EA037378B1 - Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b - Google Patents
Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b Download PDFInfo
- Publication number
- EA037378B1 EA037378B1 EA201592200A EA201592200A EA037378B1 EA 037378 B1 EA037378 B1 EA 037378B1 EA 201592200 A EA201592200 A EA 201592200A EA 201592200 A EA201592200 A EA 201592200A EA 037378 B1 EA037378 B1 EA 037378B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- mmol
- methyl
- sulfamoyl
- pyrrole
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims description 19
- 239000003814 drug Substances 0.000 title claims description 10
- 208000006454 hepatitis Diseases 0.000 title description 2
- SXZUZUQZZIEKBN-UHFFFAOYSA-N 3-sulfamoyl-1H-pyrrole-2-carboxamide Chemical class NC(=O)c1[nH]ccc1S(N)(=O)=O SXZUZUQZZIEKBN-UHFFFAOYSA-N 0.000 title 1
- 231100000283 hepatitis Toxicity 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 635
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 239000012453 solvate Substances 0.000 claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- -1 —OH Chemical group 0.000 claims description 106
- 239000000460 chlorine Substances 0.000 claims description 93
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 44
- 241000700721 Hepatitis B virus Species 0.000 claims description 38
- 125000001153 fluoro group Chemical group F* 0.000 claims description 37
- 229920006395 saturated elastomer Polymers 0.000 claims description 37
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 208000015181 infectious disease Diseases 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 10
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 125000003367 polycyclic group Chemical group 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 4
- 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 300
- 239000003112 inhibitor Substances 0.000 abstract description 7
- 150000004677 hydrates Chemical class 0.000 abstract description 3
- 230000010076 replication Effects 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 385
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 285
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 258
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 234
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 229
- 239000011541 reaction mixture Substances 0.000 description 225
- 239000000203 mixture Substances 0.000 description 224
- 238000005160 1H NMR spectroscopy Methods 0.000 description 209
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 203
- 239000000843 powder Substances 0.000 description 192
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 177
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 173
- 235000019439 ethyl acetate Nutrition 0.000 description 169
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 144
- 239000007787 solid Substances 0.000 description 129
- 239000000243 solution Substances 0.000 description 124
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 96
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- 238000005481 NMR spectroscopy Methods 0.000 description 78
- 230000015572 biosynthetic process Effects 0.000 description 69
- 238000003786 synthesis reaction Methods 0.000 description 67
- 239000002244 precipitate Substances 0.000 description 63
- 239000000047 product Substances 0.000 description 61
- 239000012044 organic layer Substances 0.000 description 60
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 59
- 238000004440 column chromatography Methods 0.000 description 55
- 239000002904 solvent Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 50
- 239000000741 silica gel Substances 0.000 description 50
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 47
- 238000010898 silica gel chromatography Methods 0.000 description 47
- 239000013078 crystal Substances 0.000 description 46
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 45
- 229910052938 sodium sulfate Inorganic materials 0.000 description 45
- 235000011152 sodium sulphate Nutrition 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- 238000010992 reflux Methods 0.000 description 40
- HHTRAISBAAXRKZ-UHFFFAOYSA-N 5-amino-2-fluorobenzonitrile Chemical compound NC1=CC=C(F)C(C#N)=C1 HHTRAISBAAXRKZ-UHFFFAOYSA-N 0.000 description 39
- 239000003921 oil Substances 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 38
- 238000000113 differential scanning calorimetry Methods 0.000 description 37
- 239000011734 sodium Substances 0.000 description 35
- 238000003756 stirring Methods 0.000 description 34
- 239000000706 filtrate Substances 0.000 description 33
- 239000007821 HATU Substances 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 29
- 238000010828 elution Methods 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000012267 brine Substances 0.000 description 26
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 25
- RUSVTHSNIQGSOQ-UHFFFAOYSA-N Cn1cc(cc1C(Cl)=O)S(Cl)(=O)=O Chemical compound Cn1cc(cc1C(Cl)=O)S(Cl)(=O)=O RUSVTHSNIQGSOQ-UHFFFAOYSA-N 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 23
- 239000010410 layer Substances 0.000 description 22
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 22
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 20
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 20
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 20
- NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 19
- 239000000284 extract Substances 0.000 description 19
- SNMLKBMPULDPTA-UWTATZPHSA-N (2r)-1,1,1-trifluoropropan-2-amine Chemical compound C[C@@H](N)C(F)(F)F SNMLKBMPULDPTA-UWTATZPHSA-N 0.000 description 18
- NQVWMPOQWBDSAI-UHFFFAOYSA-N 3-methyloxetan-3-amine Chemical compound CC1(N)COC1 NQVWMPOQWBDSAI-UHFFFAOYSA-N 0.000 description 18
- WZRPUINRCVBBFJ-UHFFFAOYSA-N 5-[(4-fluoro-3-methylphenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cc1cc(NC(=O)c2cc(cn2C)S(Cl)(=O)=O)ccc1F WZRPUINRCVBBFJ-UHFFFAOYSA-N 0.000 description 18
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 18
- 230000008025 crystallization Effects 0.000 description 18
- 238000001035 drying Methods 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 18
- YFBWGBFWVFEGEZ-UHFFFAOYSA-N 1,1,1-trifluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)C(F)(F)F YFBWGBFWVFEGEZ-UHFFFAOYSA-N 0.000 description 17
- BNTNWQPIBPBJOO-UHFFFAOYSA-N 3-chloro-2,4-difluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1F BNTNWQPIBPBJOO-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000012153 distilled water Substances 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 15
- WAOSZEIIXARGLC-UHFFFAOYSA-N 5-[(3-chloro-4,5-difluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)c(F)c(Cl)c1)S(Cl)(=O)=O WAOSZEIIXARGLC-UHFFFAOYSA-N 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
- 230000005526 G1 to G0 transition Effects 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 14
- 230000014509 gene expression Effects 0.000 description 14
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 14
- 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 13
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 13
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 13
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 13
- 229940127113 compound 57 Drugs 0.000 description 13
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 13
- 239000002808 molecular sieve Substances 0.000 description 13
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 13
- RLOQBKJCOAXOLR-UHFFFAOYSA-N 1h-pyrrole-2-carboxamide Chemical compound NC(=O)C1=CC=CN1 RLOQBKJCOAXOLR-UHFFFAOYSA-N 0.000 description 12
- KOWPUNQBGWIERF-UHFFFAOYSA-N 3-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Br)=C1 KOWPUNQBGWIERF-UHFFFAOYSA-N 0.000 description 12
- BEFPEKUQJGOBLX-UHFFFAOYSA-N 3-methyloxetan-3-amine;hydrochloride Chemical compound Cl.CC1(N)COC1 BEFPEKUQJGOBLX-UHFFFAOYSA-N 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 239000003039 volatile agent Substances 0.000 description 11
- ZVLYNMPVUNEGSL-UHFFFAOYSA-N 1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylic acid Chemical compound Cn1cc(cc1C(O)=O)S(=O)(=O)NC1(C)COC1 ZVLYNMPVUNEGSL-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- SNMLKBMPULDPTA-REOHCLBHSA-N (2s)-1,1,1-trifluoropropan-2-amine Chemical compound C[C@H](N)C(F)(F)F SNMLKBMPULDPTA-REOHCLBHSA-N 0.000 description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- FBWOFVFUKXZXKT-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropan-1-amine Chemical compound FC(F)(F)C1(N)CC1 FBWOFVFUKXZXKT-UHFFFAOYSA-N 0.000 description 8
- GKAWZQUCBBXBST-UHFFFAOYSA-N 3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylic acid Chemical compound Cn1cc(c(F)c1C(O)=O)S(=O)(=O)NC1(C)COC1 GKAWZQUCBBXBST-UHFFFAOYSA-N 0.000 description 8
- IGNFILTZSIUWBS-UHFFFAOYSA-N 4-fluoro-3,5-dimethylaniline Chemical compound CC1=CC(N)=CC(C)=C1F IGNFILTZSIUWBS-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 239000002253 acid Substances 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 239000003643 water by type Substances 0.000 description 8
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 7
- BHRZNVHARXXAHW-SCSAIBSYSA-N (2r)-butan-2-amine Chemical compound CC[C@@H](C)N BHRZNVHARXXAHW-SCSAIBSYSA-N 0.000 description 7
- XWBTZHDDWRNOQH-UHFFFAOYSA-N 3-chloro-2-fluoroaniline Chemical compound NC1=CC=CC(Cl)=C1F XWBTZHDDWRNOQH-UHFFFAOYSA-N 0.000 description 7
- BZXPLADBSZWDIH-VWMHFEHESA-N 4-methylbenzenesulfonic acid;(3s)-oxolan-3-amine Chemical compound N[C@H]1CCOC1.CC1=CC=C(S(O)(=O)=O)C=C1 BZXPLADBSZWDIH-VWMHFEHESA-N 0.000 description 7
- KBRBQFMCBXAAQY-UHFFFAOYSA-N 5-ethoxycarbonyl-4-fluoro-1-methylpyrrole-3-sulfonic acid Chemical compound CCOC(=O)c1c(F)c(cn1C)S(O)(=O)=O KBRBQFMCBXAAQY-UHFFFAOYSA-N 0.000 description 7
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- BTSURNRVAKJLGT-UHFFFAOYSA-N methyl 4-chlorosulfonyl-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(S(Cl)(=O)=O)=CN1C BTSURNRVAKJLGT-UHFFFAOYSA-N 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 6
- WRDGNXCXTDDYBZ-UHFFFAOYSA-N 2,3,4-trifluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1F WRDGNXCXTDDYBZ-UHFFFAOYSA-N 0.000 description 6
- RXLFDOQOCRNACG-UHFFFAOYSA-N 3-amino-2,6-difluorobenzonitrile Chemical compound NC1=CC=C(F)C(C#N)=C1F RXLFDOQOCRNACG-UHFFFAOYSA-N 0.000 description 6
- JBBZXOUMFRXWGF-UHFFFAOYSA-N 3-chloro-4,5-difluoroaniline Chemical compound NC1=CC(F)=C(F)C(Cl)=C1 JBBZXOUMFRXWGF-UHFFFAOYSA-N 0.000 description 6
- JCLWHQAZVFXOSC-UHFFFAOYSA-N 3-chloro-4,5-difluoroaniline;hydrochloride Chemical compound Cl.NC1=CC(F)=C(F)C(Cl)=C1 JCLWHQAZVFXOSC-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
- UFBBYRFPBBSWBU-UHFFFAOYSA-N 5-[(3,4-difluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(F)c1)S(Cl)(=O)=O UFBBYRFPBBSWBU-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102000006992 Interferon-alpha Human genes 0.000 description 6
- 108010047761 Interferon-alpha Proteins 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- GVLLVABLNQEYEJ-UHFFFAOYSA-N ethyl 4-chlorosulfonyl-1,3-dimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(C)c(cn1C)S(Cl)(=O)=O GVLLVABLNQEYEJ-UHFFFAOYSA-N 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- KLMDHEJHLURADR-ZCFIWIBFSA-N methyl 1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound CN1C(=CC(=C1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C(=O)OC KLMDHEJHLURADR-ZCFIWIBFSA-N 0.000 description 6
- PNSIPDUJIQVUCE-UHFFFAOYSA-N methyl 3-chloro-4-chlorosulfonyl-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)c1c(Cl)c(cn1C)S(Cl)(=O)=O PNSIPDUJIQVUCE-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- JTVVNUHLHRQWDZ-UHFFFAOYSA-N 1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxylic acid Chemical compound CC(C)NS(=O)(=O)C=1C=C(C(O)=O)N(C)C=1 JTVVNUHLHRQWDZ-UHFFFAOYSA-N 0.000 description 5
- BFGCKEHSFRPNRZ-UHFFFAOYSA-N 3-amino-2-fluorobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1F BFGCKEHSFRPNRZ-UHFFFAOYSA-N 0.000 description 5
- PFIDDPJPBKFVBO-UHFFFAOYSA-N 5-[(3,5-dichloro-4-fluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1cc(Cl)c(F)c(Cl)c1)S(Cl)(=O)=O PFIDDPJPBKFVBO-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- DRBWRJPFNOBNIO-KOLCDFICSA-N [(2r)-1-[(2r)-2-(pyridine-4-carbonylamino)propanoyl]pyrrolidin-2-yl]boronic acid Chemical compound N([C@H](C)C(=O)N1[C@@H](CCC1)B(O)O)C(=O)C1=CC=NC=C1 DRBWRJPFNOBNIO-KOLCDFICSA-N 0.000 description 5
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 229940126540 compound 41 Drugs 0.000 description 5
- OCUGZUVWNWTQFZ-ZCFIWIBFSA-N ethyl 3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)c(cn1C)S(=O)(=O)N[C@H](C)C(F)(F)F OCUGZUVWNWTQFZ-ZCFIWIBFSA-N 0.000 description 5
- IFVWMCYFJGRABA-UHFFFAOYSA-N ethyl 3-fluoro-1-methylpyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)ccn1C IFVWMCYFJGRABA-UHFFFAOYSA-N 0.000 description 5
- WDEBCXCPTCJPTN-UHFFFAOYSA-N ethyl 4-chlorosulfonyl-3-fluoro-1-methylpyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)c(cn1C)S(Cl)(=O)=O WDEBCXCPTCJPTN-UHFFFAOYSA-N 0.000 description 5
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 5
- KLMDHEJHLURADR-LURJTMIESA-N methyl 1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound CN1C(=CC(=C1)S(N[C@H](C(F)(F)F)C)(=O)=O)C(=O)OC KLMDHEJHLURADR-LURJTMIESA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 4
- WLXXTHPAORBNIG-UHFFFAOYSA-N (3,3-difluorocyclobutyl)azanium;chloride Chemical compound Cl.NC1CC(F)(F)C1 WLXXTHPAORBNIG-UHFFFAOYSA-N 0.000 description 4
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 4
- FGENWPIVTSYJAV-ZCFIWIBFSA-N 1,3-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=C(C(=C1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)O FGENWPIVTSYJAV-ZCFIWIBFSA-N 0.000 description 4
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 4
- FBIGHNPLYMGDIF-YFKPBYRVSA-N 1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=CC(=C1)S(N[C@H](C(F)(F)F)C)(=O)=O)C(=O)O FBIGHNPLYMGDIF-YFKPBYRVSA-N 0.000 description 4
- OEJHAUZWRVHXKE-UHFFFAOYSA-N 1-methyl-5-[(3,4,5-trifluorophenyl)carbamoyl]pyrrole-3-sulfonyl chloride Chemical compound CN1C=C(C=C1C(NC1=CC(=C(C(=C1)F)F)F)=O)S(=O)(=O)Cl OEJHAUZWRVHXKE-UHFFFAOYSA-N 0.000 description 4
- GEMLIOXWQRDDOA-UHFFFAOYSA-N 2,4-difluoro-3-methylaniline Chemical compound CC1=C(F)C=CC(N)=C1F GEMLIOXWQRDDOA-UHFFFAOYSA-N 0.000 description 4
- ISYXXORXVFRVKD-UHFFFAOYSA-N 3,4-difluoro-5-methylaniline Chemical compound CC1=CC(N)=CC(F)=C1F ISYXXORXVFRVKD-UHFFFAOYSA-N 0.000 description 4
- NKTZSKQMAITPBQ-UHFFFAOYSA-N 3,5-dichloro-4-fluoroaniline Chemical compound NC1=CC(Cl)=C(F)C(Cl)=C1 NKTZSKQMAITPBQ-UHFFFAOYSA-N 0.000 description 4
- DGAXUDKYSFUVCS-UHFFFAOYSA-N 3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxylic acid Chemical compound CC(C)NS(=O)(=O)c1cn(C)c(C(O)=O)c1F DGAXUDKYSFUVCS-UHFFFAOYSA-N 0.000 description 4
- GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 4
- WZRPUINRCVBBFJ-XBTCESIDSA-N 5-[(2,6-dideuterio-4-fluoro-3-methylphenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound [2H]c1cc(F)c(C)c([2H])c1NC(=O)c1cc(cn1C)S(Cl)(=O)=O WZRPUINRCVBBFJ-XBTCESIDSA-N 0.000 description 4
- FBIIZNGSQLWYRN-UHFFFAOYSA-N 5-[(3-cyano-4-fluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(c1)C#N)S(Cl)(=O)=O FBIIZNGSQLWYRN-UHFFFAOYSA-N 0.000 description 4
- ISMDILRWKSYCOD-GNKBHMEESA-N C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O Chemical compound C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O ISMDILRWKSYCOD-GNKBHMEESA-N 0.000 description 4
- 229940126639 Compound 33 Drugs 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 4
- 241001085205 Prenanthella exigua Species 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229940125773 compound 10 Drugs 0.000 description 4
- 229940125797 compound 12 Drugs 0.000 description 4
- 229940126208 compound 22 Drugs 0.000 description 4
- 229940125844 compound 46 Drugs 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 3
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 3
