JPH0246036B2 - Koenshoseiokishikamunoeeteruzenkuyakuzai - Google Patents
KoenshoseiokishikamunoeeteruzenkuyakuzaiInfo
- Publication number
- JPH0246036B2 JPH0246036B2 JP27058684A JP27058684A JPH0246036B2 JP H0246036 B2 JPH0246036 B2 JP H0246036B2 JP 27058684 A JP27058684 A JP 27058684A JP 27058684 A JP27058684 A JP 27058684A JP H0246036 B2 JPH0246036 B2 JP H0246036B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- methyl
- nmr
- actual value
- delta
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 57
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 239000000047 product Substances 0.000 description 51
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000000921 elemental analysis Methods 0.000 description 34
- 238000004364 calculation method Methods 0.000 description 33
- 238000010992 reflux Methods 0.000 description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical group OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 30
- 239000013078 crystal Substances 0.000 description 28
- 229960002702 piroxicam Drugs 0.000 description 28
- 239000007787 solid Substances 0.000 description 25
- -1 enol esters Chemical class 0.000 description 24
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 235000009518 sodium iodide Nutrition 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 5
- 239000008241 heterogeneous mixture Substances 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- CGKKDGMMKSOGLM-UHFFFAOYSA-N 1-chloroethyl acetate Chemical compound CC(Cl)OC(C)=O CGKKDGMMKSOGLM-UHFFFAOYSA-N 0.000 description 3
- IXMVJDKNCLOWPR-UHFFFAOYSA-N 1-chloroethyl propanoate Chemical compound CCC(=O)OC(C)Cl IXMVJDKNCLOWPR-UHFFFAOYSA-N 0.000 description 3
- DARWLDOSIAZDME-UHFFFAOYSA-N 3-chlorobutan-2-yl hydrogen carbonate Chemical compound CC(Cl)C(C)OC(O)=O DARWLDOSIAZDME-UHFFFAOYSA-N 0.000 description 3
- NIGKHKLDZOHYMT-UHFFFAOYSA-N 4-hydroxy-2-methyl-n-(6-methylpyridin-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC(C)=N1 NIGKHKLDZOHYMT-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- BOXZXICVMMSYPE-UHFFFAOYSA-N chloromethyl benzoate Chemical compound ClCOC(=O)C1=CC=CC=C1 BOXZXICVMMSYPE-UHFFFAOYSA-N 0.000 description 3
- BDPZFQLKFUONAG-UHFFFAOYSA-N chloromethyl butanoate Chemical compound CCCC(=O)OCCl BDPZFQLKFUONAG-UHFFFAOYSA-N 0.000 description 3
- JRCUJOMLYAQHDP-UHFFFAOYSA-N chloromethyl octanoate Chemical compound CCCCCCCC(=O)OCCl JRCUJOMLYAQHDP-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- HGBDENWEGVXBJB-UHFFFAOYSA-N 1-chloroethyl 2-methylpropanoate Chemical compound CC(C)C(=O)OC(C)Cl HGBDENWEGVXBJB-UHFFFAOYSA-N 0.000 description 2
- ATXWGWHZGZFBHI-UHFFFAOYSA-N 1-chloroethyl benzoate Chemical compound CC(Cl)OC(=O)C1=CC=CC=C1 ATXWGWHZGZFBHI-UHFFFAOYSA-N 0.000 description 2
- UHFYOBZZNHROFC-UHFFFAOYSA-N 1-chloroethyl butanoate Chemical compound CCCC(=O)OC(C)Cl UHFYOBZZNHROFC-UHFFFAOYSA-N 0.000 description 2
- ONZWFHWHTYZZLM-UHFFFAOYSA-N 1-chloroethyl cyclohexyl carbonate Chemical compound CC(Cl)OC(=O)OC1CCCCC1 ONZWFHWHTYZZLM-UHFFFAOYSA-N 0.000 description 2
- HWGHZJXCEIQCAZ-UHFFFAOYSA-N 1-chloroethyl cyclopropanecarboxylate Chemical compound CC(Cl)OC(=O)C1CC1 HWGHZJXCEIQCAZ-UHFFFAOYSA-N 0.000 description 2
- MIGZEIZMIDGNJM-UHFFFAOYSA-N 1-chloroethyl decyl carbonate Chemical compound CCCCCCCCCCOC(=O)OC(C)Cl MIGZEIZMIDGNJM-UHFFFAOYSA-N 0.000 description 2
