JP4422895B2 - ノイラミニダーゼインヒビターとしてのシクロヘキセンカルボキシレート - Google Patents
ノイラミニダーゼインヒビターとしてのシクロヘキセンカルボキシレート Download PDFInfo
- Publication number
- JP4422895B2 JP4422895B2 JP2000538977A JP2000538977A JP4422895B2 JP 4422895 B2 JP4422895 B2 JP 4422895B2 JP 2000538977 A JP2000538977 A JP 2000538977A JP 2000538977 A JP2000538977 A JP 2000538977A JP 4422895 B2 JP4422895 B2 JP 4422895B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- neuraminidase
- together form
- added
- ethyl acetate
- 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
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- 229940042406 direct acting antivirals neuraminidase inhibitors Drugs 0.000 title description 3
- 239000002911 sialidase inhibitor Substances 0.000 title description 3
- NMEZJSDUZQOPFE-UHFFFAOYSA-N Cyclohex-1-enecarboxylic acid Chemical class OC(=O)C1=CCCCC1 NMEZJSDUZQOPFE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 86
- 239000000203 mixture Substances 0.000 claims description 80
- 108010006232 Neuraminidase Proteins 0.000 claims description 31
- 102000005348 Neuraminidase Human genes 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 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
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 206010022000 influenza Diseases 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 8
- 239000003937 drug carrier Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 238000000034 method Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000009472 formulation Methods 0.000 description 29
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- 239000004480 active ingredient Substances 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 7
- 229940125782 compound 2 Drugs 0.000 description 7
- 239000003995 emulsifying agent Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 241000712461 unidentified influenza virus Species 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- -1 ammonium ions Chemical class 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
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- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
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- 239000003112 inhibitor Substances 0.000 description 4
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- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 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 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
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- 238000000926 separation method Methods 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- TZKBVRDEOITLRB-UHFFFAOYSA-N 4-methyl-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1h-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2C=C3C=NNC3=NC=2)=C1 TZKBVRDEOITLRB-UHFFFAOYSA-N 0.000 description 2
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/52—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/14—Compounds containing azido groups with azido groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/26—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D303/40—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| PCT/US1998/026327 WO1999031047A1 (en) | 1997-12-12 | 1998-12-10 | Cyclohexene carboxylates as neuraminidase inhibitors |
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| US5859284A (en) * | 1996-08-23 | 1999-01-12 | Gilead Sciences, Inc. | Preparation of carbocyclic compounds |
| US6518438B2 (en) | 1996-08-23 | 2003-02-11 | Gilead Sciences, Inc. | Preparation of cyclohexene carboxylate derivatives |
| US5994377A (en) | 1996-10-21 | 1999-11-30 | Gilead Sciences, Inc. | Piperidine compounds |
| US20040053999A1 (en) * | 1997-09-17 | 2004-03-18 | Bischofberger Norbert W. | Novel compounds and methods for synthesis and therapy |
| US6518305B1 (en) | 1998-04-23 | 2003-02-11 | Abbott Laboratories | Five-membered carbocyclic and heterocyclic inhibitors of neuraminidases |
| US6455571B1 (en) | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
| US6593314B1 (en) | 1999-10-19 | 2003-07-15 | Abbott Laboratories | Neuraminidase inhibitors |
| WO2001028981A1 (en) * | 1999-10-19 | 2001-04-26 | Abbott Laboratories | 1-cyclohexene-1-carboxylic acid and 1-cyclohexene-1-carboxylates as neuraminidase inhibitors |
| US6383037B2 (en) * | 2000-01-17 | 2002-05-07 | Harting Automotive Gmbh & Co., Kg | Safety disconnector |
| WO2003034071A2 (en) * | 2001-10-15 | 2003-04-24 | Therascope Ag | A method of forming a dynamic combinatorial library using a scaffold |
