DD229125A5 - Verfahren zur herstellung von ether-vorwirkstoffen von entzuendungshemmenden oxicamen - Google Patents

Verfahren zur herstellung von ether-vorwirkstoffen von entzuendungshemmenden oxicamen Download PDF

Info

Publication number: DD229125A5
Authority: DD; German Democratic Republic
Prior art keywords: mmol; methyl; found; cdcl; pyridyl
Prior art date: 1983-12-21

Application number

DD84271297A

Other languages

German (de)

English (en)

Inventor

Anthony Marfat

Original Assignee

Pfizer

Priority date (The priority date 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 date listed.)

1983-12-21

Filing date

1984-12-20

Publication date

1985-10-30

1984-12-20 Application filed by Pfizer filed Critical Pfizer

1985-10-30 Publication of DD229125A5 publication Critical patent/DD229125A5/de

Links

238000000034 method Methods 0.000 title claims description 55
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 21
238000002360 preparation method Methods 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000001257 hydrogen Substances 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
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
230000000269 nucleophilic effect Effects 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical group 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 claims 1
125000000129 anionic group Chemical group 0.000 claims 1
229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 abstract description 8
229940002612 prodrug Drugs 0.000 abstract description 6
239000000651 prodrug Substances 0.000 abstract description 6
150000002084 enol ethers Chemical class 0.000 abstract description 4
230000001166 anti-perspirative effect Effects 0.000 abstract 1
239000003213 antiperspirant Substances 0.000 abstract 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 60
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 55
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
239000000047 product Substances 0.000 description 52
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
239000003921 oil Substances 0.000 description 42
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
-1 enol esters Chemical class 0.000 description 38
238000010992 reflux Methods 0.000 description 37
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 class OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 29
239000013078 crystal Substances 0.000 description 28
229960002702 piroxicam Drugs 0.000 description 28
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 27
239000007787 solid Substances 0.000 description 23
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
229910000027 potassium carbonate Inorganic materials 0.000 description 16
239000006260 foam Substances 0.000 description 15
239000012299 nitrogen atmosphere Substances 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 14
238000003756 stirring Methods 0.000 description 14
238000004519 manufacturing process Methods 0.000 description 12
150000003254 radicals Chemical class 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
239000012267 brine Substances 0.000 description 10
239000000284 extract 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
238000004821 distillation Methods 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
235000009518 sodium iodide Nutrition 0.000 description 9
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 8
239000010410 layer Substances 0.000 description 8
239000000377 silicon dioxide Substances 0.000 description 8
239000000243 solution Substances 0.000 description 7
230000003110 anti-inflammatory effect Effects 0.000 description 6
YAIJCYICFZACKO-UHFFFAOYSA-N 2-methyl-1,1-dioxo-n-pyridin-2-yl-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound C=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 YAIJCYICFZACKO-UHFFFAOYSA-N 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
229910052799 carbon Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
JRCUJOMLYAQHDP-UHFFFAOYSA-N chloromethyl octanoate Chemical compound CCCCCCCC(=O)OCCl JRCUJOMLYAQHDP-UHFFFAOYSA-N 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
238000012800 visualization Methods 0.000 description 4
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
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 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
JUBQFNSRJOLWED-UHFFFAOYSA-N chloromethyl heptanoate Chemical compound CCCCCCC(=O)OCCl JUBQFNSRJOLWED-UHFFFAOYSA-N 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000007921 spray Substances 0.000 description 3
241000124008 Mammalia Species 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
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 2
229910052794 bromium Inorganic materials 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
MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000008241 heterogeneous mixture Substances 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
YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