- RBJBURJVGINATA-UHFFFAOYSA-N 1-chloroethyl hexanoate Chemical compound CCCCCC(=O)OC(C)Cl RBJBURJVGINATA-UHFFFAOYSA-N 0.000 description 2
- UWPISDYPHIOHLE-UHFFFAOYSA-N 1-chloroethyl octyl carbonate Chemical compound CCCCCCCCOC(=O)OC(C)Cl UWPISDYPHIOHLE-UHFFFAOYSA-N 0.000 description 2
- XPTPAIJDVFQPJT-UHFFFAOYSA-N 1-chloroethyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC(C)Cl XPTPAIJDVFQPJT-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- LHOFEKWWYLEOFE-UHFFFAOYSA-N CC(C(C1=CC=CC=C1)OC(=O)O)Cl Chemical compound CC(C(C1=CC=CC=C1)OC(=O)O)Cl LHOFEKWWYLEOFE-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- WQRYMQHLFDVPFS-UHFFFAOYSA-N butyl 1-chloroethyl carbonate Chemical compound CCCCOC(=O)OC(C)Cl WQRYMQHLFDVPFS-UHFFFAOYSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- JUBQFNSRJOLWED-UHFFFAOYSA-N chloromethyl heptanoate Chemical compound CCCCCCC(=O)OCCl JUBQFNSRJOLWED-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- AVYHGVQTWUQQMZ-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl acetate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(OC(C)=O)C)=C1C(=O)NC1=CC=CC=N1 AVYHGVQTWUQQMZ-UHFFFAOYSA-N 0.000 description 1
- JUYYJDJBHXHKIC-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl benzoate Chemical compound C=1C=CC=NC=1NC(=O)C=1N(C)S(=O)(=O)C2=CC=CC=C2C=1OC(C)OC(=O)C1=CC=CC=C1 JUYYJDJBHXHKIC-UHFFFAOYSA-N 0.000 description 1
- RMLPCSZYQNNGDG-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl butanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CCC)=C1C(=O)NC1=CC=CC=N1 RMLPCSZYQNNGDG-UHFFFAOYSA-N 0.000 description 1
- PFVAZPZPFXGYCC-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl cyclopropanecarboxylate Chemical compound C=1C=CC=NC=1NC(=O)C=1N(C)S(=O)(=O)C2=CC=CC=C2C=1OC(C)OC(=O)C1CC1 PFVAZPZPFXGYCC-UHFFFAOYSA-N 0.000 description 1
- QAIUYSZIFIHZQV-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl hexanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CCCCC)=C1C(=O)NC1=CC=CC=N1 QAIUYSZIFIHZQV-UHFFFAOYSA-N 0.000 description 1
- HJWMJHXNDBVWHP-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl octanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CCCCCCC)=C1C(=O)NC1=CC=CC=N1 HJWMJHXNDBVWHP-UHFFFAOYSA-N 0.000 description 1
- BXZIXUQYQALTRQ-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl octyl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCCCCCCCC)=C1C(=O)NC1=CC=CC=N1 BXZIXUQYQALTRQ-UHFFFAOYSA-N 0.000 description 1
- USBMASWLIWZNPT-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl propan-2-yl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OC(C)C)=C1C(=O)NC1=CC=CC=N1 USBMASWLIWZNPT-UHFFFAOYSA-N 0.000 description 1
- OATHASWKDUNQAO-UHFFFAOYSA-N 1-[[2-methyl-3-[(6-methylpyridin-2-yl)carbamoyl]-1,1-dioxo-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl acetate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(OC(C)=O)C)=C1C(=O)NC1=CC=CC(C)=N1 OATHASWKDUNQAO-UHFFFAOYSA-N 0.000 description 1
- SNESIEZMBQHCEA-UHFFFAOYSA-N 1-[[2-methyl-3-[(6-methylpyridin-2-yl)carbamoyl]-1,1-dioxo-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl propanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CC)=C1C(=O)NC1=CC=CC(C)=N1 SNESIEZMBQHCEA-UHFFFAOYSA-N 0.000 description 1
- YVRGKFXJZCTTRB-UHFFFAOYSA-N 1-chloroethyl ethyl carbonate Chemical compound CCOC(=O)OC(C)Cl YVRGKFXJZCTTRB-UHFFFAOYSA-N 0.000 description 1
