Use of flavones such as quercetin to increase cognitive function and to reduce jitterness

Abstract

The present disclosure relates to non-therapeutic uses of compounds or combinations thereof to increase cognitive performance, alertness and / or energy levels of a human or animal, as well as an oral product comprising said compounds or combinations thereof.

Description

NON-THERAPEUTIC USES AND ORAL PRODUCT FIELD

[0001] The present disclosure relates to non-therapeutic uses of a compound of Formula (I), a derivative thereof, or a combination thereof; and an oral product comprising a compound of Formula (I), a derivative thereof, or a combination thereof. In particular, the uses and oral products are intended for human or animal use. The products are configured for oral ingested use and deliver substances such as flavours and / or active ingredients during the non- therapeutic use. By ^non-therapeutic^ is meant that the use is not related to or providing therapy. BACKGROUND

[0002] Products that are easy to administer orally and which can provide a beneficial effect on particular mood states of a human or animal have become popular in recent years. For example, confectionary-type products (e.g. gummies or pastilles) containing vitamins or other mood-enhancing actives provide a convenient and pleasant mode of administration for such active ingredients. Other convenient modes of administration are food and beverages, for example energy drinks. Such products may include active ingredients that are delivered to the user in order to cause a biological response in the user that may enhance physical or mental performance of the user.

[0003] Beverages containing theanine and caffeine have been described in US 5,780,086 and US 6,268,009. More recently, EP1819241 describes beverages containing theanine and caffeine in a ratio of from 5:1 to 1:1.5. More generally, caffeinated beverages are widely consumed. In such beverages, caffeine may be naturally present such as in tea or coffee, or may be included as an added ingredient, for example in beverages such as colas and energy drinks. The presence of caffeine in such products may be considered desirable, for example to provide stimulant effects such as increased alertness, cognitive performance and / or energy levels. However, caffeine use may also be associated with other biological effects that may be considered less desirable, for example jitters, increased heart rate, ^crash^ (i.e. tiredness and / or fatigue sometime after the initial stimulant effect), and / or diuresis.

[0004] It would be desirable to provide compounds that could provide one or more of the same or related advantageous benefits of caffeine, e.g. increased alertness, cognitive performance and / or energy levels. It would further be desirable if such compounds also provided additional advantageous physiological effects, including reduced levels of one or more of the same or related disadvantageous effects of caffeine, e.g. jitteriness. Oral products configured for oraluse which may deliver such compounds to the consumer in an enjoyable and effective form, such as in the form of a liquid shot or chewable solid product, would also be desirable. BRIEF SUMMARY

[0005] In accordance with some embodiments described herein, there is provided a non- therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereof, to increase cognitive performance, alertness and / or energy levels of a human or animal:Formula (I) wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4.

[0006] In accordance with some embodiments described herein, there is provided an oral product comprising a combination of active ingredients, wherein the combination comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof:wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4; and (b) one or more B vitamins selected from B1, B2, B6 and B7; and / or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, and combinations thereof.

[0007] In accordance with some embodiments described herein, there is provided a process for preparing an oral product. The process comprising: (a) contacting at least one binding agent and at least one bulking agent selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, and optionally adding water, (b) heating the mixture of binding agent, sugar alcohol and / or sugar, and optionally water, (c) adding a combination of active ingredients, wherein the combination of active ingredients is as defined herein for the oral product, and (d) allowing the resulting mixture to set to provide an oral product in the form of a chew. Alternatively the process comprises: (a) combining active ingredients, wherein the combination of active ingredients isas defined herein for the oral product, (b) contacting the active ingredients with water, and (c) mixing the active ingredients with the water to prepare an oral product in the form of a liquid.

[0008] These and other features, aspects, and advantages of the disclosure will be apparent from a reading of the following detailed description. The invention includes any combination of two, three, four, or more of the above-noted embodiments as well as combinations of any two, three, four, or more features or elements set forth in this disclosure, regardless of whether such features or elements are expressly combined in a specific embodiment description herein. This disclosure is intended to be read holistically such that any separable features or elements of the disclosed invention, in any of its various aspects and embodiments, should be viewed as intended to be combinable unless the context clearly dictates otherwise.

[0009] For ease of reference, these and further aspects of the present invention are now discussed under appropriate section headings. However, the teachings under each section are not necessarily limited to each particular section. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Embodiments of the invention will now be described, by way of example only, with reference to accompanying drawings, in which:

[0011] Figure 1 is a dotplot from GSEA showing suppressed pathways according to KEGG classifications for consumption of galangin vs consumption of caffeine as described in Example 3. Figure 1 shows the suppression of cAMP signalling pathways which supports galangin being useful to reduce jitteriness in subjects.

[0012] Figure 2 is a graph showing the mean number of correct answers obtained for the test and control groups in the Serial 7s subtraction test after consumption of the oral product of Example 4 or the control, relative to baseline, which is the mean of three repetitions performed prior to consumption. The x-axis represents successive repetitions of the Serial 7s substraction test. A statistically significant difference versus control was observed across the whole session.

[0013] Figure 3 is a bar chart showing cognitive enhancement as measured by the Serial 7s substraction test compared to control as described in Example 5. A statistically significant difference versus control was observed across the whole session.

[0014] Figure 4 is a graph showing feelings of ^stimulation^ over time as assessed by Visual Analog Scale (VAS) compared to control as described in Example 5. A higher level of stimulation was reported for the test group versus the control group. DETAILED DESCRIPTION

[0015] It is to be understood that this invention is not limited to the particular configurations, process steps, and materials disclosed herein as such configurations, process steps, and materials may vary somewhat. It is also to be understood that the terminology employed herein is used for the purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims and equivalents thereof.

[0016] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Reference to "dry % by weight" or "dry weight basis" refers to weight on the basis of dry ingredients (i.e., all ingredients except water). Reference to "wet weight" refers to the weight of the product or composition including water. Unless otherwise indicated, reference to "% by weight" (or ^% by weight^) of a product or composition reflects the total wet weight of the product or composition (i.e., including water).

[0017] In this specification, unless otherwise stated, the term "about" modifying the quantity of an ingredient in the oral product of the invention or employed in the methods of the invention refers to variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients employed to make the oral product, or to carry out the methods; and the like. The term ^about^ also encompasses amounts that differ due to different equilibrium conditions for a product or composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalents to the quantities. Non-Therapeutic Use

[0018] Various aspects of the present disclosure described herein relate to the non- therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereof:wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4.

[0019] It has been found by the present inventors that the compounds of Formula (I) may be used as a substitute or adjunct for caffeine in oral products intended for non-therapeutic use. Caffeine (1,3,7-trimethylxanthine) is a central nervous system stimulant, a bitter tasting alkaloid that is naturally found in a variety of plant species, including tea leaves, kola nuts, cocoa, guarana, and coffee beans. Caffeine may be used to enhance alertness, attention, cognitive performance as well as physical performance. However, caffeine use may also be associated with undesirable effects such as jitters, increased heart rate, ^crash^ (i.e. tiredness and / or fatigue sometime after the initial stimulant effect), and / or diuresis. Without wishing to be bound by theory, the physiological effects of caffeine are believed to be mediated via several mechanisms including: antagonism of adenosine receptors, inhibition of phosphodiesterases, release of calcium from intracellular stores, and antagonism of benzodiazepine receptors. In particular, antagonism of adenosine receptors appears to be highly important for effects relating to behaviour and cognitive function. Due to this antagonism, caffeine also indirectly affects the release of norepinephrine, dopamine, acetylcholine, serotonin, glutamate, gamma-aminobutyric acid (GABA), and possiblyneuropeptides. There are two main classes of adenosine receptor: A1 and A2. Caffeine and its metabolite paraxanthine are non-selective antagonists for both, with in vivo concentrations associated with mild CNS stimulation generally being around 5-10 µM.

[0020] The present inventors have found that the compounds of Formula (I) of the present disclosure are adenosine receptor antagonists with at least comparable potency to caffeine, as described in more detail in the Examples of the present disclosure. Accordingly, the compounds of Formula (I) of the present disclosure may be used to induce similar CNS stimulatory effects to caffeine in a subject, for example when used in an oral product as described herein. This is unexpected because compounds of Formula (I) of the present disclosure have generally been considered as antioxidants and used as such. As described further in the below disclosure, said compounds of Formula (I) may have one or more advantages over caffeine in the non-therapeutic uses of the aspects and embodiments described herein, e.g. a more favourable profile of physiological effects, such as providing desirable CNS stimulatory effects while providing reduced undesirable effects on other physiological processes.

[0021] Thus, in various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used as a CNS stimulant in a human or animal. In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used to increase cognitive performance, alertness and / or energy levels of a human or animal.

[0022] In one aspect, the compound of Formula (I), a derivative thereof, or a combination thereof is used to increase cognitive performance of a human or animal.

[0023] In one aspect, the compound of Formula (I), a derivative thereof, or a combination thereof is used to increase alertness of a human or animal.

[0024] In one aspect, the compound of Formula (I), a derivative thereof, or a combination thereof is used to increase energy levels of a human or animal.

[0025] In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used to improve feelings of being in control for a human or animal. In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used to reduce sleepiness in a human or animal. In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used to increase mental and / or physical energy of a human or animal. In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof is used to improve attention and / or concentration of a human or animal.

[0026] In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof may be associated with the rapid onset of mental and / or physical energy. In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof may provide a short, medium or long-term mental and / or physical energy boost for the user. For example, the compound of Formula (I), a derivative thereof, or a combination thereof may be associated with increased mental energy (e.g. increased arousal, reduced mental fatigue and increased motivation of the consumer to perform mental tasks) and increased physical energy (e.g. improved endurance performance and capacity, such as reduced physical fatigue). The compound of Formula (I), a derivative thereof, or a combination thereof may be associated with improved energy levels over a short or sustained period of time. The increase in energy levels may also increase the user^s overall feelings of enjoyment and enthusiasm, with feelings of confidence, motivation, pleasure and excitement being increased.

[0027] In various aspects, the compound of Formula (I), a derivative thereof, or a combination thereof may be associated with improved mental focus, alertness, attention and / or concentration of the consumer as compared with previously known products. Alertness may be defined as a state of being awake and aware, e.g. readiness and / or speed to respond to a stimulus. The compound of Formula (I), a derivative thereof, or a combination thereof may also help to increase alertness and concentration over a short or sustained period of time, and also improve reaction times and overall mood with psychological scores being improved after consumption. The compound of Formula (I), a derivative thereof, or a combination thereof may provide a short-term increase in mental performance and cognition for the consumer when consumed. Cognitive and mental performance may be defined as improvement of attention, mental focus, ability to carry out complex tasks such as problem-solving, speed and accuracy of processing information and / or making decisions, mood enhancement as well as resistance to stress. Attention refers to the selective ability to concentrate on one task to the exclusion of others and a sustained ability to concentrate over a period of time.

[0028] As noted above and detailed in the Examples herein below, it has also been found by the present inventors that compounds according to Formula (I) as defined herein may be associated with further advantageous physiological effects other than those arising through adenosine receptor antagonism. Accordingly, the uses and oral products of the present disclosure may exhibit an improved spectrum of physiological effects compared to the use of caffeine alone. For example, compounds according to Formula (I) have been unexpectedly found by the present inventors to be implicated in suppressing muscle activity, e.g. contraction. Such an effect may counteract undesirable effects of stimulation, such as jitteriness, that may be experienced with caffeine consumption. Thus, in some embodiments, the use furthercomprises reduced jitteriness in the human or animal. As used herein, the term jitteriness refers to physical sensations such as effects on muscle contraction (e.g. involuntary contractions / spams, twitching), elevated heart rate / palpitations, and / or associated feelings such as nervous energy. Jitteriness in a subject can be measured by visual analogue scales. For example, the ^Caffeine Research Visual Analogue Scales (Caff-VAS)^ include a ^jittery^ visual analogue scale, and have been previously used in research into the effects of caffeine (see Rogers PJ, Richardson NJ, Elliman NA (1995) ^Overnight caffeine abstinence and negative reinforcement of preference for caffeine-containing drinks.^ Psychopharmacology 120:457^462; and Rogers PJ, Martin J, Smith C, Heatherley SV, Smit HJ (2003) ^Absence of reinforcing, mood and psychomotor performance effects of caffeine in habitual non-consumers of caffeine^ Psychopharmacology 167:54-62).

[0029] In some embodiments, the reduced jitteriness in the human or animal is relative to the use of caffeine in said human or animal. For example, a lower degree of jitteriness (e.g. as measured by a visual analogue scale as detailed above) may be measured in subjects at one or more time-points after consumption of an oral product (such as those described herein) comprising a compound of Formula (I), a derivative thereof, or a combination thereof as defined herein, when compared to subjects that have consumed caffeine, e.g. in a equivalent oral product that contains caffeine instead of a compound of Formula (I), a derivative thereof, or a combination thereof according to the present disclosure. Put differently, the reduced jitteriness may be relative to the use of caffeine alone. In some embodiments, reduced jitteriness may be observed versus a placebo, i.e. an equivalent oral product that does not contain any active ingredients. In any of the foregoing embodiments, the reduced jitteriness may be experienced when comparing an equivalent amount (e.g. by weight) of the compound of Formula (I), derivative thereof, or combination thereof vs an amount of caffeine. In other embodiments, the reduced jitteriness may be experienced when comparing a lower amount (e.g. by weight) of the compound of Formula (I), derivative thereof, or combination thereof relative to caffeine. Such amounts may be as further described herein below for each of the compound of Formula (I), derivative thereof, or combination thereof, and caffeine. A person of skill in the art will further recognise that reduced jitteriness as defined herein may also contribute to other effects, for example feelings of relaxation, reduced anxiety, and / or reduced tension.

[0030] In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in an oral product according to the disclosure herein below.

[0031] In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof may be used in combination with one or more B vitamins selected from B1, B2, B6, and B7.

[0032] In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with one or more B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with piperine or a geometric isomer thereof, and one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof.In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with any of the additional active ingredients as described herein below.

[0033] For example, in some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L- tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with piperine or a geometric isomer thereof, and a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof.

[0034] In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof and saffron. In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with piperine or a geometric isomer thereof, and two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitaminC, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan and saffron.

[0035] In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In some embodiments, the compound of Formula (I), a derivative thereof, or a combination thereof is used in combination with one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; piperine or a geometric isomer thereof; and one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta- alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof.

[0036] In further aspects, the uses of the present disclosure may be associated with one or more effects including boosting immune response or supporting immunity as compared with previously known products, supporting resilience of a human or animal against infection, decreasing stress and anxiety in a human or animal, providing short-term mood enhancement, increasing sexual drive and / or desire for sexual activity in a human or animal, and increasing mental and / or physical activity of a human or animal.

[0037] Such effects may be associated with the use of the compound of Formula (I), derivative thereof, or combination thereof. In any of the foregoing aspects and embodiments, some or all of the effects may be associated with the use of the compound of Formula (I), derivative thereof, or combination thereof when comprised in combination with further actives, for example in an oral product according to the disclosure herein. In such a combination of actives, the active ingredients other than the compound of Formula (I), derivative thereof, or combination thereof may be any of the active ingredients described herein. In some embodiments, the effect or combination of effects obtained from a combination of active ingredients may not be obtainable when each of the active ingredients is used in isolation.

[0038] In various embodiments, the effects described herein may be in a healthy subject, e.g. a healthy human or animal. Thus, the uses described herein may in various embodiments be in a healthy human or animal. For example, the present disclosure includes the non- therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereofto increase cognitive performance, alertness and / or energy levels of a healthy human or animal.

[0039] The present disclosure provides the use of a compound of Formula (I), a derivative thereof, or a combination thereof to increase cognitive performance of a healthy human or animal.

[0040] The present disclosure provides the use of a compound of Formula (I), a derivative thereof, or a combination thereof to increase alertness of a healthy human or animal.

[0041] The present disclosure provides the use of a compound of Formula (I), a derivative thereof, or a combination thereof to increase energy levels of a healthy human or animal.

[0042] Such uses may further comprise reduced jitteriness in the healthy human or animal; preferably, wherein the reduced jitteriness is relative to the use of caffeine in said human or animal.

[0043] In various embodiments, any of the effects described herein may be perceived effects, i.e. based on the perception of the subject.

[0044] As used herein, the term ^healthy^ refers to a subject who is not suffering from any disease or disorder. For example, uses according to the present disclosure may provide an increase in one or more attributes of a subject, such as cognitive performance, alertness and / or energy levels in a healthy subject. It will be understood that the uses and methods described herein are non-therapeutic, such that said aspects may, in various embodiments, include restoring (in part or in full) such attributes from a reduced level not caused by or associated with a disease or disorder (e.g. fatigue or tiredness caused by exercise) but does not include restoring (in part or in full) a reduced level caused by or associated with a disease or disorder (e.g. a degenerative disease or disorder such as Alzheimer^s disease).

[0045] In further aspects the present disclosure provides a non-therapeutic method for enhancing cognitive performance, alertness and / or energy levels in a human or animal, said method comprising administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof to said human or animal.

[0046] In various embodiments, the present disclosure provides a non-therapeutic method for enhancing cognitive performance in a human or animal, said method comprising administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof to said human or animal.

[0047] In various embodiments, the present disclosure provides a non-therapeutic method for enhancing alertness in a human or animal, said method comprising administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof to said human or animal.

[0048] In various embodiments, the present disclosure provides a non-therapeutic method for enhancing energy levels in a human or animal, said method comprising administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof to said human or animal.

[0049] In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with one or more (or two or more) B vitamins selected from B1, B2, B6, and B7.

[0050] In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with one or more (or at least two) compounds selected from taurine, vitamin C, vitamin D, ginseng, zinc or a salt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or combinations thereof. In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with piperine or a geometric isomer thereof, and one or more (or at least two) compounds selected from taurine, vitamin C, vitamin D, ginseng, zinc or a salt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or combinations thereof.

[0051] In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with at least two of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, taurine, vitamin C, vitamin D, ginseng, zinc or a salt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof and saffron.

[0052] In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and one or more (or two or more) compounds selected from taurine, vitamin C, vitamin D, ginseng, zinc or asalt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or combinations thereof. In various embodiments, the method comprises administering an effective amount of a compound of Formula (I), a derivative thereof, or a combination thereof, in combination with one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; piperine or a geometric isomer thereof; and one or more (or two or more) compounds selected from taurine, vitamin C, vitamin D, ginseng, zinc or a salt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or combinations thereof.

[0053] In further embodiments, the method may comprise administering an effective amount of an oral product according to any of the aspects and embodiments described herein.

[0054] In various embodiments of the foregoing methods, the human or animal is a healthy human or animal as defined hereinabove.

[0055] In any of the foregoing aspects and embodiments, the use / method may be in a human.

[0056] The effects described herein may be measured by consumer testing. For example, pleasure / arousal / dominance may be measured by the SAM (self-assessment manikin) technique, anger / confusion / depression / tension may be measured by POMS-SF (profile of mood states), galvanic skin response may be measured e.g. by Biopac monitors, contentedness may be measured by STAI-State (State Trait Anxiety Inventory-State), ^de- stress^ / tranquil may be measured by visual analogue mood scale (VAMS), calmness / nervousness / ^in control^ may be measured by visual analogue scale (VAS), vigour / friendliness / fatigue / anger / confusion / dejection / tension may be measured by POMS-SF, and general wellbeing / mood may be measured by Quality of Life Escale (QOLS) and / or STAI- State. Cognitive accuracy may be measured using a cognitive battery including RVIP (Rapid Visual Information Processing), mental arithmetic tests (e.g. serial -3 substraction), numeric working memory (NWM), and Corsi blocks. Alertness, physical energy, fatigue reduction, feeling of stimulation, and vigour may be measured using VAS. Mental fatigue may be measured by subjecting users to cognitively demanding tasks intended to cause fatigue and then assessment by POMS. Stimulation can be measured using VAS. Cognitive speed may be measured via immediate or delayed word recognition (e.g. using the COMPASS tool), and / or NWM tests. Intimacy, pleasure, sensation, arousal, ^in the moment^ and motivation may be measured using VAS. Sexual desire may be measured using the Sexual Desire Inventory (SDI) questionnaire (see Spector, Carey, Steinberg, J Sex Marital Ther (1996)).

[0057] It will be understood that all disclosure herein concerning the oral product and compound of Formula (I) applies to the disclosed uses. The disclosure is not repeated for conciseness. Similarly, all disclosure herein concerning the non-therapeutic uses applies to the disclosed non-therapeutic methods. The disclosure is not repeated for conciseness. Compound of Formula (I)

[0058] The present disclosure relates to uses of a compound of Formula (I), a derivative thereof, or a combination thereof; and oral products comprising the same:wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, and dialkenylamino; and m is an integer from 0 to 4.

[0059] In any of the aspects described herein, the compound of Formula (I) may be further defined according to any of the further embodiments described herein below. It will be understood that said embodiments of the compound of Formula (I) may be combined with any of the embodiments of the oral product and uses thereof disclosed herein.

[0060] All aspects include, where appropriate, all enantiomers and tautomers of the compounds of formula (I). The person skilled in the art will recognise compounds that possess optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and / or tautomers may be isolated / prepared by methods known in the art. Some of the compounds of Formula (I) may exist as stereoisomers and / or geometric isomers ^ e.g. they may possess one or more asymmetric and / or geometric centers and so may exist in two or more stereoisomeric and / or geometric forms. All aspects include, where appropriate, the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms.

[0061] The compound of Formula (I) or derivative thereof of the present disclosure may be used / present in different solid forms such as different crystalline forms or in the form of an amorphous solid. The present disclosure encompasses different crystalline forms as well as amorphous forms of said compound.