238000010898 silica gel chromatography Methods 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
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
YSMNECAIZNOYOW-UHFFFAOYSA-N 1,1-dioxo-2h-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound C1=CC=C2S(=O)(=O)NC(C(=O)N)=CC2=C1 YSMNECAIZNOYOW-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
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
ODQLAECNMKXOBI-UHFFFAOYSA-N 2-bromo-2h-furan-5-one Chemical compound BrC1OC(=O)C=C1 ODQLAECNMKXOBI-UHFFFAOYSA-N 0.000 description 1
VIRWKAJWTKAIMA-UHFFFAOYSA-N 2-chloroethyl acetate Chemical compound CC(=O)OCCCl VIRWKAJWTKAIMA-UHFFFAOYSA-N 0.000 description 1
IJDRTYIIAPJELW-UHFFFAOYSA-N 2-chloroethyl cyclohexyl carbonate Chemical compound ClCCOC(=O)OC1CCCCC1 IJDRTYIIAPJELW-UHFFFAOYSA-N 0.000 description 1
XUNRQBJWHFPDGB-UHFFFAOYSA-N 2-chloroethyl cyclopropanecarboxylate Chemical compound ClCCOC(=O)C1CC1 XUNRQBJWHFPDGB-UHFFFAOYSA-N 0.000 description 1
JIUOWPDPFXJIAC-UHFFFAOYSA-N 2-chloroethyl hexanoate Chemical compound CCCCCC(=O)OCCCl JIUOWPDPFXJIAC-UHFFFAOYSA-N 0.000 description 1
OBQGROSAOBAGBU-UHFFFAOYSA-N 2-chloroethyl octyl carbonate Chemical compound CCCCCCCCOC(=O)OCCCl OBQGROSAOBAGBU-UHFFFAOYSA-N 0.000 description 1
CJHNKKRUNUMBJX-UHFFFAOYSA-N 2-chloroethyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OCCCl CJHNKKRUNUMBJX-UHFFFAOYSA-N 0.000 description 1
VKSJVMZEQNIBNA-UHFFFAOYSA-N 2-chloroethyl propanoate Chemical compound CCC(=O)OCCCl VKSJVMZEQNIBNA-UHFFFAOYSA-N 0.000 description 1
ZXJZJGNOUJHEIZ-UHFFFAOYSA-N 2-chloroethyl propyl carbonate Chemical compound CCCOC(=O)OCCCl ZXJZJGNOUJHEIZ-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$l^{6},2-benzothiazine-3-carboxamide Chemical compound O1C(=O)C2=CC=CC=C2C1OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 VYSUKBITJDOEML-UHFFFAOYSA-N 0.000 description 1
YWXSCVWEJBLKTK-UHFFFAOYSA-N 2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1lambda6,2-benzothiazine-3-carboxamide Chemical compound C=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YWXSCVWEJBLKTK-UHFFFAOYSA-N 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 description 1
QPJCLMSEUYJIOV-UHFFFAOYSA-N 3-chloropropyl hydrogen carbonate Chemical compound OC(=O)OCCCCl QPJCLMSEUYJIOV-UHFFFAOYSA-N 0.000 description 1
NIGKHKLDZOHYMT-UHFFFAOYSA-N 4-hydroxy-2-methyl-n-(6-methylpyridin-2-yl)-1,1-dioxo-1$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 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-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
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 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
235000019445 benzyl alcohol Nutrition 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000002051 biphasic effect 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
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 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
238000004587 chromatography analysis Methods 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-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
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
238000005187 foaming Methods 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000010438 heat treatment Methods 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
230000004968 inflammatory condition Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
229950002252 isoxicam Drugs 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
PFDBGXHVSBXDHS-UHFFFAOYSA-N n-(6-chloropyridin-2-yl)-4-hydroxy-2-methyl-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(Cl)=N1 PFDBGXHVSBXDHS-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000000546 pharmaceutical excipient 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
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
BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
NMTDPTPUELYEPL-UHFFFAOYSA-M sodium;heptanoate Chemical compound [Na+].CCCCCCC([O-])=O NMTDPTPUELYEPL-UHFFFAOYSA-M 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C68/00—Preparation of esters of carbonic or haloformic acids
- C07C68/02—Preparation of esters of carbonic or haloformic acids from phosgene or haloformates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/14—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 three or more hetero rings

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)

DD84271297A 1983-12-21 1984-12-20 Verfahren zur herstellung von ether-vorwirkstoffen von entzuendungshemmenden oxicamen DD229125A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US56390283A	1983-12-21	1983-12-21
US06/606,113 US4551452A (en)	1983-12-21	1984-05-02	Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor

Publications (1)

Publication Number	Publication Date
DD229125A5 true DD229125A5 (de)	1985-10-30

Family

ID=27073413

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD84271297A DD229125A5 (de)	1983-12-21	1984-12-20	Verfahren zur herstellung von ether-vorwirkstoffen von entzuendungshemmenden oxicamen