- YQDLLPYWECJXLT-UHFFFAOYSA-N 1-chloroethyl hexyl carbonate Chemical compound CCCCCCOC(=O)OC(C)Cl YQDLLPYWECJXLT-UHFFFAOYSA-N 0.000 description 1
- CERXDWLUWLFFEK-UHFFFAOYSA-N 1-chloroethyl methyl carbonate Chemical compound COC(=O)OC(C)Cl CERXDWLUWLFFEK-UHFFFAOYSA-N 0.000 description 1
- JDRDAYYFGOXRNO-UHFFFAOYSA-N 1-chloroethyl octanoate Chemical compound CCCCCCCC(=O)OC(C)Cl JDRDAYYFGOXRNO-UHFFFAOYSA-N 0.000 description 1
- WSMINTWDWKPQQQ-UHFFFAOYSA-N 1-chloroethyl propyl carbonate Chemical compound CCCOC(=O)OC(C)Cl WSMINTWDWKPQQQ-UHFFFAOYSA-N 0.000 description 1
- BNXXBTOUIRFFKD-UHFFFAOYSA-N 1-o-(iodomethyl) 3-o-methyl 2,2-dimethylpropanedioate Chemical compound COC(=O)C(C)(C)C(=O)OCI BNXXBTOUIRFFKD-UHFFFAOYSA-N 0.000 description 1
- MPXMYIPXSZTWOX-UHFFFAOYSA-N 1-o-methyl 3-o-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxymethyl] 2,2-dimethylpropanedioate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OCOC(=O)C(C)(C)C(=O)OC)=C1C(=O)NC1=CC=CC=N1 MPXMYIPXSZTWOX-UHFFFAOYSA-N 0.000 description 1
- ODQLAECNMKXOBI-UHFFFAOYSA-N 2-bromo-2h-furan-5-one Chemical compound BrC1OC(=O)C=C1 ODQLAECNMKXOBI-UHFFFAOYSA-N 0.000 description 1
- VYSUKBITJDOEML-UHFFFAOYSA-N 2-methyl-1,1-dioxo-4-[(3-oxo-1h-2-benzofuran-1-yl)oxy]-n-pyridin-2-yl-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound O1C(=O)C2=CC=CC=C2C1OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 VYSUKBITJDOEML-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 description 1
- GWFALVUXAGYMHR-UHFFFAOYSA-N 4-(bromomethyl)-5-methyl-1,3-dioxol-2-one Chemical compound CC=1OC(=O)OC=1CBr GWFALVUXAGYMHR-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PZCXUBJZCWDILL-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(=O)OC(C)OC1=C(N(S(C2=C1C=CC=C2)(=O)=O)C)C(=O)NC2=NC=CC=C2 Chemical compound C(C1=CC=CC=C1)OC(=O)OC(C)OC1=C(N(S(C2=C1C=CC=C2)(=O)=O)C)C(=O)NC2=NC=CC=C2 PZCXUBJZCWDILL-UHFFFAOYSA-N 0.000 description 1
- ABWQDCVKMWJXFG-UHFFFAOYSA-N CCC(C(C)Cl)OC(O)=O Chemical compound CCC(C(C)Cl)OC(O)=O ABWQDCVKMWJXFG-UHFFFAOYSA-N 0.000 description 1
- ICWRYUDLLJPTTL-UHFFFAOYSA-N CCCCCC(C(C)Cl)OC(O)=O Chemical compound CCCCCC(C(C)Cl)OC(O)=O ICWRYUDLLJPTTL-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- NXMUYNHBKIVHDF-UHFFFAOYSA-N [2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxymethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCOC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 NXMUYNHBKIVHDF-UHFFFAOYSA-N 0.000 description 1
- CMFWUZSQMLDIFN-UHFFFAOYSA-N [2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxymethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCOC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 CMFWUZSQMLDIFN-UHFFFAOYSA-N 0.000 description 1
- WQKLPJPTEGDHLH-UHFFFAOYSA-N [2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxymethyl heptanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OCOC(=O)CCCCCC)=C1C(=O)NC1=CC=CC=N1 WQKLPJPTEGDHLH-UHFFFAOYSA-N 0.000 description 1
