JP5081161B2 - ファルネソイドｘ受容体アゴニスト - Google Patents
ファルネソイドｘ受容体アゴニスト Download PDFInfo
- Publication number
- JP5081161B2 JP5081161B2 JP2008545947A JP2008545947A JP5081161B2 JP 5081161 B2 JP5081161 B2 JP 5081161B2 JP 2008545947 A JP2008545947 A JP 2008545947A JP 2008545947 A JP2008545947 A JP 2008545947A JP 5081161 B2 JP5081161 B2 JP 5081161B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- compound
- formula
- dichlorophenyl
- isoxazolyl
- 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.)
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- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 274
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 18
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- TUOXXRMLFZBSTB-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl TUOXXRMLFZBSTB-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- ZHXAPIVBWDJTLN-UHFFFAOYSA-N 6-[4-[[3-[(2,6-dichlorophenyl)methyl]-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1CC1=C(Cl)C=CC=C1Cl ZHXAPIVBWDJTLN-UHFFFAOYSA-N 0.000 claims description 6
- KTLMJKKEKJASFK-UHFFFAOYSA-N 6-[4-[[3-[2-(2,6-dichlorophenyl)ethyl]-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1CCC1=C(Cl)C=CC=C1Cl KTLMJKKEKJASFK-UHFFFAOYSA-N 0.000 claims description 6
- MPCDMRMAXXSILO-UHFFFAOYSA-N 6-[4-[[5-cyclobutyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C2C(C(=O)O)=CC=CC2=CC=1C(C=C1)=CC=C1OCC1=C(C2CCC2)ON=C1C1=C(Cl)C=CC=C1Cl MPCDMRMAXXSILO-UHFFFAOYSA-N 0.000 claims description 6
- KVNUJCGFGCPUOA-UHFFFAOYSA-N 7-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C(C(O)=O)=CC=CC3=CC=2)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl KVNUJCGFGCPUOA-UHFFFAOYSA-N 0.000 claims description 6
- GSTNOFVRIRGPDE-UHFFFAOYSA-N 7-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-2-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=C(C=CC3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl GSTNOFVRIRGPDE-UHFFFAOYSA-N 0.000 claims description 6
- YEOXFVQGKAJALY-UHFFFAOYSA-N 7-[4-[[3-[2-(2,6-dichlorophenyl)ethyl]-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C(C(O)=O)=CC=CC3=CC=2)C=CC=1OCC1=C(C(C)C)ON=C1CCC1=C(Cl)C=CC=C1Cl YEOXFVQGKAJALY-UHFFFAOYSA-N 0.000 claims description 6
- MXNUTDJISLUBCR-UHFFFAOYSA-N 7-[4-[[3-[2-(2,6-dichlorophenyl)ethyl]-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-2-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=C(C=CC3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1CCC1=C(Cl)C=CC=C1Cl MXNUTDJISLUBCR-UHFFFAOYSA-N 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- DVZSPFZSZKKWIK-UHFFFAOYSA-N 6-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(O)=O)C(Cl)=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl DVZSPFZSZKKWIK-UHFFFAOYSA-N 0.000 claims description 5
- LSKNUTNLADXZFJ-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylic acid Chemical compound OCC(N)(CO)CO.C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl LSKNUTNLADXZFJ-UHFFFAOYSA-N 0.000 claims description 4
- KNQWLANNMODPOI-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-propan-2-yl-4-[[4-[5-(2h-tetrazol-5-yl)naphthalen-2-yl]phenoxy]methyl]-1,2-oxazole Chemical compound CC(C)C=1ON=C(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1)=CC=C1C(C=C1C=CC=2)=CC=C1C=2C1=NN=NN1 KNQWLANNMODPOI-UHFFFAOYSA-N 0.000 claims description 4
- NWFKPERKLYEWII-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carbonitrile Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C#N)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl NWFKPERKLYEWII-UHFFFAOYSA-N 0.000 claims description 4
- FMCUKPUIJFXDAZ-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxamide Chemical compound C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C(N)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl FMCUKPUIJFXDAZ-UHFFFAOYSA-N 0.000 claims description 4
