HRP20010935A2 - Respiratory syncytial virus replication inhibitors - Google Patents
Respiratory syncytial virus replication inhibitors Download PDFInfo
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- HRP20010935A2 HRP20010935A2 HR20010935A HRP20010935A HRP20010935A2 HR P20010935 A2 HRP20010935 A2 HR P20010935A2 HR 20010935 A HR20010935 A HR 20010935A HR P20010935 A HRP20010935 A HR P20010935A HR P20010935 A2 HRP20010935 A2 HR P20010935A2
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- hydrogen
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- 241000725643 Respiratory syncytial virus Species 0.000 title description 13
- 239000003112 inhibitor Substances 0.000 title 1
- 230000029812 viral genome replication Effects 0.000 title 1
- 239000000543 intermediate Substances 0.000 claims description 226
- 150000001875 compounds Chemical class 0.000 claims description 170
- -1 nitro, amino, hydroxy Chemical group 0.000 claims description 88
- 239000002904 solvent Substances 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 60
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 239000012442 inert solvent Substances 0.000 claims description 48
- 239000002253 acid Substances 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 39
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 38
- 150000002431 hydrogen Chemical group 0.000 claims description 35
- 239000002585 base Substances 0.000 claims description 32
- 150000003254 radicals Chemical class 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 239000003638 chemical reducing agent Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 150000001412 amines Chemical group 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 230000000840 anti-viral effect Effects 0.000 claims description 16
- 150000001721 carbon Chemical group 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 238000010511 deprotection reaction Methods 0.000 claims description 14
- 239000002184 metal Chemical class 0.000 claims description 14
- 229910052751 metal Inorganic materials 0.000 claims description 14
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 12
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
- 238000005576 amination reaction Methods 0.000 claims description 7
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims description 6
- 208000036142 Viral infection Diseases 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 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
- 230000009385 viral infection Effects 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 150000004696 coordination complex Chemical group 0.000 claims description 3
- 235000019253 formic acid Nutrition 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
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 2
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 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 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
- 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 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
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
- 125000001475 halogen functional group Chemical group 0.000 claims 6
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 229910000831 Steel Inorganic materials 0.000 claims 1
- 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 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
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 239000010959 steel Substances 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
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- 239000000203 mixture Substances 0.000 description 75
- 239000002244 precipitate Substances 0.000 description 61
- 235000019441 ethanol Nutrition 0.000 description 57
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 54
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
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- 239000003054 catalyst Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 125000005843 halogen group Chemical group 0.000 description 26
- 239000003480 eluent Substances 0.000 description 25
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 17
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
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- 229940079593 drug Drugs 0.000 description 9
- 229940073584 methylene chloride Drugs 0.000 description 9
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- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
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- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 231100000135 cytotoxicity Toxicity 0.000 description 7
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
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- 239000012312 sodium hydride Substances 0.000 description 7
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- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 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
- BBEZKBVEVODUNQ-UHFFFAOYSA-N tert-butyl 4-[[1-(2-hydroxy-2-phenylethyl)benzimidazol-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 BBEZKBVEVODUNQ-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
- UVUAFQFQFKXWEP-UHFFFAOYSA-N tert-butyl 4-[[1-[2-[6-(dimethylamino)pyridin-2-yl]ethoxymethyl]benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound CN(C)C1=CC=CC(CCOCN2C3=CC=CC=C3N=C2NC2CCN(CC2)C(=O)OC(C)(C)C)=N1 UVUAFQFQFKXWEP-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
- RPRPISKSXVVBBR-UHFFFAOYSA-N tert-butyl 4-[[1-[ethoxy-(6-methyl-3-phenylmethoxypyridin-2-yl)methyl]benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1C(OCC)C1=NC(C)=CC=C1OCC1=CC=CC=C1 RPRPISKSXVVBBR-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
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CVQPQLRQAKXFFF-UHFFFAOYSA-N trihydrate;trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl CVQPQLRQAKXFFF-UHFFFAOYSA-N 0.000 description 1
- 229960005486 vaccine Drugs 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Molecular Biology (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 (1)
| Publication Number | Publication Date |
|---|---|
| HRP20010935A2 true HRP20010935A2 (en) | 2003-06-30 |
Family
ID=8240373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20010935A HRP20010935A2 (en) | 1999-06-28 | 2001-12-19 | Respiratory syncytial virus replication inhibitors |