- WFXRMYGJFLYCMT-UHFFFAOYSA-N [2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxymethyl octanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OCOC(=O)CCCCCCC)=C1C(=O)NC1=CC=CC=N1 WFXRMYGJFLYCMT-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- LSNWBKACGXCGAJ-UHFFFAOYSA-N ampiroxicam Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCC)=C1C(=O)NC1=CC=CC=N1 LSNWBKACGXCGAJ-UHFFFAOYSA-N 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- ZRWKDMLCIQLGSK-UHFFFAOYSA-N benzyl 1-chloroethyl carbonate Chemical compound CC(Cl)OC(=O)OCC1=CC=CC=C1 ZRWKDMLCIQLGSK-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- KXYXAWCEDBVEEY-UHFFFAOYSA-N butyl 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCCCC)=C1C(=O)NC1=CC=CC=N1 KXYXAWCEDBVEEY-UHFFFAOYSA-N 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- WNYFCMHPHRGZBI-UHFFFAOYSA-N cyclohexyl 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl carbonate Chemical compound C=1C=CC=NC=1NC(=O)C=1N(C)S(=O)(=O)C2=CC=CC=C2C=1OC(C)OC(=O)OC1CCCCC1 WNYFCMHPHRGZBI-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- SKPFBXBLGCPJPC-UHFFFAOYSA-N decyl 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCCCCCCCCCC)=C1C(=O)NC1=CC=CC=N1 SKPFBXBLGCPJPC-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- NVIWQCSCGJHYNS-UHFFFAOYSA-N ethyl 1-[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)thieno[2,3-e]thiazin-4-yl]oxyethyl carbonate Chemical compound CN1S(=O)(=O)C=2C=CSC=2C(OC(C)OC(=O)OCC)=C1C(=O)NC1=CC=CC=N1 NVIWQCSCGJHYNS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
- MIMDPXYFJJQBRI-UHFFFAOYSA-N hexyl 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCCCCCC)=C1C(=O)NC1=CC=CC=N1 MIMDPXYFJJQBRI-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- NVQWYEQPRWTRRK-UHFFFAOYSA-N methyl 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OC)=C1C(=O)NC1=CC=CC=N1 NVQWYEQPRWTRRK-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56390283A | 1983-12-21 | 1983-12-21 | |
| US563902 | 1983-12-21 | ||
| US606113 | 1984-05-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60156688A JPS60156688A (ja) | 1985-08-16 |
| JPH0246036B2 true JPH0246036B2 (ja) | 1990-10-12 |
Family
ID=24252352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27058684A Expired - Lifetime JPH0246036B2 (ja) | 1983-12-21 | 1984-12-21 | Koenshoseiokishikamunoeeteruzenkuyakuzai |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPH0246036B2 (cs) |
| CS (1) | CS248726B2 (cs) |
| IN (1) | IN162323B (cs) |
| SU (1) | SU1503682A3 (cs) |
| ZA (1) | ZA849926B (cs) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI880177L (fi) * | 1986-05-16 | 1988-01-15 | Pfizer | Benzotiazindioxidderivat. |
| WO1989003682A1 (en) * | 1987-10-26 | 1989-05-05 | Pfizer Inc. | Benzothiazine dioxide derivatives |
| EP2084165B1 (en) * | 2006-10-11 | 2013-06-12 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of oxicams and related compounds with very high skin penetration rate |
| RU2544853C1 (ru) * | 2013-12-18 | 2015-03-20 | Открытое Акционерное Общество "Международная Научно-Технологическая Корпорация" | N-ГЕТАРИЛЗАМЕЩЕННЫЕ 4-ГИДРОКСИ-1-МЕТИЛ-2,2-ДИОКСО-1H-2λ6,1-БЕНЗОТИАЗИН-3-КАРБОКСАМИДЫ, ПРОЯВЛЯЮЩИЕ АНАЛЬГЕТИЧЕСКУЮ АКТИВНОСТЬ |
-
1984
- 1984-10-26 IN IN831/DEL/84A patent/IN162323B/en unknown
- 1984-12-19 CS CS1000284A patent/CS248726B2/cs unknown
- 1984-12-20 ZA ZA849926A patent/ZA849926B/xx unknown
- 1984-12-20 SU SU843829753A patent/SU1503682A3/ru active
- 1984-12-21 JP JP27058684A patent/JPH0246036B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CS248726B2 (cs) | 1987-02-12 |
| SU1503682A3 (ru) | 1989-08-23 |
| IN162323B (cs) | 1988-04-30 |
| JPS60156688A (ja) | 1985-08-16 |
| ZA849926B (en) | 1986-08-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |