NO329094B1 - Bensofenonderivater eller salter derav samt forebyggende eller terapeutisk middel inneholdende slike - Google Patents
Bensofenonderivater eller salter derav samt forebyggende eller terapeutisk middel inneholdende slike Download PDFInfo
- Publication number
- NO329094B1 NO329094B1 NO20042495A NO20042495A NO329094B1 NO 329094 B1 NO329094 B1 NO 329094B1 NO 20042495 A NO20042495 A NO 20042495A NO 20042495 A NO20042495 A NO 20042495A NO 329094 B1 NO329094 B1 NO 329094B1
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- Prior art keywords
- general formula
- compound represented
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- group
- alkyl
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- 150000003839 salts Chemical class 0.000 title claims description 57
- 150000008366 benzophenones Chemical class 0.000 title claims description 13
- 239000003814 drug Substances 0.000 title claims description 13
- 229940124597 therapeutic agent Drugs 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 604
- -1 C2- i2alkenyl Chemical group 0.000 claims description 428
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 125000006239 protecting group Chemical group 0.000 claims description 56
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 108010018242 Transcription Factor AP-1 Proteins 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 239000001301 oxygen Substances 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 13
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 230000003449 preventive effect Effects 0.000 claims description 7
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 7
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 5
- 125000001118 alkylidene group Chemical group 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 4
- KTKZUFRJHMUJPI-UHFFFAOYSA-N 4-[[2-(2-carboxyethyl)-4-(4-cyclopentyloxy-2-hydroxybenzoyl)phenoxy]methyl]benzoic acid Chemical compound OC(=O)CCC1=CC(C(=O)C=2C(=CC(OC3CCCC3)=CC=2)O)=CC=C1OCC1=CC=C(C(O)=O)C=C1 KTKZUFRJHMUJPI-UHFFFAOYSA-N 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000676 alkoxyimino group Chemical group 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 4
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- DALCQQSLNPLQFZ-UHFFFAOYSA-N 3-[5-(4-cyclopentyloxy-2-hydroxybenzoyl)-2-[(3-oxo-1,2-benzoxazol-6-yl)methoxy]phenyl]propanoic acid Chemical compound C=1C=C(OCC=2C=C3ON=C(O)C3=CC=2)C(CCC(=O)O)=CC=1C(=O)C(C(=C1)O)=CC=C1OC1CCCC1 DALCQQSLNPLQFZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005354 acylalkyl group Chemical group 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 230000014509 gene expression Effects 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- YBWRJVFMDUPFRX-UHFFFAOYSA-N 3-[5-(4-cyclopentyloxy-2-hydroxybenzoyl)-2-[[4-(3-oxo-1,2-oxazol-5-yl)phenyl]methoxy]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(C(=O)C=2C(=CC(OC3CCCC3)=CC=2)O)=CC=C1OCC(C=C1)=CC=C1C1=CC(O)=NO1 YBWRJVFMDUPFRX-UHFFFAOYSA-N 0.000 claims description 2
- HXXOPVULXOEHTK-UHFFFAOYSA-N 4-methyl-1,3-dioxol-2-one Chemical compound CC1=COC(=O)O1 HXXOPVULXOEHTK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 102100023118 Transcription factor JunD Human genes 0.000 claims 2
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
- ATMSHQULGVOZGL-UHFFFAOYSA-N 2-morpholin-4-ylethyl 3-[5-(4-cyclopentyloxy-2-hydroxybenzoyl)-2-[(3-oxo-1,2-benzoxazol-6-yl)methoxy]phenyl]propanoate Chemical compound C=1C=C2C(O)=NOC2=CC=1COC1=CC=C(C(=O)C=2C(=CC(OC3CCCC3)=CC=2)O)C=C1CCC(=O)OCCN1CCOCC1 ATMSHQULGVOZGL-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 414
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 303
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 189
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 186
- 239000002904 solvent Substances 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 137
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 136
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 135
- 239000000203 mixture Substances 0.000 description 128
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 123
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 122
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 117
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 112
- 239000012074 organic phase Substances 0.000 description 105
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 91
- 238000004519 manufacturing process Methods 0.000 description 88
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 76
- 239000000243 solution Substances 0.000 description 71
- 239000002253 acid Substances 0.000 description 70
- 239000002585 base Substances 0.000 description 70
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 68
- 239000011541 reaction mixture Substances 0.000 description 64
- 230000002829 reductive effect Effects 0.000 description 61
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 60
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 56
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 52
- 239000012071 phase Substances 0.000 description 51
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- 238000000034 method Methods 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 46
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 150000008282 halocarbons Chemical class 0.000 description 45
- 230000002411 adverse Effects 0.000 description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 41
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 41
- 150000002170 ethers Chemical class 0.000 description 41
