JP2005533104A - 慢性関節リウマチを処置するためのレフルノミド類似体 - Google Patents
慢性関節リウマチを処置するためのレフルノミド類似体 Download PDFInfo
- Publication number
- JP2005533104A JP2005533104A JP2004521488A JP2004521488A JP2005533104A JP 2005533104 A JP2005533104 A JP 2005533104A JP 2004521488 A JP2004521488 A JP 2004521488A JP 2004521488 A JP2004521488 A JP 2004521488A JP 2005533104 A JP2005533104 A JP 2005533104A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- leflunomide
- analogs
- rheumatoid arthritis
- formula
- 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
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical class O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 14
- 229960000681 leflunomide Drugs 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 8
- 229960001680 ibuprofen Drugs 0.000 claims description 8
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 7
- 229960003957 dexamethasone Drugs 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- -1 malononitrile amide Chemical class 0.000 claims description 5
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 2
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 claims description 2
- 229960004515 diclofenac potassium Drugs 0.000 claims description 2
- 229960001193 diclofenac sodium Drugs 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229960002009 naproxen Drugs 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 claims description 2
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 8
- 229960003940 naproxen sodium Drugs 0.000 claims 1
- 238000001727 in vivo Methods 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000002474 experimental method Methods 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000001684 chronic effect Effects 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 239000001768 carboxy methyl cellulose Substances 0.000 description 11
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 11
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 11
- 239000000679 carrageenan Substances 0.000 description 10
- 229940113118 carrageenan Drugs 0.000 description 10
- 229920001525 carrageenan Polymers 0.000 description 10
- 235000010418 carrageenan Nutrition 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 9
- 239000000725 suspension Substances 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010030124 Oedema peripheral Diseases 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GNPHAOQLHRZODS-ZQWQDMLBSA-N (1s,2s,3s,4s)-3,4-bis[butyl-[(4-phenoxyphenyl)methyl]carbamoyl]cyclobutane-1,2-dicarboxylic acid Chemical compound O=C([C@H]1[C@@H]([C@@H]([C@H]1C(O)=O)C(O)=O)C(=O)N(CCCC)CC=1C=CC(OC=2C=CC=CC=2)=CC=1)N(CCCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 GNPHAOQLHRZODS-ZQWQDMLBSA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- SKCJYQMVKYFTGQ-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;pyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1.ON1C(=O)CCC1=O SKCJYQMVKYFTGQ-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- JGMXNNSYEFOBHQ-OWOJBTEDSA-N 2-[(e)-4-morpholin-4-ylbut-2-enyl]-1,1-dioxothieno[3,2-e]thiazine-6-sulfonamide Chemical compound O=S1(=O)C=2SC(S(=O)(=O)N)=CC=2C=CN1C\C=C\CN1CCOCC1 JGMXNNSYEFOBHQ-OWOJBTEDSA-N 0.000 description 1
- ORQHHLPTMSGMQT-UHFFFAOYSA-N 2-[4-(5-fluoropyridin-2-yl)piperazin-1-yl]-n-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)acetamide Chemical compound N1=CC(F)=CC=C1N1CCN(CC(=O)NC=2SC=3CCCCC=3N=2)CC1 ORQHHLPTMSGMQT-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- OVDGUTHABMXVMI-UHFFFAOYSA-N 3-nitro-4-(propylamino)benzoic acid Chemical compound CCCNC1=CC=C(C(O)=O)C=C1[N+]([O-])=O OVDGUTHABMXVMI-UHFFFAOYSA-N 0.000 description 1
- LOPGZTFZOUEXLZ-UHFFFAOYSA-N 4-[(5-methyl-1,2-oxazole-3-carbonyl)amino]benzoic acid Chemical compound O1C(C)=CC(C(=O)NC=2C=CC(=CC=2)C(O)=O)=N1 LOPGZTFZOUEXLZ-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- BNMPIJWVMVNSRD-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NO1 BNMPIJWVMVNSRD-UHFFFAOYSA-N 0.000 description 1