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 3
- HNMJEHMYCCOQGX-ZCFIWIBFSA-N 1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=CC(=C1C)S(N[C@@H](C(F)(F)F)C)(=O)=O)C(=O)O HNMJEHMYCCOQGX-ZCFIWIBFSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- HRZXOODJZOHIPX-UHFFFAOYSA-N 1-ethyl-5-[(4-fluoro-3-methylphenyl)carbamoyl]pyrrole-3-sulfonyl chloride Chemical compound C(C)N1C=C(C=C1C(NC1=CC(=C(C=C1)F)C)=O)S(=O)(=O)Cl HRZXOODJZOHIPX-UHFFFAOYSA-N 0.000 description 3
- NYMDPDNETOLVBS-XRIVEGAOSA-N 2,6-dideuterio-4-fluoro-3-methylaniline Chemical compound [2H]c1cc(F)c(C)c([2H])c1N NYMDPDNETOLVBS-XRIVEGAOSA-N 0.000 description 3
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 3
- WMWQBBDBADQLJY-UHFFFAOYSA-N 3,3-difluoro-1-methylcyclobutan-1-amine;hydrochloride Chemical compound Cl.CC1(N)CC(F)(F)C1 WMWQBBDBADQLJY-UHFFFAOYSA-N 0.000 description 3
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 3
- IFWSBTBYKXRINT-UHFFFAOYSA-N 3-(difluoromethyl)-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C(F)F)=C1 IFWSBTBYKXRINT-UHFFFAOYSA-N 0.000 description 3
- FPGXJFRUOBTEGT-UHFFFAOYSA-N 3-(trifluoromethyl)oxolan-3-amine hydrochloride Chemical compound Cl.NC1(CCOC1)C(F)(F)F FPGXJFRUOBTEGT-UHFFFAOYSA-N 0.000 description 3
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 3
- ZZYCUYNPWPYUQK-UHFFFAOYSA-N 3-methyloxolan-3-amine;hydrochloride Chemical compound Cl.CC1(N)CCOC1 ZZYCUYNPWPYUQK-UHFFFAOYSA-N 0.000 description 3
- CFXCICAPKMGNTA-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-3-fluoro-1-methylpyrrole-2-carboxylic acid Chemical compound Cn1cc(c(F)c1C(O)=O)S(=O)(=O)NC(C)(C)C CFXCICAPKMGNTA-UHFFFAOYSA-N 0.000 description 3
- POMZQIUIOJIHIN-UHFFFAOYSA-N 4-chlorosulfonyl-1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=C(S(Cl)(=O)=O)C=C1C(O)=O POMZQIUIOJIHIN-UHFFFAOYSA-N 0.000 description 3
- YDRWDORHWWKEAP-UHFFFAOYSA-N 5-[(2,4-difluoro-3-methylphenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cc1c(F)ccc(NC(=O)c2cc(cn2C)S(Cl)(=O)=O)c1F YDRWDORHWWKEAP-UHFFFAOYSA-N 0.000 description 3
- GSGSDDFFURJGST-UHFFFAOYSA-N 5-[(3-chloro-2,4-difluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(Cl)c1F)S(Cl)(=O)=O GSGSDDFFURJGST-UHFFFAOYSA-N 0.000 description 3
- COIYJIMHHNZOGL-UHFFFAOYSA-N 5-[(3-cyano-5-fluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)cc(c1)C#N)S(Cl)(=O)=O COIYJIMHHNZOGL-UHFFFAOYSA-N 0.000 description 3
- UUCRQJJRSGSTRX-UHFFFAOYSA-N 5-[[3-(1,1-difluoroethyl)-4-fluorophenyl]carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(c1)C(C)(F)F)S(Cl)(=O)=O UUCRQJJRSGSTRX-UHFFFAOYSA-N 0.000 description 3
- 101000697277 Anemonia viridis Kappa-actitoxin-Avd4c Proteins 0.000 description 3
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 3
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 3
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 229940126543 compound 14 Drugs 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- 229940126086 compound 21 Drugs 0.000 description 3
- 229940125833 compound 23 Drugs 0.000 description 3
- 229940125961 compound 24 Drugs 0.000 description 3
- 229940125846 compound 25 Drugs 0.000 description 3
- 229940127204 compound 29 Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 229940125807 compound 37 Drugs 0.000 description 3
- 229940127271 compound 49 Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 3
- BBLNZSQGDCYZFP-MRVPVSSYSA-N ethyl 1,3-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound CN1C(=C(C(=C1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)OCC BBLNZSQGDCYZFP-MRVPVSSYSA-N 0.000 description 3
- LNWWHTDANLKBCR-UHFFFAOYSA-N ethyl 3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)c(cn1C)S(=O)(=O)NC(C)C LNWWHTDANLKBCR-UHFFFAOYSA-N 0.000 description 3
- RIQOFFNSHGMZGV-UHFFFAOYSA-N ethyl 3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)c(cn1C)S(=O)(=O)NC1(C)COC1 RIQOFFNSHGMZGV-UHFFFAOYSA-N 0.000 description 3
- IOMPVSSPJCJUPK-UHFFFAOYSA-N ethyl 4-chlorosulfonyl-1,5-dimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC(S(Cl)(=O)=O)=C(C)N1C IOMPVSSPJCJUPK-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 3
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 2
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 2
- OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 description 2
- YBRBMKDOPFTVDT-GQALSZNTSA-N 1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-amine Chemical compound [2H]C([2H])([2H])C(N)(C([2H])([2H])[2H])C([2H])([2H])[2H] YBRBMKDOPFTVDT-GQALSZNTSA-N 0.000 description 2
- NJOAEPIKHMBUTN-UHFFFAOYSA-N 1,1,1-trifluoro-2-methylbutan-2-amine;hydrochloride Chemical compound Cl.CCC(C)(N)C(F)(F)F NJOAEPIKHMBUTN-UHFFFAOYSA-N 0.000 description 2
- RFKFQYKDHZNKSW-UHFFFAOYSA-N 1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylic acid Chemical compound Cc1c(C(O)=O)n(C)cc1S(=O)(=O)NC1(C)COC1 RFKFQYKDHZNKSW-UHFFFAOYSA-N 0.000 description 2
- FGENWPIVTSYJAV-LURJTMIESA-N 1,3-dimethyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=C(C(=C1)S(N[C@H](C(F)(F)F)C)(=O)=O)C)C(=O)O FGENWPIVTSYJAV-LURJTMIESA-N 0.000 description 2
- KBRXQOAHHQJLDW-UHFFFAOYSA-N 1,5-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=CC(=C1C)S(NC1(COC1)C)(=O)=O)C(=O)O KBRXQOAHHQJLDW-UHFFFAOYSA-N 0.000 description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
- 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 2
- DBPVZLYTUXNIAQ-UHFFFAOYSA-N 1-[[5-[(3-chloro-4,5-difluorophenyl)carbamoyl]-1-methylpyrrol-3-yl]sulfonylamino]cyclopropane-1-carboxylic acid Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)c(F)c(Cl)c1)S(=O)(=O)NC1(CC1)C(O)=O DBPVZLYTUXNIAQ-UHFFFAOYSA-N 0.000 description 2
- CHODSSFYKUSDHG-UHFFFAOYSA-N 1-fluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)CF CHODSSFYKUSDHG-UHFFFAOYSA-N 0.000 description 2
- AQYUGPBECYFBND-UHFFFAOYSA-N 1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxylic acid Chemical compound CN1C=C(S(=O)(=O)NCC(F)(F)F)C=C1C(O)=O AQYUGPBECYFBND-UHFFFAOYSA-N 0.000 description 2
- FBIGHNPLYMGDIF-RXMQYKEDSA-N 1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylic acid Chemical compound CN1C(=CC(=C1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C(=O)O FBIGHNPLYMGDIF-RXMQYKEDSA-N 0.000 description 2
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 2
- SLHUWMLRDHOSEI-UHFFFAOYSA-N 2-(1,1-difluoroethyl)-1-fluoro-4-nitrobenzene Chemical compound CC(F)(F)C1=CC([N+]([O-])=O)=CC=C1F SLHUWMLRDHOSEI-UHFFFAOYSA-N 0.000 description 2
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 2
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 2
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 2
- QTMAZYGAVHCKKX-UHFFFAOYSA-N 2-[(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)methoxy]propane-1,3-diol Chemical compound NC1=NC=NC2=C1C(Br)=CN2COC(CO)CO QTMAZYGAVHCKKX-UHFFFAOYSA-N 0.000 description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
- PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 2
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 2
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 2
- SZRDJHHKIJHJHQ-UHFFFAOYSA-N 3,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C(F)=C1 SZRDJHHKIJHJHQ-UHFFFAOYSA-N 0.000 description 2
- KPFHVJDYMDWZLX-UHFFFAOYSA-N 3-(1,1-difluoroethyl)-4-fluoroaniline Chemical compound CC(F)(F)C1=CC(N)=CC=C1F KPFHVJDYMDWZLX-UHFFFAOYSA-N 0.000 description 2
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 2
- XUMSHCRPQCZRGX-UHFFFAOYSA-N 3-aminocyclobutan-1-ol;hydrochloride Chemical compound Cl.NC1CC(O)C1 XUMSHCRPQCZRGX-UHFFFAOYSA-N 0.000 description 2
- NUDDKKLQNVWKRU-UHFFFAOYSA-N 3-bromo-2,4-difluoroaniline Chemical compound NC1=CC=C(F)C(Br)=C1F NUDDKKLQNVWKRU-UHFFFAOYSA-N 0.000 description 2
- GYPOUGZGHDSUKH-UHFFFAOYSA-N 3-bromo-4,5-difluoroaniline Chemical compound NC1=CC(F)=C(F)C(Br)=C1 GYPOUGZGHDSUKH-UHFFFAOYSA-N 0.000 description 2
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 2
- RBEUQRUXEDWOGJ-UHFFFAOYSA-N 4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxylic acid Chemical compound Cn1cc(cc1C(O)=O)S(=O)(=O)NCC(F)F RBEUQRUXEDWOGJ-UHFFFAOYSA-N 0.000 description 2
- IBQNERPXIBAMMF-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=C(S(=O)(=O)NC(C)(C)C)C=C1C(O)=O IBQNERPXIBAMMF-UHFFFAOYSA-N 0.000 description 2
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 2
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 2
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 2
- GVCLNACSYKYUHP-UHFFFAOYSA-N 4-amino-7-(2-hydroxyethoxymethyl)pyrrolo[2,3-d]pyrimidine-5-carbothioamide Chemical compound C1=NC(N)=C2C(C(=S)N)=CN(COCCO)C2=N1 GVCLNACSYKYUHP-UHFFFAOYSA-N 0.000 description 2
- ACMJJQYSPUPMPN-UHFFFAOYSA-N 4-chloro-3-fluoroaniline Chemical compound NC1=CC=C(Cl)C(F)=C1 ACMJJQYSPUPMPN-UHFFFAOYSA-N 0.000 description 2
- MCCVITQSMUEWFR-UHFFFAOYSA-N 4-chlorosulfonyl-1-ethylpyrrole-2-carboxylic acid Chemical compound CCN1C=C(S(Cl)(=O)=O)C=C1C(O)=O MCCVITQSMUEWFR-UHFFFAOYSA-N 0.000 description 2
- JSMGZPOPIVVIRZ-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(F)C(OC(F)(F)F)=C1 JSMGZPOPIVVIRZ-UHFFFAOYSA-N 0.000 description 2
- XSQNSPZMNWVFRB-UHFFFAOYSA-N 5-[(3-cyanophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1cccc(c1)C#N)S(Cl)(=O)=O XSQNSPZMNWVFRB-UHFFFAOYSA-N 0.000 description 2
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 2
- APBZZGQDISHNAJ-UHFFFAOYSA-N 5-[[4-fluoro-3-(trifluoromethoxy)phenyl]carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(OC(F)(F)F)c1)S(Cl)(=O)=O APBZZGQDISHNAJ-UHFFFAOYSA-N 0.000 description 2
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 2
- IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 2
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 2
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 2
- NJIAKNWTIVDSDA-FQEVSTJZSA-N 7-[4-(1-methylsulfonylpiperidin-4-yl)phenyl]-n-[[(2s)-morpholin-2-yl]methyl]pyrido[3,4-b]pyrazin-5-amine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(C=2N=C(NC[C@H]3OCCNC3)C3=NC=CN=C3C=2)C=C1 NJIAKNWTIVDSDA-FQEVSTJZSA-N 0.000 description 2
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 2
- IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 2
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 2
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 2
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 2
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 2
- 101710132601 Capsid protein Proteins 0.000 description 2
- 108020004638 Circular DNA Proteins 0.000 description 2
- MAIRBBJVNNARDV-UHFFFAOYSA-N ClS(=O)(=O)C=1C=C(N(C1)CC)C(=O)Cl Chemical compound ClS(=O)(=O)C=1C=C(N(C1)CC)C(=O)Cl MAIRBBJVNNARDV-UHFFFAOYSA-N 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- 229940127007 Compound 39 Drugs 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- VGIYNIGLEIWPCR-QMMMGPOBSA-N N-(3-cyano-2,4-difluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C)F VGIYNIGLEIWPCR-QMMMGPOBSA-N 0.000 description 2
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 2
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 2
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229960001997 adefovir Drugs 0.000 description 2
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 229940125851 compound 27 Drugs 0.000 description 2
- 229940125878 compound 36 Drugs 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 229940126545 compound 53 Drugs 0.000 description 2
- 229940125900 compound 59 Drugs 0.000 description 2
- 229940126179 compound 72 Drugs 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- CAVGRDVEFANOTM-UHFFFAOYSA-N ethyl 1,3,5-trimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(C)c(c(C)n1C)S(=O)(=O)NC1(C)COC1 CAVGRDVEFANOTM-UHFFFAOYSA-N 0.000 description 2
- FIFHFLHRVMYBDP-UHFFFAOYSA-N ethyl 1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(C)c(cn1C)S(=O)(=O)NC1(C)COC1 FIFHFLHRVMYBDP-UHFFFAOYSA-N 0.000 description 2
- LYEKPFNLQCTNCD-UHFFFAOYSA-N ethyl 1,3-dimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)C1=C(C)C=CN1C LYEKPFNLQCTNCD-UHFFFAOYSA-N 0.000 description 2
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 2
- XKAWEJUJIOUTRS-UHFFFAOYSA-N ethyl 3-fluoro-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1F XKAWEJUJIOUTRS-UHFFFAOYSA-N 0.000 description 2
- WDOFSWPGAJJDMK-UHFFFAOYSA-N ethyl 4-(tert-butylsulfamoyl)-3-fluoro-1-methylpyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(F)c(cn1C)S(=O)(=O)NC(C)(C)C WDOFSWPGAJJDMK-UHFFFAOYSA-N 0.000 description 2
- QXEITASMDAQCCA-UHFFFAOYSA-N ethyl 4-chlorosulfonyl-1,3,5-trimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(C)c(c(C)n1C)S(Cl)(=O)=O QXEITASMDAQCCA-UHFFFAOYSA-N 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- KFJFRPADKPPZDJ-UHFFFAOYSA-N methyl 1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxylate Chemical compound CN1C(=CC(=C1)S(NCC(F)(F)F)(=O)=O)C(=O)OC KFJFRPADKPPZDJ-UHFFFAOYSA-N 0.000 description 2
- IWDXRXHHDJVGGA-UHFFFAOYSA-N methyl 3-chloro-1-methyl-4-[[1-(trifluoromethyl)cyclobutyl]sulfamoyl]pyrrole-2-carboxylate Chemical compound COC(=O)c1c(Cl)c(cn1C)S(=O)(=O)NC1(CCC1)C(F)(F)F IWDXRXHHDJVGGA-UHFFFAOYSA-N 0.000 description 2
- BMFZEADLZBHSHT-UHFFFAOYSA-N methyl 3-chloro-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=C(Cl)C=CN1C BMFZEADLZBHSHT-UHFFFAOYSA-N 0.000 description 2
- IYIPLTFQFXQEEZ-UHFFFAOYSA-N methyl 4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)c1cc(cn1C)S(=O)(=O)NCC(F)F IYIPLTFQFXQEEZ-UHFFFAOYSA-N 0.000 description 2
- DNYWOALGUYQWOL-UHFFFAOYSA-N methyl 4-(tert-butylsulfamoyl)-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(S(=O)(=O)NC(C)(C)C)=CN1C DNYWOALGUYQWOL-UHFFFAOYSA-N 0.000 description 2
- YZYBSBWSLCXXOX-UHFFFAOYSA-N methyl 4-(tert-butylsulfamoyl)-3-chloro-1-methylpyrrole-2-carboxylate Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C(=C(N(C1)C)C(=O)OC)Cl YZYBSBWSLCXXOX-UHFFFAOYSA-N 0.000 description 2
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 2
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 2
- GOWNSQPPHVFBFE-UHFFFAOYSA-N n-benzyl-3-(trifluoromethyl)oxolan-3-amine Chemical compound C=1C=CC=CC=1CNC1(C(F)(F)F)CCOC1 GOWNSQPPHVFBFE-UHFFFAOYSA-N 0.000 description 2
- LPOIGVZLNWEGJG-UHFFFAOYSA-N n-benzyl-5-(4-methylpiperazin-1-yl)-2-nitroaniline Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NCC=2C=CC=CC=2)=C1 LPOIGVZLNWEGJG-UHFFFAOYSA-N 0.000 description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 2
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- KWFPHDQBGRYWBM-UHFFFAOYSA-H scandium(3+);trisulfate;octahydrate Chemical compound O.O.O.O.O.O.O.O.[Sc+3].[Sc+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O KWFPHDQBGRYWBM-UHFFFAOYSA-H 0.000 description 2
- 238000010956 selective crystallization Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 2
- XTWWZOLSIVFHCG-UHFFFAOYSA-N tert-butyl N-(3,4-difluoro-5-methylphenyl)carbamate Chemical compound Cc1cc(NC(=O)OC(C)(C)C)cc(F)c1F XTWWZOLSIVFHCG-UHFFFAOYSA-N 0.000 description 2
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 2
- NXVYWMRPRBEXRM-UHFFFAOYSA-N tert-butyl n-(3-chloro-4,5-difluorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(F)=C(F)C(Cl)=C1 NXVYWMRPRBEXRM-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- OBMKZINZPBARIK-UHFFFAOYSA-N (1-aminocyclopropyl)methanol Chemical compound OCC1(N)CC1 OBMKZINZPBARIK-UHFFFAOYSA-N 0.000 description 1
- GHILZUOTUJGCDH-UHFFFAOYSA-N (1-methylcyclopropyl)azanium;chloride Chemical compound Cl.CC1(N)CC1 GHILZUOTUJGCDH-UHFFFAOYSA-N 0.000 description 1
- NKKPWPHIGLLMRF-UHFFFAOYSA-N (2,2-difluorocyclopentyl)azanium;chloride Chemical compound [Cl-].[NH3+]C1CCCC1(F)F NKKPWPHIGLLMRF-UHFFFAOYSA-N 0.000 description 1
- NKJASCWYRCSSQE-SCSAIBSYSA-N (2r)-1-methylsulfonylpropan-2-amine Chemical compound C[C@@H](N)CS(C)(=O)=O NKJASCWYRCSSQE-SCSAIBSYSA-N 0.000 description 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- HBGXGFLFLLDTML-UHFFFAOYSA-N (3-aminooxetan-3-yl)methanol Chemical compound OCC1(N)COC1 HBGXGFLFLLDTML-UHFFFAOYSA-N 0.000 description 1
