of the compound in a particular category of food products that are considered for approval. For example, such a test of the amide compounds of the invention could involve combining the amide compound with rat food and feeding to laboratory rats such as Crl: CD (SD) I GS BR rats, at a concentration of approximately 1 00 milligrams. / kilograms of body weight / day for 90 days, and then the rats are sacrificed and evaluated by various medical test procedures to demonstrate that the amide compound of Formula (I) does not cause adverse toxic effects in rats.

Compounds of the Invention as Flavored or Sweet Flavor Meiodores The amide compounds of Formula (I) and their various sub-genres and species of the compound, as described above, are intended to be flavorful or sweet flavoring compounds or taste modifiers for edible or medicinal products. As apparent from the teachings and Examples herein, many compounds of Formula (I) are agonists of a "tasty" receptor hT1 R1 / hT1 R3, or a receptor d ulce hT1 R2 / hT1 R3, at least a relatively high amide compound concentrations, and therefore many of the ammonium compounds of Formula (I) may have at least some utility as flavoring flavors or flavorings, at least at relatively high concentrations. However, it is preferable to use almost as little of such artificial flavors as possible, so as to minimize the cost and any undesirable side effects to the health of the administration of the compounds of Formula (I) at high concentration levels. Accordingly, it is desirable to test the compounds of Formula (I) for their effectiveness as flavor receptor agonists at lower concentration levels, so that the best and most effective amide compounds within the compounds of Formula (I) are identified. . As described in WO 03/001876, and U.S. Patent Publication US 2003-0232407 A1, and as described below, laboratory procedures now exist to measure the agonist activities of compounds for "tasty" receptors hT1 R1 / hT1 R3 and sweet hT1 R2 / hT1 R3. Such measuring methods usually measure an "EC5o", that is, the concentration at which the compound causes 50% activation of the relevant receptor. Preferably, the amide compounds of Formula (I) which are taste modifiers have an EC50 for the hT1 R1 / hT1 R3 receptor of less than about 10 μM. More preferably, such amide compounds have an EC50 for the hT1 R1 / hT1 R3 receptor of less than about 5 μM, 3 μM, 2 μM, 1 μM or 0.5 μM. Preferably, the amide compounds of Formula (I) which are sweet taste modifiers or sweet taste improvers have an EC50 for the hT1 R2 / hT1 R3 receptor of less than about 10 μM. More preferably, such amide compounds have an EC50 for the hT1 R2 / hT1 R3 receptor of less than about 5 μM, 3 μM, 1 μM or 0.5 μM. In some embodiments, the amide compounds of Formula (I) are flavor modulators or flavor enhancers of the monosodium glutamate agonist activity for a hT1 R 1 / hT1 R3 receptor. Hereinafter, a test procedure for so-called EC50 ratios is described, that is, for dissolving a compound of Formula (I) in MSG containing water, and measuring the degree to which the amide compound decreases the amount of MSG required for Activate 50% of available hT1 R1 / hT1 R3 receptors. Preferably, the amide compounds of Formula (I), when dissolved in water solution comprising about 1 μM of the amide compound will decrease the observed EC50 of monosodium glutamate for a hT1 R1 / hT1 R3 receptor expressed in the HEK293 cell line -Ga15 by at least 50%, that is, the amide compound will have an EC5o ratio of at least 2.0, or preferably 3.0, 5.0 or 7.0. Although sweet enhancers have not yet been developed for specific EC5o ratio assays, it is believed that the amide compounds of Formula (I) and more specifically many of the amides of Formula (II) can modulate the binding of a sweetener known as example, sucrose, fructose, glucose, erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, a known natural terpenoid, flavonoid, or protein sweetener, aspartame, saccharin, acesulfame-K, a cyclamate, sucralose, alitame or erythritol to a receptor hT1 R2 / hT1 R3. Appropriate assays for such sweet breeding properties can be easily developed by one of ordinary skill in the art using appropriate cell lines expressing hT1 R2 / hT1 R3 receptors. The assays identified above are useful for identifying the most potent of the amide compounds of Formula (I) for flavoring and / or sweet flavor modifying or enhancing properties., and the results of such assays are believed to correlate well with the current tasty or sweet taste perception in animals and humans, but finally the results of the assays can be confirmed, at least for the most potent of the compounds of the Formula ( I) by human taste test. Such human taste test experiments can be quantified and controlled either by testing the candidate compounds in aqueous solutions, when compared to a control aqueous solution, or alternatively by testing the amides of the inventions in current food compositions. Accordingly, in order to identify the most potent of the tasty taste modifiers or agents, an aqueous solution comprising an amount of flavor modification of the amide compound should have a tasty taste when judged by the majority of a group. of experts from at least eight tasters of human flavor. Correspondingly, in order to identify the most potent of flavor enhancers, an aqueous solution, comprising a flavor modification amount of an amide compound of Formula (I) and 12 mM monosodium glutamate, would have an enhanced flavor when compared to a control aqueous solution comprising 12 mM sodium glutamate, when determined by a majority of a panel of at least eight tasters of human taste. Preferably, in order to identify the most potent of flavor enhancers, an aqueous solution comprising a taste modification amount of flavor (preferably about 30, 10, 5 or 2 ppm) of the amide compound of the Formula ( I) and 12 mM of monosodium glutamate will have an increased flavor taste when compared to a control aqueous solution comprising 12 mM of monosodium gi utamate and 100 μM of inopine monophosphate, when determined by a majority of a group of experts of at least eight tasters of human flavor. Similar human taste test procedures can be used to identify which of the compounds of Formula (I) are the most effective sweet flavor agents or sweet taste improving agents. Preferred flavor modifiers of Formula (I) can be identified when a modified edible or medicinal product has a sweeter taste than a edible or medicinal control product that does not comprise the amide compound, when judged by the majority of a group of experts of at least eight tasters of human flavor. The preferred sweet flavor improvers of Formula (I) can be identified as an aqueous solution comprising a sweet test amount of a known sweetener selected from the group consisting of sucrose, fructose, glucose, erythritol, somatol, lactitol, mannitol, sorbitol, xylitol, a known natural terpenoid, flavonoid or protein sweetener, aspartame, saccharin, acesulfame-K, cyclamate, sucralose, and alitame and a sweet taste modification amount of the amide compound (preferably about 30, 10, 5 or 2 ppm) has a sweeter flavor than a control aqueous solution comprising the sweetest taste amount of the known sweetener, when judged by the majority of a panel of experts of at least eight tasters of human taste. In such taste test experiments, sucrose would be preferably presented at a concentration of about 6 grams / 100 milliliters, a 50:50 mixture of glucose and fructose would preferably be present at a concentration of about 6 grams / 100 milliliters, the Aspartame would preferably be present at a concentration of approximately 1.6 mM, acesulfame-K would preferably be present at a concentration of approximately 1.5 mM, cyclamate would preferably be present at a concentration of approximately 10 mM, sucralose would be preferred. in a concentration of approximately 0.4 mM, or alitame would preferably be present at a concentration of approximately 0.2 mM.

Using the Compounds of Formula (I) to Prepare Edible Compositions Flavors, flavor modifiers, flavoring agents, flavor improvers, flavoring flavoring agents ("acre") and / or flavor improvers, according to the invention have application in foods, beverages and medicinal compositions wherein the tasty compounds or ulcers are conventionally used. These compositions include compositions for human and animal consumption. This includes food for consumption by farm animals, pets and zoo animals. Those of ordinary skill in the art to prepare and seal edible compositions (ie, edible foods or beverages, or precursors or flavor modifiers thereof) as well as aware of a wide variety of classes, subclasses and species of the edible compositions, and uses well-known and recognized terms of the art to refer to those edible compositions although attempts are made to prepare and sell several of those compositions. Such a list of terms of the art is listed below, and is specifically contemplated whereby various sub-genres and species of the compounds of Formula (I) could be used to modify or improve the flavorful and / or sweet flavors of the following list of compositions. edible, either individually or in all reasonable combinations or mixtures thereof: One or more confections, chocolate confections, tablets, basic products, individual / delicate packages, packaged varieties, standard packaged varieties, screwed wrapped miniatures, seasonal chocolate , chocolate with toys, alfajores, other chocolate confections, mints, standard mints, strong mints, cooked sweets, pills, gums, jellies and chewing gums, toffee, candies and nougat, medicated confectionery, lollipops, licorice, other sugar confectionery , gums, chewable gums, sugary gums, sugar-free gums, functional gums, balloon gum, bread, bread pacado / industrial, unpacked / handmade bread, pastries, cakes, packaged / industrial cakes, unpacked / handmade cakes, biscuits, chocolate-coated biscuits, sandwiches, filled cakes, biscuits with nice flavor and cookies, bread substitutes, cereals for breakfast, ready-to-eat cereals, family breakfast cereals, flakes, granola, other ready-to-eat cereals, breakfast cereals for children, hot cereals, ice cream, patterned ice cream, single-serve cream ice cream, portion water ice cream simple, multiple pack ice cream, multi-pack water ice cream, ice cream to take home, ice cream, ice cream desserts, voluminous ice cream, ice water, frozen yogurt, homemade ice cream, milk products, milk, fresh / pasteurized milk, fresh / pasteurized whole fat milk, fresh / pasteurized semi-skimmed milk, long-term milk / at temperature ultra high, long-life / ultra high-fat milk, long-life / low-fat ultra-high-fat milk, long-life / ultra-high fat-free milk, goat's milk, condensed / evaporated milk, condensed / evaporated milk simple, flavored, functional and condensed milk, flavored milk juices, desserts only from flavored milk juices, milk juices flavored with fruit juices, soy milk, sour milk drinks, fermented creamy drinks, coffee whiteners, milk powder, milk drinks flavored powders, cream, cheese, processed cheese, processed cheese, non-spreadable processed cheese, unprocessed cheese, unprocessed cheese, durian cheese, hard cheese, unpackaged hard cheese, yogurt, simple / natural yogurt, yogurt flavored, yogurt with fruit, probiotic yogurt, yogurt to drink, yogurt for regular drinking, yogurt to drink probiotic, frozen and frozen desserts, desserts based on creams, desserts based on soybeans, frozen bocadillos, fresh cheese and immature cheese, fresh and unripe cheese, fresh and flavored immature cheese, fresh and immature flavored cheese, snacks and of pleasant flavor, fruity sandwiches, fried foods / snacks, extruded sandwiches, tortillas / corn chips, popcorn, pretzels, nuts, other sweet and tasty sandwiches, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacement products, slimming products, convalescent beverages, ready meals, canned ready meals, frozen ready meals, dry ready meals, frozen ready meals, dinner mixes, frozen pizza, refrigerated pizza , soup, canned soup, dehydrated soup, instant soup, chilled soup, ultra-high temperature soup, frozen soup, pasta, canned pasta, p dried antlers, chilled / fresh pastas, noodles, simple noodles, instant noodles, instant noodles in cups / bowls, instant noodles in bags, refrigerated noodles, noodles for snacks, canned foods, canned meat and meat products, canned fish / seafood, vegetables canned tomatoes, canned tomatoes, canned beans, canned fruit, canned ready meals, canned soup, canned pasta, other canned foods, frozen foods, frozen processed red meat, frozen processed poultry meat, frozen processed fish / seafood, vegetables frozen processed foods, frozen meat substitutes, frozen potatoes, baked potatoes, other baked potato products, frozen unbaked potatoes, frozen bakery products, frozen desserts, frozen ready meals, frozen pizza, frozen soup, frozen noodles, other frozen foods, dry foods, dessert mixes, dry ready meals, dehydrated soup, instant soup sugar, dried pasta, simple noodles, instant noodles, instant noodles in cups, instant noodles in bags, refrigerated foods, refrigerated processed meats, refrigerated fish / seafood products, refrigerated processed fish, refrigerated coated fish, refrigerated preserved fish, kits of refrigerated lunch, refrigerated ready meals, refrigerated pizza, refrigerated soup, refrigerated / fresh pasta, refrigerated noodles, oils and fats, olive oil, vegetable and seed oil, cooking fats, butter, margarine, spreadable oils and fats, oils and functional spreadable fats, sauces, dressings and condiments, tomato and puree pastes, soups / broth cubes, broth cubes, large amounts of cauliflower, liquid soups and organizers, herbs and spices, fermented sauces, soy-based sauces, pasta sauces, soaked sauces, dried sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, dressings for salads, regular salad dressings, low-fat salad dressings, vinaigrettes, dips, marinated products, other sauces, dressings and condiments, baby foods, milk formulas, standard milk formulas, dairy formulas, milk formulas for children they begin to walk, hypoallergenic milk formulas, prepared baby foods, dry baby foods, other baby foods, spreads, preserves, honey, chocolate spreads, nut-based foods, and spreads based on yeast. Preferably, the compounds of Formula (I) may be used to modify or improve the flavor or sweet taste of one or more of the following sub-genres of edible compositions: confectionery, bakery products, ice cream, creamy products, sweet and savory snacks, sandwich bars, meal replacement products, ready meals, soups, pasta, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, or spreads or a mixture thereof.

In general, a produced nibleble composition will be produced, which contains a sufficient amount of at least one compound within the scope of Formula (I) or its various sub-genera described above to produce a composition having the desired taste or flavor characteristics. such as "tasty" or "sweet" flavor characteristics. Normally, at least one amount that modulates the flavor tasty, an amount that modulates the sweet taste, a quantity of flavoring flavoring agent, or a quantity of sweet flavoring agent, of one or more of the compounds of the Formula (I) will be added to the edible or medicinal product, so that the edible or medicinal modified product with tasty or sweet flavor has a tasty and / or sweet flavor increased when compared to the edible or medicinal product prepared without the amide compound, when judged by humans or animals in general, or in the case of formulation testing, when judged by a majority of an expert group of at least eight tasters of human taste through procedures described elsewhere in the present. The concentration of the flavoring or sweet flavoring agent necessary to modulate or improve the flavor of the edible or medicinal product or composition will of course vary depending on many variables, including the specific type of ingestible composition, what flavorful compounds are present and the concentrations thereof, and the effect of the particular compound on such tasty compounds. As noted, a significant application of the compounds of Formula (I) is to modulate (induce, enhance or inhibit) the flavorful or sweet flavors or other flavor properties of other flavorful natural or synthetic tasters. A broad but also low range of concentrations of the amide compounds of Formula (I) would also normally be required, i.e., from about 0.001 ppm to 100 ppm, or narrower alternative ranges from about 0.1 ppm to about 10 ppm, from about 0.01 ppm to about 30 ppm, from about 0.05 ppm to about 15 ppm, from about 0.1 ppm to about 5 ppm, or from about 0.1 ppm to about 3 ppm. Examples of foods and beverages wherein the compounds according to the invention can be incorporated include by way of example, the Soaked Soup Category, the Dehydrated and Culinary Food Category, the Beverage Category, the Frozen Food Category, the Snacks, and seasonings and mixtures of dressings. "Soaked Soup Category" means soaked / liquid soups regardless of concentration or container, including frozen soups. For the purpose of this or these definition soups means a food prepared from meat, poultry, fish, vegetables, grains, fruits and other ingredients, cooked in a liquid which may include visible pieces of some or all of these ingredients. It can be clear (like a broth) or thick (like a stew), thin, pureed or thick, ready to serve, semi-condensed or condensed and can be served hot or cold, like a first dish or as the main dish of a food or as between meals (sipped as a drink). The soup can be used as an ingredient to prepare other components for food and can vary from broths (consomme) to sauces (soups based on creams or cheese). "Dehydrated and Culinary Food Category" means: (i) cooking auxiliary products such as: powders, granules, pastes, concentrated liquid products, including concentrated cauliflower, cauliflower and products similar to pressed cube cakes, tablets, powder or granulated form, which are sold separately as a finished product or as an ingredient within a product, sauces and recipe mixes (regardless of technology); (ii) food solutions products such as dried and frozen dry soups, including mixtures of dehydrated soups, instant dehydrated soups, ready-to-cook dehydrated soups, dehydrated or ambient preparations of prepared dishes, meals and simple service tickets including pastries, potato and rice dishes; e (iii) products for dressing foods such as: condiments, marinades, salad dressings, salad dressings, dips, breaded, whipped mixtures, freestanding spreads, barbecue sauces, mixtures of liquid recipes, concentrates, sauces or sauces mixtures, including recipe mixes for salads, sold as a finished product or as an ingredient within a product, whether dehydrated, liquid or frozen. The "Beverage Category" means beverages, mixtures and beverage concentrates, including but not limited to alcoholic or non-alcoholic ready for powdered drinks. Other examples of foods and beverages wherein the compounds according to the invention can be incorporated include, by way of example, carbonated and non-carbonated beverages, for example sodas, fruit and vegetable juices, alcoholic and non-alcoholic beverages, confectionery products, for example cakes, cookies, cakes, candies, chewable gums, jellies, ice cream, sorbets, bud ines, jams, jellies, salad dressings, and other condoms, cereals and other foods for breakfast, fruit preserves and compotes and the like. Additionally, the subject compounds can be used in flavor preparations to be added to foods and beverages. In preferred examples, the composition will comprise another flavor modifier or taster such as a savory taster. Accordingly, in some embodiments, the inventions relate to methods for modulating the savory or sweet flavor of an edible or medicinal product, comprising: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the edible or medicinal product or precursor thereof with at least an amount that modulates the flavor tasty or an amount that modulates the sweet taste of at least one amide compound of non-natural origin, or an edible acceptable salt thereof, so that a modified edible or medicinal product is formed; wherein the amide compound has the formula: wherein the amide compound is an amide of the Formula (I), or any of its various subgenus or species compounds described herein, wherein R1, R2 and R3 can be defined in the many ways also described above. The invention also relates to edible or modified medicinal products produced by such processes, and similar processes for producing edible or medicinal products well known to those of ordinary skill in the art. The amide compounds of Formula (I) and its subgeneral manifolds may be combined with or applied to edible or medicinal products or precursors thereof in any of innumerable ways known to cook throughout the world, or producers of edible or medicinal products. . For example, the amide compounds of Formula (I) could be dissolved in, or dispersed in, or one of many edible acceptable liquids, solids, or other carriers, such as water at neutral, acidic or basic pH, fruit juices. or vegetables, vinegar, marinades, beers, wine, water emulsions / natural fats such as milk or condensed milk, edible oils and fats, fatty acids, certain oligomers of low molecular weight of propylene glycol, glyceryl esters of fatty acids, and dispersions or emulsions of such hydrophobic substances in aqueous media, salts such as sodium chloride, vegetable flours, solvents such as ethanol, solid edible diluents such as vegetable powders or flours, and the like, and then combined with precursors of edible or medicinal products, or They are directly applied to edible or medicinal products.

Making the Amide Compounds of Formula (I) The starting materials used to prepare the compounds of the invention, ie, the various structural subclasses and species of the amide compounds of Formula (I) and their synthetic precursors, especially the organic carboxylic acids and benzoic acids, isocyanates, and the various amines, anilines, amino acids, etc. , are compounds often known or made by methods known from the literature, or are commercially available from various sources well known to those of skill in the art, such as, for example, Sigma-Aldrich Corporation of St. Louis Missouri USA and its subsidiaries Fluka and Riedel-de Haén, in its various offices around the world, and other well-known suppliers such as Fisher Scientific, TCI America of Philadelphia PA, Chem Div of San Diego CA, Chembridge of San Diego, CA, Asinex of Moscow Russia, SPECS / BIOSPECS of the Netherlands, Maybridge of Cornwall England, Acros, TimTec of Russia, Comgenex of South San Francisco CA and ASD I Biosciences of Newark Delaware. It will be apparent to the skilled artisan that the methods for preparing precursors and functionally related to the compounds claimed herein are generally described in the literature. The skilled technician given the literature and this description is well equipped to prepare any of the required starting materials and / or claimed compounds. In some of the Examples cited above, the starting materials are not readily available, and therefore they were synthesized and the synthesis of the starting materials is thus exemplified. It is recognized that the technician skilled in the art of organic chemistry can easily perform manipulations without additional direction, that is, it is well within the scope and practice of the qualified technician to carry out these manipulations. These include the reduction of carbonyl compounds to their corresponding alcohols, oxidations, acylations, aromatic substitutions, both electrophilic and nucleophilic, etherification, esterification, saponification, miration, hydrogenation, reductive amination, and the like. These manipulations are discussed in standard texts such as March's Advanced Organic Chemistry (3d Ed ition, 1985, Wiley-I nterscience, New York), Feiser and Feiser's Reagents for Organic Synthesis, Carey and Sundberg, Advanced Organic Chemistry and the like, the total descriptions of which are incorporated herein for reference in their entireties for their teachings with regarding the methods to synthesize organic compounds. The skilled artisan will readily appreciate that certain reactions are best carried out when another functionality is masked or protected in the molecule, thereby avoiding any undesirable side reactions and / or increasing the yield of the reaction. Frequently, the qualified technician uses the protective groups to achieve such increased yields or to avoid undesired reactions.

These reactions are found in the literature and are also within the reach of the qualified technician. Examples of many of these manipulations can be found, for example, in T. Greene and P. Wuts, Protecting Groups in Organic Synthesis, 3a. Ed., John Wiley & Sons (1999). The following abbreviations have the indicated meanings: CH3CN = Acetonitrile CHCI3 = Chloroform DIC = N, N'-diisopropylcarbodiimide DIPEA = Diisopropyletilamine DMAP = 4- (dimethylamino) -pyridine DMF = N, N-dimethylformamide EDCI = hydrochloride of 1 - (3-Dimethylaminoporyl) -3-ethylcarbodiimide DCM = dichloromethane ESIMS = electron dispersion mass spectrometry Et3N = triethylamine EtOAc = ethyl acetate EtOH = Ethyl alcohol Fmoc = N- (9-fluoroenylmethoxycarbonyl HCl = Hydrochloric acid H2SO4 = Sulfuric acid HOBt = 1-Hydroxybenzotriazole 'MeOH = Methyl Alcohol MgSO4 = Magnesium Sulphate NaHCO3 = Sodium Bicarbonate NaO H = H Sodium Oxide Na2SO4 = Sodium Sulfate Ph = Phenyl rt = Room Temperature SPOS = Solid Phase Organic Synthesis THF = Tetrahydrate rofuran TLC = thin layer chromatography Abbreviations of alkyl group Me = methyl Et = ethyl n-Pr = normal propyl i-Pr = isopropyl n-Bu = normal butyl i-Bu = isobutyl t-Bu = tertiary butyl s-Bu = secondary butyl n-Pen = normal pentyl i-Pen = isopentyl n-Hex = normal hexyl i-Hex = isohexyl Abbreviations of reagent supported by polymer PS-Trisamine = polystyrene of Tris- (2-aminoethyl) amine PS-Chloroacetyl = PS-NCO = polystyrene of methylisocyanate PS-benzaldehyde = PS-TsNHNH2 = Polystyrene Toluenesulfonylhydrazone The following schemes of the example are provided for reader guidance, and preferred methods depicted for making the compounds exemplified herein. These methods are not limiting, and it will be apparent that other routes can be used to prepare these compounds. Such methods specifically include solid-phase based chemistries, including combinatorial chemistry. The skilled worker is fully equipped to prepare the necessary compounds and / or claimed by those methods given by the literature and this description.

Scheme 1a D2 As shown in Scheme 1a, the amide derivatives (I) are prepared from the coupling of the acid derivatives (II) with amines (III) in the presence of a coupling reagent such as 1-ethyl-hydrochloride. 3- (3-dimethylaminopropyl) -carbodiimide and a base. In Method A, a carbodiimide supported by a polymer (PS) is used. Method B uses a carbodiimide supported without polymer.

Scheme 1b - Alternative Method for the Preparation of Amides X = halide As shown in Scheme 1b, the amide derivatives (I) are prepared, alternatively from the coupling of acid halides, esters or anhydrides (IV) with amines (III) in the presence of a base.

Scheme 1c - Synthesis of the Amides through the Combinatorial Arrangements The following procedure was used and can be used to synthesize amides in the combinatorial array arrangement. • Use acetonitrile as the system solvent. • Weigh amines in 8 ml bottles. • Use Tecan dissolved amines at 100 mM in DCM / CH3CN (1: 2 from low point). • Weigh the acid in 8 ml bottles. • Use dissolved Tecan acids at 110 mM in DCM / CH3CN (1: 2 low).

Preload 1 .2 ml of Greiner plate with 30 mg of resin PS-carbod iimide using plate I I Titrator Peli Case 1400. Use acetonitrile as the system solvent for synthesis. Add 200 ml (20 mmol, 1 equivalent) of amine to each well of the synthesis plates. Add 200 ml (22 mmol, 1 .1 equivalent) of acid to each well of the synthesis plates. Add 1 1 0 ml (22 mmol, 1 .1 equivalent) of HOBt (0.20 M in DM F) to each well of the synthesis plates per 8-channel pipette. Seal plates with lid knot: and shake (normal speed) at room temperature overnight. Load 20 mg / well of PS-Trisamine resin into the synthesis plates using the plate charger Thin titulator-l. Adjust the amount of resin based on your load. Add 200 ml of DCM / CH3CN to the plate. Plate and agitator seal plates (fast speed) at room temperature at night. Use methanol as the system solvent to transfer to the storage plate. Transfer 150 ml to the storage plate, then wash twice with 150 ml of methanol (stir slowly for 5 minutes). Make transfers from the Upper Part in each well. (Altu ra de ag uja -2). Dry the plates in Genevac. Remove the analytical plates (2.5 mM theory) and submit for analysis. Removal plates removed based on analytical results. Scheme 1c - Preparation of Oxalamides As a general procedure, one was allowed to react with ethyl oxalyl chloride in the presence of tertiary amine in organic solvent, such as dioxane, aceton ityl, tetrahydrofuran, tetrahydropyran, and dimethylformamide at room temperature for 0.5-2 hours. . Then the second amide is added and the suspension is heated to 80 ° C using the oil bath overnight at 160 ° C in a microwave reactor for 5 minutes. The reaction mixture can be subjected to preparative H PLC, or an aqueous development and the unpurified product can usually be easily purified by recrystallization, flash column chromatography, or other methods well known to those with ordinary experience in the art to produce the pure oxalamide. The returns reported later were not optimized.

Scheme 1d - Preparation of Urea R9 -NCO + Scheme 2 X1, X, and X3 are each independently alkyl or alkoxy Scheme 2 describes a method for the preparation of pyrazine derivatives (Vlll). For example, the reaction of substituted or unsubstituted 2,3-diaminopropionic acids (V) with 2,3-diones (VI) under heating conditions in the presence of base yields, after acidification, pyrazin-2 acid -carboxylic substituted (VII). The acid is condensed with several amines (III) to produce the desired amide (Xlll) using the conditions shown in Scheme 1a.

Scheme 3 X 4 is alkyl, halide, alkoxy or thioalkyl.

Scheme 3 describes a method for the preparation of benzofuran derivatives (XII). For example, a reaction of 2-hydroxybenzaldehydes (IX) with diethyl ester of 2-bromo-malonic acid (X), under heating conditions in the presence of base yields of substituted benzofuran-2-carboxylic acid (XI). The acid is connected with several amines (III) to produce the desired amide (XII) using conditions shown in Scheme 1a.

Scheme 4 Xs is H, alkyl, aryl, aryl-alkyl, heteroaryl-alkyl, Xe is alkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl, X is halide. Scheme 4 describes methods for the preparation of an alkoxyalkyl amide (XX). In one method the phthalic anhydride (Xlll) is heated with aminoalcohol (XIV) to give the alcohol (XV) which is then reacted with the alkyl halide (XVI) in the presence of a base to produce the alkoxy (XVII). Treatment of the phthalimide (XVII) with hydrazine produces the desired amine (XVIII) which is further condensed with the acid (II) as described in scheme 1a to provide the alkoxyalkylamide (XX). Alternatively, the acid (II) is condensed with the amino alcohol (XIV) using the method described in scheme 1a to provide the alcohol (XIX) which is further alkylated to give (XX).

Scheme 5 X is halide X7 is H, alkyl, alkoxyalkyl, aryl, aryl-alkyl, heteroaryl-alkyl, and Xs are each independently H, alkyl, alkoxyalkyl, arylalkyl and hetero Scheme 5 describes methods for the preparation of amido-amide (XXIV). The alkyl halide (IV) is treated with amino acid (XXI) as described in scheme 1b to give the corresponding acid (XXII) which is further condensed with amine (XXIII) as described in scheme 1a to provide the amido derivative amide (XXIV).

Scheme 6 XXV XXVI XXVII XXVIII Scheme 6 describes methods for the preparation of benzoxazole (XXVIII). The aminophenol (XXV) can be condensed with a variety of reagents to form the benzoxazole (XXVI) having a wide variety of Xg substituent using a method described in the literature (see for example, J. Med. Chem. 28 (1985) 1255) and / or by the method recited in Examples 39 to 47. The benzoxazole intermediate (XXVI) is then condensed with amine (V) using the method described in scheme 1a to give the amide (XXVII). Alternatively, the amide (XXVII) is first prepared by condensing the amino phenol (XXV) with the amine (V) to give the intermediate aminophenol (XXVIII) which is further converted to the benzoxazole (XXVII) using the various methods described above.

Measuring the Biological Activity of the Compounds of the Invention Cell-based technologies and assays, such as those described in WO 02/064631, and WO 03/001876, and US Patent Publication 2003-0232407 A1 were both used to initially screen a wide variety of classes of compounds for agonist and antagonist activity for "tasty" taste receptors T1 R1 / T1 R3 or "sweet" taste receptors T1 R2 / T1 R3 that had been expressed in appropriate cell lines. Once initial "hits" for amide compounds were obtained in such cell lines, the same assays and also certain cell-based and / or receptor-based assays were used as analytical tools to measure the capacity of the compounds of Formula (I) , to improve the tasty taste of MSG or the sweet taste of known sweeteners such as sucrose, fructose and were used to provide empirical data to guide an interactive process to synthesize and test structural variants of the amide compounds, in combination with the test of Occasional human flavor of compounds of high interest, so that species and genera of compounds are designed, tested and identified with increased and optimized levels of desirable biological activities. Many embodiments of the inventions relate to the identification of specific compounds and classes of the amide compounds of Formula (I) that modulate (increase or decrease) the activity of the taste-tasty receptor T1 R1 / T1 R3 (preferably hT1 R1 / hT1 R3) (acrid receptor), alone or in combination with another compound that activates hT1 R 1 / hT1 R3, e.g., MSG. Particularly, in many embodiments the invention relates to the amides of Formula (I) that modulate the activity of hT1 R1 / hT1 R3 (human acre receptor) in vtro and / or in vivo. In another aspect, the invention relates to compounds that modulate the human perception of tasty (acrid) flavor alone or in combination with another compound or flavoring, when added to an edible or medicinal product or composition. Many embodiments of the inventions relate to the identification of class and / or species of the amide compounds of Formula (I) which modulate (increase or decrease) the activity of sweet taste receptor T1 R2 / T1 R3 (preferably hT1 R2 / hT1 R3) (alone or in combination with another compound that activates hT1 R2 / hT1 R3, or otherwise induces a sweet taste, for example, sucrose, glucose, fructose and the like.) Particularly, the invention relates to amides of the formula (I) that modulate the activity of hT1 R2 / hT1 R3 (human sweet receptor) in vitro and / or in vivo In another aspect, the invention relates to compounds that modulate the human perception of sweet taste, alone or in combination with another compound or flavoring composition, when added to an edible or medicinal product or composition In some embodiments of the invention, it has been found with great surprise that at least some of the amide compounds of Formula (I) can modular l to human perception of the pungent and sweet flavor, alone or in combination with another compound or flavoring composition, when added to a product or an edible or medicinal composition.

