WO2012059818A1 - Methods of treatment using lipid compounds - Google Patents
Methods of treatment using lipid compounds Download PDFInfo
- Publication number
- WO2012059818A1 WO2012059818A1 PCT/IB2011/002925 IB2011002925W WO2012059818A1 WO 2012059818 A1 WO2012059818 A1 WO 2012059818A1 IB 2011002925 W IB2011002925 W IB 2011002925W WO 2012059818 A1 WO2012059818 A1 WO 2012059818A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- condition
- compound
- disease
- formula
- atherosclerosis
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/60—Unsaturated compounds containing ether groups, groups, groups, or groups the non-carboxylic part of the ether being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/26—Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
Definitions
- the present disclosure relates to methods of treating at least one disease or condition in a subject in need thereof, comprising administering to the subject a
- Rj and R 2 are independently chosen from a hydrogen atom or linear, branched, and/or cyclic Ci-Ce alkyl groups, with the proviso that Ri and R 2 are not both hydrogen.
- diseases and/or conditions may, for example, relate to cardiovascular functions, immune functions, and/or insulin action.
- the present disclosure also provides for a method of treating atherosclerosis and reducing and/or slowing the progression of its development.
- Dietary polyunsaturated fatty acids including omega-3 fatty acids, have effects on diverse physiological processes impacting normal health and chronic diseases, such as the regulation of plasma lipid levels, cardiovascular and immune functions, insulin action, neuronal development, and visual function.
- Omega-3 fatty acids e.g., (5Z,8Z, l lZ,14Z, 17Z)-icosa-5,8,l l, 14, 17-pentaenoic acid (EPA) and (4Z,7Z, 10Z, 13Z, 16Z, 19Z)-docosa-4,7, 10, 13, 16, 19-hexaenoic acid (DHA), regulate plasma lipid levels, cardiovascular and immune functions, insulin action, and neuronal development, and visual function. Omega-3 fatty acids have been shown to have beneficial effects on the risk factors for cardiovascular diseases, for example hypertension and
- HMG hypertriglyceridemia
- Omega-3 fatty acids have also been shown to lower serum triglycerides, increase serum HDL cholesterol, lower systolic and diastolic blood pressure and/or pulse rate, and lower the activity of the blood coagulation factor VH-phospholipid complex.
- cholesterol and triglycerides are part of lipoprotein complexes in the bloodstream that can be separated via ultracentrifugation into high-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) fractions.
- HDL high-density lipoprotein
- IDL intermediate-density lipoprotein
- LDL low-density lipoprotein
- VLDL very-low-density lipoprotein
- Cholesterol and triglycerides are synthesized in the liver, incorporated into VLDL, and released into the plasma.
- Conditions characterized by abnormally high blood cholesterol and/or lipid values include hypercholesterolemia, hyperlipidemia (hyperlipoproteinemia), HTG, and mixed dyslipidemia.
- High levels of total cholesterol (total- C), LDL-C, and apolipoprotein B 100 may promote human coronary heart disease (CHD
- Factors such as, high LDL/non-HDL cholesterol, hypertriglyceridemia (HTG), and low HDL cholesterol are features of metabolic syndrome, which represents a collection of lipid and non-lipid (e.g., hypertension) risk factors of metabolic origin. Metabolic syndrome is closely linked to a generalized metabolic disorder called insulin resistance in which the normal actions of insulin are impaired.
- HMG hypertriglyceridemia
- NCEP ATP III National Cholesterol Education Program Adult Treatment Panel III recommends treating of lipid and non-lipid factors associated with metabolic syndrome, such as reducing HTG and non-HDL cholesterol, as a secondary target in the primary prevention of
- omega-3 fatty acids EPA and DHA
- EPA and DHA are well established treatment of HTG and have beneficial effects upon other risk factors associated with CHD, such as hypertension and a prothrombotic state.
- cardiovascular risk factors such as LDL
- Several research groups have studied chemical modification of omega-3 fatty acids to influence their biological effects. See, e.g., Rossmeisl et al. (Obesity, Jan. 15, 2009); Flock et al. (Acta Chemica Scandinavica, 53:436, 1999); Pitt et al. (Synthesis, 1240-42, 1997).
- the present disclosure generally relates to a method of treating or preventing at least one disease or condition in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a compound of Formula (I):
- Ri and R 2 are independently chosen from a hydrogen atom or linear, branched, and/or cyclic Ci-C 6 alkyl groups, with the proviso that R] and R 2 are not both hydrogen.
- the at least one disease or condition is chosen from atherosclerosis, peripheral insulin resistance, a diabetic condition, or a dyslipidemic condition.
- the present disclosure also includes a method of reducing atherosclerosis development in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of 2-((5Z,8Z,l lZ,14Z, 17Z)-icosa-5,8,l 1, 14,17-pentaen-l- yloxy)butanoic acid:
- FIGURE 1 shows cholesterol and triglyceride levels in APOE*3Leiden mice after administration of Compound A (0.3 mmol/kg) according to the present disclosure or OmacorTM (3.3 mmol/kg).
- FIGURE 2 shows cholesterol and triglyceride levels in APOE*3Leiden.CETP mice after administration of Compound A according to the present disclosure or fenofibrate.
- FIGURE 3 shows HDL levels in APOE*3Leiden.CETP mice after administration of Compound A according to the present disclosure or fenofibrate.
- FIGURE 4 shows total cholesterol levels in APOE*3Leiden CETP mice after administration of Compound A according to the present disclosure, fenofibrate, or a negative control.
- FIGURE 5 shows HDL levels in APOE*3Leiden CETP mice after administration of Compound A according to the present disclosure, fenofibrate, or a negative control.
- FIGURE 6 shows diseased lesion area in APOE*3Leiden CETP mice after administration of Compound A according to the present disclosure, fenofibrate, or a negative control.
- FIGURE 7 shows undiseased lesion area in APOE*3Leiden CETP mice after administration of Compound A according to the present disclosure, fenofibrate, or a control.
