CA2812109A1 - Methods and compositions for treatment of diabetes and dyslipidemia - Google Patents
Methods and compositions for treatment of diabetes and dyslipidemia Download PDFInfo
- Publication number
- CA2812109A1 CA2812109A1 CA2812109A CA2812109A CA2812109A1 CA 2812109 A1 CA2812109 A1 CA 2812109A1 CA 2812109 A CA2812109 A CA 2812109A CA 2812109 A CA2812109 A CA 2812109A CA 2812109 A1 CA2812109 A1 CA 2812109A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- cycloalkyl
- alkoxy
- hydroxy
- reaction mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 33
- 208000032928 Dyslipidaemia Diseases 0.000 title claims abstract description 17
- 208000017170 Lipid metabolism disease Diseases 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims description 36
- 239000000203 mixture Substances 0.000 title claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 136
- 150000001875 compounds Chemical class 0.000 claims abstract description 83
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 64
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 59
- 150000001412 amines Chemical class 0.000 claims abstract description 41
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 20
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 20
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 17
- 125000000524 functional group Chemical group 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims abstract description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 206010022489 Insulin Resistance Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 285
- 239000011541 reaction mixture Substances 0.000 description 150
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 140
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 137
- 239000000047 product Substances 0.000 description 101
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 92
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- 238000001704 evaporation Methods 0.000 description 71
- 230000008020 evaporation Effects 0.000 description 71
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 59
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 239000012043 crude product Substances 0.000 description 54
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 45
- 229910052938 sodium sulfate Inorganic materials 0.000 description 43
- 235000011152 sodium sulphate Nutrition 0.000 description 43
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- 238000004949 mass spectrometry Methods 0.000 description 34
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- 230000015572 biosynthetic process Effects 0.000 description 32
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- 239000000741 silica gel Substances 0.000 description 31
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- 239000003039 volatile agent Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 20
- 235000019253 formic acid Nutrition 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- -1 cycloalkyl aliphatic carboxylic acids Chemical class 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 229940043279 diisopropylamine Drugs 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
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- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 229940086542 triethylamine Drugs 0.000 description 8
- 239000011534 wash buffer Substances 0.000 description 8
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 7
- 102000004877 Insulin Human genes 0.000 description 7
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- 238000012512 characterization method Methods 0.000 description 7
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- 229940125396 insulin Drugs 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- FTEAAYMAQFBUJJ-UHFFFAOYSA-N tert-butyl cyclopropanecarboxylate Chemical compound CC(C)(C)OC(=O)C1CC1 FTEAAYMAQFBUJJ-UHFFFAOYSA-N 0.000 description 7
- 150000003626 triacylglycerols Chemical class 0.000 description 7
- ZJJATABWMGVVRZ-UHFFFAOYSA-N 1,12-dibromododecane Chemical compound BrCCCCCCCCCCCCBr ZJJATABWMGVVRZ-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
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- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
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- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/58—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C31/27—Polyhydroxylic alcohols containing saturated rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/04—Saturated ethers
