CZ20023473A3 - Makrocyklická sloučenina a farmaceutický prostředek - Google Patents
Makrocyklická sloučenina a farmaceutický prostředek Download PDFInfo
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- CZ20023473A3 CZ20023473A3 CZ20023473A CZ20023473A CZ20023473A3 CZ 20023473 A3 CZ20023473 A3 CZ 20023473A3 CZ 20023473 A CZ20023473 A CZ 20023473A CZ 20023473 A CZ20023473 A CZ 20023473A CZ 20023473 A3 CZ20023473 A3 CZ 20023473A3
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- Prior art keywords
- mmol
- alkyl
- compound
- solution
- conhch
- Prior art date
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- 150000002678 macrocyclic compounds Chemical class 0.000 title claims abstract description 38
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 194
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 108091005804 Peptidases Proteins 0.000 claims abstract description 20
- 239000004365 Protease Substances 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 7
- 239000000460 chlorine Substances 0.000 claims description 167
- -1 alkyaryl Chemical group 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 241000711549 Hepacivirus C Species 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 239000004480 active ingredient Substances 0.000 claims description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 239000004202 carbamide Substances 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 229910005965 SO 2 Inorganic materials 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 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 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- 150000001346 alkyl aryl ethers Chemical class 0.000 claims description 3
- 150000005215 alkyl ethers Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- 102000006992 Interferon-alpha Human genes 0.000 claims description 2
- 108010047761 Interferon-alpha Proteins 0.000 claims description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 2
- 229940100389 Sulfonylurea Drugs 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 150000008378 aryl ethers Chemical class 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 2
- UZMZVDOOVXLRID-UHFFFAOYSA-N azanylidyne-(nitrosulfonylamino)methane Chemical compound [O-][N+](=O)S(=O)(=O)NC#N UZMZVDOOVXLRID-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 2
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 229960000329 ribavirin Drugs 0.000 claims description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 239000003443 antiviral agent Substances 0.000 claims 2
- 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 125000001511 cyclopentyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000001544 thienyl group Chemical class 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical class [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims 1
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- MGQNMYSRDBFUIR-UHFFFAOYSA-N nitro cyanoformate Chemical compound [O-][N+](=O)OC(=O)C#N MGQNMYSRDBFUIR-UHFFFAOYSA-N 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 268
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 193
- 239000011541 reaction mixture Substances 0.000 description 167
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 85
- 239000007787 solid Substances 0.000 description 79
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- 239000000203 mixture Substances 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
- 238000002360 preparation method Methods 0.000 description 59
- 239000011734 sodium Substances 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
- 239000012044 organic layer Substances 0.000 description 54
- 238000000746 purification Methods 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 43
- 239000012267 brine Substances 0.000 description 42
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 42
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 41
- 238000004587 chromatography analysis Methods 0.000 description 41
- 239000011347 resin Substances 0.000 description 40
- 229920005989 resin Polymers 0.000 description 40
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000002253 acid Substances 0.000 description 36
- 239000000543 intermediate Substances 0.000 description 36
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 34
- 229910004298 SiO 2 Inorganic materials 0.000 description 34
- 239000010410 layer Substances 0.000 description 33
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
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- 239000000758 substrate Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 235000019441 ethanol Nutrition 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 22
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 21
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- 101710144111 Non-structural protein 3 Proteins 0.000 description 17