- treat include any therapeutic application that can benefit a human or non-human mammal. Both human and veterinary treatments are within the scope of the present disclosure. Treatment may be responsive to an existing condition or it may be prophylactic, i.e., preventative.
- administer refers to (1) providing, giving, dosing and/or prescribing by either a health practitioner or his authorized agent or under his direction a compound or composition according to the present disclosure, and (2) putting into, taking or consuming by the human patient or person himself or herself, or non-human mammal a compound or composition according to the present disclosure.
- the term "pharmaceutically effective amount” means an amount sufficient to achieve the desired pharmacological and/or therapeutic effects, i.e., an amount of the disclosed compound that is effective for its intended purpose. While individual subject/patient needs may vary, the determination of optimal ranges for effective amounts of the disclosed compound is within the skill of the art. Generally, the dosage regimen for treating a disease and/or condition with the compounds presently disclosed may be determined according to a variety of factors such as the type, age, weight, sex, diet, and/or medical condition of the subject/patient.
- composition means a compound according to the present disclosure in any form suitable for medical use.
- the compounds of Formula (I) may exist in various stereoisomeric forms, including enantiomers, diastereomers, or mixtures thereof. It will be understood that the invention encompasses all optical isomers of the compounds of Formula (I) and mixtures thereof. Hence, compounds of Formula (I) that exist as diastereomers, racemates, and/or enantiomers are within the scope of the present disclosure.
- the present disclosure includes a method of treating or preventing at least one disease or condition in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a compound of Formula (I):
- Ri and R 2 are independently chosen from a hydrogen atom or linear, branched, and/or cyclic Ci-C 6 alkyl groups, with the proviso that Ri and R 2 are not both hydrogen.
- R] and R 2 are chosen from hydrogen, methyl, ethyl, n-propyl, and isopropyl.
- the compound is present in its various stereoisomeric forms, such as an enantiomer (R or S), diastereomer, or mixtures thereof.
- the compound is present in racemic form.
- the compound according to Formula (I) is a salt of a counter-ion with at least one stereogenic center, or ester of an alcohol with at least one stereogenic center
- the compound may have multiple stereocenters.
- the compounds of the present disclosure may exist as diastereomers.
- the compounds of the present disclosure are present as at least one diastereomer.
- the compound of the present disclosure is 2- ((5Z,8Z, 1 lZ, 14Z, 17Z)-i d:
- At least one disease or condition is chosen from atherosclerosis, peripheral insulin resistance, a diabetic condition, or a dyslipidemic condition.
- blood cholesterol levels are reduced, triglycerides are reduced, HDL is increased, and/or the incidence of atherosclerosis lesions is reduced.
- Compounds of Formula (I) can be prepared as described, for example, in PCT Application No. PCT/IB 10/001251 filed May 7, 2010, and according to Examples 1-11 below. Examples 1-11 are exemplary and one skilled in the art would understand how to apply these general methods to arrive at other compounds within the scope of Formula (I).
- Compounds of the present disclosure may be in the form of a pharmaceutically acceptable salt or ester.
- the compounds of Formula (I) may be in the form of esters, such as a phospholipid, a triglyceride, a 1,2-diglyceride, a 1,3 diglyceride, a 1-monoglyceride, or a 2-monoglyceride.
- Salts suitable for the present disclosure include, but are not limited to, salts of
- metal ions such as Li + , Na + , K + , Mg 2+ , or Ca 2+ ; a protonated primary amine such as tert- butyl ammonium, (3S,5S,7S)-adamantan-l-ammonium, l ,3-dihydroxy-2-
- suitable salts include salts of a diprotonated diamine such as ethane- 1,2- diammonium or piperazine-l,4-diium.
- Other salts according to the present disclosure may comprise protonated Chitosan:
- the present disclosure provides for methods of treating and/or preventing at least one disease or condition in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a compound of Formula (I).
- the subject may be a human or a non-human mammal.
- the compounds presently disclosed may be administered as a medicament, such as in a pharmaceutical composition.
- composition presently disclosed may comprise at least one compound of Formula (I) and optionally at least one non-active pharmaceutical ingredient, i.e., excipient.
- Non-active ingredients may solubilize, suspend, thicken, dilute, emulsify, stabilize, preserve, protect, color, flavor, and/or fashion active ingredients into an applicable and efficacious preparation, such that it may be safe, convenient, and/or otherwise acceptable for use.
- excipients include, but are not limited to, solvents, carriers, diluents, binders, fillers, sweeteners, aromas, pH modifiers, viscosity modifiers, antioxidants, extenders, humectants, disintegrating agents, solution-retarding agents, absorption accelerators, wetting agents, absorbents, lubricants, coloring agents, dispersing agents, and preservatives.
- Excipients may have more than one role or function, or may be classified in more than one group; classifications are descriptive only and are not intended to be limiting.
- the at least one excipient may be chosen from corn starch, lactose, glucose, macrocrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, ethanol, glycerol, sorbitol, polyethylene glycol, propylene glycol, cetylstearyl alcohol,
- compositions presently disclosed comprise at least one compound of Formula (I) and at least one pharmaceutically acceptable antioxidant, e.g., tocopherol and 3- BHA.
- the compositions presently disclosed may be formulated in oral administration forms, e.g., tablets or gelatine soft or hard capsules,
- the dosage form can be of any shape suitable for oral administration, such as spherical, oval, ellipsoidal, cube-shaped, regular, and/or irregular shaped. Conventional formulation techniques known in the art, may be used to formulate the compounds according to the present disclosure.
- the composition may be in the form of a gelatin capsule or a tablet.
- a suitable daily dosage of a compound of Formula (I) may range from about 5 mg to about 3 g.
- the daily dose ranges from about 5 mg to about 1 g, from about 10 mg to about 1 g, from about 10 mg to about 800 mg, from about 10 mg to about 600 mg, from about 10 mg to about 500 mg, from about 50 mg to about 500 mg.
- the daily dose ranges from about 50 mg to about 500 mg.
