KR20040047862A - Ｃｏｘ ⅱ 억제제로서의 인돌 유도체 - Google Patents
Ｃｏｘ ⅱ 억제제로서의 인돌 유도체 Download PDFInfo
- Publication number
- KR20040047862A KR20040047862A KR10-2004-7004428A KR20047004428A KR20040047862A KR 20040047862 A KR20040047862 A KR 20040047862A KR 20047004428 A KR20047004428 A KR 20047004428A KR 20040047862 A KR20040047862 A KR 20040047862A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- compound
- methanesulfonyl
- indole
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 11
- 150000002475 indoles Chemical class 0.000 title abstract description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 136
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 72
- 239000001257 hydrogen Substances 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- XAOIOAYWZAVEIW-UHFFFAOYSA-N 3-(2,4-difluorophenyl)sulfanyl-6-methylsulfonyl-1h-indole-2-carbonitrile Chemical compound N#CC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1F XAOIOAYWZAVEIW-UHFFFAOYSA-N 0.000 claims description 6
- GVUYJYPBPIQKHW-UHFFFAOYSA-N (6-methylsulfonyl-3-phenylsulfanyl-1h-indol-2-yl)methanol Chemical compound OCC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=CC=C1 GVUYJYPBPIQKHW-UHFFFAOYSA-N 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- VHSYYXRBWBHMNB-UHFFFAOYSA-N 3-(4-fluorophenoxy)-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1OC1=CC=C(F)C=C1 VHSYYXRBWBHMNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- OHVHHRUUBCGBLX-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-6-methylsulfonyl-1h-indole-2-carbonitrile Chemical compound N#CC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1 OHVHHRUUBCGBLX-UHFFFAOYSA-N 0.000 claims description 3
- JGGHRZWTRXUNBK-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1CC1=CC=CC=C1Cl JGGHRZWTRXUNBK-UHFFFAOYSA-N 0.000 claims description 3
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 3
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 201000003068 rheumatic fever Diseases 0.000 claims description 3
- VNYCGFXZOQHLEM-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfinyl-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1S(=O)C1=CC=C(F)C=C1 VNYCGFXZOQHLEM-UHFFFAOYSA-N 0.000 claims description 2
- 208000004998 Abdominal Pain Diseases 0.000 claims description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 208000008035 Back Pain Diseases 0.000 claims description 2
- 206010006811 Bursitis Diseases 0.000 claims description 2
- 208000002881 Colic Diseases 0.000 claims description 2
- 201000005569 Gout Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 201000002481 Myositis Diseases 0.000 claims description 2
- 208000010040 Sprains and Strains Diseases 0.000 claims description 2
- 208000000491 Tendinopathy Diseases 0.000 claims description 2
- 206010043255 Tendonitis Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims description 2
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- 125000001475 halogen functional group Chemical group 0.000 claims 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 1
- 230000000386 athletic effect Effects 0.000 claims 1
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- 230000006735 deficit Effects 0.000 claims 1
- 201000004595 synovitis Diseases 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 description 77
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 125000000753 cycloalkyl group Chemical group 0.000 description 22
- 125000003545 alkoxy group Chemical group 0.000 description 21
- 125000005843 halogen group Chemical group 0.000 description 21
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- 125000003884 phenylalkyl group Chemical group 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000003110 anti-inflammatory effect Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 150000003180 prostaglandins Chemical class 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 125000001188 haloalkyl group Chemical group 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical class CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 7