[0062] As used herein, the term ^alkyl^ refers to substituted or unsubstituted, saturated straight, branched, primary, secondary or tertiary hydrocarbons. The alkyl group may, for instance, be a C1-C12group, which is an alkyl group having 1 to 12 carbon atoms. In some embodiments, alkyl groups will include C1-C10, C1-C8, C1-C6, C1-C4or C1-C3alkyl groups. Examples of C1-C10alkyl groups include, but are not limited to, methyl, ethyl, propyl, 1- methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2- methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2- dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3- dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1- methylpropyl, 1-ethyl-2-methylpropyl, heptyl, octyl, 2-ethylhexyl, nonyl and decyl and their isomers. Examples of C1-C6 alkyl groups include, but are not limited to, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2- dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3- dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, and their isomers. C1-C4-alkyl means, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl.

[0063] Cyclic alkyl groups, may be referred to as ^cycloalkyl^ and include those with 3 to 10 carbon atoms having single or multiple fused rings. Non-limiting examples of cycloalkyl groups include adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

[0064] Carbocyclic groups are cyclic groups composed exclusively of carbon. The carbocyclic groups include both aromatic rings such as phenyl and non-aromatic rings such cyclohexyl and include those with 3 to 14 carbon atoms having single or multiple fused rings.

[0065] The term ^alkenyl^ refers to both straight and branched carbon chains, substituted or unsubstituted, which have at least one carbon-carbon double bond. In some embodiments, alkenyl groups may include C2-C12alkenyl groups. In other embodiments, alkenyl includes C2-C10, C2-C8, C2-C6or C2-C4alkenyl groups. In one embodiment of alkenyl, the number of double bonds is 1-3; in another embodiment of alkenyl, the number of double bonds is one. Other ranges of carbon-carbon double bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. ^C2-C10-alkenyl^ groups may include more than one double bond in the chain. Examples of C2-C6alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-methyl-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2- propenyl; 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1- butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1- methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2- dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1- hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1- pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2- pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3- pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4- pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3- butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl- 1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3- dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1- butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2- propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl.

[0066] The alkyl and cycloalkyl and carbocyclic groups described herein can be unsubstituted or substituted with one or more moieties selected from the group consisting of alkyl, halo, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, alkyl- or dialkylamino, amido, arylamino, alkoxy, aryloxy, nitro, cyano, azido, thiol, imino, sulfonic acid, sulfate, sulfonyl, sulfanyl, sulfinyl, sulfamoyl, ester, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphonic acid, phosphate, phosphonate, or any other viable functional group that does not inhibit the biological activityof the compounds of the invention, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene and Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999, hereby incorporated by reference.^Cycloalkenyl^ refers to monovalent cyclic alkenyl groups of from 4 to 10 carbon atoms having single or multiple fused rings which fused rings may or may not be cycloalkenyl provided that the point of attachment is to a cycloalkenyl ring atom. Examples of cycloalkenyl groups include, by way of example, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl and the like. Alkenyl and cycloalkenyl groups may be unsubstituted or substituted with one or more substituents as described for alkyl above.

[0067] ^Alkynyl^ refers to both straight and branched carbon chains, unsubstituted or substituted, which have at least one carbon-carbon triple bond. In one embodiment of alkynyl, the number of triple bonds is 1-3; in another embodiment of alkynyl, the number of triple bonds is one. In some embodiments, alkynyl groups include from 2 to 12 carbon atoms. In other embodiments, alkynyl groups may include C2-C10, C2-C8, C2-C6or C2-C4alkynyl groups. Other ranges of carbon-carbon triple bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. For example, the term ^C2-C10-alkynyl^ as used herein refers to a straight-chain or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms and containing at least one triple bond, such as ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl, n-but-1-yn-1-yl, n-but-1-yn-3-yl, n-but-1-yn-4-yl, n-but-2-yn-1-yl, n-pent-1-yn- 1-yl, n-pent-1-yn-3-yl, n-pent-1-yn-4-yl, n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n- pent-2-yn-5-yl, 3-methylbut-1-yn-3-yl, 3-methylbut-1-yn-4-yl, n-hex-1-yn-1-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5-yl, n-hex-1-yn-6-yl, n-hex-2-yn-1-yl, n-hex-2-yn-4-yl, n-hex-2- yn-5-yl, n-hex-2-yn-6-yl, n-hex-3-yn-1-yl, n-hex-3-yn-2-yl, 3-methylpent-1-yn-1-yl, 3- methylpent-1-yn-3-yl, 3-methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl, 4-methylpent-1-yn-1-yl, 4-methylpent-2-yn-4-yl or 4-methylpent-2-yn-5-yl and the like.

[0068] The term ^haloalkyl^ refers to an alkyl group, as defined herein, which is substituted by one or more halogen atoms. For example, C1-C4-haloalkyl includes, but is not limited to, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and the like.

[0069] The term ^haloalkenyl^ refers to an alkenyl group, as defined herein, which is substituted by one or more halogen atoms.

[0070] The term ^haloalkynyl^ refers to an alkynyl group, as defined herein, which is substituted by one or more halogen atoms.

[0071] ^Alkoxy^ refers to alkyl-O- or O-alkyl (the terms being used interchangeably herein), wherein alkyl is as defined above. Similarly, the terms ^alkenyloxy,^ ^alkynyloxy,^ ^haloalkoxy,^ ^haloalkenyloxy,^ ^haloalkynyloxy,^ ^cycloalkoxy,^ ^cycloalkenyloxy,^ ^halocycloalkoxy,^ and ^halocycloalkenyloxy^ refer to the groups alkenyl-O-, alkynyl-O-, haloalkyl-O-, haloalkenyl-O-, haloalkynyl-O-, cycloalkyl-O-, cycloalkenyl-O-, halocycloalkyl-O-, and halocycloalkenyl-O-, respectively, wherein alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, and halocycloalkenyl are as defined above. Examples of C1-C6- alkoxy include, but are not limited to, methoxy, ethoxy, OCH2-C2H5, OCH(CH3)2, n-butoxy, OCH(CH3)-C2H5, OCH2^CH(CH3)2,OC(CH3)3, n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3- methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethyl-propoxy, 1- ethylpropoxy, n-hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4- methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, 1-ethyl-2- methylpropoxy and the like.

[0072] ^Aryl^ refers to an unsubstituted or substituted monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring or multiple fused rings. Aryl groups include, but are not limited to, phenyl, biphenyl, tolyl, xylyl, and naphthyl. In some embodiments aryl includes tetrahydronaphthyl, phenylcyclopropyl and indanyl. Aryl groups may be unsubstituted or substituted by one or more moieties selected from halogen, cyano, nitro, hydroxy, mercapto, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, cycloalkenyloxy, halocycloalkoxy, halocycloalkenyloxy, alkylthio, haloalkylthio, cycloalkylthio, halocycloalkylthio, alkylsulfinyl, alkenylsulfinyl, alkynyl-sulfinyl, haloalkylsulfinyl, haloalkenylsulfinyl, haloalkynylsulfinyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, haloalkyl-sulfonyl, haloalkenylsulfonyl, haloalkynylsulfonyl, -SF5, alkylamino, alkenylamino, alkynylamino, di(alkyl)amino, di(alkenyl)-amino, di(alkynyl)amino, or trialkylsilyl.

[0073] The term ^aralkyl^ refers to an aryl group that is bonded to the parent compound through a diradical alkylene bridge, (-CH2-)n, where n is 1-12 and where ^aryl^ is as defined above.

[0074] ^Heteroaryl^ refers to a monovalent aromatic group of from 1 to 15 carbon atoms having one or more oxygen, nitrogen, and sulfur heteroatoms within the ring, preferably 1 to 4heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized. Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple fused rings provided that the point of attachment is through a heteroaryl ring atom. Examples of heteroaryls include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinnyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl benzofuranyl, benzothiophenyl, imidazopyridyl, imidazopyrimidyl, or pyrrolopyrimidyl. Heteroaryl rings may be unsubstituted or substituted by one or more moieties as described for aryl above.

[0075] ^Heterocyclyl,^ ^heterocyclic^ or ^heterocyclo^ refers to fully saturated or unsaturated, cyclic groups, for example, 3 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring systems, which have one or more oxygen, sulfur or nitrogen heteroatoms in ring, preferably 1 to 4 heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system and may be unsubstituted or substituted by one or more moieties as described for aryl groups above.

[0076] Exemplary monocyclic heterocyclic groups include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2- oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, triazinyl, and the like.

[0077] Exemplary bicyclic heterocyclic groups include, but are not limited to, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetra- hydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl]or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl and the like.

[0078] The term "alkylthio^ refers to alkyl-S-, where ^alkyl^ is as defined above. In some embodiments, the alkyl component of the alkylthio group will include C1-C10, C1-C8, C1-C6, C1- C4 or C1-C3 alkyl groups. For example, C1-C6 alkylthio include, but are not limited to,methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2- methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3- methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4- methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2- dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1-ethylbutylthio, or 2- ethylbutylthio. C1-C4-alkylthio include, but are not limited to, methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio or 1,1-dimethylethylthio.

[0079] Similarly, the terms ^haloalkylthio,^ ^cycloalkylthio,^ ^halocycloalkylthio^ refer to the groups ^S-haloalkyl, -S-cycloalkyl, and ^S-halocycloalkyl, respectively, where the terms ^haloalkyl,^ ^cycloalkyl,^ and ^halocycloalkyl^ are as defined above.

[0080] The term alkenylthio refers to alkenyl-S-, where ^alkenyl^ is as defined above. In some embodiments, the alkenyl component of the alkenylthio group will include C2-C10, C2-C8, C2- C6, C2-C4or C2-C3alkenyl groups. For example, C2-C6alkenylthio include, but are not limited to ethenylthio, 1-propenylthio, 2-propenylthio, 1-methyl-ethenylthio, 1-butenylthio, 2- butenylthio, 3-butenylthio, 1-methyl-1-propenylthio, 2-methyl-1-propenylthio, 1-methyl-2- propenylthio, 2-methyl-2-propenylthio; 1-pentenylthio, 2-pentenylthio, 3-pentenylthio, 4- pentenylthio, 1-methyl-1-butenylthio, 2-methyl-1-butenylthio, 3-methyl-1-butenylthio, 1- methyl-2-butenylthio, 2-methyl-2-butenylthio, 3-methyl-2-butenylthio, 1-methyl-3-butenylthio, 2-methyl-3-butenylthio, 3-methyl-3-butenylthio, 1,1-dimethyl-2-propenylthio, 1,2-dimethyl-1- propenylthio, 1,2-dimethyl-2-propenylthio, 1-ethyl-1-propenylthio, 1-ethyl-2-propenylthio, 1- hexenylthio, 2-hexenylthio, 3-hexenylthio, 4-hexenylthio, 5-hexenylthio, 1-methyl-1- pentenylthio, 2-methyl-1-pentenylthio, 3-methyl-1-pentenylthio, 4-methyl-1-pentenylthio, 1- methyl-2-pentenylthio, 2-methyl-2-pentenylthio, 3-methyl-2-pentenylthio, 4-methyl-2- pentenylthio, 1-methyl-3-pentenylthio, 2-methyl-3-pentenylthio, 3-methyl-3-pentenylthio, 4- methyl-3-pentenylthio, 1-methyl-4-pentenylthio, 2-methyl-4-pentenylthio, 3-methyl-4- pentenylthio, 4-methyl-4-pentenylthio, 1,1-dimethyl-2-butenylthio, 1,1-dimethyl-3-butenylthio, 1,2-dimethyl-1-butenylthio, 1,2-dimethyl-2-butenylthio, 1,2-dimethyl-3-butenylthio, 1,3- dimethyl-1-butenylthio, 1,3-dimethyl-2-butenylthio, 1,3-dimethyl-3-butenylthio, 2,2-dimethyl-3- butenylthio, 2,3-dimethyl-1-butenylthio, 2,3-dimethyl-2-butenylthio, 2,3-dimethyl-3- butenylthio, 3,3-dimethyl-1-butenylthio, 3,3-dimethyl-2-butenylthio, 1-ethyl-1-butenylthio, 1- ethyl-2-butenylthio, 1-ethyl-3-butenylthio, 2-ethyl-1-butenylthio, 2-ethyl-2-butenylthio, 2-ethyl- 3-butenylthio, 1,1,2-trimethyl-2-propenylthio, 1-ethyl-1-methyl-2-propenylthio, 1-ethyl-2- methyl-1-propenylthio or 1-ethyl-2-methyl-2-propenylthio.

[0081] The term ^alkylsulfinyl" refers to the group alkyl-S(=O)-, where ^alkyl^ is as defined above. In some embodiments, the alkyl component in alkylsulfinyl groups will include C1-C12, C1-C10, C1-C8, C1-C6, C1-C4 or C1-C3 alkyl groups. Examples include, but are not limited to, - SO^CH3, -SO^C2H5, n-propylsulfinyl, 1-methylethylsulfinyl, n-butylsulfinyl, 1- methylpropylsulfinyl, 2-methylpropylsulfinyl, 1,1-dimethylethylsulfinyl, n-pentylsulfinyl, 1- methylbutylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 1,1-dimethylpropylsulfinyl, 1,2- dimethylpropylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, n-hexylsulfinyl, 1- methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1- dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,2- dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1- methylpropylsulfinyl or 1-ethyl-2-methylpropylsulfinyl.

[0082] Similarly, the terms ^alkenylsulfinyl,^ ^alkynylsulfinyl,^ ^haloalkylsulfinyl,^ ^haloalkenylsulfinyl,^ and ^haloalkynylsulfinyl^ refer to the groups alkenyl-S(=O)-, alkynyl- S(=O)-, and haloalkyl-S(=O)-, haloalkenyl-S(=O)-, and haloalkynyl-S(=O)-, where the terms ^alkenyl,^ ^alkynyl,^ ^haloalkyl,^ ^haloalkenyl,^ and ^haloalkynyl^ are as defined above.

[0083] The term "alkylsulfonyl" refers to the group alkyl-S(=O)2-, where the term ^alkyl^ is as defined above. In some embodiments, the alkyl component in alkylsulfonyl groups will include C1-C12, C1-C10, C1-C8, C1-C6or C1-C4alkyl groups. Examples include, but are not limited to, - SO2^CH3, -SO2^C2H5, n-propylsulfonyl, -SO2^CH(CH3)2, n-butylsulfonyl, 1- methylpropylsulfonyl, 2-methylpropylsulfonyl, -SO2^C(CH3)3, n-pentylsulfonyl, 1- methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, n-hexylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl,methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3- dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3- dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl or 1-ethyl-2-methylpropylsulfonyl and the like.

[0084] The terms ^alkenylsulfonyl,^ ^alkynylsulfonyl,^ ^haloalkylsulfonyl,^ ^haloalkenylsulfonyl,^ and ^haloalkynylsulfonyl^ refer to the groups alkenyl-S(=O)2-, alkynyl-S(=O)2-, and haloalkyl- S(=O)2-, haloalkenyl-S(=O)2-, and haloalkynyl-S(=O)2-, where the terms ^alkenyl,^ ^alkynyl,^ ^haloalkyl,^ ^haloalkenyl,^ and ^haloalkynyl^ are as defined above.

[0085] The terms ^alkylamino,^ ^dialkylamino,^ ^alkenylamino,^ ^alkynylamino,^ ^di(alkenyl)amino,^ and ^di(alkynyl)amino^ refer to the groups -NH(alkyl), -N(alkyl)2, - NH(alkenyl), -NH(alkynyl), -N(alkenyl)2 and -N(alkynyl)2, where the terms ^alkyl,^ ^alkenyl,^ and ^alkynyl^ are as defined above. Also contemplated are the groups ^N(alkyl)(alkenyl) wherein the terms ^alkyl^ and ^alkenyl^ are as defined above. In some embodiments, the alkyl component in alkylamino or dialkylamino groups will include C1-C12, C1-C10, C1-C8, C1-C6or C1-C3alkyl groups. In some embodiments, the alkenyl component in alkenylamino or dialkenylamino groups will include C1-C12, C1-C10, C1-C8, C1-C6or C1-C3alkenyl groups.

[0086] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylamino, or dialkylamino. In various embodiments, R1is H, OH, O- alkyl, or O-alkenyl. In various embodiments, R1is H, OH or O-alkyl. In such embodiments, the alkyl groups may be preferably C1-6alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups.

[0087] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R1is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, R1is H, OH and OMe.

[0088] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylamino, or dialkylamino. In various embodiments, R2is H, OH, O- alkyl, or O-alkenyl. In various embodiments, R2is H, OH or O-alkyl. In such embodiments, the alkyl groups may be preferably C1-6 alkyl groups and the alkenyl groups may be preferably C2-6 alkenyl groups. More preferably, the alkyl groups may be C1-3 alkyl groups and the alkenyl groups may be preferably C2-3 alkenyl groups.

[0089] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, R2is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R2is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, R2is H, OH or OMe.

[0090] In various embodiments of the compound of Formula (I), m is an integer from 0 to 4. Thus, in various embodiments, m may be 0, 1, 2, 3, or 4. In various embodiments, m is an integer from 1 to 4, such as 1, 2, 3, or 4. In various embodiments, m is an integer from 0 to 3, such as 0, 1, 2, or 3. In various embodiments, m is an integer from 1 to 3, such as 1, 2, or 3. In other embodiments, m is an integer from 2 to 4, such as 2, 3, or 4. In some embodiments, m is 2 or 3. When m is 2, in various embodiments the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0091] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 1 to 4 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 1 to 4 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 1 to 4 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 1 to 4 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylamino, or C1-6dialkylamino. In various embodiments, m is 1 to 4 and R1is H, OH, O-C1-6alkyl, or O-C2-6alkenyl. In various embodiments, m is 1 to 4 and R1is H, OH or O- C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 1 to 4 and R1is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, m is 1 to 4 and each R1is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 1 to 4 and R1is H, OH and OMe.

[0092] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 2 or 3 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1- 6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2- 6dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-6alkyl, O-C2- 6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-6alkyl, O-C2- 6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylamino, or C1-6dialkylamino. In various embodiments, m is 2 or 3 and R1is H,OH, O-C1-6alkyl, or O-C2-6alkenyl. In various embodiments, m is 2 or 3 and R1is H, OH or O- C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 2 or 3 and R1is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, m is 2 or 3 and each R1is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 2 or 3 and R1is H, OH and OMe. In any of the foregoing embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0093] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 2 or 3 and R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2-3dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2-3dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2-3dialkenylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylamino, or C1-3dialkylamino. In various embodiments, m is 2 or 3 and R1is H, OH, O-C1-3alkyl, or O-C2-3alkenyl. In various embodiments, m is 2 or 3 and R1is H, OH or O- C1-3alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, m is 2 or 3 and R1is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, m is 2 or 3 and each R1is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 2 or 3 and R1is H, OH and OMe. In any of the foregoing embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0094] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, m is 1 to 4 and R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1- 6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2- 6dialkenylamino. In various embodiments, m is 1 to 4 and R2is H, OH, O-C1-6alkyl, O-C2- 6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 1 to 4 and R2is H, OH, O-C1-6alkyl, O-C2- 6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 1 to 4 and R2is H, OH, O-C1-6alkyl, O-C2- 6alkenyl, C1-6alkylamino, or C1-6dialkylamino. In various embodiments, m is 1 to 4 and R2is H, OH, O-C1-6alkyl, or O-C2-6alkenyl. In various embodiments, m is 1 to 4 and R2is H, OH or O-C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, m is 1 to 4 and R2is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R2is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 1 to 4 and R2is H, OH or OMe. In any of the foregoing embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0095] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, m is 2 or 3 and R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino or C2-6dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylamino, or C1-6dialkylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-6alkyl, or O-C2-6alkenyl. In various embodiments, m is 2 or 3 and R2is H, OH or O- C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, m is 2 or 3 and R2is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R2is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 2 or 3 and R2is H, OH or OMe. In any of the foregoing embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0096] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, m is 2 or 3 and R2is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1- 3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2- 3dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-3alkyl, O-C2- 3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2-3dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-3alkyl, O-C2- 3alkenyl, C1-3alkylthio, C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino or C2-3dialkenylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-3alkyl, O-C2- 3alkenyl, C1-3alkylamino, or C1-3dialkylamino. In various embodiments, m is 2 or 3 and R2is H, OH, O-C1-3alkyl, or O-C2-3alkenyl. In various embodiments, m is 2 or 3 and R2is H, OH or O- C1-3alkyl. In various embodiments of the compound of Formula (I) wherein (i) R1is an optionallysubstituted phenyl group, m is 2 or 3 and R2is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R2is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, m is 2 or 3 and R2is H, OH or OMe. In any of the foregoing embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0097] In various embodiments, each R4is independently selected from OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, each R4is independently selected from OH and O-alkyl. In any of the foregoing embodiments, m may be an integer from 0 to 4, an integer from 1 to 4, an integer from 0 to 3, or an integer from 1 to 3. In any of the foregoing embodiments, m may be 2 or 3. When m is 2, in various embodiments the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0098] In various embodiments m is 1 to 4 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, m is 1 to 4 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, m is 1 to 4 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, m is 1 to 4 and each R4is independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, m is 1 to 4 and each R4is independently selected from OH and O-alkyl.

[0099] In various embodiments m is 2 or 3 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, m is 2 or3 and each R4is independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, m is 2 or 3 and each R4is independently selected from OH and O-alkyl.

[0100] In any of the foregoing embodiments, the alkyl groups may be preferably C1-6 alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups. For instance, in various embodiments m is 2 or 3 and each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylamino, and C1-6dialkylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-6alkyl, and O- C2-6alkenyl. In various embodiments, m is 2 or 3 and each R4is independently selected from OH and O-C1-6alkyl. In any of the foregoing embodiments, when m is 2, the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0101] In various embodiments, each R4is independently selected from OH, O-C1-3alkyl, O- C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1- 3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1- 3alkylthio, C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2- 3dialkenylamino. In various embodiments, each R4is independently selected from OH, O-C1- 3alkyl, O-C2-3alkenyl, C1-3alkylamino, and C1-3dialkylamino. In various embodiments, each R4is independently selected from OH, O-C1-3alkyl, and O-C2-3alkenyl. In various embodiments, each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoing embodiments, m may be an integer from 0 to 4, an integer from 1 to 4, an integer from 0 to 3, or an integer from 1 to 3. In any of the foregoing embodiments, m may be 2 or 3.