- the compounds may be administered, for example, once, twice, or three times per day.
- the compound of Formula (I) is administered in an amount ranging from about 10 mg to about 500 mg per dose.
- the compound of Formula (I) is administered once per day.
- the compounds of Formula (I) disclosed herein may be administered to treat and/or prevent at least one disease, condition or risk factor associated with coronary heart disease (CHD).
- at least one disease or condition is chosen from atherosclerosis; peripheral insulin resistance and/or a diabetic condition such as type 2 diabetes; a dyslipidemic condition such as hypertriglyceridemia (HTG), elevated total cholesterol, elevated non-HDL cholesterol, elevated LDL-cholesterol, elevated Apo B, low HDL-cholesterol, primary hypercholesterolemia (heterozygous familial and nonfamilial), mixed dyslipidemia (Fredrickson Types Ila and lib), primary dysbetalipoproteinemia (Fredrickson Type III); metabolic syndrome; obesity or an overweight condition; and a fatty liver disease such as a non-alcoholic fatty liver disease (NAFLD).
- At least one disease or condition is atherosclerosis.
- the present disclosure further encompasses a method of reducing and/or slowing the progression of atherosclerosis development.
- the methods presently disclosed may, for example, reduce at least one of plasma insulin, blood glucose, and serum triglycerides in a subject in need thereof.
- the present disclosure also provides for a method of treating and/or preventing at least one of elevated triglyceride levels, elevated VLDL/LDL cholesterol levels and low HDL cholesterol levels in a subject in need thereof.
- compounds of Formula (I) may exhibit comparable or higher biological activity than other cholesterol-lowering pharmaceutical agents, e.g., fenofibrate, without the side-effects associated with fibrates such as myopathy, gallstones, and dyspepsia.
- Example 1 Preparation of tert-butyl 2-((5Z,8Z,llZ,14Z,17Z)-icosa- 5,8,ll > 14,17-pentaen-l-yloxy)butanoate:
- Tetrabutylammonium chloride (0.55 g, 1.98 mmol) was added to a solution of
- Trifluoroacetic acid 50 mL was added and the reaction mixture was stirred at room temperature
- Example 3 Preparation of (4S,5R)-3-((S)-2-((5Z,8Z,llZJ4Z,17Z)-icosa- 5,8,ll,14,l'7-pentaenyloxy)butanoyl)-4-methyI-5-phenyloxazolidin-2-one and (4S,5R)-3- ((R)-2-((5Z,8Z,llZ,14Z,17Z)-icosa-5,8,ll,14,17-pentaenyloxy)butanoyl)-4-methyl-5- phenyioxazolidin-2-one:
- Trifluoroacetic acid (2 mL) was added to a solution of 2-((5Z,8Z,l lZ, 14Z,17Z)-icosa- 5,8, l l,14, 17-pentaenyloxy)propanoate (1.40 g, 3.36 mmol) in dichloromethane (10 mL) held under nitrogen and the reaction mixture was stirred at room temperature for three hours. Diethyl ether (50 mL) was added and the organic phase was washed with water (30 mL), dried (Na 2 S0 4 ) and concentrated.
- Example 8 Preparation of tert-butyl 2-((5Z,8Z,llZ,14Z,17Z)-icosa- -pentaenyloxy)-2-methylpropanoate:
- Example 9 Preparation of 2-((5Z,8Z,llZ,14Z,17Z)-icosa-5,8,ll,14,17- pentaenyloxy)-2-methylpropanoic acid : Trifluoroacetic acid (5 mL) was added to a solution of tert-butyl 2- ((5Z,8Z, 1 lZ, 14Z, 17Z)-icosa-5,8, l l, 14, 17-pentaenyloxy)-2-methylpropanoate (600 mg, 1.39 mmol) in dichloromethane (20 mL) under nitrogen and the reaction mixture was stirred at room temperature for two hours.
- Example 10 Preparation of tert-butyl 2-ethyl-2-((5Z,8Z,llZ,14Z,17Z)-icosa- 5,8,11, 14,17-pentaen-l-yloxy)butanoate:
- fer/-Butyl 2-((5Z,8Z, l lZ, 14Z, 17Z)-icosa-5,8, l l, 14, 17-pentaen-l-yloxy)butanoate (480 mg, 1.1 1 mmol) was added dropwise over 30 minutes to a solution of lithium diisopropylamine (LDA) (2.0 M, 750 ⁇ , 1.50 mmol) in dry tetrahydrofuran (10 mL) held at -70°C under nitrogen. The reaction mixture was stirred for 30 minutes. Ethyl iodide (312 mg, 2.00 mmol) was added in one portion and the resulting mixture was warmed to ambient temperature during 1 hour.
- LDA lithium diisopropylamine
- the reaction mixture was stirred at ambient temperature for 17 hours.
- the mixture was poured into saturated NH 4 C1 (aq.) (50 mL) and extracted with heptane (2 ⁇ 50 mL).
- the combined organic phases was washed successiveively with brine (50 mL), 0.25 M HC1 (50 mL) and brine (50 mL), dried (MgS0 4 ), filtered and concentrated.
- the residue was purified by flash chromatography on silica gel using increasingly polar mixtures of heptane and ethyl acetate (100:0 -> 95:5) as eluent. Concentration of the appropriate fractions afforded 343 mg (67% yield) of the title compound as an oil.
- Example 11 Preparation of 2-ethyl-2-((5Z,8Z,llZ,14Z,17Z)-icosa- 5,8,11, 14,17-pentaen-l-yloxy)butanoic acid: A mixture of formic acid (5 ml) and tert-butyl 2-ethyl-2-((5Z,8Z,l lZ, 14Z, 17Z)-icosa- 5,8, 1 l, 14, 17-pentaen-l-yloxy)butanoate (250 mg, 0.55 mmol) was stirred vigorously under nitrogen at room temperature for 4.5 hours. The formic acid was removed in vacuo.
