AU2013307337B2 - Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of Hepatitis B - Google Patents
Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of Hepatitis B Download PDFInfo
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- AU2013307337B2 AU2013307337B2 AU2013307337A AU2013307337A AU2013307337B2 AU 2013307337 B2 AU2013307337 B2 AU 2013307337B2 AU 2013307337 A AU2013307337 A AU 2013307337A AU 2013307337 A AU2013307337 A AU 2013307337A AU 2013307337 B2 AU2013307337 B2 AU 2013307337B2
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- 238000011282 treatment Methods 0.000 title description 16
- 239000003814 drug Substances 0.000 title description 9
- 208000002672 hepatitis B Diseases 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 370
- 229910052739 hydrogen Inorganic materials 0.000 claims description 173
- 229920006395 saturated elastomer Polymers 0.000 claims description 122
- 239000001257 hydrogen Substances 0.000 claims description 86
- 229910052757 nitrogen Inorganic materials 0.000 claims description 60
- 125000005842 heteroatom Chemical group 0.000 claims description 58
- 150000002431 hydrogen Chemical class 0.000 claims description 57
- 229910052760 oxygen Inorganic materials 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 229910052717 sulfur Inorganic materials 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical class 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 18
- 101100495923 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr2 gene Proteins 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 229910052799 carbon Inorganic materials 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
- 125000002619 bicyclic group Chemical group 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 4
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229930192474 thiophene Chemical group 0.000 claims description 4
- RLSXYAPFVRQJES-UHFFFAOYSA-N 2-fluoro-n-(3-fluoro-4-methylphenyl)-5-piperidin-1-ylsulfonylbenzamide Chemical compound C1=C(F)C(C)=CC=C1NC(=O)C1=CC(S(=O)(=O)N2CCCCC2)=CC=C1F RLSXYAPFVRQJES-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- DIRXYOYCANRGFJ-UHFFFAOYSA-N 2-fluoro-n-(4-fluoro-3-methylphenyl)-5-piperidin-1-ylsulfonylbenzamide Chemical compound C1=C(F)C(C)=CC(NC(=O)C=2C(=CC=C(C=2)S(=O)(=O)N2CCCCC2)F)=C1 DIRXYOYCANRGFJ-UHFFFAOYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000010076 replication Effects 0.000 abstract description 4
- 150000004677 hydrates Chemical class 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 250
- 239000000203 mixture Substances 0.000 description 236
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 174
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
- 238000005481 NMR spectroscopy Methods 0.000 description 141
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 103
- 239000000243 solution Substances 0.000 description 103
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 97
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- 239000011541 reaction mixture Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 85
- 235000019439 ethyl acetate Nutrition 0.000 description 85
- 239000012071 phase Substances 0.000 description 69
- 239000012044 organic layer Substances 0.000 description 67
- 239000002904 solvent Substances 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 56
- 239000010410 layer Substances 0.000 description 53
- 239000003480 eluent Substances 0.000 description 52
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 50
- 230000015572 biosynthetic process Effects 0.000 description 48
- 239000012267 brine Substances 0.000 description 48
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 48
- 238000003786 synthesis reaction Methods 0.000 description 48
- 150000001412 amines Chemical class 0.000 description 46
- 241000700721 Hepatitis B virus Species 0.000 description 44
- 229940093499 ethyl acetate Drugs 0.000 description 44
- 239000007787 solid Substances 0.000 description 43
- 239000007832 Na2SO4 Substances 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
- -1 fluoro-3-(piperidin-l-ylsulfonyl)benzamide Chemical compound 0.000 description 41
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- 238000010898 silica gel chromatography Methods 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000010626 work up procedure Methods 0.000 description 36
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 35
- 238000002953 preparative HPLC Methods 0.000 description 35
- 239000007821 HATU Substances 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
- 239000003208 petroleum Substances 0.000 description 29
- 239000003039 volatile agent Substances 0.000 description 29
- NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 24
- 208000015181 infectious disease Diseases 0.000 description 21
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 239000003960 organic solvent Substances 0.000 description 19
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 239000005711 Benzoic acid Substances 0.000 description 16
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 16
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 235000010233 benzoic acid Nutrition 0.000 description 16
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- NQTBKYKRAOANGR-UHFFFAOYSA-N 3-[(4-fluoro-3-methylphenyl)carbamoyl]benzenesulfonyl chloride Chemical compound C1=C(F)C(C)=CC(NC(=O)C=2C=C(C=CC=2)S(Cl)(=O)=O)=C1 NQTBKYKRAOANGR-UHFFFAOYSA-N 0.000 description 14
- 230000005526 G1 to G0 transition Effects 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000004808 supercritical fluid chromatography Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 12
- 238000010828 elution Methods 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 9
- LMRKXSDOAFUINK-UHFFFAOYSA-N 3-chlorosulfonylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S(Cl)(=O)=O)=C1 LMRKXSDOAFUINK-UHFFFAOYSA-N 0.000 description 9
- XWEBTVZIZWEJOO-UHFFFAOYSA-N 3-chlorosulfonylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(S(Cl)(=O)=O)=C1 XWEBTVZIZWEJOO-UHFFFAOYSA-N 0.000 description 9
- NQVWMPOQWBDSAI-UHFFFAOYSA-N 3-methyloxetan-3-amine Chemical compound CC1(N)COC1 NQVWMPOQWBDSAI-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 7
- JQZGYPHOWZMCNK-UHFFFAOYSA-N 2-fluoro-6-methyl-3-[(3-methyloxetan-3-yl)sulfamoyl]benzoic acid Chemical compound FC1=C(C(O)=O)C(C)=CC=C1S(=O)(=O)NC1(C)COC1 JQZGYPHOWZMCNK-UHFFFAOYSA-N 0.000 description 6
- IFWSBTBYKXRINT-UHFFFAOYSA-N 3-(difluoromethyl)-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C(F)F)=C1 IFWSBTBYKXRINT-UHFFFAOYSA-N 0.000 description 6
- KYDKEDOKJHAVBZ-UHFFFAOYSA-N 3-(propan-2-ylsulfamoyl)benzoic acid Chemical compound CC(C)NS(=O)(=O)C1=CC=CC(C(O)=O)=C1 KYDKEDOKJHAVBZ-UHFFFAOYSA-N 0.000 description 6
- PGFQDLOMDIBAPY-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)aniline Chemical compound NC1=CC=C(F)C(C(F)(F)F)=C1 PGFQDLOMDIBAPY-UHFFFAOYSA-N 0.000 description 6
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- 239000002552 dosage form Substances 0.000 description 6
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- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 5
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- 150000003254 radicals Chemical class 0.000 description 5
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- ZUBQTNFHDPACBZ-UHFFFAOYSA-N 3-(cyclopentylsulfamoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(S(=O)(=O)NC2CCCC2)=C1 ZUBQTNFHDPACBZ-UHFFFAOYSA-N 0.000 description 4
- DFNDHTNAOKAPGX-UHFFFAOYSA-N 3-ethyloxetan-3-amine Chemical compound CCC1(N)COC1 DFNDHTNAOKAPGX-UHFFFAOYSA-N 0.000 description 4
- BEFPEKUQJGOBLX-UHFFFAOYSA-N 3-methyloxetan-3-amine;hydrochloride Chemical compound Cl.CC1(N)COC1 BEFPEKUQJGOBLX-UHFFFAOYSA-N 0.000 description 4
- RGHJWZADAWEIFE-UHFFFAOYSA-N 4-amino-2-methylbenzonitrile Chemical compound CC1=CC(N)=CC=C1C#N RGHJWZADAWEIFE-UHFFFAOYSA-N 0.000 description 4
- HGOBOSIOGKNCFL-UHFFFAOYSA-N 4-fluoro-3-(fluoromethyl)aniline Chemical compound NC1=CC=C(F)C(CF)=C1 HGOBOSIOGKNCFL-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
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- 241001085205 Prenanthella exigua Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102100030302 TBC1 domain family member 8 Human genes 0.000 description 4
- 239000003957 anion exchange resin Substances 0.000 description 4
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
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- WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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| AU2018226485A AU2018226485B2 (en) | 2012-08-28 | 2018-09-07 | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of Hepatitis B |
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| EP12182076.5 | 2012-08-28 | ||
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| EP13169574.4 | 2013-05-28 | ||
| EP13169574 | 2013-05-28 | ||
| PCT/EP2013/067829 WO2014033176A1 (en) | 2012-08-28 | 2013-08-28 | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
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| AU2018226485A Division AU2018226485B2 (en) | 2012-08-28 | 2018-09-07 | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of Hepatitis B |
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| AU2013307337A1 AU2013307337A1 (en) | 2015-02-19 |
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