ES2197486T3 - Ligandos del receptor tiroideo. - Google Patents
Ligandos del receptor tiroideo.Info
- Publication number
- ES2197486T3 ES2197486T3 ES98935008T ES98935008T ES2197486T3 ES 2197486 T3 ES2197486 T3 ES 2197486T3 ES 98935008 T ES98935008 T ES 98935008T ES 98935008 T ES98935008 T ES 98935008T ES 2197486 T3 ES2197486 T3 ES 2197486T3
- Authority
- ES
- Spain
- Prior art keywords
- hydroxy
- isopropylphenoxy
- acid
- compound
- dibromo
- 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
Links
- 210000001685 thyroid gland Anatomy 0.000 title claims description 8
- -1 alkenyl carboxylic acid Chemical class 0.000 claims abstract description 103
- 238000000034 method Methods 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 208000003532 hypothyroidism Diseases 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 230000002989 hypothyroidism Effects 0.000 claims abstract description 9
- 239000003446 ligand Substances 0.000 claims abstract description 8
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 6
- 208000008589 Obesity Diseases 0.000 claims abstract description 6
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 235000020824 obesity Nutrition 0.000 claims abstract description 6
- 230000001105 regulatory effect Effects 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 5
- 230000001419 dependent effect Effects 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
- 239000005495 thyroid hormone Substances 0.000 claims description 29
- 229940036555 thyroid hormone Drugs 0.000 claims description 29
- 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 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 18
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- OKARMSOGGGWFDN-UHFFFAOYSA-N [3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]methylphosphonic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CP(O)(O)=O)=CC=2Br)Br)=C1 OKARMSOGGGWFDN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 230000004075 alteration Effects 0.000 claims description 3
- QEIMLVPITPFUIG-UHFFFAOYSA-N 2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetonitrile Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC#N)=CC=2Br)Br)=C1 QEIMLVPITPFUIG-UHFFFAOYSA-N 0.000 claims description 2
- DQLDGNUFEBSACT-UHFFFAOYSA-N 2-[3-bromo-4-(4-hydroxy-3-propan-2-ylphenoxy)-5-methylphenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2C)Br)=C1 DQLDGNUFEBSACT-UHFFFAOYSA-N 0.000 claims description 2
- GYDSAWQKNHDGMQ-UHFFFAOYSA-N 2-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenyl]acetonitrile Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC#N)=CC=2C)C)=C1 GYDSAWQKNHDGMQ-UHFFFAOYSA-N 0.000 claims description 2
- XNMACMIMVUWZRF-UHFFFAOYSA-N 4-[2,6-dichloro-4-(hydroxymethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CO)=CC=2Cl)Cl)=C1 XNMACMIMVUWZRF-UHFFFAOYSA-N 0.000 claims description 2
- NLVPRWUCENXJCF-UHFFFAOYSA-N 4-[2,6-dichloro-4-(iodomethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CI)=CC=2Cl)Cl)=C1 NLVPRWUCENXJCF-UHFFFAOYSA-N 0.000 claims description 2
- PWSMKMSJUYSIGD-UHFFFAOYSA-N 4-[4-(hydroxymethyl)-2,6-dimethylphenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CO)=CC=2C)C)=C1 PWSMKMSJUYSIGD-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- FDLOBNTWQDSHPF-UHFFFAOYSA-N 2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Br)Br)=C1 FDLOBNTWQDSHPF-UHFFFAOYSA-N 0.000 claims 1
- OZYQIQVPUZANTM-UHFFFAOYSA-N 2-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Cl)Cl)=C1 OZYQIQVPUZANTM-UHFFFAOYSA-N 0.000 claims 1
- CVKPBBUSVHRKRR-UHFFFAOYSA-N 2-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetonitrile Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC#N)=CC=2Cl)Cl)=C1 CVKPBBUSVHRKRR-UHFFFAOYSA-N 0.000 claims 1
- OQNYVSDHIHAEET-UHFFFAOYSA-N 2-[3-bromo-5-chloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Cl)Br)=C1 OQNYVSDHIHAEET-UHFFFAOYSA-N 0.000 claims 1