Country Status (26)

Country	Link
US (1)	US4551452A (fr)
EP (1)	EP0147177B1 (fr)
KR (1)	KR860002035B1 (fr)
AU (1)	AU552940B2 (fr)
BG (1)	BG47946A3 (fr)
CA (1)	CA1255302A (fr)
DD (1)	DD229125A5 (fr)
DE (1)	DE3466776D1 (fr)
DK (1)	DK166678B1 (fr)
EG (1)	EG17049A (fr)
ES (1)	ES8604215A1 (fr)
FI (1)	FI79850C (fr)
GR (1)	GR82512B (fr)
HK (1)	HK58589A (fr)
HU (1)	HU201063B (fr)
IE (1)	IE57680B1 (fr)
IL (1)	IL73873A (fr)
MX (2)	MX174596B (fr)
NO (1)	NO161317C (fr)
NZ (1)	NZ210632A (fr)
PH (1)	PH21447A (fr)
PL (1)	PL145989B1 (fr)
PT (1)	PT79700B (fr)
RO (1)	RO90048A (fr)
SG (1)	SG27001G (fr)
YU (1)	YU43677B (fr)

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* Cited by examiner, † Cited by third party
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US4778795A (en) *	1983-11-25	1988-10-18	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4616012A (en) *	1983-11-25	1986-10-07	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4906635A (en) *	1983-11-25	1990-03-06	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US5017567A (en) *	1983-11-25	1991-05-21	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4623486A (en) *	1985-05-29	1986-11-18	Pfizer Inc.	[4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity
KR890001236B1 (ko) *	1985-10-02	1989-04-28	화이자 인코포레이티드	소염제 조성물의 제조방법
US4771071A (en) *	1986-05-05	1988-09-13	Merck & Co., Inc.	Antihypercholesterolemic compounds
US4829062A (en) *	1986-05-16	1989-05-09	Pfizer Inc.	Benzothiazine dioxide derivatives
WO1989003682A1 (fr) *	1987-10-26	1989-05-05	Pfizer Inc.	Derives de dioxyde de benzothiazine
NZ226477A (en) *	1987-10-29	1990-07-26	Cl Pharma	Substituted thieno (2,3-e)-1,2 thiazine derivatives and pharmaceutical compositions
ZA945190B (en) *	1993-07-30	1995-02-24	Kotobuki Seiyaku Co Ltd	Carboxymethylidenecycloheptimidazole derivatives method or manufacturing the same and therapeutic agents containing these compounds
IT1308633B1 (it)	1999-03-02	2002-01-09	Nicox Sa	Nitrossiderivati.
CN100389114C (zh) *	2006-01-17	2008-05-21	南京新港医药有限公司	一种安吡昔康的精制方法
US20090221703A1 (en)	2006-07-09	2009-09-03	Chongxi Yu	High penetration composition and uses thereof
US20090238763A1 (en) *	2006-07-09	2009-09-24	Chongxi Yu	High penetration compositions and uses thereof
CN101522692A (zh) *	2006-10-11	2009-09-02	于崇曦	具有快速皮肤穿透速度的带正电荷的水溶性的昔康及其相关化合物的前药
MX377501B (es) *	2007-06-04	2025-03-10	Techfields Inc	Profarmacos de nsaias con el piel y membranas con indices de penetracion muy altos y nuevos usos medicinales.
RU2630577C2 (ru)	2008-12-04	2017-09-11	Чунси ЮЙ	Композиции интенсивного проникновения и их применение
WO2013093931A2 (fr)	2011-09-19	2013-06-27	Sun Pharma Advanced Research Company Ltd.	Nouveaux promédicaments de médicaments phénoliques

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3591584A (en) *	1968-08-27	1971-07-06	Pfizer	Benzothiazine dioxides
US3787324A (en) *	1971-03-01	1974-01-22	Warner Lambert Co	4-hydroxy-3-(3-isoxazolocarbamyl)-2h-1,2-benzothiazine 1,dioxides and process for their production
US3892740A (en) *	1974-10-15	1975-07-01	Pfizer	Process for the production of carboxamides of oxo-1,2-benzothiazine-1,1-dioxides
AU518216B2 (en) *	1977-09-06	1981-09-17	Hafslund Nycomed Pharma Aktiengesellschaft	Thienothiazine derivatives
US4309427A (en) *	1981-01-15	1982-01-05	Pfizer Inc.	Benzothiazine dioxide derivatives
IT1168064B (it) *	1981-11-12	1987-05-20	Prodotti Antibiotici Spa	Composto ad azione antinfiammatoria
IT8219486A0 (it) *	1982-02-05	1982-02-05	Chiesi Farma Spa	Nuovi composti ad attivita'antiinfiammatoria, procedimento per la loro preparazione e relative composizioni farmaceutiche.

