SK12862000A3 - Spôsob výroby inhibítorov 5-lipoxygenázy s rôznymi heterocyklickými systémami - Google Patents

Spôsob výroby inhibítorov 5-lipoxygenázy s rôznymi heterocyklickými systémami Download PDF

Info

Publication number: SK12862000A3
Authority: SK; Slovakia
Prior art keywords: formula; group; compound; aryl; carbon atoms
Prior art date: 1999-08-31

Application number

SK1286-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Timothy Norris

Elizabeth Hnatow Megan

Original Assignee

Pfizer Products Inc.

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.)

1999-08-31

Filing date

2000-08-25

Publication date

2002-02-05

2000-08-25 Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.

2002-02-05 Publication of SK12862000A3 publication Critical patent/SK12862000A3/sk

Links

238000004519 manufacturing process Methods 0.000 title claims description 34
239000000867 Lipoxygenase Inhibitor Substances 0.000 title description 14
125000000623 heterocyclic group Chemical group 0.000 title description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 231
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 171
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 155
150000001875 compounds Chemical class 0.000 claims abstract description 142
238000000034 method Methods 0.000 claims abstract description 125
239000003446 ligand Substances 0.000 claims abstract description 111
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 81
230000008569 process Effects 0.000 claims abstract description 77
239000011541 reaction mixture Substances 0.000 claims abstract description 72
229910052763 palladium Inorganic materials 0.000 claims abstract description 57
239000003054 catalyst Substances 0.000 claims abstract description 52
-1 palladium metal complex Chemical class 0.000 claims abstract description 44
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical group [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims abstract description 35
239000007787 solid Substances 0.000 claims abstract description 33
239000003444 phase transfer catalyst Substances 0.000 claims abstract description 31
238000010438 heat treatment Methods 0.000 claims abstract description 28
239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 25
229910052723 transition metal Inorganic materials 0.000 claims abstract description 25
150000003624 transition metals Chemical class 0.000 claims abstract description 25
239000002904 solvent Substances 0.000 claims abstract description 23
239000000010 aprotic solvent Substances 0.000 claims abstract description 15
150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 12
150000001491 aromatic compounds Chemical class 0.000 claims abstract description 11
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 74
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 54
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
239000002585 base Substances 0.000 claims description 41
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 40
238000010992 reflux Methods 0.000 claims description 40
239000000203 mixture Substances 0.000 claims description 38
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 34
239000001257 hydrogen Substances 0.000 claims description 34
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 30
YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 claims description 30
OQNBCJNBUPLGQN-UHFFFAOYSA-N 2-phenyl-2H-pyran-4-carboxamide Chemical compound C1(=CC=CC=C1)C1OC=CC(=C1)C(=O)N OQNBCJNBUPLGQN-UHFFFAOYSA-N 0.000 claims description 28
125000004076 pyridyl group Chemical group 0.000 claims description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
239000004305 biphenyl Substances 0.000 claims description 27
235000010290 biphenyl Nutrition 0.000 claims description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 26
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 24
239000000243 solution Substances 0.000 claims description 24
230000003197 catalytic effect Effects 0.000 claims description 23
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 21
VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 20
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 20
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 19
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 18
125000001624 naphthyl group Chemical group 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 18
CALLTGJPWMIDPC-UHFFFAOYSA-M tetraethylazanium;chloride;hydrate Chemical compound O.[Cl-].CC[N+](CC)(CC)CC CALLTGJPWMIDPC-UHFFFAOYSA-M 0.000 claims description 18
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 17
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 17
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 claims description 17
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 16
LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 16
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 16
229910000024 caesium carbonate Inorganic materials 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 claims description 16
RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 claims description 16
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 15
229910052736 halogen Inorganic materials 0.000 claims description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 15
OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 14
230000002950 deficient Effects 0.000 claims description 14
150000002367 halogens Chemical group 0.000 claims description 14
239000011734 sodium Substances 0.000 claims description 14
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 13
125000002619 bicyclic group Chemical group 0.000 claims description 13
125000002950 monocyclic group Chemical group 0.000 claims description 13
229910052698 phosphorus Inorganic materials 0.000 claims description 13
239000011574 phosphorus Substances 0.000 claims description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
229910052794 bromium Inorganic materials 0.000 claims description 12
OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 claims description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 11
125000000168 pyrrolyl group Chemical group 0.000 claims description 11
101150003085 Pdcl gene Proteins 0.000 claims description 10
125000001246 bromo group Chemical group Br* 0.000 claims description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 claims description 10
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 10
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 claims description 9
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 9
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 9
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
125000002541 furyl group Chemical group 0.000 claims description 9
239000011630 iodine Chemical group 0.000 claims description 9
229910052740 iodine Chemical group 0.000 claims description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 9
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
125000005493 quinolyl group Chemical group 0.000 claims description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
125000003944 tolyl group Chemical group 0.000 claims description 9
229910052721 tungsten Inorganic materials 0.000 claims description 9
229910052727 yttrium Inorganic materials 0.000 claims description 9
GFEJZIULYONCQB-UHFFFAOYSA-M 1-benzylquinolin-1-ium;chloride Chemical compound [Cl-].C=1C=CC2=CC=CC=C2[N+]=1CC1=CC=CC=C1 GFEJZIULYONCQB-UHFFFAOYSA-M 0.000 claims description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
UDYGXWPMSJPFDG-UHFFFAOYSA-M benzyl(tributyl)azanium;bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 UDYGXWPMSJPFDG-UHFFFAOYSA-M 0.000 claims description 8
CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 claims description 8
WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
229940098779 methanesulfonic acid Drugs 0.000 claims description 8
150000002825 nitriles Chemical class 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 8
WPPGURUIRLDHAB-UHFFFAOYSA-M triethyl(hexadecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](CC)(CC)CC WPPGURUIRLDHAB-UHFFFAOYSA-M 0.000 claims description 8
AQZSPJRLCJSOED-UHFFFAOYSA-M trimethyl(octyl)azanium;chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(C)C AQZSPJRLCJSOED-UHFFFAOYSA-M 0.000 claims description 8
XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 claims description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 7
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 7
229910052783 alkali metal Inorganic materials 0.000 claims description 7
150000001340 alkali metals Chemical class 0.000 claims description 7
229910052792 caesium Inorganic materials 0.000 claims description 7
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
229910052744 lithium Inorganic materials 0.000 claims description 7
UJNZOIKQAUQOCN-UHFFFAOYSA-N methyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C)C1=CC=CC=C1 UJNZOIKQAUQOCN-UHFFFAOYSA-N 0.000 claims description 7
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 7
239000011591 potassium Substances 0.000 claims description 7
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 7
229910052701 rubidium Inorganic materials 0.000 claims description 7
IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 claims description 7
229910052708 sodium Inorganic materials 0.000 claims description 7
NLWBEORDOPDUPM-UHFFFAOYSA-N 1,2,3,4-cyclopentanetetracarboxylic dianhydride Chemical compound O=C1OC(=O)C2C1C1C(=O)OC(=O)C1C2 NLWBEORDOPDUPM-UHFFFAOYSA-N 0.000 claims description 6
MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 6
CUGPDVWIMLFIQR-UHFFFAOYSA-N 2-methylpropan-2-olate;rubidium(1+) Chemical compound [Rb+].CC(C)(C)[O-] CUGPDVWIMLFIQR-UHFFFAOYSA-N 0.000 claims description 6
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
NVBVGMKBMCZMFG-UHFFFAOYSA-N cesium;2-methylpropan-2-olate Chemical compound [Cs+].CC(C)(C)[O-] NVBVGMKBMCZMFG-UHFFFAOYSA-N 0.000 claims description 6
XDPCFUNJJWMBFH-UHFFFAOYSA-N cesium;ethanolate Chemical compound [Cs+].CC[O-] XDPCFUNJJWMBFH-UHFFFAOYSA-N 0.000 claims description 6
239000000470 constituent Substances 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
JBOAOTRFANJYGJ-UHFFFAOYSA-N ethanolate;rubidium(1+) Chemical compound [Rb+].CC[O-] JBOAOTRFANJYGJ-UHFFFAOYSA-N 0.000 claims description 6
125000004438 haloalkoxy group Chemical class 0.000 claims description 6
125000006303 iodophenyl group Chemical group 0.000 claims description 6
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 claims description 6
LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 6
AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 claims description 6
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims description 6
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
239000000539 dimer Substances 0.000 claims description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
JKOSHCYVZPCHSJ-UHFFFAOYSA-N benzene;toluene Chemical compound C1=CC=CC=C1.C1=CC=CC=C1.CC1=CC=CC=C1 JKOSHCYVZPCHSJ-UHFFFAOYSA-N 0.000 claims description 3
SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 claims description 3
238000002425 crystallisation Methods 0.000 claims description 3
230000008025 crystallization Effects 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
238000002955 isolation Methods 0.000 claims description 3
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
238000000926 separation method Methods 0.000 claims description 3
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
230000007704 transition Effects 0.000 claims description 3
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USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
238000010586 diagram Methods 0.000 description 1
150000001987 diarylethers Chemical class 0.000 description 1
BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 1
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
150000001993 dienes Chemical class 0.000 description 1
CXQRZKIIGJLWPJ-UHFFFAOYSA-N diphenylphosphane;1-naphthalen-1-ylnaphthalene Chemical group C=1C=CC=CC=1PC1=CC=CC=C1.C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 CXQRZKIIGJLWPJ-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
229960001123 epoprostenol Drugs 0.000 description 1
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
DGYUNNISKYKIDM-UHFFFAOYSA-N ethyl 4-(2-methylimidazol-1-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1C(C)=NC=C1 DGYUNNISKYKIDM-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
230000036251 extravasation Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
MDQRDWAGHRLBPA-UHFFFAOYSA-N fluoroamine Chemical compound FN MDQRDWAGHRLBPA-UHFFFAOYSA-N 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
238000007172 homogeneous catalysis Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
238000006459 hydrosilylation reaction Methods 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000006872 improvement Effects 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910001412 inorganic anion Inorganic materials 0.000 description 1
DCYOBGZUOMKFPA-UHFFFAOYSA-N iron(2+);iron(3+);octadecacyanide Chemical compound [Fe+2].[Fe+2].[Fe+2].[Fe+3].[Fe+3].[Fe+3].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] DCYOBGZUOMKFPA-UHFFFAOYSA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
YQCIWBXEVYWRCW-UHFFFAOYSA-N methane;sulfane Chemical compound C.S YQCIWBXEVYWRCW-UHFFFAOYSA-N 0.000 description 1
MSEBQGULDWDIRW-UHFFFAOYSA-N methyl 4-fluorobenzoate Chemical group COC(=O)C1=CC=C(F)C=C1 MSEBQGULDWDIRW-UHFFFAOYSA-N 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical class O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
230000000414 obstructive effect Effects 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
125000005564 oxazolylene group Chemical group 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
150000002940 palladium Chemical class 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000005501 phase interface Effects 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
238000006116 polymerization reaction Methods 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000000634 powder X-ray diffraction Methods 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000011165 process development Methods 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
125000005551 pyridylene group Chemical group 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
241000894007 species Species 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
150000008054 sulfonate salts Chemical class 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000005557 thiazolylene group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003595 thromboxanes Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
150000003623 transition metal compounds Chemical class 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Rheumatology (AREA)
Plural Heterocyclic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrane Compounds (AREA)
Pyridine Compounds (AREA)
Catalysts (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