| US6964784B2 (en) * | 2002-03-07 | 2005-11-15 | Optigenex, Inc. | Method of preparation and composition of a water soluble extract of the bioactive component of the plant species uncaria for enhancing immune, anti-inflammatory, anti-tumor and dna repair processes of warm blooded animals |
| US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
| DK2318832T3 (da) | 2008-07-15 | 2014-01-20 | Academia Sinica | Glycan-arrays på PTFE-lignende aluminiumcoatede objektglas og relaterede fremgangsmåder |
| BRPI1010981A2 (pt) | 2009-05-15 | 2018-12-04 | Redx Pharma Ltd | "derivados de fármaco redox" |
| US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
| WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
| CN102964267B (zh) * | 2011-09-01 | 2015-06-10 | 中山大学 | 一种具有流感病毒神经氨酸酶抑制活性的环己烯化合物及其制备方法以及其应用 |
| US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
| US9914956B2 (en) | 2012-08-18 | 2018-03-13 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
| CN103224464B (zh) * | 2013-04-15 | 2016-05-04 | 广州市恒诺康医药科技有限公司 | 环己烯类衍生物或其药学上可接受的盐及其用途 |
| WO2014210397A1 (en) | 2013-06-26 | 2014-12-31 | Academia Sinica | Rm2 antigens and use thereof |
| EP3013347B1 (en) | 2013-06-27 | 2019-12-11 | Academia Sinica | Glycan conjugates and use thereof |
| EP3041484B1 (en) | 2013-09-06 | 2021-03-03 | Academia Sinica | Human inkt cell activation using glycolipids with altered glycosyl groups |
| US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| KR20160104727A (ko) | 2014-01-16 | 2016-09-05 | 아카데미아 시니카 | 암의 치료 및 검출을 위한 조성물 및 방법 |
| TWI797430B (zh) | 2014-03-27 | 2023-04-01 | 中央研究院 | 反應性標記化合物及其用途 |
| EP4116329A1 (en) | 2014-05-27 | 2023-01-11 | Academia Sinica | Anti-her2 glycoantibodies and uses thereof |
| KR20170010003A (ko) | 2014-05-27 | 2017-01-25 | 아카데미아 시니카 | 박테로이드 기원의 푸코시다제 및 이의 사용 방법 |
| US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
| JP2017518989A (ja) | 2014-05-27 | 2017-07-13 | アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ | 抗ｃｄ２０糖操作抗体群およびその使用 |
| JP7063538B2 (ja) | 2014-05-28 | 2022-05-09 | アカデミア シニカ | 抗ＴＮＦα糖操作抗体群およびその使用 |
| GB2532178A (en) * | 2014-06-09 | 2016-05-18 | Redx Pharma Plc | Antiviral compounds |
| EP3191500A4 (en) | 2014-09-08 | 2018-04-11 | Academia Sinica | HUMAN iNKT CELL ACTIVATION USING GLYCOLIPIDS |
| US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
| US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
| AU2015378564A1 (en) | 2015-01-24 | 2017-07-13 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
| CN109195996A (zh) | 2016-03-08 | 2019-01-11 | 中央研究院 | N-聚醣及其阵列的模组化合成方法 |
| CN107325040B (zh) * | 2016-04-28 | 2019-05-03 | 广州市恒诺康医药科技有限公司 | 环己烯类衍生物或其药学上可接受的盐及其用途 |
| CA3034057A1 (en) | 2016-08-22 | 2018-03-01 | CHO Pharma Inc. | Antibodies, binding fragments, and methods of use |
| CN106496100B (zh) * | 2016-09-09 | 2021-01-22 | 广州市恒诺康医药科技有限公司 | 环己烯类化合物及其用途 |
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| US4968788A (en) * | 1986-04-04 | 1990-11-06 | Board Of Regents, The University Of Texas System | Biologically reversible phosphate and phosphonate protective gruops |
| US5206400A (en) * | 1986-07-07 | 1993-04-27 | Ohio State University | Diastereomeric mono- and di-substituted diamino cyclohexane compounds and the method of preparation thereof |
| US5175273A (en) * | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5270340A (en) * | 1988-12-27 | 1993-12-14 | Bayer Aktiengesellschaft | Substituted 2-cyclohexen-1-yl-amine fungicidal and herbicidal agents |
| SK282950B6 (sk) * | 1990-04-24 | 2003-01-09 | Biota Scientific Management Pty Ltd | Deriváty alfa-D-neuramínovej kyseliny, spôsob ich prípravy, ich použitie a farmaceutické prípravky na ich báze |
| WO1992006691A1 (en) * | 1990-10-19 | 1992-04-30 | Biota Scientific Management Pty. Ltd. | Anti-viral compounds that bind the active site of influenza neuramidase and display in vivo activity against orthomyxovirus and paramyxovirus |
| DE4033415A1 (de) * | 1990-10-20 | 1992-04-23 | Bayer Ag | Antimikrobielle mittel sowie substituierte 2-cyclohexan-1-yl-amin-derivate und deren herstellung |
| DE4131311A1 (de) * | 1991-09-20 | 1993-04-01 | Basf Ag | Dihydropyranderivate und diese enthaltende pflanzenschutzmittel |
| AU659501B2 (en) * | 1991-10-23 | 1995-05-18 | Biota Scientific Management Pty Ltd | Antiviral 4-substituted-2-deoxy-2,3-didehydro-derivatives of alpha-D-neuraminic acid |
| GB9126725D0 (en) * | 1991-12-17 | 1992-02-12 | Glaxo Group Ltd | Process |