- TVQYCFFCYRSFQF-UHFFFAOYSA-N 3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)benzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)C(O)=O)Cl)=C1 TVQYCFFCYRSFQF-UHFFFAOYSA-N 0.000 claims 1
- UGEBMEYZKKASGB-UHFFFAOYSA-N 4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylbenzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2C)C(O)=O)C)=C1 UGEBMEYZKKASGB-UHFFFAOYSA-N 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 238000004821 distillation Methods 0.000 claims 1
- 230000002124 endocrine Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 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
- 108090000721 thyroid hormone receptors Proteins 0.000 abstract description 7
- 102000004217 thyroid hormone receptors Human genes 0.000 abstract description 7
- 208000001132 Osteoporosis Diseases 0.000 abstract description 4
- 206010018498 Goitre Diseases 0.000 abstract description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 abstract description 3
- 230000004064 dysfunction Effects 0.000 abstract description 3
- 201000003872 goiter Diseases 0.000 abstract description 2
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 150000001733 carboxylic acid esters Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 34
- 239000000203 mixture Substances 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 27
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 238000000605 extraction Methods 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 150000004702 methyl esters Chemical class 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 102000001708 Protein Isoforms Human genes 0.000 description 8
- 108010029485 Protein Isoforms Proteins 0.000 description 8
- 229940088597 hormone Drugs 0.000 description 8
- 239000005556 hormone Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- SSQJHTBDVVULTC-UHFFFAOYSA-N 4-[2,6-dibromo-4-(hydroxymethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CO)=CC=2Br)Br)=C1 SSQJHTBDVVULTC-UHFFFAOYSA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 229910052782 aluminium Inorganic materials 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- MDTLKWMKIKPPCU-UHFFFAOYSA-N 4-[2,6-dibromo-4-(bromomethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CBr)=CC=2Br)Br)=C1 MDTLKWMKIKPPCU-UHFFFAOYSA-N 0.000 description 3
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- 201000001320 Atherosclerosis Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 206010020850 Hyperthyroidism Diseases 0.000 description 3
- 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 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 206010003119 arrhythmia Diseases 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
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- 229910052740 iodine Inorganic materials 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- QOHGMEYPUKSMST-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)propanoate Chemical class COC(=O)C(C)C1=CC=C(O)C=C1 QOHGMEYPUKSMST-UHFFFAOYSA-N 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 230000001012 protector Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- BSWWXRFVMJHFBN-UHFFFAOYSA-N 2,4,6-tribromophenol Chemical compound OC1=C(Br)C=C(Br)C=C1Br BSWWXRFVMJHFBN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 description 2
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Classifications
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- C07C43/02—Ethers
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C07C65/24—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups polycyclic
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- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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Landscapes
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| WO2006128058A2 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
