ES2326326T3 - Compuestos y procedimientos para tratar la dislipidemia. - Google Patents
Compuestos y procedimientos para tratar la dislipidemia. Download PDFInfo
- Publication number
- ES2326326T3 ES2326326T3 ES05725968T ES05725968T ES2326326T3 ES 2326326 T3 ES2326326 T3 ES 2326326T3 ES 05725968 T ES05725968 T ES 05725968T ES 05725968 T ES05725968 T ES 05725968T ES 2326326 T3 ES2326326 T3 ES 2326326T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- aryl
- cycloalkyl
- alkenyl
- heterocyclic
- 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.)
- Expired - Lifetime
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 143
- 238000000034 method Methods 0.000 title description 63
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 237
- 125000003118 aryl group Chemical group 0.000 claims abstract description 139
- -1 NR11R12 Chemical group 0.000 claims abstract description 125
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 81
- 239000000203 mixture Substances 0.000 claims abstract description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 50
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 43
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 33
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 32
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 28
- 150000002367 halogens Chemical class 0.000 claims abstract description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 27
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 150000001412 amines Chemical class 0.000 claims abstract description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011593 sulfur Substances 0.000 claims abstract description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims abstract description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims abstract description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229930192474 thiophene Natural products 0.000 claims abstract description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims abstract description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 20
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 9
- 239000002253 acid Substances 0.000 claims description 79
- 150000002148 esters Chemical class 0.000 claims description 58
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 42
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 30
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 208000029078 coronary artery disease Diseases 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 15
- 201000001320 Atherosclerosis Diseases 0.000 claims description 13
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- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 11
- 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- PHPQWAVLQLGBBW-UHFFFAOYSA-N propan-2-yl 4-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-ethyl-7-methyl-3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound C12=CC=C(C)N=C2N(C(=O)OC(C)C)C(CC)CC1N(C(C)=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PHPQWAVLQLGBBW-UHFFFAOYSA-N 0.000 claims description 4
- FWFBXCGTTOEINR-UHFFFAOYSA-N propan-2-yl 7-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-5-ethyl-6,7-dihydro-5h-thieno[3,2-b]pyridine-4-carboxylate Chemical compound C1=2SC=CC=2N(C(=O)OC(C)C)C(CC)CC1N(C(C)=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FWFBXCGTTOEINR-UHFFFAOYSA-N 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 claims description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 208000026758 coronary atherosclerosis Diseases 0.000 claims description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 3