- Example 12 Evaluation of PPAR activation in vitro
- the positive controls were GW7647 (PPARD), GW501516 (PPARD) and rosiglitazone (PPARD).
- the efficacy of the controls were set to 100%.
- Assays were carried out in vitro using mammalian-one-hybrid assays (M1H) comprising GAL4-DNA binding domain-PPAR-LBD fusion constructs in conjunction with 5xGAL4-sites driven Photinus pyralis luciferase reporter constructs in transiently transfected HEK293 cells.
- M1H mammalian-one-hybrid assays
- the cells were transfected 4-6 hours and grown overnight before compounds were added. Compound incubation was 16-20 hours. Renilla reniformis luciferase, driven by a constitutive promoter, was included as internal control to improve experimental accuracy.
- Table 1 PPAR activation in vitro.
- Example 13 Evaluation of the effects on in vivo lipid metabolism in a dvslipidemic mouse model (APOE*3Leiden transgenic mice)
- the dyslipidemic mouse model has proven to be representative of the human situation with respect to plasma lipoprotein levels and responsiveness to hypolipidemic drugs, such as statins and fibrates, and nutritional intervention.
- hypolipidemic drugs such as statins and fibrates
- nutritional intervention depending on the level of plasma cholesterol, APOE*3Leiden mice develop atherosclerotic lesions in the aorta resembling those found in humans with respect to cellular composition and morphological and
- Test substances were administered orally as admix to the Western-type diet .
- sunflower oil was added to a total oil volume of 10 mL/kg diet.
- Compound (A) of Example 2 above was tested at 0.3 mmol/kg bw/day.
- a reference compound of omega-3 acid ethyl esters (OmacorTM/LovazaTM) was tested at 3.3 mmol/kg bw/day.
- t 0 and 4 weeks, blood samples were taken after a 4 hour-fast to measure plasma cholesterol and triglycerides. Results are shown in FIGURE 1.
- Example 14 Evaluation of the effects on in vivo lipid metabolism in a dvslipidemic mouse model (APOE*3Leiden.CETP transgenic mice)
- the APOE*3Leiden.CETP transgenic mouse is a model where the human cholesterol ester transfer protein has been introduced to the APOE*3Leiden transgenic mouse. This results in a more human-like lipoprotein profile and is well-suited for testing the effects of drugs on plasma HDL and triglyceride levels.
- Example 15 Evaluation of the effects on in vivo atherosclerosis development in a mouse model (APOE*3Leiden.CETP transgenic mice)
- the APOE*3Leiden.CETP transgenic mouse has proven to be representative of the human situation with respect to plasma lipoprotein levels and its responsiveness to hypolipidemic drugs (like statins, fibrates etc.) and nutritional intervention.
- APOE*3Leiden.CETP mice develop atherosclerotic lesions in the aorta resembling those found in humans with respect to cellular composition and morphological and immunohistochemical characteristics.
- TC plasma total cholesterol
- HDL-C HDL cholesterol
- TG triglycerides
- test substances were administered orally as admix to the Western-type diet.
- sunflower oil was added to a total oil volume of 10 mL/kg diet.
- Compound (A) was tested at initially at 0.1 mmol/kg bw/day and reduced to 0.04 mmol/kg bw/day at 4 weeks; the initial dose was based on a prior dose-finding study to establish the required dosage that would reduce VLDL/LDL cholesterol by 25-30%.
- the fenofibrate dose was initially 10 mg/kg bw/day, and later reduced to 4.2 mg/kg bw/day to parallel reductions in VLDL/LDL cholesterol induced by Compound A.
- Compound A significantly decreased total cholesterol (pO.001) and significantly increased HDL cholesterol (p ⁇ 0.003) as compared to control.
- Compound A also significantly decreased lesion area (p ⁇ 0.003) and undiseased segments (p ⁇ 0.003) as compared to control (FIGURES 6 and 7).
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11837647.4A EP2635270B1 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
KR1020207008118A KR20200034814A (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
BR112013010890-8A BR112013010890B1 (en) | 2010-11-05 | 2011-11-03 | USE OF A COMPOUND FOR THE MANUFACTURE OF A MEDICINE TO TREAT OR PREVENT A HIGH APO B CONDITION |
KR1020137014384A KR20130132836A (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
EA201390659A EA028535B1 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
MX2013005022A MX350720B (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds. |
CA2816949A CA2816949C (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
ES11837647.4T ES2618604T3 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
CN2011800640854A CN103347508A (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compound |
AU2011324909A AU2011324909B2 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
US13/883,405 US9394228B2 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
JP2013537218A JP2014505017A (en) | 2010-11-05 | 2011-11-03 | Treatment method using lipid compounds |
KR1020197016734A KR102265409B1 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
SG2013033832A SG190114A1 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
UAA201305822A UA111475C2 (en) | 2010-11-05 | 2011-11-03 | Method of treatment using lipid substances |
NZ610705A NZ610705A (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
