AU741946B2 - Substituted benzimidazole antiviral agents - Google Patents
Substituted benzimidazole antiviral agents Download PDFInfo
- Publication number
- AU741946B2 AU741946B2 AU50809/99A AU5080999A AU741946B2 AU 741946 B2 AU741946 B2 AU 741946B2 AU 50809/99 A AU50809/99 A AU 50809/99A AU 5080999 A AU5080999 A AU 5080999A AU 741946 B2 AU741946 B2 AU 741946B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- ylmethyl
- benzimidazol
- compound
- formula
- 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.)
- Ceased
Links
- 239000003443 antiviral agent Substances 0.000 title description 4
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 106
- 238000000034 method Methods 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- 229910000104 sodium hydride Inorganic materials 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 28
- 239000012312 sodium hydride Substances 0.000 description 28
- 230000008878 coupling Effects 0.000 description 27
- 238000010168 coupling process Methods 0.000 description 27
- 238000005859 coupling reaction Methods 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- CITBCYZJEBVHPS-UHFFFAOYSA-N 1-(1h-benzimidazol-2-ylmethyl)benzotriazole Chemical compound N1=NC2=CC=CC=C2N1CC1=NC2=CC=CC=C2N1 CITBCYZJEBVHPS-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 101150041968 CDC13 gene Proteins 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- -1 1-substituted 2-(benzotriazolylmethyl)-benzimidazoles Chemical class 0.000 description 16
- 239000000284 extract Substances 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 239000012964 benzotriazole Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 241000725643 Respiratory syncytial virus Species 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- WRCSVDCKXNLOCV-UHFFFAOYSA-N 2-(1h-benzimidazol-2-ylmethyl)benzotriazole Chemical compound N1=C2C=CC=CC2=NN1CC1=NC2=CC=CC=C2N1 WRCSVDCKXNLOCV-UHFFFAOYSA-N 0.000 description 8
- 230000000840 anti-viral effect Effects 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- OEBXWWBYZJNKRK-UHFFFAOYSA-N 1-methyl-2,3,4,6,7,8-hexahydropyrimido[1,2-a]pyrimidine Chemical compound C1CCN=C2N(C)CCCN21 OEBXWWBYZJNKRK-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound 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 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 150000001556 benzimidazoles Chemical class 0.000 description 4
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229960000329 ribavirin Drugs 0.000 description 4
- 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 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QOXXZTPKJWPIDK-UHFFFAOYSA-N 2-(benzotriazol-1-yl)acetic acid Chemical class C1=CC=C2N(CC(=O)O)N=NC2=C1 QOXXZTPKJWPIDK-UHFFFAOYSA-N 0.000 description 3
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- WXGAATRPKUWXKF-UHFFFAOYSA-N 1-(1h-benzimidazol-2-ylmethyl)-5,6-dimethylbenzotriazole Chemical compound C1=CC=C2NC(CN3N=NC=4C=C(C(=CC=43)C)C)=NC2=C1 WXGAATRPKUWXKF-UHFFFAOYSA-N 0.000 description 2
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 2
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 2
- SPMLMLQATWNZEE-UHFFFAOYSA-N 2-(chloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CCl)=NC2=C1 SPMLMLQATWNZEE-UHFFFAOYSA-N 0.000 description 2
- GDWRVZPLJSKFEI-UHFFFAOYSA-N 2-(iodomethyl)-1-methylsulfonylbenzimidazole Chemical compound C1=CC=C2N(S(=O)(=O)C)C(CI)=NC2=C1 GDWRVZPLJSKFEI-UHFFFAOYSA-N 0.000 description 2