In Vitro Acid Flavor Receptor Activation Assay hT1R1 / hT1R3 In order to identify new flavored flavoring and improving agents, including compounds with tasty agonist and enhancer activities (dual activity), the compounds of Formula (I) were selected in assays primary and secondary trials including the dose response of the compound and the breeding trial. In a primary assay for the potential ability to modulate the pungent taste, the amide compounds of Formula (I) which can be either flavorful flavoring agents in their own ratio or MSG flavor enhancers are identified and the classifications of their activities are give as a percentage of the maximum MSG intensity (%). In the dose response of the compound, an EC50 is calculated to reflect the potency of the compound as an agonist or as a tasty enhancer. A cell line derivative HEK293 (see for example, Chandrashekar, et al., Cell (2000) 100: 703-711) stably expressing Ga15 and hT1R1 / hT1R3 under an inducible promoter (see WO 03/001876 A2) was used for identify compounds with tasty flavor properties. The compounds covered in this document were initially selected based on their activity in the cell line hT1 R 1 / hT1 R3-H EK293-Ga15. The activity was determined using an automated fluorometric imaging assay on a FLIPR instrument (Fluorometric Intensity Plate Reader, Molecular Devices, Sunnyvale, CA) (designated FLIPR assay). Cells from one clone (designated clone 1-17) were seeded into 384 well plates (at approximately 48,000 cells per well) in a medium containing Dulbecco's Modified Eagle Medium (DMEM) supplemented with GlutaMAX (I nvitrogen , Carisbad, CA), 10% of fetal bovine serum, dialyzed (Invitrogen, Carisbad, CA), 1 00 Units / ml of Penicillin G, 100 μg / ml of Streptomycin (Invitrogen, Carisbad, CA) and 60 pM of mifepristone (to induce the expression of hT1 R1 / hT1 R3 (see WO 03/001876 A2) Cells 1-17 were cultured for 48 hours at 37 ° C. Cells 1-17 were then loaded with calcium dye Fluo-3AM (Molecular Probes, Eugene, OR), 4 μM in a phosphate buffer saline solution (D-PBS) (I nvitrogen, Carisbad, CA) for 1.5 hours at room temperature After replacement with 25 μL of D-PBS, the stimulation was performed on the FLIPR instrument and at room temperature by the addition of 25 μl of D-PBS supplemented with different Mules in concentrations that correspond to twice the desired final level. The receptor activity was quantified by determining the maximum fluorescence increases (using an excitation of 480 nm and an emission of 535 nm) after normalization to the basal fluorescence intensity measured before the stimulation. For dose response analysis, stimuli were presented in duplicate in 10 different concentrations ranging from 1.5 nM to 30 μM. The activities were normalized to the response obtained with 60 mM of monosodium glutamate, a concentration that produces the maximum receptor response. The EC5o (concentration of the compound that causes 50% activation of the receptor) were determined using a non-linear regression algorithm, where the Hill slope, the straight background lines and the upper straight lines were allowed to vary. Identical results were obtained when analyzing dose response data using commercially available software for non-linear regression analysis such as GraphPad PRISM (San Diego, California). In order to determine the dependence of hT1R1 / hT1R3 for the cellular response to different stimuli, the selected compounds were subjected to a similar analysis in cells 1-17 that has not been induced for receptor expression with mifepristone (designated as cells). -17 induced). Uninduced 1-17 cells do not show any functional response in the FLIPR assay to monosodium glutamate or other flavorful substances. Compounds were presented to uninduced acre cells at 10 μM or three times the maximum stimulation used in the dose response analysis. The compounds covered in this document do not show any functional response when uninduced acre cells are used in the FLIPR assay. In some aspects of the present invention, an EC50 lower than approximately 10 mM is indicative of compounds that induce T1R1 / T1R3 activity and is considered a tasty agonist. Preferably, a tasty agonist will have EC50 values of less than about 1 mM; and more preferably will have EC50 values of less than about 20 μM, 15 μM, 10 μM, 5 μM, 3 μM, 2 μM, 1 μM, 0.8 μM or 0.5 μM. In the acre taste enhancement activity assay experiments, which produce a measure of the "EC50 ratio" of how effectively the amide compounds of the invention improve the flavor taste. (usually MSG) already in a test solution. A series of measurements of dose response is operated on solutions comprising MSG alone, then a second dose response is operated with MSG in combination with predetermined amounts of a candidate compound of Formula (I) at the same time. In this assay, increased concentrations of monosodium glutamate (ranging from 12 μM to 81 mM) were presented, in duplicate, in the presence or absence of a fixed concentration of the test compound. The concentrations of the typical compound tested were 30 μM, 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM and 0.03 μM. The relative efficacy of compounds of Formula (I) in the enhancement of the receptor was determined by calculating the magnitude of a change in EC50 for monosodium glutamate. The improvement was defined as a ratio (EC50R) corresponding to the EC50 of sodium glutamate, determined in the absence of the test compound, divided by the EC50 of the monosodium glyutamate, determined in the presence of the test compound. Compounds that exhibit EC50R > 2.0 were considered breeders. Alternatively established, "ratio of EC50" when compared to MSG is calculated based on the following definitions: Ratio of EC50 against MSG = EC50 (MSG) / EC5o (MSG + [Compound]). Wherein "[compound]" refers to the concentration of the compound of Formula (I) used to produce (or enhance or potentiate) the dose response of MSG. It should be noted that the ratio of EC50 measured may depend a little on the concentration of the compound itself. Preferred savory improvers would have a high EC50 ratio against MSG at a low concentration of the compound used. Preferably, the EC50 ratio experiments for measuring the acre enhancement are operated at a concentration of a compound of Formula (I) between about 10 μM to about 0.1 μM, or preferably at 1.0 μM or 3.0 μM.

An EC50 ratio of more than 1 is indicative of a compound that modulates (potentiates) the hT1 R1 / hT1 R3 activity and is a tasty enhancer. More preferably, the flavor enhancer compounds of Formula (I) will have EC5o ratio values of at least 1.2, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 or 10.0 or even higher. In one aspect, the degree of flavor modulation of a particular compound is evaluated based on its effect on MSG activation of T1R1 / T1R3 in vitro. It is anticipated that similar assays can be designed using other known compounds to activate the T 1 R 1 / T 1 R 3 receptor. The specific compounds and generic classes of compounds which have been shown to modulate hT1 R1 / hT1 R3 based on their EC50 ratios evaluated according to the above formula are identified in the detailed description of the invention, the examples and the claims. The procedures used for taste testing of the pungent / palatable compounds of Formula (I) are reported below. Comparable EC50 assays for the activity of the compounds of Formula (I) for sweet receptor agonism and / or the perception of sweet taste in human beings are also reported below.

Sweet Taste Receptor Activation Assay hT1R2 / hT1R3 In Vitro A cell line derivative HEK293 (Chandrashekar, J., Mueller, KL, Hoon, MA, Adler, E., Feng, L., Guo, W., Zuker, CS, Ryba, NJ, Cel, 1 2000, 100, 703-711), which stably express Ga15 and hT1R2 / hT1R3 (Li, X., Staszewski, L., Xu, H., Durick, K., Zoller, M ., Adler, E. Proc. Nati Acad Sci USA 2002, 99, 4692-4696). See also World Patent # WO 03/001876 A2) was used to identify compounds with sweet taste improving properties. The compounds covered in this document were initially selected based on their activity in the hT1 R2 / hT1 R3-HEK293-Ga15 cell line (Li, et al., Vide supra). The activity was determined using an automated fluorometric imaging assay on a FLIPR instrument (Fluorometric Intensity Plate Reader, Molecular Devices, Sunnyvale, CA) (designated FLIPR assay). Cells from one clone (designated S-9 cells) were seeded in 384-well plates (in approximately 50,000 cells per well) in medium containing Low Glucose in DMEM (Invitrogen, Carisbad, CA), 10% serum of dialyzed fetal bovine (Invitrogen, Carisbad, CA), 100 units / ml of Penicillin G, and 100 μg / ml of Streptomycin (Invitrogen, Carisbad, CA) (Li, et al., vide supra) see also World Patent # WO 03/001876 A2). The S-9 cells were cultured for 24 hours at 37 ° C. The S-9 cells were then loaded with calcium dye Fluo-3AM (Molecular Probes, Eugene, OR), 4 μM in a phosphate buffer saline solution (D-PBS) (Invitrogen, Carisbad, CA), for 1 hour at room temperature. After replacement with 25 μl of D-PBS, stimulation was performed on the FLIPR instrument and at room temperature by the addition of 25 μl of D-PBS supplemented with different stimulus in concentrations corresponding to twice the desired final level. The receptor activity was quantified by determining the maximum fluorescence increases (using an excitation of 480 nm and 535 nm emission) after normalization to basal fluorescence intensity measured before stimulation. For analysis of dose responses, the stimuli were presented in duplicate at 10 different concentrations ranging from 60 nM to 30 μM. The activities were normalized to the response obtained with 400 mM D-fructose, a concentration that produces the maximum receptor response. The EC50 were determined using a non-linear regression algorithm (using Senomyx software, Inc.), where the Hill slope, the straight line, and the upper straight line were allowed to vary. Identical results were obtained when the dose response data were analyzed using commercially available software for non-linear regression analysis such as GraphPad PRISM (San Diego, CA). In order to determine the dependence of hT1 R2 / hT1 R3 for the cellular response to different stimuli, the selected compounds were subjected to a similar analysis in HEK293-Ga15 cells (which do not express the human sweet receptor). The EK293-Ga15 H cells do not show any functional response in the FLI PR assay to D-Fructose or any other known sweeteners. Similarly, the compounds covered in this document do not induce any functional response when H EK293-Ga15 cells are used in the FLIPR assay.

EXAMPLES The following examples are given to illustrate a variety of exemplary embodiments of the invention and are not intended to be limiting in any way. For the purpose of this document, the compounds individually described in the following Examples 1-174 and the corresponding Tables A-E may be referred to in stenography by the example number. For example, as shown immediately below, Example 1 describes a synthesis of a particular compound (N- (heptan-4-yl) benzo [d] [1,3] dioxol-5-carboxamide) and the results of experimental tests. of its biological effects, which compound is and can be referred to herein in the form of stenography as Compound 1. Similarly, the first compound illustrated in Table A can be referred to elsewhere as Compound A1 herein.

Example 1 N- (heptan-4 l) benzordU1, 31-dioxo-5-carboxamide To a solution of heptan-4-amine (8.06 ml, 54 mmol) in triethylamine (15.3 ml, 108 mmol) and dichloromethane (135 ml), in drops at 0 ° C, a solution of benzo chloride [1, 3] dioxol-5-carbonyl (10 g, 54 mmol) dissolved in dichloromethane (135 ml). The reaction mixture was stirred for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc. The organic layer was washed successively with 1N aqueous HCl, 1N aqueous NaOH, water, brine, dried (MgSO4) and concentrated. The residue was recrystallized from EtOAc and the Hexanes produced 6.9 g of N- (heptan-4-yl) benzo [d] [1,3] dioxol-5-carboxamide (48.3%) as a white solid. H NMR (500 MHz, CDCl 3): d 0.92 (t, 6H), 1.38 (m, 6H), 1.53 (m, 2H), 4.11 (m, 1H), 5.63 (m, 1H), 6.01 (s, 2H) ), 7.98 (d, 1H), 7.27 (s, d, 2H). MS (M + H, 264). The compound had EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.2 μM and when presented in 0.03 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 6.92.

Example 2 N- (2-methylheptan-4-yl) benzordU1.31dioxol-5-carboxamide Prepared in a manner similar to Example 1 using benzo [d] [1, 3] dioxol-5-carbonyl chloride and 2-methylheptan-4-amine (example 2a). 1 H NMR (500 MHz, CDCl 3): d 0.93 (m, 9H); 1.38 (m, 5H); 1.53 (m, 1 H); 1.66 (m, 1 H); 4.21 (m, 1 H); 5.61 (d, 1 H); 6.01 (s, 2H); 6.82 (d, 1 H); 7.26 (m, 2H). MS (278, M + H) a. Preparation of 2-methylheptan-4-amine: To a solution of 2-methylheptan-4-one (4.24 g, 33. 07 mmoles), in methanol (60 ml), ammonium acetate (25.50 g, 330.71 mmol) and sodium cyanoborohydride were added. (2.08 g, 33.07 mmoles). The reaction mixture was stirred at room temperature for about 24 hours. The solvent was removed under pressure and the residue was diluted with water and basified with 15% aqueous NaOH and extracted with ether. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to give 3.3 g of 2-methy1-heptane-4-amine (77%). MS (M + H, 130). The compound had EC50 for activation of an acre receptor hT1 R1 / hT1 R3 expressed in a HEK293 cell line of 0.22 μM.

Example 3 N- (2-methylhexan-3-yl) benzordip, 31-dioxol-5-carboxamide Prepared in a manner similar to Example 1 using benzo [d] [1, 3] dioxol-5-carbonyl chloride and 2-methylhexan-3-amine (Example 3a). 1 H NMR (500 MHz, CDCl 3): d 0.93 (m, 9H); 1.37 (m, 3H); 1.56 (m, 1H); 1.83 (m, 1H); 4.01 (m, 1H); 5.67 (d, 1H); 6.02 (s, 2H); 6.82 (d, 1H); 7.28 (m, 2H). MS (M + H, 264). to. 2-Methylhexan-3-amine was prepared using the same procedure described in example 2a starting from 2-methylhexan-3-one. Performance: 40%. 1 H NMR (500 MHz, CDCl 3): d 0. 86 (d, 3 H); 0.91 (m, 6H); 1.20-1.29 (m, 2H); 1.38-1.47 (m, 2H); 1.47 (s, 2H); 1.58 (m, 1H); 2.51 (m, 1H). MS (M + H, 116). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.61 μM.

Example 4 N- (2,3-dimethylcyclohexylbenzide U1.31d) oxo-5-carboxamide They were each dissolved in acetonitrile / dichloromethane (200 μL, 2: 1), 2,3-dimethylcyclohexamine (20 μmol) and benzo [d] [1,3] dioxol-5-carboxylic acid (1.1 equivalents). PS-carbodiimide resin (2 equivalents) was loaded into a Greiner 1.2 ml 96-well plate, followed by the addition of amine and acid solutions. Hydroxybenzotriazole (1.1 equivalents) was dissolved in DMF (100 ml) and added into the reaction well. The reaction was stirred overnight at room temperature. Once the reaction was completed, PS-Trisamine resin (1.5 equivalents) was added into the reaction mixture and the solution allowed to stir overnight at room temperature. Acetonitrile (200 mL) was added into the reaction well and the top clear solution was transferred into a new plate. The solution was evaporated to give N- (2,3-dimethylcyclohexyl) benzo [d] [1,3] dioxol-5-carboxamide. MS (M + H, 276.20). The compound had EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.45 μM and when presented at 1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 8.4.

Example 5 N- (5-methylhexan-3-yl) benzord1M, 31d -oxo-5-carboxamide Prepared in a manner similar to Example 1 using benzo [d] [1, 3] dioxol-5-carbonyl chloride and 5-methylhexan-3-amine (example 5a). Yield: 48%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 9H); 1.37 (t, 3H); 1.45 (m, 1H); 1.64 (m, 2H); 4.13 (m, 1H); 5.61 (d, 1H); 6.01 (s, 2H); 6.82 (d, 1H); 7.27 (m, 2H). MS (M + H, 264). to. 2-Methylhexan-3-amine was prepared using the same procedure described in Example 2a from 5-methylhexan-3-one. Yield: 54%. MS (M + H, 116). The compound had EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.57 μM.

Example 6 2- (benzordip.31dioxol-6-carboxamido) -4-methyl entanoate of (R) -methyl Prepared in a manner similar to Example 1 using benzo [d] [1,33-dioxol-5-carbonyl chloride and methyl ester D-leucine hydrochloride. Performance: 83%. 1 H NMR (500 MHz, CDCl 3): d 0. 98 (m, 6H); 1.63-1.67 (m, 1H); 1.71-1.76 (m, 2H); 3.76 (s, 3H); 4.83 (m, 1H); 6.03 (s, 2H); 6.38 (d, 1H); 6.83 (d, 1H); 7.32 (s, 1H); 7.33 (d, 1H). MS (M + H, 294). p.f: 89-90 ° C. The compound had EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.34 μM, and when presented in 0.1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 4.9.

Example 7 N- (1,2,3,4-tetrahydronaphthalen-1-yl) benzordU1,31dioxol-5-carboxamide Prepared in a manner similar to Example 4 using benzo [d] [1,3] dioxol-5-carboxylic acid and 1,2,3,4-tetrahydronaphthalen-1-amine. MS (M + H, 296.6). The compound had EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.71 μM and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 7.8.

Example 8 (R) -N-f 1 -hydroxy-4-methyl I penta n-2-i I) benzo rdU1,31 dioxide 1-5-carboxamide Prepared in a manner similar to Example 4 using benzo [d] [1, 3] dioxol-5-carboxylic acid and (R) -aminoleucinol. MS (M + H, 266.1). The compound had an EC5o for activation of the acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 9 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC5o ratio of 2.

Example 9 Acid (R.). -N- (1-methoxy-4-metHpentan-2-benzordip, 31-dioxol-5- benzo rdip.31-dioxol-5-carboxylic acid Prepared in a manner similar to Example 4 using (R) -1-methoxy-4-methyl and pentan-2-amine (example 9a). Performance: 55%. 1 H NMR (500 MHz, CDCl 3): d 0.95 (m, 6H); 1.43 (m, 1H); 1.55 (m, 1H); 1.65 (m, 1H); 3.36 (s, 3H); 3.46 (m, 2H); 4.33 (m, 1H); 6. 01 (s, 2H); 6.13 (d, 1H); 6.82 (d, 1H); 7.28 (m, 2H). MS (M + H, 280). to. (R) -1-methoxy-4-methylpentan-2-amine To a solution of (R) -2- (1-methoxy-4-methylpentan-2-yl) isoindoline-1,3-dione (example 9b) ( 3.87 g, 14.84 mmol) in methanol (30 ml), hydrazine hydrate (0.866 ml, 17.81 mmol) was added and the reaction mixture was heated at 45 ° C for about 3 hours. The mixture was acidified with 2N HCl and stirred at 45 ° C for 30 minutes. The solution was cooled to room temperature, filtered and evaporated. The residue was stirred with 2N NaOH and extracted with ether, dried over MgSO 4, filtered and evaporated to give 1.51 g of (R) -1-methoxy-4-methylpentan-2-amine. Performance 77%. 1 H NMR (500 MHz, CDCl 3): d 0.91 (m, 6H); 1.17 (m, 2H); 1.58 (s, 2H); 1.71 (m, 1H); 3. 02 (m, 1H); 3.10 (m, 1H); 3.32 (m, 1H); 3.35 (s, 3H). b. (R) -2- (1-methoxy-4-methylpentan-2-yl) iso indo lin-1,3-dione (R) -2- (1-hydroxy-4-methylpentan-2-yl) isoindoline was dissolved -1,3-dione (example 9c) (5.888 g, 23.87 mmol) in dry THF (25 ml) and hexamethylphosphoramide (30 ml) and the solution was cooled to 0 ° C. Sodium hydride (60% in mineral oil, 1.15 g, 28.65 mmol) was added and after 10 minutes iodomethane (7.43 mL, 119.35 mmol) was added dropwise and the solution was slowly warmed to room temperature and stirred overnight . The reaction mixture was poured into ice / water, extracted with EtOAc, washed with brine, dried over MgSO 4, filtered and evaporated. The residue was purified on silica gel (20% EtOAc in hexane) to give 3.92 g of (R) -2- (1-methoxy-4-methyipentan-2-yl) isoindoin-1,3-dione (63%). ). c. (R) -2- (1-hydroxy-4-methylpentan-2-yl) isoindoline-1,3-dione: Phthalic anhydride (10.30 g, 69.55 mmol) and D-Leucinol (8.15 g, 69.55 mmol) were mixed in THF (100 mL), the reaction mixture was heated to 85 ° C and refluxed for 18 hours. After cooling to room temperature, water was added and the solution was extracted with EtOAc, the extracts were washed with 1N HCl, water, aqueous NaHC 3, water and brine, dried over MgSO 4, filtered and evaporated to give 8.1 g of (R) -2- (1-hydroxy-4-methylpentan-2-M) isoindoline-1,3-dione (47%). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 6H); 1.54 (m, 2H); 1.99 (m, 1H); 3.86 (m, 1H); 4.04 (m, 1H); 4.47 (m, 1H); 7.72 (m, 2H); 7.83 (m, 2H). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.5 μM.

Example 10 2- (benzordU1, 31dioxol-6-carboxamido) -3-methylbutanoate of IR-methyl Prepared in a manner similar to Example 4, using benzo [d] [1, 3] dioxol-5-carboxylic acid and 2-amino-3-methylbutanoate of (R) -methyl. Yield: 50%. MS (M + H; 280.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.16 μM.

Example 11 Diacid phosphate 2- (benzordU1.31dioxol-ß-carboxamido) -4- methylpentyl It was dissolved in anhydrous acetonitrile (2 mL) N- (1-hydroxy-4-methylpentan-2-yl) benzo [d] [1,3] dioxol-5-carboxamide (example 11a) (0.57 mmol, 151 mg) and A solution of 0.45 M tetrazole in acetonitrile was added under nitrogen and stirred for 5 minutes. Then 0.627 (1.1 equivalents, 207 μl) of dibenzyl diisopropylphosphoramide was added dropwise under nitrogen. The mixture was stirred for 1 hour. The solvent was evaporated and an unpurified intermediate was dissolved in DCM and washed twice with 2% potassium carbonate and brine and dried with sodium sulfate. The material was dried and oxidized with 5 ml of tert-butylhydroperoxide (4M solution in an unborn) for 30 minutes. The solvent was evaporated and the dibenzylester intermediate was purified (preparative TLC). The benzyl groups were hydrolysed using trifluoroacetic acid (3 ml of a mixture of 95% TFA and 5% water, 1.5 hours, room temperature). The final product was dried giving 69 mg (35%) of pure material. 1 H NMR (500 MHz, CDCl 3): d 0. 88-0.90 (t, 6H), 1.23-1.27 (m, 2H), 1.36-1.37 (m, 1H), 1.53-1.62 (m, 2H), 3.93 ( s, 1H), 3.98 (s, 1H), 4.32 (s, 1H), 5.90 (s, 2H), 6.66-6.67 (d, 1H), 6.98-6.99 (b, 2H), 7.14 (s, 2H); 31p: d 0.51 (s). MS (M + H, 346.0). to. N- (1-hydroxy-4-methylpentan-2-yl) benzo [d] [1, 3] dioxol-5-carboxamide was prepared in a manner similar to Example 4 from piperonyl acid and 2-amino-4 -methyl-pentan-1-ol. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 10.9 μM.

Example 12 N - (h ex n -3-i I) -4-m ethoxy -3-methyl benzamide Prepared in a similar manner to example 4, using 4-methoxy-3-methylbenzoic acid and hexan-3-amine (example 28a). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 6H); 1.41 (m, 4H); 1.46 (m, 1H); 1.64 (m, 1H); 2.24 (s, 3H); 3.87 (s, 3H); 4.08 (m, 1H); 5.69 (d, 1H); 6.83 (d, 1H); 7.54 (s, 1H); 7.62 (d, 1H). MS (M + H, 250). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.12 μM.

Example 13 (R) -N- (1- (dimethylamino) -4-methyl-1-oxopentan-2-I) benzo rdU1.31 di oxo I-5 -carboxam id a (R) -2- (Benzo [d] [1,3] dioxol-6-carboxamido) -4-methylpentanoic acid (example 13a) (52 mg, 0.19 mmol) was condensed in DMF (4 mL) and dimethylamine (2M). in methanol, 36 μL, 2 equivalents) in the presence of HOBt (26 mg, 1 equivalent) and of 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (44 mg, 1.2 equivalents) at room temperature during the night. The reaction mixture was evaporated and the residue was dissolved in ethyl acetate and washed successively with saturated NaHCO 3 and water, dried over MgSO, filtered and evaporated to give 48.6 mg of the product (84%). The material was further purified using RPHPLC. 1 H NMR (500 MHz, CDCl 3): d 0.93-0.94 (d, 3 H), 1.03-1.05 (d, 3 H), 1. 48-1.52 (m, 1 H), 1.59-1.63 (m, 1 H), 2.98 ( s, 3H), 3.14 (s, 3H), 5.17-5.21 (m, 1H), 6.01 (s, 2H), 6.80-6. 82 (d, 1H), 6.89-6.91 (d, 1H), 7.29-3.30 (d, 1H), 7.33-7.35 (dd, 1H). MS (M + H; 307.2). to. (R) -2- (Benzo [d] [1, 3] dioxol-6-carboxamido) -4-methylpentanoic acid: Prepared in a manner similar to Example 1, using benzo [d] [1, 3] dioxol chloride -5-carbonyl and D-Leucine. Performance: 55%. MS (M + H, 280.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.06 μM.

Example 14 2- (benzordU1.31dioxol-6-carboxamido) pentyl acetate To a solution of N- (1-hydroxypentan-2-yl) benzo [d] [1, 3] dioxol-5-carboxamide (example 14a) (59.8 mg, 0.238 mmol) in dichloromethane (5 mL) was added triethylamine (166 mL, 1.19 mmol). Acetyl anhydride (112.5 mL, 1.19 mmol) was added slowly and the mixture was stirred under argon at room temperature overnight. The solution was washed successively with a saturated solution of sodium bicarbonate, water and brine. The organic layer was dried over anhydrous sodium sulfate. Filtration followed by solvent removal under reduced pressure yielded 50.8 mg of 2- (benzo [d] [1,3] dioxol-6-carboxamido) pentyl acetate (73%). 1 H NMR (CDCl 3): d 0. 95 (t, 3 H, J = 7.2 Hz), 1.43 (m, 2 H), 1.57 (m, 2 H), 2.1 (s, 3 H), 4.11 (dd, 1 H, J = 3.5 Hz, J = 11.5 Hz), 4.27 (dd, 1H, J = 3.5 Hz, J = 11.4 Hz), 4.29 (m, 1H), 6.02 (s, 2H), 6.1 (m, 1H), 6.82 (d , 1H, J = 8.4 Hz), 7.27 (m 2H). MS (M + H, 294). to. N- (1-hydroxypentan-2-yl) benzo [d] [1,3] dioxol-5-carboxamide was prepared in a manner similar to Example 4 using benzo [d] [1, 3] dioxol-5 acid carboxylic acid and 2-aminopentan-1-ol. Yield: 76%. MS (M + H, 252). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 11.9 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 4.1.

Example 15 (R) -N- (4-methy1-1-oxo-1- (2-pyridin-3-yl) eti lam) pentan-2- i) ben zordl M .31dioxol-5 -carboxam ida Prepared in a manner similar to example 13, using 2- (3-pyridyl) ethylamine and (R) -2- (benzo [d] [1,3] dioxol-6-carboxamido) -4-methylpentanoic acid (example 13a) . (MS M + 384.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.7 μM.

Example 16 N - ((R) -1- (2- (hydroxymethyl) pyrrolidin-1-yl) -4-methy1-1-oxopentan-2-yl) benzordiri.31-dioxol-5-carboxamide Prepared in a manner similar to example 13 using R / S propinol and (R) -2- (benzo [d] [1,3] dioxol-6-carboxamido) -4-methylpentanoic acid (example 13a). (MS M + 363.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3 μM.

Example 17 N- (he tan-4-yl) -β-methylbenzordU1,31dioxol-5-carboxamide Prepared in a manner similar to Example 4 using 6-methylbenzo [d] [1,3] dioxol-5-carboxylic acid and heptan-4-amine. MS (M + H, 278.67). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.11 μM.

Example 18 N- (heptan-4-yl) -2-methylbenzordip .31dioxol-5-carboxamide N- (Heptan-4-yl) -3,4-dihydroxybenzamide (example 18a) (0.5 mmol) was dissolved in toluene (1.6 mL). P-Toluenesulfonic acid monohydrate (0.3 equivalents) was added to the reaction, followed by the addition of acetaldehyde (2 equivalents). The reaction was performed using microwave (180C, 300W) and was activated for 10 minutes. The solvent was evaporated. The residue was dissolved in methanol (1 mL) and purified by HPLC. Yield 20% MS (M + H 278.10). to. N- (Heptan-4-yl) -3,4-dihydrobenzamide was prepared in a manner similar to Example 4 using 3,4-dihydroxybenzoic acid and heptan-4-amine. Performance: 25%. MS (M + H, 252.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 0.1 μM and when presented in 0.03 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 3.68.

Example 19 2- (5-heptan-4-ylcarbamoyl) benzo [d] [1,3] dioxol-2-yl) ethyl acetate It was dissolved in dry acetone N- (heptan-4-yl) -3,4-dihydroxybenzamide (example 18a) (0.29 mmol, 75 mg) with excess of 6 equivalents (242 mg) of potassium carbonate, then 1.2 equivalents was added Excess (36 μl) of propionic acid ethyl ester and a mixture was refluxed for 24 hours. The solvent was evaporated and a solid was dissolved in dichloromethane and extracted with 10% NaHCO 3 and water. The crude product was purified by chromatography on silica gel to give 72 mg of the desired product (71%). 1 H NMR (500 MHz, CDCl 3): d 0.91-0. 94 (t, 6H), 1.23-1.30 (m, 4H), 1.37-1.41 (4H), 2.97-2.98 (d, 2H), 3.70-3.74 (dd, 2H), 4.12-4.17, (m, 1H) , 4.2-4.24 (m, 3H), 5.61-5.64 (d, 1H), 6.58-6.60 (t, 1H), 6.79-6.81 (d, 1H), 7.23 (s, 1H), 7.60-7.85 (b, 1 HOUR). MS (M + H, 350.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 14 μM and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 2.5.

Example 20 N- (heptan-4-yl) -2.2-d, methylbenzordip, 31dioxol-5-carboxamide Prepared in a manner similar to Example 4, using sodium 2,2-dimethylbenzo [d] [1,3] dioxol-5-carboxylate and 4-heptylamine (example 20a). Yield 30%. 1H NMR: d 0.92 (t, 6H, J = 7.2 Hz), 1.42 (m, 6H), 1.53 (m, 2H), 1.68 (s, 6H), 4.12 (m, 1H), 5.61 (d, 1H, J = 8.9 Hz), 6.72 (d, 1H, J = 8Hz), 7.16 (d, 1H, J = 1.5 Hz), 7.22 (dd, 1H, J = 1.5 Hz, J = 17 Hz). MS (M + H, 292). to. 2,2-dimethylbenzo [d] [1,3] dioxol-5-carboxylic acid sodium and 4-heptylamine: 2,2-dimethylbenzo [d] [1,3] dioxol-5-carboxylic acid ethyl ester (example 20b) was stirred ) (461 mg, 2.08 mmol) in dioxane (16 mL) and 1.0N aqueous NaOH (4.16 mL) for 20 hours at room temperature. The solvent was removed under reduced pressure to produce the desired product (449 mg). (M-H, 193). b. Ethyl 2,2-dimethylbenzo [d] [1, 3] dioxol-5-carboxylate: Ethyl 3,4-dihydroxybenzoate (910.9 mg, 5 mmol) was combined with 2,2-dimethoxypropane (1.23 ml, 10 mmol) and a catalytic amount of p-toluenesulfonic acid in toluene. The mixture was heated to reflux using a Dean-Stark trap for 20 hours. After removal of the solvent under reduced pressure, the crude was dissolved in ethyl acetate and washed successively with a saturated aqueous solution of sodium bicarbonate, water and brine. The organic layer was dried over anhydrous sodium sulfate. Purification by chromatography on silica gel using a gradient of hexane: ethyl acetate, 90:10 to 75:25 yielded a white powder (539.1 mg, 49%). 1 H NMR (CDCl 3): d 1.36 (t, 3 H, J = 7.2 Hz), 1.69 (s, 6 H), 432 (q, 2 H, J = 7.1 Hz, J = 14.2 Hz), 6.74 (d, 1 H, d , J = 8.2 Hz), 7.3cj (d, 1h, J = 1.7 Hz), 7.61 (dd, 1H, J = 1.8 Hz, J = 8.3 Hz). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.7 μM.

Example 21 N -f hepta n-4-i I) -2-is or propyl benzo rdlM, 31 di oxo I-5 -carboxam ida Prepared in a similar to example 4, using 2-isopropylbenzo [d] [1,3] dioxol-5-carboxylic acid (example 21a) and 4-heptylamine. Yield: 34%. 1 H NMR (CDCl 3): d 0. 92 (t, 6H, J- 7. 2Hz), 1.04 (d, 6H, J = 6.9 Hz), 1.40 (m, 6H), 1.43 (m, 2H), 2.15 ( m, 1H), 4.11 (m, 1H), 5.62 (d, 1H, J = 8.9Hz), 5.96 (d, 1H, J = 4.4 Hz), 6.75 (d, 1H, J = 8.0 Hz), 7.19 ( d, 1H, J = 1.8 Hz), 7.22 (d, 1H, J = 1.9 Hz), 7.23 (d, 1H, J = 1.6 Hz). MS (M + H, 291). to. 2-isopropylbenzo [d] [1,3] dioxol-5-carboxylic acid: 3,4-dihydrobenzoic acid (154.12 mg, 1 mmol) and isobutyraldehyde (182 μl, 2 mmol) in toluene (3 mL) were combined and a catalytic amount of the p-toluenesulfonic acid was added. The mixture was subjected to microwave for 10 minutes at 180 ° C with a power system at 275. The solution was filtered and evaporated to yield 100 mg of the desired product (48%). MS (M-H, 207). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 11.5 μM and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC5o ratio of 2.2.

Example 22 2,2-difluoro-N- (heptan-4-yl) benzordU1.31dioxol-5-carboxamide Prepared in a manner similar to Example 4, using 2,2-difluorobenzo [d] [1,3] dioxol-5-carboxylic acid and 4-heptylamine. (M + H, 300.2). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.51 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 2.87.