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- SKKXZAXLYWERGC-UHFFFAOYSA-N 1,1-difluoropropan-2-amine Chemical compound CC(N)C(F)F SKKXZAXLYWERGC-UHFFFAOYSA-N 0.000 description 1
- YNXXSCOUIRMNHT-UHFFFAOYSA-N 1,3-difluoropropan-2-amine;hydrochloride Chemical compound Cl.FCC(N)CF YNXXSCOUIRMNHT-UHFFFAOYSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BCXOSCQTHVTUET-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC=C1F BCXOSCQTHVTUET-UHFFFAOYSA-N 0.000 description 1
- UYHQDFQKVUGCAQ-UHFFFAOYSA-N 1-(trifluoromethyl)cyclobutan-1-amine Chemical compound FC(F)(F)C1(N)CCC1 UYHQDFQKVUGCAQ-UHFFFAOYSA-N 0.000 description 1
- WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 description 1
- ORRMJQIQJVQVJU-UHFFFAOYSA-N 1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]-N-(3,4,5-trifluorophenyl)pyrrole-2-carboxamide Chemical compound CN1C(=CC(=C1)S(NC1(COC1)C)(=O)=O)C(=O)NC1=CC(=C(C(=C1)F)F)F ORRMJQIQJVQVJU-UHFFFAOYSA-N 0.000 description 1
- UQIRIYLHJWSYKA-UHFFFAOYSA-N 1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]-N-[3-methyl-5-(trifluoromethyl)phenyl]pyrrole-2-carboxamide Chemical compound CN1C(=CC(=C1)S(NC1(COC1)C)(=O)=O)C(=O)NC1=CC(=CC(=C1)C(F)(F)F)C UQIRIYLHJWSYKA-UHFFFAOYSA-N 0.000 description 1
- ILAOVOOZLVGAJF-UHFFFAOYSA-N 1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=CC=C1C(O)=O ILAOVOOZLVGAJF-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- OVRWUZYZECPJOB-UHFFFAOYSA-N 2,2-difluoroethanamine Chemical compound NCC(F)F OVRWUZYZECPJOB-UHFFFAOYSA-N 0.000 description 1
- YCCQGFYAVUTQFK-UHFFFAOYSA-N 2,3-difluoroaniline Chemical compound NC1=CC=CC(F)=C1F YCCQGFYAVUTQFK-UHFFFAOYSA-N 0.000 description 1
- QMYVWJVVVMIBMM-UHFFFAOYSA-N 2,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C=C1F QMYVWJVVVMIBMM-UHFFFAOYSA-N 0.000 description 1
- SZRDJHHKIJHJHQ-QDNHWIQGSA-N 2,6-dideuterio-3,4,5-trifluoroaniline Chemical compound [2H]c1c(N)c([2H])c(F)c(F)c1F SZRDJHHKIJHJHQ-QDNHWIQGSA-N 0.000 description 1
- NHNHWBFFDARHFO-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)acetamide Chemical compound NC(=O)CC1=CC=CN1 NHNHWBFFDARHFO-UHFFFAOYSA-N 0.000 description 1
- JTQCSLLDJIBJGP-UHFFFAOYSA-N 2-(3-aminooxetan-3-yl)ethanol Chemical group OCCC1(N)COC1 JTQCSLLDJIBJGP-UHFFFAOYSA-N 0.000 description 1
- XCFOTIBTBRXEBU-UHFFFAOYSA-N 2-[[5-[(4-fluoro-3-methylphenyl)carbamoyl]-1-methylpyrrol-3-yl]sulfonylamino]-2-methylpropanoic acid Chemical compound FC1=C(C=C(C=C1)NC(=O)C1=CC(=CN1C)S(=O)(=O)NC(C(=O)O)(C)C)C XCFOTIBTBRXEBU-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- XRAKCYJTJGTSMM-UHFFFAOYSA-N 2-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Cl XRAKCYJTJGTSMM-UHFFFAOYSA-N 0.000 description 1
- YKPDYPPZLUZONK-UHFFFAOYSA-N 2-fluoro-3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1F YKPDYPPZLUZONK-UHFFFAOYSA-N 0.000 description 1
- SEAUMIGQJNLHSL-UHFFFAOYSA-N 2-methyl-1h-pyrrole-3-sulfonyl chloride Chemical compound CC=1NC=CC=1S(Cl)(=O)=O SEAUMIGQJNLHSL-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- GELMWIVBBPAMIO-UHFFFAOYSA-N 2-methylbutan-2-amine Chemical compound CCC(C)(C)N GELMWIVBBPAMIO-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NGZVNONVXYLYQW-UHFFFAOYSA-N 3,3,3-trifluoropropan-1-amine Chemical compound NCCC(F)(F)F NGZVNONVXYLYQW-UHFFFAOYSA-N 0.000 description 1
- QLOHXGYAULHFOG-UHFFFAOYSA-N 3,3-difluorocyclopentan-1-amine Chemical compound NC1CCC(F)(F)C1 QLOHXGYAULHFOG-UHFFFAOYSA-N 0.000 description 1
- RNAYJQUWVKDTJZ-UHFFFAOYSA-N 3,4-difluoro-5-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(F)=C1F RNAYJQUWVKDTJZ-UHFFFAOYSA-N 0.000 description 1
- TZZRJHPOIFSVBD-UHFFFAOYSA-N 3-(trifluoromethyl)pentan-3-amine;hydrochloride Chemical compound [Cl-].CCC([NH3+])(CC)C(F)(F)F TZZRJHPOIFSVBD-UHFFFAOYSA-N 0.000 description 1
- JRBVDAQXMNYPHC-UHFFFAOYSA-N 3-amino-5-chlorobenzonitrile Chemical compound NC1=CC(Cl)=CC(C#N)=C1 JRBVDAQXMNYPHC-UHFFFAOYSA-N 0.000 description 1
- FJHVWOFTAJCONF-UHFFFAOYSA-N 3-amino-5-fluorobenzonitrile Chemical compound NC1=CC(F)=CC(C#N)=C1 FJHVWOFTAJCONF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LQKLVOWNBKJRJE-UHFFFAOYSA-N 3-bicyclo[1.1.1]pentanylazanium;chloride Chemical compound Cl.C1C2CC1(N)C2 LQKLVOWNBKJRJE-UHFFFAOYSA-N 0.000 description 1
- HYPQOSVTIONWSN-UHFFFAOYSA-N 3-bromo-2-fluoroaniline Chemical compound NC1=CC=CC(Br)=C1F HYPQOSVTIONWSN-UHFFFAOYSA-N 0.000 description 1
- CIJUAFFSMAKNNH-UHFFFAOYSA-N 3-chloro-2,6-difluoroaniline Chemical compound NC1=C(F)C=CC(Cl)=C1F CIJUAFFSMAKNNH-UHFFFAOYSA-N 0.000 description 1
- RRJYBDSJDKWHOS-UHFFFAOYSA-N 3-chloro-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(Cl)=C1 RRJYBDSJDKWHOS-UHFFFAOYSA-N 0.000 description 1
- AWYFAIDUCHWGNV-SSDOTTSWSA-N 3-chloro-N-(3,4-difluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)F AWYFAIDUCHWGNV-SSDOTTSWSA-N 0.000 description 1
- ROKIVTSLSXYRRI-ZCFIWIBFSA-N 3-chloro-N-(3-chloro-2,4-difluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=C(C(=C(C=C1)F)Cl)F ROKIVTSLSXYRRI-ZCFIWIBFSA-N 0.000 description 1
- AJRXEKSZRLJWRM-UHFFFAOYSA-N 3-chloro-N-(3-chloro-2,4-difluorophenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclobutyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(NC1(CCC1)C(F)(F)F)(=O)=O)C)C(=O)NC1=C(C(=C(C=C1)F)Cl)F AJRXEKSZRLJWRM-UHFFFAOYSA-N 0.000 description 1
- UTOZMYNUJPWMIQ-SSDOTTSWSA-N 3-chloro-N-(3-chloro-4-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)Cl UTOZMYNUJPWMIQ-SSDOTTSWSA-N 0.000 description 1
- RGCJEVNRQDNLKT-MRVPVSSYSA-N 3-chloro-N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)C#N RGCJEVNRQDNLKT-MRVPVSSYSA-N 0.000 description 1
- RGCJEVNRQDNLKT-QMMMGPOBSA-N 3-chloro-N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(N[C@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)C#N RGCJEVNRQDNLKT-QMMMGPOBSA-N 0.000 description 1
- FUUJMEDEHYINDE-UHFFFAOYSA-N 3-chloro-N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclobutyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(N(C=C1S(NC1(CCC1)C(F)(F)F)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)C#N FUUJMEDEHYINDE-UHFFFAOYSA-N 0.000 description 1
- COHKRZLMNRLZOV-UHFFFAOYSA-N 3-cyano-N-(3-cyano-4-fluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C1=C(N(C=C1S(NC(C)C)(=O)=O)C)C(=O)NC1=CC(=C(C=C1)F)C#N COHKRZLMNRLZOV-UHFFFAOYSA-N 0.000 description 1
- LRUWDVFBAJHDRL-UHFFFAOYSA-N 3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)-N-(2,3,4-trifluorophenyl)pyrrole-2-carboxamide Chemical compound FC1=C(N(C=C1S(NC(C)C)(=O)=O)C)C(=O)NC1=C(C(=C(C=C1)F)F)F LRUWDVFBAJHDRL-UHFFFAOYSA-N 0.000 description 1
- IVOSNOQXRNIBDM-UHFFFAOYSA-N 3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]-N-(2,4,5-trifluorophenyl)pyrrole-2-carboxamide Chemical compound FC1=C(N(C=C1S(NC1(COC1)C)(=O)=O)C)C(=O)NC1=C(C=C(C(=C1)F)F)F IVOSNOQXRNIBDM-UHFFFAOYSA-N 0.000 description 1
- JLLBTCGFNIWANP-ZCFIWIBFSA-N 3-fluoro-1-methyl-N-(2,3,4-trifluorophenyl)-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(N(C=C1S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(=O)NC1=C(C(=C(C=C1)F)F)F JLLBTCGFNIWANP-ZCFIWIBFSA-N 0.000 description 1
- WQKQODZOQAFYPR-UHFFFAOYSA-N 3-fluoro-5-(trifluoromethyl)aniline Chemical compound NC1=CC(F)=CC(C(F)(F)F)=C1 WQKQODZOQAFYPR-UHFFFAOYSA-N 0.000 description 1
- DPHBKGYVIHTBDG-UHFFFAOYSA-N 3-fluoro-5-methylaniline Chemical compound CC1=CC(N)=CC(F)=C1 DPHBKGYVIHTBDG-UHFFFAOYSA-N 0.000 description 1
- WYDJMBLMXGCHOL-UHFFFAOYSA-N 3-methyl-5-(trifluoromethyl)aniline Chemical compound CC1=CC(N)=CC(C(F)(F)F)=C1 WYDJMBLMXGCHOL-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HKEQNJJYWZWKMC-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-amine Chemical compound CC(N)CC(F)(F)F HKEQNJJYWZWKMC-UHFFFAOYSA-N 0.000 description 1
- UNUPCHYIHXMCLJ-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-amine;hydrochloride Chemical compound [Cl-].CC([NH3+])CC(F)(F)F UNUPCHYIHXMCLJ-UHFFFAOYSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- OWCHUAQNWOMINU-UHFFFAOYSA-N 4-(1-bicyclo[1.1.1]pentanylsulfamoyl)-N-(3-chloro-4,5-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C12(CC(C1)C2)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C(=C1)F)F)Cl OWCHUAQNWOMINU-UHFFFAOYSA-N 0.000 description 1
- BYGSGIXWFDPRMR-UHFFFAOYSA-N 4-(2,2-difluoroethylsulfamoyl)-N-(3,4-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound FC(CNS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)F)F BYGSGIXWFDPRMR-UHFFFAOYSA-N 0.000 description 1
- RQKMAAHKWVENSN-UHFFFAOYSA-N 4-(propan-2-ylsulfamoyl)-1h-pyrrole-2-carboxylic acid Chemical compound CC(C)NS(=O)(=O)C1=CNC(C(O)=O)=C1 RQKMAAHKWVENSN-UHFFFAOYSA-N 0.000 description 1
- VDGYICRBXAAYDZ-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-1-methyl-N-(3,4,5-trifluorophenyl)pyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)c(F)c(F)c1)S(=O)(=O)NC(C)(C)C VDGYICRBXAAYDZ-UHFFFAOYSA-N 0.000 description 1
- CTOPAIJVTWYVOV-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-3-chloro-N-(3,4-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C(=C(N(C1)C)C(=O)NC1=CC(=C(C=C1)F)F)Cl CTOPAIJVTWYVOV-UHFFFAOYSA-N 0.000 description 1
- YRILAPORWOAYFA-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-3-chloro-N-(3-chloro-2,4-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(c(Cl)c1C(=O)Nc1ccc(F)c(Cl)c1F)S(=O)(=O)NC(C)(C)C YRILAPORWOAYFA-UHFFFAOYSA-N 0.000 description 1
- KTSMKHGHODDORA-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-3-chloro-N-(3-chloro-4-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C(=C(N(C1)C)C(=O)NC1=CC(=C(C=C1)F)Cl)Cl KTSMKHGHODDORA-UHFFFAOYSA-N 0.000 description 1
- JEZSOSCCXFZWSG-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-3-fluoro-1-methyl-N-(2,3,4-trifluorophenyl)pyrrole-2-carboxamide Chemical compound Cn1cc(c(F)c1C(=O)Nc1ccc(F)c(F)c1F)S(=O)(=O)NC(C)(C)C JEZSOSCCXFZWSG-UHFFFAOYSA-N 0.000 description 1
- KDVJTAVWBYNTMV-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(2,4-difluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cc1c(F)ccc(NC(=O)c2cc(cn2C)S(=O)(=O)NC(C)(C)C)c1F KDVJTAVWBYNTMV-UHFFFAOYSA-N 0.000 description 1
- GGGLSONLXHUGKA-XNOGNMAASA-N 4-(tert-butylsulfamoyl)-N-(2,6-dideuterio-4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound [2H]C1=CC(F)=C(C)C([2H])=C1NC(=O)C1=CC(=CN1C)S(=O)(=O)NC(C)(C)C GGGLSONLXHUGKA-XNOGNMAASA-N 0.000 description 1
- HBOPEXMSWRCIEM-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3,4-difluorophenyl)-3-fluoro-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(c(F)c1C(=O)Nc1ccc(F)c(F)c1)S(=O)(=O)NC(C)(C)C HBOPEXMSWRCIEM-UHFFFAOYSA-N 0.000 description 1
- DKYZZKJUVQKLLS-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3,5-dichloro-4-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C1)C)C(=O)NC1=CC(=C(C(=C1)Cl)F)Cl DKYZZKJUVQKLLS-UHFFFAOYSA-N 0.000 description 1
- ZFQGUVGFWLGMKZ-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-chloro-2,4-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=C(C(=C(C=C1)F)Cl)F ZFQGUVGFWLGMKZ-UHFFFAOYSA-N 0.000 description 1
- IQMUSWAHXIRIEY-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-chloro-2,4-difluorophenyl)-3-fluoro-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C(=C(N(C1)C)C(=O)NC1=C(C(=C(C=C1)F)Cl)F)F IQMUSWAHXIRIEY-UHFFFAOYSA-N 0.000 description 1
- QJXAYLZTXOSEDC-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-chloro-2-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1cccc(Cl)c1F)S(=O)(=O)NC(C)(C)C QJXAYLZTXOSEDC-UHFFFAOYSA-N 0.000 description 1
- UVQKICNEWHORLE-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-chloro-4,5-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)c(F)c(Cl)c1)S(=O)(=O)NC(C)(C)C UVQKICNEWHORLE-UHFFFAOYSA-N 0.000 description 1
- IUGOMVIJAALYOT-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-chloro-4-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C1)C)C(=O)NC1=CC(=C(C=C1)F)Cl IUGOMVIJAALYOT-UHFFFAOYSA-N 0.000 description 1
- KSRLRYYAURIVQP-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-cyano-2-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1cccc(C#N)c1F)S(=O)(=O)NC(C)(C)C KSRLRYYAURIVQP-UHFFFAOYSA-N 0.000 description 1
- VKKKOCDCDKPFHO-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-cyano-4-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(c1)C#N)S(=O)(=O)NC(C)(C)C VKKKOCDCDKPFHO-UHFFFAOYSA-N 0.000 description 1
- PXNPKFUPXIULDI-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-cyano-4-fluorophenyl)-3-fluoro-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(c(F)c1C(=O)Nc1ccc(F)c(c1)C#N)S(=O)(=O)NC(C)(C)C PXNPKFUPXIULDI-UHFFFAOYSA-N 0.000 description 1
- YQMVSZIMUNBLLC-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-cyano-5-fluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(cc1C(=O)Nc1cc(F)cc(c1)C#N)S(=O)(=O)NC(C)(C)C YQMVSZIMUNBLLC-UHFFFAOYSA-N 0.000 description 1
- IWJAYSKPQCAATF-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(3-cyanophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C1)C)C(=O)NC1=CC(=CC=C1)C#N IWJAYSKPQCAATF-UHFFFAOYSA-N 0.000 description 1
- GGGLSONLXHUGKA-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-(4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C1)C)C(=O)NC1=CC(=C(C=C1)F)C GGGLSONLXHUGKA-UHFFFAOYSA-N 0.000 description 1
- YGWIQJSMHIEWET-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-[3-(1,1-difluoroethyl)-4-fluorophenyl]-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C(C)(F)F YGWIQJSMHIEWET-UHFFFAOYSA-N 0.000 description 1
- GIYCZFQTWJRYNB-UHFFFAOYSA-N 4-(tert-butylsulfamoyl)-N-[4-fluoro-3-(trifluoromethoxy)phenyl]-1-methylpyrrole-2-carboxamide Chemical compound C(C)(C)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)OC(F)(F)F GIYCZFQTWJRYNB-UHFFFAOYSA-N 0.000 description 1
- OWTXHERLFKABLD-UHFFFAOYSA-N 4-(trifluoromethyl)oxan-4-amine;hydrochloride Chemical compound Cl.FC(F)(F)C1(N)CCOCC1 OWTXHERLFKABLD-UHFFFAOYSA-N 0.000 description 1
- JYRZNSSGSKWFOE-UHFFFAOYSA-N 4-[(1-amino-2-methyl-1-oxopropan-2-yl)sulfamoyl]-N-(4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound NC(C(C)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C)=O JYRZNSSGSKWFOE-UHFFFAOYSA-N 0.000 description 1
- NUGTWBLGHSUNTP-UHFFFAOYSA-N 4-[(1-carbamoylcyclopropyl)sulfamoyl]-N-(3-chloro-4,5-difluorophenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(N)(=O)C1(CC1)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C(=C1)F)F)Cl NUGTWBLGHSUNTP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- UOORPRJOUSENQB-UHFFFAOYSA-N 4-[[1-(cyanomethyl)cyclopropyl]sulfamoyl]-N-(4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(#N)CC1(CC1)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C UOORPRJOUSENQB-UHFFFAOYSA-N 0.000 description 1
- JQRGUNMHZVNNBH-UHFFFAOYSA-N 4-[[1-(dimethylamino)-2-methyl-1-oxopropan-2-yl]sulfamoyl]-N-(4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound CN(C(C(C)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C)=O)C JQRGUNMHZVNNBH-UHFFFAOYSA-N 0.000 description 1
- IYWGEGSBVNBRPK-UHFFFAOYSA-N 4-[[3-(cyanomethyl)oxetan-3-yl]sulfamoyl]-N-(4-fluoro-3-methylphenyl)-1-methylpyrrole-2-carboxamide Chemical compound C(#N)CC1(COC1)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C IYWGEGSBVNBRPK-UHFFFAOYSA-N 0.000 description 1
- NGUXWEHRQIGWMQ-UHFFFAOYSA-N 4-amino-1-methylpyrrolidin-2-one;hydrochloride Chemical compound Cl.CN1CC(N)CC1=O NGUXWEHRQIGWMQ-UHFFFAOYSA-N 0.000 description 1
- PMDYLCUKSLBUHO-UHFFFAOYSA-N 4-amino-2-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C#N)C(C(F)(F)F)=C1 PMDYLCUKSLBUHO-UHFFFAOYSA-N 0.000 description 1
- RGHJWZADAWEIFE-UHFFFAOYSA-N 4-amino-2-methylbenzonitrile Chemical compound CC1=CC(N)=CC=C1C#N RGHJWZADAWEIFE-UHFFFAOYSA-N 0.000 description 1
- HIHCTGNZNHSZPP-UHFFFAOYSA-N 4-chloro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1Cl HIHCTGNZNHSZPP-UHFFFAOYSA-N 0.000 description 1
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