- ZGRHLDTXNJVJLX-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-2-carboxylic acid Chemical compound C=1C=C(C=2C=C3C=CC(=CC3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl ZGRHLDTXNJVJLX-UHFFFAOYSA-N 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- XHGMGDRRDBNXIR-UHFFFAOYSA-M sodium;6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-1-carboxylate Chemical compound [Na+].C=1C=C(C=2C=C3C=CC=C(C3=CC=2)C([O-])=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl XHGMGDRRDBNXIR-UHFFFAOYSA-M 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- NBYFMFAXGSZXDW-UHFFFAOYSA-N methyl 6-[4-[[3-[2-(2,6-dichlorophenyl)ethyl]-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]naphthalene-2-carboxylate Chemical compound C1=CC2=CC(C(=O)OC)=CC=C2C=C1C(C=C1)=CC=C1OCC(=C(ON=1)C(C)C)C=1CCC1=C(Cl)C=CC=C1Cl NBYFMFAXGSZXDW-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 75
- 239000008194 pharmaceutical composition Chemical class 0.000 abstract description 24
- 230000008569 process Effects 0.000 abstract description 5
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 150000002545 isoxazoles Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
- 239000000243 solution Substances 0.000 description 137
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 106
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000000203 mixture Substances 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 102100038495 Bile acid receptor Human genes 0.000 description 48
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 48
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- 238000011282 treatment Methods 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- 239000007787 solid Substances 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 206010016654 Fibrosis Diseases 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
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- 238000006243 chemical reaction Methods 0.000 description 27
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
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- 208000019425 cirrhosis of liver Diseases 0.000 description 21
- 239000012267 brine Substances 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 241000282412 Homo Species 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 18
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- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 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 16
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 8
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- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Child & Adolescent Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75159705P | 2005-12-19 | 2005-12-19 | |
| US60/751,597 | 2005-12-19 | ||
| PCT/US2006/061966 WO2007076260A2 (en) | 2005-12-19 | 2006-12-13 | Farnesoid x receptor agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009519965A JP2009519965A (ja) | 2009-05-21 |
| JP2009519965A5 JP2009519965A5 (https=) | 2009-09-10 |
| JP5081161B2 true JP5081161B2 (ja) | 2012-11-21 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2008545947A Active JP5081161B2 (ja) | 2005-12-19 | 2006-12-13 | ファルネソイドｘ受容体アゴニスト |
Country Status (6)
| Country | Link |
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| US (2) | US7705028B2 (https=) |
| EP (1) | EP1962838B1 (https=) |
| JP (1) | JP5081161B2 (https=) |
| AT (1) | ATE526318T1 (https=) |
| ES (1) | ES2374165T3 (https=) |
| WO (1) | WO2007076260A2 (https=) |
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| CA2640476A1 (en) * | 2006-02-03 | 2007-08-16 | Eli Lilly And Company | Compounds and methods for modulating fx-receptors |
| CL2007003035A1 (es) * | 2006-10-24 | 2008-05-16 | Smithkline Beechman Corp | Compuestos derivados de isoxazol sustituidos, agonistas de receptores farnesoid x; procedimiento de preparacion; composicion farmaceutica que lo comprende; y uso del compuesto en el tratamiento de la obesidad, diabetes mellitus, fibrosis en organos, |
| US7943619B2 (en) | 2007-12-04 | 2011-05-17 | Hoffmann-La Roche Inc. | Isoxazolo-pyridazine derivatives |
| KR101175859B1 (ko) | 2007-12-04 | 2012-08-24 | 에프. 호프만-라 로슈 아게 | 이속사졸로-피라진 유도체 |
| US7902201B2 (en) | 2007-12-04 | 2011-03-08 | Hoffmann-La Roche Inc. | Isoxazolo-pyrazine derivatives |
| CA2744817C (en) * | 2008-11-26 | 2020-07-07 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of obesity and diabetes |
| TW201033201A (en) | 2009-02-19 | 2010-09-16 | Hoffmann La Roche | Isoxazole-isoxazole and isoxazole-isothiazole derivatives |
