NO322458B1 - Benzimidazoler og imidazopyridiner, deres fremstilling og sammensetninger omfattende dem, samt deres anvendelse - Google Patents
Benzimidazoler og imidazopyridiner, deres fremstilling og sammensetninger omfattende dem, samt deres anvendelse Download PDFInfo
- Publication number
- NO322458B1 NO322458B1 NO20016369A NO20016369A NO322458B1 NO 322458 B1 NO322458 B1 NO 322458B1 NO 20016369 A NO20016369 A NO 20016369A NO 20016369 A NO20016369 A NO 20016369A NO 322458 B1 NO322458 B1 NO 322458B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- methyl
- amine
- pyridinyl
- piperidinyl
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 75
- 238000002360 preparation method Methods 0.000 title description 18
- 150000001556 benzimidazoles Chemical class 0.000 title description 2
- 150000005232 imidazopyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 120
- 239000002904 solvent Substances 0.000 claims description 75
- 238000006243 chemical reaction Methods 0.000 claims description 38
- -1 d-alkyl Chemical group 0.000 claims description 38
- 239000012442 inert solvent Substances 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 31
- 239000002585 base Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 17
- 150000001412 amines Chemical group 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 239000003638 chemical reducing agent Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 3
- 238000005576 amination reaction Methods 0.000 claims description 3
- ITHFMXUNCGKKML-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-[2-(6-bromopyridin-2-yl)ethoxymethyl]benzimidazol-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=CC=C2N1COCCC1=CC=CC(Br)=N1 ITHFMXUNCGKKML-UHFFFAOYSA-N 0.000 claims description 3
- WKAYRRDIBGZUEO-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-[2-ethoxyethoxy-(6-phenylpyridin-2-yl)methyl]benzimidazol-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=CC=C2N1C(OCCOCC)C(N=1)=CC=CC=1C1=CC=CC=C1 WKAYRRDIBGZUEO-UHFFFAOYSA-N 0.000 claims description 3
- LGHANUAZYINPCD-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-3-[2-methoxyethoxy-(6-methylpyridin-2-yl)methyl]-7-methylimidazo[4,5-b]pyridin-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=C(C)C=CN=C2N1C(OCCOC)C1=CC=CC(C)=N1 LGHANUAZYINPCD-UHFFFAOYSA-N 0.000 claims description 3
- XBFLEAOBNOWGRN-UHFFFAOYSA-N n-[1-(2-aminopropyl)piperidin-4-yl]-1-[ethoxy-(6-methylpyridin-2-yl)methyl]benzimidazol-2-amine Chemical compound C1CN(CC(C)N)CCC1NC1=NC2=CC=CC=C2N1C(OCC)C1=CC=CC(C)=N1 XBFLEAOBNOWGRN-UHFFFAOYSA-N 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 2
- MLJSFVJKUOQFMW-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-[ethoxy-(6-methylpyridin-2-yl)methyl]benzimidazol-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=CC=C2N1C(OCC)C1=CC=CC(C)=N1 MLJSFVJKUOQFMW-UHFFFAOYSA-N 0.000 claims description 2
- KEWOBSMGDOVGLX-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-6-chloro-1-[2-methoxyethoxy-(6-methylpyridin-2-yl)methyl]-4-methylbenzimidazol-2-amine;trihydrate;trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl.C1CN(CC(N)C(C)C)CCC1NC1=NC2=C(C)C=C(Cl)C=C2N1C(OCCOC)C1=CC=CC(C)=N1 KEWOBSMGDOVGLX-UHFFFAOYSA-N 0.000 claims description 2
