Fatty acid analogs and their use in treatment of cognitive impairment, behavioral conditions and chronic pain

Abstract

To provide compositions and methods for treating and preventing cognitive impairment, movement disorders, chronic pain, depression, decreased appetite, and addiction.SOLUTION: Also provided are methods for the diagnosis and monitoring of cognitive impairment, movement disorders, chronic pain, depression, decreased appetite, addiction, and other conditions such as convulsion or seizure. These compositions comprise fatty acid compounds and salts thereof which may be administered either alone, in combination with other medicaments, or as part of various treatment regimens. The provided compositions are effective for modulating markers, including, but not limited to, behavior associated with cognitive impairment, movement disorders, chronic pain, depression, decreased appetite, opiate addiction, and other related conditions. Methods for administering the compositions are also provided.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, addiction, seizures and convulsions, and other Compositions comprising the fatty acid analogs are provided for treating conditions, including cognitive disorders. , movement disorders, chronic pain, depression, loss of appetite, addiction, seizures, convulsions and other conditions Methods for monitoring are also provided. [Background technology]

[0002] Cognition is the mental act or process of gaining knowledge and understanding through thought, experience, and sensation. Cognitive impairment (also known as cognitive decline) is a neurodegenerative condition (e.g., Brain damage due to trauma (such as in Alzheimer's disease), brain damage due to injury, infection, or substances Abuse, substance withdrawal, psychosis, vitamin and other important nutrient deficiencies, hormonal problems, Cognitive impairment can be caused by a cognitive imbalance or a side effect of medication. Cognitive impairment can also occur as a process. This may be related to cognitive impairment and confusion, due in large part to the increasing number of elderly people worldwide. Novel therapies are urgently needed to prevent, manage and treat intellectual disability.

[0003] Movement disorders are neurological conditions that cause problems with movement. Examples include dystonia, chorea, Huntington's disease, Parkinson's disease, and parkinsonism. , tics, Tourette's syndrome, ataxia, tremor, essential tremor, myoclonus, polyphasic Sclerosis, startle syndrome, restless legs syndrome, stiff person syndrome, gait disorders and Movement disorders can be caused by damage to the brain, spinal cord or peripheral nerves, metabolic disorders, stroke and It can be caused by vascular disease, toxins, infections, medications and genetics.

[0004] Chronic pain is defined as any pain that lasts for more than 12 weeks and may persist for months or years. Causes of chronic pain include past injuries, back pain, migraines and other headaches, and arthritis. Chronic pain can be caused by a variety of conditions, including: rheumatoid arthritis, ... It may result in or be accompanied by sleep disturbances, loss of appetite and mood changes. Formula changes may help manage chronic pain, but there are many other medications that may be prescribed to help manage this condition. Herbal treatment is often necessary. Opiates are the most effective for pain. Some prescription drug treatments are addictive, contributing to the prevalence of drug addiction and its resulting Therefore, new, non-addictive, and effective pain management treatments are needed. are.

[0005] Depression is a mood disorder that affects the way an individual feels, thinks, and cope with daily activities. The forms of depression include persistent depressive disorder (dysthymia), postpartum depression, and psychotic depression. These include depression, seasonal affective disorder, bipolar disorder, severe mood dysregulation disorder, and premenstrual dysphoric disorder. The causes of depression include genetic, biological, environmental and psychological factors. Depression occurs alongside chronic illnesses such as diabetes, cancer, heart disease, and Parkinson's disease. Chronic pain can be a persistent, painful condition that can be exacerbated by chronic illness. or moods of anxiety, hopelessness, irritability, lack of energy, fatigue, difficulty concentrating, difficulty sleeping, changes in appetite This can lead to weight gain, weight changes, pain, headaches and digestive problems. Although it can often be treated with change and medication, the best way to target both depression and the associated chronic illness is to New, more targeted treatments are needed.

[0006] Loss of appetite is common to many chronic, life-threatening illnesses, and lack of proper nutrition can contribute to the progression of these conditions. This cycle of chronic illness and loss of appetite can have detrimental effects on the health and well-being of the individual. This can lead to a vicious cycle. Anorexia is the absence or loss of appetite, which results in Loss of appetite. This can be common in advanced cancer. Weight loss can result from loss of appetite. Cachexia is a state of general poor health and malnutrition that results in a loss of fat, muscle, and Characterized by weakness and thinness due to bone loss, it is associated with advanced cancer, AIDS, and congestive heart failure. It can occur with other severe symptoms, including loss of appetite. An estimated 80% of cancer patients have cachexia. Causes of dysgeusia / cachexia syndrome include metabolic changes, chronic inflammation, pain, dysgeusia, and loss of taste. , hypersomnia, swallowing problems, difficulty breathing, nausea, vomiting, constipation, diarrhea, drug side effects, psychological distress changes associated with aging and life-threatening chronic diseases, such as oral or esophageal infections Current treatments for anorexia and cachexia include steroids, cannabis, and These treatments include benzodiazepines and prokinetic drugs. However, these treatments are associated with anorexia and They do not treat the underlying chronic conditions that are the primary cause of tremors and cachexia.

[0007] A spasm is a condition in which the muscles of the body contract and relax rapidly, resulting in uncontrollable contractions. Convulsions can occur during seizures, drug reactions, severe infections, sepsis, hyperthermia, and severe Vomiting and / or diarrhea, acute onset of diabetes (extremely high or low blood sugar levels), hydration Abnormalities (severe dehydration or overhydration), severe malnutrition, excess fluids due to trauma or internal bleeding Excessive blood loss, organ failure (e.g., acute renal failure), allergic reactions, drug overdose, drug withdrawal or may be caused by heat stroke. Epileptic seizures usually involve convulsions, hence the term "Convulsion" is sometimes used as a synonym for "seizure." However, not all seizures Not all epileptic seizures lead to convulsions, and not all convulsions are caused by epileptic seizures. Non-epileptic seizures are similar to epileptic seizures but are caused by abnormalities in cortical neurons. They are paroxysmal events without normal rhythmic discharges. They may be physiological or psychological. Psychogenic non-epileptic seizures (PNES) are seizures that resemble epileptic seizures. These are events that occur without the characteristic discharges associated with epilepsy. PNES is a type of non-epileptic seizure mimic caused by a non-epileptic seizure disorder ( Also known as Neuro-Abnormalities and Functional Neurological Disorders (NEAD), but less well known not present.

[0008] Opioids bind to opiate receptors in the cell membrane of neurons and exert their analgesic effects. These are controlled substances that provide pain relief and control pain, including morphine, codeine, These include fentanyl, methadone, and buprenorphine. Opiate addiction is becoming an epidemic. This has led to an increase in opioid overdose deaths, including 49,000 deaths in the United States in 2017. Opiate withdrawal is a leading cause of death in Americans under 50. Symptoms are severe and include muscle aches, pain, agitation, anxiety, nausea, gastrointestinal upset, frequent Symptoms include palpitations, rhinorrhea, and chills (Wesson DR, Ling W. The Cli nical Opiate Withdrawal Scale(COWS)J Psy (Vocative Drugs. 2003;35:253-259). The severity of the condition makes it difficult for individuals to stop using opioids, leading to opioid withdrawal. Novel approaches to attenuate symptom reduction and novel non-addictive medications to control pain are needed. It is urgently needed. Summary of the Invention

[0009] To treat and prevent cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, and addiction Compositions and methods for treating cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, addiction and other conditions Methods for diagnosing and monitoring symptoms, such as convulsions or seizures, are also provided. These compositions may be administered alone or in combination with other drugs or as part of various treatment regimens. The provided compositions comprise fatty acid compounds and salts thereof, which can be administered to treat cognitive impairment, movement disorders, and the like. This includes behaviors related to addiction, chronic pain, depression, loss of appetite, opiate addiction, and other related conditions. These compositions are effective in modulating markers including, but not limited to, A method is provided.

[0010] Therefore, the first aspect of broad applicability (i.e., the aspect identified herein) In a first aspect, which may be combined independently with any of the above or embodiments, cognitive impairment, Treating or preventing movement disorders, chronic pain, depression, loss of appetite, convulsions, seizures and opiate addiction A method for preventing a disease is provided, which method comprises administering to a patient in need thereof a compound of formula (I) or In various embodiments, a compound of formula (I) is administered in the presence of a pharmaceutically acceptable salt thereof. ) can be represented by the formula (Ia), the formula (Ib), the formula (Ic), the formula (Id), the formula (Ie), the formula (I The compound may be a compound of formula (If), formula (Ig) or formula (Ih).

[0011] Therefore, the second aspect of the invention (i.e., the aspect specified herein) is broadly applicable. In a second aspect, which may be combined independently with any of the above or embodiments, a compound or a pharmaceutically acceptable salt thereof, wherein the compound is 2- Ethyl, 2,2-diethyl, 3-oxa, 2,2-dimethyl-3-oxa, 1-tetrazo 1-oxazolone, 1-oxadiazolone, N-hydroxyamide, 2-methyl- one or more substituents selected from the group consisting of 1-tetrazole and 2-methyl-2-ethyl The fatty acids are saturated fatty acids substituted with substituted groups; Stearic acid (C14:0), pentadecanoic acid (C15:0), palmitic acid (C16:0) , heptadecanoic acid (C17:0) and stearic acid (C18:0) and pharmaceutically acceptable The compound of these embodiments has the structure: These include, but are not limited to: [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table 15 Table 16 Table 17 Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29 Table 30 Table 31 Table 32 Table 33 Table 34 Table 35 Table 36 Table 37 Table 38 Table 39 Table 40 Table 41 Table 42 Table 43 Table 44 Table 45 Table 46 Table 47 Table 48 Table 49 Table 50 Table 51 Table 52 Table 53 Table 54 Table 55 Table 56 Table 57 Table 58 [Table 59] [Table 60] [Table 61] [Table 62] [Table 63] [Table 64] [Table 65] [Table 66] [Table 67] [Table 68] [Table 69] [Table 70] [Table 71] [Table 72]

[0012] Therefore, the broadly applicable third aspect (i.e., the aspect specified herein) In a third aspect, which can be combined independently with any of the above aspects or embodiments, A drug comprising a compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In various embodiments, the compound of formula (I) is represented by formula (Ia): Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (Ig) or Formula ( Ih).

[0013] Any of the features of the embodiments of the first to third aspects may be used in any of the embodiments specified herein. The present invention is applicable to all aspects and embodiments. Any of the features may be partially or fully compatible with other embodiments described herein. are individually combinable, e.g., one, two, three or more The embodiments may be combined in whole or in part. None of the features of such embodiments may be essential to other aspects or embodiments. The method of any aspect or embodiment may be combined with the system or apparatus of another aspect or embodiment. and the system of any aspect or embodiment may be implemented by another aspect or embodiment. The method may be configured to perform the method of the present invention. [Brief explanation of the drawings]

[0014] [Figure 1] Figure 1 provides a summary of the effective concentrations (EC50 μM) for PPAR-alpha, PPAR-delta, and CB1 receptor agonist activity and inhibitory concentrations (IC50 μM) for OPRM1 antagonist activity of substituted saturated fatty acids (2-methyl-C15:0, 2-ethyl-C15:0, and 1-tetrazole-C15:0) compared to assays treated with unsubstituted saturated fatty acids (C15:0).

[0015] [Figure 2]Figure 2 provides a summary of the maximal activity (%) of PPAR-alpha, PPAR-delta, and CB1 receptor agonist activity and inhibitory concentration (IC50) for OPRM1 antagonist activity of substituted saturated fatty acids (2-methyl-C15:0, 2-ethyl-C15:0, and 1-tetrazole-C15:0) compared to assays treated with unsubstituted saturated fatty acids (C15:0) and a positive control. DETAILED DESCRIPTION OF THE INVENTION

[0016] a composition comprising a compound, for example a compound of formula (I) or a pharmaceutically acceptable salt thereof; as well as cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, addiction, seizures, convulsions and related Related methods for treating disorders are provided. The compounds provided are saturated fatty acids substituted with 2-alkyl or 2,2-di-alkyl groups. or an acid isostere and / or a pharmaceutically acceptable salt thereof.

[0017] Some embodiments relate to pharmaceutical compositions and methods of treatment using the pharmaceutical compositions. 1. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has the structure: [ka] Formula (I) or a pharmaceutically acceptable salt thereof, wherein G is an alkyl group; Substitution or substitution C 10 -C 17 Alkyl, unsubstituted or substituted C 10 -C 17 Alkenyl or 1, 2 or 3 oxa or thia substitutions, e.g., alkyl chains or alkyl groups one or more oxygen atoms and / or sulfur atoms replacing one or more carbon atoms of the alkenyl chain; Unsubstituted or substituted C with children10 -C 17 alkyl; X is selected from O and C R 1 R 2 where R 1 and R 2 are each independently H or unsubstituted or substituted C1-C6 alkyl; Y 1 and Y 2 are independently H, non Substituted or substituted C1-C6 alkoxy or unsubstituted or substituted C1-C6 alkyl Yes or Y 1 and Y 2 together represent unsubstituted or substituted cycloalkyl, may form a chloroalkenyl, aryl, heteroaryl or heterocyclyl; Z is a carboxylic acid, a C1-C6 alkyl ester, an unsubstituted or substituted amide, a 5- or 6-membered unsubstituted or substituted heterocyclyl and 5- or 6-membered unsubstituted or substituted heteroaryl In formula (I), when a group is designated as "substituted", that group is selected from: C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C7 cyclo Alkyl, C1-C7 cycloalkenyl, acyl (C1-C6 alkyl), C1-C6 acyl Alkoxy (C1-C6 alkyl), amino (C1-C6 alkyl), amino acid, C6-C 10 Aryl, heteroaryl, heterocyclyl, C6-C 10 Aryl (C1-C6 Heteroaryl(C1-C6 alkyl), heterocyclyl(C1-C6 alkyl) hydroxyl (C1-C6 alkyl), acyl, cyano, halogen, thiocarbonyl O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C- Amide, N-Amide, S-Sulfonamide, N-Sulfonamide, C-Carboxy, O- Carboxy, isocyanato, thiocyanato, isothiocyanato, azido, nitro, silyl , sulfenyl, sulfinyl, sulfonyl, halo(C1-C6 alkyl), C1-C6 Haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamide and amine and substituted with one or more substituents individually and independently selected from the group consisting of The pharmaceutical composition may further comprise a pharmaceutically acceptable carrier.

[0018] In some embodiments, Y 1 and Y 2 are each independently H or one In a further embodiment, Y is C1-C6 alkyl substituted with the above halogens. 1 and Y 2 are each independently H, unsubstituted methyl, or substituted with 1 to 3 halogens. methyl, unsubstituted ethyl, and ethyl substituted with 1 to 5 halogens. In still further embodiments, each halogen is independently selected from F, Cl, Br, and I. In some embodiments, each halogen is selected from: In the embodiment, Y 1 and Y 2 are each independently selected from H and unsubstituted methyl will be done.

[0019] In some embodiments, Z is a 5-membered unsubstituted or substituted heteroaryl. In some embodiments, Z is a 5-membered unsubstituted heteroaryl. In certain embodiments, the 5-membered unsubstituted heteroaryl is an unsubstituted tetrazole or an unsubstituted 1,2, In some embodiments, Z is 4-oxadiazol-5(4H)-one. carboxylic acid or C1-C6 alkyl ester. is an unsubstituted or substituted amide. In yet a further embodiment, Z is C-C 1 or 2 selected from C1-C6 alkyl, hydroxy and C1-C6 hydroxyalkyl It is an amide substituted by two groups.

[0020] In some embodiments, R 1 and R 2 are each independently H or one In some embodiments, the alkyl group is C1-C6 alkyl substituted with the above halogen. R 1 and R 2 are each independently H.

[0021] In some embodiments, G is C substituted by one or more halogens. 10 - C 15 In some embodiments, G is an unsubstituted C 12 -C 14 Al It's a kill.

[0022] In some embodiments, the compound of formula (I) is selected from the group consisting of formula (Ia), formula (Ib), formula (I c), having the structure of formula (Id), formula (Ie), formula (If), formula (Ig) or formula (Ih) , Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (I In each of formulas (g) and (Ih), G, X, Y 1 , Y 2 and all groups containing Z , as indicated for formula (I). [ka] Formula (Ia) [ka] Formula (Ib) [ka] Formula (Ic) [ka] Formula (Id) [ka] Formula (Ie) [ka] Expression (If) [ka] Formula (Ig) [ka] Formula (Ih)

[0023] In various embodiments, the compound of formula (I) may be selected from the following, in each instance: , G is unsubstituted C 10 -C 15 Alkyl: [ka]

[0024] In some embodiments, the compound of formula (I) is [ka] and [ka] may be selected from:

[0025] In further embodiments, the compound is 2,2-dimethyl, 2-ethyl, 2,2- Diethyl, 3-oxa or 3-oxa-2,2-dimethyl substituted tridecanoic acid (C13:0), myristic acid (C14:0), pentadecanoic acid (C15:0), palmitic acid acetic acid (C16:0), heptadecanoic acid (C17:0) or stearic acid (C18: 0) saturated fatty acids, or tetrazole acid isosteres, oxazolonic acid isosteres, Oxadiazolonic acid isosteres, amides, N-hydroxyamides, (2-hydroxyethyl) It may be an amide or a pharmaceutically acceptable salt thereof.

[0026] In some embodiments, the compound is 2-ethylpentadecanoic acid or 1-ethylpentadecanoic acid. Trazolpentadecanoic acid.

[0027] In some embodiments, the oxadiazolonic acid isostere is an unsubstituted 1,2,4-oxadiazolonic acid isostere. In a further embodiment, the compound is an oxazoline-5(4H)-one isostere. Ronic acid isosteres are unsubstituted oxazol-2(3H)-onic acid isosteres.

[0028] Increased dietary intake of the odd-chain saturated fatty acid heptadecanoic acid significantly alters the metabolic status of bottlenose dolphins. was associated with an improvement in the syndrome (Venn-Watson et al. d dietary intake of saturated fatty acids heptadecanoic acid(C17:0)associated wit h decreasing ferritin and alleviated met abolic syndrome in dolphins,(2016)PLOS O NE 10(7):e0132117). Therefore, modified odd-chain saturated fats Oral administration of niacin has been shown to reduce the risk of multiple conditions, including diabetes, heart disease, stroke, neurodegenerative diseases, and depression. The study could be useful in treating metabolic syndrome, a condition that increases the risk of chronic diseases in people with diabetes. do.

[0029] Certain lipid compounds are disclosed in WO2017 / 093732 as being useful in treating retinal degenerative disorders and These lipids have been proposed for the treatment of ophthalmic disorders such as inflammatory diseases of the eye. The substance is an unsaturated fatty acid derivative (e.g., an alkyl group containing 1 to 5 double bonds). Arson et al., in Lipids, Vol. 40, No. 1 (2005), Alpha- and alpha-glycoproteins of various fatty acids, including saturated fatty acids (palmitic acid, i.e., C16:0) Demonstrated increased PPAR-alpha and PPAR-gamma activity through methylation However, these derivatives were not effective as PPARδ activators. In contrast, C15:0 is a part of PPAR delta. It is a partial agonist of PPAR-delta and its derivatives have improved EC50 and / or It has been observed that the highest concentrations are often observed at or above the threshold.

[0030] Peroxisome proliferator-activated receptors (PPARs) regulate mammalian metabolism. PPARs are known to inhibit the growth of the thyroid gland and are therefore therapeutic targets for many diseases. There are three isotypes: alpha, delta, and gamma. The molecules that bind and activate each type differently are involved in inflammation, dyslipidemia, prediabetes, and diabetes. Diabetes, fatty liver disease, non-alcoholic steatohepatitis and insulin resistance It has been demonstrated to treat various symptoms associated with metabolic syndrome. The scientist is a specialist in the treatment of autoimmune diseases, asthma, anemia, cancer, cardiovascular disease, dermatitis, hypertension, and pulmonary diseases (pulmonary fibrosis and systemic sclerosis), psoriasis, iron overload, and Alzheimer's disease and It has been proposed as a therapeutic target for neurodegenerative diseases, including other forms of dementia. Acids have a specific action on the PPAR isoforms PPAR-alpha and PPAR-delta. It is believed that PPARs are endogenous ligands, and structural features such as carbon chain length are important for the PPAR It has been hypothesized that this may affect anti-inflammatory activity (Forman BM, Chen J, Eva ns RM (1997) Hypolipidemic drugs, polyunsat urated fatty acids,and eicosanoids are l igands for peroxisome proliferator-activ ated receptors α and δ.Proc Natl Acad Sc i 94:4312-4317).

[0031] Pentadecanoic acid (C15:0) and heptadecanoic acid in attenuating components of the metabolic syndrome The proven effectiveness of citric acid (C17:0) is the inhibition of PPAR-alpha and PPAR-delta It can be hypothesized that this may be due in part to their role as agonists. The association with PPARs is described in the following references: Aleshin S et al. l.(2013)Peroxisome proliferator-activate d receptor(PPAR)β / δ,a possible nexus of PPARα-and PPARγ-dependent molecular path ways in neurodegenerative diseases:revie w and novel hypotheses.Neurochem Int 63: 322-330;Barish GD et al.(2006)PPARδ:a da gger in the heart of metabolic syndrome. J Clin Invest 116:590-597;Bonomo LDF et al.(2012)Iron overload potentiates diet- induced hypercholesterolemia and reduces liver PPAR-α expression in hamsters.J B iochem Mol Toxicol 26:224-229;Chiba T et al.(2012)Topical application of PPARα(b ut not β / δ or γ)suppresses atopic dermat itis in NC / Nga mice.Allergy 67:936-942;C hoi JM and Bothwell ALM(2012)The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune disea ses.Mol Cell 33:217-222;Hosokawa M et al .(2004)Fucoxanthin induces apoptosis and enhances the antiproliferative effect o f the PPARγ ligand,troglitazone,on colon cancer cells.BBA Gen Subj 1675:113-119; Janani C and Kumari BDR(2015)PPAR gamma gene-a review.Diab Metab Synd Clin Res R ev 9:46-50;Leibovitz E et al.(2007)PPAR activation:a new target for the treatmen t of hypertension.J Cardio Pharmacol 50: 120-125;Lee HY et al.(2015)PPAR-α and gl ucocorticoid receptor synergize to promo te erythroid progenitor self-renewal.Nat ure 522:474-477;Madrazo JA and Kelly DP( 2008)The PPAR trio:Regulators of myocard ial energy metabolism in health and dise ase.J Mol Cell Cariol 44:968-975;Milam J E et al.(2008)PPAR-γ agonists inhibit pr ofibrotic phenotypes in human lung fibro blasts and bleomycin-induced pulmonary f ibrosis.Am J Physiol Lung Cell Mol Physi ol 294:L891-L901;Sertznig P et al.(2008) Peroxisome proliferator-activated recept ors(PPARs)and the human skin.Am J Clin D Ermatol 9:15-31;Sokolowska M et al.(2005 )Peroxisome proliferator-activated receipt tor gamma(PPAR-gamma)and their role in i mmunoregulation and inflammation control .Postepy Higieny 59:472-484;Trifillieff A et al. (2009) PPAR-α and-γ but not-δ ago nists inhibit airway inflammation in am urine model of asthma:in vitro evidence for an NF-kβ-independent effect.Br J Pha rmacol 139:163-171; and Wei et al. (2010) Pe roxisome proliferator-activated receptor γ:innate protection from excessive fibr inogenesis and potential therapeutic tar get in systemic sclerosis.Curr Opin Rhem atol 22:671–676.