- 101100237347 Escherichia coli (strain K12) metN gene Proteins 0.000 claims description 2
- 108010092277 Leptin Proteins 0.000 claims description 2
- 102000016267 Leptin Human genes 0.000 claims description 2
- 101100444360 Mycoplasma mycoides subsp. mycoides SC (strain PG1) ecfA1 gene Proteins 0.000 claims description 2
- 101100464186 Oryzias latipes pkd1l1 gene Proteins 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims description 2
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims description 2
- 229940039781 leptin Drugs 0.000 claims description 2
- 102000004311 liver X receptors Human genes 0.000 claims description 2
- 108090000865 liver X receptors Proteins 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 5
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims 2
- KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 claims 1
- 102100037637 Cholesteryl ester transfer protein Human genes 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 85
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 18
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 9
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 abstract 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 3
- 125000001054 5 membered carbocyclic group Chemical group 0.000 abstract 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 abstract 1
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 55
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 55
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 238000002360 preparation method Methods 0.000 description 40
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 39
- 108010010234 HDL Lipoproteins Proteins 0.000 description 32
- 102000015779 HDL Lipoproteins Human genes 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
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- 238000012360 testing method Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 239000003480 eluent Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000009472 formulation Methods 0.000 description 18
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- 230000002829 reductive effect Effects 0.000 description 15
- 235000012000 cholesterol Nutrition 0.000 description 13
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- 150000002923 oximes Chemical class 0.000 description 1
- XXEBDPRHFAWOND-UHFFFAOYSA-M p-chloromercuribenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C([Hg]Cl)C=C1 XXEBDPRHFAWOND-UHFFFAOYSA-M 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
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- 239000011591 potassium Chemical class 0.000 description 1
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- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- NDNUMSSRCMHEKO-UHFFFAOYSA-N propan-2-yl 5-ethyl-7-oxo-5,6-dihydrothieno[3,2-b]pyridine-4-carboxylate Chemical compound CC(C)OC(=O)N1C(CC)CC(=O)C2=C1C=CS2 NDNUMSSRCMHEKO-UHFFFAOYSA-N 0.000 description 1
- HUIIETPXPUSSKP-UHFFFAOYSA-N propan-2-yl 7-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-5-ethyl-6,7-dihydro-5h-thieno[3,2-b]pyridine-4-carboxylate Chemical compound C1=2SC=CC=2N(C(=O)OC(C)C)C(CC)CC1NCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HUIIETPXPUSSKP-UHFFFAOYSA-N 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
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- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero 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
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (4)
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| US557134P | 2004-03-26 | ||
| US62116204P | 2004-10-22 | 2004-10-22 | |
| US621162P | 2004-10-22 |