Example 23 (1-propyl-butiDamide of 2,3-Dihydro-benzoM, 41-dioxin-5-carboxylic acid Prepared in a manner similar to Example 4, using 2,3-dihydro-benzo [1,4] dioxin-6-carboxylic acid and a heptan-4-amine. MS (M + H, 278.2). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.49 μM.

Example 24 N- (heptan-4-yl) -3,4-dihydro-2H-benzorbU1.41dioxepin-7-carboxamide Prepared in a manner similar to Example 4, using 2,3-dihydro-benzo [1,4] dioxin-6-carboxylic acid and heptan-4-amine. MS (M + H, 292.2). The compound had an EC5o for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 6.4 μM.

Example 25 Benzofuran-2-carboxylic (1-propylbutyl) amide Prepared in a manner similar to Example 1, using benzofuran-2-carbonyl chloride and heptan-4-amine. Performance: 73%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6 H, J = 7.2 Hz), 1.41 (m, 8 H), 3.01 (s, 3 H), 4.18 (m, 1 H), 6.29 (d, 1 H, J = 9.94 Hz), 7.20 (d, 1H, J = 8.62 Hz), 7.37 (m, 2H), 7.44 (s, 1H). MS (M + H, 260) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.88 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with a relationship of EC50 of 2.6.

Example 26 N -f he ptan-4-i I) -5-m eti I benzofuran -2 -carboxam ida Prepared in a manner similar to Example 4, using 5-methylbenzofuran-2-carboxylic acid (example 26a) and heptan-4-amine. Yield: 46%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (t, 6 H, J = 7.2 Hz), 1.41 (m, 10 H), 2.44 (s, 1 H), 4.18 (m, 1 H), 6.29 (d, 1 H, J = 8.6 Hz), 7.21 (d, 1H, J = 8.4 Hz), 7.37 (m, 2H), 7.44 (s, 1H). MS (M + H, 274). to. 5-methylbenzofuran-2-carboxylic acid: 2-Hydroxy-5-methylbenzaldehyde (544.2 mg, 4 mmol) was combined with diethylbromomalonate (1 mL, 6 mmol) and potassium carbonate (1.1 g, 8 mmol) in methyl ethyl ketone (5 mM). mL) and the mixture was heated to reflux overnight. The solvent was removed by rotary evaporation to produce an unpurified oil. The oil was then taken in a solution of 10% potassium hydroxide in ethanol (10 mL) and heated to reflux for 45 minutes. The solvent was removed under reduced pressure and the residue was then treated with a 2.0 N solution of H2SO4. The free acid was then extracted with copious amounts of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. Removal of ethyl acetate yielded 566 mg of 5-methyl-2-carboxybenzofuran (80%) as a yellowish powder. 1H NMR (500 MHz, CD3OD): (s, 3H), 7.30 (d, 1H, J = 8.7 Hz), 7.45 (d, 1H, J = 8.5 Hz), 7.51 (d, 2H, J = 7.5 Hz). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.94 μM.Example 27 (R) -methyl 4-methyl-2- (5-methylbenzofuran-2-carboxamido) pentanoate Prepared in a manner similar to Example 4, using 5-methylbenzofuran-2-carboxylic acid (example 26a) and methyl ester D-leucine. 1 H NMR (500 MHz, CDCl 3): d 0.98 (d, 3 H, J = 6.26 Hz), 1.00 (d, 3 H, J = 6.17 Hz), 1.56 (s, 3 H), 1.76 (m, 3 H), 2.48 ( s, 3H), 3.78 (s, 3H), 4.86 (m, 1H), 6.95 (m, 1H), 7.23 (dd, 1H, J = 8.54 Hz, J = 1.55 Hz), 7.40 (m, 2H), 7.44 (dd, 1H, J = 1.72, J = 0.9 Hz). MS 304 (M + H, 304) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.11 μM.

Example 28 N- (hexan-3-yl) -5-methylbenzofuran-2-carboxamide Prepared in a manner similar to example 4, using 5-methylbenzofuran-2-carboxylic acid (example 26a) and hexan-3-amine (example 28a). Performance: 49%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 6H), 1.40-1.68 (m, 6H), 2.36 (s, 3H), 4.07 (m, 1H), 5.74 (d, 1H, J = 8.97 Hz ), 7.16 (d, 1H, J = 7.80 Hz), 7.31 (dd, 1H, J = 1.73 Hz, J = 1.73 Hz), 7.66 (d, 1H, J = 1.72 Hz). MS (M + H, 260). to. Hexan-3-amine was prepared using the same procedure described in Example 2a from hexan-3-one. Yield: 58%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 6H); 1.36-1.58 (m, 6H); 2.83 (m, 1H); 3.12 (s, 2H). MS: (102, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.74 μM.

Example 29 N- (hexan-3-ih-5-methoxy benzofuran-2 -carboxam ida) Prepared in a manner similar to Example 4, using 5-methoxybenzofuran-2-carboxylic acid and hexan-3-amine (example 28a). Performance: 32%. 1 H NMR (500 MHz, CDCl 3): d 0.96 (m, 6H); 1.40-1.67 (m, 6H); 3.85 (s, 3H); 4.09 (m, 1H); 6.28 (d, 1H); 7.01 (dd, 1H); 7.08 (d, 1H); 7.38 (m, 2H). MS (276, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.4 μM.

Example 30 3-C 2-hexyl-2- (5-methoxybenzofuran-2-carboxamido) propionate of (R) -methyl Prepared in a manner similar to Example 4, using 5-methoxybenzofuran-2-carboxylic acid and (R) -methyl 2-amino-3-cyclohexylpropionate. Yield: 45: MS (M + H, 260.3). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.14 μM.

Example 31 5-methoxy-N- (5-methylhexan-3-yl) benzofuran-2-carboxamide Prepared in a manner similar to Example 4, using 5-methoxybenzofuran-2-carboxylic acid and 5-methylhexan-3-amine (example 5a). Performance: 67%. 1 H NMR (500 MHz, CDCl 3): d 0.96 (m, 9H); 1.39-1.52 (m, 3H); 1.66 (m, 2H); 3.85 (s, 3H); 4.17 (m, 1H); 6.24 (d, 1H); 7.01 (dd, 1H); 7.08 (d, 1H); 7.38 (m, 2H). MS (290, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.04 μM.

Example 32 Preparation of 4-chloro-2- (5-methylbenzofuran-2-carboxamido) pentanoate of (R -methyl) Prepared in a manner similar to Example 4 using 5-chlorobenzofuran-2-carboxylic acid and methyl ester D-leucine. MS (M + H, 324). The compound had an EC50 for the activation of an acre receptor hT1 R1 / hT1 R3 expressed in a HEK293 cell line of 0.82 μM.

Example 33 4-methyl-2- (3-methylbenzofuran-2-carboxamido) pentanoate of (R) - Prepared in a manner similar to Example 4, using 3-methylbenzofuran-2-carboxylic acid and D-leucine methyl ester. MS (M + H, 304). The compound had an EC50 for the activation of an acre receptor hT1 R1 / hT1 R3 expressed in a HEK293 cell line of 1.118 μM.

Example 34 N- (heptan-4-yl) benzorb-1-tofen-2-carboxamide Prepared in a manner similar to Example 4, using benzo [b] thiophene-2-carboxylic acid and 4-heptylamine. MS (M + H, 276). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.21 μM.

Example 35 N- (heptan-4-yl) - H -indole-2-carboxamide Prepared in a manner similar to Example 4, using 1H-indole-2-carboxylic acid and 4-heptylamine. MS (M + H, 259). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 6.8 μM.

Example 36 4-Methyl-2- (5-methyl-1 H-indole-2-carboxamido) pentanoate of (R) -methyl Prepared in a manner similar to Example 4, using 5-methyl-1 H-indole-2-carboxylic acid and the methyl ester of D-leucine. Yield: 50%. 1 H NMR (500 MHz, CDCl 3): d 0.98 (d, 3 H, J = 6.3 Hz), 1.00 (d, 3 H, J = 6.1 Hz), 2.44 (s, 3 H), 3,784 (s, 3 H), 4.87 ( m, 1H), 6.56 (d, 1H, J = 8.39 Hz), 6.85 (dd, 1H, J = 1.94 Hz, J = 0.68 Hz), 7.12 (dd, 1H, J = 8.46 Hz, J = 1.55 Hz) , 7.31 (d, 1H, J = 8.45 Hz), 7.42 (s, 1H) .. MS (MH +, 303). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 6.6 μM.

Example 37 N- (he tan-4-yl) -1-methyl-1H-indole-2-carboxamide Prepared in a manner similar to Example 4, using 1-methyl-1 H-indole-2-carboxylic acid and 4-heptylamine. Performance 45%. 1 H NMR (500 MHz, CDCl 3): d 0.95 (t, 6 H, J = 7.2 Hz), 1.46 (m, 4 H), 1.57 (m, 4 H), 4.05 (s, 3 H), 4.15 (m, 1 H), 5.85 (d, 1H), 6.80 (s, 1H), 7.14 (t, 1H, J = 7.4 Hz), 7.31 (t, 1H, J = 7.5 Hz), 7.38 (d, 1H, J = 8.4 Hz), 7.62 (d, 1H, J = 8 Hz). MS (M + H, 273). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.79 μM.

Example 38 N- (heptan-4-yl) -1H-benzord-1-imidazole-5-carboxamide Prepared in a manner similar to Example 4, using 1 H-benzo [d] imidazole-5-carboxylic acid and 4-heptylamine. Performance: 80%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (t, 6 H, J = 7.2 Hz), 1.42 (m, 6 H), 1.57 (m, 2 H), 4.21 (m, 1 H), 6.18 (m, 1 H), 7.64 (m, 2H), 8.16 (m, 1H), 8.28 (s, 1H). MS (M + H, 260). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 18.6 μM.

Example 39 (l-propyl butyl) benzoxazole-5-carboxylic acid amide Prepared in a manner similar to Example 4, using benzoxazole-5-carboxylic acid (Example 39a) and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3): d 8.16 (d, J = 5.4 Hz, 1 H) 7.89 (d, J = 8.6 Hz, 1 H), 7.64 (d, J = 8.6 Hz, 1 H), 5.82 (d, J = 8.6 Hz, 1H) 4.10-4.22 (m, 1H), 1.58-1.62 (m, 4H), 1.40-1.49 (m, 4H), 0.95 (t, J = 7.2 Hz, 6H); ESIMS: 261 (M + H). to. Benzoxazole-5-carboxylic acid: A mixture of 3-amino-4-hydroxybenzoic acid (500 mg, 3.26 mmol) and trimethyl orthoformate (5 mL) was heated at 65 ° C for 2 hours under argon. The reaction mixture was cooled to room temperature, filtered and washed with hexane. The filtrate was concentrated in vacuo to yield the product as a white solid (78 mg, 15%). 1 H NMR (500 MHz, CDCl 3): d 8.57 (d, J = 1.5 Hz, 1H), 8.20 (dd, J = 8.4, 1.8 Hz, 1H), 8.20 (s, 1H), 7.67 (d, J = 9.0 Hz, 1H). MS (M + H, 164). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.91 μM.

Example 40 (2-Methyl-benzoxazole-5-carboxylic acid 1-propyl-butylamide Prepared in a manner similar to Example 4 from 2-methylbenzoxazole-5-carboxylic acid (example 40) and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3) d 8.00 (d, J = 1.6 Hz, 1H), 7.77 (d, J = 8.5.1.6 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 5.79 (d , J = 8.9 Hz, 1H for NH) 4.10-4.22 (m, 1H), 2.66 (s, 3H), 1.58-1.65 (m, 4H), 1.38-1.55 (m, 4H), 0.94 (t, J- 7.2 Hz, 6H); MS (APCI, M + 1): 275.2. to. 2-methylbenzoxazole-5-carboxylic acid: A mixture of 3-amino-4-hydroxybenzoic acid (1.5 g, 9.79 mmol) and trimethyl orthoacetate (15 mL, large excess) was heated at 65 ° C for 5 hours under argon. The reaction mixture was cooled to room temperature, filtered and washed with hexanes. The filtrate was concentrated in vacuo to yield the product as a yellow solid (1.4 g, 80%). 1H NMR (500 MHz, CD3OD) d 8.26 (d, J = 1.7 Hz, 1H), 8.07 (dd, J = 8.5, 1.6 Hz, 1H), 7.67 (d, J = 8.2 Hz, 1H), 2.67 (s) , 1 HOUR); MS (APCI, M + 1): 178.10. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.33 μM, Example 41 (2-ethyl-benzoxazole-5-carboxylic acid 1-propyl-butiD-amide A mixture of 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide (example 41a) and trimethyl ortopropyrate was heated at 65 ° C for 5 hours under N2. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting residue was purified on silica gel through a Preparative TLC (3% MeOH in CH 2 Cl 2) to yield the product as a white solid (42 mg, 73%): mp 107-108 ° C; MS (APCI, M + 1): 289.10. to. 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide was prepared in a manner similar to Example 4 using 3-Amino-4-hydroxybenzoic acid and 4-heptylamine. Yield 57%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6H); 1.26-1.51 (m, 8H); 4.09 (m, 1H); 6.74 (m, 1H); 7.05 (s, 1H); 7.43 (m, 2H); 7.77 (m, 2H). MS: (251, M + H). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.68 μM.

Eime 42 2-Methoxy-benzoxazole-5-carboxylic acid H-propyl-butiD-amide Prepared in a manner similar to Example 41, using 3-amino-4-hydroxy-N- (1-propyl-butyl) benzamide (example 4aa) and tetramethyl orthocarbonate. Yield: 60%. p.f. 137-138 ° C; MS (M + H, 291.10). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.69 μM.

Example 43 (2-Ethoxy-benzoxazole-5-carboxylic acid 1-propyl-butylamide Prepared in a manner similar to Example 41 using 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide (example 41a) and tetraethoxymethane: p.p. 128-129 ° C; MS (M + H), 305.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 5 μM.

Example 44 N- (heptan-4-yl) -2- (methylthio benzord-oxazole-5-carboxamide To a solution of the N- (Heptan-4-yl) -2- (mercapto) benzo [cf] oxazole-5-carboxamide (example 44a) (50 mg, 0.17 mmol) in DMF (3 mL) at 0 ° C K2CO3 (29 mg, 0.17 mmol) and Mel (29 mg, 0.20) were added. The resulting reaction mixture was heated at 80 ° C overnight. The solvent was removed under reduced pressure. The residue was diluted with dichloromethane and washed with water, dried (Na2SO4), filtered and concentrated in vacuo, purified through PLTC (15% ETOAc in hexanes) to yield the product as a white solid (50%). mg, 96%): mp 113-114 ° C; 1 H NMR (500 MHz, CDCl 3) d 7.94 (d, J = 1.8 Hz, 1 H), 7.73 (dd, J = 8.5, 1.6 Hz, 1 H), 7.46 (d, J = 8.4 Hz, 1 H), 5.76 (d , J = 8.4 Hz, 1H), 4.15-4.25 (m, 1H), 2.77 (s, 3H), 1.58-1.65 (m, 2H), 1.1.38-1.55 (m, 6H), 0.94 (t, J = 7.2 Hz, 6H); MS (APCl, M +): 307.2. to. N- (Heptan-4-yl) -2- (mercapto) benzo [d] oxazole-5-carboxamide: To a solution of 3-amino-4-hydroxy-N- (1-propylbuty!) Benzamide (example 41a) ) (250 mg, 1.0 mmol) in EtOH was added KSCSOEt (160 mg, 1.0 mmol). The resulting reaction mixture was heated at 80 ° C overnight. The solvent was removed under reduced pressure. And the residue was stirred in water. The resulting mixture was acidified with HOAc to pH ~ 5 and then filtered. The residue was washed with water to produce the product as a white solid (160 mg, 55%). MS (M + H, 293.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.1 μM.

Example 45 (1-Chloromethylbenzoxazole-5-carboxylic acid-1-propyl-butyDamide Prepared in a manner similar to Example 41, using 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide (example 41a) and trimethyl chloro-orthoacetate. Performance: 65%. p.f. 108.5-109 ° C. MS (M + H, 309.05).

The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.23 μM. Example 46 (2-Methyl-benzoxazole-6-carboxylic acid 1-propyl-butiD-amide Prepared in a manner similar to Example 4, using 2-methyl benzoxazole-6-carboxylic acid (example 46a) and 4-heptylamine. Yield 50%: 1H NMR (500 MHz, CD3OD) d 8.19 (d, J = 1.4 Hz, 1H), 8.05 (dd, J = 8.3.1.5 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H) 2.68 (s, 1H); MS (M + 1, 178.10): 2-methyl benzoxazole-6-carboxylic acid was prepared in a manner similar to Example 40a from 4-amino-3-hydroxybenzoic acid ( 50%): 1H NMR (500 MHz, CD3OD) d 8.19 (d, J = 1.4 Hz, 1H), 8.05 (dd, J = 8.3, 1.5 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H) 2.68 (s, 1H); MS (M + H, 178.10) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.1 μM.

Example 47 2-chloromethyl-benzoxazole-6-carboxylic acid d-propyl-butylamide Prepared in a manner similar to example 41, using 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide (example 47a) and trimethyl chloro orthoacetate. The product was obtained as a white solid (45 mg, 73%): m.p. 173.0-137.5 ° C; MS (M + H, 309. 05. a. 3-amino-4-hydroxy-N- (1-propylbutyl) benzamide was prepared in a manner similar to Example 41a from 4-amino-3-hydroxybenzoic acid. Yield: 50% 1H NMR (500 MHz, CDCl 3): d 0.91 (t, 6H); 1.41 (m, 6H); 1.54 (m, 2H); 4.13 (m, 1H); 5.81 (d, 1H); 6.63 (d, 1H), 6.95 (d, 1H); 7.82 (s, 1H). MS: (251, M + H) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.45 μM.

Example 48 4-methyl-3-methylsulfanyl-N- (1-propyl butiDbenza mi da Prepared in a similar manner as example 4, using 4-methyl-3- (methylthio) benzoic acid (example 48a) and 4-heptylamine. Yield: 50%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t 6H, J = 7.2 Hz), 1.40-1.41 (m, 8H), 2.35 (s, 3H), 2.51 (s, 1H), 4.15 (m, 1H) , 5.75 (d, 1H, J = 8.5 Hz), 7.15 (d, 1H, J = 7.8 Hz), 7.31 (d, 1H, J = 7.8 Hz), 7.65 (d, 1H, J = 1.5 Hz). MS (M + H, 280). to. 4-methyl-3- (methylthio) benzoic acid: 3-Amino-4-methylbenzoic acid was suspended in ice water (55 mL) and the concentrated HCl (8.56 mL) was slowly added. An aqueous solution of sodium nitrite (2.4 g in 5.5 mL) was added to the suspension for a period of 15 minutes and the mixture was stirred for another 15 minutes. Then, an aqueous solution of sodium acetate (9.31 g, 18 mL) was added dropwise. The reaction was allowed to proceed for 45 minutes. An intense orange precipitate was obtained. The precipitate was removed by filtration and washed with small portions of ice water. The solid was combined with a solution of potassium xanthogenate (11.93 g) and potassium carbonate (8.22 g) in 250 ml of water. The reaction vessel was placed in a preheated oil bath at 70 ° C and the mixture was stirred for 25 minutes. The reddish solution was removed from the bath and stirred for 15 minutes or until the temperature reached 30 ° C. Sodium hydroxide (0.782 g) was added and stirred until dissolved. Dimethyl sulfate (5.70 mL) was added. The mixture was stirred for 1 hour at room temperature, then refluxed briefly. Removal of the solvent under reduced pressure yielded an orange solid. The solid was treated with a 2.0 N solution of H2SO4 and extracted with EtOAc. The extracts were washed with water, then dried over anhydrous MgSO 4. The solvent was removed under reduced pressure to give a solid without purifying reddish. The solid was adsorbed on silica gel and purified by column chromatography (gradient 5 to 50% ethyl acetate in hexane) to give 4-methyl-3- (methylthio) benzoic acid as a pale yellow powder (2 g ). 1 H NMR (500 MHz, CDCl 3): d 2.39 (s, 3 H), 2.54 (s, 3 H), 7.24 (d, 1 H, J = 7.8 Hz), 7.79 (d, 1 H, J = 7.8 Hz), 7.86 ( d, 1H, J = 1.5 Hz). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.21 μM.

Example 49 4-methyl-2- (4-methyl-3- (methylthio) benzamido pentanoate of (R) -1 methyl Prepared in a manner similar to Example 4 using 3-methyl-4- (methylthio) benzoic acid (example 48a) and D-leucine methyl ester. Performance: 45%. 1 H NMR (500 MHz, CDCl 3): d 0.97 (d, 3 H, J = 6.36 Hz), 0.99 (d, 3 H, J = 6.1 Hz), 1.64-1.77 (m, 2 H), 2.36 (s, 3 H), 2.51 (s 3H), 3.77 (s, 3H), 4.85 (m, 1H), 6.50 (d, 1H, J = 8.10 Hz), 7.18 (d, 1H, J = 7.83 Hz), 7.38 (dd, 1H, J = 7.77 Hz, J = 1.78 Hz), 7.65 Hz (d, 1 H, J = 1.65 Hz). MS (M + H, 310). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.1 μM.

Example 50 4-Methyl-2- (4- (meth- thio) benzamido) pentanoate of (R) -methyl Prepared in a manner similar to Example 4 using 4- (methylthio) benzoic acid and D-Leucine methyl ester. Ms (M + H, 296). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.16 μM.

Example 51 N - (he ptan-4-i I) -3-methyl-4- (m-ethylthio) benzamide Prepared in a manner similar to Example 4 using 3-methyl-4- (methylthio) benzoic acid (example 51a) and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6H); 1.37-1.46 (m, 6H); 1.54-1.56 (m, 2H); 2.35 (s, 3H); 2.49 (s, 3H); 4.17 (m, 1H); 5.73 (d, 1H); 7.14 (d, 1H); 7.52 (s, 1H); 7.58 (d, 1H). MS (280, M + H) mp: 129-131 ° C. to. 3-methyl-4- (methylthio) benzoic acid was prepared using the same procedure described in Example 48a from 3-Amino-4-methylbenzoic acid. Yield 30%. 1 H NMR (500 MHz, CDCl 3): d 2.36 (s, 3 H); 2.53 (s, 3H); 7.17 (d, 1H); 7.85 (s, 1H); 7.93 (d, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.12 μM.

Example 52 4-methoxy-3-methyl-N- (2-methylheptan-4-yl) benzamide Prepared in a similar manner as described in example 4 using 4-methoxy-3-methylbenzoic acid and 2-methyl-4-heptanamine (example 2a). Performance: 45%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (m, 9H); 1.39 (m, 5H); 1.53 (m, 1H); 1.67 (m, 1H); 2.24 (s, 3H); 3.86 (s, 3H); 4.23 (m, 1H); 5.64 (d, 1H); 6.82 (d, 1H); 7.54 (s, 1H); 7.61 (d, 1H). MS (278, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.1 μM.

Example 53 4-m ethoxy -3-methi I -N- (5-methyloxy-3-yl) benzamide Prepared in a manner similar to Example 4 using 4-methoxy-3-methylbenzoic acid and 5-methylhexan-3-amine (example 5a). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 9H); 1.38 (m, 2H); 1.47 (m, 1H); 1.65 (m, 2H); 2.24 (s, 3H); 3.86 (s, 3H); 4.16 (m, 1H); 5.65 (d, 1H); 6.83 (d, 1H); 7.54 (s, 1H); 7.61 (d, 1H). MS (264, M + H). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.09 μM.

Example 54 4-methoxy-N-M- (4-methoxyphenyl) butyl) -3-methyl-1-benzamide Prepared in a manner similar to Example 4 using 3-methyl-4-methoxy-benzoic acid and 1- (4-methoxyphenyl) butan-1-amine (example 54a). Yield 52%. 1 H NMR (500 MHz, CDCl 3): d 0.94 (t, 3H); 1.31-1.41 (m, 2H); 1.82-1.92 (m, 2H); 2.22 (s, 3H); 3.79 (s, 3H); 3.86 (s, 3H); 5.11 (m, 1H); 6.14 (d, 1H); 6.81 (d, 1H); 6.88 (d, 2H); 7.28 (d, 2H); 7.53 (s, 1H); 7.61 (d, 1H). MS (328, M + H). ? to. The 1- (4-methoxyphenyl) butan-1-amine was prepared as described in Example 2a from 1- (4-methoxyphenyl) butan-1-one, yield 90%, MS (M + H, 180.) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 3.14 μM, Example 55 f R) -4-m-ethoxy-3-methyl-N- (3-methyl-1- (3-methylene-1,2,2,4-oxadiazo I-5-D-butybenzamide Prepared in a manner similar to Example 4 using 4-methoxy-3-methylbenzoic acid and 3-methy! -1- (3-methyl [1,2,4] oxadiazol-5-yl) -butylamine (Example 55a). MS (M + H, 318). to. (R) -3-methyl-1- (3-methyl-1,2,4-oxadiazol-5-yl) butan-1-amine: Boc-D-Leu-OH (0.23 g, 1 mmol) was treated with N-hydroxyacetamidine (74 mg, 1 equivalent) and DIC (155 μL, 1 equivalent) in dioxane (2 mL) at room temperature overnight. Another portion of DIC (1 equivalent) was added and the reaction mixture was heated at 110 ° C for 4 hours. After removal of the solvent, the residue was treated with 50% TFA / DCM (2 mL) for 1 hour and then the solvent was evaporated. The unpurified mixture was purified by preparative HPLC (column C-18, mobile phase MeOH-H2O and formic acid as modifier) to give 75 mg of the amine (45% yield). 1 H NMR (500 MHz, CDCl 3): d 0.95 (d, 3 H), 0.99 (d, 3 H), 1.70-1.78 (m, 1 H), 1.92- 1.98 (m, 2 H), 2.39 (s, 3 H), 3.50 (b, 2H, NH2), 4.65 (t, 1H). MS (M + H, 170). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 5.4 μM.

Example 56 4-ethoxy-N- (heptan-4-yl) -3-methyl benzamide Prepared in a similar manner as example 4 using 4-ethoxy-3-methyl-benzoic acid (example 56a) and 4-heptylamine. Performance: 75%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6H) 1.37-1.45 (m, 6H); 1.53-1.59 (m, 2H); 2.24 (s, 3H); 4.07 (q, 2H); 4.15 (m, 1H); 5.67 (d, 1H); 6.80 (d, 1H); 7.54 (s, 1H); 7.58 (d, 1H). MS (278, M + H). to. 4-ethoxy-3-methylbenzoic acid: 4-hydroxy-3-methylbenzoic acid (10 g) was dissolved in DMF (400 mL) followed by the addition of sodium carbonate (3 equivalents). Ethyl iodide (3 equivalents) was dissolved in DMF (50 mL), added dropwise to the reaction mixture and the solution was stirred overnight. After the reaction was finished, the solvent was evaporated. The residue was dissolved in ethyl acetate and washed with water. The organic layer was isolated and evaporated. The residue was dissolved in 200 ml of methanol / water (3: 1). Lithium hydroxide (3 equivalents) was added and allowed to stir overnight. Until the completion of hydrolysis, the solvent was removed and the product was crystallized using a mixture of ethyl acetate / hexane to give 8.2 g of 4-ethoxy-3-methylbenzoic acid. Yield: 70%, MS (M-H, 179.20). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.17 μM.

Example 57 4-ethoxy -N - (1 -methoxy pe n tan -2 -i I) -3 -methyl benzamide Prepared in a similar manner as example 4 using 4-ethoxy-3-methylbenzoic acid (example 56a) and 1-methoxypentan-2-amine (example 57a). Performance: 33%. MS (M + H, 280.1). to. 1-metolxypentan-2-amine was prepared in a manner similar to Example 9a from 2- (1-methoxypentan-2-yl) isoindoline-1,3-dione (example 57b). Performance 67%. 1 H NMR (500 MHz, CDCl 3): d 0.91 (t, 3H); 1.24-1.45 (m, 4H); 1.52 (s, 2H); 2.94 (m, 1H); 3.12 (t, 1H); 3.33 (m, 1H); 3.35 (s, 3H). b. 2- (1-methoxypentan-2-yl) isoindoline-1,3-dione was prepared in a manner similar to Example 9b from 2- (1-hydroxypentan-2-yl) isoindoline-1,3-dione ( example 57c). Performance: 82%. 1 H NMR (500 MHz, CDCl 3): d 0.91 (t, 3H); 1.32 (m, 2H); 1.64 (m, 1H); 2.03 (m, 1H); 3.31 (s, 3H); 3.54 (m, 1H); 3.98 (t, 1H); 4.50 (m, 1H); 7.70 (m, 2H); 7.82 (m, 2H). c. 2- (1-hydroxypentan-2-yl) isoindoline-1,3-dione was prepared in a manner similar to Example 9c using isobenzofuran-1,3-dione and 2-aminopentan-1-ol. Performance 62%. 1 H NMR (500 MHz, CDCl 3): d 0.92 (t, 3H); 1.33 (m, 2H); 1.76 (m, 1H); 1.95 (m, 1H); 3.88 (m, 1H); 4.06 (m, 1H); 4.39 (m, 1H); 7.72 (m, 2H); 7.83 (m, 2H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.69 μM.

Example 58 4-h id roxi -3-m eti l-N-M-propyl-bu ti I) -benzamide Prepared in a similar manner as described in Example 4 using 4-hydroxy-3-methyl-benzoic acid and 4-heptylamine. MS (M + H, 250.2).

The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.92 μM.

Example 59 N - (he pta n -4-í I) -4- (2-methoxyethoxy) -3-methyl benzamide It was dissolved in ethanol (5 mL) potassium hydroxide (4 mmol) and heated to 80 ° C. 4-Hydroxy-3-methyl-N- (1-propyl-butyl) -benzamide (Example 58) was added in the solution (1 mmol) followed by chloroethanol (3 mmol). The reaction was stirred overnight at 80 ° C. The reaction mixture was concentrated and dissolved in 5% citric acid. The mixture was stirred for 1 hour. The aqueous mixture was extracted three times with ethyl acetate. The combined ethyl acetate was washed with water and dried over sodium sulfate. The organic layer was concentrated and purified by HPLC to yield 39% of the N- (heptan-4-yl) -4- (2-methoxyethoxy) -3-methylbenzamide. MS (M + H, 308.25). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.21 μM.

Example 60 2- (3-Fluoro-4-methoxybenzamido) -4-methylpentanoate of (R) -methyl Prepared in a manner similar to Example 4, using 3-fluoro-4-methoxybenzoic acid and the methyl ester of D-leucine. MS (M + H, 298). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.3 μM.

Example 61 3-chloro-4-methoxy-N- (pentan-3-p-benzamide Prepared in a manner similar to Example 4, using 3-pentylamine and 3-chloro-4-methoxybenzoic acid. Yield: 40% MS (M + H, 256.20). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.56 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 6.28.

Example 62 2- (3-chloro-4-methoxybenzamido) -4-methylpentanoate of (R) -methyl Prepared in a manner similar to Example 4, using 3-chloro-4-methoxybenzoic acid and D-leucine methyl ester hydrochloride. MS (M + H, 314.10). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 0.08 μM, and when presented in 0.01 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 13.18.

Example 63 (R) -3-Chloro-4-methoxy-N- (1-phenylethylbenzamide) Prepared in a manner similar to Example 4 using (R) -l-phenylethanamine and 3-chloro-4-methoxybenzoic acid. MS (M + H, 290.0).

The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.3 μM, improved the effectiveness of monosodium glutamate with an EC5o ratio of 2.7.

Example 64 4-Chloro-3-methyl-N- (1-pro-butyl) -benzamide Prepared in a manner similar to Example 4, using 4-chloro-3-methylbenzoic acid and heptan-4-amine. MS (M + H, 268). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.8 μM.

Example 65 3.4-D i methoxy-N - (1-propyl-butyl) -benzamide Prepared in a manner similar to Example 4, using 3,4-dimethoxybenzoic acid and heptan-4-amine. MS (M + H, 279.37). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.36 μM.

Example 66 2- (4-Fluoro-3-methylbenzamido) -4-methylpentanoate of (R) -methyl Prepared in a manner similar to Example 4 using 4-fluoro-3-methylbenzoic acid and D-leucine methyl ester. MS (M + H, 282). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.32 μM.

Example 67 4-m ethoxy-3, 5-di metí I-N - (2 -metí I heptan -4-i I) benzamide Prepared in a manner similar to Example 4, using 4-methoxy-3,5-dimethylbenzoic acid and 2-methyheptan-4-amine (example 2a). MS (M + H, 292.2). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.85 μM.