[0032] Modified saturated fatty acids improve hydrophilic binding in the AF2 pocket of Arm-II. Therefore, certain analogs of fatty acids may provide improved performance compared to natural fatty acid forms. By improving the PPAR agonist activity, Thus, saturated fatty acid analogs, such as the compounds provided herein, have the potential to provide a wide range of fatty acid analogs compared to naturally occurring fatty acids. It is hypothesized that these compounds may be more effective in treating metabolic syndrome and its components. can.

[0033] Thus, the compounds described above, for example compounds of formula (I), or pharmaceutically acceptable salts thereof, The salts or metabolites thereof may advantageously activate PPARs.

[0034] Cannabinoid receptors are endocannabinoids, phytocannabinoids, and syncannabinoids. It binds to endocannabinoids and affects cognition, memory, mood, movement, pain sensation, appetite, and skin G protein-coupled receptors mediate cannabinoid-induced health-related effects Therefore, cannabinoid receptors are therapeutic targets for a number of diseases. There are two subtypes of cannabinoid receptors: cannabinoid receptor 1 (CNR1) or CB1 receptor) and cannabinoid receptor 2 (CNR2 or CB1 receptors are found in the brain and spinal cord. Sceptor is the primary target of cannabinoids, glutamate and gamma-aminobutyric acid It exerts its primary action by inhibiting neurotransmission mediated by CB Molecules that bind differently to the 1 receptor may be involved in chronic pain, depression, and loss of appetite (anorexia and dysphoria). It has been demonstrated to treat a variety of conditions related to inflammatory bowel disease (including urinary tract infections) and inflammation. B1 receptor agonists have been proposed as therapeutic targets for cognitive and motor impairments. Dietary fatty acids are known to have effects that can target both CB1 receptors and PPAR-α. It can affect the tissue levels of endocannabinoids. The combined CB1 receptor / PPAR-α agonist activity provides synergistic anti-inflammatory, neuroprotective, and and orexigenic (appetite-stimulating) effects. It has been hypothesized that this may affect the direct or precursor role of cannabinoids ( Artman A, Petersen G, Hellgren LI, Boberg J ,Skonberg C,Nellermann C,Honore Hansen S ,Hansen HS(2008)Influence of dietary fat ty acids on endocannabinoid and N-acylet hanolamine levels in the rat brain,liver and small intestine.BBA Mol Cell Biol L (See IPIDs 1781:200-212).

[0035] Opioid receptors are receptors for endogenous opioids such as beta-endorphin and enkephalin. It is a G protein-coupled receptor that binds to opioids and exogenous opioids. There are three subtypes of steroid receptors: mu (OPRM1), delta (OPRD), OPRM1 is a receptor for morphine, codeine, and kappa (OPRK1). It is the most common target of opioids, including benzodiazepines and fentanyl. The primary treatment for overdose is naloxone, a potent OPRM1 antagonist; Loxone cannot be used as a long-term solution to aid in the opioid withdrawal process. Opioid addiction induced by short-acting OPRM1 agonists with high risk of side effects To help treat people with addiction, methadone, a full agonist, and partial agonists are available. Long-acting OPRM1 agonists, including the anti-inflammatory drug buprenorphine, are currently in use. However, these treatments also cause dangerous decreases in breathing and heart rate, This can lead to overdose and death. Endocannabinoids and opioids are linked. There is extensive crosstalk between these systems, and cannabinoids may play a role in preventing opioid addiction. CB1 receptor agonists have been shown to attenuate opioid withdrawal symptoms, It has been proposed as a means of treating drug addiction, including idiopathic drug addiction (Scavone JL, Sterling RC, Bockstaele EJ (2013) Cannab inoid and opioid interactions: implicati ons for opiate dependence and withdrawal (See Neurosci 248:637-654).

[0036] The target of certain of the above embodiments is to treat cognitive impairment, movement disorders, chronic pain, Methods for detecting protective and risk factors for depression, appetite loss, and addiction are provided. Cognitive and motor impairments in mammalian subjects, including companion animals and humans , methods for diagnosing and monitoring chronic pain, depression, loss of appetite and addiction. Certain embodiments of the present invention are directed to mammalian subjects, including companion animals and humans. for treating cognitive impairment, movement disorder, chronic pain, depression, appetite loss or addiction in a patient with rheumatoid arthritis - Patents.com The goal of certain of the above embodiments is to provide a method for treating a subject's blood and the like, which increases the level of the compound of formula (I) or its corresponding fatty acid in companion animals and Cognitive impairment, movement disorders, chronic pain, depression, loss of appetite or The object of the present invention is to provide a method for detecting addiction. The goal of the embodiment is to detect opioid addiction and to evaluate the efficacy of methadone or other OPRM1 agonists. The present invention provides a method for treating opioid addiction without resorting to opioid use. In certain embodiments, the target of the condition is cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, The present invention provides a supplement for detecting and treating withdrawal or addiction. The goal of certain embodiments of the present invention is to provide companion animals that are easy to achieve in a cost-effective manner. cognitive impairment, movement disorders, chronic pain, depression, appetite disorders in mammalian subjects, such as animals and humans The present invention provides a method for detecting and treating depression or addiction. The goal of certain embodiments thereof is to improve cognitive impairment, movement disorders, chronic pain, caries, etc. in subjects. and to provide a method for modulating appetite loss or addiction markers or behaviors. The goal of certain of the above embodiments is to improve cognitive, motor, and cognitive function in a subject. and to provide a method for detecting a disorder, chronic pain, depression, loss of appetite or addiction. The goal of certain of the above embodiments is to improve cognitive and motor impairment in a subject. The present invention provides a method for treating neurological disorders, chronic pain, depression, loss of appetite, or addiction. The goal of certain of the above embodiments is to improve cognitive and motor impairment in a subject. and to provide a method for preventing the onset of chronic pain, depression, loss of appetite, or addiction. The goal of certain of the above embodiments is to detect the presence of a compound of formula (I) in the serum of a subject. The present invention also provides a method for increasing the amount of fatty acids in a plant or its corresponding fatty acids. A goal of certain embodiments of the present invention is to provide a method for treating opioid addiction. is.

[0037] One or more of the above goals may be achieved in the manner described herein. These are provided or achieved by various compositions, methods and uses. definition

[0038] The term "alcohol" as used herein is a broad term and will be understood by those skilled in the art. Its ordinary and customary meaning should be given (no special or customized meaning). The term also refers to compounds incorporating one or more hydroxy groups. or substituted by one or more hydroxy groups or refers to any compound, as described herein, that has been functionalized to include a group But not limited to this.

[0039] The term "derivative" as used herein is a broad term and its meaning is understood by those skilled in the art. The ordinary and customary meaning should be given (not a special or customized meaning). The term also includes, but is not limited to, flavors that incorporate one or more derivative groups or or functionalized to contain one or more derivative groups or substituted by one or more derivative groups. This refers to, but is not limited to, any compound as described herein that has been functionalized. Derivatives include esters, amides, anhydrides, acid halides, thioesters and Examples of suitable phosphates include, but are not limited to, phosphates and phosphates.

[0040] The term "hydrocarbon" as used herein is a broad term and is understood by those skilled in the art. should be given their ordinary and customary meaning (without special or customized meanings). (The meaning of this term should not be limited to the above.) The term refers to any compound containing only carbon and hydrogen atoms. This refers to, but is not limited to, a functionalized or substituted hydrocarbon moiety. , bearing one or more substituents as described elsewhere herein.

[0041] The term "lipid" as used herein is a broad term and its familiarity to those skilled in the art is well known. The usual and customary meaning should be given (no special or customized meanings). The term includes, but is not limited to, saturated and unsaturated oils and waxes, derivatives, amides, glycerides, fatty acids, fatty alcohols, sterols and sterol derivatives, In particular, this refers to, but is not limited to, tocopherols and carotenoids.

[0042] The term "pharmaceutically acceptable" as used herein is a broad term and is understood by those of skill in the art. Its ordinary and customary meaning for (and should not be limited to its intended meaning) and the term does not include excessive toxicity, irritation, allergies, without problems of hypersensitivity reactions or other complications that are commensurate with a reasonable risk / benefit ratio without regard to contact with human and animal tissue and / or human tissue within the scope of sound medical judgment. and refers to compounds, materials, compositions and / or dosage forms suitable for consumption by animals. But not limited to these.

[0043] As used herein, the terms "pharmaceutically acceptable salt" and "a pharmaceutically acceptable salt thereof" are used interchangeably. The terms "acceptable salts" and "acceptable salts" are broad terms and are given their ordinary and customary meaning to those of ordinary skill in the art. should be given (and not be limited to a special or customized meaning) ), these terms refer to salts prepared from pharmaceutically acceptable non-toxic acids or bases. Suitable pharmaceutically acceptable salts include, but are not limited to, metal salts, e.g. For example, aluminum salts, zinc salts, alkali metal salts (e.g., lithium salts, sodium salts and and potassium salts), alkaline earth metal salts (e.g., calcium and magnesium salts); Organic salts, such as lysine, N,N'-dibenzylethylenediamine, chloroprocaine, Choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) , procaine and tris salts; free acid and free base salts; inorganic salts, e.g., sulfate salts, hydrochloride and hydrobromide salts; and salts currently in widespread pharmaceutical use and well known to those skilled in the art. Sources of information, e.g., other salts listed in The Merck Index. Any suitable constituents may be selected to form salts of the therapeutic agents discussed herein. It may be used in combination with other compounds, provided that it is non-toxic and does not substantially interfere with the desired activity. In addition to salts, pharmaceutically acceptable precursors and derivatives of the above compounds may also be used. Pharmaceutically acceptable amides, lower alkyl derivatives and protected derivatives are also preferred. They may be suitable for use in the compositions and methods of the embodiments. Although it may be possible to administer the compound in the form of a pharmaceutically acceptable salt, it is also possible to administer the compound It is generally preferred to administer them in neutral form.

[0044] The term "pharmaceutical composition" as used herein is a broad term and will be understood by those skilled in the art. should be given its ordinary and customary meaning (without special or customized meaning) The term should not be limited to the meaning given herein, but may refer to one or more compounds disclosed herein. refers to a mixture of a compound with other chemical components (e.g., a diluent or carrier) Pharmaceutical compositions facilitate the administration of a compound to an organism. The composition can be prepared by reacting the compound with an inorganic acid or base or an organic acid or base. Pharmaceutical compositions are typically formulated for a specific intended route of administration. will be adjusted accordingly.

[0045] As used herein, the term "carrier" is used broadly to refer to any and should be given their ordinary and customary meaning to those skilled in the art (without special meaning). or customized meaning), the term refers to cells or tissues This refers to, but is not limited to, a compound that facilitates the incorporation of a compound into the Without limitation, dimethyl sulfoxide (DMSO) may be used to treat cells or tissues of a subject. It is a commonly used carrier that facilitates the incorporation of many organic compounds into water. Saline, ethanol, and mineral oil are also carriers used in certain pharmaceutical compositions. A.

[0046] As used herein, "diluent" is a broad term. and should be given its ordinary and customary meaning to those skilled in the art (including without limitation special meanings). (and should not be limited to any specific or customized meaning) and the term refers to any substance lacking pharmacological activity. A component in a pharmaceutical composition that may be pharmaceutically necessary or desirable. For example, a diluent may be used to refer to a substance that is too thick to be prepared and / or administered by mass. Diluents can be used to increase the bulk of drugs that are too potent for injection, oral ingestion, or other purposes. Or it can be a liquid for dissolving drugs to be administered by inhalation. A common form of diluent used is a buffered aqueous solution (e.g., phosphate buffered saline, which mimics the composition of human blood). buffered saline).

[0047] As used herein, "excipient" is a broad term. and should be given its ordinary and customary meaning to those skilled in the art (including without limitation special meanings). or customized meaning), the term refers to a pharmaceutical composition that To provide, but not limited to, bulk, consistency, stability, binding, lubricity, disintegration, etc. "Diluent" refers to, but is not limited to, a substance added to a composition to It is a type of excipient.

[0048] As used herein, "subject" is a broad term. and should be given its ordinary and customary meaning to those skilled in the art (including without limitation special meanings). (and should not be limited to a specific or customized meaning) the term refers to treatment, observation or "Animal" refers to, but is not limited to, animals that are the subject of experiments. "Animal" includes both cold-blooded and warm-blooded animals. Blood vertebrates and invertebrates, including fish, crustaceans, reptiles and especially mammals. "Mammals" include dolphins, mice, rats, rabbits, guinea pigs, dogs, and cats. dogs, sheep, goats, cattle, horses, primates (e.g., monkeys, chimpanzees, and apes) and and particularly, but not limited to, humans. The body is human.

[0049] As used herein, the terms "treat," "treatment," "therapeutic," or "cure" are used interchangeably. "Medicine" is a broad term and should be given its ordinary and customary meaning (e.g., These terms are used in conjunction with the terms "disease" and "disease-related" (and should not be limited to a different or customized meaning). It does not necessarily mean, but is not limited to, a complete cure or disappearance of the disease or symptoms. Some alleviation of any unwanted markers, signs or symptoms of the disease or condition constitutes treatment. and / or may be considered a treatment. Additionally, treatment may involve improving the overall health or appearance of a patient. This may include conduct that could worsen the public perception of the company.

[0050] As used herein, the terms "therapeutically effective amount" and "effective amount" are broad terms and include: Their ordinary and customary meaning to those skilled in the art should be given (even if they have no special meaning). and (and should not be limited to any other or customized meaning) these terms include, but are not limited to: active compounds that induce a biological or medical response, i.e., drugs, that are not specifically targeted to the body For example, a therapeutically effective amount of a compound may be a marker for a condition. or a subject in which symptoms are prevented, alleviated, or ameliorated, or treated. This response can be the amount necessary to extend the survival time of a tissue, system, animal or human. Treatment may result in relief of symptoms, including alleviation of the signs or symptoms of the disease being treated. Determination of a therapeutically effective amount is well within the capabilities of those skilled in the art in light of the disclosure provided herein. The therapeutically effective amount of the compounds disclosed herein required as a dose is within the range: The route of administration, the type of animal (including humans) being treated, and the specific animal body under consideration Dosage may be adjusted to achieve the desired effect, depending on body weight, diet, It depends on factors such as concurrent medications, and other factors recognized by those of ordinary skill in the medical arts.

[0051] The term "solvent" as used herein is a broad term and its meaning is understood by those skilled in the art. The usual and customary meaning should be given (no special or customized meanings). (This term should not be limited to, but should not be construed as limiting, to, or be used in conjunction with, any compound or agent that has some solubility in relation to other compounds or agents.) Compounds with ionic properties, polar or non-polar, straight or branched chain, cyclic or aliphatic It refers to compounds that may be aliphatic, aromatic, or naphthenic, among others, but are not limited to these. ke, alcohols, derivatives, diesters, ketones, acetates, terpenes, sulfoxides, These include glycols, paraffins, hydrocarbons, anhydrides, and heterocyclic compounds. Not limited.

[0052] The term "fatty acid" as used herein is a broad term and its meaning is understood by those skilled in the art. The ordinary and customary meaning should be given (not a special or customized meaning). The term refers to, but is not limited to, unnatural fatty acids. Non-naturally occurring fatty acids, including but not limited to, may be hydrolyzed by the acid isostere of the compound of formula (I). or may result from metabolic cleavage.

[0053] As used herein, any group (e.g., R 1 , R 2 , Y 1 and Y 2 is The groups represented by the formula (including but not limited to) correspond to the substituents that may be attached to the indicated atom. When described as "joined together," the group and atom to which they are attached are cycloalkyl. , cycloalkenyl, aryl, heteroaryl or heterocyclic rings. Below are some examples, including but not limited to: 1 and Y 2 When it is indicated that "becomes one flesh," it means that These are covalently bonded to each other via 0 to 5 intervening atoms to form a ring. Additionally, two groups may "combine" with the atoms to which they are attached to form a ring as an option. When a group is described as having a group, it is not limited to the variables or substituents defined above.

[0054] As provided herein, an "oxa" fatty acid or a "thia" fatty acid is an oxalate at the indicated position. The methylene group in the fatty acid chain is replaced by an oxygen atom (so that the number of chain atoms in the fatty acid chain remains the same). Non-limiting examples include 3-oxa- and 4-oxa-substituted fatty acids. Pentadecanoic acid has the structure: [ka] The sulfur atom may be, for example, sulfenyl. , sulfinyl, or sulfonyl groups. The sulfur atom is part of a sulfenyl moiety.

[0055] As used herein, the term "optionally substituted" refers to a chemical group, e.g., G, X , Y 1 , Y 2 or Z may be unsubstituted or substituted with one or more of the substituents shown; If no substituents are named, the "optionally substituted" shown indicates that the group may be optionally substituted. The "substituted" or "substituted" group includes C1-C6 alkyl, C1-C6 alkenyl, C1-C6 Alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, acyl (C1- C6 alkyl), C1-C6 alkoxy (C1-C6 alkyl), amino (C1-C6 alkyl Amino acid, C6-C 10 Aryl, heteroaryl, heterocyclyl, C6- C 10 Aryl (C1-C6 alkyl), heteroaryl (C1-C6 alkyl), heteroaryl Cyclyl (C1-C6 alkyl), hydroxyl (C1-C6 alkyl), acyl, cyclohexyl Ano, halogen, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl N-thiocarbamyl, C-amide, N-amide, S-sulfonamide, N-sulfone Amide, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato Nato, azido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, halo(C1 -C6 alkyl), C1-C6 haloalkoxy, trihalomethanesulfonyl, trihalome and one or more substituents individually and independently selected from benzenesulfonamide or amino. It can be substituted.

[0056] As used herein, "C a -C b ” (where “a” and “b” are integers) is the range of carbon atoms in an alkyl, alkenyl, or alkynyl group, or a cyclo the ring of an alkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl group Therefore, for example, a "C1-C4 alkyl" group refers to the number of carbon atoms in the represents all alkyl groups with 1 to 4 carbons, i.e., CH3-, CH3CH2- , CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3C H2CH(CH3)- and (CH3)3C-. "a" and "b" are alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heptane Unless otherwise specified for the heteroaryl or heteroalicyclyl group, The widest range of available information should be assumed.

[0057] The term "alkyl" as used herein is a broad term and its meaning is understood by those skilled in the art. should be given their ordinary and customary meaning (without special or customized meanings). The term should not be limited in meaning to fully saturated (double or triple bonds). An alkyl group is a straight or branched hydrocarbon chain containing a hydrocarbon group (without It can be a lower alkyl group having 1 to 6 carbon atoms. Typical alkyl groups include: Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, butyl The alkyl group may be, but is not limited to, methyl and hexyl. The alkyl group may be a medium alkyl group having 15 or more carbon atoms, e.g. For example, a higher alkyl group having 15 to 30 carbon atoms or 15 to 25 carbon atoms. The alkyl group may be, for example, 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 , having 21, 23 or 25 carbon atoms, for example 15 or 17 carbon atoms, It may be an odd-chain alkyl group.

[0058] As used herein, "alkenyl" is a broad term and will be understood by those skilled in the art. should be given its ordinary and customary meaning (without special or customized meaning) (and should not be limited to the meaning given herein) the term refers to a group of molecules having one or more carbon-carbon double bonds in the chain. Alkenyl refers to a straight or branched, unsubstituted or substituted hydrocarbon chain, including alkyl, alkylene, alkene, alkene, alkene-containing alkyl groups. Non-limiting examples of alkyl groups include allenyl, vinyl and isoprenyl.

[0059] As used herein, "alkynyl" is a broad term and will be understood by those of ordinary skill in the art. should be given its ordinary and customary meaning (without special or customized meaning) (and should not be limited to the meaning given herein) the term refers to a group of molecules having one or more carbon-carbon triple bonds in the chain. refers to a straight or branched, unsubstituted or substituted hydrocarbon chain, including alkyl groups. Non-limiting examples of yl include ethynyl and propynyl.

[0060] As used herein, "heteroaryl" is a broad term and will be understood by those of ordinary skill in the art. should be given their ordinary and customary meaning (without special or customary meanings) (The meaning of this term should not be limited to a specific meaning.) The term also refers to a compound having one or more heteroatoms in an aromatic ring. The heteroatom is a monocyclic or fused polycyclic ring system containing an aromatic ring. The term "n-membered heteroaryl" refers to an n-membered heteroaryl, which may be, but is not limited to, hydrogen, oxygen, or sulfur. is a ring or ring system in which a total of n atoms form the ring or ring system; Heteroaryl refers to heteroaromatic rings and ring systems substituted with oxo. Heteroaryl and heterocyclic ring systems, as well as their hydroxy tautomers, are included. Examples of such compounds include those described herein and below. Non-limiting: 1,2,4-oxadiazol-5(4H)-one, tetrazole, furazoline phenanthone, furazan, thiophene, pyrrole, oxazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole, 1,2,3-thiadiazole, 1,2,4 -Thiadiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzisoxazole, isothiazol azoles, triazoles, benzotriazoles, thiadiazoles, tetrazoles, pyridines, Pyridazine, pyrimidine, pyrazine, purine, quinoline, isoquinoline, quinazoline, quinoline Noxalins, cinnolines and triazines.

[0061] As used herein, "heterocyclyl" is a broad term and will be understood by those skilled in the art. should be given their ordinary and customary meaning (without special or customary meanings) (and should not be limited to a more specific meaning), the term includes monocyclic ring systems, spirocyclic ring systems and and / or fused polycyclic ring systems, not containing any aromatic rings, with one or more rings or ring systems Monocyclic, spirocyclic and / or fused polycyclic ring systems containing 1 or more heteroatoms The heteroatom may be, but is not limited to, nitrogen, oxygen, or sulfur. "n-membered heterocyclyl" means a ring or ring system having a total of n atoms in the ring or ring system. Heterocyclyl refers to a ring or ring system that forms a ring of a heterocyclic group. Substituted heterocyclic rings and ring systems and their hydroxy tautomers are included. Examples of heteroaryl rings include those described herein and the following: The group includes, but is not limited to, those described herein and the following: These include, but are not limited to: oxazolidinones, 1,3-dioxins, 1,4- Dioxane, 1,2-dioxolane, 1,3-oxathiane, 1,3-oxathiolane, 1,3-Dithiol, 1,3-Dithiolane, 1,4-Oxathiane, Tetrahydro-1, 4-Thiazine, 1,3-Thiazinane, 2H-1,2-Oxazine, Maleimide, Succinic Imides, barbituric acids, thiobarbituric acids, dioxopiperazines, hydantoins, dioxopiperazines Hydrouracil, trioxane, imidazoline, imidazolidine, isoxazoline, isopropyl alcohol Thioxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolinone Azolidine, morpholine, oxirane, piperidine N-oxide, piperidine, piperazine pyrrolidine, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran Thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone and the like their benzo-fused analogues (e.g., benzimidazolidinones, tetrahydroquinolines and and 3,4-methylenedioxyphenyl).

[0062] As used herein, "cycloalkyl" refers to a group that is fully saturated (with double bonds or refers to a monocyclic or polycyclic hydrocarbon ring system (having no triple bonds). When configured, the rings may be joined in a fused fashion. The rings may contain 3 to 10 atoms, or the rings may contain 3 to 8 atoms. Cycloalkyl groups may be unsubstituted or substituted. Examples of the cycloalkyl group include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples include, but are not limited to, cyclohexyl, cycloheptyl, and cyclooctyl.

[0063] As used herein, "cycloalkenyl" means a group having at least one alkyl group in one ring. It refers to a monocyclic or polycyclic hydrocarbon ring system containing one or more double bonds, but If more than one double bond is present, the double bonds are fully delocalized across all rings. cannot form a π-electron system (otherwise the group cannot be When the ring is composed of two or more rings, the rings are joined in a fused form. A cycloalkenyl group can be unsubstituted or substituted.

