EA002305B1 - Производные бензимидазола - Google Patents

Info

Publication number

EA002305B1

EA002305B1 EA199901031A EA199901031A EA002305B1 EA 002305 B1 EA002305 B1 EA 002305B1 EA 199901031 A EA199901031 A EA 199901031A EA 199901031 A EA199901031 A EA 199901031A EA 002305 B1 EA002305 B1 EA 002305B1

Authority

EA

Eurasian Patent Office

Prior art keywords

hydrogen

alkyl

8alkyl

halogen

benzimidazole

Prior art date

1997-06-10

Links

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• Global Dossier
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• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 4
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 252
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 154
• 239000001257 hydrogen Substances 0.000 claims abstract description 152
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 126
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 120
• -1 ester salt Chemical class 0.000 claims abstract description 110
• 150000002367 halogens Chemical class 0.000 claims abstract description 109
• 238000000034 method Methods 0.000 claims abstract description 107
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 94
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 81
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 58
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 54
• 150000003839 salts Chemical class 0.000 claims abstract description 37
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 30
• 150000002148 esters Chemical class 0.000 claims abstract description 28
• 125000001424 substituent group Chemical group 0.000 claims abstract description 28
• 238000011282 treatment Methods 0.000 claims abstract description 28
• 230000009385 viral infection Effects 0.000 claims abstract description 27
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 24
• 208000036142 Viral infection Diseases 0.000 claims abstract description 22
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 21
• 150000002576 ketones Chemical class 0.000 claims abstract description 21
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
• 241001465754 Metazoa Species 0.000 claims abstract description 12
• 238000004519 manufacturing process Methods 0.000 claims abstract description 10
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 9
• 230000000694 effects Effects 0.000 claims abstract description 9
• 125000001627 3 membered heterocyclic group Chemical group 0.000 claims abstract description 8
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims abstract description 8
• 208000024891 symptom Diseases 0.000 claims abstract description 8
• WKTYQVXOAVBLIO-ZYHUDNBSSA-N (1r,2r)-2-(2-bromo-5,6-dichlorobenzimidazol-1-yl)cyclohexan-1-ol Chemical compound O[C@@H]1CCCC[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Br WKTYQVXOAVBLIO-ZYHUDNBSSA-N 0.000 claims abstract description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 230000002265 prevention Effects 0.000 claims abstract description 7
• 208000002672 hepatitis B Diseases 0.000 claims abstract description 3
• 206010011831 Cytomegalovirus infection Diseases 0.000 claims abstract 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 42
• 208000015181 infectious disease Diseases 0.000 claims description 33
• 125000003118 aryl group Chemical group 0.000 claims description 29
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 26
• 125000004429 atom Chemical group 0.000 claims description 23
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
• 125000002009 alkene group Chemical group 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 150000001540 azides Chemical class 0.000 claims description 6
• FHXXWAWFWPVOAX-UHFFFAOYSA-N benzimidazole-2-thione Chemical compound C1=CC=CC2=NC(=S)N=C21 FHXXWAWFWPVOAX-UHFFFAOYSA-N 0.000 claims description 6
• 230000001225 therapeutic effect Effects 0.000 claims description 6
• 206010019972 Herpes viral infections Diseases 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 229940126601 medicinal product Drugs 0.000 claims 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 16
• 150000001336 alkenes Chemical class 0.000 abstract description 9
• 238000011321 prophylaxis Methods 0.000 abstract description 4
• ASICPWKBTMIXNS-GMTAPVOTSA-N (2r,3r,4r)-2-(2-bromo-5,6-dichlorobenzimidazol-1-yl)oxane-3,4-diol Chemical compound O[C@@H]1[C@H](O)CCO[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Br ASICPWKBTMIXNS-GMTAPVOTSA-N 0.000 abstract description 3
