ES2898069T3 - Derivados de N-(piridin-2-il)piridinosulfonamida y su uso en el tratamiento de la enfermedad - Google Patents
Derivados de N-(piridin-2-il)piridinosulfonamida y su uso en el tratamiento de la enfermedad Download PDFInfo
- Publication number
- ES2898069T3 ES2898069T3 ES17771589T ES17771589T ES2898069T3 ES 2898069 T3 ES2898069 T3 ES 2898069T3 ES 17771589 T ES17771589 T ES 17771589T ES 17771589 T ES17771589 T ES 17771589T ES 2898069 T3 ES2898069 T3 ES 2898069T3
- Authority
- ES
- Spain
- Prior art keywords
- pyridin
- trifluoromethyl
- sulfonamide
- chloro
- methylphenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 66
- 201000010099 disease Diseases 0.000 title claims description 47
- 238000011282 treatment Methods 0.000 title claims description 38
- HGLLHXBAIVABRJ-UHFFFAOYSA-N n-pyridin-2-ylpyridine-2-sulfonamide Chemical class C=1C=CC=NC=1S(=O)(=O)NC1=CC=CC=N1 HGLLHXBAIVABRJ-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 278
- 150000001875 compounds Chemical class 0.000 claims abstract description 239
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 115
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 111
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 101
- 239000001257 hydrogen Substances 0.000 claims abstract description 100
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 92
- 150000002367 halogens Chemical group 0.000 claims abstract description 72
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 72
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 71
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 49
- 125000001424 substituent group Chemical group 0.000 claims abstract description 49
- 125000005913 (C3-C6) cycloalkyl group Chemical class 0.000 claims abstract description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 45
- 150000002825 nitriles Chemical group 0.000 claims abstract description 38
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims abstract description 34
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 25
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 25
- WCYWZMWISLQXQU-FIBGUPNXSA-N trideuteriomethane Chemical group [2H][C]([2H])[2H] WCYWZMWISLQXQU-FIBGUPNXSA-N 0.000 claims abstract description 12
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 229940124530 sulfonamide Drugs 0.000 claims description 615
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- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims description 96
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 85
- 239000008194 pharmaceutical composition Substances 0.000 claims description 66
- -1 C4-6heterocycle Chemical group 0.000 claims description 62
- 125000003944 tolyl group Chemical group 0.000 claims description 57
- YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 claims description 53
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- 239000003937 drug carrier Substances 0.000 claims description 39
- DWJMBQYORXLGAE-UHFFFAOYSA-N pyridine-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=N1 DWJMBQYORXLGAE-UHFFFAOYSA-N 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
- 208000006673 asthma Diseases 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 230000001404 mediated effect Effects 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 239000008177 pharmaceutical agent Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 10
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- 239000000126 substance Substances 0.000 claims description 10
- 206010006451 bronchitis Diseases 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 239000003242 anti bacterial agent Substances 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 7
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- 239000003172 expectorant agent Substances 0.000 claims description 6
