DE69924846T2 - Thyroidhormon-analoga und verfahren zu ihrer herstellung - Google Patents
Thyroidhormon-analoga und verfahren zu ihrer herstellung Download PDFInfo
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- DE69924846T2 DE69924846T2 DE69924846T DE69924846T DE69924846T2 DE 69924846 T2 DE69924846 T2 DE 69924846T2 DE 69924846 T DE69924846 T DE 69924846T DE 69924846 T DE69924846 T DE 69924846T DE 69924846 T2 DE69924846 T2 DE 69924846T2
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- Prior art keywords
- compound
- hydrogen
- alkyl
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- mmol
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- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 title claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 238000000034 method Methods 0.000 title abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 325
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- -1 C 5-12 alkenol Chemical group 0.000 claims description 43
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000006239 protecting group Chemical group 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 239000005495 thyroid hormone Substances 0.000 claims description 18
- 229940036555 thyroid hormone Drugs 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 239000005557 antagonist Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 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 description 8
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 206010020850 Hyperthyroidism Diseases 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 92
- 238000006243 chemical reaction Methods 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 42
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 41
- 239000002904 solvent Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 238000002390 rotary evaporation Methods 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- 239000000460 chlorine Substances 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 229920006395 saturated elastomer Polymers 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 108090000721 thyroid hormone receptors Proteins 0.000 description 24
- 102000004217 thyroid hormone receptors Human genes 0.000 description 24
- 229960003742 phenol Drugs 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012267 brine Substances 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 239000002253 acid Substances 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- 230000027455 binding Effects 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000007796 conventional method Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 239000007983 Tris buffer Substances 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 10
- 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 10
- 239000012442 inert solvent Substances 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 9
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 9
- 108700008625 Reporter Genes Proteins 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 102000006255 nuclear receptors Human genes 0.000 description 9
- 108020004017 nuclear receptors Proteins 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 7
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 0 CC1(C(O)=C(C(*)c2c(*)cc(C)cc2I=O)C(*)=C(*)C1O)O Chemical compound CC1(C(O)=C(C(*)c2c(*)cc(C)cc2I=O)C(*)=C(*)C1O)O 0.000 description 7
- 239000005089 Luciferase Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 239000006188 syrup Substances 0.000 description 7
- 235000020357 syrup Nutrition 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 6
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
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- RLBVVOLDXFINKU-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-propan-2-ylphenyl)methoxy]-1,3-dimethylbenzene Chemical compound CC1=CC(OC)=CC(C)=C1OCC1=CC=C(OC)C(C(C)C)=C1 RLBVVOLDXFINKU-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- HYWCXWRMUZYRPH-UHFFFAOYSA-N trimethyl(prop-2-enyl)silane Chemical compound C[Si](C)(C)CC=C HYWCXWRMUZYRPH-UHFFFAOYSA-N 0.000 description 5
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
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- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
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- 125000004093 cyano group Chemical group *C#N 0.000 description 4
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- 238000002955 isolation Methods 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
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- NNZRVXTXKISCGS-UHFFFAOYSA-N 1-methoxy-2-propan-2-ylbenzene Chemical compound COC1=CC=CC=C1C(C)C NNZRVXTXKISCGS-UHFFFAOYSA-N 0.000 description 3
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- CFNMTRKNNCKHBM-UHFFFAOYSA-N 4-bromo-1-methoxy-2-propan-2-ylbenzene Chemical compound COC1=CC=C(Br)C=C1C(C)C CFNMTRKNNCKHBM-UHFFFAOYSA-N 0.000 description 3
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
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- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
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- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
-
- 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
- C07C69/67—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 saturated acids
- C07C69/708—Ethers
- C07C69/712—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
-
- 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
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/16—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- 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
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
- C07C59/70—Ethers of hydroxy-acetic acid, e.g. substitutes on the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9118598P | 1998-06-30 | 1998-06-30 | |
| US91185P | 1998-06-30 | ||