Example 68 3,4-dimethyl-N- (2-methylhexan-3-yl) benzamifja Prepared in a manner similar to Example 4, using 3,4-dimethylbenzoic acid and hexan-3-amine (example 3a). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 9H); 1.39 (m, 3H); 1.56 (m, 1H); 1.84 (m, 1H); 2.30 (s, 3H); 2.31 (s, 3H); 4.04 (m, 1H); 5.76 (d, 1H); 7.18 (d, 1H); 7.46 (d, 1H); 7.55 (s, 1H); MS (248, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.11 μM.

Example 69 3.4-d i methyl-N- (2-methylheptan-4-yl) benzamide Prepared in a manner similar to Example 4, using 3,4-dimethylbenzoic acid and 2-methylheptan-4-amine (example 2a). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 9H); 1.40 (m, 5H); 1.53 (m, 1H); 1.68 (m, 1H); 2.29 (s, 3H); 2.30 (s, 3H); 4.24 (m, 1H); 5.69 (d, 1H); 7.17 (d, 1H); 7.46 (d, 1H); 7.54 (s, 1H). MS (262, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.13 μM.

Example 70 3, 4-d i m eti-N- (5-m eti I hexan-3-yl) benzamide Prepared in a manner similar to Example 4 using 3,4-dimethylbenzoic acid and 5-methylhexan-3-amine (example 5a). 1 H NMR (500 MHz, CDCl 3): d 0.94 (m, 9H); 1.38 (m, 2H); 1.46 (m, 1H); 1.65 (m, 2H); 2.29 (s, 3H); 2.30 (s, 3H); 4.18 (m, 1H); 5.70 (d, 1H); 7.17 (d, 1H); 7.46 (d, 1H); 7.55 (s, 1H). MS (248, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.17 μM.

Example 71 R) -N - (1-methoxy-4-methy I pe n tan -2 -i I) -3.4-d i methyl benzamide To a solution of the (R) -N- (1-hydroxy-4-methylpentan-2-yl) -3,4-dimethylbenzamide (1.59 g, 6.39 mmol) (example 71a) in dry DMF (20 mL) was added Powdered NaOH (281 mg, 7 mmol) and the solution was stirred at 0 ° C for 2 hours. Iodomethane (1 equivalent, 6.39 mmol) in DMF (10 mL) was added dropwise over a period of 1 hour. The temperature was maintained at 0 ° C and the mixture was stirred for 1 hour. The reaction was quenched by adding 300 ml of water. The aqueous layer was extracted with dichloromethane, dried over MgSO4 and evaporated. The residue was purified by flash chromatography on silica gel (toluene-ethyl acetate: 5-20% gradient) to give 1.23 g of (R) -N- (1-methoxy-4-methylpentan-2-yl) - 3,4-dimethylbenzamide (73%). 1 H NMR (500 MHz, CDCl 3): d 0.94-0.97 (t, 6H), 1.41-1.47 (M, 1H), 1.54-1.60 (m, 1H), 1.64-1.68 (m, 1H), 2.29 (d, 6H), 3.36 (s, 3H), 3.45-3.50 (m, 2H), 4.34-4.39 (m, 1H) , 6.23-6.25 (d, 1H), 7.16-7.17 (d, 1H), 7.47-7.49 (dd, 1H), 7.56 (s, 1H). MS (M + H, 264.3) a. The (R) -N- (1-hydroxy-4-methylpentan-2-yl) -3,4-dimethylbenzamide was prepared in a similar manner as described in Example 4 using 3,4-dimethylbenzoic acid and with ( R) -aminoleucinol. Performance: 75%. MS (M + H, 250.3). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.2 μM.

Example 72 (R) -N- (1- (methoxymethoxy) -4-methylpentan-2-yl) -3,4-dimethylbenzamide To a solution of the (R) -N- (1-hydroxy-4-methylpentan-2-yl) -3,4-dimethylbenzamide (Example 71a) (0.24 mmol) dissolved in dry DMF (2 mL) was added at 0 ° C powdered NaOH (0.36 mmol, 14.5 mg, 1.5 equivalents) and the mixture was stirred for 1 hour at 0 ° C. Then, chloro-methoxy-methane (19.3 μl, 1 equivalent) was added and the reaction was stirred at 0 ° C for 1 hour. The reaction was quenched with water (30 mL) and the mixture was extracted with dichloromethane. The organic phase was dried over MgSO4 and evaporated. The crude product was purified by preparative TLC (20% ethyl acetate / hexanes) to give 37.7 mg of the (R) -N- (1- (methoxymethoxy) -4-methylpentan-2-yl) -3.4 dimethylbenzamide (53%). 1 H NMR (500 MHz, CDCl 3): d 0.98-1.00 (t, 6H), 1.49-1.53 (m, 1H), 1.58-1.64 (m, 1H), 1.69-1.73 (m, 2H), 2.32-2.33 ( d, 6H), 3.38-3.39 (t, 3H), 3.64-3.72 (ddd, 2H), 4.41-4.44 (m, 1H), 4.65-4.69 (dd, 2H), 6.37-6.39 (d, 1H), 7.19-7.21 (d, 1H), 7.50-7.52 (dd, 1H), 7.60 (sb, 1H). MS (M + H, 294.3). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.06 μM.

Example 73 N - (1-Methoxy met I -2 -meti I -pro pi I) -3.4-d i methyl-benzamide Prepared in a manner similar to Example 71 using N- (1-hydroxy-3-methylbutan-2-yl) -3,4-dimethylbenzamide (example 73a) and methyl iodide. Performance 87%. 1 H NMR (500 MHz, CDCl 3): d 0.97-1.00 (dt, 6H), 1.96-2.00 (m, 1H), 2.29 (s, 3H), 2.30 (s, 3H), 3.35 (s, 3H), 3.42. -3.45 (dd, 1H), 3.60-3.62 (dd, 1H), 4.01-4.05 (m, 1H), 6 31-6.33 (d, 1H), 7.16-7.18 (d, 1H), 7.48-7.50 (dd) , 1H), 7.56-7.57 (d, 1H). MS (M + H, 250). to. N- (1-Hydroxy-3-methylbutan-2-yl) -3,4-dimethylbenzamide was prepared in a manner similar to Example 71a using 3,4-dimethoxybenzoic acid and 2-amino-3-methylbutan-1- ol. Performance: 75%. MS (M + H, 236.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.87 μM.

Example 74 2- (2-methoxy-4- (methylthio) benzamido) -4-methylpentanoate of (R) -methyl Prepared in a manner similar to Example 4, using 2-methoxy-4- (methylthio) benzoic acid and D-leucine methyl ester. MS (M + H, 326). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 15.8 μM.

Example 75 N- (2-methylheptan-4-yl) benzordU1.31 dioxo I -5 -carboxamide Prepared in a manner similar to Example 4 using 3- (4-methoxy-phenyl) -acrylic acid and 5-methylhexan-3-amine (example 5a). Yield: 59%. 1 H NMR (500 MHz, CDCl 3): d 0.93 (m, 9H); 1.33 (t, 2H); 1.43 (m, 1H); 1.58-1.67 (m, 2H); 3.83 (s, 3H); 4.11 (m, 1H); 5.19 (d, 1H); 6.25 (d, 1H); 6.88 (d, 2H); 7.44 (d, 2H); 7.58 (d, 1H). MS (276, M + H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.24 μM.

Example 76 N-1-Ethyl-propyl) -3-r4-2-hydroxy-ethoxy) -phenylacrylamide N- (1-ethyl-propyl) -3- (4-hydroxy-phenyl) -acrylamide (example 76a) (0.44 mmole, 103 mg) was dissolved in absolute ethanol with KOH (0.7 mmole, 37 mg). The mixture was stirred at 80 ° C for 1 hour. Then, 2-chloro-ethanol (1.76 mmol, 118 μL) was added dropwise and the mixture was refluxed overnight. After evaporation the unpurified product was dissolved in dichloromethane and washed with water and 5% citric acid. The organic phase was evaporated and the residue was purified by chromatography on silica gel to give 73 mg of the desired product (60%). 1 H NMR (500 MHz, CDCl 3): d 0.92-0.95 (t, 6H), 1.25 (s, 1H), 1.40-1.46 (m, 2H), 1.59-1.64 (m, 2H), 3.93-3.94 (m, 1H), 3.95-3.98 (m, 2H), 4.09-4.11 (m, 2H), 5.28-5.30 (d, 1H), 6.26-6.29 (d, 1H), 6.88-6.90 (d, 2H), 7.43- 7.45 (d, 2H), 7.56-7.59 (d, 1H). MS (M + H, 278.1). to. N- (1-Ethyl-propyl) -3- (4-hydroxy-phenyl) -acrylamide was prepared in a similar manner as described in Example 4 from 4-hydroxy cinnamic acid and 3-pentylamine. MS (M + H, 234.10). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 5.8 μM.

Example 77 (E) -N- (heptan-4-yl) -3- (thiophen-2-yl) acrylamide Prepared in a similar manner as described in example 4 from (E) -3- (thiophen-2-yl) acrylic acid and 4-heptylamine. MS (M + H, 252). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.44 μM.

Example 78 4-methyl-2-oct-2-enamidopentanoate of (R.E) -methyl Prepared in a similar manner as described in example 4 from (E) -oct-2-enoic acid and D-leucine methyl ester. MS (M + H, 270). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.92 μM.

Example 79 3- (4-Methoxy-phenyl) -N- (3-methyl-1-propyl-butyl) -acrylamide Prepared in a manner similar to Example 4 using 3- (4-methoxy-phenyl) -acrylic acid and 3-methyl-1-propyl-butylamine (example 2a). Performance: 65%. 1 H NMR (500 MHz, CDCl 3): d 0.90-0.95 (m, 9H), 1.30-1.39 (m, 5H), 1.49-1.50 (m, 1H), 1.64-1.67 (m, 1H), 3.82 (s, 3H), 4.17-4.18 (m, 1H), 5.18-5.20 (d, 1H), 6.22-6.26 (d, 1H), 6.86-6.89 (d, 2H), 7.42-7.45 (d, 2H), 7.56- 7.59 (d, 1H). MS (M + H, 290.1). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.84 μM.

Example 80 N-M-Methoxymethyl-3-methyl-butyl) -3- (4-methoxy-phenyl) -acrylamide Prepared in a similar manner as described in Example 71 from 3- (4-methoxy-phenyl) -acrylic acid and D-leucinol. Yield: 41% .1H NMR (500 MHz, CDCl 3): d 0.93-0.96 (t, 6H), 1.38-1.42 (m, 1H), 1.48-1.54 (m, 1H), 1.63-1.66 (m, 1H) , 3.36 (s, 3H), 3.41-3.46 (m, 2H), 3.82-3.83 (s, 3H), 4.29-4.31 (m, 1H), 5.69-5.71 (d, 1H), 6.24-6.27 (d, 1H), 6.87-6.89 (d, 2H), 7.43 (s, 1H), 7.44 (s, 1H), 7.56-7.59 (d, 1H). MS (M + H, 292.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.90 μM.

Example 81 N- (1-Benzyl-2-hydroxy-ethyl) -3- (4-methoxy-phenyl) -acrylamide Prepared in a similar manner as described in Example 4 from 3- (4-methoxy-phenyl) -acrylic acid and D-phenylalaninol. MS (M + H, 312.3). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 1.1 μM.

Example 82 3- (4-Ethoxy-phenyl) -N-f1-ethyl-propyl) -acrylamide Prepared in a manner similar to Example 4, using 3- (4-ethoxy-phenyl) -acrylic acid and 3-pentylamine. MS (M + H, 262.2). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.35 μM.

Example 83 Methyl ester of 4-methyl-2- (3-thiophen-2-yl-acryloylamino) pentanoic acid Prepared in a similar manner as described in Example 4 from 3-thiophene-2-yl-acrylic acid and D-leucine methyl ester. MS (M + H, 282.2). The compound had an EC50 for the activation of an acre receptor hT1 R1 / hT1 R3 expressed in a H EK293 cell line of 0.59 μM.

Example 4-methyl-pent-2-enoic acid 84 p, 2,3,4-tetrahydro-naphthalene-1-yl) -amide Prepared in a similar manner as described in Example 4 from 4-methyl acid -pent-2-enoic and 1, 2,3,4-tetrahydro-naphthalen-1-ylamine. MS (M + H, 244.2). The compound had an EC50 for the activation of an acre receptor hT1 R 1 / hT1 R3 expressed in a HEK293 cell line of 1-5 μM.

Example 85 3- (2-Fluoro-phenyl) -N- (1-propyl-butyl) -acrylamide Prepared in a similar manner as described in example 4 from 3- (2-fluoro-phenyl) -acrylic acid and 4-heptylamine. MS (M + H, 264.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.16 μM.

Example 86 3 - (2-Methoxy-phen i) -N- (1-pro i-b) -acrylamide Prepared in a similar manner as described in example 4 from 3- (2-methoxy-phenyl) -acrylic acid and 4-heptylamine. MS (M + H, 276.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.90 μM.

Example 87 3- (3,4-Dimethoxy-phenyl) -N- (1-propyl-butyl) -acrylamide Prepared in a similar manner as described in Example 4 from 3- (3,4-dimethoxy-phenyl) -acrylic acid and 4-heptylamine. MS (M + H, 306.2). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.97 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 2.4.

Example 89 3- (2-Methoxy-phenyl) -N- (2-methyl-cyclohexyl) -acrylamide Prepared in a similar manner as described in Example 4 from 3- (2-methoxy-phenyl) -acrylic acid and 2-methyl-cyclohexylamine. MS (M + H, 274.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.4 μM.

Example 90 N-fhe tan-4-yl) benzofuran-4-carboxamide Prepared in a manner similar to Example 4 using benzofuran-5-carboxylic acid and heptan-4-amine. Performance 41%. MS (M + H, 260.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.19 μM.

Example 91 N - (he pta n-4-i I) -5.6-d methyl picol i n amide Prepared in a manner similar to Example 4, using 5,6-dimethylpicolinic acid (Example 91a) and 4-heptylamine. Yield: 49% .1H NMR (500 MHz, CDCl 3): d 0.91-0.94 (t, 6H), 1.38-1.48 (m, 4H), 1.49-1.61 (m, 4H), 2.32 (s, 3H), 2.52 (s, 3H), 4.11-4.13 (m, 1H) 7.52-7.53 (d, 1H), 7.93-7.94 (d, 1H). MS (M + H, 249.1). to. 5,6-Dimethylpicolinic acid. 5,6-Dimethylpicolinonitrile (example 91b) in concentrated HCl (15 mL) was refluxed overnight. The solvent was evaporated and the solid residue was co-evaporated several times with EtOH. Drying afforded 453 mg of 5,6-Dimethylpicolinic acid (80%) as a white solid. MS (M + H, 152.1). b. 5,6-dimethylpicolinonitrile: 2,3-lutidine (13.25 mmoles) was refluxed overnight with 18 ml of glacial AcOH and 6 ml of hydrogen peroxide. The solvent was evaporated and the residue was co-evaporated twice with water, basified with Na 2 CO 3 and extracted with chloroform. The organic layer was dried over Na2SO4 and evaporated to give 1.45 g of a crystalline product. The product (615 mg, 5 mmol) was reacted with trimethylsilane carbonitrile (5.5 mmol) in dichloromethane (10 mL) at room temperature for 5 minutes followed by the addition of dimethylcarbamoyl chloride (5 mmol) and the solution was stirred at room temperature. environment for 3 days. The reaction mixture was treated with 10% potassium carbonate (10 mL), the organic layer was separated and the aqueous layer was extracted 2 times with dichloromethane. The organic phase was dried over Na2SO4 and evaporated to give 495 mg of 5,6-dimethylpicolinonitrile (75%). 1 H NMR (500 MHz, CDCl 3): d 2.35 (s, 3 H), 2.53 (s, 3 H), 7.43-7.45 (d, 1 H), 7.51-7.52 (d, 1 H); 13C: d 19.71, 22.80, 117.87, 126.36, 130.60, 136.58, 137.66, 159. 84). MS (M + H, 133.1).

The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.98 μM.

Example 92 4- (diethylamino) -N- (heptan-4-yl) benzamide Prepared in a manner similar to Example 4, using 4-diethylaminobenzoic acid and 4-heptylamine. (31%) 1 H NMR (500 MHz, CDCl 3): d 0.92 (t, 6H, J = 7.17 Hz), 1.18 (t, 6H, J = 7.04 Hz), 1.41 (m, 4H), 1.55 (m, 4H), 3.39 ( m, 4H), 4.15 (m, 1H), 5.62 (m, 1H), 6.64 (d, 2H, J = 10.26Hz), 7.64 (d, 2H, J-10.26 Hz). MS (M + H, 291). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 7.6 μM.

Example 93 2- (2,6-dimethoxyisonicotinamido) -4-methylpentanoate (R-methyl) Prepared in a manner similar to Example 4 using 2,6-dimethoxy-isonicotinic acid and D-leucine methyl ester. 1 H NMR (500 MHz, CDCl 3): d 0.92 (d, 3 H, J = 7.27 Hz), 0.93 (d, 3 H, J = 7.26 Hz), 1.41-1.58 (m, 8 H), 3.95 (s, 3 H), 4.08 (s, 3H), 4.15 (m, 1H), 6.43 (d, 1H, J = 8.32 Hz), 7.47 (m, broad, 1H), 8.41 (d, 1H, J = 8.34 Hz). MS (M + H; 311). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.91 μM.

Example 94 N -f heptan-4-i I) -6-methoxy nicotinamide Prepared in a manner similar to Example 4 using sodium 6-methoxynicotinate (example 94a) and 4-heptylamine.

Performance 44%. MS (M + H, 251). to. methyl 6-methoxynicotinate (2.097 g, 12.56 mmol) was dissolved in dioxane (30 mL). An aqueous solution of NaOH (1.0 N, 25 mL) was added to the solution and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure to provide 2.2 g of sodium 6-Tnetoxinicotinate. The compound had an EC or for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.66 μM.

Example 95 (5,6-dimethylpyrazine-2-carboxylic acid 1-propylbutyDamide Prepared in a manner similar to Example 4 using 5,6-dimethyl-pyrazine-2-carboxylic acid (example 95a) and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3): d 0.91-0.94 (t, 6H), 1.35-1.42 (m, 4H), 1.48-1.51 (m, 2H), 1.55-1.60 (m, 2H), 2.57-2.60 ( d, 6H), 4.13-4.16 (m, 1H), 7.52-7.53 (d, 1H), 9.09 (s, 1H); MS (M + H, 250). to. 5,6-Dimethyl-pyrazine-2-carboxylic acid. To a solution of 2,3-diaminopropionic acid (1.0 g, 9.6 mmol) in ethanol (20 mL) was added butan-2,3-dione (728 μL, 11.5 mmol) and NaOH (1.4 g, 56.6 mmol). The mixture was refluxed for 2 hours and then cooled to room temperature while the air was bubbled to the end for 1 hour. The white precipitate was filtered and the gelatinous product was concentrated under vacuum. The crude product was stirred in dichloromethane, washed with 10% citric acid, dried over MgSO 4 and filtered. The solvent was removed under reduced pressure to give the 5,6-dimethyl-pyrazine-2-carboxylic acid as a volatile solid. The compound was used as it is in the next step. The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.01 μM.

Example 96 2-chloro-N- (heptan-4-yl) -6-methyl I nicotinamide Prepared in a manner similar to Example 4, using 2-chloro-6-methylnicotinic acid and 4-heptylamine. MS (M + H, 269). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 3.9 μM.

Example 97 2 -c ia n o -N- (e n ota-4-yl) -4-methoxy benzamide Prepared in a similar manner example 4, using 2-cyano-4-methoxybenzoic acid and 4-heptylamine. Performance: 73%. 1H NMR (CD3OD): d 0.94 (t, 6H, J = 7.3 Hz), 1.38 (m, 4H), 1.53 (m, 4H), 4.02 (s, 3H), 4.12 (m, 1H), 7.27 (d , 1H, J = 9.40 Hz), 8.11 (d, 2H, J = 2.21 Hz). MS (M + H, 275). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 1.39 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 4.52.

Example 98 2- (2,3-dimethyl-furan-5-carboxamido) -4-methylpentanoate of (R) - Prepared in a manner similar to Example 4 using 4,5-dimethyl-furan-2-carboxylic acid and D-leucine methylester.

Yield: 27%. 1 H NMR (500 MHz, CDCl 3): d 0.96 (t, 6 H), 1.66 (m, 3 H), 1.96 (s, 3 H), 2.26 (s, 3 H), 3.75 (s, 3 H), 4.78 (m, 1 H) ), 6.51 (d, 1H), 6.89 (s, 1H). MS (M + H, 268). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.59 μM.

Example 99 N - (heptan-4-yl) -1, 3 -dime ti l-1H-pyrazole -5 -carboxamide Prepared in a manner similar to Example 4, using 1,3-dimethyl-1H-pyrazole-5-carboxylic acid and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3): d 0.90 (t, 6 H, J = 7.2 Hz) 1.41 (m, 4 H), 1.50 (m, 4 H), 2.27 (s, 3 H), 3.77 (s, 3 H), 4.09 (m, 1H), 6.49 (d, 1H), 6.53 (s, 1H). MS (M + H, 238). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 7.8 μM.

Example 100 N- (heptan-4-yl) -2-methylthiazole-4-carboxamide Prepared in a manner similar to Example 4, using 1,3-dimethyl-1H-pyrazole-5-carboxylic acid and 4-heptylamine. MS (M + H, 241). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 7.2 μM.

Example 101 N- (heptan-4-yl) quinoline-6-carboxamide Prepared in a manner similar to Example 4, using quinoline-6-carboxylic acid and 4-heptylamine. 1 H NMR (500 MHz, CDCl 3) d 0.96 (t, J = 7.2 Hz, 6H), 1.42-1.58 (m, 6H), 1.62-1.70 (m, 2H), 4.18-4.20 (m, 1H), 5.95 ( d, J = 9.0 Hz, 1H), 7.49 (br s, 1H), 8.04 (dd, J = 8.5, 1.5 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.27 (d, J = 8.2 Hz, 1H), 8.30 (s, 1H), 8.99 (br s, 1H); MS (M + H, 271.2).

The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.2 μM.

Example 102 N- (heptan-4-yl) quinoline-3-carboxamide Prepared in a manner similar to Example 4 using quinoline-3-carboxylic acid and heptylamine. 1 H NMR (500 MHz, CDCl 3) d 0.96 (t, J = 7.3 Hz, 6H), 1.40-1.58 (m, 6H), 1.60-1.67 (m, 2H), 4.20-4.30 (m, 1H), 6.01 ( d, J = 8.8 Hz, 1H), 7.61 (t, J = 7.5.1H), 7.80 (t, J = 7.6 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 8.57 (d, J = 1.2 Hz, 1H), 9.26 (br s, 1H); MS (M + H, 271.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 15.8 μM.

Example 103 N - (he pta n-4-i I) isoqu i noli n-1 -carboxam ida Prepared in a manner similar to Example 4 using isoquinoline-1-carboxylic acid and heptamine. 1 H NMR (500 MHz, CDCl 3) d 0.98 (t, J = 7.05 Hz, 6H), 1.42-1.56 (m, 6H), 1.58-1.66 (m, 2H), 4.20-4.32 (m, 1H), 5.83 ( d, J = 9.1 Hz, 1H), 7.36 (d, J = 4.2, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.88 (d, J = 4.9, 1H); MS (APCl, M +): 271.2. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 14.2 μM.

Example 104 4-Methoxy-N - (1-methoxymethyl-3-methyl I-bu ti l) -3-methyl-benzamide Prepared in a similar manner as described in Example 71 from 4-methoxy-3-methylbenzoic acid and D-leucinol. Performance: 86%. 1 H NMR (500 MHz, CDCl 3): d 0.94- 0.97 (t, 6H), 1.42-1.47 (m, 1H), 1.54-1.60 (m, 1H), 1.64-1.68 (m, 2H), 2.24 (s, 3H), 3.37 (s, 3H), 3.46-3.48 (m, 2H), 3.87 (s, 3H), 4.35-4.38 (m, 1H), 6.14-6.16 (d, 1H), 6.82-6.84 (d, 1H), 7.56 (d, 1H), 7.61-7.63 (dd, 1H). MS (M + H, 280.3). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.24 μM.

Example 105 N -f 4-f tr if I uoro m ethoxy) benzyl) thiof in -2 -carboxamide Prepared in a similar manner as described in Example 4 from thiophene-2-carboxylic acid and (4- (trifluoromethoxy) phenyl) methanamine. MS (M + H, 303). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.4 μM.

Example 106 N- (2- (furan-2-i I methylthio etih-4-methoxy-3-methyl benzamide Prepared in a similar manner as described in example 4 from 4-methoxy-3-methylbenzoic acid and 2- (furan-2-ylmethylthio) ethanamine. Performance 58%. 1 H NMR (500 MHz, CDCl 3) 2.23 (s, 3 H), 2.76 (t, 2 H, J = 6.37 Hz), 3.59 (q, 2 H, J = 12.2 Hz), 3.76 (s, 2 H), 3.86 (s, 3H), 6.22 (dd, 1H, J = 3.49 Hz, J = 2.67 Hz), 6.30 (dd, 1H, J = 3.04 Hz, J = 1.78 Hz), 6.46 (m, 1H, broad), 6.83 (d, 1H, J = 8.51 Hz), 7.34 (dd, 1H, J = 1.97 Hz, J = 1 Hz), 7.56 (d, 1H, J = 1.72 Hz), 7.61 (dd, 1H, J = 8.53 Hz, J = 2.25 Hz). MS (M + H, 306). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 5.6 μM.

Example 107 4-trifluoromethoxy-benzylamine of thiophene-3-carboxylic acid Prepared in a manner similar to Example 4 using thiophene-3-carboxylic acid and 4-trifluoromethoxy-benzylamine. MS (M + H, 302.0). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.2 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 8.5.

Example 108 2.4-dimethoxy-benzylamine 3-methyl-thiophene-2-carboxylic acid Prepared in a manner similar to Example 4 using 3-methyl-thiophene-2-carboxylic acid and 2,4-dimethoxy-benzylamine. MS (M + H, 292.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 5.6 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 5.8.

Example 109 5-pyridin-2-yl-thiophene-2-carboxylic 2,4-dimethoxy-benzylamide Prepared in a manner similar to Example 4 using 5-pyridin-2-yl-thiophene-2-carboxylic acid and 2,4-dimethoxy-benzylamine. MS (M + H, 355.2).

The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.86 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 8.

Example 110 2-Methyl-2H-pyrazole-3-carboxylic acid 2,4-dimethoxy-benzylamide Prepared in a manner similar to Example 4 using 2-methyl-2H-pyrazole-3-carboxylic acid and 2,4-dimethoxy-benzylamine. MS (M + H, 276.2). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 6 μM, and when presented in 3 μM improves the effectiveness of monosodium glutamate with an EC5o ratio of 7.9.

Example 111 4-Hydroxy-3-methyl-N- (1-methyl-3-phenyl-propyl) -benzamide Prepared in a manner similar to Example 4 using 4-hydroxy-3-methyl-benzoic acid and 1-methyl-3-phenyl-propylamine. MS (M + H, 284.2). The compound had an EC 0 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 2.7 μM, and when presented at 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 7.

Example 112 r2- (4-ethyl-phenyl) -ethyl-amide of benzoH-31-dioxol-5-carboxylic acid Prepared in a manner similar to Example 4 using benzo [1,3] dioxol-5-carboxylic acid and 2- (4-ethyl-phenyl) -ethylamine. MS (M + H, 298.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.86 μM.

Example 113 4-Methoxy-3-methyl-N- (1-phenyl-butyl) -benzamide Prepared in a manner similar to example 4, using the acid. 4-methoxy-3-methyl-benzoic acid and 1-phenyl-butylamine. MS (M + H, 298.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.5 μM.

Example 114 4-Methoxy-3-methyl-N- (1-pyridin-2-yl-butyl) -benzamide Prepared in a manner similar to Example 4 using 4-methoxy-3-methyl-benzoic acid and 1-pyridin-2-yl-butylamine. 1 H NMR (500 MHz, CDCl 3): d 0.91-0.92 (t, 3H), 1.25-1.3 (m, 2H, 1.85-1.9 (m, 2H), 3.86 (s, 3H), 5.25-5.3 (m, 1H ), 6.80-6.82 (d, 1H), 7.2-7.3 (m, 2H), 7.42-7.44 (d, 1H), 7.6-7.7 (m, 3H), 8.6 (d, 1H) MS (M + H , 299.1) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.54 μM.

Example 115 BenzoM .31dioxol-5-carboxylic acid ri- (4-methoxy-phenyl) -butylamide Prepared in a manner similar to Example 4, using benzo [1,3] dioxol-5-carboxylic acid and 1- (4-methoxy-phenyl) -butylamine. 1 H NMR (500 MHz, CDCl 3): d 0.93-0.95 (t, 3H), 1.30-1.39 (m, 2H), 1.80-1.90 (m, 2H), 3.79 (s, 3H), 5.08-5.09 (dd, 1H), 6.00 (s, 2H), 6.10-6.12 (d, 1H), 6.79-6.80 (d, 1H), 6.87 (s, 1H), 6.88 (s, 1H), 7.25-7.28 (m, 4H). MS (M + H, 328.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 4.12 μM.

Example 116 4-Ethoxy-N-p - (4-methoxy-phenyl) -buty-3-methyl-benzamide Prepared in a manner similar to Example 4, using 4-ethoxy-3-methyl-benzoic acid and 1- (4-methoxy-phenyl) -butylamine. 1 H NMR (500 MHz, CDCl 3): d 0.93-0.96 (t, 3H), 1.31-1.41 (m, 2H), 1.41-1.45 (t, 3H), 1.82-1.92 (m, 2H), 2.28 (s, 3H), 3.79 (s, 3H), 4.04-4.08 (q, 2H), 5.10-5.12 (d, 1H), 6.12-6.14 (d, 1H), 6.78-6.80 (d, 1H), 6.87 (s, 1H), 6.88 (s, 1H), 7.26-7.29 (m, 2H), 7.52-7.53 (d, 1H), 7.57-7.59 (d, 1H). MS (M + H, 342.1). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.9 μM.

Example 117 4-Methoxy-N-p-fR) - (4-methoxy-f in i D-etiH-3-methyl-benzamide Prepared in a manner similar to Example 4 using 4-methoxy-3-methyl-benzoic acid and 1- (R) - (4-methoxy-phenyl) -ethylamine. MS (M + H, 300.1). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 2.8 μM.

Example 118 lndan-1-ylamide of BenzoH, 31-dioxol-5-carboxylic acid Prepared in a manner similar to Example 4, using benzo [1,3] dioxol-5-carboxylic acid and indan-1-ylamine. MS (M + H, 282.2). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.2 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC5o ratio of 5.33. Example 119 4-m ethoxy -3-meti I -N- (penta n -3 -i I) benzamide Prepared in a similar manner as described in Example 4, starting with 4-methoxy-3-methylbenzoic acid and pentan-3-amine. MS (M + H, 236). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.4 μM.

Example 120 3-methy1-N- (p-tolylethyl) furan-2-carboxamide Prepared in a similar manner as described in example 4 from 3-methyl-furan-2-carboxylic acid and 2-p-tolylethanamine. MS (M + H, 244). The compound had an EC5o for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 6 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC5o ratio of 3.3.

Example 121 N -f 2, 4-d i mtoto be nc i I) -2- (1 H-pyrrol-1-yl) benzamide Prepared in a manner similar to Example 4, using 1- (2- (1 H -pyrrol-1-yl) phenyl) ethanone and 2,4-dimethoxy-benzylamine. MS (M + H, 337.2). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.66 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC 0 ratio of 11. The compounds Additional "amide" that was synthesized and tested experimentally and found to have a relatively high level of effectiveness as an activator of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line. The results of that test are shown later in Table A.

Numerous amide compounds of Formula (I) which fall within the subgenus of the compounds "oxalamide" described elsewhere herein are also synthesized and tested experimentally for effectiveness as an activator of an acre receptor hT1 R1 / hT1 R3 expressed in a HEK293 cell line.