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 7
- 125000004442 acylamino group Chemical group 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 210000002683 foot Anatomy 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 239000012425 OXONE® Substances 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 6
- 230000000202 analgesic effect Effects 0.000 description 6
- 235000010418 carrageenan Nutrition 0.000 description 6
- 229920001525 carrageenan Polymers 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 125000004404 heteroalkyl group Chemical group 0.000 description 6
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- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- UHGDAIAKKIZOFL-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1SC1=CC=C(F)C=C1 UHGDAIAKKIZOFL-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 125000004438 haloalkoxy group Chemical group 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 4
- RSUVYRBOKYIZED-UHFFFAOYSA-N 1-(4-fluorophenoxy)propan-2-one Chemical compound CC(=O)COC1=CC=C(F)C=C1 RSUVYRBOKYIZED-UHFFFAOYSA-N 0.000 description 4
- BICHBFCGCJNCAT-UHFFFAOYSA-N 2,4-difluorobenzenethiol Chemical compound FC1=CC=C(S)C(F)=C1 BICHBFCGCJNCAT-UHFFFAOYSA-N 0.000 description 4
- IGFNZUZQPDXVHU-UHFFFAOYSA-N 2-methyl-6-methylsulfonyl-1h-indole Chemical compound C1=C(S(C)(=O)=O)C=C2NC(C)=CC2=C1 IGFNZUZQPDXVHU-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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- 125000002252 acyl group Chemical group 0.000 description 4
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- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
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- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 4
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- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
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- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32538901P | 2001-09-27 | 2001-09-27 | |
| US60/325,389 | 2001-09-27 | ||
| PCT/EP2002/010557 WO2003029212A1 (en) | 2001-09-27 | 2002-09-20 | Indole derivatives as cox ii inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20040047862A true KR20040047862A (ko) | 2004-06-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7004428A Ceased KR20040047862A (ko) | 2001-09-27 | 2002-09-20 | Ｃｏｘ ⅱ 억제제로서의 인돌 유도체 |
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| Country | Link |
|---|---|
| US (3) | US6872744B2 (enExample) |
| EP (1) | EP1438289B1 (enExample) |
| JP (1) | JP4141954B2 (enExample) |
| KR (1) | KR20040047862A (enExample) |
| CN (1) | CN1261412C (enExample) |
| AR (1) | AR036624A1 (enExample) |
| AT (1) | ATE292115T1 (enExample) |
| BR (1) | BR0212925A (enExample) |
| CA (1) | CA2461670A1 (enExample) |
| CO (1) | CO5560557A2 (enExample) |
| DE (1) | DE60203529T2 (enExample) |
| DK (1) | DK1438289T3 (enExample) |
| ES (1) | ES2238616T3 (enExample) |
| HR (1) | HRPK20040271B3 (enExample) |
| HU (1) | HUP0401499A3 (enExample) |
| IL (1) | IL160752A0 (enExample) |
| MX (1) | MXPA04002824A (enExample) |
| NO (1) | NO20041237L (enExample) |
| NZ (1) | NZ531577A (enExample) |
| PL (1) | PL370342A1 (enExample) |
| PT (1) | PT1438289E (enExample) |
| RU (1) | RU2004113111A (enExample) |
| SI (1) | SI1438289T1 (enExample) |
| WO (1) | WO2003029212A1 (enExample) |
| ZA (1) | ZA200402360B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210014374A (ko) | 2019-07-30 | 2021-02-09 | 부산대학교 산학협력단 | 신규한 인돌 유도체 및 이를 포함하는 염증성 질환 예방 또는 치료용 조성물 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60203529T2 (de) * | 2001-09-27 | 2006-03-16 | F. Hoffmann-La Roche Ag | Indolderivate als cox-ii-inhibitoren |
| SE0202241D0 (sv) * | 2002-07-17 | 2002-07-17 | Astrazeneca Ab | Novel Compounds |