- HNXLESNHAMSHBA-UHFFFAOYSA-N 4-fluoro-3-methyl-5-(trifluoromethyl)aniline Chemical compound CC1=CC(N)=CC(C(F)(F)F)=C1F HNXLESNHAMSHBA-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OEJHAUZWRVHXKE-PBNXXWCMSA-N 5-[(2,6-dideuterio-3,4,5-trifluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound [2H]C1=C(C(=C(C(=C1F)F)F)[2H])NC(=O)C1=CC(=CN1C)S(=O)(=O)Cl OEJHAUZWRVHXKE-PBNXXWCMSA-N 0.000 description 1
- LMOSRQUSAQWBAA-UHFFFAOYSA-N 5-[(3-bromo-4,5-difluorophenyl)carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound BrC=1C=C(C=C(C1F)F)NC(=O)C1=CC(=CN1C)S(=O)(=O)Cl LMOSRQUSAQWBAA-UHFFFAOYSA-N 0.000 description 1
- DWNYZAKGFIIQDT-UHFFFAOYSA-N 5-[[3-(difluoromethyl)-4-fluorophenyl]carbamoyl]-1-methylpyrrole-3-sulfonyl chloride Chemical compound Cn1cc(cc1C(=O)Nc1ccc(F)c(c1)C(F)F)S(Cl)(=O)=O DWNYZAKGFIIQDT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010057573 Chronic hepatic failure Diseases 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 101100166531 Drosophila melanogaster CycC gene Proteins 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- CBZGLXXLWXZMRD-UHFFFAOYSA-N N-(2,4-difluoro-3-methylphenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C1)S(NC(C)C)(=O)=O)C CBZGLXXLWXZMRD-UHFFFAOYSA-N 0.000 description 1
- VKJWMWBAKJTQCQ-UHFFFAOYSA-N N-(2,4-difluoro-3-methylphenyl)-1-methyl-4-[(1,1,1-trifluoro-2-methylpropan-2-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C1)S(NC(C(F)(F)F)(C)C)(=O)=O)C VKJWMWBAKJTQCQ-UHFFFAOYSA-N 0.000 description 1
- OLMIQJJACUSURF-UHFFFAOYSA-N N-(2,4-difluoro-3-methylphenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C OLMIQJJACUSURF-UHFFFAOYSA-N 0.000 description 1
- BJCKIUWDOFWGSI-SECBINFHSA-N N-(2,4-difluoro-3-methylphenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C BJCKIUWDOFWGSI-SECBINFHSA-N 0.000 description 1
- ICBGSEFFUKSNPD-UHFFFAOYSA-N N-(2,4-difluoro-3-methylphenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclopropyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C=1)S(NC1(CC1)C(F)(F)F)(=O)=O)C ICBGSEFFUKSNPD-UHFFFAOYSA-N 0.000 description 1
- VKNJIDDIRTWQAO-UHFFFAOYSA-N N-(2,4-difluoro-3-methylphenyl)-3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC(=C1C)F)NC(=O)C=1N(C=C(C=1F)S(NC1(COC1)C)(=O)=O)C VKNJIDDIRTWQAO-UHFFFAOYSA-N 0.000 description 1
- LQDFLBOYDOZPBQ-UHFFFAOYSA-N N-(3,4-difluoro-5-methylphenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound CC(C)NS(=O)(=O)c1cc(C(=O)Nc2cc(C)c(F)c(F)c2)n(C)c1 LQDFLBOYDOZPBQ-UHFFFAOYSA-N 0.000 description 1
- WFLYGWRQUOYHEV-VIFPVBQESA-N N-(3,4-difluoro-5-methylphenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC=1C=C(C=C(C=1F)C)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C WFLYGWRQUOYHEV-VIFPVBQESA-N 0.000 description 1
- QKRKYXVGICYSNI-SNVBAGLBSA-N N-(3,4-difluoro-5-methylphenyl)-4-[[(2R)-1-hydroxypropan-2-yl]sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound FC=1C=C(C=C(C=1F)C)NC(=O)C=1N(C=C(C=1)S(N[C@@H](CO)C)(=O)=O)C QKRKYXVGICYSNI-SNVBAGLBSA-N 0.000 description 1
- FDYZSUCVKOEIGE-UHFFFAOYSA-N N-(3,4-difluorophenyl)-1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1C)S(NC1(COC1)C)(=O)=O)C FDYZSUCVKOEIGE-UHFFFAOYSA-N 0.000 description 1
- JEMRIBBLPGHBBY-VIFPVBQESA-N N-(3,4-difluorophenyl)-1,3-dimethyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(N[C@H](C(F)(F)F)C)(=O)=O)C JEMRIBBLPGHBBY-VIFPVBQESA-N 0.000 description 1
- VRUFKGJXQMWCSU-SECBINFHSA-N N-(3,4-difluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC=1F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C VRUFKGJXQMWCSU-SECBINFHSA-N 0.000 description 1
- KAYMOWLSJWHPDI-UHFFFAOYSA-N N-(3,4-difluorophenyl)-1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NCC(F)(F)F)(=O)=O)C KAYMOWLSJWHPDI-UHFFFAOYSA-N 0.000 description 1
- RWYLZOKADSUVIP-NSHDSACASA-N N-(3,4-difluorophenyl)-1-methyl-4-[[(3S)-oxolan-3-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@@H]1COCC1)(=O)=O)C RWYLZOKADSUVIP-NSHDSACASA-N 0.000 description 1
- YSOWTPVEWMVSHX-UHFFFAOYSA-N N-(3,4-difluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1F)S(NC(C)C)(=O)=O)C YSOWTPVEWMVSHX-UHFFFAOYSA-N 0.000 description 1
- VZIHQCAQKZUMJA-UHFFFAOYSA-N N-(3,4-difluorophenyl)-4-[(3-hydroxycyclobutyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound FC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1CC(C1)O)(=O)=O)C VZIHQCAQKZUMJA-UHFFFAOYSA-N 0.000 description 1
- PIUAAYQMDSKXHC-UHFFFAOYSA-N N-(3,5-dichloro-4-fluorophenyl)-1-methyl-4-[(1,1,1-trifluoro-2-methylpropan-2-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C1F)Cl)NC(=O)C=1N(C=C(C1)S(NC(C(F)(F)F)(C)C)(=O)=O)C PIUAAYQMDSKXHC-UHFFFAOYSA-N 0.000 description 1
- ATXRZWCKDQKEKL-UHFFFAOYSA-N N-(3,5-dichloro-4-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)Cl)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C ATXRZWCKDQKEKL-UHFFFAOYSA-N 0.000 description 1
- YIFSUNWTJNFHCS-ZETCQYMHSA-N N-(3-bromo-2,4-difluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C)F YIFSUNWTJNFHCS-ZETCQYMHSA-N 0.000 description 1
- OVDUWWGCJRSJMF-ZCFIWIBFSA-N N-(3-bromo-2,4-difluorophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F OVDUWWGCJRSJMF-ZCFIWIBFSA-N 0.000 description 1
- LFHNTHHNJAKWCP-MRVPVSSYSA-N N-(3-bromo-2-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C(=C(C=CC=1)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F LFHNTHHNJAKWCP-MRVPVSSYSA-N 0.000 description 1
- KZCYGDWQVZXDEE-UHFFFAOYSA-N N-(3-bromo-4,5-difluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound CC(C)NS(=O)(=O)c1cc(C(=O)Nc2cc(F)c(F)c(Br)c2)n(C)c1 KZCYGDWQVZXDEE-UHFFFAOYSA-N 0.000 description 1
- PDKFQFOXFUJUHR-SSDOTTSWSA-N N-(3-bromo-4,5-difluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C PDKFQFOXFUJUHR-SSDOTTSWSA-N 0.000 description 1
- KXXCAEMXUBKDNY-SECBINFHSA-N N-(3-bromo-4-fluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C KXXCAEMXUBKDNY-SECBINFHSA-N 0.000 description 1
- VSULPEXSMNPVPH-UHFFFAOYSA-N N-(3-bromo-4-fluorophenyl)-1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NCC(F)(F)F)(=O)=O)C VSULPEXSMNPVPH-UHFFFAOYSA-N 0.000 description 1
- BAWWMUZGLXAGQN-UHFFFAOYSA-N N-(3-bromo-4-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NC1(COC1)C)(=O)=O)C BAWWMUZGLXAGQN-UHFFFAOYSA-N 0.000 description 1
- TXFBWILTORLMNK-MRVPVSSYSA-N N-(3-bromo-4-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C TXFBWILTORLMNK-MRVPVSSYSA-N 0.000 description 1
- TXFBWILTORLMNK-QMMMGPOBSA-N N-(3-bromo-4-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C TXFBWILTORLMNK-QMMMGPOBSA-N 0.000 description 1
- VVTQXQHXVAWNHF-UHFFFAOYSA-N N-(3-bromo-4-fluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC(C)C)(=O)=O)C VVTQXQHXVAWNHF-UHFFFAOYSA-N 0.000 description 1
- RSBBGPWXXHKGGI-UHFFFAOYSA-N N-(3-bromo-4-fluorophenyl)-4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NCC(F)F)(=O)=O)C RSBBGPWXXHKGGI-UHFFFAOYSA-N 0.000 description 1
- SFMRAIRAFCAPKP-MRVPVSSYSA-N N-(3-bromophenyl)-3-chloro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC=1)NC(=O)C=1N(C=C(C=1Cl)S(N[C@@H](C(F)(F)F)C)(=O)=O)C SFMRAIRAFCAPKP-MRVPVSSYSA-N 0.000 description 1
- CALIAQPAFCKZEM-UHFFFAOYSA-N N-(3-bromophenyl)-3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound BrC=1C=C(C=CC1)NC(=O)C=1N(C=C(C1F)S(NC1(COC1)C)(=O)=O)C CALIAQPAFCKZEM-UHFFFAOYSA-N 0.000 description 1
- FXZKHDVDYJGPPL-MRVPVSSYSA-N N-(3-chloro-2,4-difluorophenyl)-1,3-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F FXZKHDVDYJGPPL-MRVPVSSYSA-N 0.000 description 1
- FXZKHDVDYJGPPL-QMMMGPOBSA-N N-(3-chloro-2,4-difluorophenyl)-1,3-dimethyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(N[C@H](C(F)(F)F)C)(=O)=O)C)F FXZKHDVDYJGPPL-QMMMGPOBSA-N 0.000 description 1
- NOBWFRZAGUMRQO-MRVPVSSYSA-N N-(3-chloro-2,4-difluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C)F NOBWFRZAGUMRQO-MRVPVSSYSA-N 0.000 description 1
- NGOZIFMBELDHMN-UHFFFAOYSA-N N-(3-chloro-2,4-difluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NC(C)C)(=O)=O)C)F NGOZIFMBELDHMN-UHFFFAOYSA-N 0.000 description 1
- DCHXFYMZJPKHJL-SSDOTTSWSA-N N-(3-chloro-2,4-difluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F DCHXFYMZJPKHJL-SSDOTTSWSA-N 0.000 description 1
- BPIXXYSYANFJRA-UHFFFAOYSA-N N-(3-chloro-2,4-difluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC(C)C)(=O)=O)C)F BPIXXYSYANFJRA-UHFFFAOYSA-N 0.000 description 1
- RXUKAOFUMYZMDA-UHFFFAOYSA-N N-(3-chloro-2,4-difluorophenyl)-3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC1(COC1)C)(=O)=O)C)F RXUKAOFUMYZMDA-UHFFFAOYSA-N 0.000 description 1
- XRBZSMRSRGFLSR-ZCFIWIBFSA-N N-(3-chloro-2,4-difluorophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F XRBZSMRSRGFLSR-ZCFIWIBFSA-N 0.000 description 1
- XYROINWDRLJTMU-UHFFFAOYSA-N N-(3-chloro-2,4-difluorophenyl)-4-[(2,2-difluorocyclopentyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound ClC=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1C(CCC1)(F)F)(=O)=O)C)F XYROINWDRLJTMU-UHFFFAOYSA-N 0.000 description 1
- JWDYQKAYDFSAOY-SSDOTTSWSA-N N-(3-chloro-2,6-difluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C(=C(C(=CC=1)F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F JWDYQKAYDFSAOY-SSDOTTSWSA-N 0.000 description 1
- WJSIAIZFQRZMRH-MRVPVSSYSA-N N-(3-chloro-4,5-difluorophenyl)-1,3-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1C)S(N[C@@H](C(F)(F)F)C)(=O)=O)C WJSIAIZFQRZMRH-MRVPVSSYSA-N 0.000 description 1
- WJQNMYJUKOFCJI-MRVPVSSYSA-N N-(3-chloro-4,5-difluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C WJQNMYJUKOFCJI-MRVPVSSYSA-N 0.000 description 1
- XTVUUAJNGJLDCQ-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NCC(F)(F)F)(=O)=O)C XTVUUAJNGJLDCQ-UHFFFAOYSA-N 0.000 description 1
- WGJMJUBQBZQLEO-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-(2-methylbutan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound CCC(C)(C)NS(=O)(=O)C1=CN(C)C(=C1)C(=O)NC1=CC(Cl)=C(F)C(F)=C1 WGJMJUBQBZQLEO-UHFFFAOYSA-N 0.000 description 1
- BPPQUJVQWWJZMF-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-(3,3,3-trifluoropropylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NCCC(F)(F)F)(=O)=O)C BPPQUJVQWWJZMF-UHFFFAOYSA-N 0.000 description 1
- XOBVNWHZLBHSNM-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound CC(C)NS(=O)(=O)c1cc(C(=O)Nc2cc(F)c(F)c(Cl)c2)n(C)c1 XOBVNWHZLBHSNM-UHFFFAOYSA-N 0.000 description 1
- JNPOAZWLILIFEA-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[(1,1,1-trifluoro-2-methylpropan-2-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C1F)F)NC(=O)C=1N(C=C(C1)S(NC(C(F)(F)F)(C)C)(=O)=O)C JNPOAZWLILIFEA-UHFFFAOYSA-N 0.000 description 1
- ATIQHMDHUWUIGY-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C ATIQHMDHUWUIGY-UHFFFAOYSA-N 0.000 description 1
- YHZGGEVHNLXBMS-ZETCQYMHSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C YHZGGEVHNLXBMS-ZETCQYMHSA-N 0.000 description 1
- QDUJWFYPPXIPAW-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[[1-(methylcarbamoyl)cyclopropyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1(CC1)C(NC)=O)(=O)=O)C QDUJWFYPPXIPAW-UHFFFAOYSA-N 0.000 description 1
- UZZJPHDLVCIOME-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclobutyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1(CCC1)C(F)(F)F)(=O)=O)C UZZJPHDLVCIOME-UHFFFAOYSA-N 0.000 description 1
- WYYBLKSXKDEBFV-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclopropyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1(CC1)C(F)(F)F)(=O)=O)C WYYBLKSXKDEBFV-UHFFFAOYSA-N 0.000 description 1
- PKDJPHLESLLIKR-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1F)S(NC1(COC1)C)(=O)=O)C PKDJPHLESLLIKR-UHFFFAOYSA-N 0.000 description 1
- SNFPSMLCSZYPFL-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NCC(F)F)(=O)=O)C SNFPSMLCSZYPFL-UHFFFAOYSA-N 0.000 description 1
- TWRRCXSLIJRCFZ-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-4-[(3,3-difluoro-1-methylcyclobutyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C1F)F)NC(=O)C=1N(C=C(C1)S(NC1(CC(C1)(F)F)C)(=O)=O)C TWRRCXSLIJRCFZ-UHFFFAOYSA-N 0.000 description 1
- MIRJYIVYVHMVNZ-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-4-[(3,3-difluorocyclobutyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1CC(C1)(F)F)(=O)=O)C MIRJYIVYVHMVNZ-UHFFFAOYSA-N 0.000 description 1
- AIZHFAVZPDTOQH-UHFFFAOYSA-N N-(3-chloro-4,5-difluorophenyl)-4-[(3,3-difluorocyclopentyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C=1F)F)NC(=O)C=1N(C=C(C=1)S(NC1CC(CC1)(F)F)(=O)=O)C AIZHFAVZPDTOQH-UHFFFAOYSA-N 0.000 description 1
- UBILMGCKOVQSNN-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(NC1(COC1)C)(=O)=O)C UBILMGCKOVQSNN-UHFFFAOYSA-N 0.000 description 1
- PBTWAHAQLLZLGW-VIFPVBQESA-N N-(3-chloro-4-fluorophenyl)-1,3-dimethyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(N[C@H](C(F)(F)F)C)(=O)=O)C PBTWAHAQLLZLGW-VIFPVBQESA-N 0.000 description 1
- RPVPJMFGHHXZEG-SECBINFHSA-N N-(3-chloro-4-fluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C RPVPJMFGHHXZEG-SECBINFHSA-N 0.000 description 1
- MMBRHAQVCHDOSB-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NCC(F)(F)F)(=O)=O)C MMBRHAQVCHDOSB-UHFFFAOYSA-N 0.000 description 1
- GJORZXLUQUABFE-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(C)C)(=O)=O)C GJORZXLUQUABFE-UHFFFAOYSA-N 0.000 description 1
- IBZABHBRRQAEOS-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC1F)NC(=O)C=1N(C=C(C1)S(NC1(COC1)C)(=O)=O)C IBZABHBRRQAEOS-UHFFFAOYSA-N 0.000 description 1
- OFBACEGEZOISKV-MRVPVSSYSA-N N-(3-chloro-4-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C OFBACEGEZOISKV-MRVPVSSYSA-N 0.000 description 1
- OFBACEGEZOISKV-QMMMGPOBSA-N N-(3-chloro-4-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C OFBACEGEZOISKV-QMMMGPOBSA-N 0.000 description 1
- MCIHZSKLJALANJ-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC(C)C)(=O)=O)C MCIHZSKLJALANJ-UHFFFAOYSA-N 0.000 description 1
- BAPVTAFEYHWYAC-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound CN1C=C(C=C1C(=O)NC1=CC(Cl)=C(F)C=C1)S(=O)(=O)NCC(F)F BAPVTAFEYHWYAC-UHFFFAOYSA-N 0.000 description 1
- GWZUWJJCYZSCPY-UHFFFAOYSA-N N-(3-chloro-5-cyanophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC=1C=C(C=C(C1)C#N)NC(=O)C=1N(C=C(C1)S(NC1(COC1)C)(=O)=O)C GWZUWJJCYZSCPY-UHFFFAOYSA-N 0.000 description 1
- RWMQGMHIDFMSLG-UHFFFAOYSA-N N-(3-cyano-2,4-difluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(C)C)(=O)=O)C)F RWMQGMHIDFMSLG-UHFFFAOYSA-N 0.000 description 1
- XUESEZMRIQXSQB-UHFFFAOYSA-N N-(3-cyano-2,4-difluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC(C)C)(=O)=O)C)F XUESEZMRIQXSQB-UHFFFAOYSA-N 0.000 description 1
- OMBCLHASIYHQOG-SSDOTTSWSA-N N-(3-cyano-2,4-difluorophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F OMBCLHASIYHQOG-SSDOTTSWSA-N 0.000 description 1
- ANMDXRMGQCBCKO-UHFFFAOYSA-N N-(3-cyano-2-fluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1)NC(=O)C=1N(C=C(C=1)S(NC(C)C)(=O)=O)C)F ANMDXRMGQCBCKO-UHFFFAOYSA-N 0.000 description 1
- NJWHJNRMDNWBFY-SECBINFHSA-N N-(3-cyano-2-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F NJWHJNRMDNWBFY-SECBINFHSA-N 0.000 description 1
- NJWHJNRMDNWBFY-VIFPVBQESA-N N-(3-cyano-2-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C)F NJWHJNRMDNWBFY-VIFPVBQESA-N 0.000 description 1
- VOQKFUBZBFRKAH-MRVPVSSYSA-N N-(3-cyano-2-fluorophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C(=C(C=CC=1)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)F VOQKFUBZBFRKAH-MRVPVSSYSA-N 0.000 description 1
- QBPAYVQIBXUXEL-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(NC1(COC1)C)(=O)=O)C QBPAYVQIBXUXEL-UHFFFAOYSA-N 0.000 description 1
- MCUCMPCFNNVXGT-JTQLQIEISA-N N-(3-cyano-4-fluorophenyl)-1,3-dimethyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1C)S(N[C@H](C(F)(F)F)C)(=O)=O)C MCUCMPCFNNVXGT-JTQLQIEISA-N 0.000 description 1
- RADOHRYQWMQHJA-SNVBAGLBSA-N N-(3-cyano-4-fluorophenyl)-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C RADOHRYQWMQHJA-SNVBAGLBSA-N 0.000 description 1
- HEBVQSDACIBTRN-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-(2,2,2-trifluoroethylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NCC(F)(F)F)(=O)=O)C HEBVQSDACIBTRN-UHFFFAOYSA-N 0.000 description 1
- WRDIZOJLHDPBHB-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(C)C)(=O)=O)C WRDIZOJLHDPBHB-UHFFFAOYSA-N 0.000 description 1