[0102] In various embodiments m is 2 or 3 and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In variousembodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-3alkyl, O-C2- 3alkenyl, C1-3alkylamino, and C1-3dialkylamino. In various embodiments, m is 2 or 3 and each R4is independently selected from OH, O-C1-3alkyl, and O-C2-3alkenyl. In various embodiments, m is 2 or 3 and each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoing embodiments, when m is 2, the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0103] In various embodiments, each R4is independently selected from OH, OMe, methylthio, methylamino, and dimethylamino. In various embodiments, each R4is independently selected from OH, OMe, methylamino, and dimethylamino. In some embodiments, each R4is independently selected from OH and OMe. In various embodiments, m may be 2 or 3 and each R4is independently selected from OH, OMe, methylamino, and dimethylamino. In some embodiments, m is 2 or 3 and each R4is independently selected from OH and OMe. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0104] Any of the embodiments of R4disclosed herein above may be combined with the embodiments of m, R1and / or R2disclosed herein.

[0105] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino, and each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2- 6dialkenylamino. In various embodiments, wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1- 3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino.

[0106] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-6alkyl, and each R4is independently selected from OH and O-C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-3alkyl; and each R4is independently selected from OH and O-C1-3alkyl. In various embodiments wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or OMe; and each R4is independentlyselected from OH and OMe. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0107] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino, and each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino. In various embodiments wherein (i) R1is an optionally substituted phenyl group R2is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino. In various embodiments wherein (i) R1is an optionally substituted phenyl group, R2is H, OH or O-C1-6alkyl; and each R4is independently selected from OH and O-C1-6alkyl. In various embodiments, R2is H, OH or O-C1-3alkyl; and each R4is independently selected from OH and O-C1-3alkyl. In various embodiments wherein (i) R1is an optionally substituted phenyl group, R2is H, OH or OMe; and each R4is independently selected from OH and OMe. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0108] In various embodiments of the compound of Formula (I), the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O- alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, O-alkyl,and O-alkenyl. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH and O-alkyl.

[0109] In any of such embodiments, the alkyl groups may be preferably C1-6 alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups.

[0110] In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, OMe, methylthio, methylamino, and dimethylamino. In various embodiments, the optional substituents of the phenyl groups are independently selected from OH, OMe, methylamino, and dimethylamino. In some embodiments, the optional substituents of the phenyl groups are independently selected from OH and OMe.

[0111] In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two of the groups disclosed herein. For example, in various embodiments the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, O- alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups independently selected from OH and O-alkyl. In some embodiments, the phenyl groups are substituted by one or two groups independently selected from OH and O-alkyl. In some embodiments, the phenyl groups are substituted by one group independently selected from OH and O-alkyl.

[0112] In any of such embodiments, the alkyl groups may be preferably C1-6 alkyl groups and the alkenyl groups may be preferably C2-6 alkenyl groups. More preferably, the alkyl groups may be C1-3 alkyl groups and the alkenyl groups may be preferably C2-3 alkenyl groups.

[0113] In some embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, or 1 to 3 or one or two groups independently selected from OH, OMe, methylthio, methylamino, and dimethylamino. In various embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, or 1 to 3 or one or two groups independently selected from OH, OMe, methylamino, and dimethylamino. In some embodiments, the phenyl groups are substituted by 1 to 5, 1 to 4, or 1 to 3 or one or two groups independently selected from OH and OMe.

[0114] In preferred embodiments the phenyl groups are substituted by one or two groups as defined in the above embodiments.

[0115] In any of the foregoing embodiments wherein the phenyl groups are substituted by two groups as defined herein above, said groups may be at the C-3^ and C-4^ positions of the phenyl ring. For example, in various embodiments the phenyl groups are substituted at the C- 3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1- 6alkylamino, and C1-6dialkylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-6alkyl, and O-C2-6alkenyl. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH and O-C1-6alkyl. In further embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2- 3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1- 3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio,C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylamino, and C1-3dialkylamino. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH, O-C1-3alkyl, and O-C2-3alkenyl. In various embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH and O-C1-3alkyl. In some embodiments, the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring by two groups independently selected from OH and OMe.

[0116] In any of the foregoing embodiments wherein the phenyl groups are substituted by one group as defined herein above, said group may in further embodiments be at the C-4^ position of the phenyl ring. For example, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1-6alkylthio, C2-6alkenylthio, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino and C2-6dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-6alkyl, O-C2-6alkenyl, C1- 6alkylamino, and C1-6dialkylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-6alkyl, and O-C2- 6alkenyl. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH and O-C1-6alkyl. In further embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1- 3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylthio, C2-3alkenylthio, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino and C2-3dialkenylamino. In various embodiments, the phenyl groups are substituted at the C- 4^ position of the phenyl ring by one group selected from OH, O-C1-3alkyl, O-C2-3alkenyl, C1-3alkylamino, and C1-3dialkylamino. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH, O-C1-3alkyl, and O-C2- 3alkenyl. In various embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH and O-C1-3alkyl. In some embodiments, the phenyl groups are substituted at the C-4^ position of the phenyl ring by one group selected from OH and OMe.

[0117] Any of the embodiments of the optionally substituted phenyl group disclosed herein above may be combined with the embodiments of m, R1, R2and / or R4disclosed herein.

[0118] In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino; each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino, and the optional substituents of the phenyl groups are independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino; each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and the optional substituents of the phenyl groups are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-6alkyl; each R4is independently selected from OH and O-C1-6alkyl, and the optional substituents of the phenyl groups are independently selected from OH and O-C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-3alkyl; each R4is independently selected from OH and O-C1-3alkyl, and the optional substituents of the phenyl groups are independently selected from OH and O-C1-3alkyl. In various embodiments wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or OMe; each R4is independently selected from OH and OMe, and the optional substituents of the phenyl groups are independently selected from OH and OMe. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C-7 positions ofthe fused ring. In any of the foregoing embodiments, the phenyl groups may be substituted by 1 to 5, 1 to 4, 1 to 3, or one or two groups according to the embodiments disclosed herein. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0119] In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, R2is H, OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino; each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino, and the optional substituents of the phenyl groups are independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group, R2is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino; each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and the optional substituents of the phenyl groups are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R1is an optionally substituted phenyl group; R2is H, OH or O-C1-6alkyl; each R4is independently selected from OH and O-C1-6alkyl, and the optional substituents of the phenyl groups are independently selected from OH and O-C1-6alkyl. In various embodiments, R2is H, OH or O-C1-3alkyl; each R4is independently selected from OH and O-C1-3alkyl, and the optional substituents of the phenyl groups are independently selected from OH and O-C1-3alkyl. In various embodiments wherein (i) R1is an optionally substituted phenyl group, R2is H, OH or OMe; each R4is independently selected from OH and OMe, and the optional substituents of the phenyl groups are independently selected from OH and OMe. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C-7 positions of the fused ring. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0120] In various embodiments of the compound of Formula (I), a double bond is not present between positions C-2 and C-3 of the fused ring. Such embodiments may be combined with any of the embodiments of m, R1, R2, R3and the optional substituents of the phenyl groups disclosed herein.

[0121] In various embodiments a double bond is not present between positions C-2 and C-3 of the fused ring, R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino; R2is an optionally substituted phenyl group wherein the optional substituents of the phenyl group are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino; and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino. In various embodiments a double bond is not present between positions C-2 and C-3 of the fused ring, R1is H, OH or O-C1-3alkyl; R2is an optionally substituted phenyl group wherein the optional substituents of the phenyl group are independently selected from OH and O-C1-3alkyl; and each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoing embodiments, the C1-3alkyl may be methyl. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C- 7 positions of the fused ring. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0122] In various embodiments a double bond is not present between positions C-2 and C-3 of the fused ring, R1is an optionally substituted phenyl group, wherein the optional substituents of the phenyl group are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1- 3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2- 3dialkenylamino; R2is H, OH, O-C1-3alkyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1- 3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino. In various embodiments a double bond is not present between positions C-2 and C-3 of the fused ring, R1is an optionally substituted phenyl group, wherein the optional substituents of the phenyl group are independently selected from OH, and O-C1-3alkyl; R2is H, OH, or O-C1-3alkyl, and each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoingembodiments, the C1-3alkyl may be methyl. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C- 7 positions of the fused ring. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0123] In other embodiments, a double bond is present between positions C-2 and C-3 of the fused ring. Such embodiments may be combined with any of the embodiments of m, R1, R2, R3and the optional substituents of the phenyl groups disclosed herein.

[0124] In various embodiments a double bond is present between positions C-2 and C-3 of the fused ring, R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino; R2is an optionally substituted phenyl group wherein the optional substituents of the phenyl group are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino; and each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino. In various embodiments a double bond is present between positions C-2 and C-3 of the fused ring, R1is H, OH, or O-C1-3alkyl; R2is an optionally substituted phenyl group wherein the optional substituents of the phenyl group are independently selected from OH and O-C1-3alkyl; and each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoing embodiments, the C1-3alkyl may be methyl. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C- 7 positions of the fused ring. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0125] In various embodiments a double bond is present between positions C-2 and C-3 of the fused ring, R1is an optionally substituted phenyl group, wherein the optional substituents of the phenyl group are independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1- 3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2- 3dialkenylamino; R2is H, OH, O-C1-3alkyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and each R4isindependently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1-3dialkylamino, C2-3alkenylamino, and C2-3dialkenylamino. In various embodiments a double bond is present between positions C-2 and C-3 of the fused ring, R1is an optionally substituted phenyl group, wherein the optional substituents of the phenyl group are independently selected from OH and O-C1-3alkyl; R2is H, OH or O-C1-3alkyl, and each R4is independently selected from OH and O-C1-3alkyl. In any of the foregoing embodiments, the C1-3alkyl may be methyl. In any of the foregoing embodiments, m may be 2 or 3. In such embodiments, when m is 2 the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups are at the C-5, C-6, C-7 positions of the fused ring. Where the phenyl groups are substituted by one group, in various embodiments the phenyl groups are substituted at the C-4^ position of the phenyl ring. Where the phenyl groups are substituted by two groups, in various embodiments the phenyl groups are substituted at the C-3^ and C-4^ positions of the phenyl ring.

[0126] In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group. In such embodiments, the compound of Formula (I) may be a compound of Formula (Ia):wherein each of R1, R3, R4and m may be as defined according to any of the embodiments disclosed herein and n is an integer from 0 to 5.

[0127] In various embodiments, m is an integer from 0 to 4. In any of the foregoing embodiments, m may be 0, 1, 2, 3, or 4. In various embodiments, m is an integer from 1 to 4, such as 1, 2, 3, or 4. In various embodiments, m is an integer from 0 to 3, such as 0, 1, 2, or 3. In various embodiments, m is an integer from 1 to 3, such as 1, 2, or 3. In other embodiments, m is an integer from 2 to 4, such as 2, 3, or 4. In some embodiments, m is 2 or 3. When m is 2, in various embodiments the R4groups may be at the C-5 and C-7 positionsof the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C- 6, C-7 positions of the fused ring.

[0128] In various embodiments of the compound of Formula (Ia), n is an integer from 0 to 5. Thus, n may be 0, 1, 2, 3, 4, or 5. In various embodiments, n is an integer from 1 to 5, such as 1, 2, 3, 4, or 5. In various embodiments, n is an integer from 0 to 4, such as 0, 1, 2, 3, or 4. In various embodiments, n is an integer from 1 to 4, such as 1, 2, 3, or 4. In various embodiments, n is an integer from 0 to 3, such as 0, 1, 2 or 3. In various embodiments, n is an integer from 1 to 3, such as 1, 2, or 3. In various embodiments, n is an integer from 0 to 2, such as 0, 1, or 2. In various embodiments, n is an 1 or 2. In some embodiments, n is 2. In such embodiments, the R3groups may be at the C-3^ and C-4^ positions of the phenyl group.

[0129] In various embodiments of the compound of Formula (Ia), m is 2 and n is 1. In various embodiments, m is 3 and n is 1. In various embodiments, m is 2 and n is 2. In various embodiments, m is 3 and n is 2.

[0130] In various embodiments of the compound of Formula (Ia), m is 2, the R4groups are at the C-5 and C-7 positions of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. In various embodiments of the compound of Formula (Ia), m is 2, the R4groups are at the C-5 and C-7 positions of the fused ring, n is 2, and the R3groups are at the C-3^ and C-4^ positions of the phenyl group.

[0131] In various embodiments of the compound of Formula (Ia), m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. In various embodiments of the compound of Formula (Ib), m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 2, and the R3groups are at the C-3^ and C-4^ positions of the phenyl group.

[0132] In some embodiments, n is 1. In such embodiments, the R3group may in further embodiments be at the C-4^ position of the phenyl group. Thus, in some embodiments, the compound of Formula (Ia) may be a compound of Formula (Iaa):

[0133] In various embodiments of the compound of Formula (Iaa), each of R1, R3, R4and m may be as defined in any of the embodiments disclosed herein.

[0134] In various embodiments of the compound of Formula (Ia), a double bond is present between positions C-2 and C-3 of the fused ring. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iab):Formula (Iab) wherein each of R1, R3, R4, m, and n may be as defined in any of the embodiments disclosed herein.

[0135] In various embodiments of the compound of Formula (Ia), a double bond is present between positions C-2 and C-3 of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iac):wherein each of R1, R3, R4, and m may be as defined according to any of the embodiments disclosed herein.

[0136] In various embodiments of the compound of Formula (Ia), m is 2 and the R4groups are at the C-5 and C-7 positions of the fused ring. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iad):Formula (Iad) wherein each of R1, R3, R4, and n may be as defined in any of the embodiments disclosed herein.

[0137] In various embodiments of the compound of Formula (Ia), a double bond is present between positions C-2 and C-3 of the fused ring, m is 2, and the R4groups are at the C-5 and C-7 positions of the fused ring. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iae):Formula (Iae) wherein each of R1, R3, R4, and n may be as defined according to any of the embodiments disclosed herein.

[0138] In various embodiments of the compound of Formula (Ia), m is 2, the R4groups are at the C-5 and C-7 positions of the fused ring, n is 1 and the R3group is at the C-4^ position of the phenyl group. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iaf):wherein each of R1, R3, and R4may be as defined according to any of the embodiments disclosed herein.

[0139] In various embodiments of the compound of Formula (Ia), a double bond is present between positions C-2 and C-3 of the fused ring, m is 2, the R4groups are at the C-5 and C- 7 positions of the fused ring, n is 1 and the R3group is at the C-4^ position of the phenyl group. Thus, in various embodiments, the compound of Formula (Ia) is a compound of Formula (Iag):wherein each of R1, R3, and R4may be as defined according to any of the embodiments disclosed herein.

[0140] In various embodiments of the compound of Formula (Ia), m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. In further embodiments, m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 1, the R3group is at the C-4^ position of the phenyl group, and a double bond is present between positions C-2 and C-3 of the fused ring. Thus, in various embodiments the compound of Formula (Ia) is a compound of Formula (Iah):wherein each of R1, R3, and R4may be as defined according to any of the embodiments disclosed herein.

[0141] In any of the foregoing embodiments where the double bond between positions C-2 and C-3 of the fused ring is absent, the compound may be in the form of a racemic or scalemicmixture. In such scalemic mixtures, the S-enantiomer may be in excess. The enantiomeric excess is not necessarily limited. In various embodiments, the S-enantiomer may be present in an enantiomeric excess of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[0142] In some embodiments of the compound of Formula (I), R1is an optionally substituted phenyl group; R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and a double bond is present between positions C-2 and C-3 of the fused ring. In such embodiments, the compound of Formula (I) may be a compound of Formula (Ib):wherein each of R2, R3, R4and m may be as defined according to any of the embodiments disclosed herein and n is an integer from 0 to 5.

[0143] In various embodiments of the compound of Formula (Ib), m is an integer from 0 to 4. Thus, in various embodiments, m may be 0, 1, 2, 3, or 4. In various embodiments, m is an integer from 1 to 4, such as 1, 2, 3, or 4. In various embodiments, m is an integer from 0 to 3, such as 0, 1, 2, or 3. In various embodiments, m is an integer from 1 to 3, such as 1, 2, or 3. In other embodiments, m is an integer from 2 to 4, such as 2, 3, or 4. In some embodiments, m is 2 or 3. When m is 2, in various embodiments the R4groups may be at the C-5 and C-7 positions of the fused ring. When m is 3, in various embodiments the R4groups may be at the C-5, C-6, C-7 positions of the fused ring.

[0144] In various embodiments of the compound of Formula (Ib), n is an integer from 0 to 5. Thus, n may be 0, 1, 2, 3, 4, or 5. In various embodiments, n is an integer from 1 to 5, such as 1, 2, 3, 4, or 5. In various embodiments, n is an integer from 0 to 4, such as 0, 1, 2, 3, or 4. In various embodiments, n is an integer from 1 to 4, such as 1, 2, 3, or 4. In various embodiments, n is an integer from 0 to 3, such as 0, 1, 2 or 3. In various embodiments, n isan integer from 1 to 3, such as 1, 2, or 3. In various embodiments, n is an integer from 0 to 2, such as 0, 1, or 2. In various embodiments, n is an 1 or 2.

[0145] In various embodiments of the compound of Formula (Ib), m is 2 and n is 1. In various embodiments, m is 3 and n is 1. In various embodiments, m is 2 and n is 2. In various embodiments, m is 3 and n is 2.

[0146] In various embodiments of the compound of Formula (Ib), n is 2 and the R3groups are at the C-3^ and C-4^ positions of the phenyl group.

[0147] In various embodiments of the compound of Formula (Ib), m is 2, the R4groups are at the C-5 and C-7 positions of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. In various embodiments of the compound of Formula (Ib), m is 2, the R4groups are at the C-5 and C-7 positions of the fused ring, n is 2, and the R3groups are at the C-3^ and C-4^ positions of the phenyl group.

[0148] In various embodiments of the compound of Formula (Ib), m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 1, and the R3group is at the C-4^ position of the phenyl group. In various embodiments of the compound of Formula (Ib), m is 3, the R4groups are at the C-5, C-6, C-7 positions of the fused ring, n is 2, and the R3groups are at the C-3^ and C-4^ positions of the phenyl group.

[0149] In various embodiments of the compound of Formula (Ib), n is 1 and the R3group is at the C-4^ position of the phenyl group. Thus, in various embodiments, the compound of Formula (Ib) is a compound of Formula (Iba):wherein each of R2, R3, R4, and m may be as defined according to any of the embodiments disclosed herein.

[0150] In various embodiments of the compound of Formula (Ib), n is 1, the R3group is at the C-4^ position of the phenyl group, m is 2 and the R4groups are at the C-5 and C-7 positions of the fused ring. Thus, in various embodiments, the compound of Formula (Ib) is a compound of Formula (Ibb):Formula (Ibb) wherein each of R2, R3, R4, and m may be as defined above.

[0151] In further embodiments of the Compound of Formula (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag) or (Iah), R1is OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R1is H, OH, O-alkyl, O-alkenyl, alkylamino, or dialkylamino. In various embodiments, R1is H, OH, O- alkyl, or O-alkenyl. In various embodiments, R1is H, OH or O-alkyl.

[0152] In any of such embodiments, the alkyl groups may be preferably C1-6alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups.

[0153] In various embodiments of the Compound of Formula (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag) or (Iah), R1is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R1is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, R1 is H, OH or OMe. In any of the foregoing embodiments, R1is H, OH or OMe; preferably wherein R1is H or OH. In some embodiments, R1is H.

[0154] In further embodiments of the Compound of Formula (Ib), (Iba), or (Ibb), R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio,NH2, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino or dialkenylamino. In various embodiments, R2is H, OH, O-alkyl, O-alkenyl, alkylamino, or dialkylamino. In various embodiments, R2is H, OH, O-alkyl, or O-alkenyl. In various embodiments, R2is H, OH or O-alkyl.

[0155] In any of such embodiments, the alkyl groups may be preferably C1-6alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups.

[0156] In various embodiments of the Compound of Formula (Ib), (Iba), or (Ibb), R2is H, OH, OMe, methylthio, methylamino, or dimethylamino. In various embodiments, each R2is H, OH, OMe, methylamino, or dimethylamino. In some embodiments, R2is H, OH or OMe. In any of the foregoing embodiments, R2is H, OH or OMe; preferably wherein R2is H or OH. In some embodiments, R2is H.

[0157] In any of the foregoing embodiments of the Compound of Formula (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), or (Ibb), each R4may be independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O- alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, each R4is independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, each R4is independently selected from OH and O-alkyl. In any of such embodiments, the alkyl groups may be preferably C1-6 alkyl groups and the alkenyl groups may be preferably C2-6 alkenyl groups. More preferably, the alkyl groups may be C1-3 alkyl groups and the alkenyl groups may be preferably C2-3 alkenyl groups.

[0158] In any of the foregoing embodiments of the Compound of Formula (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), or (Ibb), each R3may be independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino. In various embodiments, each R3is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R3is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino,alkenylamino and dialkenylamino. In various embodiments, each R3is independently selected from OH, O-alkyl, O-alkenyl, alkylthio, alkenylthio, alkylamino, dialkylamino, alkenylamino and dialkenylamino. In various embodiments, each R3is independently selected from OH, O-alkyl, O-alkenyl, alkylamino, and dialkylamino. In various embodiments, each R3is independently selected from OH, O-alkyl, and O-alkenyl. In various embodiments, each R3is independently selected from OH and O-alkyl. In any of such embodiments, the alkyl groups may be preferably C1-6alkyl groups and the alkenyl groups may be preferably C2-6alkenyl groups. More preferably, the alkyl groups may be C1-3alkyl groups and the alkenyl groups may be preferably C2-3alkenyl groups.