- C07C43/115—Saturated ethers containing carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/132—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/12—Saturated polycyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/15—Saturated compounds containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/608—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38444610P | 2010-09-20 | 2010-09-20 | |
| US61/384,446 | 2010-09-20 | ||
| PCT/US2011/052318 WO2012040177A1 (en) | 2010-09-20 | 2011-09-20 | Methods and compositions for treatment of diabetes and dyslipidemia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2812109A1 true CA2812109A1 (en) | 2012-03-29 |
Family
ID=45818296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2812109A Abandoned CA2812109A1 (en) | 2010-09-20 | 2011-09-20 | Methods and compositions for treatment of diabetes and dyslipidemia |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8623897B2 (enExample) |
| EP (1) | EP2618824A4 (enExample) |
| JP (1) | JP2013537240A (enExample) |
| KR (1) | KR20140009125A (enExample) |
| CN (1) | CN103327974A (enExample) |
| AU (1) | AU2011305610A1 (enExample) |
| BR (1) | BR112013008675A2 (enExample) |
| CA (1) | CA2812109A1 (enExample) |
| MX (1) | MX2013003078A (enExample) |
| RU (1) | RU2013118021A (enExample) |
| SG (1) | SG188996A1 (enExample) |
| WO (1) | WO2012040177A1 (enExample) |
| ZA (1) | ZA201301936B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013537240A (ja) * | 2010-09-20 | 2013-09-30 | カリウス セラピューティクス エスエー | 糖尿病および脂質異常症の処置のための方法および組成物 |
| US20140121267A1 (en) * | 2011-09-20 | 2014-05-01 | Kareus Therapeutics, Sa | Methods and compositions for treatment of diabetes and dyslipidemia |
| EP2981260B1 (en) * | 2013-04-04 | 2021-01-13 | Sphaera Pharma Pvt. Ltd. | Novel analogues of epicatechin and related polyphenols |
| US9827222B2 (en) | 2013-07-01 | 2017-11-28 | Emory University | Treating or preventing nephrogenic diabetes insipidus |
| CA2942100A1 (en) * | 2014-03-20 | 2015-09-24 | Esperion Therapeutics, Inc. | Carboxy-cyclopropyl undecanol compounds for treatment of liver disease and other medical disorders |
| MX392182B (es) | 2015-03-13 | 2025-03-21 | Esperion Therapeutics Inc | Combinaciones de dosis fija y formulaciones que comprenden ácido 8-hidroxi-2,2,14,14 tetrametilpentadecanodioico (etc1002) y ezetimiba y métodos para tratar o reducir el riesgo de enfermedad cardiovascular. |
| MA41793A (fr) | 2015-03-16 | 2018-01-23 | Esperion Therapeutics Inc | Associations de doses fixes comprenant du etc1002 et une ou plusieurs statines permettant de traiter ou de réduire un risque cardiovasculaire |
| CN107118098B (zh) * | 2016-02-25 | 2020-07-14 | 中国科学院上海药物研究所 | 一类脂肪酸类化合物、其制备方法及其用途 |
| WO2018144570A1 (en) * | 2017-01-31 | 2018-08-09 | Emory University | Managing nephrogenic diabetes insipidus |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3280169A (en) * | 1962-09-18 | 1966-10-18 | Union Carbide Corp | Sulfo-substituted aromatic dicarboxylic compounds |
| US3773946A (en) | 1969-09-02 | 1973-11-20 | Parke Davis & Co | Triglyceride-lowering compositions and methods |
| US3853951A (en) * | 1971-07-14 | 1974-12-10 | American Cyanamid Co | Preparation of 9-oxo-13-trans-prostenoic acid esters by alanate addition to cyclopentenone |
| IL64542A0 (en) | 1981-12-15 | 1982-03-31 | Yissum Res Dev Co | Long-chain alpha,omega-dicarboxylic acids and derivatives thereof and pharmaceutical compositions containing them |
| DE3423166A1 (de) | 1984-06-22 | 1986-01-02 | Epis S.A., Zug | Alpha-, omega-dicarbonsaeuren, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten |
| US4739113A (en) * | 1986-05-30 | 1988-04-19 | Merck & Co., Inc. | Bis(cyclopropanecarboxamido)alkadienedioic acids as renal dipeptidase inhibitors |
| JPS63246351A (ja) * | 1987-04-02 | 1988-10-13 | Rikagaku Kenkyusho | ポリケト−ル系化合物及びその合成法 |
| US5648387A (en) | 1995-03-24 | 1997-07-15 | Warner-Lambert Company | Carboxyalkylethers, formulations, and treatment of vascular diseases |
| FR2740135B1 (fr) | 1995-10-20 | 1997-12-19 | Roussel Uclaf | Nouveaux derives de pyrazoles acides, leur procede de preparation, leur application a titre de medicaments, leur nouvelle utilisation et les compositions pharmaceutiques les renfermant |
| IL119971A (en) | 1997-01-07 | 2003-02-12 | Yissum Res Dev Co | Pharmaceutical compositions containing dicarboxylic acids and derivatives thereof and some novel dicarboxylic acids |
| JPH10273469A (ja) * | 1997-02-03 | 1998-10-13 | Takeda Chem Ind Ltd | ２環性キノン誘導体、製造法および剤 |
| DE19837620A1 (de) | 1997-08-22 | 1999-02-25 | Novartis Ag | Organische Verbindungen |
