BR112017007311B1 - Espiro-indols para o tratamento e profilaxia da infecção respiratória do vírus sincicial (rsv) - Google Patents
Espiro-indols para o tratamento e profilaxia da infecção respiratória do vírus sincicial (rsv) Download PDFInfo
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- BR112017007311B1 BR112017007311B1 BR112017007311-0A BR112017007311A BR112017007311B1 BR 112017007311 B1 BR112017007311 B1 BR 112017007311B1 BR 112017007311 A BR112017007311 A BR 112017007311A BR 112017007311 B1 BR112017007311 B1 BR 112017007311B1
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- Prior art keywords
- substituted
- alkyl
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- 238000011282 treatment Methods 0.000 title claims description 11
- 208000015181 infectious disease Diseases 0.000 title claims description 9
- 241000725643 Respiratory syncytial virus Species 0.000 title description 27
- 238000011321 prophylaxis Methods 0.000 title 1
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 72
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 72
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 58
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 40
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 32
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 27
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 25
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 24
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 11
- 239000003112 inhibitor Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000005843 halogen group Chemical group 0.000 claims description 61
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 7
- 125000003003 spiro group Chemical group 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 5
- 229910052799 carbon Chemical group 0.000 claims description 4
- 206010022000 influenza Diseases 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 229940121649 protein inhibitor Drugs 0.000 claims description 3
- 239000012268 protein inhibitor Substances 0.000 claims description 3
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims description 2
- 102000007982 Phosphoproteins Human genes 0.000 claims description 2
- 108010089430 Phosphoproteins Proteins 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 230000002128 anti-rhinoviral effect Effects 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 230000002519 immonomodulatory effect Effects 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 claims 1
- 150000003527 tetrahydropyrans Chemical class 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 40
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 39
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract description 23
- 229910052736 halogen Inorganic materials 0.000 abstract description 12
- 150000002367 halogens Chemical class 0.000 abstract description 10
- 125000004450 alkenylene group Chemical group 0.000 abstract description 6
- 125000004419 alkynylene group Chemical group 0.000 abstract description 3
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- 239000000243 solution Substances 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- -1 T-pentyl Chemical group 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- 125000003118 aryl group Chemical group 0.000 description 46
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- 239000000047 product Substances 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- 239000007787 solid Substances 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 27
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 26
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 26
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- 239000000725 suspension Substances 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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 14
- 239000012267 brine Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
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- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 5
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 5
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 5
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
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- 238000004458 analytical method Methods 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
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- 239000002244 precipitate Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
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- 241001465754 Metazoa Species 0.000 description 4
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- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
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- HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- 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
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- 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
- A61P31/14—Antivirals for RNA 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
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1417707.5 | 2014-10-07 | ||
| GBGB1417707.5A GB201417707D0 (en) | 2014-10-07 | 2014-10-07 | Pharmaceutical compounds |
| PCT/GB2015/052920 WO2016055780A1 (en) | 2014-10-07 | 2015-10-06 | Spiro-indolines for the treatment and prophylaxis of respiratory syncytial virus infection (rsv) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112017007311A2 BR112017007311A2 (pt) | 2017-12-19 |