IL226116A IL226116B (en) | 2010-11-05 | 2013-05-02 | Pharmaceutical compositions comprising lipid compounds for treatment of elevated apo b |
ZA2013/03813A ZA201303813B (en) | 2010-11-05 | 2013-05-24 | Methods of treatment using lipid compounds |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US41044510P | 2010-11-05 | 2010-11-05 | |
US61/410,445 | 2010-11-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012059818A1 true WO2012059818A1 (en) | 2012-05-10 |
Family
ID=46024069
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2011/002925 WO2012059818A1 (en) | 2010-11-05 | 2011-11-03 | Methods of treatment using lipid compounds |
Country Status (21)
Country | Link |
---|---|
US (1) | US9394228B2 (en) |
EP (1) | EP2635270B1 (en) |
JP (1) | JP2014505017A (en) |
KR (3) | KR20130132836A (en) |
CN (2) | CN103347508A (en) |
AR (1) | AR083772A1 (en) |
AU (1) | AU2011324909B2 (en) |
BR (1) | BR112013010890B1 (en) |
CA (1) | CA2816949C (en) |
CO (1) | CO6771414A2 (en) |
EA (1) | EA028535B1 (en) |
ES (1) | ES2618604T3 (en) |
IL (1) | IL226116B (en) |
MX (1) | MX350720B (en) |
MY (1) | MY170076A (en) |
NZ (1) | NZ610705A (en) |
SG (2) | SG190114A1 (en) |
TW (2) | TWI578984B (en) |
UA (1) | UA111475C2 (en) |
WO (1) | WO2012059818A1 (en) |
ZA (1) | ZA201303813B (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8735436B2 (en) | 2009-05-08 | 2014-05-27 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
US8741966B2 (en) | 2007-11-09 | 2014-06-03 | Pronova Biopharma Norge As | Lipid compounds for use in cosmetic products, as food supplement or as a medicament |
US8759558B2 (en) | 2008-07-15 | 2014-06-24 | Pronova Biopharma Norge As | Sulphur containing lipids for use as food supplement or as medicament |
JP2016510018A (en) * | 2013-02-28 | 2016-04-04 | プロノヴァ・バイオファーマ・ノルゲ・アーエスPronova BioPharma Norge AS | Composition comprising lipid compound, triglyceride and surfactant, and method of use thereof |
US9365482B2 (en) | 2013-02-28 | 2016-06-14 | Pronova Biopharma Norge As | Methods of preparing fatty acid derivatives |
US9394228B2 (en) | 2010-11-05 | 2016-07-19 | Pronova Biopharma Norge As | Methods of treatment using lipid compounds |
WO2016156912A1 (en) * | 2015-04-01 | 2016-10-06 | Pronova Biopharma Norge As | Use of thia oxo compounds for lowering apo c3 |
WO2019111048A1 (en) * | 2017-12-06 | 2019-06-13 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
US10722481B2 (en) | 2015-04-28 | 2020-07-28 | Basf As | Substituted fatty acids for treating non-alcoholic steatohepatitis |
WO2022137125A1 (en) * | 2020-12-22 | 2022-06-30 | Northsea Therapeutics B.V. | Combination therapies comprising oxygen-containing structurally enhanced fatty acids for treatment of non-alcoholic steatohepatitis |
RU2820995C2 (en) * | 2017-12-06 | 2024-06-14 | Басф Ас | Structurally enhanced oxygen-containing fatty acids for treating non-alcoholic steatohepatitis |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7341916B2 (en) * | 2015-04-01 | 2023-09-11 | ビーエーエスエフ エーエス | Use of thiaoxo compounds to lower apoC3 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009061208A1 (en) * | 2007-11-09 | 2009-05-14 | Pronova Biopharma Norge As | Lipid compounds for use in cosmetic products, as food supplement or as a medicament |
WO2009149496A1 (en) * | 2008-06-10 | 2009-12-17 | Central Northern Adelaide Health Service | Treatment of diabetes and complications thereof and related disorders |
WO2010008299A1 (en) * | 2008-07-15 | 2010-01-21 | Pronova Biopharma Norge As | Novel sulphur containing lipids for use as food supplement or as medicament |
WO2010128401A1 (en) * | 2009-05-08 | 2010-11-11 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2909554A (en) | 1956-07-23 | 1959-10-20 | Monsanto Chemicals | Process for the manufacture of (alkylmercapto) alkyl sulfates |
GB1038723A (en) | 1962-03-26 | |||
JPS4839001B1 (en) | 1970-11-09 | 1973-11-21 | ||
US4040781A (en) | 1974-06-06 | 1977-08-09 | Lever Brothers Company | Novel 2-(alkylsulfinyl)ethyl sulfates and compositions employing same |
US4032564A (en) | 1974-09-09 | 1977-06-28 | Zoecon Corporation | Esters of cyclopropylalkanols |
GB1523276A (en) | 1974-09-20 | 1978-08-31 | Lafon Labor | Sulphur-containing amino compounds |
US4009211A (en) | 1975-07-29 | 1977-02-22 | Gulf Research & Development Company | Beta,beta-dialkylethylmercaptoethoxylate as new compounds |
US4209410A (en) | 1976-04-28 | 1980-06-24 | Phillips Petroleum Company | Lubricants |
DE2861974D1 (en) | 1977-11-11 | 1982-09-16 | Ciba Geigy Ag | Pyridine dicarboxylic acid derivatives, their mixtures with metallic stabilisers and their use in stabilising chlorine-containing thermoplasts |
JPS5570841A (en) | 1978-11-24 | 1980-05-28 | Konishiroku Photo Ind Co Ltd | Forming method of dye image |
US4368190A (en) | 1980-04-17 | 1983-01-11 | Merck & Co., Inc. | Immunologically active dipeptidyl 4-O-,6-O-acyl-2-amino-2-deoxy-D-glucose derivatives and methods for their preparation |
DE3164332D1 (en) | 1980-10-21 | 1984-07-26 | Boehringer Mannheim Gmbh | Phospholipids that contain sulphur, process for their preparation and medicines containing these compounds |
US4411808A (en) | 1982-08-04 | 1983-10-25 | Exxon Research & Engineering Co. | Multifunctional additive for power transmission shift fluids |
US4775223A (en) | 1984-09-20 | 1988-10-04 | Canon Kabushiki Kaisha | Lactic acid derivative, liquid crystal composition containing same and liquid crystal device |