- WHSFHXHGQUFHOA-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[(1,1,1-trifluoro-2-methylbutan-2-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(CC)(C(F)(F)F)C)(=O)=O)C WHSFHXHGQUFHOA-UHFFFAOYSA-N 0.000 description 1
- ZHAJNTBVKULZED-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[(1,1,1-trifluoro-2-methylpropan-2-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(C(F)(F)F)(C)C)(=O)=O)C ZHAJNTBVKULZED-UHFFFAOYSA-N 0.000 description 1
- RHLBNGSABIXVCF-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[(1-methylcyclopropyl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(CC1)C)(=O)=O)C RHLBNGSABIXVCF-UHFFFAOYSA-N 0.000 description 1
- UIXDGLIPFQMWOM-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C UIXDGLIPFQMWOM-UHFFFAOYSA-N 0.000 description 1
- YCKCUUCTMCYHFT-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[3-(trifluoromethyl)pentan-3-ylsulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(CC)(C(F)(F)F)CC)(=O)=O)C YCKCUUCTMCYHFT-UHFFFAOYSA-N 0.000 description 1
- JSUWIGIMVNQUOH-OAHLLOKOSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[(2R)-1,1,1-trifluorobutan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](CC)C(F)(F)F)(=O)=O)C JSUWIGIMVNQUOH-OAHLLOKOSA-N 0.000 description 1
- JSUWIGIMVNQUOH-HNNXBMFYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](CC)C(F)(F)F)(=O)=O)C JSUWIGIMVNQUOH-HNNXBMFYSA-N 0.000 description 1
- SBVBIDUKSBJYEF-VIFPVBQESA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(N[C@H](C(F)(F)F)C)(=O)=O)C SBVBIDUKSBJYEF-VIFPVBQESA-N 0.000 description 1
- XVVOFUCYVRPKDX-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[1-(trifluoromethyl)cyclopropyl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(CC1)C(F)(F)F)(=O)=O)C XVVOFUCYVRPKDX-UHFFFAOYSA-N 0.000 description 1
- PUXABFNPJUMOMU-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[3-(trifluoromethyl)oxolan-3-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(COCC1)C(F)(F)F)(=O)=O)C PUXABFNPJUMOMU-UHFFFAOYSA-N 0.000 description 1
- SUEJDCOTDSSDRV-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-1-methyl-4-[[4-(trifluoromethyl)oxan-4-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(CCOCC1)C(F)(F)F)(=O)=O)C SUEJDCOTDSSDRV-UHFFFAOYSA-N 0.000 description 1
- BUZZJRZVKWLPMK-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-3-fluoro-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC(C)C)(=O)=O)C BUZZJRZVKWLPMK-UHFFFAOYSA-N 0.000 description 1
- LNFRSZCSNYYSDV-MRVPVSSYSA-N N-(3-cyano-4-fluorophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C LNFRSZCSNYYSDV-MRVPVSSYSA-N 0.000 description 1
- LNFRSZCSNYYSDV-QMMMGPOBSA-N N-(3-cyano-4-fluorophenyl)-3-fluoro-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(N[C@H](C(F)(F)F)C)(=O)=O)C LNFRSZCSNYYSDV-QMMMGPOBSA-N 0.000 description 1
- DDBAZWOHFNAKRS-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-(1,1-difluoropropan-2-ylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(C(F)F)C)(=O)=O)C DDBAZWOHFNAKRS-UHFFFAOYSA-N 0.000 description 1
- POMSJHSXMVGKTI-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-(1,3-difluoropropan-2-ylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(CF)CF)(=O)=O)C POMSJHSXMVGKTI-UHFFFAOYSA-N 0.000 description 1
- FOSUBXRYBNZHEN-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-(2,2-difluoroethylsulfamoyl)-1-methylpyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NCC(F)F)(=O)=O)C FOSUBXRYBNZHEN-UHFFFAOYSA-N 0.000 description 1
- NVLCGRAUANRTCT-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-[(1-fluoro-2-methylpropan-2-yl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC(CF)(C)C)(=O)=O)C NVLCGRAUANRTCT-UHFFFAOYSA-N 0.000 description 1
- OBSJLRKULBQVPL-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-[(3,3-difluoro-1-methylcyclobutyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(CC(C1)(F)F)C)(=O)=O)C OBSJLRKULBQVPL-UHFFFAOYSA-N 0.000 description 1
- QTYCHHPRZZQBFI-UHFFFAOYSA-N N-(3-cyano-4-fluorophenyl)-4-[(3,3-difluoro-1-methylcyclobutyl)sulfamoyl]-3-fluoro-1-methylpyrrole-2-carboxamide Chemical compound Cn1cc(c(F)c1C(=O)Nc1ccc(F)c(c1)C#N)S(=O)(=O)NC1(C)CC(F)(F)C1 QTYCHHPRZZQBFI-UHFFFAOYSA-N 0.000 description 1
- FRDNQJMXWMVGHY-UHFFFAOYSA-N N-(3-cyano-5-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=C(C=1)F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C FRDNQJMXWMVGHY-UHFFFAOYSA-N 0.000 description 1
- RTQMPDDULAMCOP-UHFFFAOYSA-N N-(3-cyanophenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1)NC(=O)C=1N(C=C(C1)S(NC(C)C)(=O)=O)C RTQMPDDULAMCOP-UHFFFAOYSA-N 0.000 description 1
- BFGQQIBMYQLUQY-JTQLQIEISA-N N-(3-cyanophenyl)-1-methyl-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C[C@H](NS(=O)(=O)c1cc(C(=O)Nc2cccc(c2)C#N)n(C)c1)C(F)(F)F BFGQQIBMYQLUQY-JTQLQIEISA-N 0.000 description 1
- RXEMIDGGDLMZLB-SECBINFHSA-N N-(3-cyanophenyl)-3-fluoro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1)NC(=O)C=1N(C=C(C=1F)S(N[C@@H](C(F)(F)F)C)(=O)=O)C RXEMIDGGDLMZLB-SECBINFHSA-N 0.000 description 1
- VGUYVTDAXAEFDT-UHFFFAOYSA-N N-(4-chloro-3-fluorophenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound ClC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C1)S(NC1(COC1)C)(=O)=O)C)F VGUYVTDAXAEFDT-UHFFFAOYSA-N 0.000 description 1
- UEKMFZBOMXPEHI-UHFFFAOYSA-N N-(4-fluoro-3,5-dimethylphenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1C)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C)C UEKMFZBOMXPEHI-UHFFFAOYSA-N 0.000 description 1
- DGIUUVKBWMMACA-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1,3,5-trimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C(=C(C1C)S(NC1(COC1)C)(=O)=O)C)C)C DGIUUVKBWMMACA-UHFFFAOYSA-N 0.000 description 1
- QOTDFUICSZHFGE-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1,3-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1C)S(NC1(COC1)C)(=O)=O)C)C QOTDFUICSZHFGE-UHFFFAOYSA-N 0.000 description 1
- ZKYDPDXBPAFVME-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1,5-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C(=C(C=1)S(NC1(COC1)C)(=O)=O)C)C)C ZKYDPDXBPAFVME-UHFFFAOYSA-N 0.000 description 1
- CXDSLWAUMUOJBN-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1-methyl-4-(propan-2-ylsulfamoyl)pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C1)S(NC(C)C)(=O)=O)C)C CXDSLWAUMUOJBN-UHFFFAOYSA-N 0.000 description 1
- OATMVGUHIQXAFI-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1-methyl-4-[(1-methyl-5-oxopyrrolidin-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(NC1CN(C(C1)=O)C)(=O)=O)C)C OATMVGUHIQXAFI-UHFFFAOYSA-N 0.000 description 1
- KXNGKAUBZZXIHI-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1-methyl-4-[(3-methyloxetan-3-yl)methylsulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(NCC1(COC1)C)(=O)=O)C)C KXNGKAUBZZXIHI-UHFFFAOYSA-N 0.000 description 1
- XGPWLTIIEZGAOM-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-1-methyl-4-[[2-methyl-1-(methylamino)-1-oxopropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound CC(C(=O)NC)(C)NS(=O)(=O)C=1C=C(N(C=1)C)C(=O)NC1=CC(=C(C=C1)F)C XGPWLTIIEZGAOM-UHFFFAOYSA-N 0.000 description 1
- WBIAMUPJXQUKTI-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-4-(propan-2-ylsulfamoyl)-1H-pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1NC=C(C1)S(NC(C)C)(=O)=O)C WBIAMUPJXQUKTI-UHFFFAOYSA-N 0.000 description 1
- NKYPMRRTSIEWHZ-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-4-[(3-hydroxycyclobutyl)sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(NC1CC(C1)O)(=O)=O)C)C NKYPMRRTSIEWHZ-UHFFFAOYSA-N 0.000 description 1
- BVUKUPVZLXOQEC-LLVKDONJSA-N N-(4-fluoro-3-methylphenyl)-4-[[(2R)-1-hydroxypropan-2-yl]sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(N[C@@H](CO)C)(=O)=O)C)C BVUKUPVZLXOQEC-LLVKDONJSA-N 0.000 description 1
- SUBOVCUVIPRMPN-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-4-[[1-(hydroxymethyl)cyclopropyl]sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound Cc1cc(NC(=O)c2cc(cn2C)S(=O)(=O)NC2(CO)CC2)ccc1F SUBOVCUVIPRMPN-UHFFFAOYSA-N 0.000 description 1
- CHYYIWOHVVXFTF-UHFFFAOYSA-N N-(4-fluoro-3-methylphenyl)-4-[[3-(2-hydroxyethyl)oxetan-3-yl]sulfamoyl]-1-methylpyrrole-2-carboxamide Chemical compound Cc1cc(NC(=O)c2cc(cn2C)S(=O)(=O)NC2(CCO)COC2)ccc1F CHYYIWOHVVXFTF-UHFFFAOYSA-N 0.000 description 1
- FWCAEBYGWSUEJB-MRVPVSSYSA-N N-[2-fluoro-3-(trifluoromethyl)phenyl]-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=CC=C1C(F)(F)F)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C FWCAEBYGWSUEJB-MRVPVSSYSA-N 0.000 description 1
- SZKVUKHPSRMVHU-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)-4-fluorophenyl]-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC(C)(F)C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C SZKVUKHPSRMVHU-UHFFFAOYSA-N 0.000 description 1
- YAORAMXGCFYMMI-UHFFFAOYSA-N N-[3-(difluoromethyl)-4-fluorophenyl]-3-fluoro-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC(C=1C=C(C=CC=1F)NC(=O)C=1N(C=C(C=1F)S(NC1(COC1)C)(=O)=O)C)F YAORAMXGCFYMMI-UHFFFAOYSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- QHCDMDQERDZZET-UHFFFAOYSA-N N-[4-fluoro-3-(trifluoromethoxy)phenyl]-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C)OC(F)(F)F QHCDMDQERDZZET-UHFFFAOYSA-N 0.000 description 1
- KCXPLBSTXBHRDE-SECBINFHSA-N N-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1C)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(F)(F)F KCXPLBSTXBHRDE-SECBINFHSA-N 0.000 description 1
- BHSFEGMLJLQMDY-SECBINFHSA-N N-[4-fluoro-3-(trifluoromethyl)phenyl]-1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C(=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C)C(F)(F)F BHSFEGMLJLQMDY-SECBINFHSA-N 0.000 description 1
- YAIKOADPTTZGFW-MRVPVSSYSA-N N-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1)NC(=O)C=1N(C=C(C=1)S(N[C@@H](C(F)(F)F)C)(=O)=O)C)C(F)(F)F YAIKOADPTTZGFW-MRVPVSSYSA-N 0.000 description 1
- CTZCIZDLXKZMKO-UHFFFAOYSA-N N-[4-fluoro-3-methyl-5-(trifluoromethyl)phenyl]-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound FC1=C(C=C(C=C1C(F)(F)F)NC(=O)C=1N(C=C(C=1)S(NC1(COC1)C)(=O)=O)C)C CTZCIZDLXKZMKO-UHFFFAOYSA-N 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 1
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- IIJREXIVDSIOFR-UHFFFAOYSA-N dichloromethane;heptane Chemical compound ClCCl.CCCCCCC IIJREXIVDSIOFR-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960000980 entecavir Drugs 0.000 description 1
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- NBSXNLNHQRYDTC-UHFFFAOYSA-N ethyl 1,3,5-trimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)C1=C(C)C=C(C)N1C NBSXNLNHQRYDTC-UHFFFAOYSA-N 0.000 description 1
- HNRJTIXARPYJPF-UHFFFAOYSA-N ethyl 1,3-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl-propan-2-ylsulfamoyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)c1c(C)c(cn1C)S(=O)(=O)N(C(C)C)C(=O)OC(C)(C)C HNRJTIXARPYJPF-UHFFFAOYSA-N 0.000 description 1
- GDRINQKZVHWTJE-UHFFFAOYSA-N ethyl 1,5-dimethyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylate Chemical compound CN1C(=CC(=C1C)S(NC1(COC1)C)(=O)=O)C(=O)OCC GDRINQKZVHWTJE-UHFFFAOYSA-N 0.000 description 1
- ZZCAXQNWBRTKNG-MRVPVSSYSA-N ethyl 1,5-dimethyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound CN1C(=CC(=C1C)S(N[C@@H](C(F)(F)F)C)(=O)=O)C(=O)OCC ZZCAXQNWBRTKNG-MRVPVSSYSA-N 0.000 description 1
- DOXGCQCHUPPQBH-UHFFFAOYSA-N ethyl 1,5-dimethylpyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C)N1C DOXGCQCHUPPQBH-UHFFFAOYSA-N 0.000 description 1
- XWRLQRLQUKZEEU-UHFFFAOYSA-N ethyl(hydroxy)silicon Chemical class CC[Si]O XWRLQRLQUKZEEU-UHFFFAOYSA-N 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 206010019692 hepatic necrosis Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid group Chemical group C(CCCCCC)(=O)O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000011872 intimate mixture Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- CSHMCEYIMFSLSS-UHFFFAOYSA-N methyl 1-aminocyclopropane-1-carboxylate Chemical compound COC(=O)C1(N)CC1 CSHMCEYIMFSLSS-UHFFFAOYSA-N 0.000 description 1
- DCFDDGXNWMQJIP-UHFFFAOYSA-N methyl 1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxylate Chemical compound COC(=O)c1cc(cn1C)S(=O)(=O)NC1(C)COC1 DCFDDGXNWMQJIP-UHFFFAOYSA-N 0.000 description 1
- RWQGLZSQFJJABL-UHFFFAOYSA-N methyl 2-[[5-[(4-fluoro-3-methylphenyl)carbamoyl]-1-methylpyrrol-3-yl]sulfonylamino]-2-methylpropanoate Chemical compound FC1=C(C=C(C=C1)NC(=O)C1=CC(=CN1C)S(=O)(=O)NC(C(=O)OC)(C)C)C RWQGLZSQFJJABL-UHFFFAOYSA-N 0.000 description 1
- NVWZNEDLYYLQJC-UHFFFAOYSA-N methyl 2-amino-2-methylpropanoate;hydrochloride Chemical compound Cl.COC(=O)C(C)(C)N NVWZNEDLYYLQJC-UHFFFAOYSA-N 0.000 description 1
- BSCSBXPDHOADJE-RXMQYKEDSA-N methyl 3-chloro-1-methyl-4-[[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxylate Chemical compound COC(=O)c1c(Cl)c(cn1C)S(=O)(=O)N[C@H](C)C(F)(F)F BSCSBXPDHOADJE-RXMQYKEDSA-N 0.000 description 1
- YFKTWBUEAJFGRQ-UHFFFAOYSA-N methyl 3-chloro-1h-pyrrole-2-carboxylate Chemical compound COC(=O)C=1NC=CC=1Cl YFKTWBUEAJFGRQ-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- IMCCZKHIPVEUEI-UHFFFAOYSA-N n,n-difluoroaniline Chemical compound FN(F)C1=CC=CC=C1 IMCCZKHIPVEUEI-UHFFFAOYSA-N 0.000 description 1
- FPHMSIDKCQPLKZ-SSDOTTSWSA-N n-(3,4-difluorophenyl)-3-fluoro-1-methyl-4-[[(2r)-1,1,1-trifluoropropan-2-yl]sulfamoyl]pyrrole-2-carboxamide Chemical compound FC(F)(F)[C@@H](C)NS(=O)(=O)C1=CN(C)C(C(=O)NC=2C=C(F)C(F)=CC=2)=C1F FPHMSIDKCQPLKZ-SSDOTTSWSA-N 0.000 description 1
- RCHHXFYRWSBVQU-UHFFFAOYSA-N n-(4-fluoro-3-methylphenyl)-1-methyl-4-[(3-methyloxetan-3-yl)sulfamoyl]pyrrole-2-carboxamide Chemical compound C1=C(F)C(C)=CC(NC(=O)C=2N(C=C(C=2)S(=O)(=O)NC2(C)COC2)C)=C1 RCHHXFYRWSBVQU-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 1
- JLPJFSCQKHRSQR-UHFFFAOYSA-N oxolan-3-one Chemical compound O=C1CCOC1 JLPJFSCQKHRSQR-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- FWZMWMSAGOVWEZ-UHFFFAOYSA-N potassium;hydrofluoride Chemical compound F.[K] FWZMWMSAGOVWEZ-UHFFFAOYSA-N 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- WRHZVMBBRYBTKZ-UHFFFAOYSA-M pyrrole-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-M 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 description 1
- 229960005311 telbivudine Drugs 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003970 toll like receptor agonist Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13168291 | 2013-05-17 | ||
| EP13175181 | 2013-07-04 | ||
| EP13182281 | 2013-08-29 | ||
| EP13191209 | 2013-10-31 | ||
| EP13198160 | 2013-12-18 | ||
| EP14157900 | 2014-03-05 | ||
| PCT/EP2014/060102 WO2014184350A1 (en) | 2013-05-17 | 2014-05-16 | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201592200A1 EA201592200A1 (ru) | 2016-03-31 |
| EA037378B1 true EA037378B1 (ru) | 2021-03-22 |
Family
ID=50884356
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201592200A EA037378B1 (ru) | 2013-05-17 | 2014-05-16 | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b |
Country Status (35)
Families Citing this family (160)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX359634B (es) | 2011-12-21 | 2018-10-03 | Novira Therapeutics Inc | Agentes antivirales contra la hepatitis b. |
| UY34992A (es) * | 2012-08-28 | 2014-02-28 | Janssen R & D Ireland | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b |
| PT2961732T (pt) | 2013-02-28 | 2017-06-26 | Janssen Sciences Ireland Uc | Sulfamoil-arilamidas e utilização das mesmas como medicamentos para o tratamento de hepatite b |
| WO2014161888A1 (en) | 2013-04-03 | 2014-10-09 | Janssen R&D Ireland | N-phenyl-carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| SI3786162T1 (sl) | 2013-05-17 | 2024-02-29 | Incyte Holdings Corporation | Bipirazolni derivati kot zaviralci JAK |
| PT2997019T (pt) | 2013-05-17 | 2018-11-21 | Janssen Sciences Ireland Uc | Derivados de sulfamoíltiofenamida e o seu uso como medicamentos para o tratamento da hepatite b |
| UA118680C2 (uk) | 2013-07-25 | 2019-02-25 | ЯНССЕН САЙЄНСЕЗ АЙРЛЕНД ЮСі | Похідні заміщеного гліоксамідом піроламіду та їхнє застосування як лікарських препаратів для лікування гепатиту в |