| FR2687674B1 (fr) * | 1992-02-07 | 1995-05-19 | Roussel Uclaf | Nouveaux derives de la pyridone, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
| US5292938A (en) * | 1992-04-13 | 1994-03-08 | Associated Universities, Inc. | Synthesis of 4-substituted-trans-1, 2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and spect and pet imaging |
| US5633360A (en) * | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| GB9220241D0 (en) * | 1992-09-25 | 1992-11-11 | Glaxo Group Ltd | Process |
| GB9220327D0 (en) * | 1992-09-25 | 1992-11-11 | Glaxo Group Ltd | Process |
| US5514798A (en) * | 1993-06-02 | 1996-05-07 | Gilead Sciences, Inc. | Method and cyclic carbonates for nucleotide analogues |
| GB9311892D0 (en) * | 1993-06-09 | 1993-07-28 | Glaxo Wellcome Australia Ltd | Device |
| GB9311873D0 (en) * | 1993-06-09 | 1993-07-28 | Glaxo Group Ltd | Process |
| GB9312531D0 (en) * | 1993-06-17 | 1993-08-04 | Glaxo Group Ltd | Process |
| GB9325841D0 (en) * | 1993-12-17 | 1994-02-23 | Glaxo Group Ltd | Chemical compounds |
| GB9400206D0 (en) * | 1994-01-07 | 1994-03-02 | Glaxo Group Ltd | Chemical compound |
| AUPM354694A0 (en) * | 1994-01-27 | 1994-02-17 | Biota Scientific Management Pty Ltd | Chemical compounds |
| US5985859A (en) * | 1994-04-14 | 1999-11-16 | The University Of Alabama | Methods of inhibiting bacterial sialidase |
| GB9410817D0 (en) * | 1994-05-28 | 1994-07-20 | Glaxo Group Ltd | Medicaments |
| AUPM725794A0 (en) * | 1994-08-03 | 1994-08-25 | Biota Scientific Management Pty Ltd | Chemical compounds |
| US5556963A (en) * | 1994-08-05 | 1996-09-17 | Oklahoma Medical Research Foundation | Synthesis of 4-alkoxy-N-acetylneuraminic acid |
| US5512596A (en) * | 1994-09-02 | 1996-04-30 | Gilead Sciences, Inc. | Aromatic compounds |
| EP0789695A2 (en) * | 1994-11-04 | 1997-08-20 | Gilead Sciences, Inc. | Thiepane compounds inhibiting and detecting hiv protease |
| US5866601A (en) * | 1995-02-27 | 1999-02-02 | Gilead Sciences, Inc. | Carbocyclic compounds |
| CN100409844C (zh) * | 1995-02-27 | 2008-08-13 | 吉里德科学公司 | 神经氨酸苷酶抑制剂 |
| US5602277A (en) * | 1995-03-30 | 1997-02-11 | Biocryst Pharmaceuticals, Inc. | Substituted benzene derivatives useful as neuraminidase inhibitors |
| US5714509A (en) * | 1995-05-03 | 1998-02-03 | The University Of Alabama | Inhibitors of bacterial sialidase and methods of making and using the same |
| GB9525389D0 (en) | 1995-12-12 | 1996-02-14 | Biota Scient Management Ltd | Chemical compounds |
| GB9510141D0 (en) | 1995-05-19 | 1995-07-12 | Biota Scient Management | Chemical compounds |
| ATE206116T1 (de) * | 1995-05-19 | 2001-10-15 | Biota Scient Management | 6-carboxamido-dihydropyran-derivate |
| GB9516276D0 (en) * | 1995-08-08 | 1995-10-11 | Biota Scient Management | Chemical compounds |
| US5763483A (en) * | 1995-12-29 | 1998-06-09 | Gilead Sciences, Inc. | Carbocyclic compounds |
-
1998
- 1998-12-08 TW TW087120362A patent/TW477783B/zh not_active IP Right Cessation
- 1998-12-08 TW TW090111328A patent/TW480247B/zh not_active IP Right Cessation
- 1998-12-10 WO PCT/US1998/026327 patent/WO1999031047A1/en not_active Ceased
- 1998-12-10 DE DE69813616T patent/DE69813616T2/de not_active Expired - Lifetime
- 1998-12-10 AT AT98962059T patent/ATE237582T1/de not_active IP Right Cessation
- 1998-12-10 ES ES98962059T patent/ES2196636T3/es not_active Expired - Lifetime
- 1998-12-10 EP EP98962059A patent/EP1040095B1/en not_active Expired - Lifetime
- 1998-12-10 AU AU17226/99A patent/AU1722699A/en not_active Abandoned
- 1998-12-10 US US09/208,646 patent/US6111132A/en not_active Expired - Lifetime
- 1998-12-10 ZA ZA9811314A patent/ZA9811314B/xx unknown
- 1998-12-10 CA CA002313638A patent/CA2313638C/en not_active Expired - Lifetime
- 1998-12-10 JP JP2000538977A patent/JP4422895B2/ja not_active Expired - Lifetime
- 1998-12-11 AR ARP980106313A patent/AR015493A1/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| HK1033932A1 (en) | 2001-10-05 |
| AU1722699A (en) | 1999-07-05 |
| AR015493A1 (es) | 2001-05-02 |
| WO1999031047A1 (en) | 1999-06-24 |
| EP1040095B1 (en) | 2003-04-16 |
| DE69813616D1 (de) | 2003-05-22 |
| EP1040095A1 (en) | 2000-10-04 |
| TW477783B (en) | 2002-03-01 |
| ES2196636T3 (es) | 2003-12-16 |
| US6111132A (en) | 2000-08-29 |
| ATE237582T1 (de) | 2003-05-15 |
| TW480247B (en) | 2002-03-21 |
| CA2313638A1 (en) | 1999-06-24 |
| CA2313638C (en) | 2008-07-22 |
| JP2002508347A (ja) | 2002-03-19 |
| ZA9811314B (en) | 1999-06-14 |
| DE69813616T2 (de) | 2004-02-05 |
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