PT85692B - Processo para a preparacao de derivados de benzimidazois (1h-imidazol-1-ilmetil)-substituidos e de composicoes farmaceuticas que os contem - Google Patents

Info

Publication number

PT85692B

PT85692B PT85692A PT8569287A PT85692B PT 85692 B PT85692 B PT 85692B PT 85692 A PT85692 A PT 85692A PT 8569287 A PT8569287 A PT 8569287A PT 85692 B PT85692 B PT 85692B

Authority

PT

Portugal

Prior art keywords

parts

formula

methyl

alkyl

phenyl

Prior art date

1986-09-15

Links

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• 238000000034 method Methods 0.000 title claims abstract description 90
• 230000008569 process Effects 0.000 title claims description 60
• 238000002360 preparation method Methods 0.000 title claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 title abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 197
• -1 1H-imidazol-1-ylmethyl Chemical group 0.000 claims abstract description 181
• 150000003839 salts Chemical class 0.000 claims abstract description 36
• 239000004480 active ingredient Substances 0.000 claims abstract description 8
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 5
• 239000000203 mixture Substances 0.000 claims description 185
• 239000002585 base Substances 0.000 claims description 134
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 56
• 125000000217 alkyl group Chemical group 0.000 claims description 55
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 46
• 238000006243 chemical reaction Methods 0.000 claims description 45
• 239000002253 acid Substances 0.000 claims description 39
• 239000002904 solvent Substances 0.000 claims description 38
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 150000003254 radicals Chemical class 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 17
• 150000001412 amines Chemical group 0.000 claims description 15
• 229910052751 metal Chemical group 0.000 claims description 13
• 239000002184 metal Chemical group 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 239000003153 chemical reaction reagent Substances 0.000 claims description 11
• 239000003638 chemical reducing agent Substances 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 10
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 239000003795 chemical substances by application Substances 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 238000011065 in-situ storage Methods 0.000 claims description 8
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 8
• GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 7
• 229910052783 alkali metal Inorganic materials 0.000 claims description 7
• 239000012442 inert solvent Substances 0.000 claims description 7
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 5
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 5
• 238000007126 N-alkylation reaction Methods 0.000 claims description 5
• 238000010934 O-alkylation reaction Methods 0.000 claims description 5
• 150000001340 alkali metals Chemical class 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 238000002955 isolation Methods 0.000 claims description 5
• 238000000746 purification Methods 0.000 claims description 5
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
• 150000001721 carbon Chemical group 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 239000002609 medium Substances 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 239000012458 free base Substances 0.000 claims description 3
• 125000000524 functional group Chemical group 0.000 claims description 3
• 231100000252 nontoxic Toxicity 0.000 claims description 3
• 230000003000 nontoxic effect Effects 0.000 claims description 3
• 125000001424 substituent group Chemical group 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
• 238000005804 alkylation reaction Methods 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl 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
• 230000009466 transformation Effects 0.000 claims description 2
• 125000004953 trihalomethyl group Chemical group 0.000 claims description 2
• 229940111121 antirheumatic drug quinolines Drugs 0.000 claims 1
• 239000000825 pharmaceutical preparation Substances 0.000 claims 1
• 229940127557 pharmaceutical product Drugs 0.000 claims 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims 1
• 239000003098 androgen Substances 0.000 abstract description 16
• 230000015572 biosynthetic process Effects 0.000 abstract description 11
• 230000002401 inhibitory effect Effects 0.000 abstract description 7
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 361
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
• 239000000543 intermediate Substances 0.000 description 118
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 107
• 239000000243 solution Substances 0.000 description 100
• 239000000047 product Substances 0.000 description 98
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 81
• 239000003480 eluent Substances 0.000 description 76
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 73
• 229960001701 chloroform Drugs 0.000 description 73
• 239000011541 reaction mixture Substances 0.000 description 63
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
• 239000000741 silica gel Substances 0.000 description 48
• 229910002027 silica gel Inorganic materials 0.000 description 48
• 238000004440 column chromatography Methods 0.000 description 47
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 40
• 239000000284 extract Substances 0.000 description 38
• 238000003756 stirring Methods 0.000 description 36
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 33
• 238000010992 reflux Methods 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 229960004592 isopropanol Drugs 0.000 description 27
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 24
• 239000000908 ammonium hydroxide Substances 0.000 description 24
• 239000000706 filtrate Substances 0.000 description 23
• 239000003054 catalyst Substances 0.000 description 21
• 229960000583 acetic acid Drugs 0.000 description 20
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
• 235000011054 acetic acid Nutrition 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• 238000001816 cooling Methods 0.000 description 18
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
• 229920006395 saturated elastomer Polymers 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 229910021529 ammonia Inorganic materials 0.000 description 16
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 15
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 14
• 150000002148 esters Chemical group 0.000 description 13
• 239000010410 layer Substances 0.000 description 13
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 238000007363 ring formation reaction Methods 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 229910052708 sodium Inorganic materials 0.000 description 12
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 8
• TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 8
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
• 238000001704 evaporation Methods 0.000 description 8
• 239000005457 ice water Substances 0.000 description 8
• 150000002576 ketones Chemical class 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 229940116269 uric acid Drugs 0.000 description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
• 239000004215 Carbon black (E152) Substances 0.000 description 7
• 241000124008 Mammalia Species 0.000 description 7
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 7
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 7
• 150000001299 aldehydes Chemical class 0.000 description 7
• 239000000460 chlorine Chemical group 0.000 description 7
• 230000008020 evaporation Effects 0.000 description 7
• 229930195733 hydrocarbon Natural products 0.000 description 7
• 229910052697 platinum Inorganic materials 0.000 description 7
• 238000006722 reduction reaction Methods 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 229910000033 sodium borohydride Inorganic materials 0.000 description 7
• 239000012279 sodium borohydride Substances 0.000 description 7
• 229930192474 thiophene Natural products 0.000 description 7
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 6
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 229910000564 Raney nickel Inorganic materials 0.000 description 6
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 150000008282 halocarbons Chemical class 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 108010044467 Isoenzymes Proteins 0.000 description 5
• 239000005909 Kieselgur Substances 0.000 description 5
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
• MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• 239000012141 concentrate Substances 0.000 description 5
• 235000008504 concentrate Nutrition 0.000 description 5
• 150000002430 hydrocarbons Chemical class 0.000 description 5
• 210000001589 microsome Anatomy 0.000 description 5
• 239000007800 oxidant agent Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 239000001294 propane Substances 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 229960003604 testosterone Drugs 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• PXICQWWMDWQBBW-UHFFFAOYSA-N 2-chloro-6-(imidazol-1-ylmethyl)-1h-benzimidazole Chemical compound C=1C=C2NC(Cl)=NC2=CC=1CN1C=CN=C1 PXICQWWMDWQBBW-UHFFFAOYSA-N 0.000 description 4
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
• 239000005711 Benzoic acid Substances 0.000 description 4
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 239000000654 additive Substances 0.000 description 4
• 125000000304 alkynyl group Chemical group 0.000 description 4
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• UMGDCJDMYOKAJW-UHFFFAOYSA-M carbamimidothioate Chemical compound NC([S-])=N UMGDCJDMYOKAJW-UHFFFAOYSA-M 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
• 239000006185 dispersion Substances 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 150000007530 organic bases Chemical class 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 4
• FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 4
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