| EP3060547B1 (en) | 2013-10-23 | 2017-10-11 | Janssen Sciences Ireland UC | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| RU2702109C1 (ru) | 2014-02-05 | 2019-10-04 | Новира Терапьютикс, Инк. | Комбинированная терапия для лечения инфекций вгв |
| EA035848B1 (ru) * | 2014-02-06 | 2020-08-20 | Янссен Сайенсиз Айрлэнд Юси | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b |
| CN106413402B (zh) | 2014-03-13 | 2020-10-30 | 美国印第安纳大学研究和技术公司 | 乙型肝炎核心蛋白变构调节剂 |
| AU2016232801A1 (en) | 2015-03-19 | 2017-10-12 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis B infections |
| US10442788B2 (en) | 2015-04-01 | 2019-10-15 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10738035B2 (en) | 2015-05-13 | 2020-08-11 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10875876B2 (en) * | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| WO2017011552A1 (en) | 2015-07-13 | 2017-01-19 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| MY197231A (en) | 2015-07-22 | 2023-06-06 | Enanta Pharm Inc | Benzodiazepine derivatives as rsv inhibitors |
| US10301255B2 (en) | 2015-07-22 | 2019-05-28 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| TWI786639B (zh) | 2015-09-15 | 2022-12-11 | 美商艾森伯利生物科學公司 | B型肝炎核心蛋白質調節劑 |
| AR106192A1 (es) | 2015-09-29 | 2017-12-20 | Novira Therapeutics Inc | Formas cristalinas de un agente antiviral contra la hepatitis b |
| US20170226129A1 (en) | 2016-01-15 | 2017-08-10 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as rsv inhibitors |
| US10280175B2 (en) | 2016-02-02 | 2019-05-07 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| MX384836B (es) | 2016-03-07 | 2025-03-14 | Enanta Pharm Inc | Agentes antivirales contra la hepatitis b |
| PE20190118A1 (es) * | 2016-03-09 | 2019-01-16 | Univ Emory | Eliminacion del virus de la hepatitis b con agentes antivirales |
| SG11201808949SA (en) | 2016-04-15 | 2018-11-29 | Novira Therapeutics Inc | Combinations and methods comprising a capsid assembly inhibitor |
| MA45088A (fr) | 2016-05-27 | 2019-04-10 | Gilead Sciences Inc | Méthodes pour traiter des infections par le virus de l'hépatite b au moyen d'inhibiteurs de ns5a, ns5b ou ns3 |
| JP2019521972A (ja) | 2016-06-10 | 2019-08-08 | エナンタ ファーマシューティカルズ インコーポレイテッド | B型肝炎抗ウイルス剤 |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| ES2906581T3 (es) | 2016-09-02 | 2022-04-19 | Gilead Sciences Inc | Compuestos moduladores de los receptores tipo Toll |
| ES2826748T3 (es) | 2016-09-02 | 2021-05-19 | Gilead Sciences Inc | Derivados de 4,6-diamino-pirido[3,2-d]pirimidina como moduladores de receptores de tipo Toll |
| CN109937201A (zh) | 2016-09-15 | 2019-06-25 | 组装生物科学股份有限公司 | 乙型肝炎核心蛋白调节剂 |
| SG11201903042VA (en) | 2016-10-14 | 2019-05-30 | Precision Biosciences Inc | Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome |
| SG11201902944TA (en) | 2016-11-07 | 2019-05-30 | Arbutus Biopharma Corp | Substituted pyridinone-containing tricyclic compounds, and methods using same |
| EA202190306A1 (ru) * | 2016-11-11 | 2021-08-17 | Новира Терапьютикс, Инк. | Комбинации и способы, включающие ингибитор сборки капсида |
| CN108264520B (zh) * | 2017-01-03 | 2021-12-07 | 上海长森药业有限公司 | 用于治疗乙型肝炎的化合物及其用途 |
| US10398706B2 (en) | 2017-01-06 | 2019-09-03 | Enanta Pharmaceuticals, Inc. | Heteroaryldiazepine derivatives as RSV inhibitors |
| CN108341810B (zh) * | 2017-01-23 | 2022-01-18 | 上海长森药业有限公司 | 环硫脲类化合物及其用途 |
| WO2018133845A1 (zh) * | 2017-01-23 | 2018-07-26 | 上海长森药业有限公司 | 硫脲类、脲类化合物及其用途 |
| TWI820984B (zh) | 2017-01-31 | 2023-11-01 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| NZ756805A (en) | 2017-02-16 | 2025-10-31 | Enanta Pharm Inc | Processes for the preparation of benzodiazepine derivatives |
| WO2018153326A1 (zh) * | 2017-02-22 | 2018-08-30 | 上海长森药业有限公司 | 磺酰肼类化合物及其用途 |
| CN110621672A (zh) | 2017-03-02 | 2019-12-27 | 组装生物科学股份有限公司 | 环状磺酰胺化合物及其使用方法 |
| MA49014A (fr) | 2017-03-21 | 2020-02-05 | Arbutus Biopharma Corp | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| CN110582500B (zh) * | 2017-05-04 | 2022-04-05 | 上海长森药业有限公司 | 双并环类核衣壳抑制剂和其作为药物用于治疗乙型肝炎的用途 |
| WO2018226801A1 (en) | 2017-06-07 | 2018-12-13 | Enanta Pharmaceuticals, Inc. | Aryldiazepine derivatives as rsv inhibitors |
| WO2019006291A1 (en) | 2017-06-30 | 2019-01-03 | Enanta Pharmaceuticals, Inc. | HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS |
| US11091501B2 (en) | 2017-06-30 | 2021-08-17 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as RSV inhibitors |
| EP3675637A4 (en) | 2017-08-28 | 2021-05-19 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| BR112020006334A2 (pt) | 2017-09-29 | 2020-09-24 | Enanta Pharmaceuticals, Inc. | combinação de agentes farmacêuticos como inibidores de rsv |
| US10647711B2 (en) | 2017-11-13 | 2020-05-12 | Enanta Pharmaceuticals, Inc. | Azepin-2-one derivatives as RSV inhibitors |
| EP3710009B1 (en) | 2017-11-13 | 2025-07-30 | Enanta Pharmaceuticals, Inc. | Processes for the resolution of benzodiazepin-2-one and benzoazepin-2-one derivatives |
| US10723733B2 (en) | 2017-12-06 | 2020-07-28 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10428070B2 (en) | 2017-12-06 | 2019-10-01 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US11203610B2 (en) | 2017-12-20 | 2021-12-21 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| WO2019123340A1 (en) | 2017-12-20 | 2019-06-27 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| US11058678B2 (en) | 2018-01-22 | 2021-07-13 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| WO2019154343A1 (zh) * | 2018-02-09 | 2019-08-15 | 正大天晴药业集团股份有限公司 | 衣壳蛋白装配抑制剂、其药物组合物和用途 |
| MX2020008404A (es) | 2018-02-13 | 2020-09-25 | Gilead Sciences Inc | Inhibidores de molecula de muerte programada 1 (pd-1)/ligando de molecula de muerte programada 1 (pd-l1). |
| CN118490690A (zh) | 2018-02-16 | 2024-08-16 | 因赛特公司 | 用于治疗细胞因子相关的病症的jak1通路抑制剂 |
| CN111788204B (zh) | 2018-02-26 | 2023-05-05 | 吉利德科学公司 | 作为hbv复制抑制剂的取代吡咯嗪化合物 |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 2,4-二胺基喹唑啉衍生物及其醫學用途 |
| WO2019175657A1 (en) | 2018-03-14 | 2019-09-19 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| WO2019191166A1 (en) | 2018-03-29 | 2019-10-03 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| WO2019185016A1 (zh) | 2018-03-30 | 2019-10-03 | 正大天晴药业集团股份有限公司 | 含有n杂五元环的衣壳蛋白装配抑制剂、其药物组合物和用途 |
| PL3773593T3 (pl) | 2018-03-30 | 2024-09-02 | Incyte Corporation | Leczenie ropnego zapalenia gruczołów potowych z zastosowaniem inhibitorów jak |
| WO2019195181A1 (en) | 2018-04-05 | 2019-10-10 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | 2,2,─環二核苷酸 |
| WO2019199908A1 (en) | 2018-04-11 | 2019-10-17 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as rsv inhibitors |
| US11142750B2 (en) | 2018-04-12 | 2021-10-12 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
| ES3035911T3 (en) | 2018-04-19 | 2025-09-11 | Gilead Sciences Inc | Pd-1/pd-l1 inhibitors |
| US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic nucleotide |
| EP3793990B1 (en) | 2018-05-16 | 2023-07-19 | Infex Therapeutics Limited | Antibacterial compounds |
| TWI848953B (zh) | 2018-06-09 | 2024-07-21 | 德商百靈佳殷格翰國際股份有限公司 | 針對癌症治療之多特異性結合蛋白 |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| TWI826492B (zh) | 2018-07-27 | 2023-12-21 | 加拿大商愛彼特生物製藥公司 | 經取代四氫環戊[c]吡咯、經取代二氫吡咯,其類似物及使用其之方法 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| CN112955142A (zh) | 2018-09-21 | 2021-06-11 | 英安塔制药有限公司 | 官能化杂环化合物作为抗病毒剂 |
| TW202028190A (zh) | 2018-10-22 | 2020-08-01 | 美商艾森伯利生物科學公司 | 用於治療hbv之5員雜芳甲醯胺化合物 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ, インコーポレイテッド | Pd-1/pd-l1阻害剤 |
| EP3873488B1 (en) | 2018-10-31 | 2025-03-19 | The University of Sydney | Pharmaceutical compositions for use in treating an hbv or hdv infection |
| CN117105933A (zh) | 2018-10-31 | 2023-11-24 | 吉利德科学公司 | 具有hpk1抑制活性的取代的6-氮杂苯并咪唑化合物 |
| LT3873903T (lt) | 2018-10-31 | 2024-05-10 | Gilead Sciences, Inc. | Pakeistieji 6-azabenzimidazolo junginiai, kaip hpk1 inhibitoriai |
| IL283190B2 (en) | 2018-11-21 | 2025-08-01 | Enanta Pharm Inc | Functionalized heterocycles as antiviral agents |
| TW202415643A (zh) | 2018-12-12 | 2024-04-16 | 加拿大商愛彼特生物製藥公司 | 經取代之芳基甲基脲類及雜芳基甲基脲類、其類似物及其使用方法 |
| EA202092159A1 (ru) | 2019-01-25 | 2020-12-15 | Чиа Тай Тянцин Фармасьютикал Груп Ко., Лтд. | Содержащий n-гетероциклическое пятичленное кольцо ингибитор сборки капсидного белка, его фармацевтическая композиция и их применение |
| CN113454077A (zh) | 2019-02-22 | 2021-09-28 | 爱尔兰詹森科学公司 | 用于治疗hbv感染或hbv诱发的疾病的酰胺衍生物 |
| EP3935066A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| CA3129022C (en) | 2019-03-07 | 2023-08-01 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides and prodrugs thereof |
| CA3132095A1 (en) | 2019-03-13 | 2020-09-17 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator solid formulation |
| WO2020190935A1 (en) | 2019-03-18 | 2020-09-24 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as rsv inhibitors |
| WO2020210246A1 (en) | 2019-04-09 | 2020-10-15 | Enanta Pharmaceuticals, Inc, | Heterocyclic compounds as rsv inhibitors |
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| WO2020214974A1 (en) | 2019-04-18 | 2020-10-22 | Janssen Pharmaceuticals, Inc. | Combination therapy for treating hepatitis b virus infection |
| CA3132170A1 (en) | 2019-04-18 | 2020-10-22 | Michael BIERMER | Combination therapy for treating hepatitis b virus infection |
| MA55879A (fr) | 2019-05-06 | 2022-03-16 | Janssen Sciences Ireland Unlimited Co | Dérivés d'amide utiles dans le traitement d'une infection par le virus de l'hépatite b ou de maladies induites par le virus de l'hépatite b |
| TWI826690B (zh) | 2019-05-23 | 2023-12-21 | 美商基利科學股份有限公司 | 經取代之烯吲哚酮化物及其用途 |
| WO2020242999A1 (en) | 2019-05-24 | 2020-12-03 | Assembly Biosciences, Inc. | Pharmaceutical compositions for the treatment of hbv |
| US11236111B2 (en) | 2019-06-03 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US11760755B2 (en) | 2019-06-04 | 2023-09-19 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| WO2020247575A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| WO2020255013A1 (en) * | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and capsid assembly modulators being amide derivatives |
| TWI772823B (zh) | 2019-06-18 | 2022-08-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | B型肝炎病毒(hbv)疫苗與蛋白殼組裝調節劑之組合 |
| CA3140707A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and quinazoline derivatives |
| JP7295283B2 (ja) | 2019-06-25 | 2023-06-20 | ギリアード サイエンシーズ, インコーポレイテッド | Flt3l-fc融合タンパク質及び使用方法 |
| WO2021007488A1 (en) | 2019-07-11 | 2021-01-14 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| WO2021011891A1 (en) | 2019-07-18 | 2021-01-21 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| CA3153358A1 (en) * | 2019-09-04 | 2021-03-11 | Taigen Biotechnology Co., Ltd. | Hepatitis b antiviral agents |
| WO2021055425A2 (en) | 2019-09-17 | 2021-03-25 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| EP4036078A4 (en) | 2019-09-29 | 2023-09-06 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | CRYSTAL FORM OF A FIVE-MEMBERED RING CAPSID PROTEIN ASSEMBLY INHIBITOR WITH N AS A HETEROATOM, AND APPLICATION THEREOF |
| CN114466837B (zh) | 2019-09-29 | 2024-05-31 | 正大天晴药业集团股份有限公司 | N杂五元环化合物的晶型及其应用 |
| CR20220129A (es) | 2019-09-30 | 2022-05-06 | Gilead Sciences Inc | Vacunas para vhb y métodos de tratamiento de vhb |
| US11505558B1 (en) | 2019-10-04 | 2022-11-22 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
| JP7681009B2 (ja) | 2019-10-04 | 2025-05-21 | エナンタ ファーマシューティカルズ インコーポレイテッド | 抗ウイルス性複素環化合物 |
| EP4069729B1 (en) | 2019-12-06 | 2025-01-22 | Precision BioSciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
| UY39032A (es) | 2020-01-24 | 2021-07-30 | Enanta Pharm Inc | Compuestos heterocíclicos como agentes antivirales |
| ES2993261T3 (en) * | 2020-02-11 | 2024-12-26 | Ospedale San Raffaele Srl | Spirocyclic inhibitors of hepatitis b virus |
| TW202146008A (zh) | 2020-02-27 | 2021-12-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | Hbv的治療 |
| TW202146011A (zh) | 2020-03-05 | 2021-12-16 | 美商詹森藥物公司 | 治療b型肝炎病毒感染之組合療法 |
| WO2021188414A1 (en) | 2020-03-16 | 2021-09-23 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
| TW202421168A (zh) | 2020-03-20 | 2024-06-01 | 美商基利科學股份有限公司 | 4’-c-經取代-2-鹵基-2’-去氧腺苷核苷之前藥及其製造與使用方法 |
| WO2021216661A1 (en) | 2020-04-22 | 2021-10-28 | Assembly Biosciences, Inc. | Pyrazole carboxamide compounds for treatment of hbv |
| US20230295096A1 (en) | 2020-04-22 | 2023-09-21 | Assembly Biosciences, Inc. | Pyrazole carboxamide compounds for treatment of hbv |
| WO2021216660A1 (en) | 2020-04-22 | 2021-10-28 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| PH12022552815A1 (en) | 2020-04-22 | 2024-03-25 | Assembly Biosciences Inc | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| SMT202400509T1 (it) | 2020-06-02 | 2025-01-14 | Incyte Corp | Procedimenti di preparazione di un inibitore di jak1 |
| WO2022010882A1 (en) | 2020-07-07 | 2022-01-13 | Enanta Pharmaceuticals, Inc, | Dihydroquinoxaline and dihydropyridopyrazine derivatives as rsv inhibitors |
| CN116194144A (zh) | 2020-08-07 | 2023-05-30 | 吉利德科学公司 | 膦酰胺核苷酸类似物的前药及其药物用途 |
| US11945824B2 (en) | 2020-10-19 | 2024-04-02 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as anti-viral agents |
| TW202406932A (zh) | 2020-10-22 | 2024-02-16 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| AU2021396231A1 (en) | 2020-12-08 | 2023-06-22 | Incyte Corporation | Jak1 pathway inhibitors for the treatment of vitiligo |
| WO2022206879A1 (zh) * | 2021-03-31 | 2022-10-06 | 苏州晶云药物科技股份有限公司 | 氨磺酰基吡咯酰胺类化合物的晶型及其制备方法 |
| JP2024516302A (ja) | 2021-05-03 | 2024-04-12 | インサイト・コーポレイション | 結節性痒疹を治療するためのjak1経路阻害薬 |
| AU2022274607A1 (en) | 2021-05-13 | 2023-11-16 | Gilead Sciences, Inc. | COMBINATION OF A TLR8 MODULATING COMPOUND AND ANTI-HBV siRNA THERAPEUTICS |
| US11999733B2 (en) | 2021-06-23 | 2024-06-04 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| US11926628B2 (en) | 2021-06-23 | 2024-03-12 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| AU2022299051B2 (en) | 2021-06-23 | 2025-03-13 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2023069545A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| WO2023069544A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| WO2023069547A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| US20250163009A1 (en) | 2022-02-25 | 2025-05-22 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164181A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164186A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164179A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| AR129003A1 (es) | 2022-04-07 | 2024-07-03 | Enanta Pharm Inc | Compuestos heterocíclicos antivirales |
| US12162857B2 (en) | 2022-04-27 | 2024-12-10 | Enanta Pharmaceuticals, Inc. | Antiviral compounds |
| WO2025043094A1 (en) | 2023-08-23 | 2025-02-27 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2025240243A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with bulevirtide and an inhibitory nucleic acid targeting hepatitis b virus |
| US20250345390A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013006394A1 (en) * | 2011-07-01 | 2013-01-10 | Institute For Hepatitis And Virus Research | Sulfamoylbenzamide derivatives as antiviral agents against hbv infection |
Family Cites Families (220)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3843662A (en) | 1971-12-09 | 1974-10-22 | Pfizer | 2-halo-5-(substituted piperidino sulfonyl)benzoic acids |
| AU1508183A (en) | 1982-06-04 | 1983-12-08 | Beecham Group Plc | Benzamide and anilide derivatives of 8-azabicyclo-(3.2.1)- -octane |
| WO1984003281A1 (en) | 1983-02-19 | 1984-08-30 | Beecham Group Plc | Azabicycloalkyl benzamide and anilide derivatives |
| JPS62142164A (ja) | 1985-12-13 | 1987-06-25 | Ishihara Sangyo Kaisha Ltd | 4,5−ジクロロイミダゾ−ル系化合物及びそれらを含有する有害生物防除剤 |