[0064] As used herein, "aryl" refers to a group that is completely delocalized throughout the ring. Carbocyclic (all carbon), monocyclic or polycyclic aromatic ring systems with a fused π-electron system ( (including fused ring systems in which two carbon rings share a chemical bond). The number of carbon atoms can vary. For example, an aryl group can be C6-C 14 Aryl group, C 6-C 10 It can be an aryl group or a C6 aryl group. Examples of aryl groups include benzophenone, ... Aryl groups include, but are not limited to, phenylene, naphthalene, and azulene. , may be substituted or unsubstituted.

[0065] As used herein, "aralkyl" and "aryl(alkyl)" refer to It refers to an aryl group bonded as a substituent via a lower alkylene group. The lower alkylene and aryl groups may be substituted or unsubstituted. Examples include benzyl, 2-phenylalkyl, 3-phenylalkyl and naphthylalkyl. These include, but are not limited to, kills.

[0066] As used herein, "heteroaralkyl" and "heteroaryl (alkyl)" are "(alkyl)" refers to a group bonded as a substituent via a lower alkylene group having 1 to 6 carbon atoms. The lower alkylene and heteroaryl of heteroaralkyl are The aryl group may be substituted or unsubstituted. Examples include 2-thienyl aryl. alkyl, 3-thienyl alkyl, furyl alkyl, thienyl alkyl, pyrrolyl alkyl , pyridyl alkyl, isoxazolyl alkyl, imidazolyl alkyl and their These include, but are not limited to, benzo-fused analogs.

[0067] "Heteroalicyclyl(alkyl)" and "heterocyclyl(alkyl)" refer to lower A heterocyclic or heteroalicyclic group bonded as a substituent via a dialkylene group. The lower alkylene and heterocyclyl of heteroalicyclyl(alkyl) are It may be substituted or unsubstituted. Examples include tetrahydro-2H-pyran- 4-yl(methyl), piperidin-4-yl(ethyl), piperidin-4-yl(propyl) tetrahydro-2H-thiopyran-4-yl(methyl) and 1,3-thiazinane Examples include, but are not limited to, -4-yl(methyl).

[0068] "Lower alkylene groups" refer to groups that link fragment molecules via their terminal carbon atoms. The bond is a linear linking -CH2- group having 1 to 6 carbon atoms. Examples include methylene (-CH2-), ethylene (-CH2CH2-), propylene (- (-CH2CH2CH2-) and butylene (-CH2CH2CH2CH2-) A lower alkylene group is one in which one or more hydrogen atoms of the lower alkylene group are replaced by a It can be substituted by replacing it with a substituent listed in the definition of "substituted."

[0069] As used herein, "alkoxy" refers to a group of formula -OR, where R is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl , heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl) ), heteroaryl(alkyl) or heterocyclyl(alkyl), A non-limiting list of alkoxy includes methoxy, ethoxy, n-propyl, ethoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, s Examples include ec-butoxy, tert-butoxy, phenoxy and benzoxy. Koxy may be substituted or unsubstituted.

[0070] As used herein, "acyl" refers to a group bonded as a substituent via a carbonyl group. hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl aryl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl Heteroaryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl) Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. The acyl may be substituted or unsubstituted.

[0071] As used herein, "acylalkyl" refers to a group that is substituted via a lower alkylene group. Refers to acyl groups bonded as substituents. Examples include aryl-C(=O)-(CH 2) n - and heteroaryl-C(=O)-(CH2) n -, where n is , an integer in the range of 1 to 6.

[0072] As used herein, "alkoxyalkyl" refers to a group that is substituted via a lower alkylene group. An example is C 1-4 Alkyl- O-(CH2) n -, where n is an integer in the range of 1 to 6.

[0073] As used herein, "aminoalkyl" refers to a group substituted via a lower alkylene group. It refers to an unsubstituted or substituted amino group attached as a substituent. Examples include H 2N(CH2) n -, where n is an integer in the range of 1 to 6.

[0074] As used herein, "amino" refers to an unsubstituted nitrogen or an optionally substituted nitrogen. refers to a nitrogen substituted by one or two C1-C6 alkyl groups Examples of amino groups include -NH2, -NHCH3, -N(CH3)2 and -N(CH 3) (CH2CH3), but are not limited to these.

[0075] As used herein, "hydroxyalkyl" means a group in which one or more hydrogen atoms are substituted with a hydroxyl group. It refers to an alkyl group substituted with a hydroxy group. Exemplary hydroxyalkyl groups Examples include 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, and and 2,2-dihydroxyethyl. Kills may be either replacement or non-replacement.

[0076] As used herein, "haloalkyl" means an alkyl group in which one or more hydrogen atoms are replaced with a halogen atom. Alkyl groups substituted by (e.g., mono-haloalkyl, di-haloalkyl and Such groups include chloromethyl, fluoromethyl, and methyltrihaloalkyl. methyl, difluoromethyl, trifluoromethyl, chloro-fluoroalkyl, chloro-di Includes, but is not limited to, fluoroalkyl and 2-fluoroisobutyl. The haloalkyl may be substituted or unsubstituted.

[0077] As used herein, "haloalkoxy" refers to an alkoxy group in which one or more hydrogen atoms are replaced with a halogen atom. alkoxy groups substituted with halogen (e.g., mono-haloalkoxy, di-haloalkoxy); Such groups include chloromethoxy, chloroalkoxy, and tri-haloalkoxy. , fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloro-fluoroa alkyl, chloro-difluoroalkoxy and 2-fluoroisobutoxy. The haloalkoxy may be substituted or unsubstituted. .

[0078] A "sulfenyl" group refers to a "-SR" group, where R is hydrogen, alkyl, or , alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl Cycloalkyl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl It can be aryl(alkyl) or heterocyclyl(alkyl). It may be substituted or unsubstituted.

[0079] A "sulfinyl" group refers to a "-S(=O)-R" group, where R is sulfinyl. The sulfinyl may be substituted as defined for phenyl. and may be unsubstituted.

[0080] A "sulfonyl" group refers to an "SO2R" group, where R is sulfenyl. The sulfonyl may be substituted or unsubstituted. It's okay to have one.

[0081] An "O-carboxy" group refers to an "RC(=O)O-" group, where R is As defined herein, hydrogen, alkyl, alkenyl, alkynyl, cycloalkoxy, aryl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl ( alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl (alkyl). The O-carboxy may be substituted or unsubstituted. stomach.

[0082] The terms "ester" and "C-carboxy" refer to the group "-C(=O)OR". where R can be the same as defined for O-carboxy. and C-carboxy may be substituted or unsubstituted.

[0083] A "thiocarbonyl" group refers to a "-C(=S)R" group, where R is O- The thiocarbonyl may be substituted or unsubstituted as defined for carboxy. It may be substituted or unsubstituted.

[0084] A "trihalomethanesulfonyl" group refers to an "X3CSO2-" group, where each X is a halogen.

[0085] The "trihalomethanesulfonamide" group is "X3CS(O)2N(R A )-"Motonoko wherein each X is a halogen and R A is hydrogen, alkyl, alkenyl, alkynyl, quinyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) Or heterocyclyl(alkyl).

[0086] As used herein, the term "hydroxy" refers to an --OH group.

[0087] A "cyano" group refers to a "-CN" group.

[0088] As used herein, the term "azido" refers to the group --N3.

[0089] An "isocyanato" group refers to a "-NCO" group.

[0090] A "thiocyanato" group refers to a "-CNS" group.

[0091] An "isothiocyanato" group refers to a "-NCS" group.

[0092] A "carbonyl" group refers to a C=O group.

[0093] The "S-sulfonamide" group is "-SO2N(R A R B ) group, where , R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkane, alkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl (alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl The S-sulfonamide may be substituted or unsubstituted. That's fine.

[0094] The "N-sulfonamide group" is "RSO2N(R A )-" group, where R and R A are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl , cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(a) alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl( The N-sulfonamide may be substituted or unsubstituted. good.

[0095] The "O-carbamyl" group is defined as "-OC(=O)N(R A R B )" group, So, R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkoxy aryl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclo O-carbamyl can be substituted or unsubstituted. Good too.

[0096] The "N-carbamyl" group is "ROC(=O)N(R A )-" group, where , R and R A are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkynyl, aryl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl ( alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl (alkyl). N-carbamyl may be substituted or unsubstituted. stomach.

[0097] The "O-thiocarbamyl" group is defined as "-OC(=S)-N(R A R B )" group , where R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, silyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cyclo Alkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heteroaryl(alkyl) O-thiocarbamyl may be substituted or unsubstituted. It may be replaced.

[0098] The "N-thiocarbamyl group" is "ROC(=S)N(R A )-" group, Here, R and R Aare independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkoxy aryl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclo N-thiocarbamyl may be substituted or unsubstituted. It is also possible.

[0099] A "C-amide" group is a group consisting of -C(=O)N(R A R B ) group, where R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl , cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(a) alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl( The C-amide may be substituted or unsubstituted.

[0100] The "N-amide" group is defined as "RC(=O)N(R A )-" group, where R and Yobi R A are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cyclohexyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl (alkoxy) aryl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(aryl) The N-amide may be substituted or unsubstituted.

[0101] As used herein, the term "halogen atom" or "halogen" refers to any element in the periodic table of the elements. Any one of the seventh row of radiostable atoms (e.g., fluorine, chlorine, bromine, and iodine) Taste.

[0102] As used herein, [ka] indicates a single or double bond unless otherwise stated.

[0103] Where the number of substituents is not specified (e.g., haloalkyl), one or more substituents may be present. For example, "haloalkyl" may include one or more halogens which may be the same or different. As another example, "C1-C3 alkoxyphenyl" refers to a group consisting of 1, 2, or 3 atoms. The alkyl group may contain one or more alkoxy groups, which may be the same or different, including

[0104] As used herein, any protecting group, amino acid and other compound abbreviations are Unless otherwise indicated, their normal usage, widely accepted abbreviations, or IUP AC-IUB Commission on Biochemical Nomencl according to the structure (see Biochem. 11:942-944 (1972)). .

[0105] As used herein, the term "amino acid" refers to any amino acid (naturally occurring amino acid and unnatural amino acids), including but not limited to α-amino acids Examples of suitable amino acids include alanine, asparagine, aspartic acid, and cysteine. , glutamic acid, glutamine, glycine, proline, serine, tyrosine, arginine, Styrene, isoleucine, leucine, lysine, methionine, phenylalanine, threonine Suitable amino acids include, but are not limited to, thiamin, tryptophan, and valine. Further examples of acids include ornithine, hypusine, 2-aminoisobutyric acid, dehydroaromatase, Inosin, gamma-aminobutyric acid, citrulline, beta-alanine, alpha-ethyl-glycine These include, but are not limited to, alpha-propyl-glycine, alpha-propyl-glycine, and norleucine. As used herein, an "amino acid" includes an amino acid in which the carboxylic acid group in the backbone is esterified. Also included are amino acids converted to alkyl groups.

[0106] As used herein, the term "protecting group" refers to a group that protects an existing group in a molecule from an unwanted reaction. Any atom or group of atoms added to a molecule so that it does not undergo a chemical reaction Examples of protecting group moieties are given in TW Greene and PG M Buts, Pr otective Groups in Organic Synthesis,3.E d.John Wiley & Sons, 1999 and JFWMcOmie, Protective Groups in Organic Chemistry P and Br. Denum Press, 1973, both of which disclose suitable protecting groups. Protecting group moieties are incorporated herein by reference for the limited purpose of: Suitable esters may be prepared using methods known in the art that are stable to certain reaction conditions and that are readily available. They can be selected so as to be easily removed at a convenient stage. Non-limiting list of protecting groups Examples include benzyl; substituted benzyl; alkylcarbonyl and alkoxycarbonyl ( For example, t-butoxycarbonyl (BOC), acetyl, or isobutyryl; aryl Alkylcarbonyl and arylalkoxycarbonyl (e.g., benzyloxycarbonyl) methyl ethers (e.g., methoxymethyl ether); substituted ethyl ethers substituted benzyl ethers; tetrahydropyranyl ethers; silyl (e.g., trimethyl silyl, triethylsilyl, triisopropylsilyl, t-butyldimethylsilyl, Tri-isopropylsilyloxymethyl, [2-(trimethylsilyl)ethoxy]methyl or t-butyldiphenylsilyl); esters (e.g., benzoates); esters (e.g., methoxymethyl carbonate); sulfonates (e.g., tosylates or or mesylate); acyclic ketals (e.g., dimethyl acetal); cyclic ketals (e.g., For example, 1,3-dioxane, 1,3-dioxolane, and those described herein. acyclic acetals; cyclic acetals (e.g., those described herein); acyclic Hemiacetals; cyclic hemiacetals; cyclic dithioketals (e.g., 1,3-dithiane or 1,3-dithiolane); orthoesters (e.g., those described herein) and triarylmethyl groups (e.g., trityl; monomethoxytrityl (MMTr); 4,4'-Dimethoxytrityl (DMTr); 4,4',4"-Trimethoxytrityl ( TMTr); and those described herein).

[0107] Terms and phrases used in this application, particularly in the appended claims, and variations thereof, To be construed as open-ended, as opposed to limited, unless expressly stated otherwise As an example of the above, the term "including" means "including but not limited to." "includes, but is not limited to," "includes, but is not limited to," etc. As used herein, the term "comprising" , "including," "containing," or Synonymous with "characterized by" and inclusive or open-ended, descriptive does not exclude additional elements or method steps not included, and the term "comprising" is used interchangeably with "comprising" The term "including" should be interpreted as "having at least..." and "including" should be interpreted as "including..." The term "examples" should be interpreted as including, but not limited to, the are used to provide illustrative examples of items that may be included, and are not intended to be exhaustive or exclusive. It is not intended to provide a comprehensive list, but rather to The use of terms such as "desired" or "preferred" and words of similar meaning is to Imply that a feature is absolutely essential, vital, or critical to the structure or function. It should not be understood that the present invention is limited to the specific embodiments described herein, but may instead be utilized in particular embodiments. are merely intended to highlight alternative or additional features that may or may not be Furthermore, the term "comprising" should be understood to include the phrase Should be interpreted as a synonym for "having at least" or "including at least" The term "comprising" is used in the context of a process. When used, the process includes at least the steps described, but may also include additional steps. The term "comprising" means that a compound may also be included. When used in the context of a compound, composition, or device, The device may include at least the features or components described, but may also include additional features or components. Similarly, the conjunction "and" is used to connect A group of items requires that each and every one of the items be present in that grouping. rather, unless expressly stated otherwise, "and / Similarly, items joined using the conjunction "or" should be read as "or." The group should not be read as requiring mutual exclusivity within the group, but rather as Unless expressly stated otherwise, it should be read as "and / or."

[0108] With respect to the use of virtually any plural and / or singular terminology herein, The reader shall transition from plural to singular and vice versa as appropriate to the context and / or use. and / or convert the singular to the plural. Number / plural interchanges may be explicitly indicated in this specification. The word "an" does not exclude a plurality. It may function as several items described. Certain criteria may differ from each other. The mere fact that it is recited in a dependent claim does not necessarily make the combination of these criteria Any reference signs in the claims do not imply that they cannot be used in any way. It should not be construed as limiting the scope.

[0109] In any compound described herein that has one or more chiral centers, the absolute configuration Unless the conformational chemistry is explicitly indicated, each center may independently be in the R or S configuration or It is understood that the compounds provided herein may be combinations of Can be enantiomerically pure, enantiomerically enriched, or a racemic mixture can be diastereomerically pure or diastereomerically enriched or may be a stereoisomeric mixture. Any compound described herein having one or more double bonds that produce possible geometric isomers. In the compound, each double bond may independently be E or Z, or a combination thereof. It is understood.

[0110] Likewise, in any compound described, all tautomers are intended to be included. It is understood that

[0111] If the valences of the compounds disclosed herein are unsatisfied, the valences may be replaced by hydrogen. or its isotopes, e.g., hydrogen-1 (protium) and hydrogen-2 (deuterium) It should be understood that the

[0112] It is understood that the compounds described herein may be isotopically labeled. Substitution with isotopes such as uranium may offer certain therapeutic advantages due to greater metabolic stability. This may result in benefits such as increased in vivo half-life or reduced dosage requirements. Each chemical element as it appears in the structure may include any isotope of that element. In the structure of a compound, hydrogen atoms may be explicitly disclosed as being present in the compound or At any position in the compound where a hydrogen atom can be present, that hydrogen atom can be It can be any isotope of hydrogen, including hydrogen-1 (protium) and hydrogen-2 (deuterium). Reference to a compound includes all compounds that may be present unless the context clearly dictates otherwise. All isotopic forms are included.

[0113] The methods and combinations described herein can be used to synthesize compounds of different crystalline forms (compounds of the same elemental composition). including different crystalline packing arrangements (also known as polymorphs), amorphous phases, salts, solvates and In some embodiments, the compounds described herein are understood to include hydrates and hydrates. The compound may be in the form of a solvate with a pharmaceutically acceptable solvent (e.g., water, ethanol, etc.). In other embodiments, the compounds described herein exist in an unsolvated form. Solvates contain stoichiometric or non-stoichiometric amounts of a solvent and are pharmaceutically acceptable. They may be formed during the process of crystallization using solvents that give the desired crystal structure (eg, water, ethanol, etc.). When the solvent is water, a hydrate is formed, or when the solvent is alcohol, an alcohol Additionally, the compounds provided herein, in their unsolvated form, In general, solvated forms are used to describe the compounds provided herein. In products and methods, the unsolvated forms are considered equivalent.

[0114] Where a range of values ​​is provided, the upper and lower limits and the values ​​that lie between the upper and lower limits of the range are It is understood that any value that exists is included.

[0115] Any percentage, ratio or other amount referred to herein is indicative of a and is based on weight. saturated fatty acids

[0116] Saturated and unsaturated fatty acids are known to exist in the body (see, e.g., Jen kins B, West J, Koulman A (2015), A review o f odd-chain fatty acid metabolism and th e role of pentadecanoic acid(C15:0)and h eptadecanoic acid(C17:0)in health and di See Sease, Molecules 20:2425-44). When provided, fatty acids are referred to and labeled using conventional nomenclature as used by those of skill in the art. Saturated fatty acids do not contain carbon-carbon double bonds. Unsaturated fatty acids contain at least Contains one carbon-carbon double bond. Monounsaturated fatty acids contain only one carbon-carbon double bond. Polyunsaturated fatty acids contain two or more carbon-carbon double bonds. The bond is usually cis, however, trans double bonds are also possible. The position of each double bonded carbon atom can be indicated by Δn, where n is the The smaller number of carbon atoms is shown. Total number of carbon atoms: Number of double bonds, Δ 二重結合の位置 Specify The following abbreviations may be used, for example, 20:4Δ 5,8,11,14 is 20 carbon atoms A fatty acid having a hydroxyl group and four double bonds, the double bonds being at the 5-position carbon atom. and the 6th carbon atom, between the 8th carbon atom and the 9th carbon atom, and between the 11th carbon atom and between the carbon atom at position 12 and the carbon atom at position 14 and the carbon atom at position 15; The carbon atom at position 1 is the carbon of the carboxylic acid group, which means that it is a fatty acid. Oleic acid (cis-Δ9-octadecenoic acid) is a saturated fatty acid. , a monounsaturated fatty acid, linolenic acid (all cis Δ9,12,15-octadeca Trienoic acid) is a polyunsaturated fatty acid.

[0117] Saturated fatty acids are sometimes called by various names, for example, heptadecanoic acid is These are sometimes called decyl and n-heptadecylic acids or C17:0. Alternatively, unsaturated fatty acids may be referred to by lipid number, as known in the art. Examples of odd-chain fatty acids are margaric acid (heptadecanoic acid, C17:0), pelargonic acid, Acid (nonanoic acid, C9:0), undecanoic acid (C11:0), nonadecanoic acid (C19:0) , arachidonic acid ((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetrate adrenic acid (all cis 7,10,13,16-docosatetraenoic acid) and osbondoic acid (all cis 4,7,10,13,16-docosapentaenoic acid). Generally, one or more saturated fatty acids have 3 to 9 carbon atoms in the longest alkyl chain. 1 carbon atom (9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29 or or 31 carbon atoms), for example, 15 to 21 carbon atoms, for example, 17 carbon atoms However, in certain embodiments, there may be more or fewer odd numbers. In some embodiments, the saturated fatty acid is an odd-chain fatty acid. In some embodiments, the saturated fatty acid may be an odd- or even-chain fatty acid. As used herein, odd-chain fatty acids are fatty acids having the longest alkyl chain length. As used herein, even-chain fatty acids are fatty acids having an odd number of carbon atoms. are fatty acids with an even number of carbon atoms in the longest alkyl chain.

[0118] Saturated fatty acids may be present as salts, e.g., at the carboxyl group. In the above, one compound of formula (I) or a pharmaceutically acceptable salt thereof is used, for example, The composition may contain two compounds of formula (I) or a pharmaceutically acceptable salt thereof. Salts may exist and the three compounds of formula (I) or pharmaceutically acceptable salts thereof may be , , or more may be present. In some embodiments, multiple saturated fatty acids in a mixture containing a fatty acid compound of formula (I) or a pharmaceutically acceptable salt thereof is determined by the amount of unsaturation, the length of the hydrocarbon chain, and derivatization. n), the number of alkyl substitutions, the identity of the acid isostere, the identity of the salt or other structural In a further embodiment, the compound of formula (I) or a pharmaceutical A physiologically acceptable salt may be, for example, a naturally occurring fatty acid or a naturally occurring fatty acid in a composition. It may be present with unsaturated fatty acids.

[0119] Odd-chain fatty acids are found in trace amounts in some dairy products, including butter, and are components of some fish oils. (e.g., Mansson HL (2008), Fatty acids in b ovine milk fat,Food Nutr.Res.52:4,Luzia LA,Sampaio GR,Castellucci CMN,Torres EAF S(2013)The influence of season on the li pid profiles of five commercially imported ant species of Brazilian fish.Food Chem. 83:93-97). Studies have shown that a daily diet of foods containing odd-chain fatty acids Increasing intake has been shown to be successful in increasing serum levels (e.g., B enatar JR,Stewart RAH(2014),The eff ects of changing dairy intake on trans a nd saturated fatty acid levels-results f rom a randomized controlled study.Nutr.J (See 13:32).

[0120] The widespread use of various fatty acids in the diet and the occurrence of metabolic syndrome in subjects There was a correlation between the ,Imamura F,Kroger J,Schulze M,et al.(201 4),Differences in the prospective associ ation between individual plasma phosphors ipid saturated fatty acids and incidents type 2 diabetes:the EPIC-InterAct case-c ohort study.Lancet Diabetes Endocrinol.2 In fact, there is a strong association between whole-fat dairy consumption and a lower risk of metabolic syndrome markers. There was a correlation between the risk and the risk of stroke (e.g., Kratz M, Marcovina S, Nelso n JE, Yeh MM, Kowdley KV, Callahan HS, et al. (2014), Dairy fat intake is associated w ith glucose tolerance,hepatic and system ic insulin sensitivity,and liver fat but not beta-cell function in humans,Am.JC lin. Nutr., 99:1385-96).

[0121] Pure or purified odd-chain fatty acids can exist in a variety of physical states. Putadecanoic acid exists as a stable off-white powder at room temperature, and this compound is Some commercial suppliers (e.g., Sigma-Aldrich Corp., St. Louis, MO) It can be purchased from Pharmacia (Philadelphia, GA, USA) in small quantities and in a form suitable for research purposes. The salts or derivatives may exist as an oil, a solid, a crystalline solid, or a gas.

