AU2010266537B2 - Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl] (2-methyl-2H-tetrazol-5-yl) amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid - Google Patents
Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl] (2-methyl-2H-tetrazol-5-yl) amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid Download PDFInfo
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- AU2010266537B2 AU2010266537B2 AU2010266537A AU2010266537A AU2010266537B2 AU 2010266537 B2 AU2010266537 B2 AU 2010266537B2 AU 2010266537 A AU2010266537 A AU 2010266537A AU 2010266537 A AU2010266537 A AU 2010266537A AU 2010266537 B2 AU2010266537 B2 AU 2010266537B2
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- Prior art keywords
- methyl
- dimethyl
- tetrahydro
- tetrazol
- amino
- 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.)
- Ceased
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- IHIUGIVXARLYHP-UXNJHFGPSA-N Evacetrapib Chemical compound C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2CC1CCC(C(O)=O)CC1 IHIUGIVXARLYHP-UXNJHFGPSA-N 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 36
- 239000002253 acid Substances 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 73
- 229910001868 water Inorganic materials 0.000 claims description 73
- 239000012453 solvate Substances 0.000 claims description 50
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 38
- 238000002360 preparation method Methods 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- -1 2-methyl-2H-tetrazol-5-yl Chemical group 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 13
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 13
- 238000001228 spectrum Methods 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 12
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- 125000000217 alkyl group Chemical group 0.000 claims description 11
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- SNDKWXRGPMCSQJ-AWQMOBFQSA-N O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 SNDKWXRGPMCSQJ-AWQMOBFQSA-N 0.000 claims description 10
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 7
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
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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 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 3
- IHIUGIVXARLYHP-YBXDKENTSA-N evacetrapib Chemical compound C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 IHIUGIVXARLYHP-YBXDKENTSA-N 0.000 claims description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-O tert-butylammonium Chemical compound CC(C)(C)[NH3+] YBRBMKDOPFTVDT-UHFFFAOYSA-O 0.000 claims description 3
- QLEFJNLJSVNIJQ-AWQMOBFQSA-N CC(O)=O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound CC(O)=O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 QLEFJNLJSVNIJQ-AWQMOBFQSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- UPVJTMAIFUGHSV-AWQMOBFQSA-N OC=O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound OC=O.C1([C@@H](N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C2=NN(C)N=N2)CCC2)=CC(C)=CC(C)=C1N2C[C@H]1CC[C@H](C(O)=O)CC1 UPVJTMAIFUGHSV-AWQMOBFQSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 68
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- 238000006243 chemical reaction Methods 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
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- BXWNLMCQIKFFQH-UHFFFAOYSA-N benzyl 7,9-dimethyl-5-oxo-3,4-dihydro-2h-1-benzazepine-1-carboxylate Chemical compound C1CCC(=O)C2=CC(C)=CC(C)=C2N1C(=O)OCC1=CC=CC=C1 BXWNLMCQIKFFQH-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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- CPCRUFNDQNKRHR-SANMLTNESA-N benzyl (5s)-5-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1-benzazepine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1CCCN(C2=C(C)C=C(C=C21)C)C(=O)OCC=1C=CC=CC=1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CPCRUFNDQNKRHR-SANMLTNESA-N 0.000 description 4
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- HXMJLMHSIJMKON-UHFFFAOYSA-N methyl 2-[(4-ethoxy-4-oxobutyl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3,5-dimethylbenzoate Chemical compound CCOC(=O)CCCN(C(=O)OC(C)(C)C)C1=C(C)C=C(C)C=C1C(=O)OC HXMJLMHSIJMKON-UHFFFAOYSA-N 0.000 description 4
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- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
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- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
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- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
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- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000000207 pro-atherogenic effect Effects 0.000 description 1
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- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
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- 239000000741 silica gel Substances 0.000 description 1
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- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- XTIVBOWLUYDHKE-UHFFFAOYSA-M sodium;cyclohexanecarboxylate Chemical compound [Na+].[O-]C(=O)C1CCCCC1 XTIVBOWLUYDHKE-UHFFFAOYSA-M 0.000 description 1