| IN164880B (enExample) | 1986-01-30 | 1989-06-24 | Ishihara Sangyo Kaisha | |
| US5272167A (en) | 1986-12-10 | 1993-12-21 | Schering Corporation | Pharmaceutically active compounds |
| CA1339133C (en) | 1987-03-13 | 1997-07-29 | Rikuo Nasu | Imidazole compounds and biocidal composition comprising the same for controlling harmful organisms |
| US5571821A (en) | 1993-05-20 | 1996-11-05 | Texas Biotechnology Corporation | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
| GB8904174D0 (en) | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
| US4962101A (en) | 1989-08-21 | 1990-10-09 | Merck & Co., Inc. | 2-(Heterocyclylalkyl)phenyl carbapenem antibacterial agents |
| GB9023082D0 (en) | 1990-10-24 | 1990-12-05 | Schering Agrochemicals Ltd | Fungicides |
| GB9109557D0 (en) | 1991-05-02 | 1991-06-26 | Wellcome Found | Chemical compounds |
| US5308826A (en) | 1993-04-22 | 1994-05-03 | Zeneca Limited | Herbicidal 4-substituted pyridyl-3-carbinols |
| GB9405347D0 (en) | 1994-03-18 | 1994-05-04 | Agrevo Uk Ltd | Fungicides |
| JPH10504525A (ja) | 1994-05-27 | 1998-05-06 | ジェイムズ・ブラック・ファウンデーション・リミテッド | ガストリンとcck拮抗薬 |
| US5795907A (en) | 1994-05-27 | 1998-08-18 | James Black Foundation Limited | Gastin and CCK receptor ligands |
| US5763618A (en) | 1995-05-12 | 1998-06-09 | Konica Corporation | Manufacturing method of sulfides |
| US5723411A (en) | 1995-10-31 | 1998-03-03 | E. I. Du Pont De Nemours And Company | Herbicidal pyridazinones |
| DE19540995A1 (de) | 1995-11-03 | 1997-05-07 | Hoechst Ag | Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| GB9612884D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| WO1997049695A1 (en) | 1996-06-25 | 1997-12-31 | Smithkline Beecham P.L.C. | Sulfonamide derivatives as 5ht7 receptor antagonists |
| WO1998023285A1 (en) | 1996-11-29 | 1998-06-04 | Smithkline Beecham Plc | Use of a combination of penciclovir and alpha-interferon in the manufacture of a medicament for the treatment of hepatitis b |
| US5939423A (en) | 1997-04-16 | 1999-08-17 | Sciclone Pharmaceuticals, Inc. | Treatment of hepatitis B infection with thymosin alpha 1 and famciclovir |
| US5919970A (en) | 1997-04-24 | 1999-07-06 | Allergan Sales, Inc. | Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity |
| US5994396A (en) | 1997-08-18 | 1999-11-30 | Centaur Pharmaceuticals, Inc. | Furansulfonic acid derivatives and pharmaceutical compositions containing the same |
| US6200995B1 (en) | 1998-01-29 | 2001-03-13 | Tularik Inc. | PPAR-γ modulators |
| BR9909666A (pt) | 1998-03-26 | 2001-09-11 | Japan Tobacco Inc | Derivados de amida e antagonistas de nociceptina |
| US6251893B1 (en) | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
| HK1040997B (en) | 1999-01-15 | 2006-07-14 | 奥坦纳医药公司 | Phenylphenanthridines with pde-iv inhibiting activity |
| CA2377092A1 (en) | 1999-07-16 | 2001-01-25 | Warner-Lambert Company | Method for treating chronic pain using mek inhibitors |
| JP2003506406A (ja) | 1999-08-10 | 2003-02-18 | ザ・チャンセラー・マスターズ・アンド・スカラーズ・オブ・ザ・ユニバーシティ・オブ・オックスフォード | 長鎖n−アルキル化合物およびそのオキサ誘導体 |
| IL155155A0 (en) | 1999-09-17 | 2003-10-31 | Cor Therapeutics Inc | BENZAMIDES AND RELATED INHIBITORS OF FACTOR Xa |
| AR025884A1 (es) | 1999-10-01 | 2002-12-18 | Takeda Pharmaceutical | Compuestos de amina ciclica, su produccion y su uso |
| JP2003519697A (ja) | 1999-12-28 | 2003-06-24 | ファイザー・プロダクツ・インク | 炎症性疾患、自己免疫疾患および呼吸器疾患の処置に有用な非ペプチド系のvla−4依存性細胞結合阻害薬 |
| WO2001055121A1 (en) | 2000-01-28 | 2001-08-02 | Kaken Pharmaceutical Co., Ltd. | Azepine derivatives |
| US6511980B2 (en) | 2000-05-05 | 2003-01-28 | Ortho Mcneil Pharmaceutical, Inc. | Substituted diamine derivatives useful as motilin antagonists |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| WO2002051410A2 (en) | 2000-12-22 | 2002-07-04 | Akzo Nobel N.V. | Phenylthiazole and thiazoline derivatives and their use as antiparasitics |
| ES2254324T3 (es) | 2000-12-27 | 2006-06-16 | Dainippon Sumitomo Pharma Co., Ltd. | Compuestos de carbapenemo, medicamento y antibacteriano que los comprende y sus usos. |
| US7015012B2 (en) | 2001-02-09 | 2006-03-21 | Massachusetts Institute Of Technology | Methods of identifying agents that mediate polypeptide aggregation |
| US6650463B2 (en) | 2001-03-13 | 2003-11-18 | Seiko Epson Corporation | Electrophoretic display device |
| IL158491A0 (en) | 2001-04-19 | 2004-05-12 | Eisai Co Ltd | 2-iminopyrrolidine derivatives |
| SE0102315D0 (sv) * | 2001-06-28 | 2001-06-28 | Astrazeneca Ab | Compounds |
| KR100713137B1 (ko) | 2001-06-28 | 2007-05-02 | 동화약품공업주식회사 | 신규의 2,4-디플루오로벤즈아미드 유도체 |
| WO2003007955A2 (en) | 2001-07-20 | 2003-01-30 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| DE10136043A1 (de) | 2001-07-25 | 2003-02-13 | Degussa | Verfahren zur Herstellung von modifiziertem Ruß |
| US6956035B2 (en) | 2001-08-31 | 2005-10-18 | Inotek Pharmaceuticals Corporation | Isoquinoline derivatives and methods of use thereof |
| EP1448560B1 (en) | 2001-11-20 | 2005-06-15 | Eli Lilly And Company | 3-SUBSTITUTED OXINDOLE beta 3 AGONISTS |
| SE0201635D0 (sv) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
| EA009523B1 (ru) | 2002-06-05 | 2008-02-28 | Инститьют Оф Медисинал Молекьюлар Дизайн. Инк. | Ингибиторы в отношении активации ар-1 и nfat |
| KR101124245B1 (ko) | 2002-06-27 | 2012-07-02 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
| PL215132B1 (pl) | 2002-06-27 | 2013-10-31 | Novo Nordisk As | Pochodna arylokarbonylowa jako srodek terapeutyczny, jej zastosowanie i kompozycja farmaceutyczna ja zawierajaca |
| AU2003256923A1 (en) | 2002-07-31 | 2004-02-16 | Smithkline Beecham Corporation | Substituted benzanilides as modulators of the ccr5 receptor |
| AU2003254177A1 (en) | 2002-07-31 | 2004-02-16 | Smithkline Beecham Corporation | Substituted benzanilides as modulators of the ccr5 receptor |
| US7186735B2 (en) | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
| US7338956B2 (en) | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
| EP1541172A1 (en) | 2002-08-09 | 2005-06-15 | Ajinomoto Co., Inc. | Remedy for intestinal diseases and visceral pain |
| US20040110802A1 (en) | 2002-08-23 | 2004-06-10 | Atli Thorarensen | Antibacterial benzoic acid derivatives |
| EP1545532A2 (en) | 2002-09-06 | 2005-06-29 | Janssen Pharmaceutica N.V. | Heterocyclic compounds |
| SE0202838D0 (sv) | 2002-09-24 | 2002-09-24 | Astrazeneca Ab | Chemical compounds |
| AU2003303483A1 (en) | 2002-12-23 | 2004-07-22 | Millennium Pharmaceuticals, Inc. | Ccr8 inhibitors |
| US7320989B2 (en) | 2003-02-28 | 2008-01-22 | Encysive Pharmaceuticals, Inc. | Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-II receptor antagonists |
| ES2378620T3 (es) | 2003-03-27 | 2012-04-16 | Cytokinetics, Inc. | Sulfonamidas para el tratamiento de insuficiencia cardiaca congestiva, sus composiciones y usos. |
| CA2523743A1 (en) | 2003-04-30 | 2004-11-18 | The Institutes For Pharmaceutical Discovery, Llc | Heterocycle substituted carboxylic acids as inhibitors of protein tyrosine phosphatase-1b |
| WO2004100947A2 (en) | 2003-05-06 | 2004-11-25 | Smithkline Beecham Corporation | Novel chemical compounds |
| PE20050555A1 (es) | 2003-05-13 | 2005-07-19 | Schering Corp | Compuestos con puente n-arilsulfonilpiperidina como inhibidores de la gamma-secretasa |
| EP1651595A2 (en) | 2003-05-30 | 2006-05-03 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| US20110275630A1 (en) | 2003-06-02 | 2011-11-10 | Abbott Laboratories | Isoindolinone kinase inhibitors |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| GB0319151D0 (en) | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Novel compounds |
| WO2005026129A1 (en) | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| US7498050B2 (en) | 2003-12-15 | 2009-03-03 | Kraft Foods Global Brands Llc | Edible spread composition and packaged product |
| DE102004009238A1 (de) | 2004-02-26 | 2005-09-08 | Merck Patent Gmbh | Arylamid-Derivate |
| WO2005087217A1 (en) | 2004-03-05 | 2005-09-22 | The General Hospital Corporation | Compositions and methods for modulating interaction between polypeptides |
| WO2005105785A2 (en) | 2004-05-04 | 2005-11-10 | Novo Nordisk A/S | Indole derivatives for treatment of obesity |
| WO2005115374A1 (en) | 2004-05-29 | 2005-12-08 | 7Tm Pharma A/S | Crth2 receptor ligands for therapeutic use |
| JP2008503585A (ja) | 2004-06-22 | 2008-02-07 | シェーリング コーポレイション | カンナビノイドレセプターリガンド |
| JP4703649B2 (ja) | 2004-07-30 | 2011-06-15 | エグゼリクシス, インコーポレイテッド | 薬学的因子としてのピロール誘導体 |
| DE102004042441A1 (de) | 2004-08-31 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Mit Aminosäuren substituierte Hexahydro-pyrazino(1,2-a)pyrimidin-4,7-dionderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AU2005278959A1 (en) | 2004-08-31 | 2006-03-09 | Astrazeneca Ab | Quinazolinone derivatives and their use as B-Raf inhibitors |
| GT200500286A (es) | 2004-10-13 | 2006-06-13 | Analogos de anilino-pirimidina | |
| KR20070072598A (ko) | 2004-10-19 | 2007-07-04 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 인돌 및 벤지미다졸 유도체 |
| TW200628463A (en) | 2004-11-10 | 2006-08-16 | Synta Pharmaceuticals Corp | Heteroaryl compounds |
| US20060122236A1 (en) | 2004-12-06 | 2006-06-08 | Wood Michael R | Substituted biaryl-carboxylate derivatives |
| MX2007007574A (es) | 2004-12-22 | 2007-07-24 | Astrazeneca Ab | Derivados de piridina-carboxamida para uso como agentes anticancerosos. |
| TW200635899A (en) | 2004-12-22 | 2006-10-16 | Astrazeneca Ab | Chemical compounds |
| FI117653B (fi) | 2005-02-21 | 2006-12-29 | Eigenor Oy | Menetelmä ja laitteisto liikkuvien kohteiden havaitsemiseksi tutkalla |
| GB0510141D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B3 |
| WO2006128172A2 (en) | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating b cell regulated autoimmune disorders |
| WO2006128129A2 (en) | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
| US7790726B2 (en) | 2005-08-16 | 2010-09-07 | Chemocentryx, Inc. | Monocyclic and bicyclic compounds and methods of use |
| ES2348332T3 (es) | 2005-09-16 | 2010-12-02 | Arrow Therapeutics Limited | Derivados de bifenilo y su uso en el tratamiento de la hepatitis c. |
| JP2009519342A (ja) | 2005-12-12 | 2009-05-14 | ジェネラブズ テクノロジーズ インコーポレーティッド | N−(6員芳香環)−アミド抗ウイルス化合物 |
| MX2008008340A (es) | 2005-12-21 | 2008-09-03 | Schering Corp | Tratamiento de enfermedad de higado graso no alcoholica usando agentes reductores de colesterol y/o antagonista/agonista inverso de receptor de histamina 3. |
| EP1981849A1 (en) | 2005-12-29 | 2008-10-22 | LEK Pharmaceuticals D.D. | Heterocyclic compounds |
| CN101437824B (zh) | 2006-05-04 | 2013-03-13 | 肝炎与病毒研究所 | 用于慢性肝炎病毒治疗的乙型肝炎病毒抗原分泌的抑制剂 |
| US8153803B2 (en) | 2006-07-18 | 2012-04-10 | The General Hospital Corporation | Compositions and methods for modulating sirtuin activity |
| US20080021063A1 (en) | 2006-07-18 | 2008-01-24 | Kazantsev Aleksey G | Compositions and methods for modulating sirtuin activity |
| FR2903985B1 (fr) | 2006-07-24 | 2008-09-05 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2904316B1 (fr) | 2006-07-31 | 2008-09-05 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique. |
| US20100016310A1 (en) | 2006-08-17 | 2010-01-21 | Boehringer Ingelheim International Gmbh | Methods of using aryl sulfonyl compounds effective as soluble epoxide hydrolase inhibitors |
| JP2010505834A (ja) * | 2006-10-06 | 2010-02-25 | メルク エンド カムパニー インコーポレーテッド | 非ヌクレオシド系逆転写酵素阻害剤 |
| WO2008076270A2 (en) | 2006-12-13 | 2008-06-26 | Temple University-Of The Commonwealth System Of Higher Education | Sulfide, sulfoxide and sulfone chalcone analogues, derivatives thereof and therapeutic uses thereof |
| US20100022517A1 (en) | 2006-12-18 | 2010-01-28 | Richards Lori A | Ophthalmic formulation of rho kinase inhibitor compound |
| US8071779B2 (en) | 2006-12-18 | 2011-12-06 | Inspire Pharmaceuticals, Inc. | Cytoskeletal active rho kinase inhibitor compounds, composition and use |
| FR2910473B1 (fr) | 2006-12-26 | 2009-02-13 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-pyrrolopyridine-2- carboxamides, leur preparation et leur application en therapeutique. |
| JP2008179621A (ja) | 2006-12-28 | 2008-08-07 | Taisho Pharmaceutical Co Ltd | 含窒素飽和複素環化合物 |
| JP2008184403A (ja) | 2007-01-29 | 2008-08-14 | Japan Health Science Foundation | 新規c型肝炎ウイルス阻害剤 |
| NZ579402A (en) | 2007-03-15 | 2012-03-30 | Novartis Ag | Organic compounds for diagnosis and treatment of pathologies relating to the Hedgehog pathway |
| US8097728B2 (en) | 2007-04-30 | 2012-01-17 | Philadelphia Health & Education Corporation | Iminosugar compounds with antiflavirus activity |
| MX2009011951A (es) | 2007-05-04 | 2009-12-11 | Irm Llc | Compuestos y composiciones como inhibidores de cinasa c-kit y pdgfr. |
| TW200901969A (en) * | 2007-06-06 | 2009-01-16 | Smithkline Beecham Corp | Chemical compounds |
| WO2008154819A1 (fr) | 2007-06-18 | 2008-12-24 | Zhang, Zhongneng | Thiazolyl-dihydropyrimidines à substitution carbéthoxy |
| WO2009018219A2 (en) | 2007-07-28 | 2009-02-05 | University Of Chicago | Methods and compositions for modulating rad51 and homologous recombination |
| EP2182935A1 (en) | 2007-08-02 | 2010-05-12 | F. Hoffmann-Roche AG | The use of benzamide derivatives for the treatment of cns disorders |
| CN101429166B (zh) | 2007-11-07 | 2013-08-21 | 上海特化医药科技有限公司 | 喹唑啉酮衍生物及其制备方法和用途 |
| AU2008345225A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| FR2926556B1 (fr) | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique |
| FR2926555B1 (fr) | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| FR2926554B1 (fr) | 2008-01-22 | 2010-03-12 | Sanofi Aventis | Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| FR2926553B1 (fr) | 2008-01-23 | 2010-02-19 | Sanofi Aventis | Derives d'indole-2-carboxamides et d'azaindole-2- carboxamides substitues par un groupe silanyle, leur preparation et leur application en therapeutique |
| CU20080028A6 (es) | 2008-02-29 | 2011-02-24 | Ct Ingenieria Genetica Biotech | Compuestos químicos obtenidos in silico para la preparación de composiciones farmacéuticas para atenuar o inhibir la infección por virus dengue y otros flavivirus |
| WO2009146013A1 (en) | 2008-03-31 | 2009-12-03 | Georgetown University | Myosin light chain phosphatase inhibitors |
| CN104352492B (zh) | 2008-04-24 | 2017-12-05 | Msd K.K.公司 | 以芳基磺酰基衍生物作为有效成分的长链脂肪酸延长酶抑制剂 |
| EP2317849A4 (en) | 2008-06-26 | 2011-11-02 | Inspire Pharmaceuticals Inc | PROCESS FOR THE TREATMENT OF LUNG DISEASES WITH RHO KINASE INHIBITOR COMPOUNDS |
| US20090325960A1 (en) | 2008-06-26 | 2009-12-31 | Fulcher Emilee H | Method for treating inflammatory diseases using rho kinase inhibitor compounds |
| US20090325959A1 (en) | 2008-06-26 | 2009-12-31 | Vittitow Jason L | Method for treating ophthalmic diseases using rho kinase inhibitor compounds |
| US20100008968A1 (en) | 2008-06-26 | 2010-01-14 | Lampe John W | Method for treating cardiovascular diseases using rho kinase inhibitor compounds |
| US8207195B2 (en) | 2008-06-26 | 2012-06-26 | Inspire Pharmaceuticals, Inc. | Method for treating neurological and neuropathic diseases using rho kinase inhibitor compounds |
| US8410147B2 (en) | 2008-06-26 | 2013-04-02 | Inspire Pharmaceuticals, Inc. | Method for treating diseases associated with alterations in cellular integrity using Rho kinase inhibitor compounds |
| CA2735392A1 (en) | 2008-08-15 | 2010-02-18 | F. Hoffmann-La Roche Ag | Bi-aryl aminotetralines |
| WO2010027996A1 (en) | 2008-09-02 | 2010-03-11 | Institute For Hepatitis And Virus Research | Novel imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity |
| US8143269B2 (en) | 2008-10-03 | 2012-03-27 | Calcimedica, Inc. | Inhibitors of store operated calcium release |
| WO2010043592A1 (en) | 2008-10-15 | 2010-04-22 | Revotar Biopharmaceuticals Ag | Lipase inhibitors for use for the treatment of obesity |
| AR074199A1 (es) | 2008-11-20 | 2010-12-29 | Glaxosmithkline Llc | Compuesto de 6-(4-pirimidinil)-1h-indazol, composiciones farmaceuticas que lo comprenden y su uso para preparar un medicamento util para el tratamiento o disminucion de la gravedad del cancer. |
