JP6757402B2 - ピラジノ［２，３−ｂ］［１，４］オキサジン−３−オン又は関連する環系を含む抗菌剤 - Google Patents
ピラジノ［２，３−ｂ］［１，４］オキサジン−３−オン又は関連する環系を含む抗菌剤 Download PDFInfo
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- JP6757402B2 JP6757402B2 JP2018507672A JP2018507672A JP6757402B2 JP 6757402 B2 JP6757402 B2 JP 6757402B2 JP 2018507672 A JP2018507672 A JP 2018507672A JP 2018507672 A JP2018507672 A JP 2018507672A JP 6757402 B2 JP6757402 B2 JP 6757402B2
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- Prior art keywords
- methyl
- amino
- pyrazino
- fluoro
- alkyl
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- 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.)
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- 239000003242 anti bacterial agent Substances 0.000 title description 10
- FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical compound O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 155
- 239000000203 mixture Substances 0.000 claims description 142
- 150000003839 salts Chemical class 0.000 claims description 84
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 45
- 239000002502 liposome Substances 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 238000009472 formulation Methods 0.000 claims description 22
- 208000035143 Bacterial infection Diseases 0.000 claims description 21
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 15
- 241000894007 species Species 0.000 claims description 8
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 241000588724 Escherichia coli Species 0.000 claims description 5
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 5
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 5
- 241000606768 Haemophilus influenzae Species 0.000 claims description 4
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 4
- 241000588770 Proteus mirabilis Species 0.000 claims description 4
- 241000191967 Staphylococcus aureus Species 0.000 claims description 4
- 241000122971 Stenotrophomonas Species 0.000 claims description 4
- 241000194017 Streptococcus Species 0.000 claims description 4
- 229940047650 haemophilus influenzae Drugs 0.000 claims description 4
- 241000588626 Acinetobacter baumannii Species 0.000 claims description 3
- 241001453380 Burkholderia Species 0.000 claims description 3
- 241000588697 Enterobacter cloacae Species 0.000 claims description 3
- 241000194032 Enterococcus faecalis Species 0.000 claims description 3
- 241000588915 Klebsiella aerogenes Species 0.000 claims description 3
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 3
- 241000588655 Moraxella catarrhalis Species 0.000 claims description 3
- 241000193985 Streptococcus agalactiae Species 0.000 claims description 3
- 229940092559 enterobacter aerogenes Drugs 0.000 claims description 3
- 229940032049 enterococcus faecalis Drugs 0.000 claims description 3
- 229960003085 meticillin Drugs 0.000 claims description 3
- 208000019206 urinary tract infection Diseases 0.000 claims description 3
- 241000217846 Bacteroides caccae Species 0.000 claims description 2
- 241000606124 Bacteroides fragilis Species 0.000 claims description 2
- 241001135228 Bacteroides ovatus Species 0.000 claims description 2
- 241000589513 Burkholderia cepacia Species 0.000 claims description 2
- 241000588923 Citrobacter Species 0.000 claims description 2
- 241000589242 Legionella pneumophila Species 0.000 claims description 2
- 241000588777 Providencia rettgeri Species 0.000 claims description 2
- 241000607715 Serratia marcescens Species 0.000 claims description 2
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
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- 239000000825 pharmaceutical preparation Substances 0.000 claims 8
- 241000194031 Enterococcus faecium Species 0.000 claims 3
- 241000315377 Bremia ovata Species 0.000 claims 1
- 241000328422 Culiseta annulata Species 0.000 claims 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 346
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 304
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 259
- 239000007787 solid Substances 0.000 description 179
- -1 n -Butyl Chemical group 0.000 description 178
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 176
- 239000000243 solution Substances 0.000 description 175
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 109
- 238000006243 chemical reaction Methods 0.000 description 99
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 88
- 239000000047 product Substances 0.000 description 87
- 229910052736 halogen Inorganic materials 0.000 description 85
- 150000002367 halogens Chemical class 0.000 description 85
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 85
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- 239000011541 reaction mixture Substances 0.000 description 62
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 60
- VUHWWMUKMLLBIC-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound O=C1CSc2nccnc2N1 VUHWWMUKMLLBIC-UHFFFAOYSA-N 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 238000005481 NMR spectroscopy Methods 0.000 description 55
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 54
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 239000007858 starting material Substances 0.000 description 54
- 238000001914 filtration Methods 0.000 description 53
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 51
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 41
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- 239000012044 organic layer Substances 0.000 description 36
- 229910052757 nitrogen Inorganic materials 0.000 description 35
- 239000012453 solvate Substances 0.000 description 35
- XISPDFMAOWZEQG-UHFFFAOYSA-N 4h-1,4-oxazin-3-one Chemical compound O=C1COC=CN1 XISPDFMAOWZEQG-UHFFFAOYSA-N 0.000 description 34
- 150000001204 N-oxides Chemical class 0.000 description 34
- 235000019441 ethanol Nutrition 0.000 description 32
- 239000000706 filtrate Substances 0.000 description 32
- 238000000034 method Methods 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 31
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 31
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 30
- 230000000694 effects Effects 0.000 description 30
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 29
- 239000012043 crude product Substances 0.000 description 29