1984
- 1984-05-02 US US06/606,113 patent/US4551452A/en not_active Expired - Lifetime
- 1984-11-28 PH PH31504A patent/PH21447A/en unknown
- 1984-12-18 PT PT79700A patent/PT79700B/pt unknown
- 1984-12-19 GR GR82512A patent/GR82512B/el unknown
- 1984-12-19 EG EG786/84A patent/EG17049A/xx active
- 1984-12-19 NZ NZ210632A patent/NZ210632A/en unknown
- 1984-12-19 IE IE3260/84A patent/IE57680B1/en not_active IP Right Cessation
- 1984-12-19 RO RO84116745A patent/RO90048A/fr unknown
- 1984-12-19 EP EP84308926A patent/EP0147177B1/fr not_active Expired
- 1984-12-19 SG SG305/89A patent/SG27001G/en unknown
- 1984-12-19 PL PL1984251040A patent/PL145989B1/pl unknown
- 1984-12-19 CA CA000470471A patent/CA1255302A/fr not_active Expired
- 1984-12-19 DE DE8484308926T patent/DE3466776D1/de not_active Expired
- 1984-12-20 BG BG067990A patent/BG47946A3/xx unknown
- 1984-12-20 HU HU844756A patent/HU201063B/hu unknown
- 1984-12-20 YU YU2160/84A patent/YU43677B/xx unknown
- 1984-12-20 FI FI845074A patent/FI79850C/fi active IP Right Grant
- 1984-12-20 IL IL73873A patent/IL73873A/xx not_active IP Right Cessation
- 1984-12-20 ES ES538907A patent/ES8604215A1/es not_active Expired
- 1984-12-20 AU AU36997/84A patent/AU552940B2/en not_active Expired
- 1984-12-20 DK DK614984A patent/DK166678B1/da active
- 1984-12-20 MX MX005836A patent/MX174596B/es unknown
- 1984-12-20 NO NO845145A patent/NO161317C/no not_active IP Right Cessation
- 1984-12-20 KR KR1019840008144A patent/KR860002035B1/ko not_active Expired
- 1984-12-20 DD DD84271297A patent/DD229125A5/de not_active IP Right Cessation
1989
- 1989-07-20 HK HK585/89A patent/HK58589A/en not_active IP Right Cessation
1992
- 1992-06-29 MX MX9203740A patent/MX9203740A/es unknown

Also Published As

Publication number	Publication date
HU201063B (en)	1990-09-28
FI845074L (fi)	1985-06-22
ES538907A0 (es)	1986-01-16
US4551452A (en)	1985-11-05
DK166678B1 (da)	1993-06-28
BG47946A3 (en)	1990-10-15
EP0147177B1 (fr)	1987-10-14
SG27001G (en)	1989-08-11
EG17049A (en)	1991-03-30
GR82512B (en)	1985-04-22
CA1255302A (fr)	1989-06-06
YU216084A (en)	1986-10-31
FI79850B (fi)	1989-11-30
PL145989B1 (en)	1988-12-31
KR860002035B1 (ko)	1986-11-17
HK58589A (en)	1989-07-28
DK614984A (da)	1985-07-17
RO90048A (fr)	1986-09-30
NO161317C (no)	1989-08-02
PT79700B (en)	1986-12-30
FI845074A0 (fi)	1984-12-20
YU43677B (en)	1989-10-31
MX174596B (es)	1994-05-30
KR850004492A (ko)	1985-07-15
ES8604215A1 (es)	1986-01-16
DK614984D0 (da)	1984-12-20
HUT37426A (en)	1985-12-28
PH21447A (en)	1987-10-28
NZ210632A (en)	1987-02-20
AU3699784A (en)	1985-07-04
PT79700A (en)	1985-01-01
EP0147177A2 (fr)	1985-07-03
MX9203740A (es)	1992-09-01
IE843260L (en)	1985-06-21
PL251040A1 (en)	1985-10-22
IL73873A (en)	1988-02-29
EP0147177A3 (en)	1985-08-14
AU552940B2 (en)	1986-06-26
FI79850C (fi)	1990-03-12
IL73873A0 (en)	1985-03-31
NO161317B (no)	1989-04-24
IE57680B1 (en)	1993-02-24
DE3466776D1 (en)	1987-11-19
NO845145L (no)	1985-06-24