| US7420059B2 (en) | 2003-11-20 | 2008-09-02 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
| US7378426B2 (en) | 2004-03-01 | 2008-05-27 | Bristol-Myers Squibb Company | Fused heterotricyclic compounds as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
| US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
| US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| US7145040B2 (en) | 2004-07-02 | 2006-12-05 | Bristol-Myers Squibb Co. | Process for the preparation of amino acids useful in the preparation of peptide receptor modulators |
| TW200611704A (en) | 2004-07-02 | 2006-04-16 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions |
| US7534763B2 (en) | 2004-07-02 | 2009-05-19 | Bristol-Myers Squibb Company | Sustained release GLP-1 receptor modulators |
| EP1778220A1 (en) | 2004-07-12 | 2007-05-02 | Phenomix Corporation | Constrained cyano compounds |
| US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
| AR051446A1 (es) | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
| WO2006038719A1 (ja) * | 2004-10-08 | 2006-04-13 | Kotobuki Pharmaceutical Co., Ltd. | ホスホン酸誘導体及び血中の高リン酸が関与する疾患の治療剤 |
| US7517991B2 (en) | 2004-10-12 | 2009-04-14 | Bristol-Myers Squibb Company | N-sulfonylpiperidine cannabinoid receptor 1 antagonists |
| US7635699B2 (en) | 2004-12-29 | 2009-12-22 | Bristol-Myers Squibb Company | Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7589088B2 (en) | 2004-12-29 | 2009-09-15 | Bristol-Myers Squibb Company | Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7314882B2 (en) | 2005-01-12 | 2008-01-01 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| US7220859B2 (en) | 2005-01-12 | 2007-05-22 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| US7368458B2 (en) | 2005-01-12 | 2008-05-06 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| US7317024B2 (en) | 2005-01-13 | 2008-01-08 | Bristol-Myers Squibb Co. | Heterocyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| US20060160850A1 (en) | 2005-01-18 | 2006-07-20 | Chongqing Sun | Bicyclic heterocycles as cannabinoid receptor modulators |
| EP1846410B1 (en) | 2005-02-10 | 2009-01-21 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
| US20060235028A1 (en) | 2005-04-14 | 2006-10-19 | Li James J | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
| US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7825139B2 (en) | 2005-05-25 | 2010-11-02 | Forest Laboratories Holdings Limited (BM) | Compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| AU2006249347A1 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| WO2006128056A2 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphinic acid-containing thyromimetics |
| US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
| TW200726765A (en) | 2005-06-17 | 2007-07-16 | Bristol Myers Squibb Co | Triazolopyridine cannabinoid receptor 1 antagonists |
| US7632837B2 (en) | 2005-06-17 | 2009-12-15 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
| US7629342B2 (en) | 2005-06-17 | 2009-12-08 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
| US7452892B2 (en) | 2005-06-17 | 2008-11-18 | Bristol-Myers Squibb Company | Triazolopyrimidine cannabinoid receptor 1 antagonists |
| US7317012B2 (en) | 2005-06-17 | 2008-01-08 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoind-1 receptor modulators |
| RU2379295C2 (ru) * | 2005-07-21 | 2010-01-20 | Ф.Хоффманн-Ля Рош Аг | Производные пиридазинона в качестве агонистов рецептора тиреоидного гормона |
| US7795436B2 (en) | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
| AR056155A1 (es) | 2005-10-26 | 2007-09-19 | Bristol Myers Squibb Co | Antagonistas del receptor 1 de la hormona de concentracion de melanina no basica |
| WO2007053819A2 (en) | 2005-10-31 | 2007-05-10 | Bristol-Myers Squibb Company | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase iv and methods |