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| ES2326326T3 true ES2326326T3 (es) | 2009-10-07 |
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| ES05725968T Expired - Lifetime ES2326326T3 (es) | 2004-03-26 | 2005-03-17 | Compuestos y procedimientos para tratar la dislipidemia. |
| ES05732643T Expired - Lifetime ES2308477T3 (es) | 2004-03-26 | 2005-03-17 | Compuestos para el tratamiento de la dislipidemia. |
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| Application Number | Title | Priority Date | Filing Date |
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| ES05732643T Expired - Lifetime ES2308477T3 (es) | 2004-03-26 | 2005-03-17 | Compuestos para el tratamiento de la dislipidemia. |
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| EP (2) | EP1732933B1 (enExample) |
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| MA (1) | MA28550B1 (enExample) |
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| EP2098512A1 (en) * | 2003-10-08 | 2009-09-09 | Eli Lilly & Company | Compounds and methods for treating dyslipidemia |
| US20070208003A1 (en) * | 2004-03-26 | 2007-09-06 | Bell Michael G | Compounds and methods for treating dyslipidemia |
| MY139887A (en) | 2004-04-02 | 2009-11-30 | Mitsubishi Tanabe Pharma Corp | Tetrahydronaphthyridine derivatives and a process for preparing the same. |
| JP2008504266A (ja) | 2004-06-24 | 2008-02-14 | イーライ リリー アンド カンパニー | 異脂肪血症を治療するための化合物及び方法 |
| US7700774B2 (en) | 2004-12-20 | 2010-04-20 | Dr. Reddy's Laboratories Ltd. | Heterocyclic compounds and their pharmaceutical compositions |
| CA2605214C (en) | 2004-12-31 | 2016-07-12 | Reddy Us Therapeutics, Inc. | Benzylamine derivatives as cetp inhibitors |
| US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| JP4681526B2 (ja) * | 2005-09-29 | 2011-05-11 | 田辺三菱製薬株式会社 | 医薬組成物 |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| US7652023B2 (en) | 2005-11-23 | 2010-01-26 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| US7790770B2 (en) | 2005-11-23 | 2010-09-07 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| TW200808731A (en) | 2006-03-30 | 2008-02-16 | Tanabe Seiyaku Co | A process for preparing tetrahydroquinoline derivatives |
| AR069165A1 (es) | 2007-11-05 | 2010-01-06 | Novartis Ag | Derivados de 4-bencilamino-1-carboxacilpiperidina como inhibidores de cetp utiles para el tratamiento de hiperlipidemia |
| ES2425776T3 (es) | 2007-12-03 | 2013-10-17 | Novartis Ag | Derivados 1,2-disustituidos de 4-bencilamino-pirrolidina como inhibidores CETP útiles para el tratamiento de enfermedades tales como hiperlipidemia o arteriosclerosis |
| US8258306B2 (en) * | 2007-12-12 | 2012-09-04 | Amgen Inc. | Glycine transporter-1 inhibitors |
| WO2010110380A1 (ja) * | 2009-03-27 | 2010-09-30 | 興和株式会社 | 縮合ピペリジン化合物及びこれを含有する医薬 |
| BRPI1012852A2 (pt) | 2009-05-15 | 2018-06-19 | Novartis Ag | derivados de benzoxazolona como inibidores da sintase de aldoesterona |
| ES2459468T3 (es) | 2009-05-15 | 2014-05-09 | Novartis Ag | Arilpiridinas como inhibidores de aldosterona sintasa |
| ES2523734T3 (es) | 2009-05-28 | 2014-12-01 | Novartis Ag | Derivados aminopropiónicos sustituidos como inhibidores de neprilisina |
| EP3048100A1 (en) | 2009-05-28 | 2016-07-27 | Novartis AG | Substituted aminobutyric derivatives as neprilysin inhibitors |
| TWI450896B (zh) | 2009-06-30 | 2014-09-01 | Lilly Co Eli | 反式－４－〔〔（５ｓ）－５－〔〔〔３，５－雙（三氟甲基）苯基〕甲基〕（２－甲基－２ｈ－四唑－５－基）胺基〕－２，３，４，５－四氫－７，９－二甲基－１ｈ－１－苯并氮呯－１－基〕甲基〕－環己基羧酸 |
| WO2011061168A1 (en) | 2009-11-17 | 2011-05-26 | Novartis Ag | Aryl-pyridine derivatives as aldosterone synthase inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| JP5575913B2 (ja) | 2009-11-30 | 2014-08-20 | ノバルティス アーゲー | アルドステロン合成酵素阻害剤としてのイミダゾール誘導体 |