CA2010000A1 (en) | 1989-04-07 | 1990-10-07 | Paul B. Merkel | Photographic recording material containing a cyan dye-forming coupler |
JPH0451149A (en) | 1990-06-19 | 1992-02-19 | Fuji Photo Film Co Ltd | Silver halide color photographic sensitive material |
FR2663928B1 (en) | 1990-06-27 | 1994-04-08 | Norsolor | NOVEL SULFUR ACRYLIC COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND THEIR APPLICATION TO THE SYNTHESIS OF NEW POLYMERS. |
EP0487809A1 (en) | 1990-11-28 | 1992-06-03 | Monsanto Europe S.A./N.V. | Rubber compositions having improved processability and improved rubber-vulcanisate properties |
JPH0543529A (en) | 1991-08-10 | 1993-02-23 | Taisho Pharmaceut Co Ltd | Alkaneamide ammonium compound |
JP2755279B2 (en) | 1992-03-19 | 1998-05-20 | 三井化学株式会社 | Thermoplastic resin composition and molded article thereof |
JP2793458B2 (en) | 1992-03-19 | 1998-09-03 | 三井化学株式会社 | Polyamide resin composition for connector and connector |
AU7044894A (en) | 1993-06-10 | 1995-01-03 | University Of North Carolina At Chapel Hill, The | (phospho)lipids for combatting hepatitis b virus infection |
JP3110918B2 (en) | 1993-06-18 | 2000-11-20 | 富士写真フイルム株式会社 | Silver halide photographic material |
US5523430A (en) | 1994-04-14 | 1996-06-04 | Bristol-Myers Squibb Company | Protein farnesyl transferase inhibitors |
GB2290789B (en) | 1994-07-01 | 1998-09-16 | Ciba Geigy Ag | Titanium and zirconium complexes of carboxylic acids as corrosion inhibitors |
ATE210640T1 (en) | 1994-10-13 | 2001-12-15 | Peptide Technology Ltd | MODIFIED POLYUNSATURATED FATTY ACIDS |
US7517858B1 (en) | 1995-06-07 | 2009-04-14 | The Regents Of The University Of California | Prodrugs of pharmaceuticals with improved bioavailability |
FR2741619B1 (en) | 1995-11-28 | 1998-02-13 | Pf Medicament | NOVEL 2,3,5-TRIMETHYL-4-HYDROXY-ANILIDES DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
CA2251780A1 (en) | 1996-04-12 | 1997-10-23 | Peptide Technology Pty. Limited | Methods of treating immunopathologies using polyunsaturated fatty acids |
US6060515A (en) | 1997-01-24 | 2000-05-09 | The Regents Of The University Of California | Treatment of skin conditions by use of PPARα activators |
PL334840A1 (en) | 1997-01-24 | 2000-03-27 | Univ California | Application of fxr, pparalpha and lxralpha activators in order to restore the barrier function, to stimulate epithelium differentation and to inhibit proliferation |
JPH11180929A (en) | 1997-12-19 | 1999-07-06 | Asahi Glass Co Ltd | Ester derivative |
AU7240398A (en) | 1998-05-08 | 1999-11-29 | Rolf Berge | Use of non-beta-oxidizable fatty acid analogues for treatment of syndrome-x conditions |
FR2786187B1 (en) | 1998-11-19 | 2001-11-09 | Univ Paris Curie | 2-ACYLAMINO-2-DEOXY-GLUCONO-1,5-LACTONE TYPE COMPOUNDS, PROCESS FOR OBTAINING SAME, COMPOSITIONS COMPRISING SAME AND USES THEREOF |
FR2792312B1 (en) | 1999-04-15 | 2001-06-08 | Oreal | THIA-ALCYNOIC (POLY) COMPOUNDS AND DERIVATIVES THEREOF, COMPOSITIONS COMPRISING SAME AND THEIR USE |
MXPA01012491A (en) | 1999-06-01 | 2002-07-02 | Univ Texas Southwestern Med Ct | Substituted biaryl ether compounds. |
US6723717B1 (en) | 1999-06-01 | 2004-04-20 | The University Of Texas Southwestern Medical Center | Sulfur-containing thyroxane derivatives and their use as hair growth promotors |
NO328803B1 (en) | 2000-03-03 | 2010-05-18 | Thia Medica | New fatty acid analogues |
UA75083C2 (en) | 2000-06-22 | 2006-03-15 | Тераванс, Інк. | Derivatives of glycopeptidephosphonates |
FR2828487B1 (en) | 2001-08-09 | 2005-05-27 | Genfit S A | NOVEL COMPOUNDS DERIVED FROM FATTY ACIDS, PREPARATION AND USES |
US20030147814A1 (en) | 2001-12-21 | 2003-08-07 | 3M Innovative Properties Company | Medicinal aerosol formulations comprising ion pair complexes |
GB2383355A (en) | 2001-12-22 | 2003-06-25 | Schlumberger Holdings | An aqueous viscoelastic fluid containing hydrophobically modified polymer and viscoelastic surfactant |
GB0202002D0 (en) | 2002-01-29 | 2002-03-13 | Leiv Eiriksson Nyotek A S | Use |
MXPA04007382A (en) | 2002-01-31 | 2004-10-11 | Tfl Ledertechnik Gmbh | Compositions and its use for imparting water repellency to leather or furskins, textiles and other fibrous materials. |
WO2003105769A2 (en) | 2002-06-13 | 2003-12-24 | New York University | Synthetic c-glycolipid and its use for treating cancer infectious diseases and autoimmune diseases |
FR2845991B1 (en) | 2002-10-16 | 2005-02-04 | Pf Medicament | ALPHA-PHENYL ACETANILIDE DERIVATIVES AND THEIR USE IN HUMAN THERAPEUTICS |
US8372430B2 (en) | 2002-12-17 | 2013-02-12 | The Procter & Gamble Company | Compositions, methods, and kits useful for the alleviation of gastrointestinal effects |
EP1600438A4 (en) | 2003-02-28 | 2007-05-02 | Kaneka Corp | Processes for the production of optically active compounds having substituents at the 2-position |
DE10326303A1 (en) | 2003-06-11 | 2004-12-30 | Celares Gmbh | Reagents for modifying biopharmaceuticals, their manufacture and use |
BRPI0507236A (en) | 2004-01-30 | 2007-06-26 | Peplin Biolipids Pty Ltd | method for the treatment or prophylaxis of a condition, and, compound |
JP4563114B2 (en) | 2004-08-30 | 2010-10-13 | 出光興産株式会社 | Additive for lubricant |
EP1856213A2 (en) | 2005-03-08 | 2007-11-21 | CIBA SPECIALTY CHEMICALS HOLDING INC. Patent Departement | Metal oxide nanoparticles coated with specific n-acylaminomethylene phosphonates |