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229940066491 mucolytics Drugs 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 5
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- 230000003115 biocidal effect Effects 0.000 claims description 4
- 229960005475 antiinfective agent Drugs 0.000 claims description 3
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- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 3
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 claims description 3
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 claims description 2
- WDVOLHDNUMLNAK-UHFFFAOYSA-N tert-butyl 1,6-diazaspiro[3.3]heptane-6-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC11NCC1 WDVOLHDNUMLNAK-UHFFFAOYSA-N 0.000 claims description 2
- IJICYBAXQSHUPE-UHFFFAOYSA-N 1-[6-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-propylpiperidine-3-carboxylic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CCC1)(C(=O)O)CCC IJICYBAXQSHUPE-UHFFFAOYSA-N 0.000 claims 1
- MPYUQOGTXCMQIU-UHFFFAOYSA-N 1-[6-[[5-chloro-6-(2-methylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-propylpiperidine-3-carboxylic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1)C)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CCC1)(C(=O)O)CCC MPYUQOGTXCMQIU-UHFFFAOYSA-N 0.000 claims 1
- SVJFMQHSCVNPCT-UHFFFAOYSA-N 1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-propylpiperidine-3-carboxylic acid Chemical compound C(CC)C1(CN(CCC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)C(=O)O SVJFMQHSCVNPCT-UHFFFAOYSA-N 0.000 claims 1
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 claims 1
- CXMWEJWJYHYBNE-UHFFFAOYSA-N 2-ethyl-1-methylpiperidine-4-carboxylic acid Chemical compound CCC1CC(C(O)=O)CCN1C CXMWEJWJYHYBNE-UHFFFAOYSA-N 0.000 claims 1
- CVKMFSAVYPAZTQ-UHFFFAOYSA-N 2-methylhexanoic acid Chemical compound CCCCC(C)C(O)=O CVKMFSAVYPAZTQ-UHFFFAOYSA-N 0.000 claims 1
- RLKXRSGTPYUDFL-UHFFFAOYSA-N 3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]cyclohexane-1-carboxylic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NC1CC(CCC1)C(=O)O)C(F)(F)F)C RLKXRSGTPYUDFL-UHFFFAOYSA-N 0.000 claims 1
- OEFQDUZNALVBRY-UHFFFAOYSA-N 3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NC1CC(CC1)C(=O)O)C(F)(F)F)C OEFQDUZNALVBRY-UHFFFAOYSA-N 0.000 claims 1
- RAKRLGRFLXTHAI-UHFFFAOYSA-N N-[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]-6-piperazin-1-ylpyridine-2-sulfonamide Chemical compound N1(CCNCC1)C1=CC=CC(=N1)S(=O)(=O)NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C RAKRLGRFLXTHAI-UHFFFAOYSA-N 0.000 claims 1
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims 1
- 239000000076 hypertonic saline solution Substances 0.000 claims 1
- XFIUZEAHIJGTTB-UHFFFAOYSA-N pyridine-4-sulfonamide Chemical compound NS(=O)(=O)C1=CC=NC=C1 XFIUZEAHIJGTTB-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 255
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 242
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
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Classifications
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- 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
- C07D405/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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KR20180030363A (ko) | 2016-09-13 | 2018-03-22 | 삼성디스플레이 주식회사 | 표시 장치 |
EP3844158A1 (en) * | 2018-08-31 | 2021-07-07 | Xenon Pharmaceuticals Inc. | Heteroaryl-substituted sulfonamide compounds and their use as sodium channel inhibitors |
JP2022514253A (ja) * | 2018-12-18 | 2022-02-10 | ノバルティス アーゲー | N-(ピリジン-2-イルスルホニル)シクロプロパンカルボキサミド誘導体及びcftr媒介疾患の処置におけるその使用 |
WO2020128925A1 (en) * | 2018-12-21 | 2020-06-25 | Novartis Ag | Macrocyclic compounds and their use in the treatment of disease |
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IL292965A (en) * | 2019-11-12 | 2022-07-01 | Genzyme Corp | Heteroarylaminosulfonamides with 6 positions and methods of using them |
