ES2881776T3 - Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus - Google Patents
Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus Download PDFInfo
- Publication number
- ES2881776T3 ES2881776T3 ES17711349T ES17711349T ES2881776T3 ES 2881776 T3 ES2881776 T3 ES 2881776T3 ES 17711349 T ES17711349 T ES 17711349T ES 17711349 T ES17711349 T ES 17711349T ES 2881776 T3 ES2881776 T3 ES 2881776T3
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- Prior art keywords
- alkyl
- ring
- haloalkyl
- halo
- benzyloxy
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 173
- 208000009620 Orthomyxoviridae Infections Diseases 0.000 title description 4
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 170
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 101
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 125000005843 halogen group Chemical group 0.000 claims abstract description 62
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 60
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 55
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 51
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 48
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims abstract description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 12
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 12
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 7
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 5
- 150000004292 cyclic ethers Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 206010022000 influenza Diseases 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910005965 SO 2 Inorganic materials 0.000 claims description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- 150000003536 tetrazoles Chemical class 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 33
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 146
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 107
- 239000000203 mixture Substances 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 99
- 239000000243 solution Substances 0.000 description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 92
- 235000019439 ethyl acetate Nutrition 0.000 description 75
- 238000000034 method Methods 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- 239000000543 intermediate Substances 0.000 description 65
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 58
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 44
- 238000011282 treatment Methods 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 229910052938 sodium sulfate Inorganic materials 0.000 description 40
- 235000011152 sodium sulphate Nutrition 0.000 description 40
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 125000001424 substituent group Chemical group 0.000 description 33
- 239000000047 product Substances 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000012267 brine Substances 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- 239000010410 layer Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 238000000746 purification Methods 0.000 description 24
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- 208000037797 influenza A Diseases 0.000 description 22
- 239000007832 Na2SO4 Substances 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 239000003795 chemical substances by application Substances 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 0 C*C(C(C[n]1c(C(C(C(O)=CNC)=O)=N)nnc1*)O)I Chemical compound C*C(C(C[n]1c(C(C(C(O)=CNC)=O)=N)nnc1*)O)I 0.000 description 18
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 208000037798 influenza B Diseases 0.000 description 17
- 208000037799 influenza C Diseases 0.000 description 17
- 238000007792 addition Methods 0.000 description 16
- 229910052805 deuterium Inorganic materials 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229940124597 therapeutic agent Drugs 0.000 description 15
- 230000009385 viral infection Effects 0.000 description 15
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 125000006413 ring segment Chemical group 0.000 description 12
- 241000712461 unidentified influenza virus Species 0.000 description 12
- 208000036142 Viral infection Diseases 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 229940015043 glyoxal Drugs 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 229910000024 caesium carbonate Inorganic materials 0.000 description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 10
- 238000010348 incorporation Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 9
- 239000005695 Ammonium acetate Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- CUQZQRIIFNWQSJ-UHFFFAOYSA-N FC(F)(F)[Cu].c1cnc2c(c1)ccc1cccnc21 Chemical compound FC(F)(F)[Cu].c1cnc2c(c1)ccc1cccnc21 CUQZQRIIFNWQSJ-UHFFFAOYSA-N 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229940043376 ammonium acetate Drugs 0.000 description 9