| EP2400969A4 (en) | 2008-12-04 | 2012-05-16 | Inspire Pharmaceuticals Inc | METHOD FOR TREATING PULMONARY DISEASES USING RHO KINASE INHIBITORY COMPOUNDS |
| US8273754B2 (en) | 2008-12-30 | 2012-09-25 | Arqule, Inc. | Substituted 1H-pyrazolo[3,4-D]pyrimidine-6-amine compounds |
| WO2010088000A2 (en) | 2009-02-02 | 2010-08-05 | Angion Biomedica Corp. | Antifibrotic compounds and uses thereof |
| WO2010123139A1 (ja) | 2009-04-24 | 2010-10-28 | 持田製薬株式会社 | スルファモイル基を有するアリールカルボキサミド誘導体 |
| BRPI1010909A2 (pt) | 2009-05-19 | 2015-09-08 | Bayer Cropscience Ag | "inseticida arilpirrolinas" |
| PL2434891T3 (pl) | 2009-05-27 | 2020-12-28 | Ptc Therapeutics, Inc. | Sposoby leczenia nowotworu złośliwego i stanów nienowotworowych |
| CN102469788A (zh) | 2009-06-30 | 2012-05-23 | 西佳技术公司 | 登革病毒感染的治疗和预防 |
| CA2689707A1 (en) * | 2009-11-16 | 2011-05-16 | Jean-Simon Diallo | Identification of the novel small molecule viral sensitizer vse1 using high-throughput screening |
| US8703938B2 (en) | 2009-09-11 | 2014-04-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8822700B2 (en) | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US20120252792A1 (en) | 2009-09-17 | 2012-10-04 | The Regents Of The University Of Michigan | Methods and compositions for modulating rho-mediated gene transcription |
| WO2011058766A1 (en) | 2009-11-16 | 2011-05-19 | Raqualia Pharma Inc. | Aryl carboxamide derivatives as ttx-s blockers |
| CN102093320B (zh) | 2009-12-09 | 2013-08-28 | 扬子江药业集团上海海尼药业有限公司 | 一种可溶性环氧化物水解酶抑制剂 |
| WO2011088015A1 (en) | 2010-01-15 | 2011-07-21 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| WO2011088561A1 (en) | 2010-01-20 | 2011-07-28 | University Of Manitoba | Anti-viral compounds and compositions |
| WO2011109237A2 (en) | 2010-03-02 | 2011-09-09 | Emory University | Uses of noscapine and derivatives in subjects diagnosed with fap |
| JP2013522192A (ja) | 2010-03-11 | 2013-06-13 | ブリストル−マイヤーズ スクイブ カンパニー | C型肝炎の処置のための化合物 |
| CN102206172B (zh) | 2010-03-30 | 2015-02-25 | 中国医学科学院医药生物技术研究所 | 一组取代双芳基化合物及其制备方法和抗病毒应用 |
| WO2011123609A1 (en) | 2010-03-31 | 2011-10-06 | Glaxo Group Limited | Imidazolyl-imidazoles as kinase inhibitors |
| BR112012028556A2 (pt) | 2010-05-07 | 2014-04-01 | Glaxosmithkline Llc | Indóis |
| US8993622B2 (en) | 2010-06-11 | 2015-03-31 | Eirium Ab | Antiviral compounds |
| WO2011163593A2 (en) | 2010-06-25 | 2011-12-29 | Philadelphia Health & Education Corporation D/B/A Drexel | Induction of immune response |
| RU2013107007A (ru) | 2010-07-19 | 2014-08-27 | Инспайр Фармасьютикалз, Инк. | Бифункциональные соединения, являющиеся ингибиторами rho-киназы, композиция и применение |
| CA2806664A1 (en) | 2010-07-26 | 2012-02-09 | Neurotherapeutics Pharma, Inc. | Arylsulfonamide derivatives, compositions, and methods of use |
| MX2013001003A (es) | 2010-07-27 | 2013-03-07 | Inspire Pharmaceuticals Inc | Compuestos inhibidores de quinasa, en formato de profarmaco, para tratar enfermedades oftalmicas. |
| WO2012016133A2 (en) | 2010-07-29 | 2012-02-02 | President And Fellows Of Harvard College | Ros1 kinase inhibitors for the treatment of glioblastoma and other p53-deficient cancers |
| WO2012033956A1 (en) | 2010-09-08 | 2012-03-15 | Mithridion, Inc. | Cognition enhancing compounds and compositions, methods of making, and methods of treating |
| CN103889428A (zh) | 2010-10-04 | 2014-06-25 | 肝炎与病毒研究所 | 乙型肝炎病毒抗原分泌的新型抑制剂 |
| GB201017345D0 (en) | 2010-10-14 | 2010-11-24 | Proximagen Ltd | Receptor antagonists |
| EP2646439B1 (en) | 2010-12-02 | 2016-05-25 | Bristol-Myers Squibb Company | Alkyl amides as hiv attachment inhibitors |
| WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
| GB201103419D0 (enExample) | 2011-02-28 | 2011-04-13 | Univ Aberdeen | |
| PL3330257T3 (pl) | 2011-04-08 | 2020-06-15 | Janssen Sciences Ireland Unlimited Company | Pochodne pirymidyny do leczenia zakażeń wirusowych |
| US8889716B2 (en) | 2011-05-10 | 2014-11-18 | Chdi Foundation, Inc. | Transglutaminase TG2 inhibitors, pharmaceutical compositions, and methods of use thereof |
| MX359634B (es) | 2011-12-21 | 2018-10-03 | Novira Therapeutics Inc | Agentes antivirales contra la hepatitis b. |
| ES2581489T3 (es) | 2012-01-06 | 2016-09-06 | Janssen Sciences Ireland Uc | 1,4-dihidropirimidinas 4,4-disustituidas y el uso de las mismas como medicamentos para el tratamiento de la hepatitis B |
| WO2013130703A2 (en) | 2012-02-29 | 2013-09-06 | Institute For Hepatitis And Virus Research | Binhibitors of hepatitis b virus convalently closed circular dna formation and their method of use |
| US20130267517A1 (en) | 2012-03-31 | 2013-10-10 | Hoffmann-La Roche Inc. | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| CA2865259A1 (en) | 2012-03-31 | 2013-10-03 | F. Hoffmann-La Roche Ag | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| MX2014014323A (es) | 2012-05-25 | 2015-02-12 | Janssen R & D Ireland | Nucleosidos de espirooxetano de uracilo. |
| SG11201407970VA (en) | 2012-06-01 | 2014-12-30 | Univ Drexel | Modulation of hepatitis b virus cccdna transcription |
| JO3300B1 (ar) | 2012-06-06 | 2018-09-16 | Novartis Ag | مركبات وتركيبات لتعديل نشاط egfr |
| TW201408652A (zh) | 2012-07-11 | 2014-03-01 | Hoffmann La Roche | 作爲RORc調節劑之芳基磺內醯胺衍生物 |
| WO2014033167A1 (en) | 2012-08-28 | 2014-03-06 | Janssen R&D Ireland | Fused bicyclic sulfamoyl derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| UY34992A (es) | 2012-08-28 | 2014-02-28 | Janssen R & D Ireland | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b |
| EA201590384A1 (ru) | 2012-09-10 | 2015-10-30 | Ф. Хоффманн-Ля Рош Аг | 6-аминокислота-гетероарилдигидропиримидины для лечения и профилактики инфекции вируса гепатита в |
| CA2896554C (en) | 2012-12-27 | 2019-11-05 | Drexel University | Novel antiviral agents against hbv infection |
| BR112015020545A2 (pt) | 2013-02-28 | 2017-07-18 | Eisai R&D Man Co Ltd | derivado de tetraidroimidazo[1,5-d][1,4]oxazepina |
| PT2961732T (pt) | 2013-02-28 | 2017-06-26 | Janssen Sciences Ireland Uc | Sulfamoil-arilamidas e utilização das mesmas como medicamentos para o tratamento de hepatite b |
| WO2014165128A2 (en) | 2013-03-12 | 2014-10-09 | Novira Therapeutics, Inc. | Hepatitis b antiviral agents |
| WO2014151958A1 (en) | 2013-03-14 | 2014-09-25 | VenatoRx Pharmaceuticals, Inc. | Beta-lactamase inhibitors |
| WO2014161888A1 (en) | 2013-04-03 | 2014-10-09 | Janssen R&D Ireland | N-phenyl-carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| WO2014184328A1 (en) | 2013-05-17 | 2014-11-20 | F. Hoffmann-La Roche Ag | 6-bridged heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| PT2997019T (pt) | 2013-05-17 | 2018-11-21 | Janssen Sciences Ireland Uc | Derivados de sulfamoíltiofenamida e o seu uso como medicamentos para o tratamento da hepatite b |
| TN2015000516A1 (en) | 2013-05-28 | 2017-04-06 | Astrazeneca Ab | Chemical compounds |
| US9688681B2 (en) | 2013-05-28 | 2017-06-27 | Bayer Cropscience Aktiengesellschaft | Heterocyclic compounds as pest control agents |
| WO2014198880A1 (en) | 2013-06-14 | 2014-12-18 | Ferrer Internacional, S.A. | 2-(2-aminophenoxy)-3-chloronaphthalene-1,4-dione compounds having orexin 2 receptor agonist activity |
| UA118680C2 (uk) | 2013-07-25 | 2019-02-25 | ЯНССЕН САЙЄНСЕЗ АЙРЛЕНД ЮСі | Похідні заміщеного гліоксамідом піроламіду та їхнє застосування як лікарських препаратів для лікування гепатиту в |
| CA2927560A1 (en) | 2013-10-18 | 2015-04-23 | Indiana University Research And Technology Corporation | Hepatitis b viral assembly effectors |
| WO2015055764A1 (en) | 2013-10-18 | 2015-04-23 | Syngenta Participations Ag | 3-methanimidamid-pyridine derivatives as fungicides |
| EP3060547B1 (en) | 2013-10-23 | 2017-10-11 | Janssen Sciences Ireland UC | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| CA2928003A1 (en) | 2013-11-14 | 2015-05-21 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis b infections |
| JO3466B1 (ar) | 2013-12-20 | 2020-07-05 | Takeda Pharmaceuticals Co | مواد ضابطة لتترا هيدرو بيريدوبيرازينات من gpr6 |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| JP6517827B2 (ja) | 2014-01-31 | 2019-05-22 | コグニション セラピューティクス,インコーポレイテッド | イソインドリン組成物および神経変性疾患の治療方法 |
| RU2702109C1 (ru) | 2014-02-05 | 2019-10-04 | Новира Терапьютикс, Инк. | Комбинированная терапия для лечения инфекций вгв |
| EA035848B1 (ru) | 2014-02-06 | 2020-08-20 | Янссен Сайенсиз Айрлэнд Юси | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b |
| KR101933844B1 (ko) | 2014-03-07 | 2018-12-28 | 에프. 호프만-라 로슈 아게 | B형 간염 바이러스 감염의 치료 및 예방을 위한 6-융합된 헤테로아릴다이하이드로피리미딘 |
| CN106413402B (zh) | 2014-03-13 | 2020-10-30 | 美国印第安纳大学研究和技术公司 | 乙型肝炎核心蛋白变构调节剂 |
| US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
| WO2015144093A1 (en) | 2014-03-28 | 2015-10-01 | Sunshine Lake Pharma Co., Ltd. | Dihydropyrimidine compounds and their application in pharmaceuticals |
| CN106459061B (zh) | 2014-05-30 | 2020-01-21 | 齐鲁制药有限公司 | 作为hbv抑制剂的二氢嘧啶并环衍生物 |
| AU2015358561A1 (en) | 2014-12-02 | 2017-06-08 | Novira Therapeutics, Inc. | Sulfide alkyl and pyridyl reverse sulfonamide compounds for HBV treatment |
| US9518057B2 (en) | 2014-12-30 | 2016-12-13 | Novira Therapeutics, Inc. | Derivatives and methods of treating hepatitis B infections |
| MA41338B1 (fr) | 2015-01-16 | 2019-07-31 | Hoffmann La Roche | Composés de pyrazine pour le traitement de maladies infectieuses |
| AU2016232801A1 (en) | 2015-03-19 | 2017-10-12 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis B infections |
| US10442788B2 (en) | 2015-04-01 | 2019-10-15 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| CA2982811A1 (en) | 2015-04-17 | 2016-10-20 | Indiana University Research And Technology Corporation | Hepatitis b viral assembly effectors |
| US10738035B2 (en) | 2015-05-13 | 2020-08-11 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| AR106192A1 (es) | 2015-09-29 | 2017-12-20 | Novira Therapeutics Inc | Formas cristalinas de un agente antiviral contra la hepatitis b |
| CN109251212A (zh) | 2017-07-14 | 2019-01-22 | 上海长森药业有限公司 | 内环硫醚酰胺-芳基酰胺类化合物及其治疗乙型肝炎的用途 |
-
2013
- 2013-05-17 JO JOP/2018/0099A patent/JO3603B1/ar active
-
2014
- 2014-05-15 TW TW103117224A patent/TWI651300B/zh not_active IP Right Cessation
- 2014-05-15 JO JOP/2014/0161A patent/JO3583B1/ar active
- 2014-05-15 TW TW107142373A patent/TWI684586B/zh not_active IP Right Cessation
- 2014-05-15 TW TW108147513A patent/TWI733288B/zh not_active IP Right Cessation
- 2014-05-15 TW TW109141723A patent/TW202126620A/zh unknown
- 2014-05-16 DK DK14727752.9T patent/DK2997011T3/en active
- 2014-05-16 MX MX2015015770A patent/MX366722B/es active IP Right Grant
- 2014-05-16 PT PT14727752T patent/PT2997011T/pt unknown
- 2014-05-16 RS RS20181420A patent/RS58140B1/sr unknown
- 2014-05-16 US US14/891,864 patent/US9884818B2/en active Active
- 2014-05-16 CA CA2909348A patent/CA2909348C/en not_active Expired - Fee Related
- 2014-05-16 ME MEP-2020-89A patent/ME03787B/me unknown
- 2014-05-16 KR KR1020187016196A patent/KR102055639B1/ko not_active Expired - Fee Related
- 2014-05-16 SG SG10202002604PA patent/SG10202002604PA/en unknown
- 2014-05-16 MX MX2020011810A patent/MX387255B/es unknown
- 2014-05-16 SM SM20200228T patent/SMT202000228T1/it unknown
- 2014-05-16 AU AU2014267220A patent/AU2014267220B2/en not_active Ceased
- 2014-05-16 EA EA201592200A patent/EA037378B1/ru unknown
- 2014-05-16 SG SG10201607293UA patent/SG10201607293UA/en unknown
- 2014-05-16 SG SG11201509428PA patent/SG11201509428PA/en unknown
- 2014-05-16 KR KR1020217006045A patent/KR20210025712A/ko not_active Ceased
- 2014-05-16 LT LTEP16180180.8T patent/LT3121164T/lt unknown
- 2014-05-16 JP JP2016513385A patent/JP6318238B2/ja not_active Expired - Fee Related
- 2014-05-16 KR KR1020197036301A patent/KR102223535B1/ko not_active Expired - Fee Related
- 2014-05-16 UY UY35573A patent/UY35573A/es not_active Application Discontinuation
- 2014-05-16 SM SM20180610T patent/SMT201800610T1/it unknown
- 2014-05-16 LT LTEP14727752.9T patent/LT2997011T/lt unknown
- 2014-05-16 CN CN201811424517.8A patent/CN110003076A/zh active Pending
- 2014-05-16 SG SG10201607294SA patent/SG10201607294SA/en unknown
- 2014-05-16 HR HRP20181544TT patent/HRP20181544T1/hr unknown
- 2014-05-16 DK DK16180180.8T patent/DK3121164T3/da active
- 2014-05-16 WO PCT/EP2014/060102 patent/WO2014184350A1/en not_active Ceased
- 2014-05-16 ES ES14727752T patent/ES2699261T3/es active Active
- 2014-05-16 PL PL14727752T patent/PL2997011T3/pl unknown
- 2014-05-16 MX MX2019008585A patent/MX384426B/es unknown
- 2014-05-16 EP EP16180180.8A patent/EP3121164B1/en active Active
- 2014-05-16 SI SI201430900T patent/SI2997011T1/sl unknown
- 2014-05-16 PL PL16180180T patent/PL3121164T3/pl unknown
- 2014-05-16 CN CN201480028413.9A patent/CN105452220B/zh not_active Expired - Fee Related
- 2014-05-16 RS RS20200472A patent/RS60285B1/sr unknown
- 2014-05-16 PT PT161801808T patent/PT3121164T/pt unknown
- 2014-05-16 HU HUE16180180A patent/HUE050236T2/hu unknown
- 2014-05-16 ES ES16180180T patent/ES2787704T3/es active Active
- 2014-05-16 KR KR1020157034169A patent/KR101867898B1/ko not_active Expired - Fee Related
- 2014-05-16 EP EP14727752.9A patent/EP2997011B1/en active Active
- 2014-05-16 EP EP19191069.4A patent/EP3594204A1/en not_active Withdrawn
- 2014-05-16 HU HUE14727752A patent/HUE039997T2/hu unknown
- 2014-05-16 UA UAA201512468A patent/UA117246C2/uk unknown
- 2014-05-16 BR BR112015028461A patent/BR112015028461A2/pt not_active Application Discontinuation
- 2014-05-16 SI SI201431550T patent/SI3121164T1/sl unknown
-
2015
- 2015-10-12 GT GT201500312A patent/GT201500312A/es unknown
- 2015-11-13 PH PH12015502579A patent/PH12015502579B1/en unknown
- 2015-11-16 CL CL2015003370A patent/CL2015003370A1/es unknown
- 2015-11-16 NI NI201500161A patent/NI201500161A/es unknown
- 2015-11-16 ZA ZA2015/08443A patent/ZA201508443B/en unknown
- 2015-11-17 EC ECIEPI201548122A patent/ECSP15048122A/es unknown
-
2017
- 2017-12-12 AU AU2017276170A patent/AU2017276170B2/en not_active Ceased
-
2018
- 2018-01-19 US US15/875,929 patent/US10457638B2/en not_active Expired - Fee Related
- 2018-03-30 JP JP2018068887A patent/JP2018118990A/ja not_active Withdrawn
- 2018-07-15 IL IL260597A patent/IL260597B/en active IP Right Grant
- 2018-08-24 PH PH12018501812A patent/PH12018501812A1/en unknown
- 2018-11-28 CY CY20181101267T patent/CY1121391T1/el unknown
-
2019
- 2019-01-29 IL IL264541A patent/IL264541B/en active IP Right Grant
- 2019-09-25 AU AU2019236657A patent/AU2019236657B2/en not_active Ceased
- 2019-10-14 US US16/601,396 patent/US20200039931A1/en not_active Abandoned
-
2020
- 2020-04-07 JP JP2020069365A patent/JP2020117530A/ja not_active Ceased
- 2020-04-22 HR HRP20200648TT patent/HRP20200648T1/hr unknown
- 2020-05-04 CY CY20201100406T patent/CY1123298T1/el unknown
-
2021
- 2021-07-21 AU AU2021206827A patent/AU2021206827A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013006394A1 (en) * | 2011-07-01 | 2013-01-10 | Institute For Hepatitis And Virus Research | Sulfamoylbenzamide derivatives as antiviral agents against hbv infection |
Non-Patent Citations (1)
| Title |
|---|
| DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002699131 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA037378B1 (ru) | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b | |
| DK3024819T3 (en) | GLYOXAMIDE-SUBSTITUTED PYRROLAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICINES FOR TREATING HEPATITIS B | |
| EA035500B1 (ru) | Производные сульфамоилтиофенамида и их применение в качестве медикаментов для лечения гепатита b | |
| HK40020332A (en) | Preparation of sulphamoylpyrrolamide derivatives for the treatment of hepatitis b | |
| OA17587A (en) | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B. | |
| NZ753038B2 (en) | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B | |
| NZ753038A (en) | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B | |
| NZ713201B2 (en) | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |