UA57002C2 - Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування - Google Patents
Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування Download PDFInfo
- Publication number
- UA57002C2 UA57002C2 UA98041875A UA98041875A UA57002C2 UA 57002 C2 UA57002 C2 UA 57002C2 UA 98041875 A UA98041875 A UA 98041875A UA 98041875 A UA98041875 A UA 98041875A UA 57002 C2 UA57002 C2 UA 57002C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- phenyl
- furan
- methylsulfonyl
- group
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims description 204
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 title claims description 52
- 150000001875 compounds Chemical class 0.000 claims abstract description 328
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 230000001404 mediated effect Effects 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 173
- 239000001257 hydrogen Substances 0.000 claims description 170
- -1 monosubstituted phenyl Chemical group 0.000 claims description 148
- 150000002367 halogens Chemical class 0.000 claims description 143
- 125000001424 substituent group Chemical group 0.000 claims description 141
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 139
- 229910052736 halogen Inorganic materials 0.000 claims description 138
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
- 125000004429 atom Chemical group 0.000 claims description 67
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 64
- 229910052799 carbon Inorganic materials 0.000 claims description 62
- 239000002253 acid Substances 0.000 claims description 61
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 58
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 56
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 52
- 125000005842 heteroatom Chemical group 0.000 claims description 40
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000002950 monocyclic group Chemical group 0.000 claims description 30
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 24
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims description 21
- 231100000252 nontoxic Toxicity 0.000 claims description 21
- 230000003000 nontoxic effect Effects 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 14
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 13
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- ONJHHYBWKLDIFI-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-propan-2-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 ONJHHYBWKLDIFI-UHFFFAOYSA-N 0.000 claims description 9
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 9
- 125000000623 heterocyclic group Chemical class 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- GJJZKGZYUTXFMK-UHFFFAOYSA-N 3-(1-benzothiophen-5-yloxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC=2C=C3C=CSC3=CC=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 GJJZKGZYUTXFMK-UHFFFAOYSA-N 0.000 claims description 4
- WTOORHANEMAYPO-UHFFFAOYSA-N 3-(1-cyclopropylethoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C1CC1C(C)OC(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 WTOORHANEMAYPO-UHFFFAOYSA-N 0.000 claims description 4
- OEUFTIBZEDUUCK-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-phenoxyfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC=C1 OEUFTIBZEDUUCK-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- NJLAGDPRCAPJIF-MHSJTTIKSA-N (8S)-1',3',9-trihydroxy-6'-methoxy-3-[(1E,3E)-penta-1,3-dienyl]spiro[6,7-dihydro-2H-cyclopenta[g]isoquinoline-8,2'-cyclopenta[b]naphthalene]-1,4',5',8',9'-pentone Chemical compound COc1cc(=O)c2c(c1=O)c(=O)c1=C(O)[C@]3(CCc4cc5cc(\C=C\C=C\C)[nH]c(=O)c5c(O)c34)C(O)=c1c2=O NJLAGDPRCAPJIF-MHSJTTIKSA-N 0.000 claims description 3
- OKKGDLZWFJTBDJ-UHFFFAOYSA-N 3-(3,4-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C(F)=C1 OKKGDLZWFJTBDJ-UHFFFAOYSA-N 0.000 claims description 3
- VRNJUSJNNZDCAE-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)C=N1 VRNJUSJNNZDCAE-UHFFFAOYSA-N 0.000 claims description 3
- LFRQDTGNFOZLCA-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-pentan-3-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC(CC)CC)=C1C1=CC=C(S(C)(=O)=O)C=C1 LFRQDTGNFOZLCA-UHFFFAOYSA-N 0.000 claims description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- HDKLIZDXVUCLHQ-BQYQJAHWSA-N (3E)-3-nonen-2-one Chemical compound CCCCC\C=C\C(C)=O HDKLIZDXVUCLHQ-BQYQJAHWSA-N 0.000 claims description 2