EP1888727B1 (en) | 2005-05-04 | 2015-04-15 | Pronova BioPharma Norge AS | New dha derivatives and their use as medicaments |
CN101213281B (en) | 2005-05-04 | 2013-03-13 | 普罗诺瓦生物医药挪威公司 | New dha derivatives and their use as medicaments |
US20070167529A1 (en) | 2006-01-17 | 2007-07-19 | Walton Rebecca A | Antimicrobial compositions for treating fabrics and surfaces |
EP2004169B1 (en) | 2006-04-12 | 2012-08-08 | Unilever PLC | Oral composition comprising a polyunsaturated fatty acid and salicylic acid for obtaining an antiinflammatory effect in skin |
EP1849449A1 (en) | 2006-04-26 | 2007-10-31 | 3M Innovative Properties Company | Filler containing composition and process for production and use thereof |
US7763607B2 (en) | 2006-04-27 | 2010-07-27 | Solvay Pharmaceuticals Gmbh | Pharmaceutical compositions comprising CBx cannabinoid receptor modulators and potassium channel modulators |
US20080075692A1 (en) | 2006-05-09 | 2008-03-27 | Perrine Susan P | Methods for treating blood disorders |
MX2009004337A (en) | 2006-11-01 | 2009-05-22 | Pronova Biopharma Norge As | Novel lipid compounds. |
CA2667211A1 (en) | 2006-11-01 | 2008-05-08 | Pronova Biopharma Norge As | Alpha-substituted omega-3 lipids that are activators or modulators of the peroxisome proliferators-activated receptor (ppar) |
WO2008053340A1 (en) | 2006-11-03 | 2008-05-08 | Pronova Biopharma Norge As | A combination product comprising at least one lipid substituted in the alpha position and at least one hypoglycemic agent |
CN101225064A (en) | 2007-01-19 | 2008-07-23 | 上海汇瑞生物科技有限公司 | New method for preparing neta-thia-alpha-alkyl fatty acid |
DE102007017179A1 (en) | 2007-04-12 | 2008-10-23 | Clariant International Ltd. | Process for the preparation of Alkylpolyglykolcarbonsäuren and Polyglykoldicarbonsäuren by direct oxidation |
EP2217558A1 (en) * | 2007-10-31 | 2010-08-18 | Pronova Biopharma Norge AS | New dha derivatives and their use as medicaments |
CN101259118B (en) * | 2008-01-31 | 2010-06-16 | 中国科学院广州生物医药与健康研究院 | Application of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethyl chalcone as PPAR gamma agonist |
FR2933006B1 (en) | 2008-06-27 | 2010-08-20 | Inst Francais Du Petrole | ABSORBENT SOLUTION CONTAINING SULFUR DEGRADATION INHIBITOR WITH CARBOXYL GROUPING AND METHOD FOR LIMITING THE DEGRADATION OF AN ABSORBENT SOLUTION |
EP2813486B1 (en) | 2008-07-08 | 2017-10-25 | Catabasis Pharmaceuticals, Inc. | Fatty acid acetylated salicylates and their uses |
EP3915554A1 (en) | 2009-03-09 | 2021-12-01 | Basf As | Compositions comprising a fatty acid oil mixture and a surfactant, and methods and uses thereof |
EP2248798A1 (en) * | 2009-05-08 | 2010-11-10 | Pronova BioPharma Norge AS | Novel lipid compounds |
BR112012004677A2 (en) | 2009-09-01 | 2020-11-03 | Catabasis Pharmaceuticals, Inc. | niacin fatty acid conjugates and their uses |
US20130046013A1 (en) | 2010-01-20 | 2013-02-21 | Ragnar Hovland | Salicylate fatty acid derivatives |
KR20130132836A (en) | 2010-11-05 | 2013-12-05 | 프로노바 바이오파마 너지 에이에스 | Methods of treatment using lipid compounds |
WO2012115695A1 (en) | 2011-02-25 | 2012-08-30 | Catabasis Pharmaceuticals, Inc. | Bis-fatty acid conjugates and their uses |
WO2013016531A2 (en) | 2011-07-26 | 2013-01-31 | Purdue Research Foundation | Compounds and methods for use in treating neoplasia and cancer |
-
2011
- 2011-11-03 KR KR1020137014384A patent/KR20130132836A/en active Search and Examination
- 2011-11-03 AU AU2011324909A patent/AU2011324909B2/en active Active
- 2011-11-03 EA EA201390659A patent/EA028535B1/en not_active IP Right Cessation
- 2011-11-03 US US13/883,405 patent/US9394228B2/en active Active
- 2011-11-03 EP EP11837647.4A patent/EP2635270B1/en active Active
- 2011-11-03 KR KR1020207008118A patent/KR20200034814A/en not_active Application Discontinuation
- 2011-11-03 NZ NZ610705A patent/NZ610705A/en unknown
- 2011-11-03 BR BR112013010890-8A patent/BR112013010890B1/en active IP Right Grant
- 2011-11-03 KR KR1020197016734A patent/KR102265409B1/en active IP Right Grant
- 2011-11-03 CN CN2011800640854A patent/CN103347508A/en active Pending
- 2011-11-03 MY MYPI2013001591A patent/MY170076A/en unknown
- 2011-11-03 ES ES11837647.4T patent/ES2618604T3/en active Active
- 2011-11-03 WO PCT/IB2011/002925 patent/WO2012059818A1/en active Application Filing
- 2011-11-03 CN CN201710806301.7A patent/CN107496395A/en active Pending
- 2011-11-03 CA CA2816949A patent/CA2816949C/en active Active
- 2011-11-03 JP JP2013537218A patent/JP2014505017A/en active Pending
- 2011-11-03 UA UAA201305822A patent/UA111475C2/en unknown
- 2011-11-03 SG SG2013033832A patent/SG190114A1/en unknown
- 2011-11-03 MX MX2013005022A patent/MX350720B/en active IP Right Grant
- 2011-11-03 SG SG10201509127YA patent/SG10201509127YA/en unknown
- 2011-11-04 AR ARP110104131A patent/AR083772A1/en unknown
- 2011-11-04 TW TW100140360A patent/TWI578984B/en active
- 2011-11-04 TW TW105133054A patent/TW201701875A/en unknown
-
2013
- 2013-05-02 IL IL226116A patent/IL226116B/en active IP Right Grant
- 2013-05-24 ZA ZA2013/03813A patent/ZA201303813B/en unknown
- 2013-06-05 CO CO13136481A patent/CO6771414A2/en not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009061208A1 (en) * | 2007-11-09 | 2009-05-14 | Pronova Biopharma Norge As | Lipid compounds for use in cosmetic products, as food supplement or as a medicament |