- UFMQJYHLIUACCG-UHFFFAOYSA-N 8-nitroindolo[2,1-b]quinazoline-6,12-dione Chemical compound C1=CC=C2C(=O)N3C4=CC=C([N+](=O)[O-])C=C4C(=O)C3=NC2=C1 UFMQJYHLIUACCG-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 0 CCc1cc(C(N(*)C2=CC=CC(C)(*)C=C2)=O)n[o]1 Chemical compound CCc1cc(C(N(*)C2=CC=CC(C)(*)C=C2)=O)n[o]1 0.000 description 1
- QMGYPNKICQJHLN-UHFFFAOYSA-M Carboxymethylcellulose cellulose carboxymethyl ether Chemical compound [Na+].CC([O-])=O.OCC(O)C(O)C(O)C(O)C=O QMGYPNKICQJHLN-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
- TZCCKCLHNUSAMQ-DUGSHLAESA-N NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N Chemical compound NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N TZCCKCLHNUSAMQ-DUGSHLAESA-N 0.000 description 1
- AKQOBHZKBDHWQI-BZEFIUHZSA-N O[C@H]1C[C@@H](CCC1)N1C(C2(C3=C1N=C(N=C3)NC1=CC=C(C=C1)S(=O)(=O)NC([2H])([2H])[2H])CC2)=O Chemical compound O[C@H]1C[C@@H](CCC1)N1C(C2(C3=C1N=C(N=C3)NC1=CC=C(C=C1)S(=O)(=O)NC([2H])([2H])[2H])CC2)=O AKQOBHZKBDHWQI-BZEFIUHZSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940127108 compound 5g Drugs 0.000 description 1
- 229940126136 compound 5i Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- JBLLRCOZJMVOAE-HSQYWUDLSA-N n-[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methoxy-1h-indole-2-carboxamide Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)C=1NC=2C=CC=C(C=2C=1)OC)C(=O)C=1SC2=CC=CC=C2N=1)[C@@H]1CCNC1=O JBLLRCOZJMVOAE-HSQYWUDLSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Images
Classifications
-
- 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
- C07D261/10—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/195,824 US6727272B1 (en) | 2002-07-15 | 2002-07-15 | Leflunomide analogs for treating rheumatoid arthritis |
| PCT/US2003/019956 WO2004006834A2 (en) | 2002-07-15 | 2003-06-25 | Leflunomide analogs for treating rheumatoid arthritis |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010108822A Division JP2010168402A (ja) | 2002-07-15 | 2010-05-10 | 慢性関節リウマチを処置するためのレフルノミド類似体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005533104A true JP2005533104A (ja) | 2005-11-04 |
| JP2005533104A5 JP2005533104A5 (OSRAM) | 2006-06-29 |
Family
ID=30115011
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004521488A Ceased JP2005533104A (ja) | 2002-07-15 | 2003-06-25 | 慢性関節リウマチを処置するためのレフルノミド類似体 |
| JP2010108822A Pending JP2010168402A (ja) | 2002-07-15 | 2010-05-10 | 慢性関節リウマチを処置するためのレフルノミド類似体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010108822A Pending JP2010168402A (ja) | 2002-07-15 | 2010-05-10 | 慢性関節リウマチを処置するためのレフルノミド類似体 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US6727272B1 (OSRAM) |
| EP (1) | EP1539143A4 (OSRAM) |
| JP (2) | JP2005533104A (OSRAM) |
| AU (1) | AU2003251611A1 (OSRAM) |
| WO (1) | WO2004006834A2 (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE59801792D1 (de) * | 1997-08-08 | 2001-11-22 | Aventis Pharma Gmbh | Kristallform von N-(4-Trifluormethylphenyl)-5-methylisoxazol-4-carbonsäureamid |
| US7125902B2 (en) * | 2004-05-28 | 2006-10-24 | Unitech Pharmaceuticals, Inc. | Methods, compounds, and diagnostics for cancer treatment |
| JP2008504292A (ja) | 2004-06-24 | 2008-02-14 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス， インコーポレイテッド | 免疫増強用の化合物 |
| US20060024376A1 (en) * | 2004-07-30 | 2006-02-02 | The University Of Chicago | Methods and compositions for reducing toxicity associated with leflunomide treatment |
| US7291743B2 (en) * | 2005-03-29 | 2007-11-06 | Geneblue Corporation | Isoxazole derivatives and methods of treating nitric oxide mediated diseases |
| KR20080038339A (ko) * | 2005-08-31 | 2008-05-06 | 코와 가부시키가이샤 | 관절 류머티즘의 예방 및/또는 치료법 |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| TW200808739A (en) | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