Example 122 General procedure A for the preparation of an oxalamide Synthesis of N- (2-Methoxy-benzyl) -N, - (2-pyridyl-2-yl-ethyl) -oxalamide: The 2-methoxybenzylamine (5 mmol) was mixed with triethylamine (2 equivalents) in anhydrous Dioxane. Ethyloxalyl chloride (1 equivalent) was added and the mixture was stirred at room temperature for 0.5-2 hours. Then, 2- (2-pyridinyl) ethylamine (1 equivalent) was added and the suspension was heated at 80 ° C overnight. The solution was concentrated and the residue was dissolved in ethyl acetate and washed with water. The organic layer was dried by sodium sulfate and the solvent was evaporated to give the crude product, which was purified by flash column chromatography to yield the title compound: yield 70%, m.p. 118-119 ° C; m / e = 314 [M + 1]; 1H NMR (CDCIs): d 3.02 (t, 2H), 3.76 (dt, 2H), 3.86 (s, 3H), 4.47 (d, 2H), 6.80-6.90 (m, 2H), 7.14-7.18 ( m, 2H), 7.20-7.30 (m, 2.H), 7.55-7.62 (m, 1H), 7.75-7.83 (m, 1H), 8.05-8.12 (m, 1H), 8.55-8.63 (m, 1H) ). The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.34 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 18.85.

Example 123 N- (2,4-Dimethoxy-benzyl) -N '- (2-pyridin-2-yl-ethyl) -oxalamide Prepared in a manner similar to Example 122 using the ethyloxyalyl chloride of 2,4-dihydroxymethoxybenzylamine and 2- (2-pyridinyl) ethylamine. Yield 72%, m.p. 123-124 ° C; m / e = 344 [M + 1]; 1 H NMR (CDCl 3): d 3.02 (t, 2H); 3.73 (dd, 2H); 3.78 (s, 3H); 3.82 (s, 3H) 4.38 (d, 2H) 6.40 (dd, 1H); 6.44 (d, 1H); 7.14 (m, 3H); 7.59 (m, 1H); 7.82 (t, 1H); 8.11 (t 1H); 8.56 (d, 1H); 13C NMR: d 36.9, 38.9, 39.4, 55.6, 55.6, 98.8, 104.1, 117.8, 121.9 123.5, 130.7, 136.8, 149.6, 158.8, 158.8, 159.6, 160.1, 161.0. The compound had an EC50 for activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.09 μM, and when presented in 0.3 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 6.51.

Example 124 N- (3-Methyl-thiophen-2-ylmethyl) -N'-f2-pyridin-2-yl-ethyl) -oxalamide Prepared in a manner similar to Example 122, using (3-methyl-thiophen-2-yl) -methylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine. Performance 40%; p.f. 122-124 ° C; m / e = 304 [M + 1]; 1H NMR (DMSO-d6): d 2.19 (s, 3H), 2.92-2.95 (t, 2H), 3.48-3.52 (dd, 2H), 4.37-4.38 (d, 2H), 6.79-6.80 (d, 1H ), 7.20-7.27 (m, 3H), 7.67-7.71 (dt, 1H) 8.48-8.49 (d, 1H), 8.87-8.89 (t, 1H), 9.25-9.28 (t, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.37 μM.

Example 125 General Procedure B for the Synthesis of an Oxalamide N- (4-methyl-benzyl-N, - (2-pyridin-2-yl-ethy-oxalamide The 4-methylbenzylamine was allowed to react (1 mmol) with ethyl oxalyl chloride (1 equivalent) in the presence of triethylamine (2 equivalents) in acetonitrile at room temperature for 0.5-1 hour. Then 2- (2-pyridinyl) ethylamine (1 equivalent) was added and the suspension was heated to 160 ° C in a microwave reactor for 5 minutes. The reaction mixture was subjected to preparative HPLC to give the pure title oxalamide: 60% yield; p.f. 152-154 ° C, m / e = 298 [M + 1]; 1 H NMR (CDCl 3): d 2.33 (s, 3 H), 3.10 (t, 2 H), 3.75 (d t, 2 H), 4.43 (d, 2 H), 7.10 7015 (m, 4 H), 7.18-7.22 (m, 2 H) ), 7.65-7.73 (m, 2H), 8.12 (b, 1H), 8.60 • (d, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.41 μM.

Example 126 N- (2-Methyl-4-methoxybenzyl) -N '- (2-pyridin-2-yl-ethyl) -oxalamide Prepared in a manner similar to Example 122 using 2-methyl-4-methoxybenzylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine. Yield 51%; p.f. 133-134 ° C m / e = 328 [M + 1]; 1 H NMR (CDCl 3): d 2.29 (s, 3H); 3.04 (t, 2H); 3.74-3.77 (m, 2H); 3.7 (s, 3H); 4.40 (d, 2H); 6.69-6.73 (m, 2H); 7.13-7.18 (m, 3H); 7.51 (t, 1H); 7.60-7.63 (m 1H); 8.17 (t, 1H); 8.58 (d, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.11 μM.

Example 127 N- (2,4-Dimethoxy-benzyl) -NX (3-pyridin-2-yl-propyn-oxalamide Prepared in a manner similar to example 125, using the ethyl oxalyl chloride of 2,4-dimethoxybenzylamine and 3- (2-pyridinyl) propylamine. Yield 60%; m / e = 358 [M + 1]; 1 H NMR (CDCl 3): d 1.99-2.04 (m, 2H); 2.84 (t, 2H); 3.36 (dd, 2H); 3.79 (s, 3H); 3.82 (s, 3H 4.60 (d, 2H), 6.41-6.45 (m, 2H), 7.10-7.17 (m, 3H), 7.57-7.60 (m, 1H), 7.81 (t, 1H), 7.89 (t, 1H); 8.54 (d, 1H) The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.84 μM.

Example 128 N- (4-Methoxybenzyl) -N '- (2-pyridin-2-yl-ethyl) -oxalamide Prepared in a manner similar to example 125 using 4-methoxybenzylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine. Yield 50%; p.f. 156-158 ° C; 1H NMR 3.05 (t, 3H), 3.72-3.77 (m, 2H), 3.79 (s, 3H), 4.40 (d, 2H), 6.86 (d, 2H), 7.16-7.22 (m, 4H) 7.65-7.69 (m, 3H), 8.15 (b, 1H), 8.62 (d, 1H). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.75 μM.

Example 129 N- (2,4-Dimethoxybenzyl) -N '- (2- (3-methylpyridin-2-ineetyl) oxalamide Prepared in a manner similar to example 125 using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (3-methylpyridin-2-yl) ethylamine (example 129a). Yield 10%; m / e = 358 [M + 1]; 1 H NMR (CDCl 3): d 2.28 (s, 3 H), 3.01 (t, 2 H), 3.75-3.82 (m, 2 H), 3.79 (s, 3 H), 3.82 (s, 3 H), 4.39 (d, 2 H) , 6.41 (dd, 1H), 6.44 (d, 1H), 7.10 (t, 1H), 7.15 (d, 1H), 7.45 (d, 1H), 7.81 (bs, 1H), 8.28 (bs, 1H), 8.40 (d, 1H). to. 2- (3-Methylpyridin-2-yl) ethylamine: To a solution of 2- (3-methylpyridin-2-yl) acetonitrile (example 129b) (95 mg, 0.72 mmol) in THF (0.5 mL) was added 1M BH3 -THF (2.2 ml, 2.2 mmol) in drops at room temperature. The resulting temperature was heated in a microwave reactor at 130 ° C for 7 minutes. Then, 6 N aqueous HCl (1 mL) was added dropwise at room temperature. The resulting mixture was heated in a microwave reactor at 120 ° C for 4 minutes. The reaction mixture was washed with Et2O (3x3 mL), then cooled to 0 ° C and 10 N aqueous NaOH (0.8 mL) was added. The aqueous solution was saturated with K2CO3. The product was extracted with CHCl3 (6x5 mL). The organic extracts were dried (1: 1 of K2C? 3 / Na2SO4), filtered, concentrated in vacuo to yield an oil (8 mg, 85%), which was used directly in Example 8. m / e = 137 [M + 1]. b. 2- (3-Methylpyridin-2-yl) acetonitrile: To a solution of n-BuLi (2.5 N in hexanes, 7.92 mL, 19.8 mmol) at -78 ° C under N2 was added dry THF (75 mL) followed immediately by a solution of dry MeCN (1.15 mL, 21.78 mmol) in anhydrous THF (30 mL) over a period of 5 minutes. The resulting reaction mixture was stirred continuously at -78 ° C for 1 hour. Then, 2-bromo-3-methylpyridine (516 mg, 3 mmol) was added. The resulting reaction mixture was stirred at -78 ° C for 1 hour, then warmed to room temperature, and quenched with water. The organic solvent was evaporated in vacuo, dissolved in CH2Cl2. The organic layer was washed with brine, dried (MgSO4), concentrated, purified by column chromatography (20% EtOAc in hexanes) to produce the product quantitatively: m / e = 133 [M + 1] . The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.64 μM.

Example 130 N- (2,5-D -methyl-furan-3-ylmetin-N '- (2-pyridin-2-yl-ethyl) -oxalamide Prepared in a manner similar to Example 122 using 2,5-dimethyl-furan-3-ylmethylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine. Yield 51%; p.f. 112-115 ° C; m / e = 302 [M + 1]; 1H NMR (DMSO-d6): d 2.14 (s, 3H), 2.18 (s, 3H), 2.91-2.94 (t, 2H), 3.47-3.51 (dd, 2H), 3.98-3.99 (d, 2H), 5.89 (s, 1H), 7.20-7.25 (m, 2H), 7.68-7.71 (dt, 1H), 8.48-8.49 (d, 1H), 8.81-8.84 (t, 1H), 8.97-9.00 (t, 1H) ). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.01 μM.

Example 131 N- (1,5-Dimethyl-1H-pyrrol-2-ylmetin-N '- (2-pyridin-2-yl-etin oxalamide Prepared in a manner similar to Example 122 using 1,5-dimethyl-1H-pyrrole-2-ylmethylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine. Yield 25%; p.f. 147-149 ° C; m / e = .301 [M + 1]; 1H NMR (DMFO-d6): d 2.11 (s, 3H), 2.92-2.95 (t, 2H), 3.38 (s, 3H), 3.48-3.52 (q, 2H), 4.24-4.25 (d, 2H), 5.64-5.65 (d, 1H), 5.79-5.65 (d, 1H), 7.20-7.25 (m, 2H), 7.68-7.71 (dt, 1H), 8.48-8.49 (d, 1H), 8.82-8.86 (m , 2H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 2.3 μM.

Example 132 N- (2-methoxy-4-methylbenzyl) -N '- (2- (pyridin-2-ynyl) oxalamide Prepared in a manner similar to example 125 using (2-methoxy-4-methylphenyl) methanamine (example 132a), etioxalyl chloride, and 2- (2-pyridinyl) ethylamine, yield 20%. mp: 128-131 ° C; m / e = 328 [M + 1]; 1 H NMR (CDCl 3): 2.33 (s, 3 H); 3.02 (t, 2H); 3.73 (m, 2H); 3.84 (s, 3H); 4.42 (d, 2H); 6.70 (m, 2H); 7.14 (m, 3H); 7.60 (m, 1H); 7.86 (s, 1H); 8.09 (s, 1H); 8.56 (d, 1H). to. (2-methoxy-4-methylphenyl) methanamine: To a solution of the 2-methoxy-4-methylbenzamide (example 132b) (200 mg, 1.21 mmol) in THF (0.5 mL) was added 1 M BH3- »THF (2.4 ml, 2.42 mmol) slowly at room temperature. The resulting mixture was heated in a microwave reactor at 130 ° C for 7 minutes. Then 6 N aqueous HCl (1 mL) was added dropwise at room temperature. The resulting mixture was heated in a microwave reactor at 120 ° C for 4 minutes. The reaction mixture was warmed to Et2O (3x3 mL), then cooled to 0 ° C and 10 N aqueous NaOH (0.8 mL) was added. The aqueous solution was saturated with K2CO3. The product was extracted with CHCl3 (6x5 mL). The organic extracts were dried (1: 1 of K2C? 3 / Na2S? 4), filtered, concentrated in vacuo to yield 180 mg of (2-methoxy-4-methylphenyl) methanamine which was used directly in Example 11 b. 2-methoxy-4-methylbenzamide: 2-methoxy-4-methylbenzoic acid (500 mg, 3.01 mmol) was mixed with 1 -et? I-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (577 mg, 3.01 mmol) and 1-hydroxybenzotriazole (407 mg, 3.01 mmol) in 25 ml of dichloromethane at room temperature and stirred for 5 minutes. A solution of 2M ammonia in methanol (4.5 ml, 9.03 mmol) was added, the reaction mixture was stirred at room temperature for about 5 hours, then diluted with dichloromethane, washed with 1N HCl, saturated NaHCO 3, water and brine, dried over MgSO 4, filtered and evaporated to give 440 mg of 2-methoxy-4-methylbenzamide, yield 88%. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.04 uM.

Example 133 N- (2,4-dimethylbenzyl) -N '- (2-fpyridin-2-yl) etnoxalamide Prepared in a manner similar to example 125 using (2,4-dimethylphenyl) methanamine (example 133a), ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine, yield 60%; p.f. 148-149 ° C; m / e = 312 [M + 1]; 1 H NMR (CDCl 3): 2.28 (s, 3 H); 2.30 (s, 3H); 3.05 (t, 2H); 3.76 (dd, 2H); 4.43 (d, 2H); 6.99 (m, 2H); 7.11 (d, 1H); 7.17 (m, 2H); 7.54 (s, 1H); 7.62 (m, 1H); 8.17 (s, 1H); 8.58 (d, 1H). to. (2,4-Dimethylphenyl) methanamine: Hydride was placed in a solution of 1M lithium-aluminum hydride in THF (15.2 m !, 15.2 mmoles) in a pre-dried flask under argon at 0 ° C, a solution of 2.4 dimethylbenzonitrile (1.0 g, 7.6 mmoles) in 15 ml of anhydrous ether was added dropwise. After the addition, the reaction mixture was slowly warmed to room temperature and stirred for 3 hours, then cooled to 0 ° C, anhydrous sodium sulfate was added and 1 ml of water was added dropwise. The mixture was diluted with ethyl acetate, the insoluble matter was removed by filtration, the filtrate was washed with water and brine, dried over MgSO 4, filtered and evaporated to give 1.03 g of the (2,4-dimethylphenyl) methanamine. pure in quantitative yield without purification.

The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.07 uM.

Example 134 N- (4-ethoxy-2-methoxybenzyl) -N, - (2- (pyridin-2-eneoxoxalamide Prepared in a manner similar to example 125 using (4-ethoxy-2-methoxyphenyl) methanamine (example 134a), ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine; 10% yield; p.f. 117-118 ° C; m / e = 358 [M + 1]; 1 H NMR (CDCl 3): 1.40 (t, 3H); 3.03 (t, 2H); 3.74 (dd, 2H); 3.82 (s, 3H); 4.01 (dd, 2H); 4.39 (d, 2H); 6.39 (d, 1H); 6.44 (s, 1H); 7.15 (m, 3H), 7.61 (m, 1H); 7.81 (s, 1H); 8.10 (s, 1H); 8.56 (d, 1H). to. (4-ethoxy-2-methoxyphenyl) methanamine: To a solution of 4-ethoxy-2-methoxybenzaldehyde (example 134b) (880 mg, 4.88 mmol) in 50 ml of anhydrous methanol, ammonium acetate (7.5 g, 97.60 g) was added. mmoles) and sodium cyanoborohydride (613 mg, 9.76 mmol). The reaction mixture was stirred at room temperature for about 4 hours, then concentrated on a rotary evaporator, the residue was diluted with water and basified with 15% aqueous NaOH, extracted with ethyl acetate, washed with water and brine, dried over MgSO 4, filtered and the solvent was evaporated, the residue was taken to column chromatography on silica gel (DCM / MeOH 9: 1) to yield 150 mg of the product; 17% yield (the method was not optimized). b. 4-Ethoxy-2-methoxybenzaldehyde: To a solution of 4-hydroxy-2-methoxybenzaldehyde (1.0 g, 6.57 mmol) in 10 ml of acetone, potassium carbonate (0.91 g, 6.57 mmol) and iodomethane (1.6 ml, 19.71 mmoles), the reaction mixture was stirred at room temperature overnight. The acetone was stirred in a rotary evaporator; the residue was diluted with water and ethyl acetate; it was extracted with ethyl acetate, washed with brine, dried over MgSO 4, filtered and evaporated to give the crude product, which was taken to column chromatography on silica gel (ethyl acetate / hexane = 1: 4) to give 943 mg of the product; 80% yield The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 0.1 uM.

Example 135 N- (4-Methoxy-3-methylbenzyl-N, -2-pyridin-2-ethyl) oxalamide Prepared in a manner similar to example 125 using (4-methoxy-3-methylphenyl) -methanamine (Example 135a), ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine, yield 12%; p.f. 145-147 ° C; m / e = 328 [M + 1]; 1 H NMR (CDCl 3): 2.19 (s, 3 H); 3.04 (t, 2H); 3.76 (dd, 2H); 3.81 (s, 3H); 4.37 (d, 2H); 6.76 (d, 1H); 7.06 (m, 2H); 7.16 (m, 2H); 7.61 (m, 1H); 7.66 (s, 1H); 8.18 (s, 1H); 8.58 (d, 1H). to. 4-Methoxy-3-methylphenyl) methanamine: Prepared in a manner similar to Example 134a using 4-methoxy-3-methylbenzaldehyde, ammonium acetate, and sodium cyanoborohydride in MeOH; yield 22% (110 mg). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.04 uM.

Example 136 N- (2-chlorobenzyl) -N '- (2- (pyridin-2-yl) etM) oxalamide: Prepared in a manner similar to example 125 using (2-chlorophenyl) methanamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine; 45% yield; m / e = 318 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.01 uM.

Example 137 N - ((2,3-dihydrobenzorbiri.41dioxin-5-yl) metl) -NX (2-pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to Example 122 using (2,3-dihydrobenzo [b] [1,4] dioxin-5-yl) methanamine, ethyl oxalyl chloride, and 2- (2-pyridinyl) ethylamine; 50% yield; m / e ~ 342 [M + 1]. The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 0.3 uM.

Example 138 N- (benzordU1,31dioxol-5-ylmethyl) -N '- (2- (pyridin-2-DetiDoxalamide Prepared in a manner similar to example 125 using benzo [d] [1, 3] dioxol-5-ylmethanamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine; 35% yield; m / e = 328 [M + 1]. The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.5 uM.

Example 139 N- (4-Ethylbenzyl) -NX (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to example 125 using 4-ethylbenzylamine, ethyl oxalyl chloride, and 2- (2-pyridinyl) ethylamine; 38% yield; m / e = 312 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.79 uM.

Example 140 N-f Benzofuran-5-ylmethyl) -N '- (2- (pyridin-2-yl) ethyl) oxalam ida Prepared in a manner similar to example 125 using benzofuran-5-ylmethylamine, ethyl oxalyl chloride and 2- (2-pyridinyl) ethylamine; 64% yield; m / e = 324 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.78 uM.

Example 141 N - ((4-Methoxycarbonitophenyl) methyl) -N '- (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to Example 122 using 4-methylcarbonylphenylmethylamine, ethyl oxalyl chloride, and 2- (2-pyridinyl) ethylamine; 52% yield; m / e = 34 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.63 uM.

Example 142 N - ((2-Carbamoylphenyl) methyl) -N '- (2- (pyridin-2-ylpethyl) oxalamide Prepared in a manner similar to Example 122 using 2-carbamoylphenylmethylamine, ethyl oxalyl chloride, and 2- (2-pyridinyl) ethylamine; 48% yield; m / e = 34 [M + 1].

The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 8.5 uM.

Example 143 N- (2,4-Dimethoxybenzyl) -N'-f1- (pyridin-2-yl) propan-2-inoxalamide Prepared in a manner similar to example 125 using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride, and 1- (pyridin-2-yl) propan-2-ylamine (example 143a); 34% yield; m / e = 357 [M + 1]. to. 1- (Pyridin-2-yl) propan-2-ylamine: Prepared in a manner similar to example 129a using 2- (pyridin-2-yl) propan-nitrile (example 143b); the unpurified product was used directly in Example 143; 53% yield; m / e = 137 [M + 1]. b. 2- (pyridin-2-yl) propan-nitrile: 5 mmoles of 2- (pyridin-2-yl) acetonitrile was dissolved in 8 ml of anhydrous THF and placed in an ice bath. Potassium t-butoxide (1 equivalent) was added and the reaction was stirred for 30 minutes. Methyl iodide (1 equivalent) was dissolved in 5 ml of anhydrous THF and added slowly for 30 minutes. The reaction was stirred overnight at room temperature. The solvent was evaporated and the unpurified mixture was dissolved in ethyl acetate and washed with water. The ethyl acetate layer was evaporated and the product was purified by preparative TLC (30% ethyl acetate / Hexane); performance 71%; m / e = 133 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEU293 cell line of 0.4 uM.

Example 144 N-f2,4-Dimethoxybenzyl) -N '- (2-fpyridin-2-yl) propipoxalamide Prepared in a manner similar to example 125, using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) pro? Ylamine (example 144a); 35% yield; m / e = 357 [M + 1]. to. 2- (pyridin-2-yl) propylamine: 10 mmoles of 2-methylpyridine was dissolved in anhydrous THF and kept under inert condition at 0 ° C. Butyl lithium (1.2 equivalents) was added dropwise and stirred for an additional 15 minutes at 0 ° C while allowing the temperature to return to room temperature. After stirring at room temperature for 1 hour, the reaction mixture was again cooled to 0 ° C and acetonitrile (2 equivalents) was added in drops. The reaction was stirred overnight at room temperature. After cooling the reaction to 0 ° C, 30 ml of methanol was added in the reaction mixture. Sodium borohydride (3 equivalents) was added in one portion slowly at 0 ° C. The reaction was stirred for another hour allowing the temperature to rise to room temperature. The reaction mixture was diluted with water and exhaustively extracted with ethyl acetate. The combined extracts were washed with water, brine and dried over sodium sulfate. The solution was concentrated and dissolved in ether. The product was extracted with aqueous 3 N HCl, and the acidic extract was washed with ether and made basic with NaOH. The product was exhaustively extracted with ether. The combined ether extracts were washed with water and dried over sodium sulfate. The solvent was evaporated to produce sufficient pure product; 47% yield; m / e = 137 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.07 uM.

Example 145 N- (2-Methoxybenzyl) -NX (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to example 125 using 2-methylbenzylamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; m / e = 298 [M + 1]; 1 H NMR (CDCl 3) d 2.32 (s, 3 H), 3.11 (t, 2 H), 3.78 (d t, 2 H), 4.46 (d, 2 H), 7.15-7.26 (m, 6 H), 7.50-7.55 (m 1 H) , 7.62-7.67 (m, 1H), 8.12-8.15 (m, 1H), 8.60 (d, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.59 uM.

Example 146 N- (2,3-Dimethoxybenz-N '- (2- (pyridin-2-inethoxalamide Prepared in a manner similar to example 125 using 2,3-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; m / e = 343 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.69 uM.

Example 147 N- (2- (Methylthio) benzyl) -NX (2- (pyridin-2-yl) ethyl) oxalamide O AAYY Prepared in a manner similar to example 125 using 2-methylthiobenzylamine, ethyl oxalyl chloride, and 2- (pyridin-2-yl) ethylamine; m / e = 330 [M + 1]; 1 H NMR (CDCl 3) d 2.49 (s, 3 H), 3.08 (t, 2 H), 3.77 (d t, 2 H), 4.55 (d, 2 H), 7.11-7.14 (m, 1 H), 7.15-7.20 (m 2 H) , 7.22-7.27 (m, 3H), 7.62 (t, 1H), 7.78-7.83 (m, 1H), 8.08-8.11 (m, 1H), 8.56 (d, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.96 uM.

Example 148 N- (2-Hydroxybenzyl) -N, - (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to example 125 using 2-hydroxybenzylamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; m / e = 300 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 3.11 uM.

Example 149 N- (BenzordU1,31d¡oxol-4-methyl) -NX (2-pyridin-2-DetiDoxalamide Prepared in a manner similar to example 125 using benzo [d] [1, 3] dioxol-4-ylmethylamine (example 149a), ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; 12% yield; m / e = 328 [M + 1]; 1 H NMR (CDCl 3): d 3.12 (m, 2 H), 3.77-3.80 (m, 2 H), 4.46-4.47 (d, 2 H), 5.98 (s, 2 H), 6.74-6.79 (m, 3 H), 7.24 ( m, 1H), 7.7-7.8 (m, 3H), 8.10-8.15 (m, 1H), 8.58-8.59 (m, 1H). to. Benzo [d] [1, 3] dioxol-4-ylmethylamine: Prepared in a manner similar to Example 134a from benzo [dj [1,3] dioxol-4-carbaldehyde and ammonium acetate. The unpurified material contained approximately 20% of the product (m / e = 152.2 [M + 1]) and was used directly in Example 149. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a line HEK293 cellular phone of 0.17 uM.

Example 150 N-fBenzorbUofen-2-ylmetin-N '- (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to example 125 using benzo [b] thiophen-2-ylmethanamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; 32% yield; m / e = 240 [M + 1]; 1 H NMR (DMSO-de): d 2.92-2.95 (t, 2H), 3.48-3.53 (m, 2H), 4.55-4.56 (d 2H), 7.20-7.25 (m, 2H), 7.38-7.41 (m, 2H), 7.50 (s, 1H), 7.66-7.70 (m, 1H), 7.95-7.99 (m 2H), 8.47-8.49 (d, 1H), 8.88-8.90 (t, 1H), 9.29-9.31 (t , 1 HOUR). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.74 uM.

Example 151 N- (Benzodiuzol-2-ylmethyl) -NX (2- (pyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to example 125 using benzo [d] thiazol-2-ylmethanamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; 33% yield; m / e = 341 [M + 1]; 1 H NMR (DMSO-de): d 2.95-2.98 (t, 2H), 3.52-3.57 (m, 2H), 4.72-4.73 (d 2H), 7.22-7.24 (m, 1H), 7.25-7.27 (d, 1H), 7.40-7.44 (t, 1H), 7.48-7.51 (t, 1H), 7.69-7.7 (dt, 1H), 7.95-7.96 (d, 1H), 8.05-8.07 (d, 1H), 8.49- 8.50 (d, 1H), 8.96-8.98 (t, 1H), 9.67 9.70 (t, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEU293 cell line of 4.4 uM.

Example 152 N-f (5-Met llfuran-2-yl) methyl) -N2- (2-fpyridin-2-yl) ethyloxalamide Prepared in a manner similar to example 125 using (5-methylfuran-2-yl) methanamine, ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; 38% yield; m / e = 288 [M + 1]; 1 H NMR (DMSO-de): d 2.20 (s, 3H), 2.92-2.95 (t, 2H), 3.48-3.52 (m, 2H) 4.23-4.24 (d, 2H), 5.96-5.97 (d, 1H) , 6.06-6.07 (d, 1H), 7.20-7.25 (m, 2H), 7.68-7.71 (1 1H), 8.48-8.49 (d, 1H), 8.85-8.87 (t, 1H), 9.04-9.07 (t , 1 HOUR). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 4.9 uM.

Example 153 N-f (2-Methylfuran-3-inmetin-N'-22- (pyridin-2-net-ethihoxalamide Prepared in a manner similar to example 125 using (2-methylfuran-3-M) methanamine (example 153a), ethyl oxalyl chloride and 2- (pyridin-2-yl) ethylamine; 50% yield; m / e = 288 [M + 1]; 1H NMR (DMSO-d6): d 2.23 (s, 3H), 2.91-2.94 (t, 2H), 3.48-3.52 (q, 2H), 4.05-4.06 (d, 2H), 6.30-6.31 (d, 1H ), 7.20-7.25 (m, 2H), 7.38-7.39 (d, 1H), 7.67-7.71 (dt, 1H), 8.48-8.49 (d, 1H), 8.83-8.86 (t, 1H), 9.04-9.07 (t, 1H). to. (2-Methylfuran-3-yl) methanamine: A solution of 10 mmol (1256 mmoles) of methyl 2-methyl-furan-3-carboxylate and 38.9 mmoles (2.1 g) of NaOMe in 20 ml of formamide was stirred at 100 ° C. for 30 minutes. The reaction mixture was poured into ice water (20 mL) and extracted with ethyl acetate (3x). The extract was dried over MgSO4 and concentrated to give 1.05 g (83%) of the 2-methylfuran-3-carboxamide as an oil (m / e = 126.2 [M + 1]). The amide was dissolved in dry THF (10 mL) and added in drops to 15 mL of 1M LiAIH4 with 15 mL of THF at 0 ° C under argon. Then, the mixture was stirred for 5 hours at 60 ° C. After cooling, 50% aqueous THF (30 mL) was added to the mixture at 5-10 ° C. The resulting precipitate was removed by filtration and the filtered solution was dried and concentrated to give an oily product (0.93 g, 84%). The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.82 uM.

Example 154 N- (2,4-Di methoxy benzyl-NX (2- (4-methylpyridin-2-yl) ethyl) oxa lam ida Prepared in a manner similar to Example 122 using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (4-methylpyridin-2-yl) ethylamine (example 154a); 11% yield; m / e = 358 [M + 1]; p.f. 144-145 ° C; H NMR (CDCl 3): d 2.31 (s, 3H), 2.97 (t, 2H), 3.71 (q, 2H), 3.79 (s, 3H), 3.83 (s, 3H), 4.39 (d, 2H), 6.40 (dd, 1H), 6.44 (d, 1H), 6.97 (s, 1H), 6.98 (d, 1H), 7.15 (d, 1H), 7.81 (br s, 1H), 8.08 (br s, 1H), 8.41 (d, 1H). to. 2- (4-Methylpyridin-2-yl) ethylamine: Prepared in a manner similar to Example 129 using 2- (4-methylpyridin-2-yl) acetonitrile (example 154b); 83% yield; m / e = 137 [M + 1]. b. 2- (4-Methylpyridin-2-yl) acetonitrile: Prepared in a manner similar to Example 129b using 2-bromo-4-methylpyridine, acetonitrile and n-BuLi; 88% yield; m / e = 133 [M + 1]. The compound had an EC5o for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 1.64 uM.

Example 155 N- (2,4-D-methoxybenzyl) -NX (2- (5-methylpyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to Example 122 using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (5-methylpyridin-2-yl) ethylamine (example 155a); 9% yield; m / e = 358 [M + 1]; p.f. 124-125 ° C; 1 H NMR (CDCl 3): d 2.30 (s, 3 H), 2.97 (t, 2 H), 3.70 (q, 2 H), 3.79 (s, 3 H), 3.82 (s, 3 H), 4.38 (d, 2 H), 6.40. (dd, 1H), 6.44 (d, 1H), 7.03 (d, 1H), 7.14 (d, 1H), 7.40 (dd, 1H), 7.81 (br s, 1H), 8.08 (br s, 1H), 8.38 (d, 1H). to. 2- (5-Methylpyridin-2-yl) ethylamine: Prepared in a manner similar to 129a using 2- (5-methylpyridin-2-yl) acetonitrile (155b); 40% yield; m / e = 137 [M + 1]. b. 2- (5-Methylpyridin-2-yl) acetonitrile: prepared in a manner similar to 129b using 2-bromo-5-methylpyridine, acetonitrile and n-BuLi; 68% yield; m / e - 133 [M + 1]. The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.07 uM.

Example 156 N- (2,4-Dimethoxybenzin-N '- (2- (thiophene-2-ynyl) oxalamide Prepared in a manner similar to Example 122, using 2,4-dimethoxybenzylamine, ethyl oxalyl chloride and 2- (thiophen-2-yl) ethylamine; 72% yield; m / e - 349 [M + 1]; mp 146-147 ° C; 1 H NMR (CDCl 3): d 3.06 (t, 2H), 3.58 (q, 2H), 3.80 (s, 3H), 3.83 (s, 3H), 4.40 (d, 2H), 6.41 (dd, 1H), 6.45 (d, 1H), 6.84 (dd, 1H), 6.93 (dd, 1H), 7.15 (d, 1H), 7.16 (d 1H), 7.61 (br s, 1H), 7.81 (br s, 1H). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 4.87 uM.

Example 157 N1- (2-methoxy-4-methylbenzyl) -N2- (2- (5-methylpyridin-2-yl) ethyl) oxalamide Prepared in a manner similar to Example 125, using 2-methoxy-4-methylbenzylamine (example 132a), ethyl oxalyl chloride and 2- (4-methylpyridin-2-yl) ethylamine (example 155a). Yield 20%; p.f. 116-117 ° C; 1 H NMR (CDCl 3): d 2.31 (s, 3 H), 2.34 (s, 3 H), 3.00 (t, 2 H), 3.71 (q, 2 H), 3.84 (s, 3 H), 4.42 (d, 2 H), 6.69 (s, 1H), 6.71 (d, 1H), 7.05 (d, 1H), 7.11 (d, 1H), 7.43 (d, 1H), 7.84 (br s, 1H), 8.04 (br s, 1H), 8.39 (s, 1H); MS (M + H, 342). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.03 uM. The additional "oxalamide" compounds were synthesized and experimentally tested and found to have a relatively high level of effectiveness as an activator of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line. The results of the test are shown later in Table B.