- 239000008096 xylene Substances 0.000 description 41
- 238000010898 silica gel chromatography Methods 0.000 description 40
- 239000003480 eluent Substances 0.000 description 39
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 37
- 150000001408 amides Chemical class 0.000 description 37
- 239000003795 chemical substances by application Substances 0.000 description 37
- 150000002148 esters Chemical class 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 34
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 34
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 34
- 150000002825 nitriles Chemical class 0.000 description 34
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 33
- 239000000654 additive Substances 0.000 description 33
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 32
- 238000010511 deprotection reaction Methods 0.000 description 30
- 150000007513 acids Chemical class 0.000 description 29
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 26
- 229910000027 potassium carbonate Inorganic materials 0.000 description 26
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 25
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 25
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 24
- 239000003054 catalyst Substances 0.000 description 24
- 150000003462 sulfoxides Chemical class 0.000 description 24
- 239000003921 oil Substances 0.000 description 23
- 235000019198 oils Nutrition 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 21
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 21
- 230000000996 additive effect Effects 0.000 description 20
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 18
- 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 18
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 17
- 229910000029 sodium carbonate Inorganic materials 0.000 description 17
- 102100023132 Transcription factor Jun Human genes 0.000 description 16
- 150000001298 alcohols Chemical class 0.000 description 16
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 16
- 150000008041 alkali metal carbonates Chemical class 0.000 description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 239000012046 mixed solvent Substances 0.000 description 15
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 150000008065 acid anhydrides Chemical class 0.000 description 14
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- 229910052500 inorganic mineral Inorganic materials 0.000 description 13
- 235000010755 mineral Nutrition 0.000 description 13
- 239000011707 mineral Substances 0.000 description 13
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 13
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- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
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PCT/JP2002/011846 WO2003042150A1 (fr) | 2001-11-16 | 2002-11-13 | Nouveaux derives de benzophenone ou sels de ceux-ci |
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US7615538B2 (en) * | 1993-10-29 | 2009-11-10 | Shunichi Shiozawa | Method for therapy of rheumatoid arthritis |
TWI355380B (en) * | 2004-05-27 | 2012-01-01 | Nihon Nohyaku Co Ltd | Substituted pyrazinecarboxanilide derivatives or s |
JP4853759B2 (ja) * | 2004-05-27 | 2012-01-11 | 日本農薬株式会社 | 置換ピラジンカルボン酸アニリド誘導体又はその塩類、その中間体及び農園芸用薬剤並びにその使用方法 |
WO2006137485A1 (ja) | 2005-06-24 | 2006-12-28 | Toyama Chemical Co., Ltd. | 新規な含窒素複素環化合物およびその塩 |
AU2012200254B2 (en) * | 2006-02-21 | 2012-08-30 | Toyama Chemical Co., Ltd. | Process for the production of 3-[5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-oxo-2-substituted-2,3-dihydro- 1,2-benzisoxazol-6-yl)methoxy]phenyl]propionate ester and intermediate for the process |
CN101389614B (zh) * | 2006-02-21 | 2012-10-31 | 富山化学工业株式会社 | 3-[5-[4-(环戊氧基)-2-羟基苯甲酰基]-2-[(3-氧代-2-取代的-2,3-二氢-1,2-苯并异*唑-6-基)甲氧基]苯基]丙酸酯的制备方法和用于该方法的中间体 |
PL2562170T3 (pl) * | 2006-02-21 | 2015-03-31 | Toyama Chemical Co Ltd | Sposób wytwarzania estru kwasu 3-{5-[4-(cyklopentyloksy)- 2-hydroksybenzoilo]-2-[(3-okso-2-podstawionego-2,3-dihydro-1,2-benzizoksazol-6-ilo)metoksy]fenylo}- propionowego i związku pośredniego dla sposobu |
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US5273999A (en) * | 1991-09-10 | 1993-12-28 | Hoffmann-La Roche Inc. | Carboxylic acid leukotriene B4 antagonists |
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JP4976617B2 (ja) | 2000-03-17 | 2012-07-18 | 富山化学工業株式会社 | 新規なベンゾフェノン誘導体およびその塩 |
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BR0214177A (pt) | 2004-09-14 |
RO123430B1 (ro) | 2012-04-30 |
MXPA04004654A (es) | 2005-05-17 |
NZ532810A (en) | 2005-03-24 |
JP4554926B2 (ja) | 2010-09-29 |
CN1602291B (zh) | 2010-05-12 |
HUP0402025A2 (hu) | 2005-02-28 |
IL161736A (en) | 2008-06-05 |
NO20042495L (no) | 2004-08-11 |
ZA200403373B (en) | 2006-01-25 |
EP1445249A4 (en) | 2006-03-08 |
IL161736A0 (en) | 2005-11-20 |
CA2467261C (en) | 2010-10-12 |
CY1113657T1 (el) | 2016-06-22 |
PL370224A1 (en) | 2005-05-16 |
DK1445249T3 (da) | 2012-12-17 |
EP1445249A1 (en) | 2004-08-11 |
PT1445249E (pt) | 2013-01-16 |
ES2394963T3 (es) | 2013-02-07 |
CN1602291A (zh) | 2005-03-30 |
JPWO2003042150A1 (ja) | 2005-04-07 |
US20050113400A1 (en) | 2005-05-26 |
KR20050044458A (ko) | 2005-05-12 |
HUP0402025A3 (en) | 2006-01-30 |
EP1445249B1 (en) | 2012-11-07 |
PL206100B1 (pl) | 2010-06-30 |
WO2003042150A1 (fr) | 2003-05-22 |
CA2467261A1 (en) | 2003-05-22 |
US7772285B2 (en) | 2010-08-10 |
AU2002349777B2 (en) | 2007-12-20 |
KR100947253B1 (ko) | 2010-03-11 |
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