DK2997019T3 - Sulfamoylthiophenamidderivativer og anvendelse deraf som lægemidler ved behandling af hepatitis b - Google Patents
Sulfamoylthiophenamidderivativer og anvendelse deraf som lægemidler ved behandling af hepatitis b Download PDFInfo
- Publication number
- DK2997019T3 DK2997019T3 DK14724109.5T DK14724109T DK2997019T3 DK 2997019 T3 DK2997019 T3 DK 2997019T3 DK 14724109 T DK14724109 T DK 14724109T DK 2997019 T3 DK2997019 T3 DK 2997019T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- methyl
- mmol
- fluoro
- hydrogen
- Prior art date
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- 239000003814 drug Substances 0.000 title claims description 9
- 208000006454 hepatitis Diseases 0.000 title description 2
- ZFWUSTBGGBUYIA-UHFFFAOYSA-N 3-sulfamoylthiophene-2-carboxamide Chemical class NC(=O)C=1SC=CC=1S(N)(=O)=O ZFWUSTBGGBUYIA-UHFFFAOYSA-N 0.000 title 1
- 231100000283 hepatitis Toxicity 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 49
- 150000002431 hydrogen Chemical class 0.000 claims description 29
- 125000001153 fluoro group Chemical group F* 0.000 claims description 27
- 229920006395 saturated elastomer Polymers 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 12
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 12
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
- 239000011737 fluorine Substances 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- YUCFVHQCAFKDQG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH] YUCFVHQCAFKDQG-UHFFFAOYSA-N 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 82
- 238000000034 method Methods 0.000 description 68
- 239000011541 reaction mixture Substances 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 55
- 238000005160 1H NMR spectroscopy Methods 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- 241000700721 Hepatitis B virus Species 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- 239000000843 powder Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 23
- -1 C-|-C3alkyl Chemical group 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- IKWDNQBCRWYWEP-UHFFFAOYSA-N 4-[(3,4-difluorophenyl)carbamoyl]-5-methylthiophene-2-sulfonyl chloride Chemical compound Cc1sc(cc1C(=O)Nc1ccc(F)c(F)c1)S(Cl)(=O)=O IKWDNQBCRWYWEP-UHFFFAOYSA-N 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- PVAJJAQXMPHKEV-UHFFFAOYSA-N 5-chlorosulfonyl-2-methylthiophene-3-carbonyl chloride Chemical compound Cc1sc(cc1C(Cl)=O)S(Cl)(=O)=O PVAJJAQXMPHKEV-UHFFFAOYSA-N 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 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 11
- 229940125878 compound 36 Drugs 0.000 description 11
- 239000003921 oil Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- FHWNSRQOLNVNDI-UHFFFAOYSA-N 4-[(3-chloro-4,5-difluorophenyl)carbamoyl]-5-methylthiophene-2-sulfonyl chloride Chemical compound Cc1sc(cc1C(=O)Nc1cc(F)c(F)c(Cl)c1)S(Cl)(=O)=O FHWNSRQOLNVNDI-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000003039 volatile agent Substances 0.000 description 9
- 229940125782 compound 2 Drugs 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 8
- GNIVOUHTLHLJDK-UHFFFAOYSA-N 4-[(3-cyano-4-fluorophenyl)carbamoyl]-5-methylthiophene-2-sulfonyl chloride Chemical compound Cc1sc(cc1C(=O)Nc1ccc(F)c(c1)C#N)S(Cl)(=O)=O GNIVOUHTLHLJDK-UHFFFAOYSA-N 0.000 description 7
- SDUIEZRKWYUKBK-UHFFFAOYSA-N 5-methyl-4-[[3-(trifluoromethyl)phenyl]carbamoyl]thiophene-2-sulfonyl chloride Chemical compound Cc1sc(cc1C(=O)Nc1cccc(c1)C(F)(F)F)S(Cl)(=O)=O SDUIEZRKWYUKBK-UHFFFAOYSA-N 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000000840 anti-viral effect Effects 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 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 6
- ISYXXORXVFRVKD-UHFFFAOYSA-N 3,4-difluoro-5-methylaniline Chemical compound CC1=CC(N)=CC(F)=C1F ISYXXORXVFRVKD-UHFFFAOYSA-N 0.000 description 6
- UXWVXKQSUVKKNI-UHFFFAOYSA-N 5-chlorosulfonylthiophene-3-carboxylic acid Chemical compound OC(=O)C1=CSC(S(Cl)(=O)=O)=C1 UXWVXKQSUVKKNI-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 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 6