| US7365090B2 (en) * | 2002-08-07 | 2008-04-29 | Idenix Pharmaceuticals, Inc. | Substituted phenylindoles for the treatment of HIV |
| US20050250794A1 (en) * | 2003-12-19 | 2005-11-10 | Andrew Napper | Methods of treating a disorder |
| US7119214B2 (en) | 2004-04-13 | 2006-10-10 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
| US7423176B2 (en) | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
| EP1589016A1 (en) * | 2004-04-13 | 2005-10-26 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
| CN101006053A (zh) | 2004-06-18 | 2007-07-25 | 比奥里波克斯公司 | 用于治疗炎症的吲哚 |
| WO2006041961A1 (en) * | 2004-10-05 | 2006-04-20 | GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTHAND HUMAN SERVICES | Arylthioindole tubulin polymerization inhibitors and methods of treating or preventing cancer using same |
| AU2005325497A1 (en) | 2005-01-19 | 2006-07-27 | Biolipox Ab | Indoles useful in the treatment of inflammation |
| US7622495B2 (en) * | 2006-10-03 | 2009-11-24 | Neurim Pharmaceuticals (1991) Ltd. | Substituted aryl-indole compounds and their kynurenine/kynuramine-like metabolites as therapeutic agents |
| CA2668959A1 (en) | 2006-11-09 | 2008-05-15 | F. Hoffmann-La Roche Ag | Indole and benzofuran 2-carboxamide derivatives |
| JP2013536200A (ja) | 2010-08-20 | 2013-09-19 | アミラ ファーマシューティカルス，インコーポレーテッド | オートタキシン阻害剤およびその使用 |
| EP2714680B1 (en) | 2011-05-27 | 2015-11-25 | Amira Pharmaceuticals, Inc. | Heterocyclic autotaxin inhibitors and uses thereof |
| WO2015042053A1 (en) | 2013-09-17 | 2015-03-26 | Pharmakea, Inc. | Vinyl autotaxin inhibitor compounds |
| US9951026B2 (en) | 2013-09-17 | 2018-04-24 | Pharmakea, Inc. | Heterocyclic vinyl autotaxin inhibitor compounds |
| US9850203B2 (en) | 2013-09-26 | 2017-12-26 | Pharmakea, Inc. | Autotaxin inhibitor compounds |
| WO2015077503A1 (en) | 2013-11-22 | 2015-05-28 | Pharmakea, Inc. | Autotaxin inhibitor compounds |
| AU2016268250B2 (en) | 2015-05-27 | 2020-08-27 | Sabre Therapeutics Llc | Autotaxin inhibitors and uses thereof |
| CN113004187B (zh) * | 2021-03-16 | 2022-09-20 | 沈阳药科大学 | 一种具有抑制有机阴离子转运体1活性的化合物及制备方法和应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4654360A (en) * | 1984-06-01 | 1987-03-31 | Syntex (U.S.A.) Inc. | 1,2,3-trisubstituted indoles for treatment of inflammation |
| JPH0347123A (ja) | 1989-05-05 | 1991-02-28 | G D Searle & Co | インドール―２―カルボキシレート化合物類を含有するｃｎｓ疾患治療用組成物 |
| DE4338770A1 (de) | 1993-11-12 | 1995-05-18 | Matthias Dr Lehr | Indol-2-alkansäuren und ihre Derivate als Hemmstoffe der Phospholipase A¶2¶ |
| WO1998008818A1 (en) | 1996-08-26 | 1998-03-05 | Genetics Institute, Inc. | Inhibitors of phospholipase enzymes |
| WO1998051667A1 (en) * | 1997-05-16 | 1998-11-19 | Chugai Seiyaku Kabushiki Kaisha | Indole derivatives and mono- and diazaindole derivatives |
| EP1062216A1 (en) | 1998-02-25 | 2000-12-27 | Genetics Institute, Inc. | Inhibitors of phospholipase a2 |
| MXPA00006605A (es) * | 1999-07-02 | 2004-12-09 | Pfizer | Compuestos de carbonil-indol biciclicos como agentes antiinflamatorios/analgesicos. |
| US6306890B1 (en) * | 1999-08-30 | 2001-10-23 | Vanderbilt University | Esters derived from indolealkanols and novel amides derived from indolealkylamides that are selective COX-2 inhibitors |
| US6376708B1 (en) * | 2000-04-11 | 2002-04-23 | Monsanto Technology Llc | Process and catalyst for dehydrogenating primary alcohols to make carboxylic acid salts |
| DE60203529T2 (de) * | 2001-09-27 | 2006-03-16 | F. Hoffmann-La Roche Ag | Indolderivate als cox-ii-inhibitoren |
| TW200400177A (en) * | 2002-06-04 | 2004-01-01 | Wyeth Corp | 1-(Aminoalkyl)-3-sulfonylindole and-indazole derivatives as 5-hydroxytryptamine-6 ligands |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210014374A (ko) | 2019-07-30 | 2021-02-09 | 부산대학교 산학협력단 | 신규한 인돌 유도체 및 이를 포함하는 염증성 질환 예방 또는 치료용 조성물 |
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