Numerous amide compounds of Formula (I) that fall within the subgenus of the "urea" compounds described elsewhere herein were synthesized and experimentally tested for effectiveness as an activator of an acre receptor hT1R1 / hT1R3 expressed in a line HEK293 cell phone Example 158 1- (4-chlorophenyl) -3-fheptan-4-yl) urea To a solution of heptan-4-amine (0.18 mL, 1 mmol) in CH2Cl2 (5 mL) was added 1-chloro-2-isocyanatobenzene (0.12 mL, 1 mmol) at room temperature. The reaction mixture was stirred for 2 hours. A white solid precipitated. The reaction mixture was filtered. The solid was washed with CH2Cl2 to yield 1- (4-chlorophenyl) -3- (heptan-4-yl) urea (180 mg, 67%) as a white solid, m.p. 135-136 ° C. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6H), 1.45 (m, 6H), 1.53 (m, 2H), 3.80 (br s, 1H), 4.33 (d, 1H), 6.00 (s, 1H), 6.95 (td, 1H), 7.23 (dt, 1H), 7.33 (dd, 1H), 8.13 (dd, 1H). MS (M + H, 269). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.37 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 4.95.

Example 159 1- (2,4-D-methoxyphenyl) -3- (he tan-4-yl) urea Prepared in a manner similar to Example 158 using heptan-4-amine and 1-isocyanato-2,4-dimethoxybenzene. Yield: 88%. p.f .: 172-173 ° C. 1 H NMR (500 MHz, CDCl 3): d 0.93 (t, 6H), 1.45 (m, 8H), 3.82 (s, 3H), 3.83 (m, 1H), 3.84 (s, 1H), 4.32 (br s, 1H), 6.34 (br s, 1H), 6.49 (d, 1H), 6.50 (s, 1H), 7.71 (d, 1H). MS (M + H, 295). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.98 μM, and when presented in 0.3 μM it improves the effectiveness of monosodium glutamate with an EC50 ratio of 7.61.

Example 160 1- (4-ethoxy-phenyl) -3- (2- (pyridin-2-yl) ethyl) urea Prepared in a manner similar to example 158 using 2- (pyridin-2-yl) ethanamine and 1-ethoxy-4-isocyanatobenzene. Yield: 95%. p.f .: 163-164 ° C. 1 H NMR (500 MHz, CDCl 3): d 1.43 (t, 3 H), 3.03 (t, 2 H), 3.68 (t, 2 H), 4.03 (q, 2 H), 5.69 (br s, 1 H), 6.45 (br s) , 1H), 6.84 (m, 2H), 7.14 (m, 3H), 7.20 (d, 1H), 7.64 (dt, 1H), 8.43 (dd, 1H). MS (M + H, 286). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a cell line HEK293 of 4.1 μM, and when presented in 1 μM improves the effectiveness of monosodium glutamate with an EC50 ratio of 4.2.

Example 161 1- (4-isopropylphenyl) -3- (2- (pyridin-2-ethyl) urea Prepared in a manner similar to example 158 using 2- (pyridin-2-yl) ethylamine and 1-isocyanato-4-isopropylbenzene. Purify by column chromatography (1% MeOH in CH 2 Cl 2 to 3% MeOH in CH 2 Cl 2) to produce 1- (4-isopropylphenyl) -3- (2- (pyridin-2-yl) ethyl) urea (130 mg, 50%) as a white solid, mp: 72-73 ° C. 1 H NMR (500 MHz, CDCI): d 1.25 (d, 6H), 2.89 (m, 1H), 3.06 (t, 2H), 3.70 (t, 2H), 5.80 (br s, 1H), 6.55 (br s , 1H), 7.19 (m, 5H), 7.24 (d, 1H), 7.68 (dt, 1H), 8.46 (d, 1H). MS (M + H, 284). The compound had an EC50 for the activation of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line of 0.98 μM. The additional "urea" compounds were synthesized and experimentally tested and found to have a relatively high level of effectiveness as an indicator of an acre receptor hT1R1 / hT1R3 expressed in a HEK293 cell line. The results of that test are shown later in Table C.

Numerous amide compounds of Formula (I) that fall within the subgenus of the "acrylamide" compounds described elsewhere herein were also synthesized and experimentally tested for effectiveness with an activator of an acre receptor hT1 R1 / hT1 R3 expressed in a HEK293 cell line. The results of that test are shown later in Table D.

Acre / Savory Tasting Experiments Using Panelists: General Selection of Panelists: The Basic Selection of Taste-Sensitive Tasters: Potential panellists tested their abilities to classify the intensities of the solutions that represent the five basic flavors. The panelists classified and evaluated the intensity of five different concentrations of each of the following compounds: sucrose (d ulce), sodium chloride (salty), citric acid (sour), caffeine (bitter) and monosodium glutamate (savory). In order to select the participation in the test, the panelists need to classify and correctly evaluate the samples for intensity, with a reasonable number of errors. Pre-Taste Tasting Tests: The panelists selected in the previous procedure were considered qualified to perform the Pre-Taste Tasting Procedures. Preliminary taste tests are used to evaluate new compounds for intensity of basic and unpleasant tastes. A small group of panelists (n = 5) tested approximately 5 concentrations of the compound (range normally between 1-100 μM, in logarithmic cycles, eg, 1, 3, 10, 30 and 1 00 μM) in water and in a solution of 12 mM of MSG to evaluate the improvement. The panelists evaluate the five basic flavors (sweet, salty, sour, bitter and tasty) as well as drainage (such as chemicals, metals, sulfur) on the scale of magnitude labeled. The samples are served in 1 0 m L portions at room temperature. The purpose of the test is to determine the highest concentration in which there is no unpleasant taste objection, and to determine whether the obvious tasty flavor or the tasty flavor improvement exist at any of the concentrations tested. If the compound is effective and has no objectionable unsealable flavor, this is tested with a (expert panel) trained in a larger study. Selection of the Trained Panelist: A trained expert panel was used to further evaluate compounds that have been tested with the pre-elimination taste test. Panelists were selected for the trained panel from a larger group of qualified flavor panelists. In addition, panelists were trained in tasty taste by classifying and evaluating experiments using MSG and I MP combinations. The panelists completed a series of classifications and evaluations and differentiated them from benchmark tests with tasty solutions. In the classification and evaluation experiments, the panelists evaluated easy MSG concentrations (0, 6, 18, 36 mM) and more difficult MSG concentrations (3, 6, 12, 1 8 mM MSG) in water. Test of the Compound with Trained Panel: The compounds tested by the trained panel were evaluated in reference experiments. The panelists were given a reference sample (12 mM MSG + 100 μM I MP) and were asked to evaluate samples on a scale of -5 to +5 in terms of taste difference tasty from the reference ( score: - 5 = flavor much less tasty than the reference; 0 = the same taste tasty as the reference; +5 = flavor much tastier than the reference). The flavor samples were solutions with varying amounts of MSG, IMP, and the compound. Normally, each session compares the reference sample to numerous test samples. The tests usually include samples with varying concentrations of MSG and I MP, as well as a blank sample of the same reference, to evaluate the accuracy of the panel. The results of the taste tests are described in Table 3 and show that the compounds of the invention have been found to provide tasty flavor or improve flavor taste at 3 μM + MSG when compared to 1 00 μM of I MP + MSG . The compounds were tested against the reference in samples with and without 12 mM MSG. All samples were presented in 10 ml volumes at room temperature. Two sessions were completed for each compound tested to evaluate the panel's reproducibility. Taste Test in Product Prototype: Could be done similarly as described above.

Table 3. Tasty Taste Test Results Examples of Sweet Amides Numerous amide compounds of Formula (I) were synthesized and experimentally tested for effectiveness as an activator of a "sweet" receptor hT1R2 / hT1R3 expressed in a HEK293 cell line. Examples of synthesis and biological effectiveness test in terms of EC50 measurements. Sweets of such sweet compounds are listed below. In addition, many of the "sweet" amides of Formula (I) were also classified for activity in EC50 and EC50 assays, and as illustrated below, some of the amide compounds of Formula (I) have significant activity. and potential to simultaneously serve as sweet and savory flavor enhancers for use in edible and medicinal products and compositions.

Example 162 2, 3, 5, 6 -tetraf I uoro-4-methyl-N- (2-methylcyclohexyl) benzamide 200 ml of anhydrous DCM and 30 ml of anhydrous DMF 2,3,5,6-tetrafluoro-p-toluic acid (4.00 g, 19.22 mmoles), HOBt (5.19 g, 38.44 mmoles) and EDCI (4.41 g, 23.06 mmoles). The mixture was cooled to 0 ° C and allowed to stir under Ar for 15 minutes. To the mixture was added 2-methylcyclohexanamine (3.05 mL, 23.06 mmol) and the reaction mixture allowed to warm slowly to room temperature and stirred overnight. The reaction mixture was diluted with DCM, washed with 1N HCl, water, aqueous NaHCO3, water and brine, drying over MgSO4, filtration and removal of the solvent in vacuo, afforded the unpurified product as a pale yellow solid. Recrystallization (EtOH / H2O) and drying in vacuo gave 5.23 g of the title compound as a white solid (mixture of 2 diastereomers, 90%). 1 H NMR (CDCl 3) d 0.95, 1.01 (d, J = 7.0, 6.6 Hz, 3H) 1.1-2.1 (m, 9H), 2.29 (m, 3H), 3.70, 4.29 (m, 1H), 5.65, 5.92 (m, 1H). MS (304.1, M + H). p.f. 202-204 ° C. The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.39 μM.

Example 163 (S) -2,3,5,6-tetrafluoro-4-methyl-N- (3-methylbutan-2-yl) benzamide Prepared in a manner similar to Example 162 using (S) -3-methylbutan-2-amine and 2,3,5,6-tetrafluoro-p-toluic acid (93%). 1H NMR (CDCl 3) d 0.98 (d, J = 6.9 Hz, 6H) 1.18 (d, J = 6.8 Hz, 3H), 2.29 (m, 3H), 4.09 (m, 1H), 5.72 (bs, 1H). MS (304.1, M + H) mp 146-147 ° C.

The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.6 μM.

Example 164 N-cycloheptyl-2,3,5,6-tetraf! Uoro-4-methyl-benzamide Prepared in a manner similar to Example 162 using cycloheptylamine and 2,3,5,6-tetrafluoro-p-toluic acid (94%). 1 H NMR (CDCl 3) d 1.53 (m, 6 H), 1.57 (m, 4 H), 2.03 (m, 2 H) 2.28 (m, 3 H), 4.17 (m, 1 H), 5.85 (bs, 1 H). MS (304.1, M + H) p.f. 164-165 ° C. The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 1.85 μM.

Example 165 N- (2,4-dimethylpentan-3-y!) - 2,3,5,6-tetrafluoro-4-methylbenzamide Prepared in a manner similar to Example 162 using 2,4-dimethylpentan-3-amine and 2,3,5,6-tetrafluoro-p-toluic acid (90%). 1 H NMR (CDCl 3) d 0.91 (d, J = 6.7 Hz, 6 H), 1.00 (d, J = 6.8 Hz, 6 H), 1.85 (m, 2 H), 2.29 (m, 3 H), 3.82 (m, 1 H) , 5.52 (bd, 1H). MS (306.1, M + H) p.f. 184-187 ° C. The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.81 μM.

Example 166 N- (5,7-dimethyl-1,2,3,4-tetrahydro ronaf talen -1 -i I) -3-methyl isoxazole-4-carboxamide To a solution of 3-methylisoxazole-4-carboxylic acid (83 mg, 0.067 mmol), HOBt (100 mg, 0.74 mmol) and EDCI HCl (142 mg, 0.74 mmol) in DMF (4 mL) was added 5.7- dimethyl-1,2,3,4-tetrahydronaphthyl-1-amine (example 166a) (130 mg, 0.74 mmol). The reaction mixture was stirred for 24 hours at room temperature, at which time the solvent was removed under reduced pressure and the residue was purified by flash column chromatography (10: 1 Hex: EtOAc) to yield 134 mg of N- (5, 7-d i met I-1,2,3,4-tetrahydro-naphthalen-1-yl) -3-methylisoxazo-1-4-carboxamide (70%) as a white foamy solid. 1 H NMR (500 MHz, DMSO-d 6): d 1.74 (m, 2 H), 1.86 (m, 2 H), 2.16 (s, 3 H), 2.19 (s, 3 H), 2.43 (s, 3 H), 2.55 (m , 2H), 5.10 (m, 1H), 6.86 (s, 1H), 6.89 (s, 1H), 8.60 (d, 1H, J = 8.40 Hz), 9.27 (s, 1H). 13 C NMR (125 MHz, DMSO-de): d 10.6, 19.1, 19.6, 20.6, 25.8, 29.4, 46.9, 115.4, 126.4, 129.1, 132.6, 134.1, 135.8, 136.6, 158.5, 159.6, 159.9. MS (M + H, 285). P.f. 57-58 ° C. to. 5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine: A catalytic amount of the Raney nickel (suspension in water) was washed with dry MeOH under argon in a round bottom flask. To a solution of the washed Raney Ni in methanolic ammonia (25 mL, 7N), 5,7-dimethyl-3,4-dihydronaphthalen-1 (2H) -one oxime (example 166b) (420 mg, 2.22 mmol) was added and The mixture was stirred under a balloon of H2 for 20 hours. After completion of the reaction, it was filtered through celite, the filtrate was concentrated in vacuo, diluted with EtOAc, washed with water and brine, dried over MgSO 4, filtered and the solvent was removed under reduced pressure to yield 360 mg of 5,7-dimethyl-1, 2,3,4-tetrahydronaphthalen-1-amine (93%). 1 H NMR (500 MHz, CDCl 3): d 1.66-1.83 (m, 4 H), 1.96 (m, 2 H), 2.19 (s, 3 H), 2.28 (s, 3 H), 2.55 (m, 1 H), 2.66 (m , 1H), 3.97 (m, 1H), 6.88 (s, 1H), 7.09 (s, 1H). b. Preparation of 5,7-dimethyl-3,4-dihydronaphthalen-1 (2H) -one oxime: To a mixture of 5,7-dimethyl-3,4-dihydronaphthalen-1 (2H) -one (2.0 g, 11.48 mmol) and hydroxylamine hydrochloride (1.6 g, 19.73 mmol) in 10 ml of water at 70 ° C, MeOH (14 mL), THF (3 mL) and sodium acetate solution (2.53 g, 30.83 mmol) were added. , in 7 mL of H2O). Stirring was continued for 85 minutes at 70 ° C, at which time a precipitate formed and 10 ml of water were added. The resulting mixture was stirred at room temperature for 2 hours. At the completion, the product was collected by filtration to yield 2.12 g of 5,7-dimethyl-3,4-dihydronaphthalen-1 (2H) -one oxime (98%). MS (M + H, 190). The compound had an EC5o for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.76 μM.

Example 167 3-chloro-2-hydroxy- / V- (5-methoxy-1.2.3.4-tetrahydronaphthalen-1 iDbenzamide Prepared in a manner similar to Example 166 using 5-methoxy-1, 2,3,4-tetrahydronaphthalen-1-amine (Example 167a). Performance 40%. 1 H NMR (500 MHz, DMSO-d 6): d 1.73 (m, 1 H), 1.83 (m, 1 H), 1.96 (m, 2 H), 2.61 (m, 2 H), 3.78 (s, 3 H), 5.27 (m , 1H), 6.78 (d, 1H, J = 7.82 Hz), 6.86 (m, 2H), 7.14 (t, 1H, J = 7.98 Hz), 7.60 (dd, 1H, J = 7.88, 1.30 Hz), 7.94 (dd, 1H, J = 8.03, 1.39 Hz), 9.30 (d, 1H, J = 8.06 Hz), 13.80 (s, 1H). 13C NMR (125 MHz, DMSO-d6): d 19.5, 22.7, 28.9, 47.4, 55.3, 108.6, 115.8, 118. 7, 119. 8, 121.1, 125.9, 126.2, 126.4, 133.8, 137.3, 156.7, 156. 8, 168.7. MS (M + H, 332). p.f. 175-176 ° C. to. 5-Methoxy-1, 2, 3,4-tetrahydrum afta len-1 -amine: Prepared in a manner similar to Example 166a using 5-methoxy-3,4-dihydronaphthalen-1 (2H) -one. Yield 94%. 1 H NMR (500 MHz, CDCl 3): d 1.63-1.79 (m, 4 H), 1.94 (m, 2 H), 2.60 (m, 1 H), 2.71 (m, 1 H), 3.82 (s, 3 H), 3.97 (m , 1H), 6.71 (d, 1H), 7.02 (d, 1H), 7.17 (t, 1H). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.21 μM.

Example 168 2, 6-d i m eti I -N - (2-methyl cid or hexyl) benzamide Prepared in a manner similar to Example 162 using 2,6-dimethylbenzoic acid and 2-methylcyclohexylamine. Yield: 59%. 1 H NMR (500 MHz, CDCl 3): d 0.88-0.94 (3H, dd), 1.14-1.89 (9H, m), 2.21-2.22 (6H, d), 3.39-3.45 (1H, m), 7.02- 7.03 ( 2H, d), 7.12-7.15 (1H, t), 8.11-8.13 (1H, d). MS (M + H, 246.2). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 1.88 μM.

Example 169 4-methoxy-2, 6-d i m eti l-N- (2-methylcic I ohexip benzamide Prepared in a manner similar to Example 166, using 4-methoxy-2,6-dimethylbenzoic acid (example 169a) and 2-methylcyclohexylamine. 1 H NMR (500 MHz, CDCl 3): d 0.86-0.92 (3H, dd), 1.00-1.85 (m, 9H), 2.18-2.19 (6H, d), 3.33-3.45 (1H, m), 3.71-3.72 ( 3H, d), 6.59 (2H, s), 7.98-8.05 (1H, m). MS (276.2, M + H). to. 4-methoxy-2,6-dimethylbenzoic acid: 2-bromo-5-methoxy-1,3-dimethylbenzene (Example 169b) (3.38 g, 15.79 mmol) was dissolved in 100 ml of dry THF without further purification. The mixture was cooled to -78 ° C and under n-buty I-lithium argon (solution of 1.6 M in hexanes, 9.9 mL, 15.8 mmol) was added in droplets for 15 minutes and the mixture was stirred for 15 more minutes. -78 ° C. Then small pieces of dry ice were added and the mixture was stirred 20 minutes at -78 ° C. Then, the cooling was removed and the mixture was stirred as long as the evolution of the carbon dioxide continued. Then, the mixture was poured onto ice (100 mL) and acidified using 6N HCl. The organic layer was separated and the aqueous phase was extracted with EtOAc. The organic extracts were combined, washed with brine, water, dried over MgSO 4 and concentrated in vacuo. The product of 4-methoxy-2,6-dimethylbenzoic acid was obtained as a white solid (2.7 g, 95%). (M + H, 181). b. 2-Bromo-5-methoxy-1,3-dimethylbenzene: 20 mmol of 1-methoxy-3,5-dimethylbenzene (2.82 mL) was dissolved in 100 mL of dry acetonitrile followed by 22 mmol (3.56 g) of N-bromosuccinimide . The mixture was stirred at room temperature overnight. Then, the solvent was evaporated under reduced pressure and a solid was filtered off and washed with hexanes to give 2-bromo-5-methoxy-1,3-dimethylbenzene (3.9 g, 92%) as a white solid. 1 H NMR (500 MHz, CDCl 3): d 2.41 (6H, s), 3.78 (3H, s), 6.67 (2H, s). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 2.1 μM.

Example 170 (R) -N-d, 2,3,4-tetrahydronaphthalen-1-yl) furan-3-carboxamide To a solution of furan-3-carboxylic acid (100 mg, 0.68 mmol), HOBt (240 mg, 1.78 mmol) and EDCI HCl (196 mg, 1.03 mmol) in CH2Cl2 (8 mL) and DMF (1.5 mL) at 0 ° C, (ft) -1,2,3,4-tetrahydronaphthalen-1-amine (160 μL, 1.06 mmol) was added. The reaction was stirred at room temperature for 24 hours, after which CH2Cl2 was added. The resulting solution was washed with saturated NaHCO3, H2O, brine, dried over MgSO4 and concentrated in vacuo. Recrystallization from EtOH / H2? produced (R) -N- (1,2,3,4-tetrahydronaphthalen-1-yl) -2,5-dihydrofuran-3-carboxamide. 1 H NMR (500 MHz, CDCl 3): d 1.89 (m, 3 H), 2.12 (m, 1 H), 2.84 (m, 2 H), 5.35 (m, 1 H), 5.96 (br d, 1 H, J = 7.75 Hz) , 6.59 (dd, 1H, J = 1.90, 0.86 Hz), 7.13 (m, 1H), 7.19 (m, 2H), 7.32 (m, 1H), 7.43 (t, 1H, J = 1.73 Hz), 7.93 ( m, 1H). MS (M + H, 242). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 6.6 μM.

Example 171 (/?) 5-methyl-JV- (1,2,3,4-tetrahydronaphthalene-1-yl) -isoxazole-4-carboxamide Prepared in a manner similar to Example 170 using 5-methylisoxazole-4-carboxylic acid. Purified by preparative TLC (5: 1 Hex: EtOAc). 1 H NMR (500 MHz, CDCl 3): d 1.80 (m, 3 H), 2.12 (m, 1 H), 2.74 (s, 3 H), 2.85 (m, 2 H), 5.35 (m, 1 H), 5.89 (br d, 1H, J- 7.75 Hz), 7.10 (m, 1H), 7.18 (m, 2H), 7.32 (m, 1H), 8.26 (s, 1H). MS (M + H, 257). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a cell line HEK293 of 8.1 μM.

Example 172 N- (4-chloro-2-methylphenyl) -andolin-2-carboxamide To a solution of isoindoline (238 mg, 2.0 mmol) in dry 1,4-dioxane (10 mL) was added 4-chloro-2-methylphenyl isocyanate (335 mg, 2.0 mmol) under argon at room temperature. The reaction mixture was then stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was purified by recrystallization from ethanol to give the title compound (540 mg, 94%) as a white solid. 1 H NMR (500 MHz, DMSO-d 6): d 2.24 (s, 2 H), 4.76 (s, 4 H), 7.20 (d, J = 2.5, 8.5 Hz, 1 H), 7.27 (d, J = 2.5 Hz, 1 H ), 7.30-7.32 (m, 2H), 7.34-7.37 (m, 2H), 7.42 (d, J = 8.5 Hz, 1H), 7.84 (s, 1H); 13 C NMR (DMSO-d 6): d 17.7, 51.9, 122.8, 125.6, 126.8, 127.3, 128.1, 129.5, 134.7, 136.8, 154.2; MS (MH +, 287); EA calculated for C16H | 5CIN2O: C, 67.02; H, 5.27; N, 9.77; Found C, 66.82; H, 5.41; N, 9.92. The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 0.89 μM.

Example 173 N- (4-methoxy-2-methylphenyl) isoindoline-2-carboxamide To a solution of isoindoline (576 mg, 4.0 mmol) in dry 1,4-dioxane (20 mL) was added 4-methoxy-2-methylphenyl isocyanate (815 mg, 5.0 mmol) under argon at room temperature. The reaction mixture was then stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was purified by chromatography on silica gel (EtOAc / hexanes: 1: 1) to give the title compound (1.18 g, 84%) as a white solid. 1 H NMR (500 MHz, DMSO-de): d 2.19 (s, 3 H), 3.72 (s, 3 H), 4.73 (s, 4 H), 6.72 (dd, J = 2.5 Hz, 8.5 Hz, 1 H), 6.78 ( d, J = 2.5 Hz, 1H), 7.17 (d, J = 8.5 Hz, 1H), 7.30-7.32 (m, 2H), 7.34-7.36 (m, 2H), 7.74 (s, 1H), 13C NMR ( DMSO-de): d 18.2, 51.9, 55.1, 110.9, 115.1, 122.8, 127.2, 127.8, 130.6, 135.1, 137.0, 154.9, 156.5; MS (MH +, 283); EA calculated for C17H18N2? 2: C, 72.32; H, 6.43; N, 9.92; Found C, 72.16; H, 6.82; N, 9.98. The compound had an EC5o for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 4.5 μM.

Example 174 N- (3,4-methylenedioxyphenyl) isoindoline-2-carboxamide To a solution of 3,4- (methylenedioxy) aniline (150 mg, 1.09 mmol) in dry DCM (4 mL) was added in drops phenyl chloroformate (0.138 mL, 1.09 mmol) and triethylamine (0.153 mL, 1.09 mmol). . After the reaction mixture was stirred at room temperature for 8 hours, isoindoline (0.123 ml, 1.09 mmol) and triethylamine (0.153 ml, 1.09 mmol) were added, and the reaction mixture was stirred overnight. The solvent was then stirred under reduced pressure and the residue was purified by chromatography on silica gel (EtOAc / Hexane: 1: 3) to give the title compound (185 mg, 60%) as a white solid: m.p. 165-166 ° C. 1 H NMR (CDCl 3, 500 MHz): 4.82 (s, 4 H); 5.93 (s, 2H); 6.20 (s, 1H); 6.73 (s, 2H); 7.17 (s, 1H); 7.30 (m, 4H). MS (MH +, 283). The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 1.05 μM.

Example 175 3-Methyl-isoxazole-4-carboxylic acid (1, 2,3,4-tetrahydro-naphthalen-1-yl) -amide To a solution of 3-Methyl-isoxazole-4-carboxylic acid (0.52 g, 4.06 mmol) in DCM (15 mL) and DMF (2 mL) was added HBOt (1.1 g, 8.14 mmol) and EDCI (0.896 g, 4.67 g). mmoles). The clear yellow solution was cooled to 0 ° C and allowed to stir under Ar for 15 minutes. To the solution was added (R) -1- Amino-1, 2,3,4-tetrahydronaphthalene (0.73 ml, 5.04 mmol) and the reaction mixture was allowed to warm slowly to room temperature and stirred overnight. Dilution with DCM (50 mL) was followed by aqueous extraction (NaHCO3), water, brine (50 mL), drying over MgSO4, filtration and removal of the solvent in vacuo. Silica gel chromatography (0-25% Hexane: EtOAC) afforded the title compound (650 mg; 62.5%) as a sticky solid. 1 H NMR (CDCl 3) d 1.88 (m, 3 H), 2.12 (m, 1 H), 2.51 (s, 3 H), 2.81 (m, 2 H), 5.32 (m, 1 H), 5.99 (bd, 1 H), 7.13 ( m, 1H), 7.20 (m, 2H) 7.20 (m, 2H); 13C NMR (CDCI3) d 11.22, 20.15, 29.41, 30.35, 47.93, 116.73, 126.72, 127.88, 128.88, 129. 65, 136.25, 138.00, 158.45, 160.28. ESIMS: 257 (M + H) EA calculated for C15H? 6N2O2: C, 70.29; H, 6.29; N, 10.93; Found C, 70.61; H, 6.11; N, 11.09. The compound had an EC50 for the activation of a sweet receptor hT1R2 / hT1R3 expressed in a HEK293 cell line of 5.8 μM. Numerous amide compounds of Formula (I) were synthesized and experimentally tested also for effectiveness as an activator of a "sweet" receptor hT1R2 / hT1R3 expressed in a HEK293 cell line. The results of that test are shown later in Table E.

Measurement of Sweet Flavor Improvement and Sweet Flavor Using Human Panelists Purpose: To investigate the intensity of various unpleasant tastes and flavors of an experimental compound. To determine the maximum concentration of the experimental compound that does not produce an undesirable characteristic to unpleasant taste. General view: Various concentrations of the experimental compound (usually aqueous solutions containing concentrations of 1, 3, 10 and 30 uM of the experimental compound, and optionally 50 uM and / or 100 uM concentrations) are individually tested by trained subjects and classified by the intensity of various flavor attributes. The experimental compound can also be tested when dissolved in a "key tasting" solution. Procedure: An appropriate amount of the experimental compound is dissolved in water usually also containing 0.1% ethanol, which is used to aid the initial dispersion of the compound in the aqueous stored solution. When appropriate, the experimental compound can also be dissolved in aqueous solutions of a "key taster" (e.g., 4% sucrose, 6% sucrose, 6% fructose / glucose, or 7% fructose / glucose, a pH 7.1 or 2.8). Five human subjects are used for pre-molar taste tests. The subjects have a demonstrated ability to test the desired flavor attributes and are trained to use a Labeled Magnitude Scale (LMS) of 0 (Barely Detectable Sweetness). Subjects refrain from eating or drinking (except water) for at least 1 hour before the test. Subjects eat a cookie and rinse with water four times to clean the mouth before taste tests. The aqueous solutions are distributed in 10 ml volumes into 1-ounce sample vessels and served to the subjects at room temperature. Samples of the experimental compound d sampled in an appropriate key taster (e.g., 4% sucrose, 6% fructose or 6% fructose / glucose, usually at pH 7.1) in various concentrations of the experimental compound can also serve the subjects . Subjects also receive a reference sample from the key taster (eg, sucrose, fructose or fructose / glucose, usually at a pH of 7.1) at different concentrations for comparison. The subjects test the solutions, starting with the lowest concentration, and the intensity of the relationship between the following attributes in the Labeled Magnitude Scale (LMS) for sweetness, salinity, acidity, bitterness, flavor (acre), and others ( Unpleasant taste). The subjects are rinsed three times with water between the tastings. If a particular concentration produces an undesirable characteristic of unpleasant taste, the subsequent tastings of higher concentrations are eliminated. After a break, the Subjects try a key tasting solution (eg, 4% sucrose, 6% fructose or 6% fructose / glucose, usually at pH 7.1) without the experimental compound. Then, the solutions of the key taster plus the experimental compound are tested by increasing the order of concentration. The key tasting solution can be placed for comparison with key tasting solutions + the experimental compound if necessary. Discussion is allowed between the panelists. The maximum concentration of an experimental compound that does not produce an objectionable characteristic of unpleasant taste is the highest concentration where a particular compound will be tested in subsequent sensory experiments. To confirm the preliminary test results, the test can be repeated with another small group of panelists. The preliminary profile test is always the first test performed on a new experimental compound.

Depending on the results of the preliminary profile test, additional quantitative tests can be performed to further characterize the experimental compound.

Human Taste Test Procedures of "Difference from Reference" Purpose: To determine how the intensity of a test sample of an experimental compound differs from that of a reference sample in terms of sweetness. This type of study requires a larger panel (usually 15-20 subjects) in order to obtain statistically significant data. Overview: A group of 10 or more panelists tests pairs of solutions where a sample is the "Reference" (which normally does not include an experimental compound and is an approved substance or a substance Generally Recognized as Safe (GRAS), ie a sweetener) and a sample is the "Proof" (which may or may not include a compound). The subjects evaluate the difference in the intensity of the test sample compared to the reference sample for the key attribute on a scale of -5 (much less sweet than the reference) to +5 (much sweeter than the reference). A score of 0 indicates that the test sample is equally as sweet as the reference sample. Procedure: Ten or more Subjects are used for the "Difference from the Reference" tests. The subjects have previously been familiarized with the taste of the key attribute and are trained to use the scale from -5 to +5. Subjects refrain from eating or drinking (except water) for at least 1 hour before the test. The subjects eat a cookie and rinse with water four times to clean the mouth. Ten solutions may include the experimental compound in water, the experimental compound plus a key taster (e.g., 4% sucrose, 6% sucrose, 6% fructose, 6% fructose / glucose or 7% fructose / glucose, at pH 7.1 or 2.8), and a key tasting range of only solutions as references. Samples of the key taster without the experimental compound are used to determine if the panel is accurately classified; that is, the reference is tested again to itself (blind) to determine how accurate the panel is classified on a given test day. The solutions are distributed in 10 ml volumes into 1-ounce sample cups and are served to Subjects at room temperature.