[0122] The compound of formula (I) or a pharmaceutically acceptable salt thereof is at least about 10%, at least At least about 20%, at least about 30%, at least about 40%, at least about 50%, or less At least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least At least about 95%, at least about 98%, at least about 99%, at least about 99.9%, At least about 99.99% pure or substantially pure (e.g., in bulk form) percentage of a compound of formula (I) or a pharmaceutically acceptable salt thereof), Substantially pure means that the physiological effects of the presence of impurities are undetectable. These may include, but are not limited to, products containing impurities at levels such that: or a pharmaceutically acceptable salt thereof, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least At least about 60%, at least about 70%, at least about 80%, at least about 90%, at least at least about 95%, at least about 98%, at least about 99%, at least about 99.9%, at least The compound of formula (I) may be present in a purity of at least about 99.99% or substantially pure. or a pharmaceutically acceptable salt thereof, which does not contain a naturally occurring fatty acid or fatty acid derivative. May be free of triglycerides or may be free of phospholipids Compounds of formula (I) or pharmaceutically acceptable salts thereof may be used, including but not limited to: The salt may be substantially free of even-chain fatty acids, either individually or considered as a group. Examples of even-chain fatty acids include myristic acid (C14:0) and palmitic acid (C 16:0), stearic acid (C18:0) or arachidic acid (C20:0). In further embodiments, including but not limited to, compounds of formula (I) or The physiologically acceptable salts may be substantially free of naturally occurring even-chain fatty acids. In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof is Short-chain fatty acids (SCFA), medium-chain fatty acids (MCFA), long-chain fatty acids (LCFA) or very long-chain fatty acids In some embodiments, the soluble fiber may be substantially free of very long chain fatty acids (VLCFAs). "Substantially free" means that the composition contains less than 5 wt.% of impurities, e.g., naturally occurring Even-chain fatty acids, or less than 1 wt.% of impurities, or This may mean that the impurities are at levels that are undetectable by the S detection method.

[0123] The compounds of formula (I) or pharmaceutically acceptable salts thereof can be prepared by methods known to those skilled in the art or by methods described herein. It may be synthesized by any method, including those provided herein. In the present invention, the compound of formula (I) or a pharmaceutically acceptable salt thereof is present in natural sources. It may be obtained from natural sources, isolated from natural sources, semi-synthetic, or synthetic. The compound of formula (I) or its derivatives may be a mixture of one or more of these. Pharmaceutically acceptable salts of the compounds of the present invention may be produced in the laboratory, naturally occurring, or by enzymes. They can be produced by natural processes, by wild microorganisms, or by genetically modified organisms. They can be produced by modified microorganisms, isolated from animal tissue, or synthesized chemically. It may be produced by one or more of these processes.

[0124] The compounds of formula (I) or pharmaceutically acceptable salts thereof may be obtained from natural sources, for example from fish oil. or can be synthesized by methods known in the art. In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof may be contaminated with even-chain fatty acids or other components present in crude or unrefined natural products. In such situations, known separation or purification techniques may be used to obtain the desired When it is desired to remove unwanted components or to increase the concentration of desired components There is.

[0125] In any compound described, all tautomers are intended to be included. Carbon-carbon double bonds and carboxyl groups and heterocyclic rings, e.g., All tautomers, for example of tetrazole, are intended to be included. Examples of tautomers provided in are tautomers of the tetrazole substituent: [ka] is.

[0126] The present invention has one or more double bonds that result in geometric isomers that can be defined as E or Z. In any compound described herein, each double bond may independently be E or Z or It can be a combination of these.

[0127] If the valences of the compounds disclosed herein are unsatisfied, the valences may be replaced by hydrogen. or its isotopes, e.g., hydrogen-1 (protium) and hydrogen-2 (deuterium) is filled with.

[0128] The compound of formula (I) or a pharmaceutically acceptable salt thereof may be in a crystalline form (a compound of the same elemental composition). different crystalline packing arrangements of compounds (also known as polymorphs), amorphous phases, salts, solvates In some embodiments, the compounds described herein include It may exist in the form of a solvate with a pharmaceutically acceptable solvent (e.g., water, ethanol, etc.). In other embodiments, the compounds described herein exist in an unsolvated form. Solvates contain stoichiometric or non-stoichiometric amounts of a solvent and are pharmaceutically acceptable solvates. It can be formed during the process of crystallization using a solvent (e.g., water, ethanol, etc.). When the solvent is water, a hydrate is formed, or when the solvent is alcohol, an alcohol Additionally, the compounds provided herein may exist in unsolvated as well as solvated forms. Solvated forms may also exist. In general, solvated forms are used with the compounds provided herein and The unsolvated forms are considered equivalent in certain procedures and methods.

[0129] The compounds described herein may be isotopically labeled. Substitution with isotopes such as deuterium may improve certain therapeutics due to higher metabolic stability. These may result in therapeutic advantages (eg, increased in vivo half-life or reduced dosage requirements). Isotopic substitution provides an opportunity to monitor the fate of certain atoms in certain compounds, for example. Providing such information is useful in monitoring a subject's response to administration of a compound. Each chemical element as it appears in the structure of a compound may include any isotope of that element. For example, in the structure of a compound, hydrogen atoms are explicitly disclosed as being present in the compound. It can be shown or understood that at any position of the compound where a hydrogen atom can be present The hydrogen atom can be any hydrogen isotope, including hydrogen-1 (protium), These include, but are not limited to, hydrogen-2 (deuterium) and hydrogen-2 (hydrogen). Therefore, reference to a compound herein is indicative of a compound of interest unless the context clearly dictates otherwise. Unless otherwise specified, all possible isotopic forms are included. Preparation of compounds

[0130] Compounds of formula (I) may be prepared by any suitable method known to those skilled in the art. For example, Francis A. Carey et al., Advanced ed Organic Chemistry:Part B:Reaction and Synthesis (5 th See Ed. 2005). Pharmaceutical compositions containing compounds of formula (I)

[0131] A formulation comprising an odd-chain fatty acid or a salt or derivative thereof and at least one excipient is provided. Although it is generally preferred to administer the compounds of the above embodiments as oral formulations, However, other routes of administration are contemplated.

[0132] The pharmaceutical compositions described herein may be administered to a subject alone or as a composition. In the case of compositions, the compositions may be mixed with other active agents, such as in combination therapy. or mixed with a carrier, diluent, excipient, or combination thereof. The formulation will depend on the route of administration selected. Techniques for formulation and administration are known to those skilled in the art (see, for example, "Remington: The Science and Practice of Pharmacy”,Li ppincott Williams & Wilkins;20th edition (June 1, 2003) and “Remington's Pharmacy "Calc Sciences," Mack Pub. Co.; 18th and 19th eds. (and (December 1985 and June 1990, respectively).

[0133] The pharmaceutical compositions disclosed herein can be prepared by processes known per se, e.g. Conventional mixing, dissolving, granulating, dragee making, wet milling, emulsifying, encapsulating, encapsulating, tableting or It can be prepared using an extraction process. Many of the compounds used can be provided as salts with pharmaceutically acceptable counterions.

[0134] There are several techniques known in the art for administering compounds, including oral, rectal, and , topical, aerosol, injection and parenteral delivery (intramuscular injection, subcutaneous injection, intravenous injection, Includes intramedullary injection, intrathecal injection, direct intraventricular injection, intraperitoneal injection, intranasal injection, and intraocular injection Any combination of the foregoing, or any combination thereof known to those skilled in the art, may be used. Other methods are contemplated herein as may be known (see, for example, "Remington: he Science and Practice of Pharmacy”,Lip pincott Williams & Wilkins;20th edition( June 1, 2003) and "Remington's Pharmaceutical al Sciences,” Mack Pub. Co.; 18th and 19th eds. (and (December 1985 and June 1990, respectively).

[0135] In practice, the compounds of formula (I) or pharmaceutically acceptable salts thereof may be formulated in a manner similar to that described above, but which may be used in conjunction with conventional pharmaceutical formulations. The active ingredient can be combined in intimate admixture with a pharmaceutical carrier according to the methods described above. The carrier can take a wide variety of forms depending on the form of preparation desired for administration. Thus, the pharmaceutical compositions provided herein may be presented in discrete units suitable for oral administration (e.g., For example, capsules, cachets or tablets, each containing a predetermined amount of the active ingredient. Additionally, the compositions may be in the form of oils, powders, granules, liquids, suspensions in aqueous liquids, non-aqueous It may be provided as a liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. In addition to the common dosage forms shown, the compounds provided herein or their pharmaceutically acceptable salts may also be administered in the form of oral or topical preparations. The compound may also be administered by controlled release means and / or delivery devices. These compositions may be prepared by any of the methods of pharmacy. Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more necessary ingredients. In general, the compositions comprise the active ingredient in a liquid carrier or a finely divided solid carrier or The product is then mixed uniformly and thoroughly with the desired It can be nicely shaped into the shape of a

[0136] The formulations may also be administered in a local rather than systemic manner, for example, directly to the infected area. The compound is also administered by injection, often as a depot or sustained-release formulation. Additionally, targeted drug delivery systems have been developed, for example, using liposomes coated with tissue-specific antibodies. It can be used in a serotype.

[0137] The pharmaceutical composition comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, administered to a subject in need of treatment. In some embodiments, the pharmaceutical composition may comprise a unit amount of dosage form, with each unit dosage form containing from about 0.1 mg or less to about 5000 mg or more In a further embodiment, the pharmaceutical composition comprises from about 1 to about 100 mg of niacin per unit dosage form. 500 mg or about 500-5000 mg per unit dosage form. Such dosage forms include: It may be a solid, semi-solid, liquid, emulsion, or may be an aerosol for inhalation administration, etc. The composition may be adapted for delivery via the endothelial cell membrane.

[0138] The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of sugars include lactose, earth, sucrose, talc, gelatin, agar, pectin, Acacia, magnesium stearate, and stearic acid. Examples are liquid sugar, peanut oil, olive oil, lower alcohols and water. Examples include carbon dioxide and nitrogen.

[0139] The pharmaceutical compositions provided herein may be administered as solutions or suspensions of the active compounds in water. Suitable surfactants, such as hydroxypropylcellulose, may also be used. Glycerol, liquid polyethylene glycols, and those in oils can be used. Dispersions in mixtures of these compounds may also be prepared. For this reason, preservatives may be included.

[0140] Pharmaceutical compositions provided herein suitable for injectable use may be prepared as sterile aqueous solutions or Furthermore, these compositions include such sterile injectable solutions. The pharmaceutical composition may be in the form of a sterile powder for extemporaneous preparation of a liquid or dispersion. It must be stable under the conditions of manufacture and storage and therefore preferably is bacterial and The carrier should be stored under conditions that protect it from the contamination of microorganisms such as bacteria and fungi. , water, ethanol, polyols (e.g., glycerol, propylene glycol, and solvents or dispersions including polyethylene glycol), vegetable oils and suitable mixtures thereof It can be a medium.

[0141] In addition to the carrier components described above, the pharmaceutical formulations described above may optionally contain one or more Further carrier ingredients, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, In addition, the intended recipe may contain additives, lubricants, preservatives (including antioxidants), etc. Other adjuvants may be included to make the formulation isotonic with the patient's blood. Compositions comprising the compounds provided herein or pharmaceutically acceptable salts or derivatives thereof may also be prepared in the form of a powder or a liquid concentrate for dilution.

[0142] The compound of formula (I) or a pharmaceutically acceptable salt thereof may be administered in the presence of at least one further active agent. Compositions containing the compounds of formula (I) in combination with other agents are contemplated herein. or a pharmaceutically acceptable salt thereof and at least one additional active agent may be used alone. They may be present in one formulation, in multiple formulations provided together, or may be unformulated. In some embodiments, a compound of formula (I) or a pharmaceutically acceptable salt thereof The salts may be administered with one or more additional agents as a single composition. For example, The compounds of formula (I) or pharmaceutically acceptable salts thereof may be administered as a single composition. At least one of the additional agents may be administered as a second composition. In an embodiment, a compound of formula (I) or a pharmaceutically acceptable salt thereof and at least One additional active agent may be packaged together in one kit. For example, a pharmaceutical manufacturer may A pharmaceutical distributor, physician, compounding store, or pharmacist may use the compounds or products of the present disclosure and send them to a patient. The kit may be provided with additional components for achieving the above.

[0143] Some embodiments described herein may be administered in combination with a therapeutically effective amount of one or more of the compounds described herein. The compounds described (e.g., compounds of formula (I) or pharmaceutically acceptable salts thereof) and and pharmaceutical compositions which may contain pharmaceutically acceptable carriers, diluents, excipients, or combinations thereof. The pharmaceutical composition relates to a pharmaceutical composition comprising one compound of formula (I) or a pharmaceutically acceptable salt thereof. The salts that can be added may be, for example, >1%, ≥2%, ≥3%, ≥4%, ≥5%, ≥6%, ≥7%, ≥8%, ≥9%, ≥10%, ≥20%, ≥30%, ≥40%, ≥50%, ≥60 %, ≥ 70%, ≥ 80%, ≥ 90%, ≥ 95% or ≥ 98%. In some embodiments, the pharmaceutical composition may comprise a plurality of compounds of formula (I) or pharmaceutically acceptable salts thereof. The salt may be present in an amount of, for example, >1%, ≥2%, ≥3%, ≥4%, ≥5%, ≥6%, ≥7%, or %, ≥8%, ≥9%, ≥10%, ≥20%, ≥30%, ≥40%, ≥50%, ≥60%, It may comprise ≧70%, ≧80%, ≧90%, ≧95% or ≧98%. food

[0144] Foods and other foodstuffs containing a compound of formula (I) or a pharmaceutically acceptable salt thereof are provided. wherein the amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof in the food is The compounds of formula (I) provided herein are enriched (e.g., enriched or concentrated). The compound or a pharmaceutically acceptable salt thereof may be added to food for consumption by a subject. The compound of formula (I) or a pharmaceutically acceptable salt thereof may be incorporated into one or more components of a food product. The compound of formula (I) or a pharmaceutically acceptable salt thereof may be incorporated into a component. The compound or compounds containing the compound may or may not be prepared as a compound. The preparation may be added before, during or after preparation. Preparations include, but are not limited to: , cooking, mixing, flavoring, seasoning, blending, boiling, cooking in oil, baking or It may include other processes known in the art. The enrichment is preferably carried out in accordance with the methods described elsewhere herein. a daily therapeutic dose of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described However, the level of enhancement is less than that of the dose The amount may also have a beneficial effect.

[0145] The compounds of formula (I) or pharmaceutically acceptable salts thereof may be prepared by known processes in nature. By manipulation, for example, by altering the metabolic processes of plants, animals, bacteria or fungi. Therefore, it can be present as a support in food. Genetic alterations of plants, animals, bacteria, or fungi that increase the concentration are contemplated. I) or a pharmaceutically acceptable salt thereof, %, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least About 20%, at least about 30%, at least about 40%, at least about 50% or more For example, 1% to 2% or 3% or 4% or 5% or 6% or 7% or 8% % or 9% or 10% or 20% or 30% or 40% or 50% concentration It can be present in food. Indications

[0146] Cognitive impairment (brain damage due to neurodegenerative conditions, brain damage due to injury, infection, substance abuse) , substance withdrawal, psychosis, vitamin and other important nutrient deficiencies, hormonal problems, metabolic disorders cognitive impairment due to balance or medication side effects and other related conditions), movement disorders (including Stone, chorea, Huntington's disease, Parkinson's disease, parkinsonism, tics, toes Tablet syndrome, ataxia, tremor, essential tremor, myoclonus, multiple sclerosis, bipolar disorder associated with morbidity, restless legs syndrome, stiff person syndrome, gait disturbances and spasticity movement disorders), chronic pain (past injury, back pain, migraines and other headaches, arthritis, nerve chronic pain due to injury, infection and fibromyalgia), depression (persistent depressive disorder) Harm (dysthymia), postpartum depression, psychotic depression, seasonal affective disorder, bipolar disorder, severe mood swings loss of appetite (including dysthymia and premenstrual dysphoric disorder), loss of appetite (due to AIDS, cancer, cancer treatment, chronic heart disease) Disease, metabolic changes, chronic inflammation, pain, dysgeusia, loss of taste, hypersomnia, dysphagia, difficulty breathing nausea, vomiting, constipation, diarrhea, drug side effects, psychological distress, and oral or esophageal infections associated anorexia and cachexia), convulsions, seizures (non-epileptic, epileptic and and psychogenic non-epileptic seizures) and addictions (opioids, cocaine, alcohol and to treat conditions including, but not limited to, addiction to alcohol and other drugs Compositions and methods are provided herein.

[0147] In some embodiments, the compositions and methods provided herein are directed to treating cognitive disorders The present invention is indicated for the treatment, prophylaxis, prevention or management of

[0148] Cognition is the mental act or process of gaining knowledge and understanding through thought, experience, and sensation. Cognitive impairment (also known as cognitive decline) is a neurodegenerative condition that affects the brain. Injury, brain damage from trauma, infections, substance abuse, substance withdrawal, mental illness, vitamins, and others caused by deficiencies of important nutrients, hormonal problems, metabolic imbalances or side effects of medications Cognitive impairment can also occur as a natural process of aging. Cognitive impairment can also occur as a result of hallucinations. , may be associated with personality changes, depression, anxiety, loss of identity, and confusion. It has been demonstrated to prevent cognitive impairment in a mouse model of Alzheimer's disease ( Aso E, Palomer E, Juves S, Maldonado R, Muno z FJ,Ferrer I(2012)CB1 agonist ACEA prot ects neurons and reduces the cognitive i mpairment of AβPP / PS1 mice.J Alz Dis 30: 439-459), and the pairing of a PPAR agonist with a CB1 agonist has been shown to improve cognitive function. It has been proposed as a novel treatment for functional disorders (Panillo LV, Justi nova Z,Goldberg SR(2013)Inhibition of FA AH and activation of PPAR:New approaches to the treatment of cognitive dysfuncti on and drug addiction.Pharmacol Ther 138 :84-102). Drugs used to treat cognitive impairment include donepezil, gotu kola, (gotu kola), cholinesterase inhibitors, rivastigmine, galantamine and and memantine.

[0149] In some embodiments, the compositions and methods provided herein are directed to treating movement disorders. The present invention is indicated for the treatment, prophylaxis, prevention or management of

[0150] Movement disorders are neurological conditions that cause problems with movement. Examples include dystonia, chorea, Huntington's disease, Parkinson's disease, and parkinsonism. , tics, Tourette's syndrome, ataxia, tremor, essential tremor, myoclonus, polyphasic Sclerosis, startle syndrome, restless legs syndrome, stiff person syndrome, gait disorders and Movement disorders can be caused by damage to the brain, spinal cord or peripheral nerves, metabolic disorders, stroke and It can be caused by vascular disease, toxins, infections, medications and genetics. Cannabinoids can regulate neurotransmission involved in motor function, and target CB1 better than cannabis. Agonists have been proposed to manage or treat several movement disorders (Kluge r B, Triolo P, Jones W, Jankovic J (2015) The therapeutic potential of cannabinoids f or movement disorders.Movement Disorders 30:313-327). Furthermore, PPAR alpha agonists It may be useful in managing and treating other components of movement disorders such as Kinson's disease (Kreisl er A,Duhamel A,Vanbesien-Maillot C,Deste e A, Bordet R (2010)Differing short-term n europrotective effects of the fibrates f enofibrate and bezafibrate in MPTP and 6 -OHDA experimental models of Parkinson's See Behav Pharmacol 21:194-205 Medications for treating movement disorders include levodopa, dopamine agonists, and MA. These include OB antagonists, COMT inhibitors, anticholinergics, amantadine, and antidepressants. It can be obtained.

[0151] In some embodiments, the compositions and methods provided herein are directed to treating chronic pain The present invention is indicated for the treatment, prophylaxis, prevention or management of

[0152] Chronic pain is defined as any pain that lasts for more than 12 weeks and may persist for months or years. Causes of chronic pain include past injuries, back pain, migraines and other headaches, and arthritis. Chronic pain can be caused by a variety of conditions, including: rheumatoid arthritis, ... It may result in or be accompanied by sleep disturbances, loss of appetite and mood changes. Formula changes may help manage chronic pain, but there are many other medications that may be prescribed to help manage this condition. Herbal treatment is often necessary. Opiates are the most effective for pain. Some prescription drug treatments are addictive, contributing to the prevalence of drug addiction and its resulting Therefore, new, non-addictive, and effective pain management treatments are needed. CB1 receptor agonists are promising, non-addictive drugs for pain control. It has appeared as a drug (Talwar R, Kumar Potluri V (2011) C annabinoid 1(CB1)receptor-pharmacology,r ole in pain and recent developments in e merging CB1 agonists.CNS and Neurol Dis- (See Drug Targets 10:536-544.) Behavioral markers of chronic pain Side effects include fatigue, sleep disturbances, loss of appetite, and mood changes. Drugs that may cause side effects include opiates, oxycodone, tramadol, morphine, and nonsteroidal antihistamines. Anti-inflammatory drugs (NSAIDs), aspirin, acetaminophen, ibuprofen, COX -2 inhibitors, celecoxib, meloxicam, tricyclic antidepressants (TCAs), serotonin- Epinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors ( SSRIs), anti-seizure medications (pregabalin and gabapentin), corticosteroids, muscle relaxants These include emollients and Lidoderm.

[0153] In some embodiments, the compositions and methods provided herein are for the treatment of depression. Indicated for the placement, prophylaxis, prevention or control of

[0154] Depression is a mood disorder that affects the way an individual feels, thinks, and cope with daily activities. The forms of depression include persistent depressive disorder (dysthymia), postpartum depression, and psychotic depression. These include depression, seasonal affective disorder, bipolar disorder, severe mood dysregulation disorder, and premenstrual dysphoric disorder. The causes of depression include genetic, biological, environmental and psychological factors. Depression occurs alongside chronic illnesses such as diabetes, cancer, heart disease, and Parkinson's disease. Depression can be a persistent feeling of sadness or Mood anxiety, hopelessness, irritability, low energy, fatigue, difficulty concentrating, difficulty sleeping, changes in appetite, May cause weight changes, pain, headaches, and digestive problems. Deficiency of CB1 receptors. Mice receiving this treatment showed signs of depression, and CB1 agonists had effects similar to those of other antidepressants. CB1 agonists can enhance the effectiveness of CB1 as an antidepressant. Therefore, the combination of a CB1 receptor agonist and a PPAR agonist may be effective against depression. It has been proposed as a promising therapeutic target for 14) Endocannabinoid signaling in the etio logy and treatment of major depressive i See llness.Curr Pharm Design 20:3795-3811 Behavioral markers or symptoms of depression, such as irritability and restlessness, Increased preoccupation with depressed feelings, poor decision-making, difficulty remembering details, and poor concentration Slowness of speech and thinking, angry outbursts, increased sleep, and refusal to do activities that were once enjoyable Increased challenges in managing stress, meeting the demands of work, family, social and school life, self-harm, Murderous thoughts, feelings of worthlessness, self-critical feelings, overwhelming sadness, anxiety, a feeling of "emptiness" inside. Feelings of helplessness, guilt, helplessness, low self-esteem, poor self-image, or death or dying and suicidal thoughts can be monitored. Prazol, doxepin, clomipramine, bupropion, amoxapine, nortriptyline linoleic acid, citalopram, duloxetine, trazodone, venlafaxine, selegiline, Rufenadine, amitriptyline, levomilnacipran, desvenlafaxine, lurasidone Don, lamotrigine, escitalopram, isocarboxazid, phenelzine, desipra amine, tranylpromine, paroxetine, fluoxetine, mirtazapine, quetiapine nefazodone, imipramine, perphenazine, vortioxetine, vilazodone, These include lotriptyline, sertraline and olanzapine.