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CA2506772A1 (en) | 2002-11-01 | 2004-05-21 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of jak and other protein kinases |
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US20040204422A1 (en) | 2003-04-14 | 2004-10-14 | Abbott Gmbh & Co. Kg. | N-[(Piperazinyl)hetaryl]arylsulfonamide compounds |
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JPWO2005040135A1 (ja) | 2003-10-24 | 2007-03-08 | 小野薬品工業株式会社 | 抗ストレス薬およびその医薬用途 |
PE20060285A1 (es) | 2004-03-30 | 2006-05-08 | Aventis Pharma Inc | Piridonas sustituidas como inhibidores de pol(adp-ribosa)-polimerasa (parp) |
CA2562075C (en) | 2004-04-20 | 2012-08-14 | Transtech Pharma, Inc. | Substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators |
FR2874011B1 (fr) | 2004-08-03 | 2007-06-15 | Sanofi Synthelabo | Derives de sulfonamides, leur preparation et leur application en therapeutique |
ATE462697T1 (de) | 2004-08-12 | 2010-04-15 | Amgen Inc | Bisaryl-sulfonamide |
EP1799647A1 (en) | 2004-10-04 | 2007-06-27 | F.Hoffmann-La Roche Ag | Alkil-pyridines as 11-beta inhibitors for diabetes |
EP1666467A1 (en) | 2004-11-08 | 2006-06-07 | Evotec AG | 11Beta-HSD1 Inhibitors |
SE0402735D0 (sv) | 2004-11-09 | 2004-11-09 | Astrazeneca Ab | Novel compounds |
WO2006106423A2 (en) | 2005-04-07 | 2006-10-12 | Pfizer Inc. | Amino sulfonyl derivatives as inhibitors of human 11-.beta.-hydrosysteroid dehydrogenase |
WO2007021941A2 (en) | 2005-08-16 | 2007-02-22 | Icagen, Inc. | Inhibitors of voltage-gated sodium channels |
WO2007023114A1 (en) | 2005-08-25 | 2007-03-01 | F. Hoffmann-La Roche Ag | P38 map kinase inhibitors and methods for using the same |
FR2896798A1 (fr) | 2006-01-27 | 2007-08-03 | Sanofi Aventis Sa | Derives de sulfonamides, leur preparation et leur application en therapeutique |
EP2016075A1 (en) | 2006-05-03 | 2009-01-21 | AstraZeneca AB | Thiazole derivatives and their use as anti-tumour agents |
US20080280891A1 (en) | 2006-06-27 | 2008-11-13 | Locus Pharmaceuticals, Inc. | Anti-cancer agents and uses thereof |
US7683176B2 (en) | 2006-07-14 | 2010-03-23 | Chemocentryx, Inc. | Triazolyl pyridyl benzenesulfonamides |
US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
DK2420494T3 (en) | 2006-08-16 | 2015-01-12 | J David Gladstone Inst A Testamentary Trust Established Under The Will Of J David Gladstone | Use of thiadiazole compounds as inhibitors of kynurenine 3-monooxygenase |
KR20090060333A (ko) | 2006-09-08 | 2009-06-11 | 노파르티스 아게 | 림프구 상호작용에 의해 매개되는 질환의 치료에 유용한 n-바이아릴 (헤테로)아릴술폰아미드 유도체 |
WO2008033455A2 (en) | 2006-09-13 | 2008-03-20 | The Institutes For Pharmaceutical Discovery, Llc | Biphenyl and heteroaryl phenyl derivatives as protein tyrosine phosphatases inhibitors |
HUE059861T2 (hu) | 2007-04-11 | 2023-01-28 | Canbas Co Ltd | N-Szubsztituált 2,5-dioxo-azolin vegyületek a rák kezelésében való felhasználásra |
WO2008157500A1 (en) | 2007-06-17 | 2008-12-24 | Kalypsys, Inc. | Aminoquinazoline cannabinoid receptor modulators for treatment of disease |
US20090069288A1 (en) | 2007-07-16 | 2009-03-12 | Breinlinger Eric C | Novel therapeutic compounds |
WO2009055418A1 (en) | 2007-10-22 | 2009-04-30 | Smithkline Beecham Corporation | Pyridosulfonamide derivatives as pi3 kinase inhibitors |
CA2714232A1 (en) | 2008-02-05 | 2009-08-13 | Pfizer Inc. | Pyridinyl amides for the treatment of cns and metabolic disorders |
WO2009152356A2 (en) | 2008-06-11 | 2009-12-17 | Irm Llc | Compounds and compositions useful for the treatment of malaria |
WO2010029300A1 (en) | 2008-09-12 | 2010-03-18 | Biolipox Ab | Bis aromatic compounds for use in the treatment of inflammation |
WO2010100475A1 (en) | 2009-03-02 | 2010-09-10 | Astrazeneca Ab | Hydroxamic acid derivatives as gram-negative antibacterial agents |