SK1286-2000A 1999-08-31 2000-08-25 Spôsob výroby inhibítorov 5-lipoxygenázy s rôznymi heterocyklickými systémami SK12862000A3 (sk)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US15161099P	1999-08-31	1999-08-31

Publications (1)

Publication Number	Publication Date
SK12862000A3 true SK12862000A3 (sk)	2002-02-05

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ID=22539510

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1286-2000A SK12862000A3 (sk)	1999-08-31	2000-08-25	Spôsob výroby inhibítorov 5-lipoxygenázy s rôznymi heterocyklickými systémami

Country Status (33)

Country	Link
EP (1)	EP1081144A3 (cs)
JP (1)	JP2001106686A (cs)
KR (1)	KR20010050274A (cs)
CN (1)	CN1286251A (cs)
AP (1)	AP2000001909A0 (cs)
AR (1)	AR022650A1 (cs)
AU (1)	AU5370200A (cs)
BG (1)	BG104730A (cs)
BR (1)	BR0003888A (cs)
CA (1)	CA2316748A1 (cs)
CO (1)	CO5180623A1 (cs)
CZ (1)	CZ20003159A3 (cs)
EA (1)	EA200000803A3 (cs)
EE (1)	EE200000513A (cs)
GT (1)	GT200000144A (cs)
HR (1)	HRP20000565A2 (cs)
HU (1)	HUP0003437A3 (cs)
ID (1)	ID27128A (cs)
IL (1)	IL138089A0 (cs)
IS (1)	IS5604A (cs)
MA (1)	MA26750A1 (cs)
NO (1)	NO20004312L (cs)
NZ (1)	NZ506633A (cs)
OA (1)	OA11451A (cs)
PA (1)	PA8499601A1 (cs)
PE (1)	PE20010523A1 (cs)
PL (1)	PL342280A1 (cs)
SG (1)	SG87145A1 (cs)
SK (1)	SK12862000A3 (cs)
SV (1)	SV2002000160A (cs)
TN (1)	TNSN00176A1 (cs)
TR (1)	TR200002530A2 (cs)
UY (1)	UY26315A1 (cs)

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Publication number	Priority date	Publication date	Assignee	Title
US20060188557A1 (en) *	2003-05-23	2006-08-24	Hisamitsu Pharmaceutical Co., Inc.	Prepartaion for external percutaneous administration containing non-steroidal anti-inflammatory drug and interleukin-1 alpha production inhibitor
US7674811B2 (en)	2006-03-14	2010-03-09	Ranbaxy Laboratories Limited	5-lipoxygenase inhibitors
CN103980312B (zh) *	2014-05-27	2016-09-07	广州大学	一种n杂环双膦配体及其合成方法
WO2025038927A1 (en) *	2023-08-16	2025-02-20	Raythera, Inc.	Modulators of tnf alpha activity and uses thereof

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Publication number	Priority date	Publication date	Assignee	Title
SK281577B6 (sk) *	1994-10-18	2001-05-10	Pfizer Inc.	Heterocyklické zlúčeniny a farmaceutický prostriedok na ich báze