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
- PZOMJAGQUNQIHB-UHFFFAOYSA-N 3-(2,3-dihydro-1h-inden-1-yloxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC2C3=CC=CC=C3CC2)=C1C1=CC=C(S(C)(=O)=O)C=C1 PZOMJAGQUNQIHB-UHFFFAOYSA-N 0.000 claims description 2
- VGLWOZUXEPKTLV-UHFFFAOYSA-N 3-(2,4-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C=C1F VGLWOZUXEPKTLV-UHFFFAOYSA-N 0.000 claims description 2
- PUYCKSKASYLLIW-UHFFFAOYSA-N 3-(3,3-dimethylcyclopentyl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C1C(C)(C)CCC1OC(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 PUYCKSKASYLLIW-UHFFFAOYSA-N 0.000 claims description 2
- DESBNISDYNFRCI-UHFFFAOYSA-N 3-(3,5-dichloropyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=NC=C(Cl)C=C1Cl DESBNISDYNFRCI-UHFFFAOYSA-N 0.000 claims description 2
- NSOLEUGGZJTHNS-UHFFFAOYSA-N 3-(3-fluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC(F)=C1 NSOLEUGGZJTHNS-UHFFFAOYSA-N 0.000 claims description 2
- MTPQCSUYJXVPPH-UHFFFAOYSA-N 3-(4-fluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C=C1 MTPQCSUYJXVPPH-UHFFFAOYSA-N 0.000 claims description 2
- XCNHDBDVIVAJHX-UHFFFAOYSA-N 3-(5-bromopyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Br)C=N1 XCNHDBDVIVAJHX-UHFFFAOYSA-N 0.000 claims description 2
- YMECDTRUPBWAKF-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-(1,3-thiazol-2-ylsulfanyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=NC=CS1 YMECDTRUPBWAKF-UHFFFAOYSA-N 0.000 claims description 2
- BXKQWMSQWNZDTH-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-pyridin-2-yloxyfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC=N1 BXKQWMSQWNZDTH-UHFFFAOYSA-N 0.000 claims description 2
- PFYCGEZLYBVOOJ-UHFFFAOYSA-N 5-methyl-4-(4-methylsulfonylphenyl)-3-propan-2-yloxy-5-propylfuran-2-one Chemical compound CCCC1(C)OC(=O)C(OC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 PFYCGEZLYBVOOJ-UHFFFAOYSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 claims 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims 2
- CSYDLWAKOSNOAE-UHFFFAOYSA-N 3-(3,5-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC(F)=CC(F)=C1 CSYDLWAKOSNOAE-UHFFFAOYSA-N 0.000 claims 1
- PQYQDILXYJVMIB-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CN=CC(Cl)=C1 PQYQDILXYJVMIB-UHFFFAOYSA-N 0.000 claims 1
- FQHQBFIVQROQKA-UHFFFAOYSA-N 3-(6-aminopyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC(N)=N1 FQHQBFIVQROQKA-UHFFFAOYSA-N 0.000 claims 1
- HSNXDRXMMFAZGU-UHFFFAOYSA-N 3-(6-chloropyridin-3-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)N=C1 HSNXDRXMMFAZGU-UHFFFAOYSA-N 0.000 claims 1
- IUPMBEGMKVHDEZ-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)-hydroxymethyl]-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1C(O)C1=CC=C(F)C(F)=C1 IUPMBEGMKVHDEZ-UHFFFAOYSA-N 0.000 claims 1
- FEOYFLSIRFBESM-UHFFFAOYSA-N 3-cyclobutyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1CCC1 FEOYFLSIRFBESM-UHFFFAOYSA-N 0.000 claims 1
- QCQWGGMDTWVKQQ-UHFFFAOYSA-N 3-cyclopentyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1CCCC1 QCQWGGMDTWVKQQ-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- HIUVVOXSYZYIBH-UHFFFAOYSA-N 5,5-dimethyl-3-(2-methylpropoxy)-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OCC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 HIUVVOXSYZYIBH-UHFFFAOYSA-N 0.000 claims 1
- HJZXSUAVCFVGNB-UHFFFAOYSA-N 5,5-dimethyl-3-(6-methylpyridin-3-yl)oxy-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C1=NC(C)=CC=C1OC(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 HJZXSUAVCFVGNB-UHFFFAOYSA-N 0.000 claims 1
- KFKIOJSNPDLTTQ-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-phenylsulfanylfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=CC=CC=C1 KFKIOJSNPDLTTQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 229910014033 C-OH Inorganic materials 0.000 claims 1
- 229910014570 C—OH Inorganic materials 0.000 claims 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- FULAPETWGIGNMT-UHFFFAOYSA-N firocoxib Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OCC1CC1 FULAPETWGIGNMT-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 abstract description 34