- GMHWLJJKLAMEJF-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-1-[2-methoxyethoxy-(6-methylpyridin-2-yl)methyl]benzimidazol-2-amine Chemical compound C1CN(CCN)CCC1NC1=NC2=CC=CC=C2N1C(OCCOC)C1=CC=CC(C)=N1 GMHWLJJKLAMEJF-UHFFFAOYSA-N 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- UOZHEKIEYHSSGM-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-[2-(6-bromopyridin-2-yl)ethoxymethyl]-4-methylbenzimidazol-2-amine;hydrate Chemical compound O.C1CN(CC(N)C(C)C)CCC1NC1=NC2=C(C)C=CC=C2N1COCCC1=CC=CC(Br)=N1 UOZHEKIEYHSSGM-UHFFFAOYSA-N 0.000 claims 1
- AJCOXCKQNFSSLE-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-1-[2-ethoxyethoxy-(6-methylpyridin-2-yl)methyl]benzimidazol-2-amine Chemical compound C1CN(CCN)CCC1NC1=NC2=CC=CC=C2N1C(OCCOCC)C1=CC=CC(C)=N1 AJCOXCKQNFSSLE-UHFFFAOYSA-N 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 172
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 62
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- 239000000243 solution Substances 0.000 description 25
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- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000003054 catalyst Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
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- 125000005843 halogen group Chemical group 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
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- 238000010790 dilution Methods 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- 210000002345 respiratory system Anatomy 0.000 description 1
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- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
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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
- OSDUDPQWLGJWGL-UHFFFAOYSA-N tert-butyl 4-(1h-benzimidazol-2-ylamino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1 OSDUDPQWLGJWGL-UHFFFAOYSA-N 0.000 description 1
- XFPMCSZSEOSWCI-UHFFFAOYSA-N tert-butyl 4-[(1-phenacylbenzimidazol-2-yl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1CC(=O)C1=CC=CC=C1 XFPMCSZSEOSWCI-UHFFFAOYSA-N 0.000 description 1
- NBWWFMNRBCTCNZ-UHFFFAOYSA-N tert-butyl 4-[[1-(2-methoxy-2-phenylethyl)benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound C=1C=CC=CC=1C(OC)CN(C1=CC=CC=C1N=1)C=1NC1CCN(C(=O)OC(C)(C)C)CC1 NBWWFMNRBCTCNZ-UHFFFAOYSA-N 0.000 description 1
- LZHSVIWHGROZQX-UHFFFAOYSA-N tert-butyl 4-[[1-[2-(6-bromopyridin-2-yl)ethoxymethyl]benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1COCCC1=CC=CC(Br)=N1 LZHSVIWHGROZQX-UHFFFAOYSA-N 0.000 description 1
- FCRRSXONVUDSGW-UHFFFAOYSA-N tert-butyl 4-[[1-[2-hydroxy-2-(6-methylpyridin-2-yl)ethyl]benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C(O)CN2C3=CC=CC=C3N=C2NC2CCN(CC2)C(=O)OC(C)(C)C)=N1 FCRRSXONVUDSGW-UHFFFAOYSA-N 0.000 description 1
- OOQRRYDVICNJGC-UHFFFAOYSA-N tert-butyl n-(1-hydroxy-3-methylbutan-2-yl)carbamate Chemical compound CC(C)C(CO)NC(=O)OC(C)(C)C OOQRRYDVICNJGC-UHFFFAOYSA-N 0.000 description 1
- RQGAABUMZBIDNX-UHFFFAOYSA-N tert-butyl n-[2-[4-[[1-[2-(6-bromopyridin-2-yl)ethoxymethyl]benzimidazol-2-yl]amino]piperidin-1-yl]ethyl]carbamate Chemical compound C1CN(CCNC(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1COCCC1=CC=CC(Br)=N1 RQGAABUMZBIDNX-UHFFFAOYSA-N 0.000 description 1