WO2009149496A1 (en) * | 2008-06-10 | 2009-12-17 | Central Northern Adelaide Health Service | Treatment of diabetes and complications thereof and related disorders |
WO2010008299A1 (en) * | 2008-07-15 | 2010-01-21 | Pronova Biopharma Norge As | Novel sulphur containing lipids for use as food supplement or as medicament |
WO2010128401A1 (en) * | 2009-05-08 | 2010-11-11 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
Non-Patent Citations (2)
Title |
---|
FLOCK S. ET AL.: "Syntheses of some polyunsaturated sulfur- and oxygen-containing fatty acids related to eicosapentaenoic acid and docosahexaenoic acids", ACTA CHEMICA SCANDINAVICA, vol. 53, no. 6, 1999, pages 436 - 445, XP001148989 * |
See also references of EP2635270A4 * |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8741966B2 (en) | 2007-11-09 | 2014-06-03 | Pronova Biopharma Norge As | Lipid compounds for use in cosmetic products, as food supplement or as a medicament |
US8759558B2 (en) | 2008-07-15 | 2014-06-24 | Pronova Biopharma Norge As | Sulphur containing lipids for use as food supplement or as medicament |
US8735436B2 (en) | 2009-05-08 | 2014-05-27 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
US9394228B2 (en) | 2010-11-05 | 2016-07-19 | Pronova Biopharma Norge As | Methods of treatment using lipid compounds |
JP2016510018A (en) * | 2013-02-28 | 2016-04-04 | プロノヴァ・バイオファーマ・ノルゲ・アーエスPronova BioPharma Norge AS | Composition comprising lipid compound, triglyceride and surfactant, and method of use thereof |
US9365482B2 (en) | 2013-02-28 | 2016-06-14 | Pronova Biopharma Norge As | Methods of preparing fatty acid derivatives |
US11351139B2 (en) | 2013-02-28 | 2022-06-07 | Basf As | Composition comprising a lipid compound, a triglyceride, and a surfactant, and methods of using the same |
EP3578170A1 (en) | 2013-02-28 | 2019-12-11 | Basf As | A composition comprising a lipid compound, a triglyceride, and a surfactant, and methods of using the same |
AU2015389862B2 (en) * | 2015-04-01 | 2021-04-15 | Pronova Biopharma Norge As | Use of thia oxo compounds for lowering Apo C3 |
WO2016156912A1 (en) * | 2015-04-01 | 2016-10-06 | Pronova Biopharma Norge As | Use of thia oxo compounds for lowering apo c3 |
RU2705991C2 (en) * | 2015-04-01 | 2019-11-13 | Пронова Биофарма Норге Ас | Use of thia oxo compounds for lowering apo c3 content |
US10722481B2 (en) | 2015-04-28 | 2020-07-28 | Basf As | Substituted fatty acids for treating non-alcoholic steatohepatitis |
US11234948B2 (en) | 2015-04-28 | 2022-02-01 | Basf As | Substituted fatty acids for treating non-alcoholic steatohepatitis |
US11911354B2 (en) | 2015-04-28 | 2024-02-27 | Basf | Substituted fatty acids for treating non-alcoholic steatohepatitis |
WO2019111048A1 (en) * | 2017-12-06 | 2019-06-13 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
IL275002B1 (en) * | 2017-12-06 | 2023-12-01 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
US11925614B2 (en) | 2017-12-06 | 2024-03-12 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
IL275002B2 (en) * | 2017-12-06 | 2024-04-01 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
RU2820995C2 (en) * | 2017-12-06 | 2024-06-14 | Басф Ас | Structurally enhanced oxygen-containing fatty acids for treating non-alcoholic steatohepatitis |
WO2022137125A1 (en) * | 2020-12-22 | 2022-06-30 | Northsea Therapeutics B.V. | Combination therapies comprising oxygen-containing structurally enhanced fatty acids for treatment of non-alcoholic steatohepatitis |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2635270B1 (en) | Methods of treatment using lipid compounds | |
KR101783817B1 (en) | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas | |
US11911354B2 (en) | Substituted fatty acids for treating non-alcoholic steatohepatitis | |
US20180110747A1 (en) | Use of thia oxo compounds for lowering apo c3 | |
EP2248798A1 (en) | Novel lipid compounds | |
CA2886957C (en) | Use of thia oxo compounds for lowering apo c3 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11837647 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2013537218 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 226116 Country of ref document: IL |
|
ENP | Entry into the national phase |
Ref document number: 2816949 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12013500893 Country of ref document: PH Ref document number: MX/A/2013/005022 Country of ref document: MX |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REEP | Request for entry into the european phase |
Ref document number: 2011837647 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011837647 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20137014384 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 201390659 Country of ref document: EA |
|
WWE | Wipo information: entry into national phase |
Ref document number: A201305822 Country of ref document: UA Ref document number: 13136481 Country of ref document: CO |
|
ENP | Entry into the national phase |
Ref document number: 2011324909 Country of ref document: AU Date of ref document: 20111103 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13883405 Country of ref document: US |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112013010890 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112013010890 Country of ref document: BR Kind code of ref document: A2 Effective date: 20130502 |