- 125000001246 bromo group Chemical group Br* 0.000 description 6
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- GMMHEZMDGDEDDZ-DFWYDOINSA-N (2S)-3,3-difluorobutan-2-amine hydrochloride Chemical compound Cl.C[C@H](N)C(C)(F)F GMMHEZMDGDEDDZ-DFWYDOINSA-N 0.000 description 5
- 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 5
- GCSHUWRZDOUZNN-UHFFFAOYSA-N 3-(trifluoromethyl)oxolan-3-amine Chemical compound FC(F)(F)C1(N)CCOC1 GCSHUWRZDOUZNN-UHFFFAOYSA-N 0.000 description 5
- JBBZXOUMFRXWGF-UHFFFAOYSA-N 3-chloro-4,5-difluoroaniline Chemical compound NC1=CC(F)=C(F)C(Cl)=C1 JBBZXOUMFRXWGF-UHFFFAOYSA-N 0.000 description 5
- NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 5
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- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 5
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- 238000002953 preparative HPLC Methods 0.000 description 5
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- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 3
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- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (19)
1. Forbindelse med formlen (I)
eller en stereoisomer eller tautomer form deraf, hvor: en X er S, og de to andre X betegner CR4; R2 er fluor eller hydrogen; R1 og R3 er uafhængigt valgt fra gruppen bestående af hydrogen, fluor, chlor, brom, CHF2, CH2F, CF3, CN og methyl, hvor mindst en af R1 og R3 ikke er hydrogen, og R1 og R3 ikke er ortho til methyl eller ortho til chlor; en R4 er hydrogen, og den anden R4 er valgt fra gruppen bestående af hydrogen, halogen, Ci-Cbalkyl, cyclopropyl, CHF2, CH2F og CF3; R5 er hydrogen; R6 er valgt fra gruppen bestående af Ci-Cbalkyl, Ci-Cbalkyl-R7 og en 3- til 7-leddet mættet ring, der eventuelt kan indeholde et eller flere heteroatomer, som hvert er uafhængigt valgt fra gruppen bestående af 0, S og N, såsom en 3- til 7-leddet mættet ring eller Ci-Cbalkyl, eventuelt substitueret med en eller flere substituenter, som hver er uafhængigt valgt fra gruppen bestående af hydrogen, fluor, OH, CF3 og Ci-Chalkyl; R7 er en 3- til 7-leddet mættet ring, der eventuelt indeholder et eller flere heteroatomer, som hvert er uafhængigt valgt fra gruppen bestående af 0, S og N, or C(=O)-R8; R8 er valgt fra gruppen bestående af Ci-Cbalkoxy og -NH2; hvor R6 ikke er methyl, hvis R1 er methyl, R2 er fluor og R3 er hydrogen; eller et farmaceutisk acceptabelt salt eller et solvat deraf.
2. Forbindelse ifølge krav 1, hvor R1 er valgt blandt enten fluor eller methyl.
3. Forbindelse ifølge krav 1 eller 2 ifølge formlen (II)
(II) hvor R4 er valgt fra gruppen bestående af hydrogen, halogen, Ci-C3alkyl, cyclopropyl, CHF2, CH2F og CF3.
4. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor mindst to af R1 og R2 og R3 er halogen.
5. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R1 er methyl, og R2 er fluor.
6. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R6 indeholder en 3- til 7-leddet mættet ring, der eventuelt indeholder et oxygenatom.
7. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R6 er en 4- eller 5-leddet mættet ring, der eventuelt indeholder et oxygenatom.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 5 hvor R6 er en forgrenet Ci-C6alkyl, der eventuelt er substitueret med et eller flere fluoratomer.
9. Forbindelse ifølge krav 1,
hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller et solvat deraf.
10. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
11. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
12. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
13. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
14. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
15. Forbindelse ifølge krav 1, hvor forbindelsen er
eller et farmaceutisk acceptabelt salt eller solvat deraf.
16. Forbindelse ifølge et hvilket som helst af de foregående krav til anvendelse som lægemiddel.
17. Forbindelse ifølge et hvilket som helst af kravene 1 til 15 til anvendelse ved forebyggelse eller behandling af en HBV-infektion hos et pattedyr.