[0155] In some embodiments, the compositions and methods provided herein are directed to treating anorexia. and is indicated for the treatment, prophylaxis, prevention or management of appetite loss, including cachexia. Medications for treating depression include fluoxetine or other SSRIs or oranthraquinone. Zapin is one example.

[0156] Loss of appetite is common to many chronic, life-threatening illnesses, and lack of proper nutrition can contribute to chronic conditions. This cycle of chronic illness and loss of appetite can be detrimental to the health and well-being of the individual. Anorexia is the absence or loss of appetite, resulting in an inability to eat. This can be common in advanced cancer. Cachexia is a state of general poor health and malnutrition in which fat, muscle, and bone are lost. It is characterized by weakness and emaciation due to loss of muscle mass and is commonly seen in advanced cancer, AIDS, congestive heart failure, and chronic It can occur with severe conditions such as anorexia nervosa. An estimated 80% of cancer patients Causes of anorexia / cachexia syndrome include cancer, AIDS, heart disease, and metabolic disorders. changes, chronic inflammation, pain, dysgeusia, loss of taste, hypersomnia, dysphagia, difficulty breathing, nausea, vomiting Vomiting, constipation, diarrhea, drug side effects, psychological distress, anorexia nervosa, and oral or esophageal irritation These changes include those associated with chronic, life-threatening illnesses, such as infections. Current treatments for fluid dyscrasia include steroids, cannabinoids, and prokinetic drugs. However, these treatments are the main cause of anorexia and cachexia. They do not help treat underlying chronic conditions. Cannabinoids increase appetite and have long-lasting effects. It is known that CB1 receptor agonists are effective in people suffering from anorexia or cachexia. It can be used to increase food intake and weight gain in mice (Kirkham TC ( 2009)Cannabinoids and appetite:Food crav ing and food pleasure.Int Rev Psychiatry 21:163-171). Significant weight loss, and staying warm can significantly reduce weight loss. Dressing in layers to fit in, obsession with weight / food / calories / fat grams / diet wearing certain clothes, refusing to eat certain foods, feeling "fat" despite losing weight Comments about feeling "unwell" and complaints of constipation, abdominal pain, cold intolerance, lethargy, and excess energy denial of hunger, meal rituals, cooking for others without eating, eating Excuses to avoid work, describing the need to "burn" calories, and strict Maintaining a healthy exercise regimen, withdrawal from friends, limited social spontaneity, and maintaining a healthy weight Emotional markers, including unsustainability and a strong desire for control and behavioral markers or signs of anorexia can be monitored.

[0157] Treatment for seizures involves determining the underlying medical condition (drug reaction, severe infection, sepsis, hyperthermia, , severe vomiting and / or diarrhea, acute onset of diabetes (extremely high or low blood sugar levels), Hydration problems (severe dehydration or overhydration), severe malnutrition, trauma, or internal bleeding excessive blood loss, organ failure (e.g., acute renal failure), allergic reactions, drug overdose, Anticonvulsants / anti-seizure medications include: Acetazolamide, carbamazepine, clonazepam, diazepam, ethosuximide, gabapentin lantin, lacosamide, lamotrigine, levetiracetam, lorazepam, methsuximide, Trazepam, oxcarbazepine, paraldehyde, phenobarbital, phenytoin , pregabalin, primidone, rufinamide, stiripentol, topiramate, valproate Examples include bromocriptine, vigabatrin, felbamate, tiagabine hydrochloride, and zonisamide. do.

[0158] In some embodiments, the compositions and methods provided herein are useful for treating addiction. Indicated for the placement, prophylaxis, prevention or control of

[0159] Opioids bind to opiate receptors in the cell membrane of neurons and exert their analgesic effects. These are controlled substances that provide pain relief and control pain, including morphine, codeine, These include fentanyl, methadone, and buprenorphine. Opiate addiction is becoming an epidemic. This has led to an increase in opioid overdose deaths, including 49,000 deaths in the United States in 2017. Opiate withdrawal is a leading cause of death in Americans under 50. Symptoms are severe and include muscle aches, pain, agitation, anxiety, nausea, gastrointestinal upset, frequent Symptoms include palpitations, rhinorrhea, and chills (Wesson DR, Ling W. The Cli nical Opiate Withdrawal Scale(COWS)J Psy (Vocative Drugs. 2003;35:253-259). Due to the severity of the condition, individuals may find it difficult to stop using opioids and may develop opioid withdrawal symptoms. Novel approaches to attenuate symptoms, as well as novel non-addictive medications to control pain, are urgently needed. opioids, including heroin, morphine, codeine, and fentanyl, It targets the mu opioid receptor (OPRM1) and acts as an OPRM1 antagonist. Drugs, primarily naloxone, are used as acute emergency treatment for opioid overdose. There is extensive crosstalk between cannabinoid and opioid-related systems, It has been demonstrated that opioids attenuate withdrawal symptoms from opioid addiction, so CB1 receptors Interferon agonists have been proposed as a means to treat drug addiction, including opioid addiction. (Scavone JL, Sterling RC, Bockstaele EJ (2013)Cannabinoid and opioid interaction s:implications for opiate dependence and withdrawal. Neurosci 248:637-654). OPRM1 agonists have been shown to be effective in treating opioid addiction as well as other addictions, including alcohol and cocaine. OPRM1 antagonists may also play a role in substance addiction. It has been proposed to be useful in the treatment of alcohol and cocaine addiction (Kranzler HR ,Gelernter J,O'Malley S,Hernandez-Avila CA, Kaufman D (2006) Association of the alc. ohol or other drug dependence with allel es of the μ opioid receptor gene(OPRM1). See Alcoholism Clin Exp Res 22:1359-1362 Furthermore, the pairing of a PPAR agonist and a CB1 agonist may be a novel therapeutic approach against drug addiction. It has been proposed as a new treatment (Panillo LV, Justinova Z, Go ldberg SR (2013) Inhibition of FAAH and ac tivation of PPAR:New approaches to the t reatment of cognitive dysfunction and dr ug addiction.Pharmacol Ther 138:84-102). Behavioral markers of drug addiction or abuse include changes in interpersonal relationships resulting from drug use. Disrupting the staff, secretive or suspicious behavior, fights, accidents, Frequent trouble with the law, including illegal activities and driving under the influence of drugs, Abandoning responsibilities at school or home (including neglecting one's own children), friends, Sudden changes in favorite hangouts and hobbies, unknown financial needs or finances problems (borrowing or stealing money), using drugs in unsafe conditions (driving under the influence of drugs, use of clean needles, unprotected sex), and increased drug resistance (the same effects previously achieved with small doses). needing to take more of the drug to get the desired effect), withdrawal symptoms (nausea, restlessness, use of drugs to avoid or relieve symptoms of Loss of control over drug use (using more than intended, not being able to stop), A life that revolves around (always thinking about what you're going to use and how to get more of) or recovery from drug use), or avoiding enjoyable activities (hobbies, sports, etc.) in order to use drugs. withdrawal from sports, social interactions, adverse outcomes (blackouts, infections, mood swings, Continuing to use despite fear, anxiety or paranoia Obsessive, lethargic for no apparent reason; tired or "spacey" appearance, unusual energy periods of increased stress, nervous or unstable periods, sudden mood swings, increased irritability or These include outbursts of anger and unexplained personality or attitude changes. Medications for treating this include buprenorphine, methadone, and naltrexone. Medications for treating alcohol use disorders include acamprosate, disulfiram, Drugs for treating nicotine use disorder include benzodiazepines, benzodiazepines, and naltrexone. Examples include bupropion, nicotine replacement therapy, and varenicline.

[0160] The conditions described herein, i.e., cognitive impairment, movement disorders, chronic pain, depression, appetite Depression and addiction may be interrelated. In some embodiments, these symptoms One of the conditions is accompanied by another condition described herein.

[0161] The compositions of the above embodiments may be administered in combination with conventional therapy for the condition being treated, if desired. For example, before, during or after the conventional treatment, and in the same or different single It can be administered in various dosage forms.

[0162] A constellation of signs and symptoms may coexist in an individual subject, but often many are affected. Due to individual differences in the vulnerability of physiological systems, only one or a few symptoms may predominate. do.

[0163] In some embodiments provided herein, the subject to be treated is an animal, e.g., For example, it may be a domestic animal such as a dog or cat, however, usually their The methods, uses and compositions of the embodiments are intended to be applied to humans. Similarly, animal subjects, including canine and feline subjects, have also experienced cognitive impairment, movement disorders, chronic pain, and depression. , and may be prone to loss of appetite.

[0164] In some embodiments, the condition being treated is a cognitive impairment that occurs with Alzheimer's disease. Cognitive impairments include, but are not limited to, intellectual disability.

[0165] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, it is a cognitive disorder as pointed out.

[0166] In some embodiments, when a marker of cognitive impairment provides a clinical indication, the present invention The methods provided herein modulate that marker.

[0167] In some embodiments, the marker is a behavioral marker.

[0168] In some embodiments, the methods provided herein reduce symptoms of cognitive impairment. do.

[0169] In some embodiments, the methods provided herein include methods for reducing the risk of cognitive impairment. Lower it.

[0170] In some embodiments, the condition being treated is multiple sclerosis or Parkinson's disease. Movement disorders include, but are not limited to, movement disorders occurring with

[0171] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, it is a movement disorder as pointed out.

[0172] In some embodiments, when a marker for movement disorder provides a clinical indication, the present invention The methods provided herein modulate that marker.

[0173] In some embodiments, the marker is a behavioral marker.

[0174] In some embodiments, the methods provided herein reduce symptoms of movement disorders. do.

[0175] In some embodiments, the methods provided herein include methods for reducing the risk of movement disorders. Lower it.

[0176] In some embodiments, the methods provided herein treat convulsions.

[0177] In some embodiments, the methods provided herein treat stroke.

[0178] In some embodiments, the condition being treated is chronic pain.

[0179] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, it is a chronic pain as pointed out.

[0180] In some embodiments, when a marker of chronic pain provides a clinical indication, the present invention The methods provided herein modulate that marker.

[0181] In some embodiments, the marker is a behavioral marker.

[0182] In some embodiments, the methods provided herein reduce symptoms of chronic pain. do.

[0183] In some embodiments, the methods provided herein include methods for reducing the risk of chronic pain. Lower it.

[0184] In some embodiments, the condition being treated is depression.

[0185] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, it is the depression that is pointed out.

[0186] In some embodiments, when a marker of depression provides a clinical indication, the present invention The methods provided herein regulate that marker.

[0187] In some embodiments, the marker is a behavioral marker.

[0188] In some embodiments, the methods provided herein reduce symptoms of depression. .

[0189] In some embodiments, the methods provided herein reduce the risk of depression. Can.

[0190] In some embodiments, the condition being treated is anorexia or cachexia.

[0191] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, anorexia or cachexia as indicated.

[0192] In some embodiments, markers of anorexia or cachexia provide a clinical indication. When the marker is detected, the methods provided herein modulate that marker.

[0193] In some embodiments, the marker is a behavioral marker.

[0194] In some embodiments, the methods provided herein are directed to treating anorexia or cachexia. Relieves the symptoms of

[0195] In some embodiments, the methods provided herein are directed to treating anorexia or cachexia. Reduces the risk of

[0196] In some embodiments, the condition being treated is an addiction.

[0197] In some embodiments, the condition being treated is associated with a marker provided herein. Therefore, it is an addiction as pointed out.

[0198] In some embodiments, the marker is a behavioral marker.

[0199] In some embodiments, when a marker of addiction provides a clinical indication, the present invention The methods provided herein regulate that marker.

[0200] In some embodiments, the methods provided herein reduce the symptoms of addiction. .

[0201] In some embodiments, the methods provided herein reduce the risk of addiction. Can.

[0202] In some embodiments, the methods provided herein involve increasing blood levels of certain fatty acids. Increase your Purification level.

[0203] In some embodiments, the compositions and methods provided herein are directed to improving cognitive function. In certain embodiments, the markers of the disorder, movement disorder, or depression are modulated. Markers are the percentage of odd-chain fatty acids in serum or red blood cell membranes, serum or red blood Percentage of Compound of Formula (I) or its Salt or Metabolite in the Bulb Membrane, Odd Chain serum concentration of fatty acids, serum concentration of the compound of formula (I) or its salt or metabolite, serum total odd-chain fatty acids, serum ferritin, serum iron, transferritin saturation, serum glucose blood sugar (e.g., fasting blood glucose), serum triglycerides, blood pressure, HDL cholesterol, uroalbuminuria (i.e., increased excretion of albumin in the urine), CRP (C-reactive protein) proteins), IL-6 and TNFα (and other cytokines associated with insulin resistance) ), c-Jun N-terminal kinase (JNK), ATM (ataxia telangiectasia mutated) or single In some embodiments, the odd-chain fatty acid or The compound (I) or its salt or metabolite is measured as a constituent of glycolipids. In further embodiments, the odd-chain fatty acid or the compound of formula (I) or a salt thereof Metabolites are measured as constituents of phospholipids.

[0204] In some embodiments, behavioral markers of cognitive impairment include confusion, poor motor coordination, Loss of tonality, short-term or long-term memory, identity confusion, impaired judgment, hallucinations, delusions, personality changes , including emotional blunting, depression, anxiety, and confusion on navigation and visuospatial tasks. Cognitive tests as known in the art can be performed to assess cognitive status, e.g., The Mini-Cog, MOCA test (Montreal), which includes three-item recall and clock drawing l Cognitive Assessment Test), SLUMS (St.Lo uis University Mental Status Examination ) and the Mini-Mental State Exam.

[0205] In some embodiments, the methods provided herein are directed to treating cognitive impairment, movement disorders, and the like. The method includes measuring the concentration of a marker of neuropathic or neurodegenerative disorders. Those skilled in the art will recognize that suitable methods for such measurements are well known. methods (including but not limited to those described herein) can be performed. do.

[0206] Behavioral markers of any of the conditions described herein may be, for example, increased, steady-state, or monitor for a decrease, or any change in rate of increase, decrease, or other degree or nature. For some markers, effective treatment may be associated with a decrease observed in the absence of treatment. The level of the marker being treated may be maintained or the rate of decline observed in the absence of treatment may be reduced. Effective treatment may slow the rate of decline compared to the rate at which an increase is observed without treatment. The levels of the markers may be maintained or increased at a rate greater than that observed in the absence of treatment. Effective treatment may result in unchanged or decreased levels in the absence of treatment. The effect of treatment may increase the level of a marker that is observed to be decreased. In some cases, unchanged or elevated levels of the marker are observed. Treatment is measured by increasing the proportion of markers compared to what would be expected to be observed without treatment. It can be changed upward or downward.

[0207] At predetermined intervals or intervals left to the discretion of the subject, a dose of a compound of formula (I) or or a pharmaceutically acceptable salt thereof. do.

[0208] The compound of formula (I) or a pharmaceutically acceptable salt thereof may be, for example, compared or measured. When used in a subject's tissue, the formula (I) can be treated in terms of the naturally occurring fatty acids in the subject's tissue. The compound or a pharmaceutically acceptable salt thereof is a naturally occurring dietary fatty acid. The compound of formula (I) or a pharmaceutically acceptable salt thereof can be taken up into the body as if it were a drug. The salts in question may undergo one or more metabolic processes in the body, and the concentrations of these metabolic products may increase. The degree may indicate the condition of the subject.

[0209] In some embodiments, the compounds and methods provided herein comprise all The formula (I) in serum or red blood cell membranes compared to serum fatty acids or red blood cell membrane fatty acids, respectively ) or a salt or metabolite thereof. For example, The threshold may range from about 0.05% or less to 90% or more, e.g., At least about 0.05%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1.0 %, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2.1%, at least about 2. 2%, at least about 2.3%, at least about 2.4%, at least about 2.5%, at least Also about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, At least about 3.0%, at least about 3.5%, at least about 4.0%, at least about 4 0.5%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, At least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, It may be at least about 80%, at least about 90% or greater than 90%.

[0210] In some embodiments, the compounds and methods provided herein comprise a compound of formula (I): or a salt or metabolite thereof or the serum concentration of a compound of formula (I) or Baseline red blood cell membrane concentrations of salts or metabolites (e.g., treatment of patients undergoing treatment) provides a rise above pre-implantation values ​​or typical values ​​observed in a specific patient population For example, the compound of formula (I) or its salt or metabolite, or the compound of formula (I) or its salt or metabolite, in serum is obtained. The erythrocyte membrane concentration of the compound of formula I) or its salt or metabolite is at least about 1 μg / m 1, at least about 2 μg / ml, at least about 3 μg / ml, at least about 4 μg / ml , at least about 5 μg / ml, at least about 6 μg / ml, at least about 7 μg / ml, at least about 8 μg / ml, at least about 9 μg / ml, at least about 10 μg / ml, At least about 15 μg / ml, at least about 20 μg / ml, at least about 25 μg / ml 1, at least about 30 μg / ml, at least about 35 μg / ml, at least about 40 μg / ml, at least about 45 μg / ml, at least about 50 μg / ml or 50 μg / m In some embodiments, the compound of formula (I) or a salt thereof may be is the serum concentration of metabolites or the red blood cell concentration of the compound of formula (I) or its salts or metabolites The membrane concentrations may be measured at baseline values ​​(e.g., pre-treatment values ​​for a patient being treated, or at the time of treatment for a particular patient). (typical values ​​observed in the general population) and at least about 0.01 × 10 -4 M. At least about 0.05 x 10 -4 M, at least about 0.1 × 10 -4 M, at least about 0 .2×10 -4 M, at least about 0.3 × 10 -4 M, at least about 0.4 × 10 -4 M , at least about 0.5 × 10 -4 M, at least about 0.6 × 10 -4 M, at least about 0 .7×10 -4 M, at least about 0.8 × 10 -4 M, at least about 0.9 × 10 -4 M , at least about 1 x 10 -4 M, at least about 2 × 10 -4 M or at least about 3 x 1 0 -4 M may rise.

[0211] In some embodiments, the compounds and methods provided herein provide a method for treating rheumatoid arthritis in serum. It can increase total odd-chain fatty acids or total odd-chain fatty acids in red blood cell membranes. For example, serum Total odd-chain fatty acids in the red blood cell membrane or total odd-chain fatty acids in the red blood cell membrane were measured at baseline values ​​(e.g., Pretreatment values ​​for the patient being treated or typical values ​​observed in a particular patient population ) higher than about 5 μg / ml, at least about 6 μg / ml, at least about 7 μg / ml μg / ml, at least about 8 μg / ml, at least about 9 μg / ml, at least about 10 μg / ml g / ml, at least about 15 μg / ml, at least about 20 μg / ml, at least about 2 5 μg / ml, at least about 30 μg / ml, at least about 35 μg / ml, at least about 40 μg / ml, at least about 45 μg / ml, at least about 50 μg / ml, at least At least about 60 μg / ml, at least about 70 μg / ml, at least about 80 μg / ml, at least about 90 μg / ml, at least about 100 μg / ml, at least about 150 μg / ml ml, at least about 200 μg / ml, at least about 250 μg / ml, at least about 3 00 μg / ml, at least about 350 μg / ml, at least about 400 μg / ml, at least about 450 μg / ml, at least about 500 μg / ml or more than 500 μg / ml; It may increase.

[0212] In some embodiments, the compounds and methods provided herein are administered in serum or are the odd number of fatty acids in serum or red blood cell membranes compared to all fatty acids in red blood cell membranes, respectively. Baseline values ​​of chain fatty acids (e.g., pretreatment values ​​for patients being treated, or values ​​for specific patients) For example, the compound of formula (I) may provide a higher increase than the general value observed in the human population. The concentration of the compound or its salt or metabolite in serum or red blood cell membranes is measured at baseline. values ​​(e.g., pretreatment values ​​in treated patients or values ​​observed in a particular patient population) (typical values ​​given in the literature) and at least about 0.01%, at least about 0.05%, Both are about 0.1%, at least about 0.2%, at least about 0.3%, and at least about 0.4% , at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 1.1%, at least at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, At least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1 0.9%, at least about 2%, at least about 2.1%, at least about 2.2%, at least About 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3% , at least about 3.5%, at least about 4%, at least about 4.5%, at least about 5% Or it could rise by more than 5%.

[0213] In some embodiments, the compounds and methods provided herein comprise serum insulin. For example, serum insulin may be reduced to a baseline value (e.g., after treatment). lower than the pretreatment values ​​of patients receiving the treatment or the typical values ​​observed in a particular patient population At least about 0.1 μIU / ml, at least about 0.2 μIU / ml, at least about 0.3μIU / ml, at least about 0.4μIU / ml, at least about 0.5μIU / ml 1, at least about 0.6 μIU / ml, at least about 0.7 μIU / ml, at least about 0.8 μIU / ml, at least about 0.9 μIU / ml, at least about 1.0 μIU / ml 1, at least about 1.1 μIU / ml, at least about 1.2 μIU / ml, at least about 1.3 μIU / ml, at least about 1.4 μIU / ml, at least about 1.5 μIU / ml l, at least about 2 μIU / ml, at least about 2.5 μIU / ml, at least about 3. 0 μIU / ml, at least about 3.5 μIU / ml, at least about 4 μIU / ml, at least about 5 μIU / ml, at least about 6 μIU / ml, at least about 7 μIU / ml, At least about 8 μIU / ml, at least about 9 μIU / ml, at least about 10 μIU / ml, at least about 11 μIU / ml, at least about 12 μIU / ml, at least about 1 3 μIU / ml, at least about 14 μIU / ml, at least about 15 μIU / ml, at least about 16 μIU / ml, at least about 17 μIU / ml, at least about 18 μIU / ml ml, at least about 19 μIU / ml, at least about 20 μIU / ml, at least about 2 5 μIU / ml, at least about 30 μIU / ml or more than 30 μIU / ml, may be reduced .

[0214] In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof is , the compound of formula (I) or its salt or metabolite, serum phospholipid percentage or The drug is administered to maintain the percent cannabinoid metabolites above a predetermined threshold. In a further variation, a compound of formula (I) or a pharmaceutically acceptable salt thereof: The compound of formula (I) or a salt or metabolite thereof reduces serum phospholipid percentage to about 0. 1%, approximately 0.2%, approximately 0.3%, approximately 0.4%, approximately 0.5%, approximately 0.6%, approximately 0.7%, approximately 0.8%, approximately 0.9%, approximately 1%, approximately 1.2%, approximately 1.4%, approximately 1.6%, approximately 1.8%, approximately It is administered to maintain the blood glucose level above 2%, about 2.2%, about 2.4% or about 2.6%. Combination therapy

[0215] In some embodiments, the compounds disclosed herein (e.g., compounds of Formula (I) or a pharmaceutically acceptable salt thereof), or a compound or Pharmaceutical compositions containing the salts thereof may be used in combination with one or more additional active agents. A compound of formula (I) or a pharmaceutically acceptable salt thereof, or a compound of formula (I) or a pharmaceutically acceptable salt thereof. Examples of suitable agents include those described herein and otherwise disclosed in medical journals. As known in the science, cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, addiction, seizures, These include agents currently used to treat convulsions and related conditions. Not limited to:

[0216] In some embodiments, a compound of formula (I) or a pharmaceutically acceptable salt thereof or a composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, Use with one, two, three or more additional active agents as described herein. Such agents may include a second compound of formula (I) or a pharmaceutically acceptable salt thereof. or a naturally occurring fatty acid or a salt or derivative thereof. However, it is not limited to these.