- XDFGPVSVSMWVQE-UHFFFAOYSA-M sodium;dodecanoic acid;hydrogen sulfate Chemical compound [Na+].OS([O-])(=O)=O.CCCCCCCCCCCC(O)=O XDFGPVSVSMWVQE-UHFFFAOYSA-M 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
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- 208000024891 symptom Diseases 0.000 description 1
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- 239000003826 tablet Substances 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000001107 thermogravimetry coupled to mass spectrometry Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22170809P | 2009-06-30 | 2009-06-30 | |
| US61/221,708 | 2009-06-30 | ||
| PCT/US2010/040125 WO2011002696A1 (en) | 2009-06-30 | 2010-06-28 | Trans-4-[[(5s)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl] (2-methyl-2h-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1h-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid |
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| AU2010266537A1 AU2010266537A1 (en) | 2012-02-02 |
| AU2010266537B2 true AU2010266537B2 (en) | 2013-04-18 |
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| AU2005267436A1 (en) * | 2004-06-24 | 2006-02-02 | Eli Lilly And Company | Compounds and methods for treating dyslipidemia |
| AR077208A1 (es) * | 2009-06-30 | 2011-08-10 | Lilly Co Eli | Derivados del acido trans-4-[[(5s)-5-[[[3,5-bis(trifluorometil) fenil] metil] (2-metil-2h-tetrazol-5-il) amino) -2,3,4,5-tetrahidro-7,9-dimetil-1h-1-benzazepin-1-il) metil)-ciclohexancarboxilico y sus formas cristalinas, composiciones farmaceuticas que los comprenden, su uso para preparar un medicam |
| ES2683350T3 (es) * | 2011-07-08 | 2018-09-26 | Novartis Ag | Método para tratar la aterosclerosis en sujetos con alto nivel de triglicéridos |
| WO2014012401A1 (zh) * | 2012-07-16 | 2014-01-23 | 上海恒瑞医药有限公司 | 苯并七元杂环类衍生物、其制备方法及其在医药上的应用 |
| WO2014119947A1 (en) | 2013-01-31 | 2014-08-07 | Chong Kun Dang Pharmaceutical Corp. | Biaryl- or heterocyclic biaryl-substituted cyclohexene derivative compounds as cetp inhibitors |
| CN105017085B (zh) * | 2014-04-28 | 2018-06-29 | 中国科学院上海药物研究所 | 一类kcnq钾通道激动剂、其制备方法和用途 |
| RU2703192C2 (ru) | 2014-07-30 | 2019-10-15 | Ф. Хоффманн-Ля Рош Аг | Генетические маркеры для прогнозирования ответа на терапию поднимающими уровень hdl или имитирующими hdl агентами |
| TWI691331B (zh) | 2014-09-26 | 2020-04-21 | 日商興和股份有限公司 | 脂質異常症治療劑 |
| CN108456213B (zh) * | 2017-02-22 | 2021-01-15 | 浙江九洲药业股份有限公司 | 一种3-氟-4-羟基环己烷羧酸酯的制备方法 |
| WO2025093129A1 (en) | 2023-11-01 | 2025-05-08 | Newamsterdam Pharma B.V. | Treatment and prevention of age-related macular degeneration using a cetp inhibitor |
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| WO2006002342A1 (en) * | 2004-06-24 | 2006-01-05 | Eli Lilly And Company | Compounds and methods for treating dyslipidemia |
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| JPS4948639B1 (https=) | 1970-12-15 | 1974-12-23 | ||
| US6197786B1 (en) | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-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 |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| CO5271716A1 (es) | 1999-11-30 | 2003-04-30 | Pfizer Prod Inc | Cristales de 4- carboxamino 1,2,3,4-tetrahidroquinolina 2- sustituida |
| HN2000000203A (es) * | 1999-11-30 | 2001-06-13 | Pfizer Prod Inc | Procedimiento para la obtencion de 1,2,3,4-tetrahidroquinolinas 4-carboxiamino-2- sustituidas. |
| ATE316957T1 (de) | 2001-04-30 | 2006-02-15 | Pfizer Prod Inc | Verbindungen verwendbar als zwischenprodukte für 4-aminochinolinderivate |
| BR0306208A (pt) | 2002-08-30 | 2004-10-13 | Japan Tobacco Inc | Compostos de dibenzilamina e seu uso farmacêutico |
| AU2003277285B2 (en) * | 2002-10-04 | 2007-12-13 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| JP2006523218A (ja) | 2003-03-04 | 2006-10-12 | 高砂香料工業株式会社 | 光学活性アミン類の製造方法 |
| US20040204450A1 (en) | 2003-03-28 | 2004-10-14 | Pfizer Inc | Quinoline and quinoxaline compounds |
| WO2005037796A1 (en) | 2003-10-08 | 2005-04-28 | Eli Lilly And Company | Compounds and methods for treating dyslipidemia |
| WO2005097805A1 (en) | 2004-03-26 | 2005-10-20 | Eli Lilly And Company | Compounds and methods for treating dyslipidemia |
| CN1972927A (zh) * | 2004-06-24 | 2007-05-30 | 伊莱利利公司 | 用于治疗血脂障碍的化合物和方法 |
| WO2006069162A1 (en) | 2004-12-20 | 2006-06-29 | Reddy Us Therapeutics, Inc. | Novel heterocyclic compounds and their pharmaceutical compositions |
| AR077208A1 (es) * | 2009-06-30 | 2011-08-10 | Lilly Co Eli | Derivados del acido trans-4-[[(5s)-5-[[[3,5-bis(trifluorometil) fenil] metil] (2-metil-2h-tetrazol-5-il) amino) -2,3,4,5-tetrahidro-7,9-dimetil-1h-1-benzazepin-1-il) metil)-ciclohexancarboxilico y sus formas cristalinas, composiciones farmaceuticas que los comprenden, su uso para preparar un medicam |
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| WO2006002342A1 (en) * | 2004-06-24 | 2006-01-05 | Eli Lilly And Company | Compounds and methods for treating dyslipidemia |
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