NO314847B1 - Benzimidazolderivater, anvendelse derav samt farmasöytisk blanding - Google Patents

Info

Publication number

NO314847B1

NO314847B1 NO19996086A NO996086A NO314847B1 NO 314847 B1 NO314847 B1 NO 314847B1 NO 19996086 A NO19996086 A NO 19996086A NO 996086 A NO996086 A NO 996086A NO 314847 B1 NO314847 B1 NO 314847B1

Authority

NO

Norway

Prior art keywords

hydrogen

benzimidazole

mmol

bromo

hydroxy

Prior art date

1997-06-10

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title description 5
• 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 description 183
• 229910052739 hydrogen Inorganic materials 0.000 claims description 113
• 239000000203 mixture Substances 0.000 claims description 99
• 239000001257 hydrogen Substances 0.000 claims description 91
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 42
• 150000002367 halogens Chemical class 0.000 claims description 42
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 38
• -1 hydroxyC1-6alkyl Chemical group 0.000 claims description 33
• 238000011282 treatment Methods 0.000 claims description 21
• 208000036142 Viral infection Diseases 0.000 claims description 14
• 230000009385 viral infection Effects 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 238000011321 prophylaxis Methods 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 10
• 241000700605 Viruses Species 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 241000701027 Human herpesvirus 6 Species 0.000 claims description 7
• 208000007514 Herpes zoster Diseases 0.000 claims description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
• 206010011831 Cytomegalovirus infection Diseases 0.000 claims description 5
• 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 5
• 241000701041 Human betaherpesvirus 7 Species 0.000 claims description 5
• 208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 4
• 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 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 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
• 241001502974 Human gammaherpesvirus 8 Species 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 22
• 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 claims 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 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 217
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 137
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
• 239000000243 solution Substances 0.000 description 98
• 238000000034 method Methods 0.000 description 89
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
• 235000019439 ethyl acetate Nutrition 0.000 description 73
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
• 238000006243 chemical reaction Methods 0.000 description 67
• 239000000047 product Substances 0.000 description 65
• 229910001868 water Inorganic materials 0.000 description 61
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
• 239000002904 solvent Substances 0.000 description 60
• 238000005481 NMR spectroscopy Methods 0.000 description 56
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
• 239000000460 chlorine Substances 0.000 description 39
• 239000007787 solid Substances 0.000 description 39
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• 239000000741 silica gel Substances 0.000 description 34
• 229910002027 silica gel Inorganic materials 0.000 description 33
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 30
• 238000009472 formulation Methods 0.000 description 29
• 238000005160 1H NMR spectroscopy Methods 0.000 description 28
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 28
• 239000004480 active ingredient Substances 0.000 description 27
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 26
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 23
• 238000004458 analytical method Methods 0.000 description 23
• 235000019441 ethanol Nutrition 0.000 description 23
• 229910052757 nitrogen Inorganic materials 0.000 description 23
• 230000002829 reductive effect Effects 0.000 description 23
• 239000012044 organic layer Substances 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
• 235000019341 magnesium sulphate Nutrition 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 20
• 235000017557 sodium bicarbonate Nutrition 0.000 description 20
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
• 239000003795 chemical substances by application Substances 0.000 description 19
• 208000015181 infectious disease Diseases 0.000 description 19
• 150000003839 salts Chemical class 0.000 description 19
• 238000010992 reflux Methods 0.000 description 18
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• 229960000583 acetic acid Drugs 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• 235000011054 acetic acid Nutrition 0.000 description 15
• 238000001704 evaporation Methods 0.000 description 15
• 230000008020 evaporation Effects 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 229910000029 sodium carbonate Inorganic materials 0.000 description 15
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• 238000004809 thin layer chromatography Methods 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
• 239000006260 foam Substances 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 10
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 239000011521 glass Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 241000701022 Cytomegalovirus Species 0.000 description 9
• 125000005843 halogen group Chemical group 0.000 description 9
• 239000004615 ingredient Substances 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 241000700721 Hepatitis B virus Species 0.000 description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• OOAVDXDURLPULP-RCWTZXSCSA-N (2s,3s,4s,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-RCWTZXSCSA-N 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 229910052801 chlorine Inorganic materials 0.000 description 7
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
• 238000003828 vacuum filtration Methods 0.000 description 7
• TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 6
• 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
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 6
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 6
• 238000002399 angioplasty Methods 0.000 description 6
• 150000001556 benzimidazoles Chemical class 0.000 description 6
• 238000009835 boiling Methods 0.000 description 6
• 150000001720 carbohydrates Chemical class 0.000 description 6
• 235000014633 carbohydrates Nutrition 0.000 description 6
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 6
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• 239000002777 nucleoside Substances 0.000 description 6
• 239000008363 phosphate buffer Substances 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• 239000001119 stannous chloride Substances 0.000 description 6
• 235000011150 stannous chloride Nutrition 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
• 238000010626 work up procedure Methods 0.000 description 6
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• HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
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• 206010028980 Neoplasm Diseases 0.000 description 5
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
• MJOQJPYNENPSSS-LPWJVIDDSA-N [(3r,4r,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O MJOQJPYNENPSSS-LPWJVIDDSA-N 0.000 description 5
• 239000000010 aprotic solvent Substances 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 239000005457 ice water Substances 0.000 description 5
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
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• 230000009467 reduction Effects 0.000 description 5
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• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 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 4
• 229910014265 BrCl Inorganic materials 0.000 description 4
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
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• 230000000840 anti-viral effect Effects 0.000 description 4
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• 230000037396 body weight Effects 0.000 description 4
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• 239000000706 filtrate Substances 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 239000011737 fluorine Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
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• 239000007903 gelatin capsule Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
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• NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 4
• 150000004986 phenylenediamines Chemical class 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 229940069328 povidone Drugs 0.000 description 4
• 230000035755 proliferation Effects 0.000 description 4
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