Country Status (33)
| Country | Link |
|---|---|
| US (3) | US6747028B1 (bg) |
| EP (1) | EP1196409B1 (bg) |
| JP (1) | JP2003503402A (bg) |
| KR (1) | KR100731271B1 (bg) |
| CN (1) | CN1210275C (bg) |
| AR (1) | AR035991A1 (bg) |
| AT (1) | ATE258928T1 (bg) |
| AU (1) | AU778218B2 (bg) |
| BG (1) | BG65328B1 (bg) |
| BR (1) | BR0012047A (bg) |
| CA (1) | CA2376676C (bg) |
| DE (1) | DE60008112T2 (bg) |
| DK (1) | DK1196409T3 (bg) |
| EA (1) | EA005027B1 (bg) |
| EE (1) | EE04591B1 (bg) |
| ES (1) | ES2215683T3 (bg) |
| HK (1) | HK1045997A1 (bg) |
| HR (1) | HRP20010935A2 (bg) |
| HU (1) | HUP0201869A3 (bg) |
| IL (2) | IL147327A0 (bg) |
| MX (1) | MXPA02000120A (bg) |
| MY (1) | MY127687A (bg) |
| NO (1) | NO322458B1 (bg) |
| NZ (1) | NZ515664A (bg) |
| PL (1) | PL200674B1 (bg) |
| PT (1) | PT1196409E (bg) |
| SI (1) | SI1196409T1 (bg) |
| SK (1) | SK19122001A3 (bg) |
| TR (1) | TR200103806T2 (bg) |
| TW (1) | TWI278454B (bg) |
| UA (1) | UA74787C2 (bg) |
| WO (1) | WO2001000612A2 (bg) |
| ZA (1) | ZA200110479B (bg) |
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| 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 |
| CA2376781A1 (en) * | 1999-06-28 | 2001-01-04 | Janssen Pharmaceutica N.V. | Benzimidazoles and imidazopyridines as respiratory syncytial virus replication inhibitors |
| TR200103806T2 (tr) | 1999-06-28 | 2002-06-21 | Janssen Pharmaceutica N. V. | Solunum sistemi sinsitiyal virüsünün replikasyonunu inhibe edici maddeler. |
| 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 |
| US8202896B2 (en) | 2002-08-09 | 2012-06-19 | Microdose Therapeutx, Inc. | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| US7582761B2 (en) * | 2002-10-17 | 2009-09-01 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| EP1682547B1 (en) | 2003-10-30 | 2012-10-24 | Boehringer Ingelheim (Canada) Ltd. | Rsv polymerase inhibitors |
| AR046771A1 (es) * | 2003-12-18 | 2005-12-21 | Tibotec Pharm Ltd | Derivados piperidina-amino-bencimidazol como inhibidores de la replicacion del virus sincitial respiratorio |
| AR046959A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Morfolinilo que contiene bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| DK1697347T3 (da) * | 2003-12-18 | 2011-06-06 | Tibotec Pharm Ltd | 5- eller 6-substituerede benzimidazolderivater som inhibitorer af replikation af respiratorisk syncytial-virus |
| PL1711485T3 (pl) | 2003-12-18 | 2009-11-30 | Tibotec Pharm Ltd | Pochodne aminobenzoimidazoli jako inhibitory replikacji wirusa zespólni układu oddechowego |
| CA2548657A1 (en) * | 2003-12-18 | 2005-06-30 | Tibotec Pharmaceuticals Ltd. | Aminobenzimidazoles and benzimidazoles as inhibitors of respiratory syncytial virus replication |
| AR046972A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Derivados de los amino-bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| DE102004010207A1 (de) * | 2004-03-02 | 2005-09-15 | Aventis Pharma S.A. | Neue 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate |
| JP5289934B2 (ja) | 2005-03-17 | 2013-09-11 | テイボテク・フアーマシユーチカルズ | 呼吸シンシチウムウイルス複製の阻害剤としての１，３−ジヒドロ−ベンズイミダゾール−２−イリデンアミン類 |
| US7884215B2 (en) | 2005-06-20 | 2011-02-08 | Bonfanti Jean-Francois | 2-substituted benzimidazoles |
| BRPI0611744B8 (pt) | 2005-06-20 | 2021-05-25 | Janssen R & D Ireland | benzimidazóis heterociclilaminoalquila substituída, seu processo de preparação e composição farmacêutica |
| EP1896473B1 (en) | 2005-06-20 | 2011-10-19 | Tibotec Pharmaceuticals | 1-[[2-amino-3-(substituted alkyl)-3h-benzimidazolyl]methyl]-3-subtituted-1,3-dihydro-benzoimidazol-2-ones as inhibitors of respiratory syncytial virus replication |
| WO2011097607A1 (en) * | 2010-02-08 | 2011-08-11 | Southern Research Institute | Anti-viral treatment and assay to screen for anti-viral agent |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| EP2797416B1 (en) | 2011-12-28 | 2017-08-09 | Global Blood Therapeutics, Inc. | Substituted benzaldehyde compounds and methods for their use in increasing tissue oxygenation |
| US9012450B2 (en) | 2011-12-28 | 2015-04-21 | 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 |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| CN105073728A (zh) | 2013-03-15 | 2015-11-18 | 全球血液疗法股份有限公司 | 化合物及其用于调节血红蛋白的用途 |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | 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 |
| US20140274961A1 (en) | 2013-03-15 | 2014-09-18 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| CN105246477A (zh) | 2013-03-15 | 2016-01-13 | 全球血液疗法股份有限公司 | 化合物及其用于调节血红蛋白的用途 |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| AP2015008722A0 (en) | 2013-03-15 | 2015-09-30 | 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 |
| EA202092627A1 (ru) | 2013-11-18 | 2021-09-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| AP2016009261A0 (en) | 2014-02-07 | 2016-06-30 | Global Blood Therapeutics Inc | Crystalline polymorphs of the free base of 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde |
| 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 |
| WO2017096230A1 (en) | 2015-12-04 | 2017-06-08 | Global Blood Therapeutics, Inc. | Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde |
| TWI825524B (zh) | 2016-05-12 | 2023-12-11 | 美商全球血液治療公司 | 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 |
| TWI778983B (zh) | 2016-10-12 | 2022-10-01 | 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 |
| WO2020072377A1 (en) | 2018-10-01 | 2020-04-09 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin for the treatment of sickle cell disease |
| US12145933B2 (en) | 2020-06-11 | 2024-11-19 | Janssen Sciences Ireland Unlimited Company | Hemi (L)-tartrate forms of 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethy)-1,3-dihydro-2H-imidazo[4,5-C]pyridin-2-one and pharmaceutical compositions comprising the same |
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| 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 |
| PH23995A (en) | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| US4588722A (en) | 1984-01-09 | 1986-05-13 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives |
| CA1327579C (en) | 1986-02-03 | 1994-03-08 | Frans Eduard Janssens | Anti-histaminic compositions containing n-heterocyclyl-4-piperidinamines |
| 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 |
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