| CN101563082A (zh) * | 2006-09-05 | 2009-10-21 | 窦德献 | 治疗免疫介导性皮肤病的组合物和方法 |
| KR20090069309A (ko) * | 2006-09-22 | 2009-06-30 | 랜박시 래보러터리스 리미티드 | 포스포디에스터라제 타입-ⅳ의 저해제 |
| US20080085912A1 (en) * | 2006-10-06 | 2008-04-10 | Unitech Pharmaceuticals, Inc. | Isoxazole derivatives and methods of treating diseases |
| US8940771B2 (en) | 2007-12-20 | 2015-01-27 | Novartis Ag | Organic compounds |
| US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
| AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
| JP5820476B2 (ja) | 2010-08-24 | 2015-11-24 | アルギアックス ファルマコウティカルス ゲーエムベーハーＡＬＧＩＡＸ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ ＧｍｂＨ | レフルノミドおよびマロノニトリラマイドの新規の使用 |
| EP2670753B1 (en) | 2011-01-31 | 2016-10-19 | Novartis AG | Novel heterocyclic derivatives |
| PH12014500912A1 (en) | 2011-10-28 | 2014-06-09 | Novartis Ag | Novel purine derivatives and their use in the treatment of disease |
| SG10201608469RA (en) | 2012-05-16 | 2016-11-29 | Novartis Ag | Dosage regimen for a pi-3 kinase inhibitor |
| PL3076969T3 (pl) | 2013-12-06 | 2022-01-17 | Novartis Ag | Schemat dawkowania selektywnego inhibitora 3-kinazy fosfatydynozytolu alfa-izoformy |
| RU2722316C2 (ru) * | 2015-06-17 | 2020-05-29 | Биокон Лимитед | Новый способ получения терифлуномида |
| MX2018005298A (es) | 2015-11-02 | 2018-06-22 | Novartis Ag | Regimen de dosificacion para un inhibidor de fosfatidilinositol 3-quinasa. |
| WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
| CN108863970A (zh) * | 2017-08-14 | 2018-11-23 | 四川省中医药转化医学中心 | 新化合物及其在治疗炎症或炎症相关疾病方面的应用 |
| KR102696521B1 (ko) * | 2021-11-24 | 2024-08-20 | 한양대학교 에리카산학협력단 | 이속사졸 유도체 또는 이의 약학적으로 허용가능한 염 및 이의 용도 |
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| JPS5353692A (en) * | 1976-10-22 | 1978-05-16 | Pfizer | Antiiworm compound |
| JPH03130270A (ja) * | 1989-09-22 | 1991-06-04 | Basf Ag | 新規カルボン酸アミド及び除草剤 |
| US5059614A (en) * | 1988-11-30 | 1991-10-22 | Novapharme | Novel isoxazole and isoxazoline compounds with anticonvulsant activity process for their preparation and therapeutic composition containing them |
| JP2005508983A (ja) * | 2001-11-09 | 2005-04-07 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４又はｐｄｅ３／４阻害剤及び抗リウマチ薬の複合薬 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5814646A (en) * | 1995-03-02 | 1998-09-29 | Eli Lilly And Company | Inhibitors of amyloid beta-protein production |
| DE19702988A1 (de) | 1997-01-28 | 1998-07-30 | Hoechst Ag | Isoxazol- und Crotonsäureamidderivate und deren Verwendung als Arzneimittel und Diagnostika |
-
2002
- 2002-07-15 US US10/195,824 patent/US6727272B1/en not_active Expired - Fee Related
-
2003
- 2003-06-25 WO PCT/US2003/019956 patent/WO2004006834A2/en not_active Ceased
- 2003-06-25 JP JP2004521488A patent/JP2005533104A/ja not_active Ceased
- 2003-06-25 EP EP03764320A patent/EP1539143A4/en not_active Withdrawn
- 2003-06-25 AU AU2003251611A patent/AU2003251611A1/en not_active Abandoned
-
2010
- 2010-05-10 JP JP2010108822A patent/JP2010168402A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5353692A (en) * | 1976-10-22 | 1978-05-16 | Pfizer | Antiiworm compound |
| US5059614A (en) * | 1988-11-30 | 1991-10-22 | Novapharme | Novel isoxazole and isoxazoline compounds with anticonvulsant activity process for their preparation and therapeutic composition containing them |
| JPH03130270A (ja) * | 1989-09-22 | 1991-06-04 | Basf Ag | 新規カルボン酸アミド及び除草剤 |
| JP2005508983A (ja) * | 2001-11-09 | 2005-04-07 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４又はｐｄｅ３／４阻害剤及び抗リウマチ薬の複合薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004006834A3 (en) | 2004-06-24 |
| EP1539143A4 (en) | 2009-12-09 |
| US6727272B1 (en) | 2004-04-27 |
| AU2003251611A8 (en) | 2004-02-02 |
| AU2003251611A1 (en) | 2004-02-02 |
| JP2010168402A (ja) | 2010-08-05 |
| WO2004006834A2 (en) | 2004-01-22 |
| EP1539143A2 (en) | 2005-06-15 |
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