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- FWQHRZXEQNUCSY-UHFFFAOYSA-N tert-butyl N-[2-(ethoxycarbonylamino)-5-[(4-fluorophenyl)methyl-prop-2-ynylamino]phenyl]carbamate Chemical compound CCOC(=O)NC1=C(C=C(C=C1)N(CC#C)CC2=CC=C(C=C2)F)NC(=O)OC(C)(C)C FWQHRZXEQNUCSY-UHFFFAOYSA-N 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- VJPIOPZUQLPHRE-UHFFFAOYSA-N tert-butyl n-[2-(dimethylamino)-2-oxo-1-phenylethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C(=O)N(C)C)C1=CC=CC=C1 VJPIOPZUQLPHRE-UHFFFAOYSA-N 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19820400P | 2000-04-19 | 2000-04-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20023473A3 true CZ20023473A3 (cs) | 2003-01-15 |
Family
ID=22732422
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20023473A CZ20023473A3 (cs) | 2000-04-19 | 2001-04-17 | Makrocyklická sloučenina a farmaceutický prostředek |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6914122B2 (OSRAM) |
| EP (1) | EP1274724A2 (OSRAM) |
| JP (1) | JP4748912B2 (OSRAM) |
| KR (1) | KR20020097220A (OSRAM) |
| CN (3) | CN101580536A (OSRAM) |
| AR (1) | AR030558A1 (OSRAM) |
| AU (1) | AU2001253621A1 (OSRAM) |
| BR (1) | BR0110104A (OSRAM) |
| CA (1) | CA2406532A1 (OSRAM) |
| CZ (1) | CZ20023473A3 (OSRAM) |
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| DK0527788T3 (da) | 1990-04-04 | 2004-09-06 | Chiron Corp | Hepatitis C virus protease |
| JPH07228594A (ja) * | 1994-02-18 | 1995-08-29 | Suntory Ltd | エンドセリン受容体拮抗ペプチド |
| IL109943A (en) * | 1994-06-08 | 2006-08-01 | Develogen Israel Ltd | Conformationally constrained backbone cyclized peptide analogs |
| WO1998007734A1 (en) | 1996-08-21 | 1998-02-26 | Hybridon, Inc. | Oligonucleotide prodrugs |
| CN1133649C (zh) | 1996-10-18 | 2004-01-07 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是丙型肝炎病毒ns3蛋白酶的抑制剂 |
| GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| US6143715A (en) * | 1997-08-11 | 2000-11-07 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C inhibitor peptide analogues |
| CN1163504C (zh) * | 1998-04-15 | 2004-08-25 | 阿温蒂斯药物公司 | 制备与树脂结合的环状肽的方法 |
| GB9812523D0 (en) * | 1998-06-10 | 1998-08-05 | Angeletti P Ist Richerche Bio | Peptide inhibitors of hepatitis c virus ns3 protease |
| AR022061A1 (es) | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
| US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| US6407066B1 (en) * | 1999-01-26 | 2002-06-18 | Elan Pharmaceuticals, Inc. | Pyroglutamic acid derivatives and related compounds which inhibit leukocyte adhesion mediated by VLA-4 |
-
2001
- 2001-04-17 PE PE2001000348A patent/PE20011288A1/es not_active Application Discontinuation
- 2001-04-17 PL PL01358591A patent/PL358591A1/xx not_active Application Discontinuation
- 2001-04-17 CN CNA2009100067369A patent/CN101580536A/zh active Pending
- 2001-04-17 JP JP2001578418A patent/JP4748912B2/ja not_active Expired - Fee Related
- 2001-04-17 AU AU2001253621A patent/AU2001253621A1/en not_active Abandoned
- 2001-04-17 CN CN01810566A patent/CN1432022A/zh active Pending
- 2001-04-17 HK HK03100478.8A patent/HK1048479A1/zh unknown
- 2001-04-17 BR BR0110104-8A patent/BR0110104A/pt not_active IP Right Cessation
- 2001-04-17 CA CA002406532A patent/CA2406532A1/en not_active Abandoned
- 2001-04-17 RU RU2002131163/04A patent/RU2002131163A/ru not_active Application Discontinuation
- 2001-04-17 NZ NZ521456A patent/NZ521456A/en unknown
- 2001-04-17 CN CNA2006101537103A patent/CN1935833A/zh active Pending
- 2001-04-17 SK SK1495-2002A patent/SK14952002A3/sk not_active Application Discontinuation
- 2001-04-17 KR KR1020027013965A patent/KR20020097220A/ko not_active Withdrawn
- 2001-04-17 CZ CZ20023473A patent/CZ20023473A3/cs unknown
- 2001-04-17 EP EP01927142A patent/EP1274724A2/en not_active Withdrawn
- 2001-04-17 AR ARP010101794A patent/AR030558A1/es unknown
- 2001-04-17 US US09/836,636 patent/US6914122B2/en not_active Expired - Fee Related
- 2001-04-17 WO PCT/US2001/012530 patent/WO2001081325A2/en not_active Ceased
- 2001-04-17 IL IL15193501A patent/IL151935A0/xx unknown
- 2001-04-17 MX MXPA02010375A patent/MXPA02010375A/es active IP Right Grant
- 2001-04-17 HU HU0302957A patent/HUP0302957A2/hu unknown
-
2002
- 2002-10-04 ZA ZA200208014A patent/ZA200208014B/en unknown
- 2002-10-18 NO NO20025030A patent/NO20025030L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AR030558A1 (es) | 2003-08-27 |
| WO2001081325A3 (en) | 2002-08-01 |
| BR0110104A (pt) | 2003-01-07 |
| CN1432022A (zh) | 2003-07-23 |
| RU2002131163A (ru) | 2004-06-27 |
| CN101580536A (zh) | 2009-11-18 |
| JP4748912B2 (ja) | 2011-08-17 |
| US6914122B2 (en) | 2005-07-05 |
| IL151935A0 (en) | 2003-04-10 |
| JP2003531199A (ja) | 2003-10-21 |
| NZ521456A (en) | 2004-07-30 |
| PE20011288A1 (es) | 2001-12-12 |
| MXPA02010375A (es) | 2003-04-25 |
| KR20020097220A (ko) | 2002-12-31 |
| US20020016294A1 (en) | 2002-02-07 |
| CN1935833A (zh) | 2007-03-28 |
| EP1274724A2 (en) | 2003-01-15 |
| WO2001081325A2 (en) | 2001-11-01 |
| CA2406532A1 (en) | 2001-11-01 |
| NO20025030L (no) | 2002-12-18 |
| HUP0302957A2 (hu) | 2003-12-29 |
| AU2001253621A1 (en) | 2001-11-07 |
| ZA200208014B (en) | 2004-02-12 |
| HK1048479A1 (zh) | 2003-04-04 |
| NO20025030D0 (no) | 2002-10-18 |
| PL358591A1 (en) | 2004-08-09 |
| SK14952002A3 (sk) | 2003-03-04 |
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