[0217] In some embodiments, a compound of formula (I) or a pharmaceutically acceptable salt thereof or a composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof for treating cognitive impairment injury, movement disorders, pain management, depression, addiction, appetite stimulation, convulsions or for the treatment, prevention, maintenance or prophylaxis of other conditions such as, or as a marker of, such conditions , for example, in combination with another agent for modulation of a biological or behavioral marker. Conventional methods for treating such conditions can be used (e.g., administered or taken orally). The known or known drugs or agents are those listed above. For example, the compound of formula (I) The compound or a pharmaceutically acceptable salt thereof is selected from the group consisting of donepezil, gotu kola, and cholinesterase inhibitors. antidepressants, rivastigmine, galantamine, memantine, levodopa, dopamine agonists, MAO-B antagonists, COMT inhibitors, anticholinergics, amantadine, antidepressants, Pyridoxine, oxycodone, tramadol, morphine, nonsteroidal anti-inflammatory drugs (NSAIs) Ds), aspirin, acetaminophen, ibuprofen, COX-2 inhibitors, celecoxib Xib, meloxicam, tricyclic antidepressants (TCAs), serotonin norepinephrine reuptake Serotonin reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), anti-seizure drugs ( pregabalin and gabapentin), corticosteroids, muscle relaxants, Lidoderm, Alli Piprazole, doxepin, clomipramine, bupropion, amoxapine, nortriptyline Chirin, citalopram, duloxetine, trazodone, venlafaxine, selegiline, Perphenazine, amitriptyline, levomilnacipran, desvenlafaxine, lula Sidon, lamotrigine, escitalopram, isocarboxazid, phenelzine, decip Ramin, tranylpromine, paroxetine, fluoxetine, mirtazapine, quetiapine pine, nefazodone, imipramine, perphenazine, vortioxetine, vilazodone, Protriptyline, sertraline, olanzapine, acetazolamide, carbamazepine, Lonazepam, diazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, Levetiracetam, lorazepam, methsuximide, nitrazepam, oxcarbazepine, aldehyde, phenobarbital, phenytoin, pregabalin, primidone, lufi Namid, stiripentol, topiramate, valproic acid, vigabatrin, felbamate , tiagabine hydrochloride, zonisamide, buprenorphine, methadone, naltrexone, Camprosate, disulfiram, bupropion, nicotine replacement therapy, and varenicline It may be used in combination with one or more agents selected from: dosage

[0218] Useful in vivo dosages and specific dosages to be administered will be readily apparent to those skilled in the art. The specific mode of administration will depend on the age, weight, severity of symptoms and species of mammal to be treated, chemicals used, etc. These compounds vary depending on the specific form of the compound, as well as the specific use for which the compound is used. Determining effective dosage levels, i.e., the dosage required to achieve the desired result. Determining the amount level can be accomplished by one skilled in the art using routine methods, for example, in vivo studies. For example, "Estimating the Maximum Safe rting Dose in Initial Clinical Trials fo r Therapeutics in Adult Healthy Volunteer rs,”US Food and Drug Administration,Jul. Reference may be made to y 2005.

[0219] In some embodiments, the methods provided herein comprise administering to a subject a therapeutically effective amount of the compounds described herein. In some embodiments, the therapeutic method may include administering the provided composition to a subject. Efficacy was shown to modulate markers of cognitive impairment, movement disorders, chronic pain, depression, appetite loss, and addiction. In some embodiments, a therapeutically effective amount can be determined by reference to by referring to the regulation of symptoms of disability, movement disorders, chronic pain, depression, appetite loss and addiction In yet other embodiments, the antibody can be determined by the antibody established for the conditions described herein. Guidelines issued by the National Institute of Clinical Oncology (NIH) (including but not limited to guidelines for the treatment of diabetes) can be referred to.

[0220] Dosages vary widely depending on the desired effect and therapeutic endpoints (e.g., marker levels). Alternatively, dosage may be based on the surface area or weight of the patient, as will be understood by those skilled in the art. It may be based on a patient's surface area or weight. The appropriate dosage will be determined on a case-by-case basis, or in some cases, at the discretion of the informed subject. The daily dosage regimen for an adult patient is, for example, about 0.01 mg to about 10 000mg, about 1mg to about 5000mg, about 5mg to about 2000mg, about 10mg to about 1 000 mg or about 50 mg to about 500 mg of a compound of formula (I) or A pharmaceutically acceptable salt or a plurality of compounds of formula (I) or their pharmaceutically acceptable salts. a mixture of a compound of formula (I) or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable salt thereof; The single dose may be a mixture of naturally occurring fatty acids or their salts or derivatives. about 0.01 mg, about 0.1 mg, about 1 mg of a short-chain fatty acid or a salt or derivative thereof, Approx. 5mg, approx. 10mg, approx. 20mg, approx. 50mg, approx. 100mg, approx. 200mg, approx. 30 0mg, approx. 400mg, approx. 500mg, approx. 600mg, approx. 800mg, approx. 900mg, approx. Dosages may include about 1000 mg, about 2000 mg, about 5000 mg or more. The dosage may be adjusted according to the subject's weight, for example, about 0.001 mg / kg, about 0. 01mg / kg, approx. 0.1mg / kg, approx. 0.5mg / kg, approx. 1mg / kg, approx. 2mg / kg, approx. 3mg / kg, approx. 4mg / kg, approx. 5mg / kg, approx. 6mg / kg, approx. 7mg / kg, approximately 8mg / kg, approximately 9mg / kg, approximately 10mg / kg, approximately 15mg / kg, approximately 2 Dosing can be about 0 mg / kg, about 25 mg / kg, about 30 mg / kg or more. , single doses over one or more days, as appropriate for the individual subject. In some embodiments, the compound may be administered consecutively or more than once. The duration of treatment, e.g., about 1 week or more (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or more), a few weeks, about a month or or longer (e.g., 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, months, 8 months, 9 months, 10 months, 11 months, 12 months or more), The administration is for about one or more years or for multiple years. In this case, the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day. It may be administered or taken orally twice per day, three or more times per day.

[0221] As one skilled in the art will appreciate, in certain circumstances, in order to effectively treat a subject, In the case of a patient receiving a compound disclosed herein, the compound is administered in an amount exceeding the preferred dosage ranges set forth above. It may be necessary to give

[0222] Unit dosage forms, e.g., pre-measured doses configured for administration on a predetermined schedule. Individual packages containing a quantity of the composition may also be provided. A unit dosage form containing 2 doses per day is preferred; however, in certain embodiments, more than three doses per day may be used. It may be desirable to form unit dosage forms for administration of more than one dose per day or for administration less than once per day. There are cases where this happens.

[0223] Dosage and intervals may be determined based on a predetermined parameter, index or marker value or a minimum effective individual to provide plasma levels of the active moiety sufficient to maintain the MEC (Method Average Clinical Concentration). The dosage required to achieve the desired result can be tailored to the subject. However, assays such as HPLC assays or Alternatively, a bioassay may be used to measure serum concentrations.

[0224] In some embodiments, the compounds and methods provided herein comprise a device and methods of using the devices, e.g., U.S. Pat. No. 7,651,845; U.S. Pat. No. 8, 251,904; U.S. Patent No. 8,251,904; U.S. Patent No. 4,985,015 ;U.S. Patent No. 8,827,957;U.S. Patent No. 4,252,159;U.S. Patent No. 5, 318,521; U.S. Patent No. 4,718,430; U.S. Patent Application Publication No. 2011 / 0 190702; devices such as those provided in DE 2615061 A1 and methods of using the devices, as well as diagnostic devices, e.g., U.S. Pat. No. 2012 / 0072236, the contents of each of which are incorporated herein by reference in their entirety. The present invention may be used in conjunction with diagnostic devices such as those provided in the US Pat. Diagnostics and Monitoring

[0225] Diagnosis and monitoring of cognitive impairment, movement disorders, chronic pain, depression, appetite loss, addiction and related conditions A method for monitoring is provided herein.

[0226] In some embodiments, the method of diagnosis or monitoring comprises administering to a subject a compound of formula (I) or or its salts or metabolites or the percentage of naturally occurring fatty acids In some embodiments, the method of diagnosis or monitoring may include a cognitive Measure markers of disability, movement disorders, chronic pain, depression, appetite loss, addiction, or metabolic syndrome. In some embodiments, the correlation between one marker and another marker may be performed. In some embodiments, metabolic syndrome may be a contributing factor. Clusters or associated symptoms include cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, or addiction. the threshold level of the compound of formula (I) or a salt or metabolite thereof, e.g., the serum concentration of the compound of formula (I) or a salt or metabolite thereof , serum concentrations of naturally occurring fatty acids (e.g., percentage of odd-chain fatty acids, odd-chain fatty acids, Diagnosis can be made by looking at serum concentrations of fatty acids (or total odd-chain fatty acids in serum). For example, thresholds may be set for cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, and addiction or related disorders. The degree of urinary incontinence may be determined by reference to symptoms or markers of urinary incontinence.

[0227] a compound of formula (I) or a salt or metabolite thereof, or cognitive impairment in a subject; The percentage of markers of movement disorders, chronic pain, depression, appetite loss or addiction was The sample for analysis can be taken from any body fluid or tissue of the subject. For example, it may be obtained from serum, plasma, red blood cell membranes, urine and feces. [Example]

[0228] Comparative Example 1 Forty C57BL / 6J mice were fed a high-fat diet (HFD) (D12492, 60% kcal). The mice were then divided into four groups of 10 each: : Vehicle control, low dose C17:0 treatment (5 mg / kg body weight), high dose C17: 0 treatment (50 mg / kg body weight) and low-dose C15:0 treatment (5 mg / kg body weight). The material was purchased from Sigma-Aldrich in the form of a synthetic powder that was stable at room temperature. The product was W433400 (≥99% C15:0) and H3500 SIGMA ( ≥98% C17:0). were provided by gavage daily for 12 weeks (84 days). The intake was measured weekly. Serum insulin, glucose, cholesterol and IL -6, TNF-α, and MCP-1 levels were measured on day 84. Data for treatment groups were Comparisons with the control group were performed using Ilcoxon rank sum analysis. Significance was determined at 0.05 or less. P value was defined.

[0229] Mice in the treatment groups tolerated the test article throughout the study. There were no deaths in the control group, but one mouse died unexpectedly at week 7. No changes in body weight, weight change rate, or food intake were observed when comparing the study groups ( not shown).

[0230] Treatment with C15:0 (5 mg / kg) compared the treated group with the vehicle control group. Subjects treated with methadone had attenuated metabolic syndrome compared to controls, including reduced glucose tolerance. cerebrospinal fluid, insulin, cholesterol and pro-inflammatory cytokines (IL-6, TNF- These included decreases in inflammatory bowel disease (e.g., inflammatory bowel disease, inflammatory bowel disease, and MCP-1) (Table 1). There was a trend toward attenuation of metabolic syndrome compared with the control (Table 1). Only 50 mg / kg of 10 ... The chemokines (TNF-α and MCP-1) were absent (Table 1).

[0231] Table 1 shows the results of oral administration of pentadecanoic acid (5 mg / kg BW), heptadecanoic acid (5 mg / kg BW) for 12 weeks. Cardiovascular metabolism in diet-induced obese mice treated daily with 50 mg / kg body weight (50 mg / kg body weight and 50 mg / kg body weight) Comparisons of the therapeutic effects compared to vehicle control are provided. "Results" values ​​are for the 6-hour Based on fasted samples. [Table 73] Comparative Example 2

[0232] This study examines the efficacy of unsubstituted odd-chain saturated fatty acids in treating metabolic syndrome and related disorders. To optimize the health benefits of unsubstituted and substituted saturated fatty acids, The structure-activity relationship was compared. Fatty acids inhibit the peroxisome proliferator-activated receptor (PP Since the AR is a natural ligand, lead compound optimization was performed using cell-based PP We started with structure-activity relationships for AR agonist activity. Specifically, in this study, three Unsubstituted saturated fatty acids (C14:0, C15:0 and C16:0) and various Substituted saturated fatty acids (2-methyl-, 2,2-dimethyl-, 1-tetrazole-, 3- Oxy-, 2-methyl-1-tetrazole-, 2-ethyl-, 2,2-diethyl- and The PPAR agonist activity of these three unsubstituted fatty acids was investigated. PPAR agonist activity of saturated fatty acids of the fatty acid type and PPAR of those with various substituents The PAR agonist activity was compared with that of PPAR-α, PPAR-δ, and PPAR-γ agonists. Agonist activity was assessed using PathHunter nuclear hormone receptor (NHR) protein phase. Interaction (Pro) Assay (DiscoverX, Freemont, California Briefly, the Chinese hamster ovary (CHO) cell line was used. The activation of PPAR-α, PPAR-δ, and PPAR-γ was measured using Enzyme Fraction (Fr) Homogeneous non-imagery using Augmented Complementation (EFC) The NHR Pro assay monitored the activity of activated full-length P PAR-α, PPAR-δ, and PPAR-γ proteins and one or more canonical L Steroid receptor coactivator peptide (S) with XXLL interaction motif This was based on the detection of protein-protein interactions with fusion proteins containing RCP (reversible cyclic phospholipid) domains. PPAR-α, PPAR-δ, and PPAR-γ were assayed using ProL™ from the EFC assay system. The SRCP domain is tagged with the ink construct and is then linked to an enzyme acceptor expressed in the nucleus. PPAR-α, PPAR-δ, or PPAR-γ was fused to the EA. Upon binding to GAND, it translocates to the nucleus and recruits the SRCP domain, thereby promoting complementation. This produces active β-galactosidase (β-Gal) units, which produce a chemiluminescent signal. The advantages associated with this approach include reduced compound incubation time. and direct measurement of PPAR-α, PPAR-δ, and PPAR-γ targets. Uses full-length human PPAR-α, PPAR-δ, and PPAR-γ sequences. The advantages of this approach include the ability to select novel compound classes based on their disruption of protein-protein interactions. PPAR-α, PPAR-δ, and PPAR-γ agonist dose curves were performed using unsubstituted lipids. Fatty acid type C14:0, C15:0, C16:0; C14:0, C15:0, C16:0 2-Methyl substituents; 2,2-dimethyl substituents at C14:0, C15:0, and C16:0; C 1-tetrazole substituents at C14:0 and C15:0; and C15:0 and C16 3-oxy substituents at C15:0; and 2-methyl-1-tetrazole, 2-ethoxy ethyl, 2,2-diethyl and 2-methyl-2-ethyl substituents, and PPAR-α( GW7647), PPAR-δ (L-165,041) and PPAR-γ (Troglyta Positive controls for benzodiazepines were prepared in duplicate at 10 concentrations. Data shown are those observed in the presence of control compound and vehicle, respectively. The percentage activity was calculated using the following formula: Calculation was made using: % activity = 100% x (mean RLU of test sample - vehicle control) (mean RLU of control ligand) / (mean MAX control ligand - mean vehicle control RLU).

[0233] Compared with unsubstituted saturated fatty acids, substituted saturated fatty acids have a higher PPAR agonist activity. showed improved concentrations, with a reduction in the concentration required to reach half-maximal effective concentrations for (Table 4). Various substituents are associated with different PPAR isotypes (PPAR-α, -δ and - γ), allowing for targeted agonist activity of desired PPAR isotypes. It became possible to select the compounds from the test group. The 2-methyl substituents on 6:0 inhibit PPAR-α compared with their unsubstituted fatty acid counterparts. The agonist EC50 was improved by 17%, 48%, and 62%, respectively. The 2,2-dimethyl substituents on C5:0 and C16:0 are equivalent to their unsubstituted fatty acid counterparts. 13%, 44%, and 90% improvement in PPAR-α agonist EC50 compared to 1-Tetrazole-C15:0, 3-oxa-C15:0 and 2-methyl-1- The tetrazole-C15:0 substituent has a lower PPAR-α agonist EC5 0 by 77%, 54%, and 44%, respectively. The 2-diethyl-C15:0 substituent has a lower PPARα agonist EC5 0 by 90% and 85%, respectively.

[0234] The 1-tetrazole substituents on C14:0 and C15:0 are the same as those of the unsubstituted fatty acids. Compared with the fatty acid form, the PPAR-δ agonist EC50 was improved by 63% and 81%, respectively. The 3-oxa substituents on C15:0 and C16:0 were similar to those of the unsubstituted fatty acids. Compared with the previous type, the PPAR-δ agonist EC50 was improved by 85% and 70%, respectively. 2-Methyl-1-tetrazole-C15:0 inhibits PPAR-δ receptors compared with C15:0. 2-Methyl-C16:0 and 2,2-dimethyl-C 16:0 had a PPAR-δ agonist EC50 of 11 and 16:0, respectively, compared with C16:0. 2-Ethyl-C15:0 significantly improved PPAR-δ activity compared to C15:0. Unsubstituted saturated fatty acids significantly improved PPAR-γ activity by 89%. However, 2-methyl-C14:0, 2-methyl-C15:0, and 2-methyl-C1 6:0, 2,2-dimethyl-C14:0, 2,2-dimethyl-C15:0, 2-ethyl- C15:0, 2,2-diethyl-C15:0 and 2-methyl-2-ethyl-C15:0 It has acquired PPAR-γ agonist activity. The potency of these analogs against cellular systems that mimic systems including the human immune and autoimmune systems. The activity was surprisingly high because it was not achieved at all with unsubstituted fatty acid C15:0. These analogs simply enhanced the activity of the unsubstituted fatty acid form of C15:0. as well as altering the targeted disease system.

[0235] In summary, substituted saturated fatty acids have a higher cell-based We succeeded in lowering the concentration of compounds required to exhibit PPAR agonist activity. Furthermore, different substituents are involved in the regulation of different PPAR isotypes (PPAR-α, -δ and - γ), we selected specific substituents to target specific PPAR-related diseases. It will be possible to choose.

[0236] Table 4 shows the results of selected saturating proteins when used in cell-based protein-protein interaction assays. A comparison of PPAR agonist activity between saturated fatty acids is provided. [Table 74]

[0237] Table 5 shows the half-maximal effective concentrations (EC50) of unsubstituted saturated fatty acids (FFA). A comparison of PPAR agonist activity between saturated fatty acids with and without substitution is provided. . [Table 75] Example 3

[0238] This study will evaluate potential differences between these compounds with respect to additional pharmacological targets. To investigate the structure-activity relationship between selected unsubstituted saturated fatty acids and their substituted saturated fatty acids, In particular, in this study, SAFETYscan E / IC50 ELEC T(DiscoverX / Eurofins, Fremont, California) Across 78 assays using C15:0, 2-methyl-C15:0, 2-ethyl Agonist and antagonistic activities of 1-tetrazole-C15:0 and 1-tetrazole-C15:0 Briefly, various standardized and optimized functional assays were performed. Using this, G protein-coupled receptors (ADORA2A, ADRA1A, ADRA2A, ADRB1, ADRB2, CB1, CB2, CCK1, D1, D2S, ETA, H1, H 2, M1 M2, M3, OPRD1, OPRK1, OPRM1, 5HTR1A, 5HTR 1B, 5HTR2A, 5HTR2B, AVPR1A), kinases (LCK, INSR, V EGFR2, ROCK1), transporters (DAT, NET, SERT), ion channels Channels (GABAA, 5-HT3, CA1.2, HERG, KVLQT1 / MINK, N A1.5, NMDAR1 / 2B, NACHR), nuclear receptors (AR, GR) and non Kinase enzymes (COX1, COX2, ACHE, MAO-A, PDE3A, PDE4D2 The pharmacological targets of selected compounds, including agonist activity (EC5 Ten-point concentration curves for both agonist (IC50) and antagonist activity (IC50) were performed for each compound. An internal positive control was established for each target. The maximum activity (%) was also determined based on a comparison with the CB1 receptor agonist activity. The positive control was CP55940 (EC50 = 0.06 nM). The positive control for PRM1 antagonist activity was naloxone (IC50 =5nm).

[0239] Across 78 assays, C15:0 and 2-methyl-C15:0 showed Surprisingly, 2-ethyl-C15:0 did not show any activity other than that of C15: Compared with 0, potent PPAR-α agonist activity was obtained at a lower concentration (170% It showed a significant increase in PPAR-δ agonist activity (maximal activity, EC50 = 1.2 μM) and sustained PPAR-δ agonist activity. In addition to the fact that it was obtained at a lower concentration (72.4% of the maximum activity, EC50 = 28 nM), It also added novel partial CB1 agonist activity at nanomolar concentrations (53.7% of maximum activity) , EC50=27nm). Even more surprisingly, 1-tetrazole-C15:0 exhibited While reducing the maximum activity of PPAR-α and PPAR-δ compared to 15:0 (PPAR- 32% against PPAR-α and 18% against PPAR-δ), partial CB1 agonist activity (48.3% maximal activity, IC50=1.3 μm) and partial OPRM1 antagonist Both the activity (46.2% of the maximum activity, IC50 = 3.9 μM) and the activity of the α-glucanase inhibitor ... 2 shows the target of the tested compounds, including EC / IC50 (Fig. 1) and maximum activity (Fig. 2). The agonist and antagonist activities of these compounds are compared.

[0240] This study aims to 1) alter the targeting of PPAR-α and PPAR-δ agonist activity; 2) to introduce novel targeting of CB1 agonists, and 3) to develop OPRM1 antagonists. This confirms that saturated fatty acid analogs can be used to introduce novel targeting of antagonists. Furthermore, based on these activities, it has been reported that steroids may be effective in treating cognitive impairment, movement disorders, chronic pain, depression, and loss of appetite. Alternatively, specific saturated fatty acid analogs can be selected to prevent, manage, and treat addiction. As an example, 2 is being used to treat cognitive impairment, movement disorders, chronic pain, depression, and loss of appetite. As another example, -ethyl-C15:0 may be selected to treat opioid addiction. 1-Tetrazole-C15:0 may be selected. Example 4

[0241] In this study, 3-oxa-C15:0, 2-methyl-C15:0-tetrazole and The cannabinoid receptor 1 agonist activity of diethyl-C15:0 was evaluated. Each of these three compounds was tested against a positive control (CP, a synthetic compound that mimics THC). 55940), it exhibited stronger cannabinoid receptor 1 agonism. [Table 76] Exemplary Compositions, Methods and Uses

[0242] Method 1: Cognitive impairment, movement disorders, chronic pain, depression, loss of appetite, convulsions, seizures and addiction A method for treating or preventing the onset of a condition selected from the group consisting of administering to a patient in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof The method includes administering a pharmaceutical composition, wherein the compound of formula (I) has the structure: [ka] Formula (I) wherein G is an unsubstituted or substituted C 10 -C 18 Alkyl, unsubstituted or substituted C1 0-C 18 Alkenyl, unsubstituted or substituted with 1, 2 or 3 oxa or thia substituents is a substitution C 10 -C 18 alkyl and one, two or three oxa or thia substituents Substitution C 10 -C 18 alkenyl; X is selected from the group consisting of O and CR 1 R 2 and R is selected from the group consisting of 1 and R 2 are each independently H and unsubstituted or substituted C1-C6 alkyl; Y 1 and Y 2 are each independently , H, unsubstituted or substituted C1-C6 alkoxy and unsubstituted or substituted C1-C6 alkyl or Y 1 and Y 2 are, together, non-substituted or Substituted C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C6-C 10 aryl, C1-C 10 Heteroaryl and C1-C 10 may form a heterocyclyl; Z may , carboxylic acid, -C(=O)-OH, C1-C6 alkyl ester, unsubstituted or substituted alkyl amide, 5- or 6-membered unsubstituted or substituted heterocyclyl and 5- or 6-membered unsubstituted or is selected from the group consisting of substituted heteroaryl; a substituted group is one that is substituted with one or more substituents. wherein each substituent is independently C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C7 cycloalkyl, C1-C7 cycloalkenyl, aryl C1-C6 alkyl, C1-C6 alkoxy (C1-C6 alkyl), amino (C 1-C6 alkyl), amino acids, C6-C 10 Aryl, C1-C 10 heteroaryl, C1-C 10 Heterocyclyl, C6-C 10 Aryl (C1-C6 alkyl), C1-C 10 Heteroaryl (C1-C6 alkyl), C1-C 10 Heterocyclyl (C1-C6 alkyl), hydroxyl (C1-C6 alkyl), acyl, cyano, halogen, thioca Carbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl , C-amide, N-amide, S-sulfonamide, N-sulfonamide, C-carboxy , O-carboxy, isocyanato, thiocyanato, isothiocyanato, azido, nitro, Silyl, sulfenyl, sulfinyl, sulfonyl, halo(C1-C6 alkyl), C1 -C6 haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamide and and amino, method.