| PCT/US1999/014627 WO2000000468A1 (en) | 1998-06-30 | 1999-06-28 | Thyroid hormone analogues and methods for their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69924846D1 DE69924846D1 (de) | 2005-05-25 |
| DE69924846T2 true DE69924846T2 (de) | 2006-04-27 |
Family
ID=22226506
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69924846T Expired - Lifetime DE69924846T2 (de) | 1998-06-30 | 1999-06-28 | Thyroidhormon-analoga und verfahren zu ihrer herstellung |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6107517A (enExample) |
| EP (2) | EP1598334A1 (enExample) |
| JP (1) | JP2002519340A (enExample) |
| KR (1) | KR20010053277A (enExample) |
| AT (1) | ATE293595T1 (enExample) |
| AU (1) | AU4840199A (enExample) |
| CA (1) | CA2335551C (enExample) |
| DE (1) | DE69924846T2 (enExample) |
| DK (1) | DK1089968T3 (enExample) |
| ES (1) | ES2241294T3 (enExample) |
| IL (1) | IL140140A0 (enExample) |
| PT (1) | PT1089968E (enExample) |
| WO (1) | WO2000000468A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5883294A (en) * | 1997-06-18 | 1999-03-16 | The Regeants Of The University Of California | Selective thyroid hormone analogs |
| US6680344B1 (en) | 1999-06-01 | 2004-01-20 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using diphenylmethane derivatives |
| WO2000072813A1 (en) * | 1999-06-01 | 2000-12-07 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using diphenylmethane derivatives |
| AR018699A1 (es) | 1999-06-01 | 2001-11-28 | Procter & Gamble | Metodo para el tratamiento de la perdida del cabello el cual comprende administrar una composicion que comprende un compuesto el cual no afecta al corazon |
| 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 |
| WO2002056880A1 (en) * | 2001-01-19 | 2002-07-25 | Cytokinetics, Inc. | Triphenylmethane kinesin inhibitors |
| US7302347B2 (en) * | 2002-12-10 | 2007-11-27 | The Regents Of The University Of California | Method for creating specific, high affinity nuclear receptor pharmaceuticals |
| SE526033C3 (sv) * | 2003-11-06 | 2009-12-08 | Metso Paper Inc | Silanordning och silkorg för silning av massasuspensioner |
| CA2546601A1 (en) | 2003-11-19 | 2005-06-09 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| US20090232879A1 (en) | 2005-05-26 | 2009-09-17 | Metabasis Therapeutics, Inc. | Thyromimetics for the Treatment of Fatty Liver Diseases |
| RU2007148927A (ru) * | 2005-05-26 | 2009-07-10 | Метабэйзис Терапьютикс, Инк. (Us) | Новые тиреомиметики, содержащие фосфиновую кислоту |
| US20060292194A1 (en) * | 2005-06-24 | 2006-12-28 | Thomas Lavin | Treatment for burns and adipose deposits using thyroid hormone compound in a human |
| JP2016517883A (ja) | 2013-05-03 | 2016-06-20 | オレゴン ヘルス アンド サイエンス ユニバーシティー | Ｘ連鎖副腎白質ジストロフィーの処置におけるソベチロムの使用 |
| KR102331596B1 (ko) * | 2016-05-18 | 2021-11-25 | 오레곤 헬스 앤드 사이언스 유니버시티 | 소베티롬의 유도체 |
| JP2020500199A (ja) | 2016-11-21 | 2020-01-09 | バイキング・セラピューティクス・インコーポレイテッド | グリコーゲン蓄積症の治療方法 |
| AU2018280118B2 (en) | 2017-06-05 | 2021-07-15 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
| EA202091979A1 (ru) | 2018-03-22 | 2021-06-22 | Вайкинг Терапьютикс, Инк. | Кристаллические формы и способы получения кристаллических форм соединения |
| US12102646B2 (en) | 2018-12-05 | 2024-10-01 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
| CA3122996A1 (en) | 2018-12-12 | 2020-06-18 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| EP3931180A1 (en) | 2019-03-01 | 2022-01-05 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| KR20220121239A (ko) | 2019-11-29 | 2022-08-31 | 아우토반 쎄라퓨틱스, 인크. | 신규한 갑상선 호르몬 모방제 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3332957A (en) * | 1964-09-02 | 1967-07-25 | Ciba Geigy Corp | Amino esters of substituted phenoxy acetic acids |
| JPS5195049A (en) * | 1975-02-12 | 1976-08-20 | * **********so*****no***tsu*****************************************ni*no | |
| US4323691A (en) * | 1979-10-09 | 1982-04-06 | Abbott Laboratories | Hydroxyaminomethyl derivatives of benzoyl di-substituted α-phenoxyalkanoyl esters |
| US5883294A (en) * | 1997-06-18 | 1999-03-16 | The Regeants Of The University Of California | Selective thyroid hormone analogs |
-
1999
- 1999-06-28 EP EP05008536A patent/EP1598334A1/en not_active Withdrawn
- 1999-06-28 EP EP99932002A patent/EP1089968B1/en not_active Expired - Lifetime
- 1999-06-28 CA CA002335551A patent/CA2335551C/en not_active Expired - Fee Related
- 1999-06-28 AT AT99932002T patent/ATE293595T1/de not_active IP Right Cessation
- 1999-06-28 ES ES99932002T patent/ES2241294T3/es not_active Expired - Lifetime
- 1999-06-28 IL IL14014099A patent/IL140140A0/xx unknown
- 1999-06-28 WO PCT/US1999/014627 patent/WO2000000468A1/en not_active Ceased
- 1999-06-28 JP JP2000557229A patent/JP2002519340A/ja not_active Withdrawn
- 1999-06-28 KR KR1020007014984A patent/KR20010053277A/ko not_active Withdrawn
- 1999-06-28 PT PT99932002T patent/PT1089968E/pt unknown
- 1999-06-28 DK DK99932002T patent/DK1089968T3/da active
- 1999-06-28 DE DE69924846T patent/DE69924846T2/de not_active Expired - Lifetime
- 1999-06-28 AU AU48401/99A patent/AU4840199A/en not_active Abandoned
- 1999-06-30 US US09/345,673 patent/US6107517A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU4840199A (en) | 2000-01-17 |
| EP1089968A4 (en) | 2002-08-21 |
| ES2241294T3 (es) | 2005-10-16 |
| CA2335551C (en) | 2009-03-03 |
| ATE293595T1 (de) | 2005-05-15 |
| IL140140A0 (en) | 2002-02-10 |
| EP1598334A1 (en) | 2005-11-23 |
| DE69924846D1 (de) | 2005-05-25 |
| DK1089968T3 (da) | 2005-08-22 |
| EP1089968A1 (en) | 2001-04-11 |
| JP2002519340A (ja) | 2002-07-02 |
| KR20010053277A (ko) | 2001-06-25 |
| WO2000000468A1 (en) | 2000-01-06 |
| EP1089968B1 (en) | 2005-04-20 |
| US6107517A (en) | 2000-08-22 |
| PT1089968E (pt) | 2005-08-31 |
| CA2335551A1 (en) | 2000-01-06 |
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| Date | Code | Title | Description |
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| 8364 | No opposition during term of opposition |