- 239000000460 chlorine Substances 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- 125000000217 alkyl group Chemical group 0.000 description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
- 125000001072 heteroaryl group Chemical group 0.000 description 25
- 239000004698 Polyethylene Substances 0.000 description 24
- 239000012535 impurity Substances 0.000 description 24
- 239000011734 sodium Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 125000000623 heterocyclic group Chemical group 0.000 description 23
- QQWWDSRPZBNPEE-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]oxazin-3-one Chemical compound C1=CN=C2NC(=O)COC2=N1 QQWWDSRPZBNPEE-UHFFFAOYSA-N 0.000 description 21
- 125000004043 oxo group Chemical group O=* 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 19
- 229910052717 sulfur Inorganic materials 0.000 description 19
- 239000004094 surface-active agent Substances 0.000 description 19
- 238000004809 thin layer chromatography Methods 0.000 description 19
- 239000012267 brine Substances 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 125000005842 heteroatom Chemical group 0.000 description 17
- 229910052760 oxygen Inorganic materials 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- 125000003545 alkoxy group Chemical group 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 150000002632 lipids Chemical class 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
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- AXVPMSMOPJYOCS-UHFFFAOYSA-N 3-oxo-4H-pyrazino[2,3-b][1,4]oxazine-6-carbaldehyde Chemical compound O=CC1=CN=C2OCC(=O)NC2=N1 AXVPMSMOPJYOCS-UHFFFAOYSA-N 0.000 description 8
- UIRSLBDCOYTZPH-UHFFFAOYSA-N 4h-1,4-thiazin-3-one Chemical compound O=C1CSC=CN1 UIRSLBDCOYTZPH-UHFFFAOYSA-N 0.000 description 8
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
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- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 6
- JTPXVCKCLBROOJ-UHFFFAOYSA-N 2-amino-6-chloropyrazine Chemical compound NC1=CN=CC(Cl)=N1 JTPXVCKCLBROOJ-UHFFFAOYSA-N 0.000 description 6
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- SXERGDOODBLTMY-UHFFFAOYSA-N cyclohexyl 4-nitrobenzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)OC1CCCCC1 SXERGDOODBLTMY-UHFFFAOYSA-N 0.000 description 6
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
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- WFXKMIJXZQSONL-IDMXKUIJSA-N 4-[2-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]ethyl]-6-methoxypyrido[2,3-b]pyrazin-3-one dihydrochloride Chemical compound Cl.Cl.COc1ccc2ncc(=O)n(CCN3CC[C@@H](CN)C3)c2n1 WFXKMIJXZQSONL-IDMXKUIJSA-N 0.000 description 5
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- 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 5
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- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 4
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- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
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- FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 1
- GPDBIGSFXXKWQR-UHFFFAOYSA-N tert-butyl n-(4-formylcyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(C=O)CC1 GPDBIGSFXXKWQR-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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Classifications
-
- 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed systems
-
- 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
- A61K31/535—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
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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- 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
- A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—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 sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- C07D513/02—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 two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US62/308,928 | 2016-03-16 | ||
| PCT/IB2016/054890 WO2017029602A2 (en) | 2015-08-16 | 2016-08-15 | Compounds for use in antibacterial applications |
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| UY36851A (es) * | 2015-08-16 | 2017-03-31 | Glaxosmithkline Ip Dev Ltd | Compuestos para uso en aplicaciones antibacterianas |
| WO2019180634A1 (en) | 2018-03-23 | 2019-09-26 | Glaxosmithkline Intellectual Property Development Limited | Synthesis of oxazinone-containing bicyclic aromatic and heteroaromatic aldehydes |
| WO2021009212A1 (en) | 2019-07-16 | 2021-01-21 | Idorsia Pharmaceuticals Ltd | Antibacterial quinolone derivatives |
| CN111269247B (zh) * | 2020-03-04 | 2020-11-24 | 河南科技大学第一附属医院 | 具有抑制大肠杆菌作用的噻嗪酮药物分子的制备方法 |
| JP2025510646A (ja) | 2022-03-14 | 2025-04-15 | スラップ ファーマシューティカルズ エルエルシー | 多環式化合物 |
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2016
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- 2016-08-15 JP JP2018507672A patent/JP6757402B2/ja not_active Expired - Fee Related
- 2016-08-15 CR CR20180111A patent/CR20180111A/es unknown
- 2016-08-15 EA EA201890412A patent/EA033314B1/ru not_active IP Right Cessation
- 2016-08-15 WO PCT/IB2016/054890 patent/WO2017029602A2/en not_active Ceased
- 2016-08-15 CA CA2995715A patent/CA2995715A1/en not_active Abandoned
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- 2016-08-15 KR KR1020187007548A patent/KR20180038046A/ko not_active Withdrawn
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- 2016-08-15 HK HK18108126.0A patent/HK1248680A1/zh unknown
- 2016-08-15 MX MX2018002033A patent/MX2018002033A/es unknown
- 2016-08-15 PE PE2018000236A patent/PE20181143A1/es unknown
- 2016-08-15 AU AU2016307969A patent/AU2016307969C1/en not_active Ceased
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2018
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- 2018-02-14 CL CL2018000403A patent/CL2018000403A1/es unknown
- 2018-02-15 PH PH12018500358A patent/PH12018500358A1/en unknown
- 2018-02-16 DO DO2018000049A patent/DOP2018000049A/es unknown
- 2018-02-27 CO CONC2018/0002204A patent/CO2018002204A2/es unknown
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2019
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- 2019-05-17 US US16/415,319 patent/US10683307B2/en not_active Expired - Fee Related
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