[0243] Method 2: Method 1, wherein G is an unsubstituted C10-C18 alkyl.

[0244] Method 3: Method 1, wherein G is unsubstituted undecyl.

[0245] Method 4: Method 1, wherein G is unsubstituted dodecyl.

[0246] Method 5: Method 1, wherein G is unsubstituted tridecyl.

[0247] Method 6: Method 1, wherein G is unsubstituted tetradecyl.

[0248] Method 7: Method 1, wherein G is unsubstituted pentadecyl.

[0249] Method 8: Method 1, wherein G is unsubstituted hexadecyl.

[0250] Method 9: Method 1, wherein G is unsubstituted heptadecyl.

[0251] Method 10: Method 1, wherein G is unsubstituted octadecyl.

[0252] Method 11: Methods 1 to 10, wherein X is CR1R2, and R1 and R2 are each H. Any one of 10.

[0253] Method 12: Any one of Methods 1 to 10, wherein X is O.

[0254] Method 13:Y 1 is H and Y 2 is hydrogen. tsu.

[0255] Method 14:Y 1 is selected from the group consisting of H and unsubstituted C1-C6 alkyl, and Y 2 Any one of methods 1 to 12, wherein is unsubstituted C1-C6 alkyl.

[0256] Method 15:Y 1 is selected from the group consisting of H, unsubstituted methyl, and unsubstituted ethyl; Y 2 Any one of methods 1-12, wherein is unsubstituted methyl or ethyl.

[0257] Method 16:Y 1 is selected from the group consisting of H and unsubstituted ethyl, and Y 2 But non-substituted Chill, any one of methods 1-12.

[0258] Method 17:Y 1 is H and Y 2 is unsubstituted ethyl Either one.

[0259] Method 18:Y 1 is unsubstituted ethyl, and Y 2 is unsubstituted ethyl, One of the following.

[0260] Method 19:Y 1 is H and Y 2 is unsubstituted methyl Either one.

[0261] Method 20: Any one of Methods 1 to 19, wherein Z is —C(═O)—OH.

[0262] Method 21: Z is [ka] Any one of methods 1 to 19.

[0263] Method 22: Z is [ka] Any one of methods 1 to 19.

[0264] Method 23: Z is [ka] and [ka] Any one of methods 1-19 selected from the group consisting of:

[0265] Method 24: G is unsubstituted C10-C18 alkyl, X is CR1R2, and R R1 and R2 are each H, and Y1 consists of H and unsubstituted C1-C6 alkyl. and Y2 is unsubstituted C1-C6 alkyl.

[0266] Method 25: Compounds of formula (I) are prepared by the process of: 2-methyl-stearic acid, 2,2-dimethyl-stearic acid Allic acid, 2-ethyloctadecanoic acid, 2-ethyl-2-methyloctadecanoic acid, 2,2- Diethyloctadecanoate, 3-oxa-stearic acid, 2-(pentadecyloxy)propanol Panic acid, 2,2-dimethyl-3-oxa-stearic acid, 2-(pentadecyloxy)butyl 2-Methyl-2-(pentadecyloxy)butanoic acid, 2-ethyl-2-(pentadecyloxy)butanoic acid Decyloxy)butanoic acid, 1-octadecyl-1H-tetrazole, 1-(nonadecane- 2-yl)-1H-tetrazole, 1-(2-methylnonadecan-2-yl)-1H-tetrazole 1-(icosan-3-yl)-1H-tetrazole, 1-(3-methylicosan-3-yl)-1H-tetrazole 1-(3-ethylicosan-3-yl)-1H-tetrazole, 1-(3-ethylicosan-3-yl)-1H-tetrazole -Tetrazole, 5-octadecyl-1H-tetrazole, 5-(nonadecan-2-yl) )-1H-tetrazole, 5-(2-methylnonadecan-2-yl)-1H-tetrazole 5-(icosan-3-yl)-1H-tetrazole, 5-(3-methylicosan-3 -yl)-1H-tetrazole, 5-(3-ethylicosan-3-yl)-1H-tetrazole 4-octadecyloxazol-2(3H)-one, 4-(nonadecan-2-yl) oxazol-2(3H)-one, 4-(2-methylnonadecan-2-yl)oxazol-2(3H)-one 2(3H)-oxazole-2(3H)-one, 4-(3-methylicosan-3-yl)oxazole-2( 3H)-one, 4-(icosan-3-yl)oxazol-2(3H)-one, 4-(3 -Ethylicosan-3-yl)oxazol-2(3H)-one, 3-octadecyl-1 ,2,4-Oxadiazol-5(4H)-one, 3-(nonadecan-2-yl-1,2 ,4-Oxadiazol-5(4H)-one, 3-(2-methylnonadecan-2-yl) -1,2,4-oxadiazol-5(4H)-one, 3-(3-methylicosan-3- yl)-1,2,4-oxadiazol-5(4H)-one, 3-(icosan-3-yl )-1,2,4-Oxadiazol-5(4H)-one, 3-(3-ethylicosane-3 -yl)-1,2,4-oxadiazol-5(4H)-one, 5-octadecyloxa 2(3H)-oxazole-2(3H)-one, 5-(nonadecan-2-yl)oxazole-2(3H)- 5-(2-methylnonadecan-2-yl)oxazol-2(3H)-one, 5- (icosan-3-yl)oxazol-2(3H)-one, 5-(3-methylicosan- 3-yl)oxazol-2(3H)-one, 5-(3-ethylicosan-3-yl)o Xazol-2(3H)-one, 5-octadecyl-1,2,3-oxadiazol-4 (5H)-one, 5-(nonadecan-2-yl)-1,2,3-oxadiazol-4( 5H)-one, 5-(2-methylnonadecan-2-yl)-1,2,3-oxadiazo 5-(icosan-3-yl)-1,2,3-oxadiazole-4(5H)-one 4(5H)-one, 5-(3-methylicosan-3-yl)-1,2,3-oxadiazo 4(5H)-ol, 5-(3-ethylicosan-3-yl)-1,2,3-oxazoline Diazol-4(5H)-one, N-hydroxystearamide, N-hydroxy-2- Methyloctadecaneamide, N-hydroxy-2,2-dimethyloctadecaneamide, 2 -Ethyl-N-hydroxyoctadecanamide, 2-ethyl-N-hydroxy-2-methyl 2,2-diethyl-N-hydroxyoctadecanamide, 1-octadecanamide, 1-(nonadecan-2-yl)-2,3-dihydro-1H-tetrazole 2,3-Dihydro-1H-tetrazole, 1-(2-methylnonadecan-2-yl)-2 ,3-Dihydro-1H-tetrazole, 1-(icosan-3-yl)-2,3-dihydro -1H-Tetrazole, 1-(3-methylicosan-3-yl)-2,3-dihydro-1 H-Tetrazole, 1-(3-ethylicosan-3-yl)-2,3-dihydro-1H- Tetrazole, 1-octadecyl-2,5-dihydro-1H-tetrazole, 1-(nonyl) Decane-2-yl)-2,5-dihydro-1H-tetrazole, 1-(2-methylnonadecane 1-(icosan-3-yl)-2,5-dihydro-1H-tetrazole, 1-(icosan-3-yl)-2,5-dihydro-1H-tetrazole )-2,5-Dihydro-1H-tetrazole, 1-(3-methylicosan-3-yl)- 2,5-Dihydro-1H-tetrazole, 1-(3-ethylicosan-3-yl)-2, 5-Dihydro-1H-tetrazole, 2-methylheptadecanoic acid, 2,2-dimethylheptadecanoic acid Tadecanoic acid, 2-ethylheptadecanoic acid, 2-ethyl-2-methylheptadecanoic acid, 2, 2-Diethylheptadecanoic acid, 2-(tetradecyloxy)acetic acid, 2-(tetradecyloxy) 2-methyl-2-(tetradecyloxy)propanoic acid, 2-(tetradecyloxy)propanoic acid 2-methyl-2-(tetradecyloxy)butanoic acid, 2-ethyl-2-(tetradecyloxy)butanoic acid, 1-Heptadecyl-2-(tetradecyloxy)butanoic acid, 1-heptadecyl-1H-tetrazole, 1 -(octadecan-2-yl)-1H-tetrazole, 1-(2-methyloctadecane- 2-yl)-1H-tetrazole, 1-(nonadecan-3-yl)-1H-tetrazole , 1-(3-methylnonadecan-3-yl)-1H-tetrazole, 1-(3-ethylnonadecan-3-yl)-1H-tetrazole Nadecane-3-yl)-1H-tetrazole, 5-heptadecyl-1H-tetrazole, 5-(octadecan-2-yl)-1H-tetrazole, 5-(2-methyloctadecane -2-yl)-1H-tetrazole, 5-(nonadecan-3-yl)-1H-tetrazole 5-(3-methylnonadecan-3-yl)-1H-tetrazole, 5-(3-ethyl nonadecan-3-yl)-1H-tetrazole, 4-heptadecyloxazole-2(3 H)-one, 4-(octadecan-2-yl)oxazol-2(3H)-one, 4-( 2-Methyloctadecan-2-yl)oxazol-2(3H)-one, 4-(nonadecan-2-yl)oxazol-2(3H)-one 4-(3-methylnonadecan-3-yl)oxazol-2(3H)-one, 4-(3-methylnonadecan-3-yl)oxazol-2(3H)-one oxazol-2(3H)-one, 4-(3-ethylnonadecan-3-yl)oxazol-2(3H)-one, 2(3H)-one, 3-heptadecyl-1,2,4-oxadiazol-5(4 H)-one, 3-(octadecan-2-yl)-1,2,4-oxadiazol-5(4 H)-one, 3-(2-methyloctadecan-2-yl)-1,2,4-oxadiazo 3-(3-methylnonadecan-3-yl)-1,2,4-oxa-5(4H)-one Diazol-5(4H)-one, 3-(nonadecan-3-yl)-1,2,4-oxazol- Azol-5(4H)-one, 3-(3-ethylnonadecan-3-yl)-1,2,4- Oxadiazol-5(4H)-one, 5-heptadecyloxazol-2(3H)-one 5-(octadecan-2-yl)oxazol-2(3H)-one, 5-(2-methyl 5-(octadecan-2-yl)oxazol-2(3H)-one, 5-(nonadecan-3- 5-(3-methylnonadecan-3-yl)oxazol-2(3H)-one, 5-(3-methylnonadecan-3-yl)oxazol-2(3H)-one oxazol-2(3H)-one, 5-(3-ethylnonadecan-3-yl)oxazole- 2(3H)-one, 5-heptadecyl-1,2,3-oxadiazol-4(5H)-one 5-(octadecan-2-yl)-1,2,3-oxadiazole-4(5H)-one 5-(2-methyloctadecan-2-yl)-1,2,3-oxadiazole-4( 5H)-one, 5-(nonadecan-3-yl)-1,2,3-oxadiazol-4(5 H)-one, 5-(3-methylnonadecan-3-yl)-1,2,3-oxadiazole -4(5H)-one, 5-(3-ethylnonadecan-3-yl)-1,2,3-oxazolidinone Azol-4(5H)-one, N-hydroxyheptadecanamide, N-hydroxy-2 -methylheptadecanamide, N-hydroxy-2,2-dimethylheptadecanamide, 2-Ethyl-N-hydroxyheptadecanamide, 2-Ethyl-N-hydroxy-2-methyl 2,2-Diethyl-N-hydroxyheptadecanamide, 1- Heptadecyl-2,3-dihydro-1H-tetrazole, 1-(octadecan-2-yl )-2,3-Dihydro-1H-tetrazole, 1-(2-methyloctadecan-2-yl )-2,3-Dihydro-1H-tetrazole, 1-(nonadecan-3-yl)-2,3- Dihydro-1H-tetrazole, 1-(3-methylnonadecan-3-yl)-2,3-di Hydro-1H-tetrazole, 1-(3-ethylnonadecan-3-yl)-2,3-dihydro 1-Heptadecyl-2,5-dihydro-1H-tetrazole, 1-heptadecyl-2,5-dihydro-1H-tetrazole , 1-(octadecan-2-yl)-2,5-dihydro-1H-tetrazole, 1-(2 -methyloctadecan-2-yl)-2,5-dihydro-1H-tetrazole, 1-(no Nadecane-3-yl)-2,5-dihydro-1H-tetrazole, 1-(3-methylnonane Decane-3-yl)-2,5-dihydro-1H-tetrazole, 1-(3-ethylnonadecan-3-yl)-2,5-dihydro-1H-tetrazole, Can-3-yl)-2,5-dihydro-1H-tetrazole, 2-methylhexadecanoic acid , 2,2-dimethylhexadecanoic acid, 2-ethylhexadecanoic acid, 2-ethyl-2-methyl 2,2-Diethylhexadecanoic acid, 2-(tridecyloxy)acetic acid, 2-(Tridecyloxy)propanoic acid, 2-methyl-2-(tridecyloxy)propane Acid, 2-(tridecyloxy)butanoic acid, 2-methyl-2-(tridecyloxy)butane Acid, 2-ethyl-2-(tridecyloxy)butanoic acid, 1-hexadecyl-1H-tetradecyl 1-(heptadecan-2-yl)-1H-tetrazole, 1-(2-methylheptadecan-2-yl)-1H-tetrazole 1-(octadecan-2-yl)-1H-tetrazole, 1-(octadecan-3-yl)-1H- Tetrazole, 1-(3-methyloctadecan-3-yl)-1H-tetrazole, 1- (3-ethyloctadecan-3-yl)-1H-tetrazole, 5-hexadecyl-1H -tetrazole, 5-(heptadecan-2-yl)-1H-tetrazole, 5-(2-methyl- 5-(octadecan-3-yl)-1H-tetrazole, 5-(octadecan-2-yl) -1H-Tetrazole, 5-(3-methyloctadecan-3-yl)-1H-tetrazole 5-(3-ethyloctadecan-3-yl)-1H-tetrazole, 4-hexadecanyl 4-(heptadecan-2-yl)oxazole-2(3H)-one, 4-(heptadecan-2-yl)oxazole-2(3H)-one (3H)-one, 4-(2-methylheptadecan-2-yl)oxazol-2(3H) -one, 4-(octadecan-3-yl)oxazol-2(3H)-one, 4-(3- Methyloctadecan-3-yl)oxazol-2(3H)-one, 4-(3-ethyloxazol-2(3H)-one 3-Hexadecyl-1,2, oxazol-2(3H)-one, 3-hexadecyl-1,2, 4-Oxadiazol-5(4H)-one, 3-(heptadecan-2-yl)-1,2, 4-Oxadiazol-5(4H)-one, 3-(2-methylheptadecan-2-yl) -1,2,4-oxadiazol-5(4H)-one, 3-(3-methyloctadecane- 3-yl)-1,2,4-oxadiazol-5(4H)-one, 3-(octadecane- 3-yl)-1,2,4-oxadiazol-5(4H)-one, 3-(3-ethyloctyl)-1,2,4-oxadiazol-5(4H)-one (tadecan-3-yl)-1,2,4-oxadiazol-5(4H)-one, 5-hexa Decyloxazol-2(3H)-one, 5-(heptadecan-2-yl)oxazole -2(3H)-one, 5-(2-methylheptadecan-2-yl)oxazol-2(3 H)-one, 5-(octadecan-3-yl)oxazol-2(3H)-one, 5-( 3-Methyloctadecan-3-yl)oxazol-2(3H)-one, 5-(3-ethyl Octadecan-3-yl)oxazol-2(3H)-one, 5-hexadecyl-1, 2,3-Oxadiazol-4(5H)-one, 5-(heptadecan-2-yl)-1, 2 ,3-Oxadiazol-4(5H)-one, 5-(2-methylheptadecan-2-yl )-1,2,3-Oxadiazol-4(5H)-one, 5-(octadecan-3-yl )-1,2,3-Oxadiazol-4(5H)-one, 5-(3-methyloctadecane -3-yl)-1,2,3-oxadiazol-4(5H)-one, 5-(3-ethyl 5H-octadecan-3-yl)-1,2,3-oxadiazol-4(5H)-one, N-Hydroxy N-hydroxypalmitamide, N-hydroxy-2-methylhexadecanamide, N-hydroxy 2,2-dimethylhexadecanamide, 2-ethyl-N-hydroxyhexadecanamide 2-Ethyl-N-hydroxy-2-methylhexadecanamide, 2,2-diethyl -N-Hydroxyhexadecanamide, 1-Hexadecyl-2,3-dihydro-1H-tetradecyl Trazol, 1-(heptadecan-2-yl)-2,3-dihydro-1H-tetrazole , 1-(2-methylheptadecan-2-yl)-2,3-dihydro-1H-tetrazole , 1-(octadecan-3-yl)-2,3-dihydro-1H-tetrazole, 1-(3 -methyloctadecan-3-yl)-2,3-dihydro-1H-tetrazole, 1-(3 -ethyloctadecan-3-yl)-2,3-dihydro-1H-tetrazole, 1-hexyl Sadecyl-2,5-dihydro-1H-tetrazole, 1-(heptadecan-2-yl)- 2,5-Dihydro-1H-tetrazole, 1-(2-methylheptadecan-2-yl)- 2,5-Dihydro-1H-tetrazole, 1-(octadecan-3-yl)-2,5-di Hydro-1H-tetrazole, 1-(3-methyloctadecan-3-yl)-2,5-di Hydro-1H-tetrazole, 1-(3-ethyloctadecan-3-yl)-2,5-di Hydro-1H-tetrazole, 2-methylpentadecanoic acid, 2,2-dimethylpentadeca Pentadecanoic acid, 2-ethylpentadecanoic acid, 2-ethyl-2-methylpentadecanoic acid, 2,2-dicarboxylic acid Ethylpentadecanoate, 2-(dodecyloxy)acetic acid, 2-(dodecyloxy)propane Acid, 2-(dodecyloxy)-2-methylpropanoic acid, 2-(dodecyloxy)butanoic acid , 2-(dodecyloxy)-2-methylbutanoic acid, 2-(dodecyloxy)-2-ethyl Butanoic acid, 1-pentadecyl-1H-tetrazole, 1-(hexadecan-2-yl)- 1H-Tetrazole, 1-(2-methylhexadecan-2-yl)-1H-tetrazole , 1-(heptadecan-3-yl)-1H-tetrazole, 1-(3-methylheptadecan-3-yl)-1H-tetrazole 1-(3-ethylheptadecan-3-yl)-1H-tetrazole, 1-(3-ethylheptadecan-3-yl)-1 H-tetrazole, 5-pentadecyl-1H-tetrazole, 5-(hexadecane-2- 5-(2-methylhexadecan-2-yl)-1H-tetrazole, 5-(2-methylhexadecan-2-yl)-1H-tetrazole 5-(heptadecan-3-yl)-1H-tetrazole, 5-(3-methylheptadecan-3-yl)-1H-tetrazole 5-(3-ethylheptadecan-3-yl)-1H-tetrazole, 5-(3-ethylheptadecan-3-yl)-1H-tetrazole 4-pentadecyloxazol-2(3H)-one, 4-( hexadecan-2-yl)oxazol-2(3H)-one, 4-(2-methylhexadecan-2-yl)oxazol-2(3H)-one 4-(heptadecan-3-yl)oxazol-2(3H)-one, 4-(heptadecan-3-yl)oxazol-2(3H)-one Xazol-2(3H)-one, 4-(3-methylheptadecan-3-yl)oxazo 4-(3-ethylheptadecan-3-yl)oxazol-2( 3H)-one, 5-pentadecyloxazol-2(3H)-one, 5-(hexadecane -2-yl)oxazol-2(3H)-one, 5-(2-methylhexadecan-2-yl)oxazol-2(3H)-one 5-(heptadecan-3-yl)oxazole-2(3H)-one, 5-(heptadecan-3-yl)oxazole- 2(3H)-one, 5-(3-methylheptadecan-3-yl)oxazol-2(3H )-one, 5-(3-ethylheptadecan-3-yl)oxazol-2(3H)-one , 3-pentadecyl-1,2,4-oxadiazol-5(4H)-one, 3-(hexa decan-2-yl)-1,2,4-oxadiazol-5(4H)-one, 3-(2-methyl- (ethylhexadecan-2-yl)-1,2,4-oxadiazol-5(4H)-one, 3 -(3-methylheptadecan-3-yl)-1,2,4-oxadiazole-5(4H) -one, 3-(heptadecan-3-yl)-1,2,4-oxadiazol-5(4H) -one, 3-(3-ethylheptadecan-3-yl)-1,2,4-oxadiazole- 5(4H)-one, 5-pentadecyl-1,2,3-oxadiazol-4(5H)-one 5-(hexadecan-2-yl)-1,2,3-oxadiazole-4(5H)-one 5-(2-methylhexadecan-2-yl)-1,2,3-oxadiazole-4( 5H)-one, 5-(heptadecan-3-yl)-1,2,3-oxadiazol-4( 5H)-one, 5-(3-methylheptadecan-3-yl)-1,2,3-oxadiazo 5-(3-ethylheptadecan-3-yl)-1,2,3-ol oxadiazol-4(5H)-one, N-hydroxypentadecanamide, N-hydroxy N-hydroxy-2,2-dimethylpentadecanamide, N-hydroxy-2,2-dimethylpentadecanamide 2-ethyl-N-hydroxypentadecanamide, 2-ethyl-N-hydroxy- 2-Methylpentadecanamide, 2,2-diethyl-N-hydroxypentadecanamide , 1-pentadecyl-2,3-dihydro-1H-tetrazole, 1-(hexadecane-2 -yl)-2,3-dihydro-1H-tetrazole, 1-(2-methylhexadecane-2 -yl)-2,3-dihydro-1H-tetrazole, 1-(heptadecan-3-yl)- 2,3-Dihydro-1H-tetrazole, 1-(3-methylheptadecan-3-yl)- 2,3-Dihydro-1H-tetrazole, 1-(3-ethylheptadecan-3-yl)- 2,3-Dihydro-1H-tetrazole, 1-pentadecyl-2,5-dihydro-1H- Tetrazole, 1-(hexadecan-2-yl)-2,5-dihydro-1H-tetrazole 1-(2-methylhexadecan-2-yl)-2,5-dihydro-1H-tetrazole 1-(heptadecan-3-yl)-2,5-dihydro-1H-tetrazole, 1-( 3-Methylheptadecan-3-yl)-2,5-dihydro-1H-tetrazole, 1-( 3-ethylheptadecan-3-yl)-2,5-dihydro-1H-tetrazole, 2-methyl 2,2-dimethyltetradecanoic acid, 2-ethyltetradecanoic acid, 2 -ethyl-2-methyltetradecanoic acid, 2,2-diethyltetradecanoic acid, 2-(undecanoic acid 2-(undecyloxy)acetic acid, 2-(undecyloxy)propanoic acid, 2-methyl-2-(undecyloxy) 2-(undecyloxy)propanoic acid, 2-(undecyloxy)butanoic acid, 2-methyl-2-(undecyloxy)butanoic acid 2-ethyl-2-(undecyloxy)butanoic acid, 1-tetradecyloxybutanoic acid Sil-1H-tetrazole, 1-(pentadecan-2-yl)-1H-tetrazole, 1 -(2-methylpentadecan-2-yl)-1H-tetrazole, 1-(hexadecane- 3-yl)-1H-tetrazole, 1-(3-methylhexadecan-3-yl)-1H- Tetrazole, 1-(3-ethylhexadecan-3-yl)-1H-tetrazole, 5- Tetradecyl-1H-tetrazole, 5-(pentadecan-2-yl)-1H-tetrazole 5-(2-methylpentadecan-2-yl)-1H-tetrazole, 5-(hexadecyl)-1H-tetrazole, Decane-3-yl)-1H-tetrazole, 5-(3-methylhexadecan-3-yl) -1H-Tetrazole, 5-(3-ethylhexadecan-3-yl)-1H-tetrazole 4-tetradecyloxazol-2(3H)-one, 4-(pentadecan-2-yl ) oxazol-2(3H)-one, 4-(2-methylpentadecan-2-yl)oxazol-2(3H)-one oxazole-2(3H)-one, 4-(hexadecan-3-yl)oxazole-2(3H) -one, 4-(3-methylhexadecan-3-yl)oxazol-2(3H)-one, 4-(3-ethylhexadecan-3-yl)oxazol-2(3H)-one, 3-tetradecanoic acid Ladecyl-1,2,4-oxadiazol-5(4H)-one, 3-(pentadecan-2 -yl)-1,2,4-oxadiazol-5(4H)-one, 3-(2-methylpenta decan-2-yl)-1,2,4-oxadiazol-5(4H)-one, 3-(3-methyl- (ethylhexadecan-3-yl)-1,2,4-oxadiazol-5(4H)-one, 3 -(hexadecan-3-yl)-1,2,4-oxadiazol-5(4H)-one, 3 -(3-ethylhexadecan-3-yl)-1,2,4-oxadiazole-5(4H) -one, 5-tetradecyloxazol-2(3H)-one, 5-(pentadecan-2- 5-(2-methylpentadecan-2-yl)oxazol-2(3H)-one, 5-(2-methylpentadecan-2-yl)oxazol-2(3H)-one Oxazol-2(3H)-one, 5-(heptadecan-3-yl)oxazol-2(3 H)-one, 5-(3-methylheptadecan-3-yl)oxazol-2(3H)-one 5-(3-ethylheptadecan-3-yl)oxazol-2(3H)-one, 5- Tetradecyl-1,2,3-oxadiazol-4(5H)-one, 5-(pentadecane -2-yl)-1,2,3-oxadiazol-4(5H)-one, 5-(2-methylphenyl)- 5-(H-pentadecan-2-yl)-1,2,3-oxadiazol-4(5H)-one oxadecan-3-yl)-1,2,3-oxadiazol-4(5H)-one, 5-(3 -methylhexadecan-3-yl)-1,2,3-oxadiazol-4(5H)-one , 5-(3-ethylhexadecan-3-yl)-1,2,3-oxadiazole-4(5 H)-one, N-hydroxytetradecane amide, N-hydroxy-2-methyltetradecane Canamide, N-hydroxy-2,2-dimethyltetradecanamide, 2-ethyl-N- Hydroxytetradecaneamide, 2-ethyl-N-hydroxy-2-methyltetradecane Amide, 2,2-diethyl-N-hydroxytetradecaneamide, 1-tetradecyl-2 ,3-Dihydro-1H-tetrazole, 1-(pentadecan-2-yl)-2,3-dihydro- 1H-tetrazole, 1-(2-methylpentadecan-2-yl)-2,3-dihydro- 1H-tetrazole, 1-(hexadecan-3-yl)-2,3-dihydro-1H -Tetrazole, 1-(3-methylhexadecan-3-yl)-2,3-dihydro-1H -Tetrazole, 1-(3-ethylhexadecan-3-yl)-2,3-dihydro-1H -tetrazole, 1-tetradecyl-2,5-dihydro-1H-tetrazole, 1-(pentadecyl)-2,5-dihydro-1H-tetrazole, pentadecan-2-yl)-2,5-dihydro-1H-tetrazole, 1-(2-methylpentadecan-2-yl)-2,5-dihydro-1H-tetrazole 1-(hexadecan-2-yl)-2,5-dihydro-1H-tetrazole -3-yl)-2,5-dihydro-1H-tetrazole, 1-(3-methylhexadecane -3-yl)-2,5-dihydro-1H-tetrazole, 1-(3-ethylhexadecane -3-yl)-2,5-dihydro-1H-tetrazole, 2-methyltridecanoic acid, 2, 2-Dimethyltridecanoic acid, 2-ethyltridecanoic acid, 2-ethyl-2-methyltridecanoic acid 2,2-Diethyltridecanoic acid, 2-(decyloxy)acetic acid, 2-(decyloxy) ) propanoic acid, 2-(decyloxy)-2-methylpropanoic acid, 2-(decyloxy)- 2-Methylbutanoic acid, 2-(decyloxy)butanoic acid, 2-(decyloxy)-2-ethyl 1-Tridecyl-1H-tetrazole, 1-(tetradecan-2-yl)- 1H-Tetrazole, 1-(2-methyltetradecan-2-yl)-1H-tetrazole , 1-(pentadecan-3-yl)-1H-tetrazole, 1-(3-methylpentadecan-3-yl)-1H-tetrazole 1-(3-ethylpentadecan-3-yl)-1H-tetrazole, 1-(3-ethylpentadecan-3-yl)-1 H-Tetrazole, 5-tridecyl-1H-tetrazole, 5-(tetradecane-2-yl) L )-1H-tetrazole, 5-(2-methyltetradecan-2-yl)-1H-tetrazole 5-(pentadecan-3-yl)-1H-tetrazole, 5-(3-methylpentadecyl)-1H-tetrazole Decane-3-yl)-1H-tetrazole, 5-(3-ethylpentadecan-3-yl) -1H-tetrazole, 4-tridecyloxazol-2(3H)-one, 4-(tetrazole decan-2-yl)oxazol-2(3H)-one, 4-(2-methyltetradecane- 2-yl)oxazol-2(3H)-one, 4-(pentadecan-3-yl)oxazo 4-(3-methylpentadecan-3-yl)oxazol-2(3H)-one, 4-(3-methylpentadecan-3-yl)oxazol-2 (3H)-one, 4-(3-ethylpentadecan-3-yl)oxazol-2(3H) -one, 3-tridecyl-1,2,4-oxadiazol-5(4H)-one, 3-(the toradecan-2-yl)-1,2,4-oxadiazol-5(4H)-one, 3-(2 -methyltetradecan-2-yl)-1,2,4-oxadiazol-5(4H)-one , 3-(3-methylpentadecan-3-yl)-1,2,4-oxadiazole-5(4 H)-one, 3-(pentadecan-3-yl)-1,2,4-oxadiazol-5(4 H)-one, 3-(3-ethylpentadecan-3-yl)-1,2,4-oxadiazo 5-Tridecyloxazol-2(3H)-one, 5-Tridecyloxazol-5(4H)-one, 5-Tridecyloxazol-2(3H)-one, 5-(tetradecyloxazol-2(3H)-one decan-2-yl)oxazol-2(3H)-one, 5-(2-methyltetradecane- 2-yl)oxazol-2(3H)-one, 5-(pentadecan-3-yl)oxazo 2(3H)-oxazole-2(3H)-one, 5-(3-methylpentadecan-3-yl)oxazole-2(3H)-one (3H)-one, 5-(3-ethylpentadecan-3-yl)oxazol-2(3H) -one, 5-tridecyl-1,2,3-oxadiazol-4(5H)-one, 5-(the toradecan-2-yl)-1,2,3-oxadiazol-4(5H)-one, 5-(2 -methyltetradecan-2-yl)-1,2,3-oxadiazol-4(5H)-one , 5-(pentadecan-3-yl)-1,2,3-oxadiazol-4(5H)-one , 5-(3-methylpentadecan-3-yl)-1,2,3-oxadiazole-4(5 H)-one, 5-(3-ethylpentadecan-3-yl)-1,2,3-oxadiazo 4(5H)-one, N-hydroxytridecanamide, N-hydroxy-2-methyl Tridecanamide, N-hydroxy-2,2-dimethyltridecanamide, 2-ethyl- N-Hydroxytridecanamide, 2-ethyl-N-hydroxy-2-methyltridecane Amide, 2,2-diethyl-N-hydroxytridecanamide, 1-tridecyl-2,3 -Dihydro-1H-tetrazole, 1-(tetradecan-2-yl)-2,3-dihydro -1H-Tetrazole, 1-(2-methyltetradecan-2-yl)-2,3-dihydro -1H-tetrazole, 1-(pentadecan-3-yl)-2,3-dihydro-1H-tetrazole Trazol, 1-(3-methylpentadecan-3-yl)-2,3-dihydro-1H-tetrazole Trazol, 1-(3-ethylpentadecan-3-yl)-2,3-dihydro-1H-tetrazole 1-Tridecyl-2,5-dihydro-1H-tetrazole, 1-(tetradecyl) 1-(2-methyltetradecane-2-yl)-2,5-dihydro-1H-tetrazole 1-(pentadecan-3-yl)-2,5-dihydro-1H-tetrazole, yl)-2,5-dihydro-1H-tetrazole, 1-(3-methylpentadecane-3- 1-(3-ethylpentadecane-yl)-2,5-dihydro-1H-tetrazole 3-yl)-2,5-dihydro-1H-tetrazole, .