- 235000019257 ammonium acetate Nutrition 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
- 102100031780 Endonuclease Human genes 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
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- 239000011591 potassium Substances 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
- 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 7
- 108010042407 Endonucleases Proteins 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
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- 238000010511 deprotection reaction Methods 0.000 description 7
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- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
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- 125000002947 alkylene group Chemical group 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000000460 chlorine Chemical group 0.000 description 6
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- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
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- 230000003287 optical effect Effects 0.000 description 6
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
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- 230000001225 therapeutic effect Effects 0.000 description 6
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 5
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- DZJJTSGLPYDYEU-XMMPIXPASA-N (8S)-8-benzhydryl-5-chloro-13-phenylmethoxy-3,6,9-triazatricyclo[7.4.0.02,6]trideca-1(13),2,4,10-tetraen-12-one Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)[C@@H]1N2C(C=3N(C1)C(=CN=3)Cl)=C(C(C=C2)=O)OCC1=CC=CC=C1 DZJJTSGLPYDYEU-XMMPIXPASA-N 0.000 description 4
- MBXXNUIUYMJMSO-UHFFFAOYSA-N 3-amino-1,1-diphenylpropan-2-ol Chemical compound C=1C=CC=CC=1C(C(O)CN)C1=CC=CC=C1 MBXXNUIUYMJMSO-UHFFFAOYSA-N 0.000 description 4
- KTZAKTCBKGPDAH-UHFFFAOYSA-N 4-oxo-5-phenylmethoxy-1-(2-trimethylsilylethoxymethyl)pyridazine-3-carbaldehyde Chemical compound C(C1=CC=CC=C1)OC=1C(C(=NN(C=1)COCC[Si](C)(C)C)C=O)=O KTZAKTCBKGPDAH-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
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- 241000124008 Mammalia Species 0.000 description 4
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- 238000009736 wetting Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- 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
- C07D491/22—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 four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662305392P | 2016-03-08 | 2016-03-08 | |
| PCT/IB2017/051338 WO2017153919A1 (en) | 2016-03-08 | 2017-03-07 | Tricyclic compounds useful to treat orthomyxovirus infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2881776T3 true ES2881776T3 (es) | 2021-11-30 |
Family
ID=58347733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17711349T Active ES2881776T3 (es) | 2016-03-08 | 2017-03-07 | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US10858366B2 (https=) |
| EP (1) | EP3426656B1 (https=) |
| JP (1) | JP6918819B2 (https=) |
| CN (1) | CN108699059B (https=) |
| ES (1) | ES2881776T3 (https=) |
| WO (1) | WO2017153919A1 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
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| BR112017022550B1 (pt) | 2015-04-28 | 2021-02-23 | Shionogi & Co., Ltd | derivados policíclicos de piridona substituída |
| AU2016374416A1 (en) | 2015-12-15 | 2018-06-14 | Shionogi & Co., Ltd. | Medicine for treating influenza characterized by comprising combination of cap-dependent endonuclease inhibitor with anti-influenza drug |
| JP6904970B2 (ja) | 2016-03-07 | 2021-07-21 | 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 | Ｂ型肝炎抗ウイルス剤 |
| ES2881776T3 (es) | 2016-03-08 | 2021-11-30 | Novartis Ag | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
| RU2727962C1 (ru) | 2016-08-10 | 2020-07-28 | Сионоги Энд Ко., Лтд. | Фармацевтические композиции, содержащие замещенные полициклические пиридоновые производные и их пролекарство |
| JOP20170169A1 (ar) | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
| US10952978B2 (en) | 2017-08-28 | 2021-03-23 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US11058678B2 (en) | 2018-01-22 | 2021-07-13 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| KR20230031990A (ko) | 2018-02-28 | 2023-03-07 | 노파르티스 아게 | 인플루엔자의 치료를 위한 오르토믹소바이러스 복제의 억제제로서의 10-(디(페닐)메틸)-4-히드록시-8,9,9a,10-테트라히드로-7h-피롤로[1',2':4,5]피라지노[1,2-b]피리다진-3,5-디온 유도체 및 관련 화합물 |
| UY38383A (es) | 2018-09-21 | 2020-04-30 | Enanta Pharm Inc | Heterociclos funcionalizados como agentes antivirales |
| US11198693B2 (en) | 2018-11-21 | 2021-12-14 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| CN111410661B (zh) * | 2019-01-04 | 2023-05-05 | 周雨恬 | 帽依赖性内切核酸酶抑制剂及其用途 |
| CN109912624B (zh) * | 2019-04-11 | 2021-05-11 | 杭州科巢生物科技有限公司 | 一种巴洛沙韦酯关键母核中间体的合成方法 |
| CN111909174B (zh) | 2019-05-08 | 2022-01-21 | 江西彩石医药科技有限公司 | 吡啶酮衍生物的晶型及制备方法和应用 |