- JDVLZSZDSGIGQW-UHFFFAOYSA-N tert-butyl n-[2-[4-[[1-[ethoxy-(6-methyl-3-phenylmethoxypyridin-2-yl)methyl]benzimidazol-2-yl]amino]piperidin-1-yl]ethyl]carbamate Chemical compound C1CN(CCNC(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1C(OCC)C1=NC(C)=CC=C1OCC1=CC=CC=C1 JDVLZSZDSGIGQW-UHFFFAOYSA-N 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99202088 | 1999-06-28 | ||
| PCT/EP2000/005675 WO2001000612A2 (en) | 1999-06-28 | 2000-06-20 | Respiratory syncytial virus replication inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20016369D0 NO20016369D0 (no) | 2001-12-27 |
| NO20016369L NO20016369L (no) | 2002-02-20 |
| NO322458B1 true NO322458B1 (no) | 2006-10-09 |
Family
ID=8240373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20016369A NO322458B1 (no) | 1999-06-28 | 2001-12-27 | Benzimidazoler og imidazopyridiner, deres fremstilling og sammensetninger omfattende dem, samt deres anvendelse |
Country Status (33)
| Country | Link |
|---|---|
| US (3) | US6747028B1 (es) |
| EP (1) | EP1196409B1 (es) |
| JP (1) | JP2003503402A (es) |
| KR (1) | KR100731271B1 (es) |
| CN (1) | CN1210275C (es) |
| AR (1) | AR035991A1 (es) |
| AT (1) | ATE258928T1 (es) |
| AU (1) | AU778218B2 (es) |
| BG (1) | BG65328B1 (es) |
| BR (1) | BR0012047A (es) |
| CA (1) | CA2376676C (es) |
| DE (1) | DE60008112T2 (es) |
| DK (1) | DK1196409T3 (es) |
| EA (1) | EA005027B1 (es) |
| EE (1) | EE04591B1 (es) |
| ES (1) | ES2215683T3 (es) |
| HK (1) | HK1045997A1 (es) |
| HR (1) | HRP20010935A2 (es) |
| HU (1) | HUP0201869A3 (es) |
| IL (2) | IL147327A0 (es) |
| MX (1) | MXPA02000120A (es) |
| MY (1) | MY127687A (es) |
| NO (1) | NO322458B1 (es) |
| NZ (1) | NZ515664A (es) |
| PL (1) | PL200674B1 (es) |
| PT (1) | PT1196409E (es) |
| SI (1) | SI1196409T1 (es) |
| SK (1) | SK19122001A3 (es) |
| TR (1) | TR200103806T2 (es) |
| TW (1) | TWI278454B (es) |
| UA (1) | UA74787C2 (es) |
| WO (1) | WO2001000612A2 (es) |
| ZA (1) | ZA200110479B (es) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6495580B1 (en) | 1998-01-29 | 2002-12-17 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| NZ515418A (en) * | 1999-06-28 | 2003-11-28 | Janssen Pharmaceutica Nv | Respiratory syncytial virus replication inhibitors |
| EP1196409B1 (en) | 1999-06-28 | 2004-02-04 | Janssen Pharmaceutica N.V. | Respiratory syncytial virus replication inhibitors |
| US6506738B1 (en) | 2000-09-27 | 2003-01-14 | Bristol-Myers Squibb Company | Benzimidazolone antiviral agents |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| US7030150B2 (en) * | 2001-05-11 | 2006-04-18 | Trimeris, Inc. | Benzimidazole compounds and antiviral uses thereof |
| US6919331B2 (en) | 2001-12-10 | 2005-07-19 | Bristol-Myers Squibb Company | Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents |
| CA2495245A1 (en) | 2002-08-09 | 2004-02-19 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| WO2004014316A2 (en) | 2002-08-09 | 2004-02-19 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| JP2006505570A (ja) * | 2002-10-17 | 2006-02-16 | アムジエン・インコーポレーテツド | ベンズイミダゾール誘導体およびそれのバニロイド受容体リガンドとしての使用 |
| CA2541618C (en) | 2003-10-30 | 2011-12-13 | Boehringer Ingelheim (Canada) Ltd. | Rsv polymerase inhibitors |
| MY140893A (en) * | 2003-12-18 | 2010-01-29 | Tibotec Pharm Ltd | Amino-benzimidazoles derivatives as inhibitors of respiratory syncytial virus replication |
| TWI349007B (en) * | 2003-12-18 | 2011-09-21 | Tibotec Pharm Ltd | Piperidine-amino-benzimidazole derivatives as inhibitors of respiratory syncytial virus replication |
| US20090036466A1 (en) | 2003-12-18 | 2009-02-05 | Jean-Francois Bonfanti | Amino-benzimidazoles derivatives as inhibitors of respiratory syncytial virus replication |
| BRPI0417273A (pt) * | 2003-12-18 | 2007-03-27 | Tibotec Pharm Ltd | derivados de benzimidazola 5- ou 6-substituìdos como inibidores de replicação do vìrus sincical respiratório |
| AR046959A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Morfolinilo que contiene bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| ATE435222T1 (de) * | 2003-12-18 | 2009-07-15 | Tibotec Pharm Ltd | Aminobenzimidazole und benzimidazole als inhibitoren der replikation von respiratory syncytial virus |
| DE102004010207A1 (de) * | 2004-03-02 | 2005-09-15 | Aventis Pharma S.A. | Neue 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate |
| EP1951704B1 (en) | 2005-03-17 | 2016-03-16 | Janssen Sciences Ireland UC | 1,3-dihydro-benzimidazol-2-ylidene amines useful for the treatment or prevention of viral infections |
| ATE529424T1 (de) | 2005-06-20 | 2011-11-15 | Tibotec Pharm Ltd | 1-ää2-amino-3-(substituiertes alkyl)-3h- benzimidazolylümethylü-3-substituierte-1,3- dihydrobenzimidazol-2-one als replikationshemmer des respiratorischen syncytialvirus |
| CA2612264C (en) | 2005-06-20 | 2014-09-23 | Tibotec Pharmaceuticals Ltd. | Heterocyclylaminoalkyl substituted benzimidazoles |
| RU2441866C2 (ru) * | 2005-06-20 | 2012-02-10 | Тиботек Фармасьютикалз Лтд | 2-замещенные бензимидазолы |
| US20130085133A1 (en) * | 2010-02-08 | 2013-04-04 | Sourthern Research Institute Office of Commercialization and Intellectual Prop. | Anti-viral treatment and assay to screenfor anti-viral agent |
| TWI530495B (zh) | 2010-12-16 | 2016-04-21 | 健生科學愛爾蘭無限公司 | 苯并咪唑呼吸道融合病毒抑制劑 |
| TWI501967B (zh) * | 2010-12-16 | 2015-10-01 | Janssen R&D Ireland | 作為呼吸道融合病毒抗病毒劑之氮雜吲哚類 |
| TWI527814B (zh) | 2010-12-16 | 2016-04-01 | 健生科學愛爾蘭無限公司 | 作為呼吸道融合病毒抗病毒劑之氮雜苯并咪唑類 |
| TWI541241B (zh) | 2010-12-16 | 2016-07-11 | 健生科學愛爾蘭無限公司 | 作為呼吸道融合病毒抗病毒劑之咪唑并吡啶類 |
| TWI515187B (zh) | 2010-12-16 | 2016-01-01 | 健生科學愛爾蘭無限公司 | 作為呼吸道融合病毒抗病毒劑之吲哚類 |
| HUE035069T2 (en) | 2011-12-28 | 2018-05-02 | Global Blood Therapeutics Inc | Substituted benzaldehyde compounds and their use to increase tissue oxygenation |
| WO2013102145A1 (en) | 2011-12-28 | 2013-07-04 | Global Blood Therapeutics, Inc. | Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation |
| ES2632914T3 (es) | 2012-06-15 | 2017-09-18 | Janssen Sciences Ireland Uc | Derivados de 1,3-dihidro-2H-bencimidazol-2-ona sustituidos con heterociclos como agentes antivirales para el virus respiratorio sincicial |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| PE20161035A1 (es) | 2013-03-15 | 2016-11-13 | Global Blood Therapeutics Inc | Compuestos y usos de estos para la modulacion de la hemoglobina |
