KR20010020472A - 새로운 타이로이드 수용체 리간드 및 방법 - Google Patents
새로운 타이로이드 수용체 리간드 및 방법 Download PDFInfo
- Publication number
- KR20010020472A KR20010020472A KR1019997012084A KR19997012084A KR20010020472A KR 20010020472 A KR20010020472 A KR 20010020472A KR 1019997012084 A KR1019997012084 A KR 1019997012084A KR 19997012084 A KR19997012084 A KR 19997012084A KR 20010020472 A KR20010020472 A KR 20010020472A
- Authority
- KR
- South Korea
- 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.)
- Ceased
Links
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- 239000003446 ligand Substances 0.000 title claims abstract description 12
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- 102000004217 thyroid hormone receptors Human genes 0.000 title claims abstract description 12
- -1 alkenyl carboxylic acid Chemical class 0.000 claims abstract description 53
- 150000002148 esters Chemical class 0.000 claims abstract description 26
- 150000002367 halogens Chemical class 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 208000003532 hypothyroidism Diseases 0.000 claims abstract description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 230000002989 hypothyroidism Effects 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 8
- 208000008589 Obesity Diseases 0.000 claims abstract description 8
- 235000020824 obesity Nutrition 0.000 claims abstract description 8
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 8
- 230000001105 regulatory effect Effects 0.000 claims abstract description 8
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 230000001419 dependent effect Effects 0.000 claims abstract description 6
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims abstract description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 206010018498 Goitre Diseases 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- 201000003872 goiter Diseases 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 33
- 239000005495 thyroid hormone Substances 0.000 claims description 17
- 229940036555 thyroid hormone Drugs 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 15
- 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 13
- 239000002253 acid Substances 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- QJSZKQGOEKSPPI-UHFFFAOYSA-N 3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)benzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Br)C(O)=O)Br)=C1 QJSZKQGOEKSPPI-UHFFFAOYSA-N 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 239000007795 chemical reaction product Substances 0.000 claims description 5
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 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
- 206010003119 arrhythmia Diseases 0.000 claims description 4
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 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 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 3
- FZZGVORNVZEJQR-UHFFFAOYSA-N 2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]propanoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Br)C(C)C(O)=O)Br)=C1 FZZGVORNVZEJQR-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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 description 3
- ZCAKHZRVFLSJSX-UHFFFAOYSA-N 2-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]propanoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)C(C)C(O)=O)Cl)=C1 ZCAKHZRVFLSJSX-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 description 3
- LOYIJBOTOWWLNE-UHFFFAOYSA-N 2-[3-chloro-4-(4-hydroxy-3-propan-2-ylphenoxy)-5-iodophenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Cl)I)=C1 LOYIJBOTOWWLNE-UHFFFAOYSA-N 0.000 claims description 3
- GMLYHVXTRJQWGY-UHFFFAOYSA-N 2-[3-chloro-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)Cl)=C1 GMLYHVXTRJQWGY-UHFFFAOYSA-N 0.000 claims description 3
- RMULTKUVQIIBQQ-UHFFFAOYSA-N 2-[3-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=2)Cl)=C1 RMULTKUVQIIBQQ-UHFFFAOYSA-N 0.000 claims description 3
- JQWXOLKWZBMICF-UHFFFAOYSA-N 2-[3-chloro-5-ethyl-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound CCC1=CC(CC(O)=O)=CC(Cl)=C1OC1=CC=C(O)C(C(C)C)=C1 JQWXOLKWZBMICF-UHFFFAOYSA-N 0.000 claims description 3
- SRMPBXOWXQCFBQ-UHFFFAOYSA-N 2-[3-ethyl-4-(4-hydroxy-3-propan-2-ylphenoxy)-5-methylphenyl]acetic acid Chemical compound CCC1=CC(CC(O)=O)=CC(C)=C1OC1=CC=C(O)C(C(C)C)=C1 SRMPBXOWXQCFBQ-UHFFFAOYSA-N 0.000 claims description 3
- CWCHTDVUZXHTLC-UHFFFAOYSA-N 2-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2C)C)=C1 CWCHTDVUZXHTLC-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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 claims description 3
- KOEJGQKJIIRANK-UHFFFAOYSA-N 4-[2,6-dibromo-4-(iodomethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CI)=CC=2Br)Br)=C1 KOEJGQKJIIRANK-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 3
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- 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 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
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| US11202789B2 (en) | 2016-11-21 | 2021-12-21 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
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| 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
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- 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
- 1998-06-26 CA CA002294098A patent/CA2294098C/en not_active Expired - Fee Related
- 1998-06-26 DK DK98935008T patent/DK1000008T3/da active
- 1998-06-26 WO PCT/EP1998/004039 patent/WO1999000353A1/en not_active Ceased
- 1998-06-26 JP JP50530199A patent/JP2002513422A/ja not_active Ceased
- 1998-06-26 EP EP98935008A patent/EP1000008B1/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11202789B2 (en) | 2016-11-21 | 2021-12-21 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
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| AU735525B2 (en) | 2001-07-12 |
| AU735525C (en) | 2002-02-21 |
| US6465687B1 (en) | 2002-10-15 |
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| 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 |
| ES2197486T3 (es) | 2004-01-01 |
| AU8440598A (en) | 1999-01-19 |
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