[0159] In various embodiments, each R3is independently selected from OH, OMe, methylthio, methylamino, and dimethylamino. In various embodiments, each R3is independently selected from OH, OMe, methylamino, and dimethylamino. In some embodiments, each R3is independently selected from OH and OMe.

[0160] In any of the foregoing embodiments of the Compound of Formula (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), or (Ibb), each R4is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino, and each R3is independently selected from OH, O-C1-6alkyl, O-C2-6alkenyl, SH, C1-6alkylthio, C2-6alkenylthio, NH2, C1-6alkylamino, C1-6dialkylamino, C2-6alkenylamino, or C2-6dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1- 3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino; each R4is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1- 3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino, and each R3is independently selected from OH, O-C1-3alkyl, O-C2-3alkenyl, SH, C1-3alkylthio, C2-3alkenylthio, NH2, C1-3alkylamino, C1- 3dialkylamino, C2-3alkenylamino, or C2-3dialkenylamino. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-6alkyl; each R4is independently selected from OH and O-C1-6alkyl, and each R3is independently selected from OH and O-C1-6alkyl. In various embodiments of the compound of Formula (I) wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or O-C1-3alkyl; each R4is independently selected from OH and O-C1-3alkyl, and each R3is independently selected from OH and O-C1-3alkyl. In various embodiments wherein (i) R2is an optionally substituted phenyl group, R1is H, OH or OMe; each R4is independently selected from OH and OMe, and each R3is independently selected from OH and OMe.

[0161] In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R3is independently H or OH. In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R4is independently H or OH. In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R3and each R4is independently H or OH.

[0162] In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R3is OH. In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R4is OH. In any of the foregoing embodiments of the Compound of Formula (I), (Ia), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Ib), (Iba), or (Ibb), each R3and each R4is OH.

[0163] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin. In other embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin. The structures of various compounds of Formula (I) are set out in the following Table 1. Table 1. Exemplary embodiments of compounds of Formula (I) Flavone 2-phenylchromen-4-one Genistein 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1- benzopyran-4-one Hispidulin 5,7-Dihydroxy-2-(4-hydroxyphenyl)-6- methoxy-4H-1-benzopyran-4-oneKaempferol 3,5,7-Trihydroxy-2-(4-hydroxyphenyl)-4H- 1-benzopyran-4-one Naringenin (2S)-5,7-Dihydroxy-2-(4-hydroxyphenyl)- 2,3-dihydro-4H-1-benzopyran-4-one Quercetin 2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy- 4H-1-benzopyran-4-oneGalangin3,5,7-Trihydroxy-2-phenyl-4H-1- benzopyran-4-one

[0164] The compounds of formula (I), or derivatives thereof, may be naturally occurring or synthetically obtained. Compounds of Formula (I) as described herein are, for instance, commercially available from sources known to a person skilled in the art. The compounds may be provided in the form of a natural extract, for example a plant extract. For instance, galangin may be provided in the form of an Alpinia galanga extract, preferably an extract of Alpinia galanga rhizome. In an exemplary embodiment, the Alpinia galanga extract may contain about 8 mg / g galangin. The compounds may be obtained from natural sources, in particular plant sources. For example, the compounds may be obtained from plant extracts. In various embodiments, the compounds are isolated compounds, e.g. isolated from plant extracts. The purity of such isolated compound is not necessarily limited. In various embodiments, the purity of the isolated compound may be at least 20%, at least 30%, at least 40%, at least 50%, atleast 60%, at least 70%, at least 80%, or at least 90%. In other embodiments, the compounds may be synthetically obtained, i.e. produced by chemical synthesis. In further embodiments, the compounds may be obtained by synthetic modification of isolated compounds, e.g. isolated compounds from natural sources such as plant extracts. In yet other embodiments, the compounds may be obtained from a genetically modified organism or cells thereof. For example, genetically modified prokaryotic or eukaryotic cells or organisms. In various embodiments, the compounds may be obtained from genetically modified bacteria, yeasts, plants or plant cells. In such embodiments, the compounds are preferably isolated from the genetically modified organism. The purity of such isolated compound is not necessarily limited. In various embodiments, the purity of the isolated compound may be at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[0165] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0166] In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0167] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, naringenin and galangin. In variousembodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, naringenin, quercetin and galangin.

[0168] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, and kaempferol. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, naringenin,and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, naringenin, and quercetin.

[0169] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, hispidulin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, naringenin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from kaempferol, naringenin, quercetin and galangin.

[0170] In various embodiments, the compound of Formula (I) is selected from flavone, genistein, and hispidulin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, and kaempferol. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, genistein, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, and kaempferol. In variousembodiments, the compound of Formula (I) is selected from flavone, hispidulin, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from flavone, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, and kaempferol. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, and naringenin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, and naringenin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol, and quercetin. In various embodiments, the compound of Formula (I) is selected from hispidulin, naringenin, and quercetin. In various embodiments, the compound of Formula (I) is selected from kaempferol, naringenin, and quercetin.

[0171] In various embodiments, the compound of Formula (I) is selected from flavone, genistein and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, hispidulin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from flavone, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, hispidulin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from genistein, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from kaempferol, naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from kaempferol, quercetin and galangin. In various embodiments, the compound of Formula (I) is selected from naringenin, quercetin and galangin.

[0172] In various embodiments, the compound of Formula (I) is selected from flavone and genistein. In various embodiments, the compound of Formula (I) is selected from flavone and hispidulin. In various embodiments, the compound of Formula (I) is selected from flavone and kaempferol. In various embodiments, the compound of Formula (I) is selected from flavone and naringenin. In various embodiments, the compound of Formula (I) is selected from flavone and quercetin. In various embodiments, the compound of Formula (I) is selected from genistein and hispidulin. In various embodiments, the compound of Formula (I) is selected from genistein and kaempferol. In various embodiments, the compound of Formula (I) is selected from genistein and naringenin. In various embodiments, the compound of Formula (I) is selected from genistein and quercetin. In various embodiments, the compound of Formula (I) is selected from hispidulin and kaempferol. In various embodiments, the compound of Formula (I) is selected from hispidulin and naringenin. In various embodiments, the compound of Formula (I) is selected from hispidulin and quercetin. In various embodiments, the compound of Formula (I) is selected from kaempferol and naringenin. In various embodiments, the compound of Formula (I) is selected from kaempferol and quercetin. In various embodiments, the compound of Formula (I) is selected from naringenin and quercetin.

[0173] In various embodiments, the compound of Formula (I) is selected from flavone and galangin. In various embodiments, the compound of Formula (I) is selected from genistein and galangin. In various embodiments, the compound of Formula (I) is selected from hispidulin and galangin. In various embodiments, the compound of Formula (I) is selected from kaempferol and galangin. In various embodiments, the compound of Formula (I) is selected from naringenin and galangin. In various embodiments, the compound of Formula (I) is selected from quercetin and galangin.

[0174] In various embodiments, combinations of compounds of Formula (I) or derivatives thereof are used in the aspects described herein. For instance, in various embodiments the present disclosure provides an oral product comprising a combination of compounds of Formula (I) or derivatives thereof. Said compounds may be according to any of the embodiments described herein. The oral product may be a liquid dosage form or a solid oral product as defined herein, and may comprise the combination of compounds of Formula (I) or derivatives thereof in combination with further active ingredients. For instance, the combination of compounds of Formula (I) or derivatives thereof may be comprised in a combination of active ingredients further comprising one or more B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine,Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, and combinations thereof.

[0175] In various embodiments, the combination of compounds of Formula (I) or derivatives thereof may be comprised in a combination of active ingredients further comprising at least two of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof and saffron.

[0176] In various embodiments, the combination of compounds of Formula (I) or derivatives thereof may be comprised in a combination of active ingredients further comprising one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In various embodiments, the combination of compounds of Formula (I) or derivatives thereof may be comprised in a combination of active ingredients further comprising one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; piperine or a geometric isomer thereof; and one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof.In various embodiments, the combination comprises at least two compounds of Formula (I) or derivatives thereof. In such embodiments, the compounds of Formula (I) or derivatives thereof may be as defined according to any of the embodiments described herein. For example, the compound of Formula (I) may be a compound of Formula (Ia) and / or (Ib) according to any of the embodiments disclosed herein. The compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), and / or (Ibb) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), and / or (Iah) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iba) and / or (Ibb) according to any of the embodiments disclosed herein.

[0177] For example, in various embodiments the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0178] In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.Iious embodiments the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0179] In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises atleast two compounds selected from flavone, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, naringenin, quercetin and galangin.In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, and kaempferol. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, naringenin, and quercetin.

[0180] In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, hispidulin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, naringenin, quercetin and galangin. In various embodiments, combination comprises at least two compounds selected from kaempferol, naringenin, quercetin and galangin.In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, and hispidulin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, and kaempferol. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, genistein, andquercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, and kaempferol. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from flavone, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, and kaempferol. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, and naringenin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from genistein, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least two compounds selected from kaempferol, naringenin, and quercetin.

[0181] In various embodiments, the combination comprises at least two compounds selected from flavone, genistein and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, hispidulin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from flavone, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, hispidulin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from genistein, quercetin and galangin. In various embodiments, the combinationcomprises at least two compounds selected from hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least two compounds selected from kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least two compounds selected from naringenin, quercetin and galangin.

[0182] In various embodiments, the combination comprises flavone and genistein. In various embodiments, the combination comprises flavone and hispidulin. In various embodiments, the combination comprises flavone and kaempferol. In various embodiments, the combination comprises flavone and naringenin. In various embodiments, the combination comprises flavone and quercetin. In various embodiments, the combination comprises genistein and hispidulin. In various embodiments, the combination comprises genistein and kaempferol. In various embodiments, the combination comprises genistein and naringenin. In various embodiments, the combination comprises genistein and quercetin. In various embodiments, the combination comprises hispidulin and kaempferol. In various embodiments, the combination comprises hispidulin and naringenin. In various embodiments, the combination comprises hispidulin and quercetin. In various embodiments, the combination comprises kaempferol and naringenin. In various embodiments, the combination comprises kaempferol and quercetin. In various embodiments, the combination comprises naringenin and quercetin.

[0183] In various embodiments, the combination comprises flavone and galangin. In various embodiments, the combination comprises genistein and galangin. In various embodiments, the combination comprises hispidulin and galangin. In various embodiments, the combination comprises kaempferol and galangin. In various embodiments, the combination comprises naringenin and galangin. In various embodiments, the combination comprises quercetin and galangin.

[0184] In various embodiments, the combination comprises at least three compounds of Formula (I) or derivatives thereof. In such embodiments, the compounds of Formula (I) or derivatives thereof may be as defined according to any of the embodiments described herein. For example, the compound of Formula (I) may be a compound of Formula (Ia) and / or (Ib) according to any of the embodiments disclosed herein. The compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), and / or (Ibb) according to any of the embodiments disclosed herein. In various embodiments, thecompound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), and / or (Iah) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iba) and / or (Ibb) according to any of the embodiments disclosed herein.

[0185] For example, in various embodiments the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0186] In various embodiments the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0187] In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0188] In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone,genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from hispidulin, kaempferol, naringenin, quercetin and galangin.In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, and kaempferol. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, and naringenin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, and naringenin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, naringenin, andquercetin. In various embodiments, the combination comprises at least three compounds selected from flavone, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least three compounds selected from hispidulin, kaempferol, naringenin, and quercetin.

[0189] In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, hispidulin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, kaempferol and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, genistein, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from flavone, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from hispidulin,kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least three compounds selected from hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least three compounds selected from hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises kaempferol, naringenin, quercetin and galangin.In various embodiments, the combination comprises flavone, genistein, and hispidulin. In various embodiments, the combination comprises flavone, genistein, and kaempferol. In various embodiments, the combination comprises flavone, genistein, and naringenin. In various embodiments, the combination comprises flavone, genistein, and quercetin. In various embodiments, the combination comprises flavone, hispidulin, and kaempferol. In various embodiments, the combination comprises flavone, hispidulin, and naringenin. In various embodiments, the combination comprises flavone, hispidulin, and quercetin. In various embodiments, the combination comprises flavone, kaempferol, and naringenin. In various embodiments, the combination comprises flavone, kaempferol, and quercetin. In various embodiments, the combination comprises flavone, naringenin, and quercetin. In various embodiments, the combination comprises genistein, hispidulin, and kaempferol. In various embodiments, the combination comprises genistein, hispidulin, and naringenin. In various embodiments, the combination comprises genistein, hispidulin, and quercetin. In various embodiments, the combination comprises genistein, kaempferol, and naringenin. In various embodiments, the combination comprises genistein, kaempferol, and quercetin. In various embodiments, the combination comprises genistein, naringenin, and quercetin. In various embodiments, the combination comprises hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises kaempferol, naringenin, and quercetin.

[0190] In various embodiments, the combination comprises flavone, genistein and galangin. In various embodiments, the combination comprises flavone, hispidulin and galangin. In various embodiments, the combination comprises flavone, kaempferol and galangin. In various embodiments, the combination comprises flavone, naringenin and galangin. In various embodiments, the combination comprises flavone, quercetin and galangin. In various embodiments, the combination comprises genistein, hispidulin and galangin. In various embodiments, the combination comprises genistein, kaempferol and galangin. In various embodiments, the combination comprises genistein, naringenin and galangin. In various embodiments, the combination comprises genistein, quercetin and galangin. In various embodiments, the combination comprises hispidulin, kaempferol and galangin. In various embodiments, the combination comprises hispidulin, naringenin and galangin. In variousembodiments, the combination comprises hispidulin, quercetin and galangin. In various embodiments, the combination comprises kaempferol, naringenin and galangin. In various embodiments, the combination comprises kaempferol, quercetin and galangin. In various embodiments, the combination comprises naringenin, quercetin and galangin.In various embodiments, the combination comprises at least four compounds of Formula (I) or derivatives thereof. In such embodiments, the compounds of Formula (I) or derivatives thereof may be as defined according to any of the embodiments described herein. For example, the compound of Formula (I) may be a compound of Formula (Ia) and / or (Ib) according to any of the embodiments disclosed herein. The compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), and / or (Ibb) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), and / or (Iah) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iba) and / or (Ibb) according to any of the embodiments disclosed herein.

[0191] For example, in various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0192] In various embodiments the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0193] In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol, and quercetin. In variousembodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least four compounds selected from flavone, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0194] In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from flavone, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least four compounds selected from hispidulin, kaempferol, naringenin, quercetin and galangin.In various embodiments, the combination comprises flavone, genistein, hispidulin, and kaempferol. In various embodiments, the combination comprises flavone, genistein, hispidulin, and naringenin. In various embodiments, the combination comprises flavone, genistein, hispidulin, and quercetin. In various embodiments, the combination comprises flavone, genistein,kaempferol, and naringenin. In various embodiments, the combination comprises flavone, genistein, kaempferol, and quercetin. In various embodiments, the combination comprises flavone, genistein, naringenin, and quercetin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises flavone, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises flavone, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises hispidulin, kaempferol, naringenin, and quercetin.

[0195] In various embodiments, the combination comprises flavone, genistein, hispidulin and galangin. In various embodiments, the combination comprises flavone, genistein, kaempferol and galangin. In various embodiments, the combination comprises flavone, genistein, naringenin and galangin. In various embodiments, the combination comprises flavone, genistein, quercetin and galangin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises flavone, hispidulin, naringenin and galangin. In various embodiments, the combination comprises flavone, hispidulin, quercetin and galangin. In various embodiments, the combination comprises flavone, kaempferol, naringenin and galangin. In various embodiments, the combination comprises flavone, kaempferol, quercetin and galangin. In various embodiments, the combination comprises flavone, naringenin, quercetin and galangin. In various embodiments, the combination comprises from genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises kaempferol, naringenin, quercetin and galangin.

[0196] In various embodiments, the combination comprises at least five compounds of Formula (I) or derivatives thereof. In such embodiments, the compounds of Formula (I) or derivatives thereof may be as defined according to any of the embodiments described herein. For example, the compound of Formula (I) may be a compound of Formula (Ia) and / or (Ib) according to any of the embodiments disclosed herein. The compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), and / or (Ibb) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), and / or (Iah) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iba) and / or (Ibb) according to any of the embodiments disclosed herein.

[0197] For example, in various embodiments the combination comprises at least five compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0198] In various embodiments the combination comprises at least five compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises at least five compounds selected from flavone, genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises at least five compounds selected from flavone, genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least five compounds selected from flavone, genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least five compounds selected from flavone, hispidulin, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises at least five compounds selected from genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0199] In various embodiments, the combination comprises flavone, genistein, hispidulin, kaempferol and galangin. In various embodiments, the combination comprises flavone, genistein, hispidulin, naringenin and galangin. In various embodiments, the combination comprises flavone, genistein, hispidulin, quercetin and galangin. In various embodiments, the combination comprises flavone, genistein, kaempferol, naringenin and galangin. In various embodiments, the combination comprises flavone, genistein, kaempferol, quercetin and galangin. In various embodiments, the combination comprises flavone, genistein, naringenin, quercetin and galangin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol, quercetin and galangin. In various embodiments,the combination comprises flavone, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises flavone, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, naringenin and galangin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, quercetin and galangin. In various embodiments, the combination comprises genistein, hispidulin, naringenin, quercetin and galangin. In various embodiments, the combination comprises genistein, kaempferol, naringenin, quercetin and galangin. In various embodiments, the combination comprises hispidulin, kaempferol, naringenin, quercetin and galangin.

[0200] In various embodiments the combination comprises at least five compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises flavone, genistein, hispidulin, kaempferol, and naringenin. In various embodiments, the combination comprises flavone, genistein, hispidulin, kaempferol, and quercetin. In various embodiments, the combination comprises flavone, genistein, hispidulin, naringenin, and quercetin. In various embodiments, the combination comprises flavone, genistein, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises flavone, hispidulin, kaempferol, naringenin, and quercetin. In various embodiments, the combination comprises genistein, hispidulin, kaempferol, naringenin, and quercetin.

[0201] In some embodiments, the combination comprises at least six compounds of Formula (I) or derivatives thereof. In such embodiments, the compounds of Formula (I) or derivatives thereof may be as defined according to any of the embodiments described herein. For example, the compound of Formula (I) may be a compound of Formula (Ia) and / or (Ib) according to any of the embodiments disclosed herein. The compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iba), and / or (Ibb) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), and / or (Iah) according to any of the embodiments disclosed herein. In various embodiments, the compound of Formula (I) may be a compound of Formula (Iba) and / or (Ibb) according to any of the embodiments disclosed herein.

[0202] For example, in some embodiments the combination comprises flavone, genistein, hispidulin, kaempferol, naringenin, and quercetin. In some embodiments, the combination comprises at least six compounds selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin and galangin.

[0203] As used herein, the term ^derivative^ includes salts and / or solvates (including hydrates).

[0204] Examples of salts of the compound of Formula (I) and embodiments thereof described herein include suitable acid addition or base salts thereof. Suitable salts include pharmaceutically acceptable salts, a review of which is found in Berge et al, J Pharm Sci, 66, 1-19 (1977). Suitable acid addition salts include carboxylate salts (e.g. formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, - hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate salts), halide salts (e.g. chloride, bromide or iodide salts), sulfonate salts (e.g. benzenesulfonate, methyl-, bromo- or chloro- benzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2- naphthalene-sulfonate or 1,5-naphthalenedisulfonate salts) or sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate or nitrate salts. Suitable base salts include metal salts, e.g. sodium, calcium, and amine salts, e.g. tromethamine.

[0205] As used herein, the term ^solvate^ includes complexes of the compound of Formula (I) with one or more solvents. For example, hydrates, wherein the solvent complexed to the compound of Formula (I) is water. Suitable solvates include but are not limited to crystalline multi-component systems in which one or more solvents are accommodated by the crystal structure in a stoichiometric or non-stoichiometric manner.

[0206] In various embodiments, the term ^derivative^ includes compounds wherein the compound of Formula (I) has been subjected to one or more chemical reactions. In various embodiments, said one or more chemical reactions comprises substitution and / or addition at the C-5, C-6, C-7, C-8, C-2^, C-3^, C-4^, C-5^, and / or C-6^ positions of the compound of Formula (I). Thus, in various embodiments the derivative of the compound of Formula (I) includes compounds wherein one or more of the C-5, C-6, C-7, C-8, C-2^, C-3^, C-4^, C-5^, and / or C-6^ positions of the compound of Formula (I) is bonded to a substituent selected from alkyl, alkenyl, halo, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, alkyl- or dialkylamino, amido, arylamino, alkoxy, aryloxy, nitro, cyano, azido, thiol, imino, sulfonic acid, sulfate, sulfonyl, sulfanyl, sulfinyl, sulfamoyl, ester, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphonic acid, phosphate,phosphonate, or any other viable functional group that does not inhibit the biological activity of the compounds of the present disclosure, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene and Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999. In the foregoing embodiments, up to 8, up to 7, up to 6, up to 5, up to 4, up to 3, up to 2, or 1 of the C-5, C-6, C-7, C-8, C-2^, C-3^, C-4^, C-5^, and / or C-6^ positions of the compound of Formula (I) may be bonded to a substituent as defined herein. In any of the foregoing embodiments, the derivative may include compounds wherein the compound of Formula (I) has been subjected to up to 5, up to 4, up to 3, up to 2, or 1 chemical reaction(s), which may comprise substitution and / or addition at the C-5, C-6, C-7, C-8, C-2^, C-3^, C-4^, C-5^, and / or C-6^ positions of the compound of Formula (I). In various embodiments, the resulting group formed by the addition / substitution reaction(s) may be selected from any of the foregoing substituents.