| WO2020247444A1 (en) | 2019-06-03 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247561A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247575A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| US11738019B2 (en) | 2019-07-11 | 2023-08-29 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| US11236108B2 (en) | 2019-09-17 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| WO2021188414A1 (en) | 2020-03-16 | 2021-09-23 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
Family Cites Families (29)
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| GB8501542D0 (en) * | 1985-01-22 | 1985-02-20 | Erba Farmitalia | 4 5 6 7-tetrahydro-imidazo(4 5-clpyridine derivatives |
| BR0211750A (pt) | 2001-08-10 | 2004-10-13 | Shionogi & Co | Agente antiviral |
| WO2004078163A2 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| TW200526635A (en) * | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| WO2005087766A1 (en) | 2004-03-09 | 2005-09-22 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Hiv integrase inhibitors |
| FR2901795A1 (fr) * | 2006-05-30 | 2007-12-07 | Fourtillan Snc | Derives de pyrimidino[1',6'-1,2]pyrido[3,4-b]indoles et leur utilisation en therapeutique |
| US9238657B2 (en) | 2008-10-31 | 2016-01-19 | Shionogi & Co., Ltd. | Cephalosporin having catechol group |
| TWI518084B (zh) | 2009-03-26 | 2016-01-21 | 鹽野義製藥股份有限公司 | 哌喃酮與吡啶酮衍生物之製造方法 |
| US8835461B2 (en) * | 2009-03-26 | 2014-09-16 | Shionogi & Co., Ltd. | Substituted 3-hydroxy-4-pyridone derivative |
| LT2444400T (lt) | 2009-06-15 | 2018-06-11 | Shionogi & Co., Ltd. | Pakeistasis policiklinis karbamoilpiridono darinys |
| TW201201813A (en) * | 2010-03-31 | 2012-01-16 | Arqule Inc | Substituted benzo-pyrido-triazolo-diazepine compounds |
| US20120195857A1 (en) | 2010-08-12 | 2012-08-02 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| MX2013003139A (es) | 2010-09-24 | 2013-06-18 | Shionogi & Co | Profarmaco de derivado de carbamoilpiridona policiclica substituida. |
| WO2012151567A1 (en) * | 2011-05-05 | 2012-11-08 | St. Jude Children's Research Hospital | Pyrimidinone compounds and methods for preventing and treating influenza |
| EP2774928B1 (en) | 2011-10-12 | 2017-08-30 | Shionogi & Co., Ltd. | Polycyclic pyridone derivative having integrase-inhibiting activity |
| AU2013318779B2 (en) | 2012-09-20 | 2016-07-28 | Celltrion, Inc. | Dolastatin-10 derivative, method of producing the same and anticancer drug composition containing the same |
| CN104918942A (zh) * | 2013-01-08 | 2015-09-16 | 萨维拉制药有限公司 | 嘧啶酮衍生物和它们用于治疗、改善或预防病毒疾病的用途 |
| NZ716822A (en) | 2013-08-21 | 2017-10-27 | Alios Biopharma Inc | Antiviral compounds |
| CN105530946A (zh) | 2013-09-11 | 2016-04-27 | 南加利福尼亚大学 | 具有高度表达的fas配体的干细胞组合物 |
| ES2724581T3 (es) | 2013-09-12 | 2019-09-12 | Janssen Biopharma Inc | Compuestos de piridazinona y usos de los mismos |
| WO2015038655A1 (en) | 2013-09-12 | 2015-03-19 | Alios Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| WO2016005330A1 (en) | 2014-07-07 | 2016-01-14 | F. Hoffmann-La Roche Ag | Dihydropyridopyrazine-1,8-diones and their use in the treatment, amelioration or prevention of viral diseases |
| WO2016145103A1 (en) | 2015-03-11 | 2016-09-15 | Alios Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| ES2881776T3 (es) * | 2016-03-08 | 2021-11-30 | Novartis Ag | Compuestos tricíclicos útiles para tratar las infecciones por ortomixovirus |
| RU2727962C1 (ru) | 2016-08-10 | 2020-07-28 | Сионоги Энд Ко., Лтд. | Фармацевтические композиции, содержащие замещенные полициклические пиридоновые производные и их пролекарство |
| JOP20170169A1 (ar) | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
| CN111848615B (zh) | 2018-01-17 | 2022-05-17 | 江西彩石医药科技有限公司 | 吡啶酮衍生物及包含其的抗流感病毒药物组合物 |
| KR20230031990A (ko) | 2018-02-28 | 2023-03-07 | 노파르티스 아게 | 인플루엔자의 치료를 위한 오르토믹소바이러스 복제의 억제제로서의 10-(디(페닐)메틸)-4-히드록시-8,9,9a,10-테트라히드로-7h-피롤로[1',2':4,5]피라지노[1,2-b]피리다진-3,5-디온 유도체 및 관련 화합물 |
-
2017
- 2017-03-07 ES ES17711349T patent/ES2881776T3/es active Active
- 2017-03-07 EP EP17711349.5A patent/EP3426656B1/en active Active
- 2017-03-07 US US16/083,089 patent/US10858366B2/en active Active
- 2017-03-07 WO PCT/IB2017/051338 patent/WO2017153919A1/en not_active Ceased
- 2017-03-07 JP JP2018547307A patent/JP6918819B2/ja active Active
- 2017-03-07 CN CN201780015673.6A patent/CN108699059B/zh active Active
-
2020
- 2020-07-20 US US16/933,000 patent/US11453677B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3426656B1 (en) | 2021-05-12 |
| EP3426656A1 (en) | 2019-01-16 |
| US11453677B2 (en) | 2022-09-27 |
| US20190092780A1 (en) | 2019-03-28 |
| JP2019512485A (ja) | 2019-05-16 |
| CN108699059A (zh) | 2018-10-23 |
| US10858366B2 (en) | 2020-12-08 |
| US20200347072A1 (en) | 2020-11-05 |
| JP6918819B2 (ja) | 2021-08-11 |
| CN108699059B (zh) | 2021-06-18 |
| WO2017153919A1 (en) | 2017-09-14 |
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