| US8389550B2 (en) | 2009-02-25 | 2013-03-05 | Hoffmann-La Roche Inc. | Isoxazoles / O-pyridines with ethyl and ethenyl linker |
| US8222246B2 (en) | 2009-04-02 | 2012-07-17 | Hoffmann-La Roche Inc. | Substituted isoxazoles |
| US20100280019A1 (en) | 2009-04-30 | 2010-11-04 | Roland Jakob-Roetne | Isoxazoles |
| JP5460858B2 (ja) | 2009-05-05 | 2014-04-02 | エフ．ホフマン−ラ ロシュ アーゲー | イソオキサゾール−ピラゾール誘導体 |
| CA2759598C (en) | 2009-05-05 | 2017-09-12 | F. Hoffmann-La Roche Ag | Isoxazole-thiazole derivatives as gaba a receptor inverse agonists for use in the treatment of cognitive disorders |
| KR101367012B1 (ko) | 2009-05-05 | 2014-03-14 | 에프. 호프만-라 로슈 아게 | 이속사졸-피리딘 유도체 |
| CA2760597C (en) | 2009-05-05 | 2017-08-22 | F. Hoffmann-La Roche Ag | Isoxazole-pyridazine derivatives |
| BRPI1013766A2 (pt) | 2009-05-07 | 2016-04-05 | Hoffmann La Roche | "derivados de isoxazol-piridina como moduladores de gaba" |
| EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| EP2575821B1 (en) | 2010-05-26 | 2015-08-12 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
| US8785435B2 (en) | 2011-10-20 | 2014-07-22 | Hoffmann-La Roche Inc. | Solid forms |
| CA2852957C (en) | 2011-10-28 | 2020-08-04 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
| CN104023727B (zh) | 2011-10-28 | 2017-04-05 | 鲁美纳医药公司 | 用于治疗小儿胆汁淤积性肝病的胆汁酸再循环抑制剂 |
| US20140275090A1 (en) | 2013-03-15 | 2014-09-18 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease |
| CN105228615A (zh) | 2013-03-15 | 2016-01-06 | 鲁美纳医药公司 | 用于治疗巴雷特食管和胃食管返流疾病的胆汁酸再循环抑制剂 |
| DK3043865T3 (da) | 2013-09-11 | 2021-02-01 | Univ Claude Bernard Lyon | Fremgangsmåder og farmaceutiske sammensætningr til behandlingen af hepatitis b-virusinfektion |
| KR102515248B1 (ko) | 2013-11-22 | 2023-03-29 | 사브레 테라퓨틱스 엘엘씨 | 오토탁신 억제제 화합물 |
| CN104045635A (zh) * | 2014-06-23 | 2014-09-17 | 华东理工大学 | 3,4,5-三取代异恶唑类化合物及其用途 |
| EP3006939A1 (en) | 2014-10-06 | 2016-04-13 | Gilead Sciences, Inc. | Histidine-rich Glycoprotein as a marker for hepatic Farnesoid X receptor activation |
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| EP3034499A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Novel FXR (NR1H4) modulating compounds |
| EP3034501A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
| TWI698430B (zh) | 2015-02-13 | 2020-07-11 | 南北兄弟藥業投資有限公司 | 三環化合物及其在藥物中的應用 |
| WO2016161003A1 (en) | 2015-03-31 | 2016-10-06 | Enanta Phamraceuticals, Inc. | Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
| US10894054B2 (en) | 2015-04-07 | 2021-01-19 | Intercept Pharmaceuticals, Inc. | FXR agonist compositions for combination therapy |
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| WO2017189663A1 (en) * | 2016-04-26 | 2017-11-02 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
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| BR112018073460A2 (pt) * | 2016-05-25 | 2019-07-09 | Akarna Therapeutics Ltd | terapias combinadas usando moduladores do receptor farnesoide x (fxr) |
| US10772813B2 (en) | 2016-06-03 | 2020-09-15 | Colradel, LLC | Compositions and methods of administering a colchicine based topical composition for the prevention of radiation fibrosis |
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| US10450306B2 (en) | 2016-10-04 | 2019-10-22 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as FXR agonists and methods of use thereof |
| WO2018081285A1 (en) | 2016-10-26 | 2018-05-03 | Enanta Pharmaceuticals, Inc. | Urea-containing isoxazole derivatives as fxr agonists and methods of use thereof |
| PT3600309T (pt) | 2017-03-28 | 2022-10-03 | Gilead Sciences Inc | Combinações terapêuticas para o tratamento de doenças hepáticas |
| WO2018178260A1 (en) | 2017-03-30 | 2018-10-04 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for reducing persistence and expression of episomal viruses |
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| PE20201170A1 (es) | 2017-11-01 | 2020-10-28 | Bristol Myers Squibb Co | Compuestos biciclicos en puente como moduladores del receptor farnesoide x |
| AU2018360575A1 (en) * | 2017-11-01 | 2020-06-18 | Bristol-Myers Squibb Company | Alkene spirocyclic compounds as farnesoid X receptor modulators |