[0207] In various embodiments, the term ^derivative^ includes compounds wherein a hydrogen atom comprised in one or more hydroxyl (OH) groups of the compound of Formula (I) has been substituted. In such embodiments, the hydrogen atom of the hydroxyl group may be substituted to form a group selected from O-alkyl, O-alkenyl, O-acyl, sulfonyl, sulfonic acid, sulfate, and phosphate. For example, up to 8, up to 7, up to 6, up to 5, up to 4, up to 3, up to 2 or one hydroxyl groups may be modified by substituting the hydrogen atom of the hydroxyl group to form a group selected from O-alkyl, O-alkenyl, O-acyl, sulfonyl, sulfonic acid, sulfate, and phosphate. In further embodiments, the term ^derivative^ includes glycosides of the compound of Formula (I) defined herein. As used herein, the term ^glycoside^ refers to the case wherein a sugar group (glycosyl group) is bonded through its anomeric carbon to the compound of Formula (I) via a glycosidic bond. Such glycosides are known to occur naturally, but may also be obtained by chemical reaction or biosynthetically (e.g. in vitro by the use of enzymes such glycosyltransferases, or in vivo e.g. in genetically modified organisms). Exemplary and non-limiting examples of common sugar groups that may form glycosides with the compound of Formula (I) include glucose, rhamnose, galactose, xylose, arabinose, glucoronic acid, and apiose. In various embodiments, the glycoside of the compound of Formula (I) is a O-glycoside, an N-glycoside, an S-glycoside, or a C-glycoside; preferably an O-glycoside or C-glycoside, more preferably an O-glycoside. In further embodiments of the glycoside, the sugar molecule is bonded through a glycosidic bond formed from a hydroxyl group comprised in the compound of Formula (I). In further embodiments, the glycosyl group of the glycoside is bonded via a glycosidic bond at the C-5, C-6, C-7, C-8, C-2^, C-3^, C-4^, C- 5^, or C-6^ position of the compound of Formula (I). In any of the foregoing embodiments, the glycoside may comprise one or more other modifications as encompassed by the definition of^derivative^ provided herein above. In particular, salts and / or solvates (including hydrates) of the glycosides of the present disclosure are also contemplated. Oral Product

[0208] As described herein, the compound of Formula (I), a derivative thereof, or a combination thereof as defined according to any of the embodiments disclosed herein may be used in an oral product. Typically, said compound of Formula (I), a derivative thereof, or a combination thereof may be comprised in a combination of active ingredients.

[0209] Accordingly, an aspect of the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; and (b) one or more B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, and combinations thereof. In various embodiments, the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L- theanine, theobromine Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, and combinations thereof; and (c) piperine or a geometric isomer thereof.

[0210] In various embodiments, the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; and (b) two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof and saffron. In various embodiments, the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan and saffron; and (c) piperine or a geometric isomer thereof.

[0211] In various embodiments, the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and (c) one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In various embodiments, the present disclosure provides an oral product comprising a combination of active ingredients, wherein the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and (c) one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof; and (d) piperine or a geometric isomer thereof.

[0212] The oral product is configured for oral use, and thus for insertion into the user^s mouth (i.e. oral cavity). In some embodiments, the oral product is a liquid oral product, such as a liquid dosage form. In such embodiments, the term ^oral^ in connection to said liquid product means that, in normal use, said product is suited to be ingested orally by the user. For example, the product may be in the form of a beverage with a volume of 250 mL or greater, or a liquid shot with a volume of from about 1 mL to about 200 mL, preferably about 20 mL to about 100 mL.

[0213] In other embodiments, the oral product is a solid oral product e.g. a lozenge or a chew. For example, the solid oral product may be a solid oral product in chewable form. In such embodiments, the oral product is configured for oral use, and thus for insertion into the user^s mouth (i.e. oral cavity). In such embodiments, the term ^oral^ in connection to said solid oral product refers to a product which, in normal use, is suited to be ingested or placed somewhere in the oral cavity of the user. For example, the product may be placed in the mouth, e.g. chewed in the oral cavity, for example in the form of a chew or chewing gum.

[0214] In various embodiments, the oral product is a nutraceutical oral product. As used herein, the term ^nutraceutical^ refers to a food or dietary supplement that is believed to provide health benefits.

[0215] The person skilled in the art will understand that the ranges provided herein may be taken alone or combined with one or more other component ranges to provide a preferred aspect of the invention. Combination of active ingredients

[0216] The product as disclosed herein includes active ingredients. In particular, the combination of active ingredients comprises the compound of Formula (I), derivative thereof, or combination thereof as disclosed herein. The combination of active ingredients comprises suitable active ingredients that cause a biological response in a human or animal. In particular, the combination of active ingredients may comprise (a) a compound of Formula (I), a derivative thereof, or a combination thereof; and (b) one or more B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron and combinations thereof. In various embodiments, the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta- alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, and combinations thereof; and (c) piperine or a geometric isomer thereof.

[0217] In various embodiments, the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; and (b) two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof and saffron. In various embodiments, the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) two or more of: vitamin B1, vitamin B2, vitamin B6, vitamin B7, maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L- theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan and saffron; and (c) piperine or a geometric isomer thereof.

[0218] In various embodiments, the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and (c) one or more (or two or more)compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta- alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or a combination thereof. In various embodiments, the combination of active ingredients comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof; (b) one or more (or two or more) B vitamins selected from B1, B2, B6 and B7; and (c) one or more (or two or more) compound(s) selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, saffron, or a combination thereof; and (d) piperine or a geometric isomer thereof.

[0219] Each of the active ingredients may be present in an amount suitable to provide the desired biological response in a human animal. The active ingredients may be naturally occurring or synthetically obtained.

[0220] The compound of Formula (I), derivative thereof, or combination thereof may be present in any suitable amount, such as in an amount of at least about 0.0001% by weight, at least about 0.001% by weight, at least about 0.01% by weight, at least about 0.1% by weight, or at least about 1% by weight. In some embodiments, the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of no greater than about 20% by weight, no greater than about 15% by weight, no greater than about 10% by weight, no greater than about 5% by weight, or no greater than about 2% by weight of the oral product.

[0221] The compound of Formula (I), derivative thereof, or combination thereof may in various embodiments be present in an amount of from about 0.001% to about 20%, from about 0.001% to about 15%, from about 0.001% to about 10%, from about 0.001% to about 5%, from about 0.001% to about 2% by weight of the oral product.

[0222] The compound of Formula (I), derivative thereof, or combination thereof may in various embodiments be present in an amount of from about 0.0001% to about 20%, from about 0.001% to about 15%, from about 0.01% to about 10%, from about 0.1% to about 5%, or from about 1% to about 2% by weight of the oral product. In some embodiments, the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of from about 0.0001% to about 2%, from about 0.001% to about 2%, from about 0.01% to about 2%, or from about 0.1% to about 2% by weight of the oral product.

[0223] Where a combination of compounds of Formula (I) and / or derivatives thereof is used in the oral product, it will be understood that the above amounts refer to the total amount of compounds of Formula (I) and / or derivatives thereof.

[0224] The combination of active ingredients may comprise one or more B vitamins selected from B1, B2, B6 and B7. In other embodiments, the combination of active ingredients may comprise a combination of at least two B vitamins selected from vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9 and vitamin B12. Preferably the combination of B vitamins comprises vitamin B2 and vitamin B6, more preferably the combination of B vitamins further comprises one or more of vitamin B1 or vitamin B7.

[0225] The term ^B vitamins^ includes a group of eight water-soluble vitamins that have effect in cellular functioning; e.g. cell metabolism and synthesis of red blood cells. B vitamins act as coenzymes in a substantial proportion of the enzymatic processes for cellular physiological functioning. The B vitamins may generally be divided into two categories: those that act as co- enzymes for catabolic enzymatic reactions (leading to generation of energy) and those that act as co-enzymes for anabolic enzymatic reactions (leading to enhanced brain function).

[0226] B vitamins are considered to have roles in aspects of brain function and energy production. The eight water soluble B vitamins are vitamin B1 (thiamin), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (panthothenic acid or salt thereof, e.g. calcium pantothenate), vitamin B6 (pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folate or folic acid), vitamin B12 (cyanocobalamin). Vitamins B2, B3, B6, B9 and B12 have been found to support anabolic metabolism and to boost brain function. Vitamins B1, B2, B3, B5 and B7 have been found to support catabolic metabolism and to boost energy levels.

[0227] In preferred embodiments, the oral product includes at least two of the B vitamins that support anabolic metabolism. In other words, according to a first aspect, the combination of at least two B vitamins is selected from vitamins B2, B3, B6, B9 and B12. It has been found that the inclusion of at least these B vitamins may reduce perceived physical and mental fatigue as well as enhance psychological and cognitive functions. In particularly preferred embodiments, the oral product includes all five B vitamins that support anabolic metabolism. In other words, according to a first aspect, the combination of active ingredients includes a combination of vitamins B2, B3, B6, B9 and B12. Each of these B vitamins may contribute to the reduction of tiredness and fatigue, and the inclusion of all five B vitamins may lead to a synergistic effect in this regard.

[0228] In some embodiments, the combination of B vitamins consists essentially of all anabolic vitamins; i.e. a combination of vitamins B2, B3, B6, B9 and B12. In some embodiments, the combination of B vitamins consists of all anabolic vitamins; i.e. a combination of vitamins B2, B3, B6, B9 and B12. The term ^anabolic B vitamin^ refers to those B vitamins that have an effect on anabolic pathways, while the term ^catabolic B vitamin^ refers to those B vitamins that have an effect on catabolic pathways.

[0229] In some embodiments, the combination of B vitamins further comprises at least one catabolic B vitamin selected from the group consisting of vitamin B1, vitamin B5, vitamin B7 and combinations thereof.

[0230] In any such embodiments, the ratio of the total amount of anabolic B vitamins (i.e. vitamins B2, B3, B6, B9 and B12) to the total amount of catabolic B vitamins (i.e. vitamins B1, B5 and B7) may be from about 5:1 to about 1:5, preferably from about 2:1 to about 1:2 and more preferably from about 2:1 to about 1:1.

[0231] In other embodiments, the combination of B vitamins may comprise at least vitamin B1 and vitamin B2, or at least vitamin B6 and vitamin B7, or at least vitamin B1 and B6, or at least vitamin B2 and vitamin B7, preferably the combination of B vitamins may comprise at least vitamin B1, vitamin B2 and vitamin B6. In such embodiments, the combination of B vitamins may comprise at least vitamin B1, vitamin B2, vitamin B6, and vitamin B7, preferably the combination of B vitamins may consist essentially of vitamin B1, vitamin B2, and vitamin B6, and vitamin B7.

[0232] The amounts of the B vitamins included in the composition may be any amount suitable to provide the desired effect while also providing a product that is safe to consume and has reduced side effects. The total amount of B vitamins included in the combination may be any suitable amount to provide the desired effect of boosting brain function. In some embodiments, the total amount of anabolic B vitamins (i.e. the total amount of the combination of vitamins B2, B3, B6, B9 and B12) may be at least about 0.0001% by weight, preferably at least about 0.001% by weight, and more preferably at least about 0.01% by weight of the oral product. For example, the total amount of anabolic B vitamins may be from about 0.0001% to about 5% by weight of the oral product, and preferably from about 0.001% to about 1%. For example, this amount may be from about 0.01% to about 0.5% by weight of the oral product, or from about 0.05% to about 0.5% by weight of the oral product.

[0233] Where present, the total amount of catabolic B vitamins (i.e. the total amount of the combination of vitamins B1, B5 and B7) may be at least about 0.0001% by weight, preferablyat least about 0.001% by weight, and more preferably at least about 0.01% by weight of the oral product. For example, the total amount of catabolic B vitamins (e.g. where the catabolic B vitamins are vitamin B1, vitamin B2, vitamin B3, vitamin B5 and / or vitamin B7) may be from about 0.0001% to about 5% by weight of the oral product, and preferably from about 0.001% to about 1%. For example, this amount may be from about 0.01% to about 0.5% by weight of the oral product.

[0234] The total amount of B vitamins included in the combination may be any suitable amount to provide the desired effect of boosting brain function. In some embodiments, the total amount of B vitamins is from about 0.001% to about 10% by weight, and preferably from about 0.001% to about 5% by weight of the oral product. In some embodiments, the total amount of B vitamins may be from about 0.01% to about 4% by weight, such as from about 0.025% to about 3% by weight, preferably from about 0.05% to about 2% by weight of the oral product.

[0235] In some embodiments, vitamin B2 may be present in an amount of from about 1% to about 20% by weight of the total amount of B vitamin in the oral product. For example, vitamin B2 may be present in an amount of from about 5% to about 15% by weight of the total amount of B vitamin in the oral product. In other embodiments, vitamin B2 may be present in an amount of from about 1% to about 40% by weight of the total amount of B vitamin in the oral product. For example, vitamin B2 may be present in an amount of from about 10% to about 40% by weight of the total amount of B vitamin in the oral product.

[0236] In some embodiments, vitamin B3 may be present in an amount of from about 20% to about 80% by weight of the total amount of B vitamin in the oral product. For example, vitamin B3 may be present in an amount of from about 40% to about 70% by weight, and preferably from about 45% to about 60% by weight of the total amount of B vitamin in the oral product. In other embodiments, the combination of B vitamins do not include vitamin B3.

[0237] In some embodiments, vitamin B6 may be present in an amount of from about 1% to about 15% by weight of the total amount of B vitamin in the oral product. For example, vitamin B6 may be present in an amount of from about 5% to about 10% by weight of the total amount of B vitamin in the oral product. In other embodiments, vitamin B6 may be present in an amount of from about 1% to about 50% by weight of the total amount of B vitamin in the oral product. For example, vitamin B6 may be present in an amount of from about 5% to about 50% by weight of the total amount of B vitamin in the oral product.

[0238] In some embodiments, vitamin B9 may be present in an amount of from about 0.1% to about 10% by weight of the total amount of B vitamin in the oral product. For example, vitaminB9 may be present in an amount of from about 1% to about 5% by weight of the total amount of B vitamin in the oral product.

[0239] In some embodiments, vitamin B12 may be present in an amount of from about 0.01% to about 30% by weight, such as from about 0.1% to about 25% by weight, such as from about 1% to about 20% by weight of the total amount of B vitamin in the oral product. For example, vitamin B12 may be present in an amount of from about 5% to about 15% by weight of the total amount of B vitamin in the oral product.

[0240] Where present, vitamin B1 may be present in an amount of from about 1% to about 10% by weight of the total amount of B vitamin in the oral product. For example, where present, vitamin B1 may be present in an amount of from about 2.5% to about 7.5% by weight of the total amount of B vitamin in the oral product. In some embodiments, the oral product may be substantially free of (i.e. include no more than 0.0001% by weight of) vitamin B1, or may be free of (i.e. include 0%) vitamin B1. In other embodiments, vitamin B1 may be present in an amount of from about 1% to about 40% by weight of the total amount of B vitamin in the oral product. For example, vitamin B1 may be present in an amount of from about 5% to about 35% by weight of the total amount of B vitamin in the oral product.

[0241] Where present, vitamin B5 may be present in an amount of from about 1% to about 20% by weight of the total amount of B vitamin in the oral product. For example, where present, vitamin B5 may be present in an amount of from about 5% to about 15% by weight of the total amount of B vitamin in the oral product. In some embodiments, the oral product may be substantially free of vitamin B5, or may be free of vitamin B5.

[0242] Where present, vitamin B7 may be present in an amount of from about 0.01% to about 5% by weight of the total amount of B vitamin in the oral product. For example, where present, vitamin B7 may be present in an amount of from about 0.01% to about 1% by weight or about 0.01% to about 2% by weight of the total amount of B vitamin in the oral product. In some embodiments, the oral product may be substantially free of vitamin B7, or may be free of vitamin B7.

[0243] Maca or Lepidium meyenii is an edible herbaceous biennial plant of the family Brassicaceae that is native to South America. It is otherwise known as ^Peruvian ginseng^ and is mainly grown for consumption of its root. Traditionally, maca is processed by boiling, baking, and drying the root and then grinding the dried root material into powder. Various maca root powders are commercially available. It may be used for its presumed benefits including increasing fertility, boosting energy and endurance, improving mood, reducing blood pressure,and improving learning and memory. Fresh maca roots have different colours due to genetic variations. The colours include yellow, red, purple, blue, black and green. Yellow maca is the sweetest-tasting and is most commonly grown for food, while red and black maca are generally considered more medicinally potent. The maca root included in the oral product can be black maca root, yellow maca root, red maca root, or any combination thereof. The maca root may be provided in the form of an extract or in the form of a powder (e.g. a powder extract).

[0244] The maca extract is a concentrated form of maca that can be obtained by standard extraction techniques that are well known in the art. For example, maca extract may be obtained by taking dried maca root that has been cut into small pieces or, preferably, pulverized to a powder form and soaking in a solution. Although maca root can be extracted in organic solutions such as chloroform, to minimise safety concerns, it is preferable that the extraction solution is an aqueous or more preferably an aqueous / alcoholic solution, for example a water and ethanol solution. The extraction solution is usually provided in excess. Preferably, the extraction temperature is from room temperature to less than boiling temperature of the solution, such as from about 20°C up to about 100°C or from about 25°C up to about 80°C. Techniques such as sonication may be used to increase extraction efficiency. Techniques such as filtration are preferably used to reduce particulate in the maca extract. The extraction solution can then be dried, preferably to powder form, to give a concentrated maca extract. The maca root of the present invention may be a ratio of concentrated maca extract to filler. For example, a 10:1 maca root ingredient purity may be obtained by using 300 mg of concentrated maca extract to give 3 grams of maca root ingredient. The type of extract is not limited in the present disclosure.

[0245] The maca root may be present in an amount of from about 0.01% to about 20% by weight of the oral product. In some embodiments, the maca root is present in an amount of from about 0.1% to about 15% by weight of the oral product. The maca root may preferably be present in an amount of from about 0.25% to about 10% by weight of the oral product.

[0246] Ginseng is the root of plants in the genus Panax, which are characterised by the presence of unique steroid saponin phytochemicals (ginsenosides) and gintonin. The putative major active components of ginseng comprise more than 100 species specific triterpene saponins or ^ginsenosides^. Ginseng and ginseng extracts also contain a range of other potentially bioactive components, including alkaloids, phytosterols, sesquiterpenes, and polyphenols. Ginseng finds use as a dietary supplement in energy drinks or herbal teas, and in traditional medicine. The ginseng may include any suitable form of ginseng, such as Panax ginseng (Korean ginseng), Panax notoginseng (China ginseng) and Panax quinquefolius(American ginseng). The ginseng may also comprise Ashwagandha (Withania somnifera), commonly known as Indian Ginseng. The ginseng may be present in the form of ginseng extract, chopped ginseng, shredded ginseng or powdered ginseng. Preferably, the ginseng is included in the form of ginseng extract or powdered ginseng extract. The ginseng may white ginseng, fresh ginseng or red ginseng. In some embodiments, the ginseng is red ginseng, such as red ginseng extract or powdered red ginseng extract. The inclusion of ginseng has been found to be beneficial in improving the cognitive effects of the composition. Ginseng also has anti-inflammatory and antioxidant properties.

[0247] In some embodiments, the ginseng is present in an amount of from about 0.01% to about 5% by weight of the oral product, such as in an amount of from about 0.05% to about 2% by weight of the oral product. In preferred embodiments, the ginseng is present in an amount of from about 0.1% to about 1% by weight of the oral product.

[0001] Coenzyme Q10 is also known as ubiquinone-10; it is a 1,4-benzoquinone, where Q refers to the quinone chemical group and 10 refers to the number of isoprenyl chemical subunits in the tail, and has the following chemical formula:

[0002] Coenzyme Q10 or CoQ10 is a crystalline powder. It acts as an antioxidant, which protects cells from damage. It also plays an important part in the human metabolism and has been used to treat many different conditions including heart failure.

[0003] In some embodiments, Coenzyme Q10 is present in an amount of from about 0.001% to about 30% by weight of the oral product. In some embodiments, Coenzyme Q10 is present in an amount of from about 0.01% to about 20% by weight of the oral product. In some embodiments, the Coenzyme Q10 is present in an amount of from about 0.1% to about 10% by weight of the oral product. In some preferred embodiments, Coenzyme Q10 is present in an amount of from about 0.01% to about 5% by weight of the oral product, and particularly preferably from about 0.1% to about 1% by weight of the oral product.

[0248] Coenzyme Q10 may in some embodiments (e.g. where the oral product is a liquid oral dosage form) be present in an amount of from about 0.01% to about 5% by weight of the oral product. In some embodiments (e.g. where the oral product is a liquid oral dosage form), theCoenzyme Q10 is present in an amount of from about 0.1% to about 1% by weight, such as from about 0.1% to about 0.75% by weight, preferably from about 0.1% to about 0.5% by weight of the oral product.

[0249] The oral product may be caffeine-free, or may include caffeine in the combination of active ingredients. Caffeine is a central nervous system stimulant. Caffeine (1,3,7- trimethylxanthine) exists as a bitter substance, an alkaloid which is naturally found in a variety of plant species, including tea leaves, kola nuts, cocoa, guarana, and coffee beans. Once ingested, caffeine is metabolised through the liver via the cytochrome P450 enzyme system and is capable of entering all body tissues, as well as crossing the blood brain barrier. Caffeine may be used to enhance alertness, attention, cognitive performance as well as physical performance.

[0250] The caffeine may be included as a natural stimulant, meaning that it is naturally derived. By ^naturally derived^ is meant that the caffeine is in a purified form, outside its natural (e.g. botanical) matrix. For example, caffeine may be obtained by extraction and purification from botanical sources (e.g. tea). Alternatively, or in addition, the caffeine may be provided in synthetic form; i.e. obtained by chemical synthesis. The caffeine may be provided in the form of an extract or in the form of a powder (e.g. a powder extract). For example, the caffeine may be included in the form of a green tea powder extract, black tea powder extract. The caffeine may also be provided in the form of guarana seed powder extract. In some embodiments, the caffeine is present in an encapsulated form. An example of an encapsulated caffeine is Vitashure®, available from Balchem Corp., 52 Sunrise Park Road, New Hampton, NY, 10958.