• OOAVDXDURLPULP-GWOFURMSSA-N (2r,3r,4r,5r)-2-(2-bromo-5,6-dichlorobenzimidazol-1-yl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@H](O)[C@H](O)CO[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Br OOAVDXDURLPULP-GWOFURMSSA-N 0.000 abstract 3
• IJLPBBAPQPMFGA-AKHDSKFASA-N [(3r,4r,5s,6r)-4,5-diacetyloxy-6-(5,6-dimethyl-2-sulfanylidene-3h-benzimidazol-1-yl)oxan-3-yl] acetate Chemical compound CC(=O)O[C@H]1[C@H](OC(C)=O)[C@H](OC(=O)C)CO[C@H]1N1C(=S)NC2=CC(C)=C(C)C=C21 IJLPBBAPQPMFGA-AKHDSKFASA-N 0.000 abstract 3
• BCGQVGLXVOKSMC-IYWMVGAKSA-N [(3r,4s,5r,6r)-4,5-diacetyloxy-6-(2,5-dimethylbenzimidazol-1-yl)oxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(=O)C)CO[C@H]1N1C2=CC=C(C)C=C2N=C1C BCGQVGLXVOKSMC-IYWMVGAKSA-N 0.000 abstract 3
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract 3
• LOMBFOAWBUJDCF-VVFBATEQSA-N (2r,3r,4r,5r)-2-(2-bromo-5,6-dichloro-4-fluorobenzimidazol-1-yl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@H](O)[C@H](O)CO[C@H]1N1C2=CC(Cl)=C(Cl)C(F)=C2N=C1Br LOMBFOAWBUJDCF-VVFBATEQSA-N 0.000 abstract 1
• ZHKNTGOJXGQPEL-DDHJBXDOSA-N (2r,3r,4r,5r)-2-(2-bromo-6-chloro-5-methylbenzimidazol-1-yl)oxane-3,4,5-triol Chemical compound C1=2C=C(Cl)C(C)=CC=2N=C(Br)N1[C@@H]1OC[C@@H](O)[C@@H](O)[C@H]1O ZHKNTGOJXGQPEL-DDHJBXDOSA-N 0.000 abstract 1
• WXZYRKDMQCTYPO-AAVRWANBSA-N (2r,3r,4r,5r)-2-[5,6-dichloro-2-(propan-2-ylamino)benzimidazol-1-yl]oxane-3,4,5-triol Chemical compound CC(C)NC1=NC2=CC(Cl)=C(Cl)C=C2N1[C@@H]1OC[C@@H](O)[C@@H](O)[C@H]1O WXZYRKDMQCTYPO-AAVRWANBSA-N 0.000 abstract 1
• YEUHNIIKVBNHKQ-YFKTTZPYSA-N (2s,3r,4r,5s)-5-(2-bromo-5,6-dichlorobenzimidazol-1-yl)-2-(hydroxymethyl)oxane-3,4-diol Chemical compound O[C@H]1[C@@H](O)[C@H](CO)OC[C@@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Br YEUHNIIKVBNHKQ-YFKTTZPYSA-N 0.000 abstract 1
• 208000029433 Herpesviridae infectious disease Diseases 0.000 abstract 1
• 239000003937 drug carrier Substances 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 339
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 214
• 239000000203 mixture Substances 0.000 description 190
• 239000000243 solution Substances 0.000 description 177
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 120
• 238000005481 NMR spectroscopy Methods 0.000 description 103
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 76
• 239000011541 reaction mixture Substances 0.000 description 74
• 239000002904 solvent Substances 0.000 description 70
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
• 239000000047 product Substances 0.000 description 68
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 51
• 239000007787 solid Substances 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 48
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
• 238000002844 melting Methods 0.000 description 45
• 230000008018 melting Effects 0.000 description 45
• 238000004458 analytical method Methods 0.000 description 43
• 235000019441 ethanol Nutrition 0.000 description 43
• 239000004480 active ingredient Substances 0.000 description 42
• 238000004949 mass spectrometry Methods 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 41
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• 238000009472 formulation Methods 0.000 description 39
• 239000000741 silica gel Substances 0.000 description 38
• 229910002027 silica gel Inorganic materials 0.000 description 38
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 35
• 239000007864 aqueous solution Substances 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 31
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
• 235000019341 magnesium sulphate Nutrition 0.000 description 30
• 239000003795 chemical substances by application Substances 0.000 description 26
• 229910052757 nitrogen Inorganic materials 0.000 description 25
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
• 125000006239 protecting group Chemical group 0.000 description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
• BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 23
• 238000001704 evaporation Methods 0.000 description 23
• 239000012044 organic layer Substances 0.000 description 23
• 230000008020 evaporation Effects 0.000 description 22
• 230000002829 reductive effect Effects 0.000 description 22
• 239000010410 layer Substances 0.000 description 21
• 235000017557 sodium bicarbonate Nutrition 0.000 description 21
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