[0267] Method 26: Method 1, wherein the pharmaceutical composition is in unit dosage form.

[0268] Method 27: 0.01 mg to 10,000 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof Method 1, which includes a salt that can be

[0269] Method 28: Method 1 for treating or preventing the onset of cognitive impairment.

[0270] Method 29: Method 28, wherein the cognitive impairment is Alzheimer's disease.

[0271] Method 30: Method 1 for treating or preventing the onset of a movement disorder.

[0272] Method 31: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 30.

[0273] Method 32: Method 1 for treating or preventing the onset of addiction.

[0274] Method 33: Method 32, wherein the addiction is opioid addiction.

[0275] Method 34: Method 1 for treating or preventing the onset of anorexia or cachexia.

[0276] Method 35: Conditions associated with anorexia or cachexia are selected from the group consisting of cancer, AIDS, or advanced age. Method 34.

[0277] Method 36: Method 1, where the symptom is chronic pain.

[0278] Method 37: Symptoms are depression, Method 1.

[0279] Method 38: The compound of formula (I) is [ka] 1 2-Ethylpentadecanoic acid That is, method 1.

[0280] Method 39: Method 38 for treating chronic pain.

[0281] Method 40: Method 38 for treating depression.

[0282] Method 41: Method 38 for treating or preventing the onset of cognitive impairment.

[0283] Method 42: Method 41, wherein the cognitive impairment is Alzheimer's disease.

[0284] Method 43: Method 38 for treating or preventing the onset of a movement disorder.

[0285] Method 44: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 43.

[0286] Method 45: Method 38 for treating or preventing the onset of an addiction.

[0287] Method 46: Method 45, wherein the addiction is an opioid addiction.

[0288] Method 47: Method 38 for treating or preventing the onset of anorexia or cachexia.

[0289] Method 48: Conditions associated with anorexia or cachexia are selected from the group consisting of cancer, AIDS, or advanced age. Method 47.

[0290] Method 49: The compound of formula (I) is [ka] 2 5-(pentadecan-2-yl)-1H-tetrazole That is, method 1.

[0291] Method 50: Method 49 for treating chronic pain.

[0292] Method 51: Method 49 for treating depression.

[0293] Method 52: Method 49 for treating or preventing the onset of cognitive impairment.

[0294] Method 53: Method 52, wherein the cognitive impairment is Alzheimer's disease.

[0295] Method 54: Method 49 for treating or preventing the onset of a movement disorder.

[0296] Method 55: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 54.

[0297] Method 56: Method 49 for treating or preventing the onset of an addiction.

[0298] Method 57: Method 56, wherein the addiction is an opioid addiction.

[0299] Method 58: Method 49 for treating or preventing the onset of anorexia or cachexia.

[0300] Method 59: Conditions associated with anorexia or cachexia are selected from the group consisting of cancer, AIDS, or advanced age. Method 58 is selected.

[0301] Method 60: The compound of formula (I) is [ka] 1 2,2-Diethylpentadecanoic acid That is, method 1.

[0302] Method 61: Method 60 for treating or preventing the onset of cognitive impairment.

[0303] Method 62: Method 60, wherein the cognitive impairment is Alzheimer's disease.

[0304] Method 63: Method 60 for treating or preventing the onset of a movement disorder.

[0305] Method 64: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 63.

[0306] Method 65: Method 60 for treating or preventing the onset of an addiction.

[0307] Method 66: Method 65, wherein the addiction is an opioid addiction.

[0308] Method 67: Method 60 for treating or preventing the onset of anorexia or cachexia.

[0309] Method 68: Conditions associated with anorexia or cachexia are selected from the group consisting of cancer, AIDS, or advanced age. Selected method 67.

[0310] Method 69: Method 60 for treating chronic pain.

[0311] Method 70: Method 60 for treating depression.

[0312] Method 71: The compound of formula (I) is [ka] 1,5-Tetradecyl-1H-tetrazole That is, method 1.

[0313] Method 72: Method 71 for treating or preventing the onset of cognitive impairment.

[0314] Method 73: Method 72, wherein the cognitive impairment is Alzheimer's disease.

[0315] Method 74: Method 71 for treating or preventing the onset of a movement disorder.

[0316] Method 75: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 74.

[0317] Method 76: Method 71 for treating or preventing the onset of an addiction.

[0318] Method 77: Method 76, wherein the addiction is an opioid addiction.

[0319] Method 78: Method 71 for treating or preventing the onset of anorexia or cachexia.

[0320] Method 79: Conditions associated with anorexia or cachexia are selected from the group consisting of cancer, AIDS, or advanced age. Selected method 77.

[0321] Method 80: Method 71 for treating chronic pain.

[0322] Method 81: Method 71 for treating depression.

[0323] Method 82: The compound of formula (I) is [ka] 2 1-pentadecyl-1H-tetrazole That is, method 1.

[0324] Method 83: Method 82 for treating or preventing the onset of cognitive impairment.

[0325] Method 84: Method 83, wherein the cognitive impairment is Alzheimer's disease.

[0326] Method 85: Method 82 for treating or preventing the onset of a movement disorder.

[0327] Method 86: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease , Method 85.

[0328] Method 87: Method 82 for treating or preventing the onset of an addiction.

[0329] Method 88: Method 87, wherein the addiction is an opioid addiction.

[0330] Method 89: Method 82 for treating or preventing the onset of anorexia or cachexia.

[0331] Method 90: The condition associated with anorexia or cachexia is selected from the group consisting of cancer, AIDS, or advanced age. Selected method 89.

[0332] Method 91: Method 82 for treating chronic pain.

[0333] Method 92: Method 82 for treating depression.

[0334] Method 93: The compound of formula (I) is [ka] That is, method 1.

[0335] Method 94: Method 93 for treating or preventing the onset of cognitive impairment.

[0336] Method 95: Method 94, wherein the cognitive impairment is Alzheimer's disease.

[0337] Method 96: Method 93 for treating or preventing the onset of a movement disorder.

[0338] Method 97: The movement disorder is selected from the group consisting of multiple sclerosis or Parkinson's disease. , Method 96.

[0339] Method 98: Method 93 for treating or preventing the onset of an addiction.

[0340] Method 99: Method 97, wherein the addiction is an opioid addiction.

[0341] Method 100: Method 93 for treating or preventing the onset of anorexia or cachexia.

[0342] Method 101: A patient is selected from the group consisting of: cancer, AIDS, or advanced age, in whom symptoms associated with anorexia or cachexia are present. The method 100 is selected from the above.

[0343] Method 102: Method 93 for treating chronic pain.

[0344] Method 103: Method 93 for treating depression.

[0345] Any of the above mentioned features of the pharmaceutical compositions, uses and methods are herein It is applicable to any other pharmaceutical composition, use or method specified. Any of the features of the pharmaceutical compositions, uses and methods described herein may be incorporated in any way. Independently, in part or in whole, from other embodiments of the pharmaceutical compositions, uses and methods described herein. Combinable, e.g., one, two, three or more features may be combined to form a Furthermore, the pharmaceutical compositions described above may be combined in whole or in part. Any of the features of the uses and methods may be used in combination with other pharmaceutical compositions, uses and methods described herein. may not be essential to any of the methods or uses described herein. Aspects or embodiments of the present invention may be used in compositions as described herein, e.g., pharmaceutical compositions. and / or a compound of formula (I), or any compound having a structure described herein The method can be carried out using a compound, such as a composition, e.g., a pharmaceutical composition and / or a compound of formula (I) ), or any embodiment of any compound having a structure described herein. The embodiments may be used to carry out the methods or uses as described herein. Can be or can be adapted.

[0346] The above description has set forth the best mode contemplated for carrying out the invention, as well as the principles by which the invention is constructed. The best mode of making and using the methods and processes will be readily apparent to those skilled in the art to which this invention pertains. A clear, concise, and precise description sufficient to enable any person to make and use the invention. However, the present invention encompasses fully equivalent modifications from those discussed above. and alternative constructions are permitted. Consequently, the invention is not limited to the specific embodiments disclosed. On the contrary, the invention particularly points out and distinctly claims the subject matter of the present invention. All modifications falling within the spirit and scope of the present invention as broadly defined by the following claims are intended to be included herein. The present disclosure is illustrated in the drawings and foregoing description and is intended to encompass modifications and alternative constructions. While such illustrations and descriptions have been described above, such illustrations and descriptions are illustrative or exemplary and not limiting. should be considered unethical.

[0347] All references cited herein are hereby incorporated by reference in their entirety. Publications and patents or patent applications incorporated by reference are included herein. To the extent that the disclosure conflicts with the disclosure of the present application, this specification shall prevail over any such conflict. are intended to supersede and / or take precedence over

[0348] Unless otherwise defined, all terms (including technical and scientific terms) are understood by those of ordinary skill in the art. and are to be given their ordinary and customary meaning for Unless so defined, it should not be constrained to a special or customized meaning. The use of certain terms when describing certain features or aspects of the disclosure The term encompasses any specific characteristic of the feature or aspect of the disclosure to which the term pertains. It is to be construed as implying that the term is redefined herein as being limited to the above. It should be noted that the term "common" used in this application, particularly in the appended claims, and phrases and variations thereof, unless expressly stated otherwise, are intended to be limiting as opposed to limiting. It should be construed as open-ended. For example, the term "including" "including, but not limited to" means "including, but not limited to" The term "is not intended to be used in any way to denote a specific purpose" or ...." "Comprising" means "including" or "including" Is it synonymous with "containing" or "characterized by" and inclusive? or open-ended and may include additional unrecited elements or method steps. Without prejudice, the term "comprises" should be interpreted as "comprises at least"; The term "includes" means "including, but not limited to." and the term "example" should be construed as providing an illustrative example of the item being discussed. It is used to provide an exhaustive or exclusive list of Instead of using adjectives such as "well-known," "ordinary," "standard," and similar terms, The term "meaning" refers to an item described for a given period or available at a given time. should not be construed as limiting, but instead as It is intended to encompass known, conventional, or standard techniques that may be available or known. and should be taken to mean "preferably," "preferably," "desired," or "desirable." The use of such terms and words of similar import indicates that a particular feature is essential to the structure or function of the invention. It is understood to imply something that is absolutely essential, vital, or important to Noh. should not be used, but may instead be utilized in certain embodiments of the present invention. It should be understood that the terms "reference" and "references" are merely intended to highlight optional, alternative, or additional features. Similarly, a group of items joined with the conjunction "and" should be It is read as requiring each and every order to be present in that grouping. rather, unless expressly stated otherwise, it should not be read as "and / or." Similarly, a group of items joined with the conjunction "or" should should not be read as requiring mutual exclusivity, but rather as not expressly stated otherwise. unless otherwise stated, it should be read as "and / or."

[0349] Where a range of values ​​is provided, the upper and lower limits and the values ​​that lie between the upper and lower limits of the range are It is understood that each of the values ​​present is included in the above embodiments.

[0350] With respect to the use of virtually any plural and / or singular terminology herein, The reader shall transition from plural to singular and vice versa as appropriate to the context and / or use. and / or convert the singular to the plural. Number / plural interchanges may be explicitly indicated in this specification. The word "an" does not exclude a plurality. It may function as several items described. Certain criteria may differ from each other. The mere fact that it is recited in a dependent claim does not make the combination of these criteria advantageous. Any reference signs in the claims do not limit their scope. It should not be construed as limiting.

[0351] If the inclusion of a specific number of claim recitations is intended, such intention shall be expressly stated in the claim. and that in the absence of such a statement, no such intention exists. It will be further understood by those skilled in the art. For example, to aid in understanding, see the attached The claims use the terms "at least one" and "one or more" to introduce the claim recitation. However, the use of such a phrase may be used to The introductory phrase "one or more" or "at least one" and an indefinite article (e.g., "a" or The introduction of claims with the indefinite article "a" or "an" is permitted even when the claimed invention includes the indefinite article "a" or "an." The applicant may, without prejudice to the accuracy of any particular claim containing such introduced claim language, It should not be construed to imply a limitation to embodiments containing only one (e.g. "a" and / or "an" usually mean "at least one" or "one or more." the same shall apply to the introduction of claims. This also applies to the use of definite articles in the context of the invention. Even if the number of described items is not specifically stated, those skilled in the art will understand that such a description will usually be sufficient to at least (e.g., when used with other modifiers) A bare statement of "two statements" that does not include the above usually means that there are at least two statements or two (The above description applies.) Furthermore, the phrase "at least one of A, B, and C, etc." Where similar conventions are used, such structures generally are consistent with those of ordinary skill in the art who understand the conventions. is intended to mean (e.g., "a system having at least one of A, B, and C" "System" refers to a system that has A alone, a system that has B alone, a system that has C alone, A system having both A and B, A system having both A and C, B and A system having both A and C, and / or A system having both A, B and C "At least one of A, B, or C, etc." When a convention similar to "one and the same" is used, such a structure is generally understood by those skilled in the art to be It is intended to mean understanding the convention (e.g., "at least one of A, B, or C"). "A system having one of these" refers to a system having A alone, a system having B alone, a system having C alone, A system with A alone, A and B together, A and C together system, a system having both B and C, and / or a system having A, B and C (This may include, but is not limited to, systems that have two or more alternatives.) Virtually any disjunctive conjunction and / or phrase presenting a term is not , one of those terms, whether present in the claims or in the drawings should be understood to contemplate the possibility of including either or both of those terms. It will be further understood by those skilled in the art that, for example, the phrase "A or B" can be used to mean " It will be understood to include the possibilities of "A" or "B" or "A and B."

[0352] All numbers expressing quantities of ingredients, reaction conditions, etc. used herein are It should be understood that all references are modified by the term "about." Therefore, unless indicated to the contrary, the numerical parameters set forth herein are the These are approximations that may vary depending on the desired properties sought. The doctrine of equivalents is applicable to the scope of any claim in any application claiming priority from As an attempt not to limit the number of significant digits, each numerical parameter and should be interpreted in light of normal rounding rules.

[0353] Furthermore, the foregoing has been described in some detail by way of illustration and example for purposes of clarity and understanding. Although the present invention has been described above, it will be apparent to those skilled in the art that certain changes and modifications can be made. Therefore, it is intended that the description and examples be used to limit the scope of the invention to the specific embodiments described herein. The embodiments and examples should not be construed as limiting the true scope and spirit of the present invention. It should be construed to encompass all modifications and alternatives that fall within the spirit of the invention.

Claims

[Claim 1] The invention described in the specification.

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