[0251] The caffeine may be present in any suitable amount, such as in an amount of at least about 0.01% by weight, at least about 0.1% by weight, at least about 1% by weight, or at least 2% by weight of the oral product. In some embodiments, the caffeine may be present in an amount of no greater than about 35% by weight, no greater than about 20% by weight, no greater than about 10% by weight, or no greater than about 5% by weight of the oral product.

[0252] The caffeine may be present in an amount of from about 0.01% to about 35% by weight of the oral product. In some embodiments, the caffeine is present in an amount of from about 0.1% to about 20% by weight of the oral product. In further embodiments the caffeine may be present in an amount of from about 0.1% to about 10% by weight of the oral product. In yet further embodiments, the caffeine may be present in an amount from about 0.1% to about 5% by weight of the oral product. The caffeine may alternatively be present in an amount of from about 1% to about 35% by weight.

[0253] As discussed herein, the compound of Formula (I), derivative thereof or combination thereof has been found to provide one or more of the desirable physiological effects of caffeine while reducing / avoiding one or more of the undesirable physiological effects of caffeine. Hence, in various embodiments the compound of Formula (I), derivative thereof or combination thereof is used in the oral product as a substitute for caffeine. In such embodiments, the oral product may not comprise caffeine, i.e. it is caffeine-free.

[0254] In other embodiments, the compound of Formula (I), derivative thereof or combination thereof may be used in combination with caffeine. For example, in various embdiments, the compound of Formula (I), derivative thereof or combination thereof is used in combination with caffeine, e.g. an amount according to the embodiments disclosed herein above, to enhance one or more desirable effects and / or reduce one or more undesirable effects of the caffeine. In some embodiments, the enhancement provided by the compound of Formula (I), derivative thereof or combination thereof may be additive. In some advantageous embodiments, the enhancement provided by the compound of Formula (I), derivative thereof or combination thereof may be synergistic, that is to say greater than additive. Such synergy is not predictable or expected when two actives are used in combination.

[0255] In further embodiments, the compound of Formula (I), derivative thereof or combination thereof may be used in combination with caffeine such that the amount of caffeine can be reduced relative to an equivalent oral product that does not contain the compound of Formula (I), derivative thereof or combination, i.e. while achieving the same desired physiological effects.

[0256] Thus, in various embodiments the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of from about 0.001% to about 20%, from about 0.001% to about 15%, from about 0.001% to about 10%, or from about 0.001% to about 5% by weight of the oral product and the caffeine may be present in an amount of from about 0.1% to about 20%, from about 0.1% to about 10%, or from about 0.1% to about 5% by weight of the oral product. In various embodiments the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of from about 0.001% to about 20%, from about 0.001% to about 15%, from about 0.001% to about 10%, or from about 0.001% to about 5% by weight of the oral product and the caffeine may be present in an amount of from about 0.01% to about 20%, from about 0.01% to about 10%, or from about 0.01% to about 5% by weight of the oral product. In various embodiments the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of from about 0.01% to about 20%, from about 0.01% to about 15%, from about 0.01% to about 10%, or from about 0.01% to about 5% by weight of the oral product and the caffeine may be present in an amount offrom about 0.01% to about 20%, from about 0.01% to about 10%, or from about 0.01% to about 5% by weight of the oral product. In various embodiments the compound of Formula (I), derivative thereof, or combination thereof may be present in an amount of from about 0.1% to about 20%, from about 0.1% to about 15%, from about 0.1% to about 10%, or from about 0.1% to about 5% by weight of the oral product and the caffeine may be present in an amount of from about 0.01% to about 20%, from about 0.01% to about 10%, or from about 0.01% to about 5% by weight of the oral product.

[0257] The combination of active ingredients may further comprise vitamin C (ascorbic acid). Vitamin C acts as an antioxidant, helping to protect cells from the damage caused by free radicals. It is also used by the body to make collagen, a protein that may help wounds heal. In addition, vitamin C improves the absorption of iron from plant-based foods and helps the immune system work properly to protect the body from disease. The inclusion of vitamin C may reduce tiredness and fatigue.

[0258] The vitamin C may be present in the oral product in any suitable amount. In some embodiments, the vitamin C may be present in an amount of from about 0.01% to about 10% by weight, such as from about 0.05% to about 8% by weight, preferably in an amount of from about 0.1% to about 5% by weight of the oral product.

[0259] In some embodiments the combination of active ingredients may include beta-alanine. Beta-alanine or 3-aminopropanoic acid is a naturally occurring beta amino acid. There is evidence that beta-alanine supplements can increase energy and cognitive performance as well as prevent muscle soreness and fatigue. Beta-alanine is converted within muscle cells to carnosine which acts as a buffer for the lactic acid produced during high intensity exercise, and can thereby help delay the onset of neuromuscular fatigue.

[0260] The beta-alanine may be present in any suitable amount, such as an amount of from about 0.01% to about 60% by weight of the oral product. In some embodiments, the beta- alanine is present in an amount of from about 0.1% to about 50% by weight of the oral product. In other embodiments (for example when the oral product is in liquid dosage form), the beta- alanine is present in an amount of from about 1% to about 10% by weight of the oral product.

[0261] In some embodiments, the combination of active ingredients further comprises theacrine (1,3,7,9-tetramethyluric acid). Theacrine is a purine alkanoid found in Theobroma grandiflorum (commonly known as copoasu, a tropical rainforest tree related to cacao) and in a Chinese tea known as kucha. Theacrine shows anti-inflammatory and analgesic effects and appears to affect adenosine signaling in a manner similar to caffeine. Structurally theacrine issimilar to caffeine; it has an additional methyl group in the 9-position, and a carbamide as a result of an additional carbonyl group at the 8-position. The inclusion of theacrine may reduce tiredness and fatigue, and improve energy metabolism.

[0262] Where present, theacrine may be present in any suitable amount, such as an amount of from about 0.001% to about 30% by weight, or from about 0.01% to about 20% by weight of the oral product. The theacrine may preferably be present in an amount of from about 0.1% to about 15% by weight of the oral product. In some embodiments, theacrine is present in an amount of from about 0.05% to about 5% by weight, and preferably from about 0.05% to about 1% by weight of the oral product.

[0263] Taurine or 2-aminoethanesulfonic acid is an organic compound widely distributed in animal tissues. Taurine is known to play a role in energy metabolism. The combination of taurine with caffeine may lead to taurine neutralising some of the negative side effects that excess caffeine may cause (e.g. the jitters or increased heart rate). The inclusion of taurine may improve muscle strength and endurance, and performance during physical activity. The addition of taurine may also enhance energy metabolism.

[0264] The taurine may be present in any suitable amount, such as an amount of from about 0.001% to about 20% by weight of the oral product. In some embodiments, the taurine is present in an amount of from about 0.01% to about 10% by weight of the oral product. The taurine may preferably be present in an amount of from about 0.05% to about 5% by weight of the oral product, or from about 0.05% to about 1% by weight of the oral product.

[0265] In any of the above embodiments, the oral product may further comprise zinc or a salt thereof. In various embodiments, the zinc salt may be zinc gluconate. In various embodiments, the zinc or salt thereof, e.g. zinc gluconate, may be present in an amount of from about 0.001% to about 2% by weight of the oral product. In preferred embodiments, zinc or a salt thereof, e.g. zinc gluconate, may be present in an amount of about 0.005% to about 1% by weight of the oral product.

[0266] L-theanine is an amino acid analogue that is also referred to as L- -glutamylethylamide and N5-ethyl-L-glutamine. It is a water-soluble amino acid isolated from green tea (Camellia sinensis) that has anti-inflammatory activity, antioxidative properties andhepatoprotective effect. The inclusion of L-theanine may improve the effects of the oral producton the immune system. For example, the inclusion of L-theanine may help to regulate immune response, prevent disease, and reduce anti-oxidation stress. Studies have shown that L-theanine can enhance innate immune function by regulating the secretion of immune cytokines.

[0267] The L-theanine may be present in the oral product in any suitable amount, such as in an amount of from about 0.01% to about 15% by weight of the oral product, such as in an amount of from about 0.05% to about 10% by weight of the oral product. In preferred embodiments, the L-theanine is present in an amount of from about 0.1% to about 8% by weight of the oral product.

[0268] In some embodiments, the combination of active ingredients further comprises theobromine (also known as xantheose or 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione). Theobromine is the principal alkanoid found in Theobroma cacao (the cacao plant). It has no significant stimulant effect on the human central nervous system and compared with caffeine, is weaker in both its inhibition of cyclic nucleotide phosphodiesterases and its antagonism of adenosine receptors. Structurally theobromine is similar to caffeine; it lacks the methyl groups in the 4- and 9-position, and the carbonyl group at the 8-position. The latter means the second ring is an imidazole.

[0269] Where present, theobromine may be present in any suitable amount, such as an amount of from about 0.001% to about 10% by weight, or from about 0.01% to about 5% by weight of the oral product. The theobromine may preferably be present in an amount of from about 0.1% to about 1% by weight of the oral product. In some embodiments, theobromine is present in an amount of from about 0.05% to about 5% by weight, and preferably from about 0.05% to about 1% by weight of the oral product. Other active ingredients

[0270] In some embodiments the oral product may comprise one or more additional active ingredients. The additional active ingredients may be any suitable active ingredient that has a biological response in a human or animal. The additional active ingredient may be naturally occurring or synthetically obtained. Non-limiting examples of additional active ingredients include those falling in the categories of botanical ingredients, amino acids, nicotine components, and / or nutraceutical, and medicinal ingredients (e.g., vitamins, such as A, B1, B2, B3, B5, B6, B7, B9, B12, and / or cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD)). The additional active ingredient may comprise for example taurine, theanine, vitamins such as B vitamins (e.g. B1, B2, B3, B5, B6, B7, B9 and / or B12), vitamin A, vitamin E, or vitamin K, melatonin, gamma-aminobutyric acid (GABA), cannabinoids, or constituents, derivatives, or combinations thereof.

[0271] In some embodiments, the one or more additional active ingredients is selected from a botanical ingredient (e.g., lavender, peppermint, chamomile, basil, rosemary, ginger, maca, lemon balm, and tisanes), an amino acid (e.g., taurine, phenylalanine, tyrosine, GABA, and tryptophan), a cannabinoid, and / or a nutraceutical, or medicinal ingredient (e.g., a vitamin, such as a B vitamin).

[0272] In some embodiments, the combination of active ingredients further comprises lemon balm. Lemon balm is also referred to as Melissa officinalis and is a perennial herbaceous plant in the mint family. Lemon balm contains a complex mixture of terpenes, terpenoids, flavonoids, polyphenols, and other molecules. The lemon balm may be in the form of leaves, stems or roots from the lemon balm plant. In some embodiments, the lemon balm is included in the form of lemon balm leaves, such as chopped, shredded or powdered lemon balm leaves. In some embodiments, the lemon balm is included in the form of a lemon balm extract, such as an aqueous extract of lemon balm. In some embodiments, the lemon balm is included in the form of lemon balm essential oil. Lemon balm has previously been found to exert antioxidant, anti-inflammatory and neuroprotective properties.

[0273] The lemon balm may be present in any suitable amount, such as in an amount of from about 0.01% to about 3% by weight of the oral product, such as in an amount of from about 0.05% by weight to about 3% by weight. In preferred embodiments, the lemon balm is present in an amount of from about 0.1% to about 2% by weight of the oral product.

[0274] In some embodiments, the combination of active ingredients further comprises chamomile. Chamomile (Matricaria recuita) is a flowering plant in the daisy (Asteraceae) family. Native to Europe and Western Asia, it is now found around the world. There are two different chamomile plants, German chamomile and Roman chamomile. German chamomile is generally considered the more potent variety and the type most widely used for medicinal purposes. Different classes of bioactive constituents are present in chamomile, such as flavanols (apigenin, luteolin, quercetin) coumarins and terpenoids. Research has shown chamomile to have benefits when it comes to boosting immunity or the immune system to help fight infections. Chamomile is also known to have anti-inflammatory and anti-oxidant effects.

[0275] The chamomile may be in the form of chamomile extract. The chamomile (e.g. chamomile extract) may be present in an amount of at least about 0.001% by weight, at least about 0.005% by weight or at least about 0.01% by weight of the oral product. In some embodiments, the chamomile (e.g. chamomile extract) is present in an amount of no greater than about 1% by weight, no greater than about 0.5% by weight, or no greater than about 0.1% by weight of the oral product.

[0276] The combination of active ingredients may further comprise vitamin D. Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate. In humans the most important compounds in this group are vitamin D3 (cholecalciferol) and D2 (ergocalciferol). Vitamin D as used herein thus refers to D2, D3 or both. The structural difference between vitamin D2 and D3 is in the side chain, which contains a double bond, between carbons 22 and 23, and a methyl group on carbon 24 in vitamin D2. As well as calcium, magnesium, and phosphate absorption, vitamin D affects the immune system and vitamin D receptors (VDRs) are expressed in several white blood cells, including monocytes and activated T and B cells. In general, vitamin D functions to activate the innate and dampen the adaptive immune systems with antibacterial, antiviral and anti-inflammatory effects.

[0277] When present in the oral product, the vitamin D may be used in any suitable amount, such as in an amount of from about 0.000001% to about 0.1% by weight of the oral product, such as in an amount of from about 0.0000025% to about 0.005% by weight of the oral product. In preferred embodiments, the vitamin D is present in an amount of from about 0.00001% to about 0.001% by weight of the oral product.

[0278] The combination of active ingredients may further comprise selenium. Selenium is a trace element that is nutritionally essential for humans as a component of multiple selenoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection. When present in the oral product, the selenium may be used in any suitable amount such as in an amount of from about 0.0000001% by weight to about 0.001% by weight of the oral product, such as in an amount of from about 0.0000005% by weight to about 0.0005% by weight of the oral product. In preferred embodiments, the selenium is present in an amount of from about 0.000001% by weight to about 0.0001% by weight of the oral product.

[0279] The combination of active ingredients may further comprise Echinacea. The Echinacea is either Echinacea purpurea, Echinacea angustifolia or Echinacea pallida and the upper parts (e.g. flowers, fruit, leaves) and / or roots of the plant may be utilized. Echinacea plants contain a variety of active compounds including caffeic acid, alkamides, phenolic acids, rosmarinic acid, polyacetylenes, flavonoids, and cichoric acid. Studies have linked Echinacea and its compounds to many health benefits including reduced inflammation, improved immunity and lower blood sugar levels. The Echinacea may be present in the form of an extract, chopped or shredded or powdered. Preferably, the Echinacea is included in the form of an extract.

[0280] The Echinacea may be present in the oral product in any suitable amount, such as in an amount of about 0.001% to about 20% by weight of the oral product, such as in an amount of from about 0.01% to about 15% by weight of the oral product. In preferred embodiments, the Echinacea is present in an amount of from about 0.05% to about 10% by weight of the oral product.

[0281] The combination of active ingredients may further comprise a vitamin selected from vitamin A, vitamin E and vitamin K, or mixtures thereof.

[0282] The combination of active ingredients may further comprise an amino acid, such as an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, gamma-aminobutyric acid (GABA), taurine (2-aminoethanesulfonic acid), hydroxyproline, and beta-alanine. In some embodiments, the combination of active ingredients comprises GABA.

[0283] In some embodiments, the combination of active ingredients comprises a cannabinoid. The cannabinoid may be a derivative or extract of cannabis. Cannabinoids are a class of natural or synthetic chemical compounds which act on cannabinoid receptors (i.e., CB1 and CB2) in cells that repress neurotransmitter release in the brain. Cannabinoids are cyclic molecules exhibiting particular properties such as the ability to easily cross the blood-brain barrier. Cannabinoids may be naturally occurring (Phytocannabinoids) from plants such as cannabis, (endocannabinoids) from animals, or artificially manufactured (synthetic cannabinoids). Cannabis species express at least 85 different phytocannabinoids, and these may be divided into subclasses, including cannabigerols, cannabichromenes, cannabidiols, tetrahydrocannabinols, cannabinols and cannabinodiols, and other cannabinoids. In some embodiments,, the cannabinoid is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), Cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabimolic acid (THCA), tetrahydrocannabivarinic acid (THCV A), and mixtures thereof. In some embodiments, the cannabinoid is or comprises at least tetrahydrocannabinol (THC). In some embodiments, the cannabinoid is or comprises at least cannabidiol (CBD).

[0284] In some embodiments, the combination of active ingredients comprises a cannabinoid (such as cannabidiol) in an amount of about 0.001% to about 10% by weight, such as fromabout 0.01% to about 5% by weight, such as from about 0.1% to about 2.5% by weight, such as from 0.5% to about 1% by weight of the oral product.

[0285] In some embodiments, the combination of active ingredients comprises magnesium glycinate. Where present, magnesium glycinate may be included in an amount of from about 0.1% to about 10% by weight, such as from about 0.5% to about 5% by weight, or from about 0.5% to about 1% by weight of the oral product.

[0286] In some embodiments, the combination of active ingredients further comprises piperine. Piperine is an alkaloid found in fruits of the pepper species in the family Piperaceae, such as black pepper (Piper nigrum), long pepper (Piper longum), red long pepper (Piper retrofactum) and voatsiperifery pepper (Piper borbonense). Piperine may be beneficial to include in the oral product because of its ability to enhance the bioavailability of one or more compounds included in the oral product. The origin of piperine is not limited; in some embodiments it may be obtained from a black pepper extract.

[0287] Piperine has, for example, been found to enhance the bioavailability of one or more P- glycoprotein substrate compounds obtained from saffron or Ashwagandha. Specifically, piperine has been found to enhance the bioavailability of crocetin, crocin, withanolide A, and withanone. Each of these compounds are P-glycoprotein substrates and their permeation across the blood-brain barrier has been found to be enhanced by combining said compounds with piperine. This is unexpected because the enhancement was not observed with another P-gp inhibitor (quercetin), and / or with other P-glycoprotein substrate compounds, e.g. ursolic acid obtained from Holy Basil. In some embodiments the combination of active ingredients may therefore include ginseng in the form of Ashwagandha and further include piperine. In such embodiments, piperine may enhance / improve the bioavailability of withanolide A and / or withanone provided by the Ashwagandha in the oral product. The enhancement / improvement is relative to an oral product without piperine, and refers to the blood-brain barrier permeation of the P-glycoprotein substrates withanolide A and / or withanone.

[0288] In some embodiments the combination of active ingredients may alternatively or additionally include crocin and / or crocetin. Crocin and / or crocetin may be obtained from a saffron extract. Saffron is disclosed herein as a possible flavouring agent for the oral product. In a similar manner to above, piperine may enhance / improve the bioavailability of crocin and / or crocetin in the oral product relative to an oral product without piperine. The enhancement / improvement refers to the blood-brain barrier permeation of the P-glycoprotein substrates crocin and / or crocetin.

[0289] The benefit of such enhancement of the blood-brain barrier permeation is that it may allow lower amounts of the active ingredients to be included in the oral product, thereby mitigating or preventing any issues that may arise from higher amounts, e.g. issues of solubility, sensorials, compliance, safety etc. The inclusion of lower amounts of actives is especially beneficial when the oral product is prepared as a liquid in the form of a shot, i.e. a drink that may be consumed quickly. The liquid oral product may, for example, have a volume of from about 10 mL to about 100 mL, such as from about 25 mL to about 75 mL. In such embodiments, the liquid oral product may be considered to be a shot. For example, the volume of liquid may be about 60 mL or about 30 mL. Inclusion of lower amounts should not, however, compromise the effect of the oral product and piperine may therefore be used for this purpose.

[0290] In some embodiments, the oral product may comprise about 0.0001 wt% to about 0.1 wt% of piperine, based on the total weight of the oral product. In preferred embodiments the oral product may comprise about 0.0005 wt% to about 0.05 wt% of piperine, based on the total weight of the oral product.

[0291] In any of the embodiments defined herein, the term ^comprises^ may be replaced with the term ^consists essentially of^ or ^consists of^.

[0292] For the avoidance of doubt, combinations of the above end points are explicitly envisaged by the present disclosure. This applies to any of the ranges disclosed herein

[0293] It will be understood that all disclosure herein concerning the oral product applies to these combinations of active ingredients. The disclosure is not repeated for conciseness. Additives

[0294] Depending on the type of oral product, the product may include one or more additional components in addition to the combination of active ingredients. For example, the oral product may further comprise an additive selected from the group consisting of a flavouring agent, sweetener, buffering agent, acidifying agent, thickener, filler, binder, humectant, preservative, salt, colouring agent, oral care additive, distintegration aid, antioxidant, water or mixtures thereof. In some embodiments, the oral product may further comprise water and one or more additives selected from the group consisting of a flavouring agent, sweetener, acidifying agent, preservative, and mixtures thereof. In other embodiments, the oral product may further comprise one or more additives selected from the group consisting of a flavouring agent, sweetener, acidifying agent, thickener, filler, binder, humectant, preservative, and mixtures thereof.

[0295] The moisture content (e.g., water content) of the oral product, prior to use by a consumer of the product, may vary according to the desired properties.

[0296] For the liquid oral product, the water content may be at least about 50%, such as at least about 60%, such as at least about 75% by weight of the oral product. Preferably, the water content of the liquid oral product may be at least about 90% by weight of the oral product. Preferably, the water content of a liquid oral product may be from about 60% to about 99.5% by weight, such as from about 75% to about 99% by weight, such as from about 80% to about 98% by weight of the oral product.