| CA2903022C (en) | 2013-03-15 | 2021-11-09 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US20140274961A1 (en) | 2013-03-15 | 2014-09-18 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| KR20150132146A (ko) | 2013-03-15 | 2015-11-25 | 글로벌 블러드 테라퓨틱스, 인크. | 헤모글로빈 조정을 위한 화합물 및 이의 용도 |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10266551B2 (en) | 2013-03-15 | 2019-04-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9604999B2 (en) | 2013-03-15 | 2017-03-28 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| JP6809681B2 (ja) | 2014-02-07 | 2021-01-06 | グローバル ブラッド セラピューティクス インコーポレイテッド | ２−ヒドロキシ−６−（（２−（１−イソプロピル−１ｈ−ピラゾール−５−イル）ピリジン−３−イル）メトキシ）ベンズアルデヒドの遊離塩基の結晶多形 |
| JP2016079168A (ja) * | 2014-10-17 | 2016-05-16 | 塩野義製薬株式会社 | ９員縮合環誘導体 |
| MA41841A (fr) | 2015-03-30 | 2018-02-06 | Global Blood Therapeutics Inc | Composés aldéhyde pour le traitement de la fibrose pulmonaire, de l'hypoxie, et de maladies auto-immunes et des tissus conjonctifs |
| TW201731509A (zh) | 2015-12-04 | 2017-09-16 | 全球血液治療公司 | 針對２-羥基-６-（（２-（１-異丙基-１ｈ-吡唑-５-基）吡啶-３-基）甲氧基）-苯甲醛之劑量方案 |
| TWI663160B (zh) | 2016-05-12 | 2019-06-21 | 全球血液治療公司 | 用於合成2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)-吡啶-3-基)甲氧基)苯甲醛之方法 |
| TW202332423A (zh) | 2016-10-12 | 2023-08-16 | 美商全球血液治療公司 | 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑 |
| EP3860975B1 (en) | 2018-10-01 | 2023-10-18 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin for the treatment of sickle cell disease |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1140119A (en) | 1978-04-03 | 1983-01-25 | Joseph Torremans | N-heterocyclyl-4-piperidinamines |
| US4556660A (en) * | 1982-07-12 | 1985-12-03 | Janssen Pharmaceutica N.V. | N-(Bicyclic heterocyclyl)-4-piperidinamines |
| US4634704A (en) | 1983-10-06 | 1987-01-06 | Janssen Pharmaceutica, N.V. | Anti-allergic five membered heterocyclic ring containing N-(bicyclic heterocycyl)-4-piperidinamines |
| EP0144101B1 (en) | 1983-11-30 | 1991-02-06 | Janssen Pharmaceutica N.V. | Bicyclic heterocyclyl containing n-(bicyclic heterocyclyl)-4-piperidinamines |
| US4695569A (en) | 1983-11-30 | 1987-09-22 | Janssen Pharmaceutica N.V. | Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines |
| US4588722A (en) | 1984-01-09 | 1986-05-13 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives |
| PH23995A (en) | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| ES2052544T3 (es) | 1986-02-03 | 1994-07-16 | Janssen Pharmaceutica Nv | Composiciones anti-histaminicas que contienen n-heterociclil-4-piperidinaminas. |
| NZ223654A (en) | 1987-03-09 | 1990-03-27 | Janssen Pharmaceutica Nv | 1-alkyl-substituted-benzimidazole-4-piperidinamines and pharmaceutical compositions |
| US4897401A (en) | 1987-06-19 | 1990-01-30 | Janssen Pharmaceutical N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives useful in treating allergic diseases |
| CA1317939C (en) * | 1987-07-01 | 1993-05-18 | Janssen Pharmaceutica Naamloze Vennootschap | ¬(bicyclic heterocyclyl)methyl and -hetero| substituted hexahydro-1h-azepines and pyrrolidines |
| GB8716313D0 (en) * | 1987-07-10 | 1987-08-19 | Janssen Pharmaceutica Nv | 2-(heterocyclylalkyl)imidazopyridines |
| KR100190299B1 (ko) | 1990-07-19 | 1999-06-01 | 디르크 반테 | 신규한 옥사졸릴 유도체 |
| NZ238863A (en) * | 1990-07-19 | 1993-03-26 | Janssen Pharmaceutica Nv | Substituted thiazolyl and pyridinyl derivatives |
| US5360807A (en) * | 1990-07-19 | 1994-11-01 | Janssen Pharmaceutica N.V. | Substituted thiazolyl and substituted pyridinyl derivatives |
| US5693661A (en) | 1995-06-07 | 1997-12-02 | Eli Lilly And Company | Anti-viral compounds |
| PE107598A1 (es) | 1996-09-11 | 1999-01-29 | Ucb Sa | Cetirizina util para el tratamiento de enfermedades de tipo virico |
| WO1998031363A1 (en) | 1997-01-22 | 1998-07-23 | Eli Lilly And Company | Anti-viral compounds |
| AU7715198A (en) | 1997-06-04 | 1998-12-21 | Eli Lilly And Company | Anti-viral compounds |
| EP1196409B1 (en) | 1999-06-28 | 2004-02-04 | Janssen Pharmaceutica N.V. | Respiratory syncytial virus replication inhibitors |
-
2000
- 2000-06-20 EP EP00943840A patent/EP1196409B1/en not_active Expired - Lifetime
- 2000-06-20 UA UA2002010360A patent/UA74787C2/uk unknown
- 2000-06-20 DK DK00943840T patent/DK1196409T3/da active
- 2000-06-20 CN CNB008095442A patent/CN1210275C/zh not_active Expired - Fee Related
- 2000-06-20 BR BR0012047-2A patent/BR0012047A/pt not_active Application Discontinuation
- 2000-06-20 NZ NZ515664A patent/NZ515664A/xx unknown
- 2000-06-20 AU AU58166/00A patent/AU778218B2/en not_active Ceased
- 2000-06-20 EA EA200200088A patent/EA005027B1/ru not_active IP Right Cessation
- 2000-06-20 PL PL352378A patent/PL200674B1/pl not_active IP Right Cessation
- 2000-06-20 DE DE60008112T patent/DE60008112T2/de not_active Expired - Fee Related
- 2000-06-20 WO PCT/EP2000/005675 patent/WO2001000612A2/en active IP Right Grant
- 2000-06-20 PT PT00943840T patent/PT1196409E/pt unknown
- 2000-06-20 HU HU0201869A patent/HUP0201869A3/hu unknown
- 2000-06-20 SI SI200030315T patent/SI1196409T1/xx unknown
- 2000-06-20 ES ES00943840T patent/ES2215683T3/es not_active Expired - Lifetime
- 2000-06-20 MX MXPA02000120A patent/MXPA02000120A/es active IP Right Grant
- 2000-06-20 AT AT00943840T patent/ATE258928T1/de not_active IP Right Cessation
- 2000-06-20 EE EEP200100688A patent/EE04591B1/xx not_active IP Right Cessation
- 2000-06-20 KR KR1020017015295A patent/KR100731271B1/ko not_active IP Right Cessation
- 2000-06-20 SK SK1912-2001A patent/SK19122001A3/sk unknown
- 2000-06-20 CA CA002376676A patent/CA2376676C/en not_active Expired - Fee Related
- 2000-06-20 TR TR2001/03806T patent/TR200103806T2/xx unknown
- 2000-06-20 JP JP2001507021A patent/JP2003503402A/ja not_active Withdrawn
- 2000-06-20 IL IL14732700A patent/IL147327A0/xx active IP Right Grant
- 2000-06-20 US US10/019,380 patent/US6747028B1/en not_active Expired - Fee Related
- 2000-06-26 TW TW089112478A patent/TWI278454B/zh not_active IP Right Cessation
- 2000-06-27 MY MYPI20002907A patent/MY127687A/en unknown
- 2000-06-27 AR ARP000103221A patent/AR035991A1/es not_active Application Discontinuation
-
2001
- 2001-12-19 HR HR20010935A patent/HRP20010935A2/hr not_active Application Discontinuation
- 2001-12-20 ZA ZA200110479A patent/ZA200110479B/xx unknown
- 2001-12-26 IL IL147327A patent/IL147327A/en not_active IP Right Cessation
- 2001-12-27 NO NO20016369A patent/NO322458B1/no unknown
-
2002
- 2002-01-08 BG BG106286A patent/BG65328B1/bg unknown
- 2002-10-21 HK HK02107622.9A patent/HK1045997A1/zh unknown
-
2004
- 2004-04-02 US US10/817,472 patent/US7179811B2/en not_active Expired - Fee Related
-
2007
- 2007-01-22 US US11/625,648 patent/US7528149B2/en not_active Expired - Fee Related
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