WO2010123822A1 (en) | 2009-04-20 | 2010-10-28 | Institute For Oneworld Health | Compounds, compositions and methods comprising pyridazine sulfonamide derivatives |
EP2253617A1 (de) | 2009-05-20 | 2010-11-24 | Bayer CropScience AG | Halogen-substituierte Verbindungen als Pestizide |
US20130022629A1 (en) | 2010-01-04 | 2013-01-24 | Sharpe Arlene H | Modulators of Immunoinhibitory Receptor PD-1, and Methods of Use Thereof |
WO2012000896A2 (de) | 2010-06-28 | 2012-01-05 | Bayer Cropscience Ag | Heterocyclische verbindungen als schädlingsbekämpfungsmittel |
WO2012004293A2 (de) | 2010-07-08 | 2012-01-12 | Bayer Cropscience Ag | Insektizide und fungizide wirkstoffkombinationen |
CN103429571A (zh) | 2010-12-22 | 2013-12-04 | 普渡制药公司 | 作为钠通道阻断剂的取代吡啶 |
US9295676B2 (en) | 2011-03-17 | 2016-03-29 | The Trustees Of The University Of Pennsylvania | Mutation mimicking compounds that bind to the kinase domain of EGFR |
EP2755652B1 (en) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituted heterocyclyl carboxamides |
EP2822931B1 (en) * | 2012-03-09 | 2017-05-03 | Inception 2, Inc. | Triazolone compounds and uses thereof |
DK2888251T3 (da) | 2012-08-21 | 2019-07-29 | Peter Maccallum Cancer Inst | Perforinhæmmende benzensulfonamidforbindelser, fremstilling og anvendelser deraf |
WO2014031928A2 (en) | 2012-08-24 | 2014-02-27 | Philip Jones | Heterocyclic modulators of hif activity for treatment of disease |
EP2968285A4 (en) | 2013-03-13 | 2016-12-21 | Flatley Discovery Lab | COMPOUNDS AND METHODS FOR THE TREATMENT OF CYSTIC FIBROSIS |
WO2014181287A1 (en) | 2013-05-09 | 2014-11-13 | Piramal Enterprises Limited | Heterocyclyl compounds and uses thereof |
EP3087074A1 (en) | 2013-12-23 | 2016-11-02 | Norgine BV | Benzene sulfonamides as ccr9 inhibitors |
AU2015229117A1 (en) | 2014-03-13 | 2016-09-29 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing CFTR activity |
CN112250627B (zh) | 2014-10-06 | 2024-02-02 | 弗特克斯药品有限公司 | 囊性纤维化跨膜转导调节因子调节剂 |
CN104844566B (zh) | 2014-12-12 | 2018-05-18 | 合肥中科普瑞昇生物医药科技有限公司 | 一种新型结构的激酶抑制剂 |
AU2016272702A1 (en) * | 2015-06-02 | 2017-12-21 | Abbvie S.A.R.L. | Substituted pyridines and method of use |
US9981945B2 (en) | 2015-10-07 | 2018-05-29 | NuBridge BioSciences | Pyrimidine derivatives as CFTR modulators |
GB201602527D0 (en) * | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
WO2017173274A1 (en) | 2016-03-31 | 2017-10-05 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
TW201811766A (zh) | 2016-08-29 | 2018-04-01 | 瑞士商諾華公司 | N-(吡啶-2-基)吡啶-磺醯胺衍生物及其用於疾病治療之用途 |
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2017
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- 2017-08-28 KR KR1020197008655A patent/KR20190040319A/ko not_active Application Discontinuation
- 2017-08-28 EP EP17771589.3A patent/EP3504194B1/en active Active
- 2017-08-28 UY UY0001037379A patent/UY37379A/es not_active Application Discontinuation
- 2017-08-28 CN CN201780052527.0A patent/CN109641873B/zh active Active
- 2017-08-28 WO PCT/IB2017/055162 patent/WO2018042316A1/en active Application Filing
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- 2017-08-28 JP JP2019532215A patent/JP7035055B2/ja active Active
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AR109437A1 (es) | 2018-11-28 |
MX2019002439A (es) | 2019-07-08 |
EP3504194A1 (en) | 2019-07-03 |
CN109641873A (zh) | 2019-04-16 |
US11066369B2 (en) | 2021-07-20 |
CA3031073A1 (en) | 2018-03-08 |
EA201990609A1 (ru) | 2019-07-31 |
BR112019003883A2 (pt) | 2019-06-18 |
AU2017319430A1 (en) | 2019-02-14 |
US20180072673A1 (en) | 2018-03-15 |
UY37379A (es) | 2018-03-23 |
US10450273B2 (en) | 2019-10-22 |
KR20190040319A (ko) | 2019-04-17 |
JP7035055B2 (ja) | 2022-03-14 |
JP2019530739A (ja) | 2019-10-24 |
WO2018042316A1 (en) | 2018-03-08 |
TW201811766A (zh) | 2018-04-01 |
CN109641873B (zh) | 2022-03-18 |
US20200002281A1 (en) | 2020-01-02 |
EP3504194B1 (en) | 2021-08-18 |
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