- 102000010907 Cyclooxygenase 2 Human genes 0.000 abstract 2
- 239000000203 mixture Substances 0.000 description 184
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 155
- 238000005481 NMR spectroscopy Methods 0.000 description 118
- 239000002904 solvent Substances 0.000 description 118
- 239000000243 solution Substances 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- NCQXDPFJWCBCEZ-UHFFFAOYSA-N 3-(4-bromophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Br)C=C1 NCQXDPFJWCBCEZ-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 44
- 239000012267 brine Substances 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- 239000002585 base Substances 0.000 description 43
- 239000012044 organic layer Substances 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 40
- 150000002596 lactones Chemical class 0.000 description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 37
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
- 238000012360 testing method Methods 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/58—One oxygen atom, e.g. butenolide
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A61K31/33—Heterocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/24—Sulfones; Sulfoxides having sulfone or sulfoxide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/64—Sulfur atoms
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
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- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
- C07D307/83—Oxygen atoms
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- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
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- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US537195P | 1995-10-13 | 1995-10-13 | |
GBGB9602939.2A GB9602939D0 (en) | 1996-02-13 | 1996-02-13 | (Methylsulfony)phenyl-2-(5h)-furanones as cox-2 inhibitors |
US1163796P | 1996-02-14 | 1996-02-14 | |
GBGB9605645.2A GB9605645D0 (en) | 1996-03-18 | 1996-03-18 | (Methylsulfonyl)phenyl-2-(5H)- furanones as cox-2 inhibitors |
PCT/CA1996/000682 WO1997014691A1 (en) | 1995-10-13 | 1996-10-09 | (methylsulfonyl)phenyl-2-(5h)-furanones as cox-2 inhibitors |
Publications (1)
Publication Number | Publication Date |
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UA57002C2 true UA57002C2 (uk) | 2003-06-16 |
Family
ID=27451401
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA98041875A UA57002C2 (uk) | 1995-10-13 | 1996-09-10 | Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування |
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PL3609877T3 (pl) | 2017-04-14 | 2021-06-28 | Cosma S.P.A. | Sposób syntezy firokoksybu |
CN108178724B (zh) * | 2017-12-22 | 2020-09-11 | 四川大学 | 化合物的制备方法 |
CN110240537B (zh) * | 2019-05-22 | 2022-06-21 | 成都阿奇生物医药科技有限公司 | 一种茚氧乙酸类化合物及其制备方法和用途 |
CN110452198B (zh) * | 2019-09-03 | 2021-03-26 | 山东鲁抗舍里乐药业有限公司 | 一种非罗考昔的制备方法 |
CN110452199B (zh) * | 2019-09-03 | 2021-03-30 | 山东鲁抗舍里乐药业有限公司 | 一种非罗考昔的制备方法 |
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CN110746390B (zh) * | 2019-11-14 | 2022-12-30 | 中国科学技术大学 | 制备5-甲酰基-2-呋喃甲酸酯的方法 |
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CN113248458B (zh) * | 2021-05-27 | 2022-09-27 | 陕西省煤田地质集团有限公司 | 一种α-羰基酰胺化合物的制备方法 |
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US5474995A (en) * | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
JPH10511089A (ja) * | 1994-12-21 | 1998-10-27 | メルク フロスト カナダ インコーポレーテツド | Cox−2阻害剤としてのジアリール−2−(5h)−フラノン |
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1996
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- 1998-04-08 NO NO19981628A patent/NO321042B1/no not_active IP Right Cessation
- 1998-04-08 MX MX9802836A patent/MX9802836A/es unknown
- 1998-05-04 BG BG102425A patent/BG63391B1/bg unknown
-
1999
- 1999-05-07 HK HK99102061A patent/HK1016980A1/xx not_active IP Right Cessation
-
2000
- 2000-12-01 JP JP2000366579A patent/JP4068802B2/ja not_active Expired - Lifetime
-
2005
- 2005-02-14 NL NL300175C patent/NL300175I2/nl unknown
- 2005-03-09 LU LU91145C patent/LU91145I2/fr unknown
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