| KR102731924B1 (ko) | 2017-11-01 | 2024-11-19 | 브리스톨-마이어스 스큅 컴퍼니 | 파르네소이드 x 수용체 조정제로서의 스피로시클릭 화합물 |
| CN111278817B (zh) | 2017-11-01 | 2023-05-16 | 百时美施贵宝公司 | 作为法尼醇x受体调节剂的多环化合物 |
| CN111511731B (zh) | 2017-11-01 | 2023-05-23 | 百时美施贵宝公司 | 作为法尼醇x受体调节剂的烯烃化合物 |
| WO2019118571A1 (en) | 2017-12-12 | 2019-06-20 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as fxr agonists and methods of use thereof |
| CN110128432B (zh) | 2018-02-02 | 2021-03-02 | 广东东阳光药业有限公司 | 含氮三环化合物及其在药物中的应用 |
| US10829486B2 (en) | 2018-02-14 | 2020-11-10 | Enanta Pharmacueticals, Inc. | Isoxazole derivatives as FXR agonists and methods of use thereof |
| EP3911647B1 (en) | 2019-01-15 | 2023-12-13 | Gilead Sciences, Inc. | Isoxazole compound as fxr agonist and pharmaceutical compositions comprising same |
| PL3923943T3 (pl) | 2019-02-12 | 2024-12-09 | Mirum Pharmaceuticals, Inc. | Zależna od genotypu i dawki odpowiedź na asbti u pacjentów z niedoborem pompy eksportu soli żółciowych |
| AU2020221371A1 (en) | 2019-02-15 | 2021-10-07 | Bristol-Myers Squibb Company | Substituted amide compounds useful as farnesoid x receptor modulators |
| CN113727973B (zh) | 2019-02-15 | 2025-08-29 | 百时美施贵宝公司 | 可用作类法尼醇x受体调节剂的取代酰胺化合物 |
| JP7465883B2 (ja) | 2019-02-15 | 2024-04-11 | ブリストル－マイヤーズ スクイブ カンパニー | ファルネソイドｘ受容体モジュレータとしての置換二環式化合物 |
| AR118050A1 (es) | 2019-02-15 | 2021-09-15 | Bristol Myers Squibb Co | Compuestos bicíclicos sustituidos como moduladores del receptor farnesoide x |
| CA3233305A1 (en) | 2019-02-19 | 2020-08-27 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
| WO2020231917A1 (en) | 2019-05-13 | 2020-11-19 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
| KR20220035365A (ko) | 2019-07-18 | 2022-03-22 | 엔요 파마 | 인터페론의 부작용을 감소시키는 방법 |
| WO2021108974A1 (en) | 2019-12-03 | 2021-06-10 | Gannex Pharma Co., Ltd | Compounds for modulating activity of fxr and uses thereof |
| IL293892A (en) | 2020-01-15 | 2022-08-01 | Inserm Institut National De La Sant? Et De La Rech M?Dicale | Use of fxr agonists for treating an infection by hepatitis d virus |
| JP2024502673A (ja) | 2021-01-14 | 2024-01-22 | ウエヌイグレックオ・ファーマ | Ｈｂｖ感染の処置のためのｆｘｒアゴニストとｉｆｎの相乗効果 |
| JP2024517181A (ja) | 2021-04-28 | 2024-04-19 | ウエヌイグレックオ・ファーマ | 組合せ治療としてｆｘｒアゴニストを使用するｔｌｒ３アゴニストの効果の強い増強 |
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| GB9706707D0 (en) | 1997-04-02 | 1997-05-21 | Glaxo Group Ltd | Chemical compounds |
| US6639076B1 (en) * | 1998-08-18 | 2003-10-28 | Eli Lilly And Company | Growth hormone secretagogues |
| DE69940958D1 (de) | 1998-12-23 | 2009-07-16 | Glaxo Group Ltd | Bestimmungsmethode fur liganden der nuklearen rezeptoren |
| US20070010562A1 (en) | 2001-08-13 | 2007-01-11 | Ulrike Bauer | Nr1h4 nuclear receptor binding compounds |
| ATE381542T1 (de) | 2001-08-13 | 2008-01-15 | Phenex Pharmaceuticals Ag | Nr1h4-kern-rezeptor-bindende verbindungen |
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| WO2003087140A1 (en) | 2002-04-13 | 2003-10-23 | Lion Bioscience Ag | NON-PRIMATE FXRb AS A LANOSTEROL SENSING NUCLEAR HORMONE RECEPTOR AND RELATED USES |
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| WO2004048349A1 (en) | 2002-11-22 | 2004-06-10 | Smithkline Beecham Corporation | Farnesoid x receptor agonists |
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| WO2007109275A2 (en) | 2006-03-20 | 2007-09-27 | Bayer Healthcare Llc. | Paclitaxel combination |
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- 2006-12-13 EP EP06840218A patent/EP1962838B1/en active Active
- 2006-12-13 ES ES06840218T patent/ES2374165T3/es active Active
- 2006-12-13 AT AT06840218T patent/ATE526318T1/de not_active IP Right Cessation
- 2006-12-13 JP JP2008545947A patent/JP5081161B2/ja active Active
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1962838A2 (en) | 2008-09-03 |
| US20080167356A1 (en) | 2008-07-10 |
| WO2007076260A3 (en) | 2007-11-01 |
| ES2374165T3 (es) | 2012-02-14 |
| EP1962838A4 (en) | 2009-11-18 |
| WO2007076260A2 (en) | 2007-07-05 |
| US7705028B2 (en) | 2010-04-27 |
| ATE526318T1 (de) | 2011-10-15 |
| JP2009519965A (ja) | 2009-05-21 |
| EP1962838B1 (en) | 2011-09-28 |
| US20100160398A1 (en) | 2010-06-24 |
| US8158665B2 (en) | 2012-04-17 |
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