| NZ506679A (en) | 1998-03-27 | 2002-11-26 | Janssen Pharmaceutica Nv | HIV inhibiting pyrimidine derivatives |
| BRPI9909191B8 (pt) | 1998-03-27 | 2021-07-06 | Janssen Pharmaceutica Nv | derivados de pirimidina inibidores do hiv, seu uso e composição farmacêutica que os compreende |
| US6387897B1 (en) | 1998-06-30 | 2002-05-14 | Neuromed Technologies, Inc. | Preferentially substituted calcium channel blockers |
| US6440996B1 (en) | 1998-10-07 | 2002-08-27 | Georgetown University | Monomeric and dimeric heterocycles, and therapeutic uses thereof |
| EP1130469A1 (en) | 2000-02-22 | 2001-09-05 | Lucent Technologies Inc. | A radiation-sensitive resist material and a process for device fabrication using the same |
| DE10010430A1 (de) | 2000-03-03 | 2001-09-06 | Bayer Ag | Substituierte 5-Ethyl-dihydropyridazinone und ihre Verwendung |
| CN1962596A (zh) | 2000-10-11 | 2007-05-16 | 埃斯佩里安医疗公司 | 用于控制胆固醇以及相关用途的酮化合物以及组合物 |
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| JP2004523638A (ja) | 2001-04-02 | 2004-08-05 | チバ スペシャルティ ケミカルズ ホールディング インコーポレーテッド | 安定化したロウソクのロウ |
| US6547840B2 (en) | 2001-04-02 | 2003-04-15 | Ciba Specialty Chemicals Corporation | Candle wax stabilized with imidazolidines |
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| US6905525B2 (en) | 2001-04-02 | 2005-06-14 | Ciba Specialty Chemicals Corporation | Candle wax stabilized with piperazinones |
| US7375115B2 (en) * | 2001-10-09 | 2008-05-20 | Kyorin Pharmaceutical Co., Ltd. | 4-(2-furoyl) aminopiperidines, intermediates in synthesizing the same, process for producing the same and medicinal use of the same |
| US20040082641A1 (en) | 2002-10-28 | 2004-04-29 | Rytved Klaus Asger | Use of glycogen phosphorylase inhibitors for treatment of cardiovascular diseases |
| US7335689B2 (en) | 2003-01-23 | 2008-02-26 | Esperion Therapeutics, Inc. | Dihydroxyl compounds and compositions for cholesterol management and related uses |
| US7705177B2 (en) * | 2003-12-24 | 2010-04-27 | Esperion Therapuetics, Inc. | Ketone compounds and compositions for cholesterol management and related uses |
| AU2003300438A1 (en) | 2003-12-24 | 2005-08-03 | Esperion Therapeutics, Inc. | Ether compounds and compositions for cholesterol management and related uses |
| FR2903695B1 (fr) * | 2006-07-13 | 2008-10-24 | Merck Sante Soc Par Actions Si | Utilisation de derives d'imidazole activateurs de l'ampk, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| IL181577A0 (en) * | 2007-02-26 | 2007-07-04 | Jacob Bar Tana | Combination therapy composition and methods for the treatment of cardiovascular disorders and immune-related disorders |
| JP5345293B2 (ja) | 2007-03-29 | 2013-11-20 | 株式会社Ａｄｅｋａ | 重合性化合物及び重合性組成物 |
| EP2190948B1 (en) | 2007-09-25 | 2011-10-26 | Merck Patent GmbH | Mesogenic dimers |
| JP2013537240A (ja) * | 2010-09-20 | 2013-09-30 | カリウス セラピューティクス エスエー | 糖尿病および脂質異常症の処置のための方法および組成物 |
-
2011
- 2011-09-20 JP JP2013529411A patent/JP2013537240A/ja active Pending
- 2011-09-20 AU AU2011305610A patent/AU2011305610A1/en not_active Abandoned
- 2011-09-20 WO PCT/US2011/052318 patent/WO2012040177A1/en not_active Ceased
- 2011-09-20 MX MX2013003078A patent/MX2013003078A/es not_active Application Discontinuation
- 2011-09-20 RU RU2013118021/15A patent/RU2013118021A/ru not_active Application Discontinuation
- 2011-09-20 US US13/236,807 patent/US8623897B2/en active Active
- 2011-09-20 EP EP11827340.8A patent/EP2618824A4/en not_active Withdrawn
- 2011-09-20 SG SG2013018833A patent/SG188996A1/en unknown
- 2011-09-20 CN CN2011800558120A patent/CN103327974A/zh active Pending
- 2011-09-20 KR KR1020137007110A patent/KR20140009125A/ko not_active Withdrawn
- 2011-09-20 BR BR112013008675A patent/BR112013008675A2/pt not_active IP Right Cessation
- 2011-09-20 CA CA2812109A patent/CA2812109A1/en not_active Abandoned
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2013
- 2013-03-14 ZA ZA2013/01936A patent/ZA201301936B/en unknown
-
2014
- 2014-01-06 US US14/148,580 patent/US20140142178A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN103327974A (zh) | 2013-09-25 |
| US20140142178A1 (en) | 2014-05-22 |
| MX2013003078A (es) | 2013-09-26 |
| SG188996A1 (en) | 2013-05-31 |
| WO2012040177A1 (en) | 2012-03-29 |
| JP2013537240A (ja) | 2013-09-30 |
| US8623897B2 (en) | 2014-01-07 |
| US20120071528A1 (en) | 2012-03-22 |
| EP2618824A4 (en) | 2015-05-06 |
| BR112013008675A2 (pt) | 2016-06-21 |
| AU2011305610A1 (en) | 2013-03-14 |
| EP2618824A1 (en) | 2013-07-31 |
| RU2013118021A (ru) | 2014-10-27 |
| KR20140009125A (ko) | 2014-01-22 |
| ZA201301936B (en) | 2014-05-28 |
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