| BR112017007311B1 true BR112017007311B1 (pt) | 2022-11-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112017007311-0A BR112017007311B1 (pt) | 2014-10-07 | 2015-10-06 | Espiro-indols para o tratamento e profilaxia da infecção respiratória do vírus sincicial (rsv) |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US10106539B2 (https=) |
| EP (1) | EP3204375B1 (https=) |
| JP (1) | JP6695334B2 (https=) |
| KR (2) | KR20230116097A (https=) |
| CN (1) | CN107108557B (https=) |
| AR (1) | AR102181A1 (https=) |
| AU (1) | AU2015329778B2 (https=) |
| BR (1) | BR112017007311B1 (https=) |
| CA (1) | CA2963740C (https=) |
| CL (1) | CL2017000839A1 (https=) |
| CO (1) | CO2017004603A2 (https=) |
| CY (1) | CY1121564T1 (https=) |
| DK (1) | DK3204375T3 (https=) |
| ES (1) | ES2718976T3 (https=) |
| GB (1) | GB201417707D0 (https=) |
| HR (1) | HRP20190808T1 (https=) |
| HU (1) | HUE043553T2 (https=) |
| LT (1) | LT3204375T (https=) |
| MX (1) | MX373233B (https=) |
| NZ (1) | NZ731323A (https=) |
| PE (1) | PE20170949A1 (https=) |
| PL (1) | PL3204375T3 (https=) |
| PT (1) | PT3204375T (https=) |
| RS (1) | RS58706B1 (https=) |
| RU (1) | RU2734248C2 (https=) |
| SG (1) | SG11201702766YA (https=) |
| SI (1) | SI3204375T1 (https=) |
| SM (1) | SMT201900249T1 (https=) |
| TR (1) | TR201903362T4 (https=) |
| TW (1) | TWI718107B (https=) |
| WO (1) | WO2016055780A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2821649T3 (es) | 2015-06-08 | 2021-04-27 | Shangdong Danhong Pharmaceutical Co Ltd | Método para preparar derivados de imidazol e intermedios de los mismos y formas cristalinas |
| ES2878058T3 (es) * | 2016-08-04 | 2021-11-18 | Reviral Ltd | Derivados de pirimidina y su uso en el tratamiento y la prevención de una infección por virus respiratorio sincitial |
| GB201711704D0 (en) * | 2017-07-20 | 2017-09-06 | Reviral Ltd | Pharmaceutical compounds |
| GB201721812D0 (en) | 2017-12-22 | 2018-02-07 | Reviral Ltd | Pharmaceutical compounds |
| CN116077494A (zh) * | 2023-01-11 | 2023-05-09 | 黑龙江中医药大学 | 一种治疗呼吸道合胞病毒的药物组合物及其制备方法 |
| WO2024174953A1 (zh) * | 2023-02-21 | 2024-08-29 | 苏州隆博泰药业有限公司 | 苯并咪唑类衍生物及其医药用途 |
| WO2024252355A1 (en) | 2023-06-08 | 2024-12-12 | Pfizer Inc. | Pediatric dosing regimens comprising a fusion inhibitor for the treatment of rsv |
| WO2025120500A1 (en) | 2023-12-06 | 2025-06-12 | Pfizer Inc. | Benzodiazepine compounds as n-protein inhibitors |
| WO2025153942A1 (en) | 2024-01-16 | 2025-07-24 | Pfizer Inc. | Benzodiazepine pyrazolo carboxamides as n-protein inhibitors |
| WO2025248535A1 (en) * | 2024-05-29 | 2025-12-04 | Zydus Lifesciences Limited | Novel spirocyclic compounds to treat viral infections |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS57102863A (en) * | 1980-12-16 | 1982-06-26 | Takeda Chem Ind Ltd | Spiroindolinone and its preparation |
| PL194216B1 (pl) * | 1998-01-23 | 2007-05-31 | Sankyo Co | Pochodne spiropiperydyny, lekarstwo oraz środek zapobiegawczy lub terapeutyczny zawierające jako składnik czynny te pochodne i zastosowanie pochodnych spiropiperydyny |
| SI1196408T1 (en) * | 1999-06-28 | 2005-02-28 | Janssen Pharmaceutica N.V. | Respiratory syncytial virus replication inhibitors |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| US6919331B2 (en) | 2001-12-10 | 2005-07-19 | Bristol-Myers Squibb Company | Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents |
| US7205328B2 (en) * | 2002-10-21 | 2007-04-17 | Irm Llc | Oxindoles with anti-HIV activity |
| JO2355B1 (en) | 2003-04-15 | 2006-12-12 | ميرك شارب اند دوم كوربوريشن | Hereditary calcitonin polypeptide receptor antagonists |
| US7390798B2 (en) | 2004-09-13 | 2008-06-24 | Merck & Co., Inc. | Carboxamide spirolactam CGRP receptor antagonists |
| BRPI0517418A (pt) | 2004-10-13 | 2008-10-07 | Merck & Co Inc | composto, composição farmacêutica, e, métodos para antagonismo de atividade do receptor de cgrp em um mamìfero, para tratar, controlar, melhorar ou reduzir o risco de dor de cabeça, enxaqueca ou cefalgia, e de tratamento ou prevenção de dores de cabeça de enxaqueca, cefalgias, e dores de cabeça |
| US20100278835A1 (en) | 2009-03-10 | 2010-11-04 | Astrazeneca Uk Limited | Novel compounds 660 |
| GB201119538D0 (en) * | 2011-11-10 | 2011-12-21 | Viral Ltd | Pharmaceutical compounds |
| MY172021A (en) | 2012-10-16 | 2019-11-12 | Janssen Sciences Ireland Uc | Rsv antiviral compounds |
| EP2997028A1 (en) | 2013-05-14 | 2016-03-23 | F.Hoffmann-La Roche Ag | Aza-oxo-indoles for the treatment and prophylaxis of respiratory syncytial virus infection |
| KR20160007629A (ko) * | 2013-05-14 | 2016-01-20 | 에프. 호프만-라 로슈 아게 | 호흡기 세포융합 바이러스 감염의 치료 및 예방을 위한 아자-옥소-인돌 |
| CN105392787B (zh) * | 2013-05-14 | 2017-11-24 | 豪夫迈·罗氏有限公司 | 用于治疗和预防呼吸道合胞病毒感染的氮杂‑氧代‑吲哚 |
| KR20160030271A (ko) * | 2013-08-12 | 2016-03-16 | 에프. 호프만-라 로슈 아게 | 호흡기 세포융합 바이러스 감염의 치료 및 예방을 위한 아자-옥소-인돌 |
| CN105408330A (zh) * | 2013-08-12 | 2016-03-16 | 豪夫迈·罗氏有限公司 | 新的用于治疗和预防呼吸道合胞病毒感染的氮杂-氧代-吲哚 |
| JP6211195B2 (ja) * | 2013-08-12 | 2017-10-11 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 呼吸器合胞体ウイルス感染症の処置および予防のための新規アザ−オキソ−インドール |
| CN105431419A (zh) * | 2013-08-15 | 2016-03-23 | 豪夫迈·罗氏有限公司 | 新的用于治疗和预防呼吸道合胞病毒感染的氮杂-氧代-吲哚 |
| HK1222855A1 (zh) * | 2013-08-15 | 2017-07-14 | F. Hoffmann-La Roche Ag | 新的用於治疗和预防呼吸道合胞病毒感染的氮杂-氧代-吲哚 |
| KR20160030569A (ko) * | 2013-08-15 | 2016-03-18 | 에프. 호프만-라 로슈 아게 | 호흡기 세포융합 바이러스 감염의 치료 및 예방을 위한 신규한 아자-옥소-인돌 |
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2014
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