Legal Events

Date	Code	Title	Description
1994-04-14	NPV	Change in the person, the name or the address of the representative (addendum to changes before extension act)
2001-06-21	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
DD229125A5 (de)	1985-10-30	Verfahren zur herstellung von ether-vorwirkstoffen von entzuendungshemmenden oxicamen
DE3789536T2 (de)	1994-08-18	Pyridin-Derivate, deren pharmazeutische Zusammenstellungen, deren Anwendung für die Herstellung von Arzneimitteln mit therapeutischem oder vorbeugendem Wert und Verfahren zu deren Herstellung.
DE69024896T2 (de)	1996-06-13	Chinonderivate und ihre pharmakologische Verwendung
DE60012883T2 (de)	2005-08-25	2,3,4,5-tetrahydro-1h-[1,4]benzodiazepin-3-hydroxamsäure als matrix metalloproteinaseinhibitoren
EP0658559A1 (fr)	1995-06-21	Dérivés thiénothianine, procédé pour leur préparation et leur application comme inhibiteurs de 5-dipoxygenase et cyclooxygenase
HU219950B (hu)	2001-09-28	Proteolitikus enzimeket gátló szacharinszármazékok és ezeket tartalmazó gyógyászati készítmények, valamint a szacharinszármazékok előállítása
CH628901A5 (de)	1982-03-31	Verfahren zur herstellung von cephalosporinantibiotika.
DE69811930T2 (de)	2003-12-18	Tricyclische triazolobenzazepinderivate, verfahren zu ihrer herstellung und antiallergische mittel
DE69018876T2 (de)	1995-08-24	Pyridazinon-Derivate.
EP0096297B1 (fr)	1988-06-15	Procédé de préparation de dérivés de 1-sulfo-2-oxoazétidine
DD213920A5 (de)	1984-09-26	Verfahren zur herstellung von dihydropyridinen
DE2537070A1 (de)	1976-03-18	Thiazinderivate
DE69408593T2 (de)	1998-07-16	4-Aryl-4-Hydroxy-Tetrahydropyrane und 3-Aryl-3-Hydroxy-Tetrahydrofurane als 5-Lipoxygenaseinhibitoren
DE69418218T2 (de)	1999-11-04	Chinolonylcarboxamidocephalosporin-derivate und diese enthaltende arzneimittel
DE60210977T2 (de)	2006-09-21	Immunmodulierende verbindungen
FR2496106A1 (fr)	1982-06-18	Derives d'acide 7-acylaminocephalosporanique et procede pour leur preparation
DE68924221T2 (de)	1996-02-15	Imidazolderivate.
WO1989005299A1 (fr)	1989-06-15	Nouveaux derives benzoglyoxaline
DE3012584A1 (de)	1980-10-16	6-substituierte pyranon-verbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel
DE2914843A1 (de)	1979-10-18	7 alpha -methoxycephalosporin-derivate, verfahren zu deren herstellung und deren verwendung
SU1503682A3 (ru)	1989-08-23	Способ получени енольных производных оксикамов
DD232045A5 (de)	1986-01-15	Verfahren zur herstellung von vorwirkstoffen entzuendungshemmender oxicame
DD259401A5 (de)	1988-08-24	Verfahren zur herstellung von 2-alkylbenzimidazol-derivaten
DE3780112T2 (de)	1992-12-24	Verfahren zur herstellung von penicillansaeure-derivaten.
DE1620249A1 (de)	1970-05-21	Verfahren zur Herstellung von Pyrimidopyrimidothiazinverbindungen und/oder Thiazinverbindungen