- YBUZCJHFTGTBHK-UHFFFAOYSA-N 2-chloro-n-(6-chlorohexyl)ethanimine;hydrochloride Chemical compound Cl.ClCCCCCCN=CCCl YBUZCJHFTGTBHK-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- JMYYNTRVGBDWDB-FYZOBXCZSA-N (2r)-2-(chloromethyl)-1-methylpyrrolidine;hydrochloride Chemical compound Cl.CN1CCC[C@@H]1CCl JMYYNTRVGBDWDB-FYZOBXCZSA-N 0.000 description 1
- JMYYNTRVGBDWDB-RGMNGODLSA-N (2s)-2-(chloromethyl)-1-methylpyrrolidine;hydrochloride Chemical compound Cl.CN1CCC[C@H]1CCl JMYYNTRVGBDWDB-RGMNGODLSA-N 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 1
- FGAGCEMOZWSMBH-UHFFFAOYSA-N 1-[(1-butylbenzimidazol-2-yl)methyl]benzotriazole Chemical compound C1=CC=C2N(CCCC)C(CN3C4=CC=CC=C4N=N3)=NC2=C1 FGAGCEMOZWSMBH-UHFFFAOYSA-N 0.000 description 1
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- VUVGMQNYJPPCCC-UHFFFAOYSA-N pyrido[1,2-a]indole Chemical class C1=CC=CC2=CC3=CC=CC=C3N21 VUVGMQNYJPPCCC-UHFFFAOYSA-N 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
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- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
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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
- C07D401/14—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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9338798P | 1998-07-20 | 1998-07-20 | |
| US60/093387 | 1998-07-20 | ||
| PCT/US1999/012398 WO2000004900A1 (en) | 1998-07-20 | 1999-07-20 | Substituted benzimidazole antiviral agents |
Publications (2)
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| AU5080999A AU5080999A (en) | 2000-02-14 |
| AU741946B2 true AU741946B2 (en) | 2001-12-13 |
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Family Applications (1)
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|---|---|---|---|
| AU50809/99A Ceased AU741946B2 (en) | 1998-07-20 | 1999-07-20 | Substituted benzimidazole antiviral agents |
Country Status (6)
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| US (2) | US6908936B2 (https=) |
| EP (1) | EP1098644A1 (https=) |
| JP (1) | JP2002521334A (https=) |
| AU (1) | AU741946B2 (https=) |
| CA (1) | CA2338147A1 (https=) |
| WO (1) | WO2000004900A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE04592B1 (et) * | 1999-06-28 | 2006-02-15 | Janssen Pharmaceutica N.V. | Respiratoorse süntsütiaalviiruse replikatsiooni inhibiitorid, nende valmistamismeetod, kasutamine ja vaheühendid, farmatseutiline kompositsioon ja selle valmistamismeetod ning produkt |
| JP2003531867A (ja) * | 2000-05-03 | 2003-10-28 | メディミューン，インコーポレイテッド | 抗体および抗炎症薬を用いた呼吸器疾患の組合せ治療法 |
| US6489338B2 (en) | 2000-06-13 | 2002-12-03 | Bristol-Myers Squibb Company | Imidazopyridine and imidazopyrimidine antiviral agents |
| 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 |
| WO2004010935A2 (en) * | 2002-07-25 | 2004-02-05 | Medimmune, Inc. | Methods of treating and preventing rsv, hmpv, and piv using anti-rsv, anti-hmpv, and anti-piv antibodies |
| US7157471B2 (en) * | 2003-08-25 | 2007-01-02 | Boehringer Ingelheim International Gmbh | Haloalkyl- and piperidine-substituted benzimidazole-derivatives |
| WO2005042530A1 (en) | 2003-10-30 | 2005-05-12 | Boehringer Ingelheim (Canada) Ltd. | Rsv polymerase inhibitors |
| GB0406280D0 (en) * | 2004-03-19 | 2004-04-21 | Arrow Therapeutics Ltd | Chemical compounds |
| GB0406282D0 (en) * | 2004-03-19 | 2004-04-21 | Arrow Therapeutics Ltd | Therapeutic compounds |
| GB0501964D0 (en) * | 2005-01-31 | 2005-03-09 | Arrow Therapeutics Ltd | Chemical compounds |