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- 2000-08-01 SG SG200004340A patent/SG87145A1/en unknown
- 2000-08-10 PA PA20008499601A patent/PA8499601A1/es unknown
- 2000-08-11 CO CO00060138A patent/CO5180623A1/es not_active Application Discontinuation
- 2000-08-17 EP EP00307046A patent/EP1081144A3/en not_active Withdrawn
- 2000-08-18 OA OA1200000224A patent/OA11451A/en unknown
- 2000-08-24 IL IL13808900A patent/IL138089A0/xx unknown
- 2000-08-24 TN TNTNSN00176A patent/TNSN00176A1/fr unknown
- 2000-08-25 IS IS5604A patent/IS5604A/is unknown
- 2000-08-25 SK SK1286-2000A patent/SK12862000A3/sk unknown
- 2000-08-28 UY UY26315A patent/UY26315A1/es not_active Application Discontinuation
- 2000-08-28 ID IDP20000710A patent/ID27128A/id unknown
- 2000-08-29 AR ARP000104489A patent/AR022650A1/es not_active Application Discontinuation
- 2000-08-29 CA CA002316748A patent/CA2316748A1/en not_active Abandoned
- 2000-08-29 PE PE2000000886A patent/PE20010523A1/es not_active Application Discontinuation
- 2000-08-29 GT GT200000144A patent/GT200000144A/es unknown
- 2000-08-29 BG BG104730A patent/BG104730A/xx unknown
- 2000-08-29 AU AU53702/00A patent/AU5370200A/en not_active Abandoned
- 2000-08-30 HU HU0003437A patent/HUP0003437A3/hu unknown
- 2000-08-30 CZ CZ20003159A patent/CZ20003159A3/cs unknown
- 2000-08-30 KR KR1020000050877A patent/KR20010050274A/ko not_active Abandoned
- 2000-08-30 NZ NZ506633A patent/NZ506633A/en unknown
- 2000-08-30 NO NO20004312A patent/NO20004312L/no not_active Application Discontinuation
- 2000-08-30 MA MA26053A patent/MA26750A1/fr unknown
- 2000-08-30 BR BR0003888-1A patent/BR0003888A/pt not_active IP Right Cessation
- 2000-08-30 HR HR20000565A patent/HRP20000565A2/hr not_active Application Discontinuation
- 2000-08-30 CN CN00126409A patent/CN1286251A/zh active Pending
- 2000-08-30 SV SV2000000160A patent/SV2002000160A/es unknown
- 2000-08-31 PL PL00342280A patent/PL342280A1/xx not_active Application Discontinuation
- 2000-08-31 EE EEP200000513A patent/EE200000513A/xx unknown
- 2000-08-31 JP JP2000262200A patent/JP2001106686A/ja active Pending
- 2000-08-31 EA EA200000803A patent/EA200000803A3/ru unknown
- 2000-08-31 AP APAP/P/2000/001909A patent/AP2000001909A0/en unknown
- 2000-08-31 TR TR2000/02530A patent/TR200002530A2/xx unknown

Also Published As

Publication number	Publication date
EE200000513A (et)	2001-04-16
CZ20003159A3 (cs)	2001-12-12
HUP0003437A3 (en)	2002-08-28
EP1081144A3 (en)	2001-04-11
OA11451A (en)	2003-12-08
SG87145A1 (en)	2002-03-19
CA2316748A1 (en)	2001-02-28
HUP0003437A2 (hu)	2001-06-28
IS5604A (is)	2001-03-01
MA26750A1 (fr)	2004-12-20
PE20010523A1 (es)	2001-04-28
NO20004312L (no)	2001-03-01
KR20010050274A (ko)	2001-06-15
SV2002000160A (es)	2002-01-23
JP2001106686A (ja)	2001-04-17
IL138089A0 (en)	2001-10-31
UY26315A1 (es)	2001-04-30
BR0003888A (pt)	2001-12-11
EA200000803A3 (ru)	2001-06-25
TR200002530A2 (tr)	2001-04-20
HRP20000565A2 (en)	2001-06-30
EA200000803A2 (ru)	2001-04-23
NZ506633A (en)	2001-12-21
TNSN00176A1 (fr)	2005-11-10
AR022650A1 (es)	2002-09-04
NO20004312D0 (no)	2000-08-30
AU5370200A (en)	2001-03-08
ID27128A (id)	2001-03-01
PA8499601A1 (es)	2002-02-21
CN1286251A (zh)	2001-03-07
HU0003437D0 (en)	2000-08-30
GT200000144A (es)	2002-02-20
EP1081144A2 (en)	2001-03-07
AP2000001909A0 (en)	2000-09-30
PL342280A1 (en)	2001-03-12
CO5180623A1 (es)	2002-07-30
BG104730A (en)	2001-09-28

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