[0297] Typically, for a solid oral product, prior to insertion into the mouth of the user, the water content is less than about 60% by weight, and generally is from about 1 to about 60% by weight, for example, from about 5 to about 55% by weight, about 10 to about 50% by weight, about 20 to about 45% by weight, or about 25 to about 40% by weight of the oral product; including water amounts of at least about 5% by weight, at least about 10% by weight, at least about 15% by weight, and at least about 20% by weight of the oral product. Flavouring Agent

[0298] As used herein, the term "flavouring agent" (or ^flavour^ or "flavourant") refers to materials which, where local regulations permit, may be used to create a desired taste, aroma or other somatosensorial sensation in a product for adult consumers. Examples of sensory characteristics that can be modified by the flavoring agent include taste, mouthfeel, moistness, coolness / heat, and / or fragrance / aroma. Flavouring agents may be natural or synthetic, and the character of the flavours imparted thereby may be described, without limitation, as fresh, sweet, herbal, confectionary, floral, fruity, or spicy.

[0299] The flavouring agent may be selected from the group consisting of naturally occurring flavour materials, botanicals, extracts of botanicals, synthetically obtained materials, or combinations thereof (e.g., tobacco, cannabis, licorice (liquorice), hydrangea, eugenol, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, maple, matcha, menthol, Japanese mint, aniseed (anise), cinnamon, turmeric, Indian spices, Asian spices, herb, wintergreen, cherry, berry, red berry, cranberry, raspberry, strawberry, peach, apple, orange, mango, pineapple, clementine, lemon, lime, tropical fruit, papaya, rhubarb, grape, durian, dragon fruit, cucumber, blueberry, mulberry, citrus fruits, Drambuie, bourbon, scotch, whiskey, gin, tequila, rum, spearmint, peppermint, lavender, aloe vera, cardamom, coconut, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, khat, naswar, betel, shisha, pine, honey essence, rose oil, vanilla, lemon oil, orange oil, orange blossom, cherry blossom, cassia,caraway, cognac, jasmine, ylang-ylang, sage, fennel, wasabi, piment, ginger, coriander, coffee, hemp, a mint oil from any species of the genus Mentha, eucalyptus, star anise, cocoa, lemongrass, rooibos, flax, ginkgo biloba, hazel, hibiscus, laurel, mate, orange skin, rose, tea such as green tea or black tea, thyme, juniper, elderflower, basil, bay leaves, cumin, oregano, paprika, rosemary, saffron, lemon peel, mint, beefsteak plant, curcuma, cilantro, myrtle, cassis, valerian, pimento, mace, damien, marjoram, olive, lemon basil, chive, carvi, verbena, tarragon, limonene, thymol, camphene), flavour enhancers, bitterness receptor site blockers, sensorial receptor site activators or stimulators, sugars and / or sugar substitutes (e.g., honey, sucralose, acesulfame potassium, aspartame, saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals, or breath freshening agents. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, liquid such as an oil, solid such as a powder, or gas.

[0300] In some embodiments, the flavouring agent comprises a natural flavoring, such as berry (e.g. raspberry, blueberry or strawberry), honey, citrus (such as lemon, bergamot, orange or lime), or other botanical material.

[0301] In some embodiments, the flavouring agent comprises menthol, spearmint and / or peppermint. In some embodiments, the flavouring agent comprises flavour components of cucumber, blueberry, citrus fruits and / or redberry. In some embodiments, the flavouring agent comprises eugenol. In some embodiments, the flavouring agent comprises flavour components extracted from tobacco. In some embodiments, the flavouring agent comprises flavour components extracted from cannabis.

[0302] In some embodiments, the flavouring agent may comprise a sensate, which is intended to achieve a somatosensorial sensation which are usually chemically induced and perceived by the stimulation of the fifth cranial nerve (trigeminal nerve), in addition to or in place of aroma or taste nerves, and these may include agents providing heating, cooling, tingling, numbing effect. A suitable heat effect agent may be, but is not limited to, vanillyl ethyl ether and a suitable cooling agent may be, but not limited to eucalyptol, WS-3.

[0303] In some embodiments, the flavouring agent may comprise a terpene. In some embodiments, the flavouring agent may comprise a monoterpene and / or a diterpene and / or a sesquiterpene. In some embodiments, the flavouring agent may comprise a monoterpene. In some embodiments, the terpene is selected from pinene (alpha and beta), geraniol, linalool, limonene, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta- bourbonene, germacrene, thymol, citral, eugenol, and mixtures thereof. In someembodiments,, the flavouring agent is selected from the group consisting of geraniol, citronellol, nerol, maltol, ethylmaltol, fenchol, homofuraneol, furaneol, norfuraneol, 1-octen-3- ol, borneol, linalool, farnesol, hydroxycitronellol, 3,7-dimethyloctanol, myrcenol, lavandulol, nerolidol, terpineol, alpha-terpineol, menthol, thymol, carvacrol, myrtenol, carveol, santalol, piperitol, perillyl alcohol, patchouli alcohol, hexanol, 1-hexanol, 3-cis-hexanol, cis-3-hexen-1- ol, phenylethanol, eugenol, sesamol, sotolone, maple furanone, methyl anthranilate, guaiacol, raspberry ketone, 2-methoxy-4-vinylphenol, 4-ethylguaiacol, benzylalcohol, homofuraneol, vanillin, ethylvanillin, and combinations thereof. In some embodiments, the flavouring agent is selected from the group consisting of geraniol, citronellol, nerol, maltol, ethylmaltol, fenchol, homofuraneol, furaneol, norfuraneol, 1-octen-3-ol, borneol, linalool, farnesol, hydroxycitronellol, 3,7-dimethyloctanol, myrcenol, lavandulol, nerolidol, terpineol, alpha- terpineol, menthol, thymol, carvacrol, myrtenol, carveol, santalol, piperitol, perillyl alcohol, patchouli alcohol, hexanol, 1-hexanol, 3-cis-hexanol, cis-3-hexen-1-ol, phenylethanol, eugenol, sesamol, sotolone, maple furanone, methyl anthranilate, guaiacol, raspberry ketone, 2-methoxy-4-vinylphenol, 4-ethylguaiacol, benzylalcohol, homofuraneol, and combinations thereof.

[0304] Where present, a flavouring agent may be included in the oral product in an amount up to about 10% by weight, such as up to about 5% by weight, such as up to about 1% by weight of the oral product. In some embodiments, a flavouring agent is present in an amount of from about 0.01% to about 5% by weight, such as in an amount of from about 0.1% to about 2.5% by weight of the oral product, preferably in an amount of from about 0.25% to about 1% by weight of the oral product. Humectants

[0305] In some embodiments, the oral product comprises at least one humectant. Examples of suitable humectants that may be included in the product include, but are not limited to, glycerin, 1,2-propanediol (propylene glycol), 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, mannitol, and the like. In some embodiments, the humectant is or comprises glycerin. In some embodiments, the oral product comprises glycerin. In some embodiments, the humectant is or comprises propylene glycol. In some embodiments, the oral product comprises propylene glycol. The amount of humectant utilised in the oral product can vary, but may be up to about 5% by weight, and certain embodiments can be characterised by a humectant content of at least about 1% by weight, such as about 2 to about 5% by weight of the oral product. In some embodiments, the humectant (such as glycerin and / or propylene glycol) may be present in an amount of from about 0.01% to about 25% by weight of the oral product, such as from about 0.1% to about 20% by weight of the oral product, such as fromabout 0.5% to about 15% by weight of the oral product, such as from about 1% to about 10% by weight of the oral product, such as from about 5% to about 10% by weight of the oral product. Sweeteners

[0306] In order to improve the sensory properties of the oral product, one or more sweeteners may be added. The sweeteners can be any sweetener or combination of sweeteners, in natural or artificial form, or as a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, and the like. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame and the like.

[0307] In some embodiments, the sweetener comprises one or more sugar alcohols. The sugar alcohol may include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, or combinations thereof. In some embodiments, the sweetener is selected from the group consisting of fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and mixtures thereof.

[0308] In some embodiments, the sweetener is selected from the group consisting of sucralose, acesulfame K, aspartame, maltodextrin, mannitol, sucrose, and mixtures thereof. Preferably, the sweetener may be sucralose and / or acesulfame K. When present in the oral product, the sweetener (such as sucralose and / or acesulfame K) may be present in an amount of from about 0.001% to about 5% by weight, such as from about 0.01% to about 3% by weight, preferably from about 0.01% to about 1% by weight of the oral product. Buffering agents

[0309] Non-limiting examples of suitable buffering agents that may be included in the oral product include alkali metals acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, hydrogen carbonates, borates, or mixtures thereof. In some embodiments, in which a buffering agent is present, the buffering agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, sodium phosphate, ammonium phosphate, dicalcium phosphate, tricalcium phosphate, and mixtures thereof. In some embodiments, the buffering agent is sodium bicarbonate and / or sodium carbonate. Where present, the buffering agent (e.g. sodium bicarbonate and / or sodium carbonate) may be included in an amount less than about 5% based on the weight of the oral product; for example, from about 0.5% to about5%, such as, e.g., from about 0.75% to about 4%, from about 0.75% to about 3%, or from about 1% to about 2% by weight, based on the total weight of the oral product. Organic acid

[0310] In some embodiments, the product comprises an organic acid. As used herein, the term "organic acid" refers to an organic (i.e., carbon-based) compound that is characterised by acidic properties. Typically, organic acids are relatively weak acids (i.e., they do not dissociate completely in the presence of water), such as carboxylic acids (-CO2H) or sulfonic acids (-SO2OH). As used herein, reference to organic acid means an organic acid that is intentionally added. In this regard, an organic acid may be intentionally added as a specific mixture ingredient as opposed to merely being inherently present as a component of another mixture ingredient (e.g., the small amount of organic acid which may inherently be present in a mixture ingredient such as a tobacco material). In some embodiments, the one or more organic acids are added neat (i.e., in their free acid, native solid or liquid form) or as a solution in, e.g. water. In some embodiments, the one or more organic acids are added in the form of a salt.

[0311] In some embodiments, the organic acid is a carboxylic acid or a sulfonic acid. The carboxylic acid or sulfonic acid functional group may be attached to any alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group having, for example, from one to twenty carbon atoms (C1-C20). In some embodiments, the organic acid is an alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl carboxylic or sulfonic acid.

[0312] In some embodiments, the organic acid is an alkyl carboxylic acid. Non-limiting examples of alkyl carboxylic acids include formic acid, acetic acid, propionic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and the like. In some embodiments, the organic acid is an alkyl sulfonic acid. Non-limiting examples of alkyl sulfonic acids include propanesulfonic acid and octanesulfonic acid.

[0313] In some embodiments, the alkyl carboxylic or sulfonic acid is substituted with one or more hydroxyl groups. Non-limiting examples include glycolic acid, 4-hydroxybutyric acid, and lactic acid.

[0314] In some embodiments, an organic acid may include more than one carboxylic acid group or more than one sulfonic acid group (e.g., two, three, or more carboxylic acid groups). Non-limiting examples include oxalic acid, fumaric acid, maleic acid, and glutaric acid. In organic acids containing multiple carboxylic acids (e.g., from two to four carboxylic acidgroups), one or more of the carboxylic acid groups may be esterified. Non-limiting examples include succinic acid monoethyl ester, monomethyl fumarate, monomethyl or dimethyl citrate, and the like.

[0315] In some embodiments, the organic acid may include more than one carboxylic acid group and one or more hydroxyl groups. Non-limiting examples of such acids include tartaric acid, citric acid, and the like. In some preferred embodiments, the organic acid is citric acid, sodium citrate, calcium citrate, or a combination thereof.

[0316] In some embodiments, the organic acid is an aryl carboxylic acid or an aryl sulfonic acid. Non-limiting examples of aryl carboxylic and sulfonic acids include benzoic acid, toluic acids, salicylic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0317] Additional non-limiting examples of suitable organic acids include 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4- aminosalicylic acid, acetic acid, adipic acid, ascorbic acid (L), aspartic acid (L), camphoric acid (+), camphor-10-sulfonic acid (+), capric acid, caproic acid, caprylic acid, cinnamic acid, cyclamic acid, decanoic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactobionic acid, lauric acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, oleic acid, palmitic acid, pamoic acid, pyroglutamic acid, sebacic acid, stearic acid, and undecylenic acid.

[0318] Preferably, the organic acid is selected from the group consisting of citric acid, malic acid, lactic acid, benzoic acid, tartaric acid, and mixtures thereof. In some preferred embodiments, the organic acid is or comprises citric acid or a salt thereof.

[0319] In some embodiments, the product comprises an alkali metal salt of an organic acid. For example, at least a portion of the organic acid may be present in the product in the form of an alkali metal salt. Suitable alkali metal salts include lithium, sodium, and potassium. In some embodiments, the alkali metal is sodium or potassium. In some embodiments, the alkali metal is sodium. In some embodiments, the product comprises an organic acid and a sodium salt of the organic acid. In some embodiments, the organic acid is or comprises sodium citrate, such as trisodium citrate.

[0320] The amount of organic acid present in the product may vary. The oral product may comprise from about 0.01% to about 10% by weight of organic acid, present as one or more organic acids, based on the total weight of the oral product. In some embodiments, the oralproduct comprises at least about 0.01%, at least about 0.1 %, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or at least about 10% organic acid by weight, based on the total weight of the oral product. In some preferred embodiments, the oral product comprises from about 0.01% to about 5% by weight of organic acid based on the weight of the oral product. For example, the oral product comprises an organic acid in an amount of from about 0.1% to about 2.5% by weight of the oral product. In the case where a salt of an organic acid is added (e.g., citric acid anhydrate), the percent by weight is calculated based on the weight of the free acid, not including any counter-ion which may be present.

[0321] In certain embodiments the organic acid inclusion is sufficient to provide a product pH of from about 4.0 to about 9.0, such as from about 4.5 to about 7.0, or from about 5.5 to about 7.0, from about 4.0 to about 5.5, or from about 7.0 to about 9.0. In some embodiments, the organic acid inclusion is sufficient to provide a product pH of from about 4.5 to about 6.5, for example, from about 4.5, about 5.0, or about 5.5, to about 6.0, or about 6.5. In some embodiments,, the organic acid is provided in a quantity sufficient to provide a pH of the product of from about 5.5 to about 6.5, for example, from about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0, to about 6.1, about 6.2, about 6.3, about 6.4, or about 6.5.

[0322] In other embodiments, a mineral acid (e.g., hydrochloric acid, sulfuric acid, phosphoric acid, or the like) is added to adjust the pH of the product to the desired value.

[0323] Organic acids (e.g., citric acid) may be added neat (i.e., as a solid) or in solution, for example, in water. In some embodiments, the organic acid is added as a 50% aqueous solution. Salts

[0324] The oral product may further comprise a salt. This may be included in an amount sufficient to provide desired sensory attributes to the product. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, flour salt, sodium acetate, sodium citrate, and the like. The salt may be included in any suitable amount, such as at least about 0.5% by weight, such as at least about 1% by weight, such as at least about 1.5% by weight of the oral product. In some embodiments, the oral product may comprise salt in an amount of from about 0.5% to about 10% by weight, such as from about 1% to about 7.5% by weight, such as from about 1.5% to about 5% by weight, based on the total weight of the oral product.Colouring agents

[0325] A colouring agent may be employed in amounts sufficient to provide the desired physical attributes to the product. Examples of colouring agents include various dyes and pigments, such as caramel colouring and titanium dioxide. Natural colouring agents such as curcumin, beet juice extract, spirulina; also a variety of synthetic pigments may also be used. The amount of colorant utilised in the oral product can vary, but when present is typically up to about 3% by weight, such as from about 0.1 %, about 0.5%, or about 1%, to about 3% by weight, based on the total weight of the oral product. Filler or Bulking Agents

[0326] Depending on the form of the product, the oral product may comprise a filler or bulking agent. Fillers or bulking agents, for example, may fulfil multiple functions, such as enhancing certain organoleptic properties such as texture and mouthfeel, enhancing cohesiveness or compressibility of the product, and the like.

[0327] In some embodiments, the filler is a porous particulate material and is cellulose-based. For example, the filler or bulking agent may be a non-tobacco plant material or derivative thereof, including cellulose materials derived from such sources. Examples of cellulosic non- tobacco plant material include cereal grains (e.g., maize, oat, barley, rye, buckwheat, and the like), sugar beet (e.g., FIBREX® brand filler available from International Fiber Corporation), bran fiber, and mixtures thereof. In some embodiments, the filler is a cellulose material selected from the group consisting of maize fiber, oat fiber, barley fiber, rye fiber, buckwheat fiber, sugar beet fiber, bran fiber, bamboo fiber, wood pulp fiber, cotton fiber, citrus pulp fiber, grass fiber, willow fiber, poplar fiber, cocoa fiber, derivatives thereof, and combinations thereof. In some embodiments, the filler is a cellulose material selected from the group consisting of sugar beet fiber, wood pulp fiber, bamboo fiber, derivatives thereof, and combinations thereof.

[0328] In some embodiments, the filler is derived from wood pulp fiber. One particularly suitable filler for use in the products described herein is microcrystalline cellulose ("MCC"). The MCC may be synthetic or semi-synthetic, or it may be obtained entirely from natural celluloses. The MCC may be selected from the group consisting of AVICEL® grades PH-100, PH-101, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-301, PH-302, VIVACEL® grades 101, 102, 12, 20 and EMOCEL® grades 50M and 90M, and the like, and mixtures thereof.

[0329] In some embodiments, the filler is a non-tobacco plant material or a derivative thereof. Non-limiting examples of derivatives of non-tobacco plant material include starches (e.g., from potato, wheat, rice, corn), natural cellulose, and modified cellulosic materials. Additional examples of potential fillers include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, mannitol, xylitol, and sorbitol. Combinations of these fillers can also be used.

[0330] "Starch" as used herein may refer to pure starch from any source, modified starch, or starch derivatives. Starch is present, typically in granular form, in almost all green plants and in various types of plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, shoots, fruits, grains, and stems). Starch can vary in composition, as well as in granular shape and size. Often, starch from different sources has different chemical and physical characteristics. A specific starch can be selected for inclusion in the product based on the ability of the starch material to impart a specific organoleptic property to product. Starches derived from various sources can be used. For example, major sources of starch include cereal grains (e.g., rice, wheat, and maize) and root vegetables (e.g., potatoes and cassava). Other examples of sources of starch include acorns, arrowroot, arracacha, bananas, barley, beans (e.g., favas, lentils, mung beans, peas, chickpeas), breadfruit, buckwheat, canna, chestnuts, colacasia, katakuri, kudzu, malanga, millet, oats, oca, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, water chestnuts, and yams. Certain starches are modified starches. A modified starch has undergone one or more structural modifications, often designed to alter its high heat properties. Some starches have been developed by genetic modifications, and are considered to be "modified" starches. Other starches are obtained and subsequently modified. For example, modified starches can be starches that have been subjected to chemical reactions, such as esterification, etherification, oxidation, depolymerization (thinning) by acid catalysis or oxidation in the presence of base, bleaching, transglycosylation and depolymerization (e.g., dextrinization in the presence of a catalyst), cross-linking, enzyme treatment, acetylation, hydroxypropylation, and / or partial hydrolysis. Other starches are modified by heat treatments, such as pregelatinization, dextrinization, and / or cold water swelling processes. Certain modified starches include monostarch phosphate, distarch glycerol, distarch phosphate esterified with sodium trimetaphosphate, phosphate distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol, hydroxypropyl starch, hydroxypropyl distarch glycerol, and starch sodium octenyl succinate.

[0331] Other suitable fillers or bulking agents include sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides that have a partially or fully hydrogenated form. Sugar alcohols have, for example, about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof. In some embodiments, where present, the filler may be selected from the group consisting of isomalt, maltitol and mixtures thereof. Binding agent

[0332] In some embodiments, the oral product may further comprise at least one binder. A binder (or combination of binders) may be employed in the product in certain embodiments, in amounts sufficient to provide the desired physical attributes and physical integrity to the product. Binders can be organic or inorganic, or a combination thereof. Representative binders include cellulose derivatives, povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof. The amount of binder utilised in the product can vary, but may be up to about 30% by weight, and certain embodiments are characterised by a binder content of at least about 0.1% by weight, such as from about 1% to about 30% by weight, or about 1% to about 10% by weight, based on the total weight of the oral product.

[0333] In some embodiments, the binder comprises pectin. Pectins are natural polymers related to carbohydrates and which are acidic heteropolysaccharides (polysaccharides comprising multiple monosaccharide units). As opposed to carbohydrates, the pectin C-6 position contains a carboxylic acid (or corresponding methyl ester or carboxamide) group instead of a hydroxymethyl group. The principal subunit is known as galacturonic acid, which can be copolymerised with L-rhamnose. Other sugars are featured as side-chain substituents. Pectin acts as a thickening and gelling agent. Pectin isolated from sources such as apple pomace, citrus peels, sugarbeet waste from sugar manufacturing, sunflower heads discarded from seed harvesting, mango waste, and other commercially available pectins may be used. In combination with certain sugars, under acidic conditions (e.g., a pH of from about 2.5 to about 5), or in the presence of a gelation agent (calcium or other divalent alkaline earth elements), pectins may provide a gel or gum consistency to products as disclosed herein. In some embodiments, the binder comprises low methoxy pectin. Suitable low methoxy pectins include, for example, "GENU® pectin type LM-104 AS", available from CP Kelco, Atlanta, GA, USA In some embodiments, the binder comprises low methoxy pectin in combination with a gelation agent. In some embodiments, the gelation agent comprises calcium ions, such as, but not limited to, calcium diphosphate. In some embodiments, the binder comprises a highmethoxy pectin in combination with an organic acid, described herein below. In some embodiments, the binder comprises a high methoxy pectin in combination with citric acid.

[0334] When present, a pectin binder is typically present in an amount of up to about 3% by weight, for example, from about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1, to about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8. about 1.9, about 2, about 2.1, about 2.2, about 2.3. about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, or about 3% by weight, based on the total weight of the oral product.