| BRPI0520554A2 (pt) | 2005-09-19 | 2009-06-13 | Arrow Therapeutics Ltd | uso de uma benzodiazepina ou um sal farmaceuticamente aceitável do mesmo, método para tratar ou prevenir uma infecção por hcv em um paciente, derivado de benzodiazepina ou um sal famaceuticamente aceitável do mesmo, e, composição farmacêutica |
| GB0520475D0 (en) * | 2005-10-07 | 2005-11-16 | Arrow Therapeutics Ltd | Chemical compounds |
| KR20080083139A (ko) * | 2006-01-11 | 2008-09-16 | 애로우 쎄라퓨틱스 리미티드 | 항-바이러스제로 사용하기 위한트리아졸로아닐리노피리미딘 유도체 |
| MX2010002278A (es) | 2007-08-27 | 2010-03-17 | Siga Technologies Inc | Farmacos antivirales para el tratamiento de una infeccion por arenavirus. |
| EP2222645B1 (en) * | 2007-11-15 | 2013-03-20 | F. Hoffmann-La Roche AG | Benzimidazole derivatives and their use as fxr agonists |
| RU2407738C1 (ru) * | 2009-07-03 | 2010-12-27 | Общество с ограниченной ответственностью "Интеллектуальный Диалог" | Противовирусный активный компонент, фармацевтическая композиция, лекарственное средство, способ лечения вирусных заболеваний |
| WO2015085844A1 (zh) | 2013-12-10 | 2015-06-18 | 南京明德新药研发股份有限公司 | 作为抗病毒剂的咪唑衍生物及其制药用途 |
| CN107709328B (zh) | 2015-06-08 | 2021-03-05 | 山东丹红制药有限公司 | 咪唑衍生物及其中间体的制备方法和晶型 |
| CN105820156A (zh) * | 2016-04-21 | 2016-08-03 | 广东工业大学 | 苯并三氮唑基苯并咪唑啉及其制备方法和应用 |
| GB201711704D0 (en) * | 2017-07-20 | 2017-09-06 | Reviral Ltd | Pharmaceutical compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3394141A (en) | 1965-11-12 | 1968-07-23 | Fabio Sparatore | Z-benzyaminobenzimidazoles |
| US4324794A (en) * | 1980-08-26 | 1982-04-13 | Research Triangle Institute | Inhibition of respiratory syncytial virus-induced cell fusion by amidino compounds |
| DK154078C (da) | 1981-02-06 | 1989-05-22 | Ucb Sa | Analogifremgangsmaade til fremstilling af 2-(2-(4-(diphenyl-methyl)-1-piperazinyl)ethoxy)-acetamider eller syreadditionssalte heraf |
| US5066656A (en) * | 1989-11-01 | 1991-11-19 | Janssen Pharmaceutica N.V. | Pharmacologically active (6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)- and (5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl) substituted 1H-benzotriazole derivatives |
| US5256668A (en) | 1993-03-17 | 1993-10-26 | American Home Products Corporation | Aminopyrimidine derivatives as antiviral agents for respiratory syncytial virus |
| BR9700939A (pt) | 1996-02-13 | 1998-09-01 | American Cyanamid Co | Compostos aniônicos contendo traiazina úteis como agentes antivirais |
| US6919331B2 (en) * | 2001-12-10 | 2005-07-19 | Bristol-Myers Squibb Company | Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents |
-
1999
- 1999-07-20 AU AU50809/99A patent/AU741946B2/en not_active Ceased
- 1999-07-20 CA CA002338147A patent/CA2338147A1/en not_active Abandoned
- 1999-07-20 EP EP99935302A patent/EP1098644A1/en not_active Withdrawn
- 1999-07-20 JP JP2000560893A patent/JP2002521334A/ja not_active Abandoned
- 1999-07-20 WO PCT/US1999/012398 patent/WO2000004900A1/en not_active Ceased
-
2002
- 2002-11-07 US US10/289,829 patent/US6908936B2/en not_active Expired - Fee Related
-
2004
- 2004-09-03 US US10/934,921 patent/US7030140B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6908936B2 (en) | 2005-06-21 |
| US20050038085A1 (en) | 2005-02-17 |
| AU5080999A (en) | 2000-02-14 |
| US7030140B2 (en) | 2006-04-18 |
| US20030139450A1 (en) | 2003-07-24 |
| JP2002521334A (ja) | 2002-07-16 |
| EP1098644A1 (en) | 2001-05-16 |
| WO2000004900A1 (en) | 2000-02-03 |
| CA2338147A1 (en) | 2000-02-03 |
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