• 238000004440 column chromatography Methods 0.000 description 19
• 238000003756 stirring Methods 0.000 description 19
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
• 239000002775 capsule Substances 0.000 description 17
• 201000010099 disease Diseases 0.000 description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
• 229920006395 saturated elastomer Polymers 0.000 description 17
• 229910000029 sodium carbonate Inorganic materials 0.000 description 17
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• 239000000126 substance Substances 0.000 description 15
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
• 125000004432 carbon atom Chemical group C* 0.000 description 14
• 125000005843 halogen group Chemical group 0.000 description 14
• 239000012299 nitrogen atmosphere Substances 0.000 description 14
• 238000010992 reflux Methods 0.000 description 14
• 239000003826 tablet Substances 0.000 description 14
• 238000004809 thin layer chromatography Methods 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 13
• 238000007429 general method Methods 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 11
• 229960000583 acetic acid Drugs 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 229910052801 chlorine Inorganic materials 0.000 description 11
• 238000000354 decomposition reaction Methods 0.000 description 11
• 239000000843 powder Substances 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• 235000011054 acetic acid Nutrition 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 238000009835 boiling Methods 0.000 description 10
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000006260 foam Substances 0.000 description 10
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 239000003039 volatile agent Substances 0.000 description 10
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
• 241000700605 Viruses Species 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 229910052799 carbon Inorganic materials 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000011521 glass Substances 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
• 125000000623 heterocyclic group Chemical group 0.000 description 8
• 238000004128 high performance liquid chromatography Methods 0.000 description 8
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 8
• 239000008101 lactose Substances 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 238000002399 angioplasty Methods 0.000 description 7
• 238000001035 drying Methods 0.000 description 7
• 239000005457 ice water Substances 0.000 description 7
• 230000001575 pathological effect Effects 0.000 description 7
• 208000037803 restenosis Diseases 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000003828 vacuum filtration Methods 0.000 description 7
• KEZMBKQTCPNSOF-UHFFFAOYSA-N 2-bromo-5,6-dichloro-1h-benzimidazole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC(Br)=N2 KEZMBKQTCPNSOF-UHFFFAOYSA-N 0.000 description 6
• JNETYVLEGPSOFY-UHFFFAOYSA-N 3-bromopyrrolidine-2,5-dione Chemical compound BrC1CC(=O)NC1=O JNETYVLEGPSOFY-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 239000007868 Raney catalyst Substances 0.000 description 6
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
• 229910000564 Raney nickel Inorganic materials 0.000 description 6
• 150000001556 benzimidazoles Chemical class 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• PFURGBBHAOXLIO-WDSKDSINSA-N cyclohexane-1,2-diol Chemical compound O[C@H]1CCCC[C@@H]1O PFURGBBHAOXLIO-WDSKDSINSA-N 0.000 description 6
• 229910052731 fluorine Inorganic materials 0.000 description 6
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 150000002500 ions Chemical class 0.000 description 6
• 230000014759 maintenance of location Effects 0.000 description 6
• 229940069328 povidone Drugs 0.000 description 6
• 238000000926 separation method Methods 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• 239000000829 suppository Substances 0.000 description 6
• IPRDZAMUYMOJTA-UHFFFAOYSA-N 5,6-dichloro-1h-benzimidazole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC=N2 IPRDZAMUYMOJTA-UHFFFAOYSA-N 0.000 description 5
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 5
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
• 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 5
• 239000000010 aprotic solvent Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
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