The subjects first test the reference sample, then immediately test the test sample and evaluate the difference in intensity of the key attribute on the Difference scale from the Reference (-5 to +5). All the samples are spit out. Subjects can retest samples but can only use the volume of the given sample. Subjects can mop at least twice with water between pairs of samples. It may be required to eat a cookie between the sample pairs depending on the samples tested. The scores for each test are averaged through Subjects and the standard error is calculated. The accuracy of the panel can be determined using the score from the blind reference test. ANOVA and multiple comparison tests (such as Tukey's Significantly Significant Difference test) can be used to determine differences between pairs, provided that the reference sample is the same between all tests. If the identical test pair is tested in another session, a Student t test (coupled, two-sided, alpha = 0.05) can be used to determine if there is any difference in the evaluations between sessions. A number of different reference sweeteners have been used for the measurement of the sweet taste improver. For example, for the test (R) -3-methyl-N- (1, 2,3,4-tetrahydronaphthalen-1-yl) isoxazole-4-carboxamide, a reference sample consisting of 4% sucrose is uses, which has a greater sweetness than the threshold level (ie 2% sucrose) and a sweetness in the region of sweet taste perception where human subjects are more sensitive to small changes in the perception of sweet taste . For the test of 2, 3,5,6-tetrafluoro-4-methyl-N- (2-methylcyclohexyl) benzamide, a 50:50 mixture of fructose.-glucose was used to better model the high fructose corn syrup solutions commonly used in the beverage industry. A 6% fructose / glucose mixture that is approximately equal in sweet taste perception as 6% sucrose was demonstrated, which is within the range where the panelists are sensitive to small changes in the taste perception of the ulce. After the initial studies at 6% fructose / glucose at pH 7.1, the studies change to evaluate the yield of the compound in a product phenotype more similar to a cola drink, ie, higher concentrations of sweetener and a pH lower. The results of some human taste tests of the sweet amide compounds of the invention in the aqueous compositions intended to model the composition of a carbonated beverage are shown below in Table F.

Table F. Sweet Taste Test Results The pH of these aqueous solutions was not measured or controlled Example 176 Preparation of Soup Using a Broth Solution in Ethanol A compound of the invention is diluted using 200 proof of ethanol at 1000x of the desired concentration in the soup. The compound can be sonicated and heated (if stable) to ensure complete solubility in ethanol. The soup from the base of caldillo is made by adding 6 g of base of vegetable stew in 500 ml of hot water in a glass or clay vessel. The water is heated to 80 ° C. The concentration of MSG in the dissolved caldillo is 2.2 g / L and there is no added IMP. After the caldillo base dissolves, the ethanol broth solution is added to the base of the soup. For 500 mL of soup, 0.5 mL of the broth in 1000x ethanol is added for a final ethanol concentration of 0.1%. If ethanol interferes with the taste of the soup, a higher concentration of ethanol broth solution can be prepared as long as the compound is soluble.

Example 177 Preparation of French Fries A salt mixture of a compound of the invention is made by mixing with salt such that 1.4% of the mixture of salt added w / w to the potato chips would result in the desired concentration of the compound. For 1 final ppm of the compound in the potato chips, 7 mg of the compound is mixed with 10 g of salt. The compound is ground using a mortar and pestle with the salt and the compound and the salt are mixed well. The chips are divided into small uniform pieces using a mixer. For each 98.6 g of potato chips, 1.4 g of the salt mixture is weighed. The pieces of French fries are first heated in a microwave for 50 seconds or until hot. The pieces are separated into a large piece of aluminum foil. The salt mixture is evenly spread on the potato chips. The French fries are then placed in a plastic bag ensuring that all the salt is placed in the bag as well. The salt mixture and the potato chips are stirred to ensure that the salt is evenly spread over the potato chips.

Example 178 Preparation of Cookies A compound of the invention is diluted using 200 proof of ethanol at 1 000x of the desired concentration in the final product. The compound can be sonicated and heated (if stable) to ensure complete solubility in ethanol. The solution containing the compound of the invention is then mixed with other liquid ingredients (ie, water, liquid eggs and flavorings) until it is mixed well. The mixture is mixed with a dry emulsifier such as lecithin and is further mixed with a fatty material. The fat is mixed with the dry components (ie, flour, sugar, salt, cocoa) that have been mixed well. The pasta is distributed on a baking sheet, and baked at a desired temperature until the end.

Example 179 Preparation of Juice A compound of the invention is diluted using 200 proof of ethanol at 1 000x of the desired concentration in juice. The compound is then mixed with the alcohol component of natural and / or artificial flavors to make a "key". The flavor key is mixed with a portion of concentrated juice to ensure homogeneity. The rest of the juice concentrate is diluted with water and mixed. Sweeteners, such as HFCS (High Fructose Corn Syrup), aspartame or sucralose, are mixed and combined. The flavor / compound portion is added as a final step, and mixed.

Example 180 Seasoned Tomato Juice or Mixture of Tomato Juice A compound of the invention is added as a dry ingredient to the seasoned mixture and mixed thoroughly. The seasoned mixture is dispersed within a portion of the tomato paste, mixed, and that mixed pasta is further mixed into the remaining dough. The paste is then diluted with water. This can be processed to elevated temperature for a short time. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those of skill in the art from consideration of the specification and practice of the invention described herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention indicated by the following claims.

Claims (31)

1. CLAIMS 1. A method for modulating the flavor of an edible or medicinal product, characterized in that it comprises: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the edible or medicinal product or precursor thereof with at least one amount that modulates the savory flavor of at least one amide compound of non-natural origin, or an edible acceptable salt thereof, so as to form a modified edible or medicinal product; wherein the amide compound has the formula: wherein R1 comprises a hydrocarbon residue having at least three carbon atoms and optionally one or ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphorus; and wherein one of R2 and R3 is H the other R2 and R3 comprise a hydrocarbon residue having at least three carbon atoms and optionally one or ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphorus; and wherein the amide compound has a molecular weight of 500 grams per mole or less.
2. 2. The method according to claim 1, characterized in that the amide compound has a molecular weight of 175 to 500 grams per mole.
3. 3. The method according to claim 1, characterized in that the amide compound has a molecular weight of 200 to 450 grams per mole.
4. 4. The method according to claim 1, characterized in that the amine compound has a molecular weight of 225 to 400 grams per mole.
5. 5. The method according to claim 1, characterized in that the amine compound has a molecular weight of 225 to 400 grams per mole.
6. 6. The method according to claim 1, characterized in that R1 and one of R2 and R3 have between 3 and 14 carbon atoms. The method according to claim 1, characterized in that R1 and one of R2 and R3 have between 4 and 12 carbon atoms. 8. The method according to claim 1, characterized in that R1 and one of R2 and R3 have between 4 and 10 carbon atoms. 9. The method according to claim 1, characterized in that R1 has between 3 and 16 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms selected from oxygen, nitrogen, sulfur, fluorine, or chlorine. The method according to claim 1, characterized in that one of R or R3 has between 3 and 16 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur, fluorine, or chlorine. The method according to claim 1, characterized in that one of R2 or R3 has between 4 and 14 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur. The method according to claim 1, characterized in that one of R2 or R3 has between 5 and 12 carbon atoms and 0, 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur. The method according to claim 1, characterized in that R1 has between 3 and 16 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms selected from oxygen, nitrogen, sulfur, fluorine, or chlorine, and one of R2 or R3 has between 5 and 12 carbon atoms and 0, 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur. The method according to claim 1, characterized in that R1 and one of R2 and R3 are independently selected from the group consisting of arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyl, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, -R4OH, -R4O R5 -R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5, and -R4SO2R5, and an optionally substituted derivative thereof comprising 1, 2, 3 or 4 carbonyl, amino, hydroxyl or halogen groups , and wherein R4 and R5 are hydrocarbon residues of C -? - C6. The method according to claim 7, characterized in that R1 and one of R2 and R3 are independently selected from the group consisting of arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyl, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclic, aryl, and heteroaryl groups, and optionally substituted derivatives thereof comprising 1, 2, 3 or 4 substituent groups, independently selected from hydrogen groups, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3) SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups. 16. The method according to claim 1, characterized in that one of R2 and R3 is a branched or cyclic organic residue having a carbon atom directly attached to (a) the amide nitrogen atom and (b) two carbon atoms. additional carbon, and wherein the branched or cyclic organic residue comprises hydrogen atoms, up to 10 additional optional carbon atoms, and from zero to five heteroatoms independently selected from oxygen, nitrogen, sulfur, fluorine, and chlorine. 17. The method according to claim 1, characterized in that one of R2 and R3 has the formula wherein na and nb are independently selected from 1, 2, and 3, and each R2a or R2b substituent residue is independently selected from hydrogen, a halogen, a hydroxy, or a carbon-containing residue optionally having from zero to five heteroatoms independently selected from oxygen, nitrogen, sulfur, a halogen . 18. The method according to claim 1, characterized in that R2 and R3 is a branched alkyl radical having five to 12 carbon atoms. The method according to claim 1, characterized in that one of R2 and R3 is a cycloalkyl or cycloalkenyl ring comprising from 5 to 12 carbon atoms in the ring that can be optionally substituted with 1, 2, 3 or 4 independently selected of groups hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 20. The method according to claim 1, characterized in that one of R2 and R3 have the structure wherein Ar is a phenyl, pyridyl, furanyl, thiofuranyl, or pyrrole ring, m is 0, 1, 2 or 3, each R2 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy, and trifluoromethoxy and R2a is selected from the group consisting of an alkyl, alkoxy-alkyl, alkenyl, cycloalkenyl, cycloalkyl, R4OH -R4O-R5, R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5, and -R4SO2R5 comprising 1 to 12 carbon atoms. 21. The method according to claim 1, characterized in that the amide compound has the formula: wherein A comprises a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 3 or 4; each R1 'is independently selected from alkyl, alkoxy, alkoxy-alkyl, hydroxyalkyl, OH, CN, CO2H, CO2R6, CHO, COR6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl and R6 is C-alkyl -? - C6. 22. The method according to claim 21, characterized in that A is a phenyl ring or pyridyl ring. 23. The method according to claim 22, characterized in that m is 1, 2 or 3. 24. The method according to claim 23, characterized in that each R1 is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH 3, N (CH 3) 2, COOCH 3, SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, or a monocyclic aryl or heteroaryl group. 25. The method according to claim 21 characterized in that A is a phenyl ring and each R1 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy, and trifluoromethoxy. 26. The method according to claim 24, characterized in that R2 is a C3-C10 branched alkyl. 27. The method according to claim 21, characterized in that R2 is a C3-C10 branched alkyl substituted with one or two substituents independently selected from hydrogen, hydroxy, fluorine, chlorine, NH, NHCH3, N (CH3) 2, O2CCH3 , CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 28. The method according to claim 9, characterized in that R2 is a ring of 1- (1,2,3,4) tetrahydronaphthalene or a 2,3-d ihydro-1 H-indene ring having the formula: where m is 0, 1, 2 or 3, and each R 2 can be attached to either an aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy groups. 29. The method according to claim 25, characterized in that R2 is optionally a phenyl ring optionally substituted with one or two substituents independently selected from hydroxy groups., fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 30. The method according to claim 21, characterized in that R2 is a lower alkylester of the a-substituted carboxylic acid or an a-substituted carboxylic acid. 31. The method according to claim 25, characterized in that R2 is a methyl ester of the a-substituted carboxylic acid 32. The method according to claim 31, characterized in that the a-substituted carboxylic acid or carboxylic acid ester residue a -substituted correspond to that of an a-amino acid occurring naturally or an ester thereof, or its opposite enantiomer. 33. The method according to claim 21, characterized in that A is a monocyclic heteroaryl wherein each R1 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3) SCH3 groups, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 34. The method according to claim 21, characterized in that A has one of the following formulas wherein m is 0, 1, 2 or 3 and each R is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, or a monocyclic aryl or heteroaryl group. 35. The method according to claim 34, characterized in that R2 has the formula wherein m is 0, 1, 2 or 3, and each Rr can be attached to any aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3í SEt groups , methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 36. The method according to claim 21, characterized in that A is a monocyclic, bicyclic bound or aromatic bicyclic fused heteroaryl, optionally substituted with 0, 1, 2, 3 or 4 substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3 groups , N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 37. The method according to claim 1, characterized in that the amide compound has the formula wherein m is 0, 1, 2 or 3 and each R1 can be attached together with the phenyl or heteroaryl rings and each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 38. The method according to claim 37, characterized in that m is 1 or 2. 39. The method according to claim 1, characterized in that the amide compound has the formula wherein m is 0, 1, 2 or 3 and each Rr is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 40. The method according to claim 39, characterized in that m is 1 or 2. 41. The method according to claim 1, characterized in that the amide compound has the formula wherein R-? a or R-ib are independently hydrogen or a lower alkyl. 42. The method according to claim 41, characterized in that R-? A or R-? D are independently hydrogen or methyl. 43. The method according to claim 41, characterized in that R2 is a C3-C10 branched alkyl. 44. The method according to claim 41, characterized in that R2 has the formula wherein m is 0, 1, 2 or 3, and each R 2 'can be attached together with the aromatic or non-aromatic ring and each R 2' is independently selected from hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) group 2, CO2CH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 45. The method according to claim 1, characterized in that the amide compound has the formula wherein R-ta or R- | D is independently hydrogen or a lower alkyl. 46. The method according to claim 45, characterized in that RIA is a lower alkyl and R2 is a branched C3-C10 alkyl. 47. The method according to claim 1, characterized in that the amide compound has the formula: wherein A comprises a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 304; each R1 is independently selected from alkyl, alkoxy, alkoxy-alkyl, hydroxyalkyl, OH, CN, CO2H, CHO, COR6, CO2R6, SH, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl and R6 is C-alkyl ? -C6; B is a 5 or 6 membered aryl or heteroaryl ring; m 'is 0, 1, 2, 3 or 4; R2 is selected from the group consisting of alkyl, alkoxy, alkoxy-alkyl, OH, CN, CO2H, CHO, COR6, CO2R6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl, and heteroaryl: and R6 is C-alkyl -? - C6. 48. The method according to claim 47, characterized in that A is a fused monocyclic or bicyclic heteroaryl ring wherein each R1 'and each R2' are independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, groups methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups. 49. The method according to claim 47, characterized in that A is a monocyclic heteroaryl ring. 50. The method according to claim 47, characterized in that A has one of the formulas wherein m is 0, 1, 2 or 3, and each R1 can be attached together with the aromatic or non-aromatic ring and each R2 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2 groups , CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups. 51. The method according to claim 47, characterized in that radical (Rr) m-A has the formula wherein R a and R-? D are independently hydrogen or lower alkyl. 52. The method according to claim 48, characterized in that B is a phenyl ring and each R2 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3) methyl groups , ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 53. The method according to claim 47, characterized in that A is a substituted phenyl ring and B is a substituted cyclohexyl ring. 54. The method according to claim 1, characterized in that the amide compound has the formula wherein A is a 5 or 6 membered aryl or heteroaryl ring; m is 0, 1, 2, 304; each R1 'is independently selected from alkyl, alkoxy, alkoxy-alkyl, OH, CN, CO2H, CO2R6, CHO, COR6, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl. 55. The method according to claim 54 characterized in that A is a phenyl, pyridyl, furanyl, or thiofuranyl ring and each R1 'is independently selected hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2 groups, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy. 56. The method according to claim 55, characterized in that A is a phenyl ring and m has 1, 2, 3 or 4. 57. The method according to claim 56, characterized in that m is 1 or 2. 58. The method according to claim 55, characterized in that R2 is a C3-C10 branched alkyl. 59. The method according to claim 55, characterized in that R2 is a lower alkyl ester of a-substituted carboxylic acid. 60. The method according to claim 1, characterized in that the amide compound is a urea compound having the formula: wherein R9 and one or two of R7 and R8 comprise a hydrocarbon residue having at least three carbon atoms and optionally one to ten heteroatoms selected from oxygen, nitrogen, sulfur, halogens, or phosphorus; and wherein optionally one of R7 and R8 is hydrogen. 61. The method according to claim 60, characterized in that R7 and R8 together form a heterocyclic or heteroaryl ring having 5, 6 or 7 ring atoms that can be optionally substituted with 1, 2 or 3 substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 62. The method according to claim 61, characterized in that the urea compound has the structure 63. The method according to claim 60, characterized in that one of R7 and R8 is hydrogen 64. The method according to claim 63, characterized in that R9 and one of R7 and R8 are independently selected from arylalkenyl, heteroarylalkenyl, arylalkyl, heteroarylalkyl, alkyls, alkoxyalkyls, alkenyls, cycloalkyls, cycloalkenyls, aryls and heteroaryls, each of which carbon-containing groups may be optionally substituted with 1, 2, or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2 groups , NHCH 3, N (CH 3) 2, COOCH 3, SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 65. The method according to claim 63, characterized in that R9 and one of R7 and R8 is independently selected from alkyl, phenyl, cyclohexyl, or pyridyl each of which may optionally comprise one to four substituents independently selected from hydroxy, fluoro, chloro, MH2, NHCH3, N (CH3 ) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 66. The method according to claim 63, characterized in that one of R7 and R8 has one of the formulas wherein m is 0, 1, 2 or 3, and each R1 'independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl , trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 67. The method according to claim 63, characterized in that one of R7 and R8 is a phenyl ring optionally substituted with 1, 2 or 3 substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 68. The method according to claim 63, characterized in that R9 is a branched alkyl of C3-C? O- 69. The method according to claim 63, characterized in that R9 has the structure wherein B is a phenyl ring, pyridyl, furanyl, thiofuranyl, pyrrole, cyclopentyl, cyclohexyl, or piperidyl, m is 0, 1, 2 or 3, and each R 2 is independently selected from hydrogen, hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, and R9a is one selected from the group consisting of an alkyl, alkoxy-alkyl, alkenyl, cycloalkenyl, cycloalkyl, -R4OH , -R4O-R5-R4CN, -R4CO2H, -R4CO2R5, -R4COR5, -R4SR5, and -R4SO2R5 comprising 1 to 12 carbon atoms. 70. The method according to claim 63, characterized in that the urea compound has the formula: 1- (2-chlorophenyl) -3- (heptan-4-yl) urea, 1- (2,4-d-chloro-phenyl) - 3- (1-phenylpropyl) u rea, 1- (2,4-dimethoxyphenyl) -3- (heptan-4-yl) urea, 1- (2-fluorophenyl) -3- (heptan-4-yl) urea , or 1- (4-isopropylphenyl) -3- (2- (pyridin-2-yl) ethyl) urea, 71. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula : wherein R10 and R30 are independently selected from hydrocarbon residues having at least three carbon atoms and optionally one to ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogens or phosphors, and wherein R20 and R40 are independently selected from hydrogen and a hydrocarbon residue having at least three carbon atoms and optionally one to ten heteroatoms independently selected from oxygen, nitrogen, sulfur, halogen os or matches. 72. The method according to claim 71, characterized in that R20 and R40 are hydrogen. 73. The method according to claim 71, characterized in that R10 and R30 is independently selected from the group consisting of arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocyclealkyls comprising five to 15 carbon atoms, and wherein each of R10 and R30 may optionally comprise one to one to four substituents independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3lN (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy , ethoxy, isopropoxy, and trifluoromethoxy. 74. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula: wherein A and B are independently aryl, heteroaryl, cycloalkyl or a heterocycle comprising from 5 to 12 ring atoms; m and n are independently 0, 1, 2, 3 or 4-8; R 20 and R 40 are hydrogen, R 50 is hydrogen or an alkyl or substituted alkyl residue comprising one to four carbon atoms; R60 is absent or a C1-C5 alkylene or a substituted C1-C5 alkylene; R70 and R80 are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxy-alkyl, OH, SR9, halogen, CN, NO2, CO2R9, COR9, CONR9R10, NR9R10, NR9COR10, SOR9, SO2R9, SO2NR9R10, NR9SO2R10 , alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle; R9 and R10 are independently selected from H, C-i-Cß alkyl, C3-C6 cycloalkyl and C-i-Cß alkenyl. 75. The method according to claim 74, characterized in that A and B are independently a phenyl, pyridyl, furanyl, benzofuranyl, pyrrole, benzothiophene, piperidyl, cyclopentyl, cyclohexyl, or cycloheptyl ring; m and n are independently 0, 1, 2 or 3; R20 and R40 is hydrogen; R50 is hydrogen or methyl; R60 is an alkylene of C2; R70 and R80 are independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 76. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula: wherein A is a phenyl, pyridyl, furanyl, pyrrole, piperidyl, cyclopentyl, cyclohexyl or cycloheptyl ring; m and n are independently 0, 1, 2 or 3; R50 is hydrogen or methyl; P is 1 or 2; and R70 and R80 are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3l SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy, or two of R70 together form a methylenedioxy ring. 77. The method according to claim 76, characterized in that the pyridyl radical R80 has the structure: 78. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula wherein AR1 is a substituted aryl or heteroaryl ring comprising five to 12 carbon atoms; R50 is hydrogen or methyl; n is 0, 1, 2, 3; each R80 is independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy . 79. The method according to claim 78, characterized in that AR1 is a phenyl of 2-, 3-, or 4- mono substituted, 2,4-, 2,3-, 2,5, 2,6, 3, 5-, or 3,6-disubstituted phenyl, 3-substituted alkyl-4-phenyl, a tri-substituted phenyl wherein the substituent groups are independently selected from the group consisting of hydroxy, fluoro, chloro, NH 2, NHCH 3, N ( CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, or two of the substituents together form a methylenedioxy ring on the phenyl ring. 80. The method according to claim 78, characterized in that AR1 is a substituted heteroaryl ring comprising from 5 to 12 carbon atoms and wherein the substituent groups are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2 , NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 81. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula wherein A is a substituted aryl or heteroaryl ring comprising five to 12 carbon atoms; R50 is hydrogen or methyl; m and n are independently 0, 1, 2 or 3; each R70 or R80 is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 82. The method according to claim 1, characterized in that the amide compound is an oxalamide compound having the formula: wherein m and n are independently 0, 1, 2 or 3; and R70 and R80 are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxy-alkyl, OH, SR9, halogen, CN, NO2, CO2R9, COR9, CONR9R10, NR9R10, NR9COR10, SOR9, SO2R9, SO2NR9R10, NR9SO2R10, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocycle; R9 and R10 are independently selected from H, C -? - C6 alkyl, C3 - C6 cycloalkyl, and C -? - C6 alkenyl. 83. The method according to claim 82, characterized in that R70 and R80 are independently selected from groups consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, O2CCH3, SH, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy and trifluoromethoxy. 84. The method according to claim 82, characterized in that the pyridyl-R80 radical has the structure: 85. The method according to any of claims 1-84, characterized in that the log10 of the partition coefficient of the amide compound between n-octanol and water is less than 5.5 86. The method according to claim 1, characterized in that the edible product or modified medicinal is an article for animal consumption. 87. The method according to claim 1-84, characterized in that the modified edible or medicinal product is an article for human consumption. 88. The method according to any of claims 1-84, characterized in that the modified edible or medicinal product is selected from the group consisting of, confectionery, bakery products, ice cream, creamy products, sweet and savory snacks, snack bars , meal replacement products, ready meals, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, or spreads. 89. The method according to any of claims 1-84, characterized in that the modified edible or medicinal product comprises one or more of meat, poultry, fish, vegetables, grains, or fruits. 90. The method according to claim 1, characterized in that the modified edible or medicinal product is a frozen food, a raw food, or a whole or partially cooked food. 91. The method according to claim 1, characterized in that the modified edible or medicinal product is a soup, a dehydrated or instant soup, or a dry soup. 92. The method according to claim 1, characterized in that the modified edible or medicinal product is a sandwich. 93. The method according to claim 1, characterized in that the modified edible or medicinal product is an auxiliary product for cooking, food solution product, a product for dressing meals, a condiment or a marinade. 94. The method according to claim 1, characterized in that the modified edible or medicinal product is a cake, biscuit, cake, caramel, chewable gum, gelatin, ice cream, sorbet, pudding, jam, jelly, salad dressing, condiments, cereal, preserved fruit, or compote. 95. The method according to any of claims 1-84, characterized in that the modified edible or medicinal product is a beverage, a beverage mixture, or a beverage concentrate. 96. The method according to claim 1, characterized in that the modified edible or medicinal product is a soda, or juice. 97. The method according to claim 1, characterized in that the modified edible or medicinal product is an alcoholic beverage. 98. The method according to claim 1-84, characterized in that the modified edible or medicinal product is a pharmaceutical composition for oral administration. 99. The method according to claim 1, characterized in that the modified edible or medicinal product is an oral hygiene product. 100. The method according to claim 1-84, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.01 ppm to about 30 ppm. 101. The method according to claim 1, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.05 ppm to about 15 ppm. 102. The method according to claim 1, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 5 ppm. 103. The method according to claim 1, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 3 ppm. 104. The method according to claim 1- 84, characterized in that an aqueous solution comprising the amount of flavor modification of the amide compound has a tasty flavor when determined by a majority of a group of experts of at least eight human flavor tasters. 105. The method according to claim 1-84, characterized in that an aqueous solution comprising the amount of flavor modification of the amide compound and 12 mM of monosodium glutamate will have an increased flavor taste when compared to a control aqueous solution. which comprises 12 mM of monosodium glutamate, when determined by the majority of a panel of experts from at least eight human flavor tasters. 106. The method according to claim 1, characterized in that an aqueous solution comprising a flavor modification amount of the amide compound and 12 mM of monosodium glutamate will have an increased flavor taste when compared to a control aqueous solution comprising 12 mM of monosodium glutamate and 100 μM of inosine monophosphate, when determined by a majority of a panel of at least eight human flavor tasters. 107. The method according to claim 1, characterized in that an aqueous solution comprising about 10 ppm of the amide compound and about 12 mM of monosodium glutamate will have an increased flavor taste when compared to a control aqueous solution comprising only glutamate. of monosodium, when determined by the majority of a group of experts of at least eight tasters of human taste. 108. The method according to any of claims 1, characterized in that the amide compound is a tasty agonist for a hT1R1 / hT1R3 receptor. 109. The method according to any of claims 1-84, characterized in that the amide compound has an EC50 for the hT1R1 / hT1R3 receptor less than about 2 μM. 110. The method according to claim 1, characterized in that the amide compound, when dissolved in an aqueous solution comprising about 1 μW? of the amide compound decreases the observed EC50 of monosodium glutamate for a hT1R1 / hT1R3 receptor expressed in a HEK293-Ga15 cell line by at least 50%. 111. The method according to claim 1, characterized in that the modified edible or medicinal product has an increased tasty taste when compared to the edible or medicinal product prepared without the amide compound, when determined by the majority of a group of experts. of at least eight tasters of human flavor. 112. The method according to claim 1, characterized in that the amide compound is edible acceptable. 113. The method according to claim 1, characterized in that the amide compound is or can be generally shown to be recognized as safe. 114. The method according to claim 1, characterized in that the amide compound, when combined with the rat feed and fed to Crl: CD (SD) IGS BR rats at a concentration of approximately 100 milligrams / Kilogram-Body- Weight / day for 90 does not cause adverse toxic effects in rats. 115. The modified edible or medicinal product produced by any of claims 1-84. 116. A method for increasing the sweet taste of an edible or medicinal product, characterized in that it comprises: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the edible or medicinal product or precursor thereof with at least one amount that modulates the flavor tasty or an amount that modulates the sweet taste of at least one amide compound of non-natural origin, or an edible acceptable salt thereof, so that a modified edible or medicinal product is formed; where the amide compound has the structure wherein A is an aryl or heteroaryl ring having 3 or 12 ring atoms; m is 0, 1, 2, 304; each R1 'is independently selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkoxyalkyl, hydroxyalkyl of C -, - C4, OH , NH2, NHR6, NR62, CN, CO2H, CHO, CO2R6, SH, SR6, and halogen, wherein R6 is C1-C4 alkyl; R2 comprises an optionally branched alkyl or cycloalkyl with one to four substituents independently selected from alkyl, alkoxy, alkoxy alkyl, hydroxyalkyl, OH, NH2, NHR6, NR62, CN, CO2H, CHO, COR6, SH, SR6, halogen, alkenyl, cycloalkyl, cycloalkenyl, aryl and heteroaryl and R6 is Ci-Cß alkyl; and and wherein the amide compound has a molecular weight of 500 grams per mole or less. 117. The method according to claim 56, characterized in that each Rr and each optional substituent for R2 are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3 , SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 118. The method according to claim 117, characterized in that A is an aryl ring comprising 6 to 12 carbons in the ring. 119. The method according to claim 117, characterized in that A is a naphthyl ring. 120. The method according to claim 117, characterized in that A is a phenyl ring. 121. The method of compliance with the claim 120, characterized in that m is 1, 2, 3 or 4. 122. The method according to the claim 121, characterized in that R2 is a C3-C10 branched alkyl. 123. The method according to claim 121, characterized in that R2 is a C3-C? Ram branched alkyl substituted with 1, 2 or 3 substituent groups independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenyl, and pyridyl. 124. The method according to claim 121, characterized in that R2 is a cycloalkyl or cycloalkenyl ring having 3 to 10 carbon atoms in the ring optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro groups, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 125. The method according to claim 121, characterized in that R2 is a cycloalkyl or cycloalkenyl ring having 5 to 8 carbon atoms in the ring, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3l SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy groups. 126. The method according to claim 121, characterized in that R2 is a cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl ring, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CHs) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 127. The method according to claim 121, characterized in that R2 is a cyclohexyl, optionally substituted with 1, 2 or 3 methyl groups. 128. The method according to claim 121, characterized in that R2 has the formula 129. The method according to claim 121, characterized in that R2 is a 1-indane having the formula wherein m is 0, 1, 2 or 3 and each R2 can be attached to either an aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 130. The method according to claim 121, characterized in that R2 is a 1- (1, 2,3,4) tetrahydronaphthalene having the formula wherein m is 0, 1, 2 or 3 and each R 2 'can be attached to either an aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 131. The method according to claim 121, characterized in that R2 has the formula wherein R2 is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy; sopropoxy and trifluoromethoxy. 132. The method according to claim 121, characterized in that R2 has the formula 133. The method according to claim 121, characterized in that R2 has the formula 134. The method in accordance with the claim 121, characterized in that R2 is a ring of 1- (1,2,3,4) tetrahydroftalene having the formula 135. The method according to claim 121, characterized in that R2 is a ring of 1- (1,2,3,4) tetrahydroftalene having the formula 136. The method according to claim 121, characterized in that R2 is a ring of 1- (1,2,3,4) tetrahydroftalene having the formula 137. The method according to claim 117, characterized in that A is a monocyclic heteroaryl. 138. The method according to claim 117, characterized in that A has one of the formulas wherein m, is 0, 1, 2 or 3, and each R1 'is independently selected from, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy or trifluoromethoxy. 139. The method according to claim 117, characterized in that A has the formula wherein R1 is hydrogen, hydroxy, fluoro, chloro, NH2, NHCH 3, N (CH 3) 2, O 2 CCH 3, SH, SCH 3) methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy or trifluoromethoxy. 140. The method according to claim 138, characterized in that R2 is a branched alkyl of C3-C? 0-141. The method according to the claim 138, characterized in that R2 is a branched alkyl of C3.C-10, substituted with groups of 1, 2 or 3 substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3 , methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenyl, and pyridyl. 142. The method according to claim 138, characterized in that R2 is a cycloalkyl having 3 to 10 carbon atoms in the ring, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro , NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy groups. 143. The method according to claim 138, characterized in that R2 is a cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of the hydroxy, fluoro, chloro, NH2 groups , NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 144. The method according to claim 138, characterized in that R2 is a cyclohexyl, methyl groups optionally substituted with 1, 2 or 3. 145. The method according to claim 138, characterized in that R2 has the formula 146. The method according to claim 138, characterized in that R2 is a 1-indane having the formula wherein m is 0, 1, 2 or 3 and each R2 'can be attached to either the aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3 > SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 147. The method according to claim 138, characterized in that R2 is a 1- (1, 2,3,4) tetrahydronaphthalene having the formula wherein m is 0, 1, 2 or 3 and each R2 'can be attached to either the aromatic or non-aromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3) methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy. 148. The method according to claim 138, characterized in that R2 has the formula wherein each R2 'is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, O2CCH3 > SH, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy or trifluoromethoxy. 149. The method according to claim 138, characterized in that R2 has the formula 150. The method according to claim 138, characterized in that R2 has the formula 151. The method according to claim 138, characterized in that R2 is a ring of 1- (1, 2,3,4) tetrahydroftalene having the formula 152. The method according to claim 116, characterized in that the modified edible or medicinal product is an article for animal consumption. 153. The method according to claim 116, characterized in that the modified edible or medicinal product is an article for human consumption. 154. The method according to any of claims 116-151, characterized in that the modified edible or medicinal product is selected from the group consisting of, confectionery, bakery products, ice cream, creamy products, sweet and savory snacks, snack bars , meal replacement products, prepared foods, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, and spreads. 155. The method according to any of claims 116-151, characterized in that the modified edible or medicinal product comprises one or more meats, poultry, fish, vegetables, grains, or fruits. 156. The method according to claim 116, characterized in that the modified edible or medicinal product is a frozen food, a raw food, or a whole or partially cooked food. 157. The method of compliance with the claim 116, characterized in that the edible or medicinally modified product is a soup, a dehydrated or instant soup, or a dry soup. 158. The method according to claim 116, characterized in that the modified edible or medicinal product is a sandwich. 159. The method according to claim 116, characterized in that the modified edible or medicinal product is an auxiliary product for cooking, food solution product, a product for dressing meals, a condiment or a marinade. 160. The method according to claim 116, characterized in that the modified edible or medicinal product is a cake, biscuit, cake, caramel, chewable gum, gelatin, ice cream, sorbet, pudding, jam, jelly, salad dressing, condiments, cereal, preserved fruit, or compote. 161. The method according to any of claims 116-151, characterized in that the modified edible or medicinal product is a beverage, a beverage mixture, or a beverage concentrate. 162. The method according to claim 116-151, characterized in that the modified edible or medicinal product is a soda, or juice. 163. The method of compliance with the claim 116-151, characterized in that the modified edible or medicinal product is an alcoholic beverage. 164. The method according to claim 116-151, characterized in that the modified edible or medicinal product is a pharmaceutical composition for oral administration. 165. The method according to claim 116, characterized in that the modified edible or medicinal product is an oral hygiene product. 166. The method according to claim 116-151, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.001 ppm to about 100 ppm. 167. The method of compliance with the claim 117, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 30 ppm. 168. The method according to claim 116, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.05 ppm to about 15 ppm. 169. The method according to claim 116-151, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 5 ppm. 170. The method according to claim 116, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 3 ppm. 171. The method according to claim 116-151, characterized in that the modified edible or medicinal product has an increased tasty taste when compared to the edible or medicinal product prepared without the amide compound, when determined by the majority of a group of Experts from at least eight tasters of human taste. 172. The method according to claim 116, characterized in that an aqueous solution comprises a sweet taste amount of a sweetener selected from the group consisting of sucrose, fructose, glucose, erythritol, somatol, lactitol, mannitol, sorbitol, xylitol, a known natural terpenoid, flavonoids, or protein sweetener, aspartame, saccharin, acelsufame-K, cyclamate, sucralose and alitame or mixtures thereof and an amount that modulates the flavor taste of at least one amide compound has a sweeter taste than an aqueous control solution comprising the sweet taste amount of the known sweetener, when determined by a majority of a panel of experts of at least eight human flavor tasters. 173. The method of compliance with the claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 6 grams / 100 milliliters of sucrose has a sweeter taste than a control aqueous solution comprising 6% grams / 100 milliliters of sucrose, when it is determined by the majority of a group of experts of at least eight tasters of human flavor. 174. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and 6% grams / 100 milliliters of a 50:50 mixture of sucrose and fructose will have a more sweet than a control aqueous solution comprising 6% grams / 100 milliliters of a 50:50 mixture of sucrose and fructose, when determined by the majority of a panel of experts of at least eight human flavor tasters. 175. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 1.6 mM of aspartame has a sweeter taste than a control aqueous solution comprising about 1.6 mM of aspartame, when determined by the majority of a group of experts of at least eight tasters of human flavor. 176. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 1.5 mM of acesulfame-K has a sweeter flavor than a control aqueous solution comprising about 1.5 mM of acesulfame-K, when determined by most of a group of experts of at least eight taste tasters human. 177. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 10 mM of cyclamate has a sweeter taste than a control aqueous solution comprising about 10 mM of cyclamate, when determined by the majority of a group of experts of at least eight tasters of human taste. 178. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 0.4 mM of sucralose has a sweeter flavor than a control aqueous solution comprising approximately 0.4 mM of sucralose, when determined by the majority of a group of experts of at least eight tasters of human flavor. 179. The method according to claim 116, characterized in that an aqueous solution comprising the amount that modifies the sweet taste of the amide compound and about 0.2 mM of alitame has a sweeter taste than a control aqueous solution comprising approximately 0.2 mM of alitame, when determined by the majority of a group of experts of at least eight tasters of human flavor. 180. The method according to claim 116, characterized in that the modified edible or medicinal product has a sweeter taste when compared to the edible or medicinal product prepared without the amide compound, when determined by the majority of a group of experts. of at least eight tasters of human flavor. 181. The method according to claim 116, characterized in that the amide compound that modulates the binding of a sweetener selected from the group consisting of sucrose, fructose, glucose, erythritol, isomalt, lactitol, mannitol, sorbitol, tol, certain natural terpenoids known, flavonoids, or protein sweeteners, aspartame, saccharin, acesufame-K, cyclamate, sucralose and alitame or erythritol for a hT1R2 / hT1R3 receptor expressed in a HEK293-Ga15 cell line. 182. The method according to claim 116, characterized in that the amide compound has an EC5o to bind a hT1R2 / hT1R3 receptor expressed in a HEK293-Ga15 cell line of less than about 10 μM. 183. The method according to any of claims 116-151, characterized in that the amide compound has an EC50 for binding a hT1R2 / hT1R3 receptor expressed in a HEK293-Ga15 cell line of less than about 5 μM. 184. The method according to claim 116, characterized in that the amide compound has an EC50 for binding a hT1R2 / hT1R3 receptor expressed in a HEK293-Ga15 cell line of less than about 2 μM. 185. The method according to claim 116, characterized in that the amide compound has an EC50 for binding a hT1R2 / hT1R3 receptor expressed in a HEK293-Ga15 cell line of less than about 1 μM. 186. The method according to claim 116-151, characterized in that the amide compound is not a peptide compound. 187. The method according to claim 116, characterized in that the amide compound is edible acceptable. 188. The method according to claim 116, characterized in that the amide compound is or can be determined generally to be recognized as safe for use in food products at a specified concentration in the finished product. 189. The method according to claim 116, characterized in that the amide compoundwhen combined with rat feed and fed to rats Crl: CD (SD) IGS BR at a concentration of approximately 100 milligrams / Kilogram-Body-Weight / day for 90 days does not cause adverse toxic effects in rats. 190. The modified edible or medicinal product produced by any of claims 116-189. 191. A method for increasing the sweet taste of an edible or medicinal product, characterized in that it comprises: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the edible or medicinal product or precursor thereof with about 0.001 ppm to about 100 ppm of at least one non-naturally occurring amide compound, or an edible acceptable salt thereof, so that they form a modified edible or medicinal product; where the amide compound has the structure wherein A is an aryl or heteroaryl ring having 3 or 12 ring atoms; m is 0, 1, 2, 3 or 4; each R1 'is independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; R2 is a phenyl ring, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3l SEt, SCH3, methyl, ethyl, isopropyl, vinyl , trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; and wherein the amide compound has a molecular weight of 500 grams per mole or less. 192. The method according to claim 191, characterized in that the modified edible or medicinal product is selected from the group consisting of confectionery, bakery products, ice cream, creamy products, sweet and tasty snacks, sandwich bars, replacement products of meals, prepared meals, soups, pasta, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, or spreads. 193. The method according to claim 191, characterized in that the modified edible or medicinal product is a cake, biscuit, cake, caramel, chewable gum, gelatin, ice cream, sorbet, pudding, jam, jelly, salad dressing, condiments, cereal, preserved fruit, or compote. 194. The method according to claim 191, characterized in that the modified edible or medicinal product is a beverage, a beverage mixture, or a beverage concentrate. 195. The method according to claim 191, characterized in that the modified edible or medicinal product is a soda, or juice. 196. The method according to claim 191, characterized in that the modified edible or medicinal product is an alcoholic beverage. 197. The method according to claim 191, characterized in that the modified edible or medicinal product is a pharmaceutical composition for oral administration. 198. The method according to claim 191, characterized in that the modified edible or medicinal product is an oral hygiene product. 199. The method according to claim 191, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.001 ppm to about 100 ppm. 200. The method according to claim 191, characterized in that the amide compound is present in the edible or medicinally modified product in a concentration of about 0.1 ppm to about 10 ppm. 201. The modified edible or medicinal product produced by the method according to claims 191-200. 202. A method for modulating the sweet taste of an edible or medicinal product characterized in that they comprise: a) providing at least one edible or medicinal product, or a precursor thereof, and b) combining the edible or medicinal product or precursor thereof with approximately 0.001 ppm to about 100 ppm of at least one non-naturally occurring urea compound, or an edible acceptable salt thereof, so that they form a modified edible or medicinal product; where the urea compound has the structure wherein m and n are independently 0, 1, 2 or 3 and each R1 'and R2' is independently selected from fluoro, chloro, NH2, NHCH3, N (CH3) 2 CO2CH3 > SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 203. The method according to claim 202, characterized in that n is 0. 204. An edible or medicinal product produced by the method according to claim 202. 205. An edible or medicinal product, or a precursor thereof comprising about 0.001 ppm to about 100 ppm of at least one non-naturally occurring amide compound, or an edible acceptable salt thereof, wherein the amide compound has the formula: wherein A comprises a 5 or 6 membered aryl or heteroaryl ring; m has 0, 1, 2, 3 or 4; each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3lN (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; and R2 comprises between 4 and 14 carbon atoms and 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from oxygen, nitrogen, sulfur. 206. The edible or medicinal product, or a precursor thereof according to claim 205, characterized in that A is a phenyl ring. 207. The edible or medicinal product, or a precursor thereof according to claim 206, characterized in that m is 1, 2 or 3. 208. The edible or medicinal product, or a precursor thereof according to claim 206, characterized in that R2 a branched alkyl of C3.C10. 209. The edible or medicinal product, or a precursor thereof according to claim 206, characterized in that R2 is an α-substituted carboxylic acid or α-substituted carboxylic acid methyl ester. 210. The edible or medicinal product, or a precursor thereof according to claim 205, characterized in that the amide compound has the formula wherein R-? a and R-ib is independently hydrogen or methyl. 211. The edible or medicinal product, or a precursor thereof according to claim 210, characterized in that R2 is a branched alkyl of C3..C10. 212. The edible or medicinal product, or a precursor thereof according to claim 210, characterized in that R2 an a-substituted carboxylic acid or a-substituted carboxylic acid methyl ester. 213. The edible or medicinal product, or a precursor thereof according to claim 205, characterized in that A is a monocyclic heteroaryl having one of the formulas wherein m is 0, 1, 2 or 3, and each R1 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 214. The edible or medicinal product, or a precursor thereof according to claim 213, characterized in that R2 is an alkyl of C3.C10. 215. The edible or medicinal product, or a precursor thereof according to claim 213, characterized in that R2 an a-substituted carboxylic acid or a-substituted carboxylic acid methyl ester. 216. The edible or medicinal product, or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is an article for human consumption. 217. The edible or medicinal product, or a precursor thereof according to any of claims 205-215, characterized in that the modified edible or medicinal product is selected from the group consisting of, confectioneries, bakery products, ice creams, creamy products, sandwiches sweet and tasty, snack bars, meal replacement products, prepared foods, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, or spreads. 218. An edible product or a precursor thereof according to claim 205, characterized in that it comprises one or more of meat, poultry, fish, vegetables, grains, or fruits. 219. An edible product or a precursor thereof according to claim 205, characterized in that it is a frozen food, a raw food, or a whole or partially cooked food. 220. An edible product or a precursor thereof according to claim 205, characterized in that it is a soup, a dehydrated or concentrated soup, or a dry soup. 221. An edible product or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is a sandwich. 222. An edible product or a precursor thereof according to any of claims 205-215, characterized in that the modified edible or medicinal product is an auxiliary product for cooking, food solution product, a product for dressing foods, a condiment or a marinade. 223. An edible product or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is a cake, biscuit, cake, caramel, chewable gum, gelatin, ice cream, sorbet, pudding, jam, jelly, dressing for salads, condiments, cereal, preserved fruit, or compote. 224. An edible product or a precursor thereof according to any of claims 205-215, characterized in that the modified edible or medicinal product is a beverage, a beverage mixture, or a beverage concentrate. 225. An edible product or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is a soda, or juice. 226. An edible product or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is an alcoholic beverage. 227. An edible product or a precursor thereof according to any of claims 205-215, characterized in that the modified edible or medicinal product is a pharmaceutical composition for oral administration. 228. An edible product or a precursor thereof according to claim 205, characterized in that the modified edible or medicinal product is an oral hygiene product. 229. An edible or medicinal product, or a precursor thereof comprising at least one amount that modulates the flavor taste of at least one oxalamide compound, or an edible acceptable salt thereof, wherein the oxalamide compound has the formula wherein A and B are independently an aryl, heteroaryl, cycloalkyl, or a heterocycle comprising 5 to 12 ring atoms; m and n independently have 0, 1, 2, 3 or 4-8, R50 is hydrogen or an alkyl comprising one to four carbon atoms; R60 is absent or an alkylene of C -? - C5; R70 and R80 are independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy , and trifluoromethoxy, or two of R70 together form a methylenedioxy ring. 230. An edible product, or a precursor thereof according to claim 229, characterized in that A and B are independently a phenyl, pyridyl, furanyl, benzofuranyl, pyrrole, benzothiophene, piperidyl, cyclopentyl, cyclohexyl, or cycloheptyl ring; m and n are independently 0, 1, 2 or 3; R50 is hydrogen or methyl; R60 is -CH2- or -CH2CH2-. 231. An edible product or a precursor thereof according to claim 230, characterized in that B is an optionally substituted pyridine ring. 232. An edible product or a precursor thereof according to claim 231 characterized in that the pyridyl radical-R80 has the structure 233. An edible product, or a precursor thereof according to claim 229, characterized in that the amide compound is an oxalamide compound having the formula wherein A is a substituted aryl or heteroaryl ring comprising five to 12 carbon atoms; m and n so n O, 1, 2 or 3; each R70 and R80 is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2 (CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, or two of R70 together form a methylenedioxy ring 234. An edible product, or a precursor thereof according to claim 233, characterized in that A is a phenyl of 2-, 3-, or 4-mono substituted, 2,4, 2,3, 2,5, 2,6, 3,5- or 3,6-disubstituted phenyl, substituted 3-alkyl-4-phenyl, a tri-substituted phenyl wherein the R70 groups are independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3 2, CO2CH3, SEt, SCH3) methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy, and trifluoromethoxy, or two of R70 together form a methylenedioxy ring. 235. An edible product, or a precursor thereof according to claim 233, characterized in that A is a substituted heteroaryl ring comprising from 5 to 12 carbon atoms and wherein the substituent groups are independently selected from the group consisting of the hydrogen group , hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 236. An edible product, or a precursor thereof according to claim 233, characterized in that A has one of the formulas wherein m is 0, 1, 2 or 3, and each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 237. An oxalamide compound that has the formula wherein A and B are a substituted aryl or heteroaryl ring comprising three to twelve carbon atoms in the ring; m and n are independently 0, 1, 2 or 3; each R70 and R80 is independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy, and trifluoromethoxy, or two of R70 together form a methylenedioxy ring; or an edible acceptable salt thereof. 238. The oxalamide compound according to claim 237, characterized in that B is a pyridyl ring. 239. The oxalamide compound according to claim 237, characterized in that the pyridyl radical-R80 has the structure 240. The oxalamide compound according to claim 238, characterized in that A is a phenyl ring. 241. The oxalamide compound according to claim 240, characterized in that B is a pyridyl ring. 242. The oxalamide compound according to claim 240, characterized in that the pyridyl radical-R80 has the structure 243. The oxalamide compound according to claim 237, characterized in that A has one of the formulas wherein m is 0, 1, 2 or 3, and each R1 is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl , methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 244. The oxalamide compound according to claim 243, characterized in that B is a pyridyl ring. 245. The oxalamide compound according to claim 244, characterized in that the pyridyl radical-R80 has the structure 246. An oxalamide compound according to claim 237 having the formula N 1 - (2-methoxy-4-methyl benzyl) -N 2 - (2- (5-methylpyridin-2-yl) etiI) oxalamide, N 1 - (2-methoxy) -4-methylbenzyl) -N2- (2- (pyridin-2-yl) ethyl) oxalamide, N1- (2,4-dimethoxybenzyl) -N2- (2- (5-methylpyridin-2-yl) ethyl) oxalamide, N1- (2,4-dimethylbenzyl) -N2- (2- (pyridin-2-yl) ethyl) oxalamide, N1- (2,4-dimethoxybenzyl) -N2- (2- (pyridin-2-yl) ethyl) oxalamide, N- (2,4-dimethoxy-benzyl) -N '- (2-pyridin-2-yl- ethyl) -oxalamide; or an edible acceptable salt thereof. 247. An edible or medicinal product, or a precursor thereof comprising at least an amount that modulates the sweet taste of at least one non-naturally occurring amide compound, or an edible acceptable salt thereof, wherein the amide compound has the formula wherein A is an optionally substituted phenyl ring or is a heteroaryl ring having one of the formulas wherein m is 0, 1, 2 or 3, and each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, and wherein R2 is a branched alkyl of C3.C10, or a cyclohexyl, tetrahydronaphthalene, or indanyl group, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 248. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a branched C3-C10 alkyl. 249. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is an optionally substituted cyclohexyl ring. 250. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a cyclohexyl, optionally substituted with 1, 2 or 3 methyl groups. 251. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 has the formula 252. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a 1-indanyl having the formula wherein m is 0, 1, 2 or 3, and each R2 'is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2l COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl , trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 253. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a 1- (1, 2,3,4) tetrahydronaphthalene having the formula wherein m is 0, 1, 2 or 3, and each R 2 can be attached to any of the aromatic or nonaromatic ring and is independently selected from hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) 2, COOCH 3, SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, sodiumpropoxy, and trifluoromethoxy. 254. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 has the formula wherein R2 'is hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3 >; SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 255. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 has the formula 256. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 has the formula 257. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a 1- (1, 2,3,4) tetrahydronaphthalene ring having the formula 258. The edible product or medicinal product, or a precursor thereof according to claim 247, characterized in that R2 is a ring (R) -1 (1, 2,3,4) tetrahydronaphthalene having the formula 259. The edible product or medicinal product, or a precursor thereof according to claim 247 characterized in that R2 is a ring (R) -1- (1, 2,3,4) tetrahydronaphthalene having the formula 260. The edible or medicinal product, or a precursor thereof according to claim 247, characterized in that the edible product or modified medicinal product is a food for human consumption. 261. The edible or medicinal product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is selected from the group consisting of confectionery, bakery products, ice cream, creamy products, sweet and tasty snacks, bars of snacks, meal replacement products, prepared foods, soups, pastas, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods, or spreads. 262. An edible product, or a precursor thereof according to claim 247, characterized in that it comprises one or more of meat, poultry, fish, vegetables, grains, or fruits. 263. An edible product, or a precursor thereof according to claim 247, characterized in that the edible or medicinally modified product is a frozen food, a raw food, or a whole or partially cooked food. 264. An edible product, or a precursor thereof according to claim 247, characterized in that it is a soup, a dehydrated or concentrated soup, or a dry soup. 265. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is a sandwich. 266. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is an auxiliary product for cooking, food solution product, a product for dressing meals, a condiment or a marinade. 267. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is a cake, biscuit, cake, caramel, chewable gum, gelatin, ice cream, sorbet, pudding, jam, jelly , dressing for salads, condiments, cereal, preserved fruit, or compote. 268. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is a beverage, a beverage mixture, or a beverage concentrate. 269. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is a soda, or juice. 270. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is an alcoholic beverage. 271. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is a pharmaceutical composition for oral administration. 272. An edible product, or a precursor thereof according to claim 247, characterized in that the modified edible or medicinal product is an oral hygiene product. 273. An amide compound that has the formula wherein A is a phenyl ring or is a heteroaryl ring having one of the formulas wherein m is 0, 1, 2 or 3, and each R1 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, and wherein R2 is (a) a branched C3-C10 alkyl, or (b) a cyclohexyl, teydronaphthalene, or indanyl group, optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; or an edible acceptable salt thereof. 274. The amide compound according to claim 273, characterized in that R2 is a branched alkyl of C3-C? O. 275. The amide compound according to claim 274, characterized in that A is an optionally substituted phenyl ring. 276. The amide compound according to claim 274, characterized in that A is an optionally substituted pyridyl ring. 277. The amide compound according to claim 274, characterized in that A is a heteroaryl ring having the formula wherein R1 'is hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 278. The amide compound according to claim 275, characterized in that R2 is an optionally substituted cyclohexyl ring. 279. The amide compound according to claim 275, characterized in that the cyclohexyl ring is substituted with 1, 2 or 3 methyl groups. 280. The amide compound according to claim 275, characterized in that R2 has the formula 281. The amide compound according to claim 275, characterized in that R2 is 1-indanyl having the formula wherein m is 0, 1, 2 or 3, and each R2 'is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 282. The amide compound according to claim 275, characterized in that R2 is a 1- (1, 2,3,4) teydronaphthalene having the formula wherein m is 0, 1, 2 or 3, and each R 2 can be attached to any of the aromatic or nonaromatic ring and is independently selected from hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) 2, COOCH 3) SCH 3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 283. The amide compound according to claim 275, characterized in that R2 has the formula wherein each R .2 'is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3 > SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 284. The amide compound according to claim 275, characterized in that R2 has the formula 285. The amide compound according to claim 275 characterized in that R2 has the formula 286. The amide compound according to claim 275, characterized in that R2 is a 1- (1, 2,3,4) teydronaphthalene ring having the formula 287. The amide compound according to claim 275 characterized in that R2 is a ring (R) -1- (1, 2,3,4) teydronaphthalene having the formula 288. The amide compound according to claim 277, characterized in that R2 is an optionally substituted cyclohexyl ring. 289. The amide compound according to claim 277, characterized in that the cyclohexyl ring is substituted with 1, 2 or 3 methyl groups. 290. The amide compound according to claim 277, characterized in that R2 has the formula 291. The amide compound according to claim 277, characterized in that R2 is 1-indanyl having the formula wherein m is 0, 1, 2 or 3, and each R2 'can be attached to any aromatic or non-aromatic ring and is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 292. The amide compound according to claim 277, characterized in that R2 is 1- (1, 2,3,4) tetrahydronaphthalene having the formula wherein m is 0, 1, 2 or 3, and each R can be attached to either the aromatic or nonaromatic ring and is independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 293. The amide compound according to claim 277, characterized in that R2 has the formula wherein each R2 'is independently selected from the group consisting of hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy , Sopropoxy, and trifluoromethoxy. 294. The amide compound according to claim 277, characterized in that R2 has the formula 295. The amide compound according to claim 277, characterized in that R2 has the formula 296. The amide compound according to claim 277, characterized in that R2 is a 1- (1, 2,3,4) tetrahydronaphthalene ring having the formula 297. The amide compound according to claim 277, characterized in that R2 is a ring (R) -1- (1, 2,3,4) tetrahydronaphthalene having the formula 298. An amide compound characterized in that it has the formula: 3-chloro-2-hydroxy-N- (2-methyl-1, 2,3,4-tetrahydronaphthalen-1-yl) benzamide, 3-chloro-2-hydroxy-N- (5-methoxy-1, 2,3,4-tetrahydronaphthalene-1-yl) benzamide, (R) -3-chloro-2-hydroxy-N- (1,2,3,4-tetrahydronaphthalen-1-yl) benzamide, 3-chloro-2-hydroxy-N- (5-hydroxy-1, 2,3,4-tetrahydronaphthalen-1-yl) benzamide, 3-chloro-2-hydroxy-N- (4-methyl-1, 2,3,4-tetrahydronaphthalen-1-yl) benzamide, 3-chloro-2-hydroxy-N- (6-methoxy-1, 2,3,4-tetrahydronaphthalen-1-yl) benzamide, 3-chloro-2- hydroxy-N- (1, 2,3,4-tetrahydronaphthalen-1-yl) benzamide, 2,3-dihydroxy-N- (2-methyl-1,2,3,4-tetrahydrophthalene- 1- il) benzamide, 2-hydroxy-N- (2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl) benzamide, 2,3-dihydroxy-N- (5-methoxy-1, 2,3) , 4-tetrahydronaphthalen-1-yl) benzamide, (S) -2,6-dimethyl-N- (1,2,3,4-tetrahydronaphthalen-1-yl) benzamide, N- (5,7-di methyl- 1, 2, 3, 4-tetrah id ronaphthalen-1-yl) -3-methylisoxazole-4-carboxamide, 3-methyl-N- (2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl) isoxazol-4-ca rboxamide, 3-methyl-N- (4-methyl-1,2,3,4-tetrah id ronaphthalen-1-yl) isoxazole-4-carboxamide, N- (5-methoxy-1, 2, 3, 4- tetrah id ronaphthalen-1-yl) -3-methylisoxazole-4-carboxamide, (R) -5-bromo-N- (1, 2, 3, 4-tetrah id ronaphthalen-1-yl) nicotinamide, (R) - 3-methyl-N- (1, 2, 3, 4-tetrahydrate apta I in -1-yl) isoxazole-4-carboxamide, (S) -5-bromo-N- (1,2, 3, 4 -tetrah id afta afta I en- 1-il) nicotinamide, (R) -N- (1,2, 3, 4-tetrah id ronaphthalen-1-yl) furan -3-carboxamide, (R) -5- methyl-N- (1, 2,3,4-tetrahydronaphthalen-1-yl) isoxazole-4-carboxamide, (R) -N- (1,2,3,4-tetrah id ronaphthalen-1-yl) furan- 3-carboxamide, 3-methyl-N- (1, 2,3,4-tetrahydronaphthalen-1-yl) isoxazole-4-carboxamide, N- (3, 3-d imethylbutan-2-yl) -2, 3, 5,6-tetraf luoro-4-methylbenzamide, 2,3,5,6-tetrafluoro-4-methyl-N- (3-methylbutan-2-yl) benzamide, 2,3,5,6-tetrafluoro-4- methyl-N- (2-methylcyclohexyl) benzamide, N- (2-methyl and Icy-hexyl) -3- (trifluoro methoxy) benzamide, 3-chloro-5-fluoro-N- (2-methylcyclohexyl) benzamide, (R) -N- (3, 3-dimethylbutan-2-yl) -2,3,5,6-tetraf-4-methylbenzamide, 4-fluoro-N- (2-methylcyclohexyl) -3- (trifluoro methyl) benzamide, (S) -2 , 3, 5, 6-tetraf luoro-4-methyl-N- (3-methylbutan-2-l) benzamide, 2,5-dichloro-N- (2-methylcyclohexyl) benzamide, 3,5-dichloro -2,6-dimethoxy-N- (2-methylcyclohexyl) benzamide, or 2,6-dimethyl-N- (2-methylcyclohexyl) benzamide; or an edible acceptable salt thereof. 299. A urea compound having the formula: wherein R7 is an aryl or heteroaryl comprising three to ten ring carbon atoms which are optionally substituted with 1, 2 or 3 substituents independently selected from, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, CO2CH3, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, and R9 is a branched alkyl group of C3.C10, or a cyclohexyl, tetrahydronaphthalene, or indanyl, optionally substituted with , 2 or 3 substituents independently selected from the group consisting of hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3) SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy; or an edible acceptable salt thereof. 300. The compound according to claim 299, characterized in that R7 is an optionally substituted phenyl ring. 301. The compound in accordance with the claim 300, characterized in that R9 is a branched alkyl of C3.C? 0. 302. The compound in accordance with the claim 300, characterized in that R9 is an optionally substituted cyclohexyl ring. 303. The compound according to claim 302, characterized in that the cyclohexyl ring is substituted with 1, 2 or 3 methyl groups. 304. The compound according to claim 302, characterized in that R9 has the formula 299, characterized in that R9 is a 1-indanyl having the formula wherein m is 0, 1, 2 or 3, and each R9 is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3), COOCH3l SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl , methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 306. The amide compound according to claim 299, characterized in that R9 is 1- (1, 2,3,4) tetrahydronaphthalene having the formula wherein m is 0, 1, 2 or 3, and each R9 can be attached to any aromatic or non-aromatic ring and is independently selected from, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3), COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 307. The amide compound according to claim 299, characterized in that R9 is a 1- (1, 2,3,4) tetrahydronaphthalene ring having the formula 308. The amide compound according to claim 299, characterized in that R7 is a heteroaryl ring having one of the formulas wherein m is 0, 1, 2 or 3, and each R r is independently selected from hydrogen, hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3), COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl , trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. 309. The compound according to claim 308, characterized in that R9 is a C3-C10 branched alkyl. 310. The compound according to claim 308, characterized in that Rg is an optionally substituted cyclohexyl ring. 311. The compound according to claim 308, characterized in that the cyclohexyl ring is substituted with 1, 2 or 3 methyl groups. 312. The compound according to claim 308, characterized in that R9 has the formula 313. A food product or medicinal product, or a precursor thereof, characterized in that it comprises at least a modular amount of tasty taste of at least one compound according to claims 299-312. 314. A urea compound having the formula: wherein R7 is an aryl or heteroaryl ring comprising three to ten ring carbon atoms which are optionally substituted with 1, 2 or 3 substituents independently selected from hydroxy, fluoro, chloro, NH2, NHCH3, N (CH3) 2, COOCH3, SCH3, SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy, and R9 has the structure wherein R9 is hydrogen, a C1-C10 alkyl, B is a phenyl, pyridyl ring , furanyl, thiofuranyl, pyrrole, cyclopentyl, cyclohexyl, or piperidyl, m is 0, 1, 2 or 3, and each R 2 is independently selected from hydrogen, hydroxy, fluoro, chloro, NH 2, NHCH 3, N (CH 3) 2, COOCH 3, SCH 3 , SEt, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy. or an edible acceptable salt thereof. 315. The compound according to claim 314, characterized in that R7 is an optionally substituted phenyl ring and B is phenyl or pyridyl. 316. The compound according to claim 314, characterized in that R7 is an optionally substituted phenyl ring and B is optionally substituted cyclohexyl. 317. An edible or medicinal product, or a precursor thereof characterized in that it comprises at least one modulated amount of tasty flavor of at least one compound according to claim 314. 318. An amide compound having the formula: (R) - methyl 2- (3-chloro-4-methoxybenzamido) -4-methylpentanoate, 4-methoxy-3-methyl-N- (5-methylhexan-3-yl) benzamide, N- (heptan-4-yl) -2- methylbenzo [d] [1,3] dioxol-5-carboxamide, 4-met i l-2- (4-methyl-3- (methylthio) benzamido) pentanoate of (S) -metMo, 4-methoxy-3- methyl-N- (2-methylheptan-4-yl) benzamide, N- (heptan-4-yl) -6-methylbenzo [d] [1,3] dioxol-5-carboxamide, 3,4-dimethyl-N- (2-methylhexan-3-yl) benzamide, 4-met i I -2- (5-met i I benzofuran-2-carboxamido) pentanoate of (R) -methyl, N - (hexan-3-i) -4-m-ethoxy -3-m eti I benzamide, N- (heptan-4-yl) -3-methyl-4- (methylthio) benzamide, N- (hexan-3-yl) -3-methyl-4- (methytio) benzamide, methyl 2- (3-chloro-4-methoxybenzamido) hexanoate, 3,4-d-methylo- N - (2-methyl heptan-4-i) benza mide, N - (h Exa n -3- i I) -3,4-di methyl benzamide, N - (he pta n -4-i I) -3, 4-d imeti I benzamide, 4-methyl-2- (4- (methylthio ) benzamido) pentanoate of (R) -methyl, 4-ethoxy-N- (heptan-4-yl) -3-methylbenzamide, 3,4-dimethyl-N- (5-methylhexan-3-yl) benzamide, 4-Methyl-2- (4-vinylbenzamido) pentanoate of (R) -methyl, 4-methoxy-3-methyl-N- (2-methylhexan-3-yl) benzamide, N - (heptan -4-i I) benzo [d] [1,3] dioxol-5-carboxamide, 2- (benzo [d] [1,3] di oxo I -6-carboxamio) -4-methylpentanoate of (R) -methyl, (R) -N- (1-methoxy-4-methylpentan-2-yl) -3,4-dimethylbenzamide, (R) -m ethyl -2- (2,3-di-methyl-uram-5-carboxamido) -4-methylpentanoate , or 4-Methoxy-N- (1-methoxymethyl-3-methyl-butyl) -3-methyl-benzamide; 0 an edible acceptable salt thereof. 319. An amide compound having the formula: N- (heptan-4-yl) benzo [d] [1, 3] dioxol-5-carboxamide or N- (2,4-dimethoxy-benzyl) -N '- ( 2-pyridin-2-yl-ethyl) -oxalamide; or an edible acceptable salt thereof. 320. An edible or medicinal product comprising the compounds according to claim 319 at a concentration between about 0.01 to about 10 ppm. 321. The edible or medicinal product according to claim 320, characterized in that the edible or medicinal product is a food for human consumption. 322. A urea compound having the formula: 1- (2-chlorophenyl) -3- (heptan-4-yl) urea, 1- (2,4-di-chloroform) -3- (1-phenylpropyl) urea, 1- (2,4-dimethoxyphenyl) -3- (heptan-4-yl) urea, 1- (2-fluorophenyl) -3- (heptan-4-yl) urea, 1- (4-isopro? il-phenyl) ) -3- (2- (pyridin-2-yl) ethyl) urea; or an edible acceptable salt thereof.