18. Farmaceutisk sammensætning, som omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 15 og en farmaceutisk acceptabel bærer.
19. Produkt, der indeholder (a) en forbindelse med formlen (I) som defineret i et hvilket som helst af kravene 1 til 15 og (b) en anden HBV-hæmmer, som et kombineret præparat til samtidig, separat eller sekventiel anvendelse ved behandling af HBV-infektioner.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13168295 | 2013-05-17 | ||
| EP13185227 | 2013-09-19 | ||
| EP14157917 | 2014-03-05 | ||
| PCT/EP2014/060132 WO2014184365A1 (en) | 2013-05-17 | 2014-05-16 | Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2997019T3 true DK2997019T3 (da) | 2018-12-03 |
Family
ID=50729521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14724109.5T DK2997019T3 (da) | 2013-05-17 | 2014-05-16 | Sulfamoylthiophenamidderivativer og anvendelse deraf som lægemidler ved behandling af hepatitis b |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US10160743B2 (da) |
| EP (1) | EP2997019B1 (da) |
| JP (1) | JP6441315B2 (da) |
| CN (1) | CN105960400B (da) |
| AU (1) | AU2014267235B2 (da) |
| BR (1) | BR112015028538A2 (da) |
| CA (1) | CA2909742C (da) |
| CY (1) | CY1122337T1 (da) |
| DK (1) | DK2997019T3 (da) |
| EA (1) | EA035500B1 (da) |
| ES (1) | ES2695182T3 (da) |
| HR (1) | HRP20181863T1 (da) |
| HU (1) | HUE040446T2 (da) |
| IL (1) | IL242141B (da) |
| LT (1) | LT2997019T (da) |
| MX (1) | MX366787B (da) |
| PL (1) | PL2997019T3 (da) |
| PT (1) | PT2997019T (da) |
| RS (1) | RS57999B1 (da) |
| SI (1) | SI2997019T1 (da) |
| SM (1) | SMT201800577T1 (da) |
| WO (1) | WO2014184365A1 (da) |
Families Citing this family (122)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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- 2014-05-16 BR BR112015028538A patent/BR112015028538A2/pt not_active Application Discontinuation
- 2014-05-16 PL PL14724109T patent/PL2997019T3/pl unknown
-
2015
- 2015-10-18 IL IL242141A patent/IL242141B/en active IP Right Grant
-
2018
- 2018-11-08 CY CY20181101182T patent/CY1122337T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014267235B2 (en) | 2017-10-05 |
| EA035500B1 (ru) | 2020-06-25 |
| AU2014267235A1 (en) | 2015-11-12 |
| US20160115149A1 (en) | 2016-04-28 |
| WO2014184365A1 (en) | 2014-11-20 |
| MX2015015771A (es) | 2016-03-15 |
| CY1122337T1 (el) | 2020-07-31 |
| HK1225387A1 (zh) | 2017-09-08 |
| EP2997019B1 (en) | 2018-08-08 |
| HRP20181863T1 (hr) | 2018-12-28 |
| JP2016518437A (ja) | 2016-06-23 |
| MX366787B (es) | 2019-07-23 |
| SI2997019T1 (sl) | 2018-12-31 |
| ES2695182T3 (es) | 2019-01-02 |
| CN105960400B (zh) | 2019-05-31 |
| PL2997019T3 (pl) | 2019-03-29 |
| AU2014267235A8 (en) | 2015-12-10 |
| RS57999B1 (sr) | 2019-01-31 |
| SMT201800577T1 (it) | 2019-01-11 |
| BR112015028538A2 (pt) | 2017-07-25 |
| CA2909742A1 (en) | 2014-11-20 |
| IL242141B (en) | 2019-09-26 |
| US10160743B2 (en) | 2018-12-25 |
| EP2997019A1 (en) | 2016-03-23 |
| HUE040446T2 (hu) | 2019-03-28 |
| JP6441315B2 (ja) | 2018-12-19 |
| CA2909742C (en) | 2020-08-04 |
| EA201592198A1 (ru) | 2016-03-31 |
| CN105960400A (zh) | 2016-09-21 |
| PT2997019T (pt) | 2018-11-21 |
| LT2997019T (lt) | 2018-11-26 |
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