| CN102858347B (zh) * | 2010-02-24 | 2016-11-02 | 瑞立普萨公司 | 用作胆汁酸螯合剂的聚咪唑 |
| ES2764733T3 (es) | 2010-05-06 | 2020-06-04 | Alphacore Pharma Llc | Administración de esteres de colesterilo a tejidos esteroidogénicos |
| US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| BR112014000333A2 (pt) | 2011-07-08 | 2017-02-07 | Novartis Ag | método de tratamento de aterosclerose em sujeitos com triglicerídeo alto |
| JP5964965B2 (ja) | 2011-08-18 | 2016-08-03 | ドクター レディズ ラボラトリーズ リミテッド | コレステリルエステル転送タンパク質（ｃｅｔｐ）インヒビターとしての置換複素環式アミン化合物 |
| KR101803866B1 (ko) | 2011-09-27 | 2017-12-04 | 닥터 레디스 레보러터리즈 리미티드 | 동맥경화증 치료에 유용한 콜레스테릴 에스테르-전달 단백질(cetp) 억제제로서 5-벤질아미노메틸-6-아미노피라졸로[3,4-b]피리딘 유도체 |
| JO3210B1 (ar) | 2011-10-28 | 2018-03-08 | Merck Sharp & Dohme | مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة |
| EP2789347A4 (en) | 2011-11-29 | 2015-12-16 | Kowa Co | MEANS TO INHIBIT THE EXPRESSION OF NPC1L1 AND / OR LIPG-MRNA AND MEDICAMENTS FOR THE PREVENTION AND / OR TREATMENT OF ADIPOSITAS |
| UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
| CN105073762B (zh) | 2013-02-14 | 2017-03-08 | 诺华股份有限公司 | 作为nep(中性内肽酶)抑制剂的取代的联苯丁酰膦酸衍生物 |
| MX2016001021A (es) | 2013-07-25 | 2016-08-03 | Novartis Ag | Bioconjugados de polipeptidos de apelina sinteticos. |
| AU2014293386B2 (en) | 2013-07-25 | 2016-11-17 | Novartis Ag | Cyclic polypeptides for the treatment of heart failure |
| PE20171328A1 (es) | 2015-01-23 | 2017-09-12 | Novartis Ag | Conjugados de acidos grasos y apelina sintetica con mayor vida media |
| JOP20190086A1 (ar) | 2016-10-21 | 2019-04-18 | Novartis Ag | مشتقات نافثيريدينون جديدة واستخدامها في معالجة عدم انتظام ضربات القلب |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| AR127698A1 (es) | 2021-11-23 | 2024-02-21 | Novartis Ag | Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno |
| CN121219288A (zh) | 2023-05-24 | 2025-12-26 | 诺华股份有限公司 | 用于治疗疾病或障碍的萘啶酮衍生物 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1515540A (en) * | 1975-12-16 | 1978-06-28 | Labaz | 4-amino-trans-decahydroquinoline derivatives |
| DE19627430A1 (de) | 1996-07-08 | 1998-01-15 | Bayer Ag | Bicyclisch kondensierte Pyridine |
| DE19627431A1 (de) | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| US6207671B1 (en) | 1996-07-08 | 2001-03-27 | Bayer Aktiengesellschaft | Cycloalkano-pyridines |
| HRP970330B1 (en) | 1996-07-08 | 2004-06-30 | Bayer Ag | Cycloalkano pyridines |
| AU6279598A (en) * | 1997-02-18 | 1998-09-08 | Neurocrine Biosciences, Inc. | Biazacyclic CRF antagonists |
| DE19709125A1 (de) | 1997-03-06 | 1998-09-10 | Bayer Ag | Substituierte Chinoline |
| JPH10287662A (ja) | 1997-04-08 | 1998-10-27 | Kitasato Inst:The | Ｆｏ−５６３７ａ物質及びｂ物質並びにそれらの製造法 |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6147090A (en) | 1998-09-17 | 2000-11-14 | Pfizer Inc. | 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6147089A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6197786B1 (en) | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines |
| DE10148436A1 (de) | 2001-10-01 | 2003-04-17 | Bayer Ag | Tetrahydrochinoline |
| WO2003057671A1 (en) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Biaryl compound and use thereof |
| PL371416A1 (en) | 2002-02-01 | 2005-06-13 | Pfizer Products Inc. | Controlled release pharmaceutical dosage forms of a cholesteryl ester transfer protein inhibitor |
| JP2003321472A (ja) | 2002-02-26 | 2003-11-11 | Takeda Chem Ind Ltd | Ｇｒｋ阻害剤 |
| US7332514B2 (en) | 2002-08-30 | 2008-02-19 | Japan Tobacco Inc. | Dibenzylamine compound and medicinal use thereof |
| MXPA05003456A (es) * | 2002-10-04 | 2005-07-05 | Millennium Pharm Inc | Antagonistas del receptor de pgd2 para el tratamiento de enfermedades inflamatorias. |
| EP2098512A1 (en) * | 2003-10-08 | 2009-09-09 | Eli Lilly & Company | Compounds and methods for treating dyslipidemia |
| US20070208003A1 (en) | 2004-03-26 | 2007-09-06 | Bell Michael G | Compounds and methods for treating dyslipidemia |
| MY139887A (en) | 2004-04-02 | 2009-11-30 | Mitsubishi Tanabe Pharma Corp | Tetrahydronaphthyridine derivatives and a process for preparing the same. |
| JP2008504266A (ja) | 2004-06-24 | 2008-02-14 | イーライ リリー アンド カンパニー | 異脂肪血症を治療するための化合物及び方法 |
-
2005
- 2005-03-17 US US10/598,686 patent/US20070208003A1/en not_active Abandoned
- 2005-03-17 AU AU2005230915A patent/AU2005230915A1/en not_active Abandoned
- 2005-03-17 WO PCT/US2005/009294 patent/WO2005097805A1/en not_active Ceased
- 2005-03-17 EP EP05732643A patent/EP1732933B1/en not_active Expired - Lifetime
- 2005-03-17 AT AT05725968T patent/ATE433984T1/de not_active IP Right Cessation
- 2005-03-17 PL PL05732643T patent/PL1732933T3/pl unknown
- 2005-03-17 ES ES05725968T patent/ES2326326T3/es not_active Expired - Lifetime
- 2005-03-17 CA CA002557010A patent/CA2557010A1/en not_active Abandoned
- 2005-03-17 KR KR1020067019800A patent/KR20070007112A/ko not_active Ceased
- 2005-03-17 WO PCT/US2005/009301 patent/WO2005097806A1/en not_active Ceased
- 2005-03-17 JP JP2007505054A patent/JP2007530550A/ja active Pending
- 2005-03-17 PT PT05732643T patent/PT1732933E/pt unknown
- 2005-03-17 ES ES05732643T patent/ES2308477T3/es not_active Expired - Lifetime
- 2005-03-17 US US10/598,473 patent/US7470705B2/en not_active Expired - Fee Related
- 2005-03-17 BR BRPI0508966-2A patent/BRPI0508966A/pt not_active Application Discontinuation
- 2005-03-17 EA EA200601785A patent/EA200601785A1/ru unknown
- 2005-03-17 EP EP05725968A patent/EP1735320B1/en not_active Expired - Lifetime
- 2005-03-17 DE DE602005014955T patent/DE602005014955D1/de not_active Expired - Fee Related
- 2005-03-17 DK DK05732643T patent/DK1732933T3/da active
- 2005-03-17 AT AT05732643T patent/ATE402180T1/de not_active IP Right Cessation
- 2005-03-17 SI SI200530352T patent/SI1732933T1/sl unknown
- 2005-03-17 DE DE602005008416T patent/DE602005008416D1/de not_active Expired - Fee Related
-
2006
- 2006-09-07 IL IL177962A patent/IL177962A0/en unknown
- 2006-09-26 EC EC2006006886A patent/ECSP066886A/es unknown
- 2006-10-20 NO NO20064763A patent/NO20064763L/no not_active Application Discontinuation
- 2006-10-23 MA MA29410A patent/MA28550B1/fr unknown
-
2008
- 2008-09-24 CY CY20081101030T patent/CY1110398T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT1732933E (pt) | 2008-10-20 |
| US20070208003A1 (en) | 2007-09-06 |
| BRPI0508966A (pt) | 2007-08-21 |
| US7470705B2 (en) | 2008-12-30 |
| JP2007530550A (ja) | 2007-11-01 |
| PL1732933T3 (pl) | 2008-12-31 |
| IL177962A0 (en) | 2006-12-31 |
| SI1732933T1 (sl) | 2008-10-31 |
| EA200601785A1 (ru) | 2007-02-27 |
| DE602005008416D1 (de) | 2008-09-04 |
| EP1735320A1 (en) | 2006-12-27 |
| DK1732933T3 (da) | 2008-10-27 |
| NO20064763L (no) | 2006-11-22 |
| EP1732933A1 (en) | 2006-12-20 |
| ES2308477T3 (es) | 2008-12-01 |
| US20070173526A1 (en) | 2007-07-26 |
| WO2005097805A1 (en) | 2005-10-20 |
| ATE402180T1 (de) | 2008-08-15 |
| DE602005014955D1 (de) | 2009-07-30 |
| ECSP066886A (es) | 2006-11-24 |
| CA2557010A1 (en) | 2005-10-20 |
| EP1732933B1 (en) | 2008-07-23 |
| AU2005230915A1 (en) | 2005-10-20 |
| KR20070007112A (ko) | 2007-01-12 |
| EP1735320B1 (en) | 2009-06-17 |
| CY1110398T1 (el) | 2015-04-29 |
| MA28550B1 (fr) | 2007-04-03 |
| WO2005097806A1 (en) | 2005-10-20 |
| ATE433984T1 (de) | 2009-07-15 |
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