[0335] In some embodiments, the binder comprises a cellulose derivative. In certain embodiments, the cellulose derivative is a cellulose ether (including carboxyalkyl ethers), meaning a cellulose polymer with the hydrogen of one or more hydroxyl groups in the cellulose structure replaced with an alkyl, hydroxyalkyl, or aryl group. Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropylcellulose ("HPC"), hydroxypropylmethylcellulose ("HPMC"), hydroxyethyl cellulose, and carboxymethylcellulose ("CMC"). In some embodiments, the cellulose derivative is or comprises HPC. In some embodiments, the cellulose derivative is a combination of HPC and HPMC. In some embodiments, the oral product comprises from about 1% to about 10% of the cellulose derivative (such as HPC) by weight of the oral product, with certain embodiments comprising from about 1% to about 5% by weight of cellulose derivative (such as HPC), based on the weight of the product.

[0336] In certain embodiments, the binder includes a gum, for example, a natural gum. As used herein, a natural gum refers to polysaccharide materials of natural origin that have binding properties, and which are also useful as a thickening or gelling agents. Representative natural gums derived from plants, which are typically water soluble to some degree, include xanthan gum, guar gum, gum arabic, ghatti gum, gum tragacanth, karaya gum, locust bean gum, gellan gum, and combinations thereof. When present, natural gum binder materials may be present in an amount of up to about 5% by weight, for example, from about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1%, to about 2, about 3, about 4, or about 5% by weight, based on the total weight of the product. Thickeners

[0337] The oral product may comprise a thickening agent in some embodiments. Suitable thickening agents may include a hydrocolloid, such as xanthan gum, guar gum, konjac gum, gum tragacanth and gum Arabic. For example, xanthan gum is understood to be a thickeningagent that thickens compositions when added during cold processing (i.e. when heat is not applied). Where present, a thickening agent (e.g. xanthan gum) may be included in an amount of from about 0.001% to about 5% by weight, and preferably from about 0.01% to about 1% by weight of the oral product. Other additives

[0338] Other ingredients such as preservatives (e.g., potassium sorbate), disintegration aids (e.g., croscarmellose sodium, crospovidone, sodium starch glycolate, pregelatinized corn starch, and the like), and / or antioxidants can also be used. Typically, such ingredients, where used, are used in amounts of up to about 10% by weight, for example at least about 0.1% by weight, such as about 0.5 to about 10% by weight of the oral product. A disintegration aid may be employed in an amount sufficient to provide control of desired physical attributes of the oral product such as, for example, by providing loss of physical integrity and dispersion of the various component materials upon contact of the formulation with water (e.g., by undergoing swelling upon contact with water).

[0339] Examples of further types of additives include zinc or magnesium salts selected to be relatively water soluble for compositions with greater water solubility (e.g., magnesium or zinc gluconate) or selected to be relatively water insoluble for compositions with reduced water solubility (e.g., magnesium or zinc oxide), or combinations thereof. See, for example, those representative components, combination of components, relative amounts of those components, and manners and methods for employing those components, set forth in US Pat. No.9,237,769 to Mua et al., US Pat. No.7,861,728 to Holton, Jr. et al., US Pat. App. Pub. No. 2010 / 0291245 to Gao et al., and US Pat. App. Pub. No 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference. Typical inclusion ranges for such additional additives can vary depending on the nature and function of the additive and the intended effect on the final product, with an example range of up to about 10% by weight, based on total weight of the oral product (e.g., about 0.1 to about 5% by weight).

[0340] In some embodiments, the oral product comprises a magnesium salt. A non-limiting example of a suitable magnesium salt is magnesium gluconate. In some embodiments, the oral product comprises magnesium in an amount by weight from about 0.1% to about 2%, or from about 0.2 to about 1%, based on elemental magnesium.

[0341] The aforementioned additives can be employed together (e.g., as additive formulations) or separately (e.g., individual additive components can be added at different stages involved in the preparation of the final product).Oral Product

[0342] The products or compositions as described herein are configured for oral use. The term "configured for oral use" as used herein means that the product is provided in a form such that during use, saliva in the mouth of the user causes one or more of the components of the product (e.g., active ingredients) to pass into the mouth of the user. In certain embodiments, the product is adapted to deliver active ingredients and optionally flavouring agent to a user through mucous membranes in the user's mouth, the user's digestive system, or both.

[0343] The combination of active ingredients may be present in an amount of from about 0.01% to about 20% by weight. For example, the combination of active ingredients may be present in an amount of from about 0.05% to about 15% by weight, such as from about 0.1% to about 10% by weight. Preferably, the combination of active ingredients is present in an amount of from about 0.1% to about 15% by weight of the oral product, more preferably from about 1% to about 10% by weight of the oral product.

[0344] The liquid oral product may be in the form of a shot; i.e. a drink that may be consumed quickly, e.g. in a single gulp or a couple of gulps. Formulating the oral product in the form of a shot may be advantageous as it provides a convenient and easy-to-use mode of administration that does not take up much room during storage (e.g. in a fridge or cupboard) and is easily portable by the user so can be taken on the go. Shots may also provide an efficient delivery vehicle for actives, whereby a level of active sufficient to provide good efficacy can be delivered to the user without the need to consume large volumes of liquid. Additionally, the shots may be formulated to have a pleasant taste. Drinking a shot may be considered to be more palatable and easier to a user than swallowing a tablet, for example.

[0345] The liquid oral product may also be in the form of a larger beverage that is consumed more slowly over several gulps. The liquid oral product may have a volume of from about 1 mL to about 250 mL, such as from about 1 mL to about 200 mL. The liquid oral product may have a volume of from about 100 mL to about 250 mL and be provided in a package such as a carton, cup, can or bottle of liquid.

[0346] The liquid oral product may have a volume of from about 10 mL to about 100 mL, such as from about 25 mL to about 75 mL. In such embodiments, the liquid oral product may be considered to be a shot. For example, the volume of liquid may be about 60 mL or about 30 mL.

[0347] As noted above, the oral product may further comprise water in an amount of from about 50% to about 99.9% by weight of the oral product. In some embodiments, the oral product comprises water in an amount of from about 75% to about 99.5% by weight, such as from about 80% to about 99% by weight, such as from about 90% to about 97.5% by weight of the oral product. In some embodiments, the oral product comprises water in an amount of from about 90% to about 99.5% by weight of the oral product, and may be from about 95% to about 99% by weight of the oral product. Where present, the water may include tap water, rain water, mineralised water, or distilled water.

[0348] The liquid oral product may comprise the combination of active ingredients in an amount of from about 0.1% to about 15% by weight of the oral product, and water in an amount of from about 85% to about 99.9% by weight of the oral product. The liquid oral product may comprise the combination of active ingredients in an amount of from about 0.5% to about 12% by weight of the oral product, and water in an amount of from about 88% to about 99.5% by weight of the oral product.

[0349] In some embodiments, there is provided a package in the form of a bottle or can that contains the liquid oral product. The package may be a bottle containing the desired volume of liquid oral product. Solid oral dosage forms

[0350] In some embodiments, the oral product is a solid oral dosage form. A solid oral product as described herein may take various forms, including pastilles and chews. As used herein, the term ^solid^ means that the products can substantially sustain their physical shape when unsupported by external means, e.g. packaging etc. Thus, they are considered to be solid, solid-like, in solid form or in solid-like form at room temperature. For the avoidance of doubt the solid product remains substantially solid at up to 30°C. In some embodiments, the oral product is in solid form, such as in the form of chews or pastilles. In some embodiments, the oral product is a chew or pastille.

[0351] The oral products as disclosed herein can be formed into a variety of shapes, including pills, tablets, spheres, strips, films, sheets, coins, cubes, beads, ovoids, obloids, cylinders, bean-shaped, sticks, or rods. Cross-sectional shapes of the product can vary, and example cross-sectional shapes include circles, squares, ovals, rectangles, and the like. Such shapes can be formed in a variety of manners using equipment such as moving belts, nips, extruders, granulation devices, compaction devices, and the like.

[0352] In some embodiments, the solid oral product is in a form selected from the group consisting of a chew, or a pastille. In other embodiments, the oral product is in solid form, such as in the form of loose moist snuff, loose dry snuff, chewing tobacco-type form, pelletized pieces, extruded or formed strips, pieces, rods, or sticks, finely divided ground powders, finely divided or milled agglomerates of powdered pieces and components, flake-like pieces, molded processed pieces, gums, films, readily water-dissolvable or water-dispersible films or strips, capsule-like materials, tablets, lozenges. In some embodiments, the oral product is a tablet or lozenge. In some embodiments, the oral product may be a chewing gum product. In some embodiments, the oral product is in the form of moist snuff or snus, which may or may not contain tobacco. Chews

[0353] In some embodiments, the product can be chewable, meaning the product has a mild resilience or "bounce" upon chewing, and possesses a desirable degree of malleability. A product in chewable form may be entirely dissolving, or may be in the form of a non-dissolving gum in which only certain components (e.g., active ingredients, flavour, sweetener) dissolve, leaving behind a non-dissolving matrix.

[0354] As described herein a ^chew^ is a confectionary-type product that may be chewed by the user before dissolving in the mouth (i.e. a dissolvable chew) or may be a chewing gum. Preferably, the ^chew^ dissolves fully in the mouth of the user. The product may be dissolvable. As used herein, the terms "dissolve," "dissolving," and "dissolvable" refer to products having aqueous-soluble components that interact with moisture in the oral cavity and enter into solution, thereby causing gradual consumption of the product. According to one aspect, the dissolvable product is capable of lasting in the user's mouth for a given period of time until it completely dissolves. Dissolution rates can vary over a wide range, from about 1 minute or less to about 60 minutes. For example, fast release products typically dissolve and / or release the desired component(s) (e.g., active ingredient, flavour, and the like) in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or about 20 seconds or less). Dissolution can occur by any means, such as melting, mechanical disruption (e.g., chewing), enzymatic or other chemical degradation, or by disruption of the interaction between the components of the product.

[0355] In other embodiments, the products do not dissolve during the product's residence in the user's mouth.

[0356] Chewable embodiments generally include a binding agent, such as a natural gum, pectin, agar, carrageenan, starch, or a combination thereof. In some embodiments, the binding agent comprises or is pectin.

[0357] In some embodiments, the chewable product (i.e. ^chew^) comprises the combination of active ingredients, at least one bulking agent selected from the group consisting of a sugar alcohol, or at least one a sugar, or a combination of at least one sugar alcohol and at least one sugar, and at least one binding agent. In some embodiments, the chewable product (i.e. ^chew^) comprises the combination of active ingredients in an amount of from about 0.1% to about 10% by weight of the oral product, at least one bulking agent selected from the group consisting of a sugar alcohol, or at least one a sugar, or a combination of at least one sugar alcohol and at least one sugar, and at least one binding agent. The chewable product or chew may also optionally include a sweetening agent and / or a flavouring agent.

[0358] Representative chew compositions and products may incorporate from about 0.1% to about 20% by weight of the combination of active ingredients, from about 0.1% to about 10% of a binding agent (e.g. pectin, agar, carrageenan, starch, or a combination thereof), and at least about 30% by weight of at least one bulking agent selected from the group consisting of a sugar alcohol, or at least one a sugar, or a combination of at least one sugar alcohol and at least one sugar, based on the total weight of the oral product. Optionally, the oral product may further comprise about 0.01 to about 2% by weight of a sweetening agent, and / or from about 0.1% to about 5% by weight of at least one flavoring agent, based on the total weight of the oral product. The particular percentages and choice of ingredients will vary depending upon the desired flavor, texture, and other characteristics. For example, the combination of active ingredients may be present in a chew in an amount of from about 0.1% to about 10% by weight of the oral product.

[0359] In some embodiments, the oral chew product comprises pectin and an organic acid, along with one or more sugar alcohols in an amount of at least 30% by weight of the oral product.

[0360] In some embodiments, the oral chew product comprises at least one bulking agent selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar. In some embodiments, the at least one bulking agent is selected from a sugar alcohol, or a sugar. In some embodiments, the at least one bulking agent is selected from sugar alcohol(s). In some embodiments, the at least one bulking agent is selected from sugar(s). In some embodiments, the at least one bulking agent is selected from a combination of at least one sugar alcohol and at least one sugar.

[0361] The total amount of bulking agent(s) (preferably sugar alcohol) may be at least about 30% by weight, such as at least about 40% by weight, such as at least about 45% by weight of the oral product. In some preferred embodiments, the total amount of bulking agent(s) (preferably sugar alcohol) may be at least about 50% by weight of the oral product.

[0362] In some embodiments, the total amount of sugar alcohol is present in an amount of from about 30% to about 99% by weight, such as from about 40% to about 99% by weight, such as from about 45% to about 99% by weight, such as from about 50% to about 99% by weight, such as from about 60% to about 95% by weight, and preferably from about 70% to about 90% by weight of the oral product. The sugar alcohol may preferably be present in an amount of from about 80% to about 95% by weight of the oral product. In some preferred embodiments, the total amount of bulking agent(s) (preferably sugar alcohol) is present in an amount of from about 40% to about 60% by weight of the oral product. Alternatively, in some preferred embodiments, the total amount of sugar alcohol is from about 50% to about 90% by weight of the oral product. In such embodiments, the bulking agent may consist of sugar alcohol(s).

[0363] The sugar alcohol may be selected from the group consisting of isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or mixtures thereof. In some embodiments, the sugar alcohol is selected from the group consisting of maltitol, sorbitol, erythritol, mannitol, lactitol, xylitol, isomalt, and mixtures thereof. In some embodiments, the sugar alcohol is selected from the group consisting of maltitol, isomalt, and mixtures thereof. In some embodiments, the sugar alcohol is or comprises isomalt. In some embodiments, the sugar alcohol is or comprises maltitol. In some embodiments, the sugar alcohol comprises a combination of isomalt and maltitol.

[0364] In some embodiments, a sugar substitute may be an alternative to sugar alcohols, or used in combination with one or more sugar alcohols. Suitable sugar substitutes include allulose, soluble tapioca fiber, inulin, and combinations thereof. In some embodiments, sugar is included as an alternative to sugar alcohols, or is used in combination with one or more sugar alcohols. Where present, sugar may be included in the form of glucose, fructose, galactose, sucrose, or mixtures thereof. In some embodiments, the oral chew product comprises sugar (e.g. sucrose) in combination with at least one sugar alcohol (e.g. maltitol and / or isomalt). The sugar may be present in any suitable amount, such as from 10% to about 50%, such as from about 20% to about 40% by weight of the oral product.

[0365] In some embodiments the bulking agents consists of at least one sugar alcohol selected from maltitol and / or isomalt and sucrose. In some embodiments the at least onebulking agent consists of maltitol and sucrose. In some embodiments the at least one bulking agent consists of isomalt and sucrose. In some embodiments, the bulking agent comprises a combination of maltitol and sugar. The maltitol may be present in an amount of from about 20% to about 50%, and the sugar may be present in an amount of from about 10% to about 50% by weight of the oral product. In some embodiments, the bulking agent comprises a combination of isomalt and sugar. The isomalt may be present in an amount of from about 20% to about 50%, and the sugar may be present in an amount of from about 10% to about 50% by weight of the oral product.

[0366] In some embodiments, the binding agent is selected from the group consisting of pectin, agar, carrageenan, starch, and mixtures thereof. In some preferred embodiments, the binding agent is or comprises pectin. In some embodiments, the binding agent (e.g. pectin) is present in an amount of from about 0.1% to about 10% by weight of the oral product. Preferably, the binding agent (e.g. pectin) is present in an amount of from about 1% to about 5% by weight of the oral product.

[0367] The oral product may also comprise an organic acid, a gelation agent or both to crosslink the pectin.

[0368] In some embodiments, the oral chew product comprises an acidifying agent. The acidifying agent may be an organic or inorganic acid. The organic acid may be any suitable organic acid. Suitable organic acids are as described hereinabove in the section titled ^Additives^. For example, the organic acid may be selected from the group consisting of citric acid, malic acid, lactic acid, benzoic acid, tartaric acid, and mixtures or salts thereof. The organic acid may, for example, include a combination of citric acid and a salt of citric acid (e.g. a sodium salt).

[0369] Oral products of the present disclosure in the form of a chew may contain various amounts of water. For example, the water content of the chew product may be provided within a specified range so as to dictate the final form of the product. The water content of the chew products described herein, prior to use by a consumer of the product, may vary within such ranges according to the desired properties and characteristics, in addition to dictating the final form of the product. For example, chew-type products may possess a water content in the range of from about 1% to about 20%, such as from about 1% to about 10% by weight of the oral product.

[0370] The oral product in the form of a chew may comprise:

[0371] (a) the combination of active ingredients as described herein in an amount of from about 0.1% to about 10% by weight of the oral product;

[0372] (b) at least one bulking agent selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, wherein the total amount of sugar alcohol and / or sugar is from about 40% to about 99% by weight of the oral product;

[0373] (c) at least one binding agent in an amount of from about 0.1% to about 10% by weight of the oral product;

[0374] optionally (d) a flavouring agent, an organic acid and / or a sweetening agent.

[0375] The oral chew product may have a weight of from about 0.1 g to about 10 g, such as from about 0.5 g to about 5 g. Preferably, the oral ch...

Claims

CLAIMS 1. Non-therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereof, to increase cognitive performance of a human or animal::Formula (I) wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4.

2. Non-therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereof, to increase alertness of a human or animal:wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4 3. Non-therapeutic use of a compound of Formula (I), a derivative thereof, or a combination thereof, to increase energy levels of a human or animal:Formula (I) wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; andm is an integer from 0 to 4.

4. The use of any of claims 1 to 3, wherein said use further comprises reduced jitteriness in the human or animal, optionally wherein the reduced jitteriness in the human or animal is relative to the use of caffeine in said human or animal.

5. The use of any of claims 1 to 4, wherein m is 2 or 3.

6. The use of claim 5, wherein m is 2; preferably wherein the R4groups are at the C-5 and C-7 positions of the fused ring.

7. The use of any one of claims 1 to 6, wherein the phenyl groups are substituted by one or two groups independently selected from OH and O-alkyl; and / or wherein a double bond is present between positions C-2 and C-3 of the fused ring.

8. The use of any one of claims 1 to 5, wherein the compound of Formula (I) is a compound of Formula (Ia):wherein: R1is H, OH or O-alkyl; preferably H, OH, or OMe; more preferably H or OH; each R3is independently selected from OH and O-alkyl; each R4is independently selected from OH and O-alkyl; m is an integer from 0 to 4; and n is an integer from 0 to 5.

9. The use of any one of claims 1 to 5, wherein the compound of Formula (I) is a compound of Formula (Ib):wherein: R2is H, OH or O-alkyl; preferably H, OH or OMe; more preferably H or OH; each R3is independently selected from OH and O-alkyl; each R4is independently selected from OH and O-alkyl; m is an integer from 0 to 4; and n is an integer from 0 to 5.

10. The use of any one of claims 1 to 9, wherein: each R3is OH; and / or each R4is OH.

11. The use of any one of claims 1 to 5, wherein the compound of Formula (I) or derivative thereof is selected from flavone, genistein, hispidulin, kaempferol, naringenin, quercetin, galangin, and combinations thereof; optionally wherein the compound of Formula (I) is selected from flavone, genistein, hispidulin, kaempferol, naringenin, galangin, and combinations thereof.

12. The use of any one of claims 1 to 11, wherein the compound of Formula (I) is used in combination with one or more B vitamins selected from B1, B2, B6, and B7; optionally wherein the compound of Formula (I) is further used in combination with one or more compounds selected from taurine, vitamin C, vitamin D, ginseng, zinc or a salt thereof, L-theanine, maca root, beta-alanine, theacrine, coenzyme Q10, theobromine, caffeine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, or combinations thereof.

13. An oral product comprising a combination of active ingredients, wherein the combination comprises: (a) a compound of Formula (I), a derivative thereof, or a combination thereof:wherein: (i) R1is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; and R2is an optionally substituted phenyl group; or (ii) R1is an optionally substituted phenyl group; and R2is H, OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, or dialkenylamino; wherein the optional substituents of the phenyl groups are independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; each R4is independently selected from OH, O-alkyl, O-alkenyl, SH, alkylthio, alkenylthio, NH2, alkylamino, dialkylamino, alkenylamino, and dialkenylamino; and m is an integer from 0 to 4; and (b) one or more B vitamins selected from B1, B2, B6 and B7; and / or a compound selected from maca root, ginseng, coenzyme Q10, caffeine, vitamin C, beta-alanine, theacrine, taurine, zinc or a salt thereof, L-theanine, theobromine, Echinacea, selenium, lemon balm, chamomile, L-tryptophan, piperine or a geometric isomer thereof, saffron, and combinations thereof.

14. The oral product of claim 13, wherein the compound of Formula (I), derivative or combination thereof is present in an amount of from about 0.01 % to about 20 % by weight of the oral product.

15. The oral product of claim 13 or claim 14, wherein the oral product does not comprise caffeine or a salt or solvate thereof.

16. The oral product of any one of claims 13 to 15, wherein the oral product is a liquid dosage form, optionally wherein the liquid oral dosage form has a volume of from about 20 mL to about 100 mL of liquid.

17. The oral product of claim 16, wherein the product comprises water in an amount of from about 50 wt% to about 99.9 wt%, based on the total weight of the oral product.

18. The oral product of any one of claims 13 to 15, wherein the oral product is a solid oral product, wherein the solid oral product is in chewable form, optionally wherein the product further comprises at least one binding agent, and at least one bulking agent selected from the group consisting of a sugar alcohol, a sugar, or a combination thereof.

19. The oral product of any one of claims 13 to 18, wherein the compound of Formula (I) is a compound as defined by any one of claims 5 to 11.

20. The oral product of any one of claims 13 to 19, wherein the oral product is a nutraceutical product.

Images