| US7592461B2 (en) | 2005-12-21 | 2009-09-22 | Bristol-Myers Squibb Company | Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
| EP2021014A1 (en) | 2006-05-26 | 2009-02-11 | Brystol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| US7919598B2 (en) | 2006-06-28 | 2011-04-05 | Bristol-Myers Squibb Company | Crystal structures of SGLT2 inhibitors and processes for preparing same |
| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| EA017925B1 (ru) | 2006-08-02 | 2013-04-30 | Цитокинетикс, Инкорпорэйтед | ПРОИЗВОДНЫЕ 1Н-ИМИДАЗО[4,5-b]ПИРАЗИНА |
| US7727978B2 (en) | 2006-08-24 | 2010-06-01 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| US7968577B2 (en) | 2006-11-01 | 2011-06-28 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| WO2008057857A1 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
| TW200904405A (en) | 2007-03-22 | 2009-02-01 | Bristol Myers Squibb Co | Pharmaceutical formulations containing an SGLT2 inhibitor |
| WO2008130951A1 (en) | 2007-04-17 | 2008-10-30 | Bristol-Myers Squibb Company | Fused heterocyclic 11-beta-hydroxysteroid dehydrogenase type i inhibitors |
| PE20090696A1 (es) | 2007-04-20 | 2009-06-20 | Bristol Myers Squibb Co | Formas cristalinas de saxagliptina y procesos para preparar las mismas |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| US20090011994A1 (en) | 2007-07-06 | 2009-01-08 | Bristol-Myers Squibb Company | Non-basic melanin concentrating hormone receptor-1 antagonists and methods |
| WO2009018065A2 (en) | 2007-07-27 | 2009-02-05 | Bristol-Myers Squibb Company | Novel glucokinase activators and methods of using same |
| CN101801954B (zh) | 2007-09-20 | 2013-10-09 | Irm责任有限公司 | 作为gpr119活性调节剂的化合物和组合物 |
| US8076334B2 (en) | 2007-09-20 | 2011-12-13 | Hoffmann-La Roche Inc. | Prodrugs of thyroid hormone analogs |
| EP2209780B1 (en) | 2007-11-01 | 2014-01-01 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and/or nf- kappa b activity and use thereof |
| PE20091928A1 (es) | 2008-05-29 | 2009-12-31 | Bristol Myers Squibb Co | Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| EA201101231A1 (ru) | 2009-03-27 | 2012-06-29 | Бристол-Майерс Сквибб Компани | Способы предотвращения или снижения риска смертности |
| WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| WO2011038207A1 (en) * | 2009-09-25 | 2011-03-31 | Metabasis Therapeutics, Inc. | Phosphorus-containing thyroid hormone receptor agonists and methods of use |
| JP2013507366A (ja) | 2009-10-09 | 2013-03-04 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性モジュレーターとしての化合物および組成物 |
| SMT201800564T1 (it) | 2009-11-13 | 2018-11-09 | Astrazeneca Ab | Formulazioni in compressa a rilascio immediato |
| BR112012011274A2 (pt) | 2009-11-13 | 2016-04-12 | Astrazeneca Uk Ltd | formulação de metformina de massa reduzida e sua combinação |
| ES2689107T3 (es) | 2009-11-13 | 2018-11-08 | Astrazeneca Ab | Formulaciones de tabletas bicapa |
| US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
| TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
| JP2013523894A (ja) | 2010-04-14 | 2013-06-17 | ブリストル−マイヤーズ スクイブ カンパニー | 新規グルコキナーゼアクチベーターおよびその使用方法 |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| TWI631963B (zh) | 2011-01-05 | 2018-08-11 | 雷西肯製藥股份有限公司 | 包含鈉－葡萄糖共同輸送體１與２之抑制劑的組合物與應用方法 |
| US9499482B2 (en) | 2012-09-05 | 2016-11-22 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
| US9586900B2 (en) | 2012-09-05 | 2017-03-07 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
| WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| DK2925735T3 (da) | 2012-11-20 | 2019-06-17 | Lexicon Pharmaceuticals Inc | Inhibitorer for natriumglucose-cotransporter 1 |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| US10092627B2 (en) | 2013-04-08 | 2018-10-09 | President And Fellows Of Harvard College | Methods and compositions for rejuvenating skeletal muscle stem cells |
| EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| US9593113B2 (en) | 2013-08-22 | 2017-03-14 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
| WO2017180988A2 (en) | 2016-04-15 | 2017-10-19 | Indiana University Research And Technology Corporation | Fgf21 c-terminal peptide optimization |
| HUE056357T2 (hu) * | 2016-05-18 | 2022-02-28 | Univ Oregon Health & Science | Szobetirom származékok |
| AU2017363206A1 (en) | 2016-11-21 | 2019-06-13 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
| EP3634426A4 (en) | 2017-06-05 | 2021-04-07 | Viking Therapeutics, Inc. | COMPOSITIONS FOR TREATMENT OF FIBROSE |
| WO2019119673A1 (zh) | 2017-12-19 | 2019-06-27 | 北京吉源生物科技有限公司 | 一种双基因修饰的干细胞及其用途 |
| MX2020009843A (es) | 2018-03-22 | 2020-12-11 | Viking Therapeutics Inc | Formas cristalinas y metodos de produccion de formas cristalinas de un compuesto. |
| MY210508A (en) | 2018-07-19 | 2025-09-28 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
| AU2019324405B2 (en) | 2018-08-23 | 2022-09-22 | Qingdao Rising Biotechnology Co., Ltd. | Phenoxy carboxylic acid compounds and medical uses thereof |
| CA3113037A1 (en) | 2018-09-26 | 2020-04-02 | Lexicon Pharmaceuticals, Inc. | Crystalline forms of n-(1-((2-(dimethylamino)ethyl)amino)-2-methyl-1-oopropan-2-yl)-4-(4-(2-methyl-5-(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2h-pyran-2-yl)benzyl)phenl)butanamide and methods of their synthesis |
| WO2020117962A1 (en) | 2018-12-05 | 2020-06-11 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
| AU2019397067A1 (en) * | 2018-12-12 | 2021-07-22 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| AU2020232205A1 (en) | 2019-03-01 | 2021-10-21 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| MX2021015468A (es) | 2019-06-27 | 2022-01-24 | Cytokinetics Inc | Polimorfos de 1-(2-((((trans)-3-fluoro-1-(3-fluoropiridin-2-il)cic lobutil)metil)amino)pirimidin-5-il)-1h-pirrol-3-carboxamida. |
| US12466781B2 (en) | 2019-11-29 | 2025-11-11 | Autobahn Therapeutics, Inc. | Thyromimetics |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1072998B (de) * | 1957-08-21 | 1960-01-14 | Farbwerke Hoechst Aktiengesellschaft vormals Meister Lucius &. Brüning, Frankfurt/M | Verfahren zur Herstellung von substituierten Diphenyläthern |
| DE1078582B (de) * | 1958-10-29 | 1960-03-31 | Hoechst Ag | Verfahren zur Herstellung substituierter Thyropropionsaeuren |
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1997
- 1997-06-27 GB GBGB9713739.2A patent/GB9713739D0/en not_active Ceased
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1998
- 1998-06-26 KR KR1019997012084A patent/KR20010020472A/ko not_active Ceased
- 1998-06-26 DE DE69815852T patent/DE69815852T2/de not_active Expired - Fee Related
- 1998-06-26 AT AT98935008T patent/ATE243672T1/de not_active IP Right Cessation
- 1998-06-26 US US09/445,888 patent/US6465687B1/en not_active Expired - Fee Related
- 1998-06-26 PT PT98935008T patent/PT1000008E/pt unknown
- 1998-06-26 AU AU84405/98A patent/AU735525C/en not_active Ceased
- 1998-06-26 ES ES98935008T patent/ES2197486T3/es not_active Expired - Lifetime
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- 1998-06-26 EP EP98935008A patent/EP1000008B1/en not_active Expired - Lifetime
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| AU735525C (en) | 2002-02-21 |
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| DE69815852D1 (de) | 2003-07-31 |
| ATE243672T1 (de) | 2003-07-15 |
| GB9713739D0 (en) | 1997-09-03 |
| EP1000008B1 (en) | 2003-06-25 |
| JP2002513422A (ja) | 2002-05-08 |
| CA2294098A1 (en) | 1999-01-07 |
| EP1000008A1 (en) | 2000-05-17 |
| PT1000008E (pt) | 2003-10-31 |
| CA2294098C (en) | 2009-02-10 |
| DE69815852T2 (de) | 2004-05-19 |
| WO1999000353A1 (en) | 1999-01-07 |
| DK1000008T3 (da) | 2003-10-20 |
| AU8440598A (en) | 1999-01-19 |
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