KR20180038046A - 항박테리아 적용에 사용하기 위한 화합물 - Google Patents
항박테리아 적용에 사용하기 위한 화합물 Download PDFInfo
- Publication number
- KR20180038046A KR20180038046A KR1020187007548A KR20187007548A KR20180038046A KR 20180038046 A KR20180038046 A KR 20180038046A KR 1020187007548 A KR1020187007548 A KR 1020187007548A KR 20187007548 A KR20187007548 A KR 20187007548A KR 20180038046 A KR20180038046 A KR 20180038046A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- amino
- pyrazino
- thiazin
- cyclohexyl
- 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.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 195
- 230000000844 anti-bacterial effect Effects 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 78
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 19
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 510
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 404
- -1 3H, 4H-pyrrolo [2,3-d] pyrimidin- Pyrazino [2,3-b] [1,4] thiazin-3-one Chemical compound 0.000 claims description 207
- 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 141
- 239000000203 mixture Substances 0.000 claims description 138
- 229910052736 halogen Inorganic materials 0.000 claims description 97
- 150000002367 halogens Chemical class 0.000 claims description 97
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 88
- VUHWWMUKMLLBIC-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound O=C1CSc2nccnc2N1 VUHWWMUKMLLBIC-UHFFFAOYSA-N 0.000 claims description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 58
- 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 claims description 56
- JOVAUDVABACMQW-UHFFFAOYSA-N 3,4-dihydro-2h-pyrazino[2,3-b][1,4]thiazine Chemical compound C1=CN=C2NCCSC2=N1 JOVAUDVABACMQW-UHFFFAOYSA-N 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- NDTSIDOTKVWMRI-UHFFFAOYSA-N 3,4-dihydro-2h-pyrazino[2,3-b][1,4]oxazine Chemical compound C1=CN=C2NCCOC2=N1 NDTSIDOTKVWMRI-UHFFFAOYSA-N 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 238000009472 formulation Methods 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 23
- XISPDFMAOWZEQG-UHFFFAOYSA-N 4h-1,4-oxazin-3-one Chemical compound O=C1COC=CN1 XISPDFMAOWZEQG-UHFFFAOYSA-N 0.000 claims description 22
- 125000004043 oxo group Chemical group O=* 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- UIRSLBDCOYTZPH-UHFFFAOYSA-N 4h-1,4-thiazin-3-one Chemical compound O=C1CSC=CN1 UIRSLBDCOYTZPH-UHFFFAOYSA-N 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 14
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- CFPBYGKISUKURJ-UHFFFAOYSA-N 3h-quinolin-2-one Chemical compound C1=CC=CC2=NC(=O)CC=C21 CFPBYGKISUKURJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 8
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- GAGAICHLGQDUTL-UHFFFAOYSA-N 4h-thiazin-3-one Chemical compound O=C1CC=CSN1 GAGAICHLGQDUTL-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- APSYYKGWNWKKOC-UHFFFAOYSA-N quinoxaline-5-carboxamide Chemical compound C1=CN=C2C(C(=O)N)=CC=CC2=N1 APSYYKGWNWKKOC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 3
- UZHUJHQUJHHUTQ-UHFFFAOYSA-N 2-methyl-4h-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound C1=CN=C2NC(=O)C(C)SC2=N1 UZHUJHQUJHHUTQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 6
- ALDYFKCYVAOMJY-UHFFFAOYSA-N 2,3-dihydroquinoline Chemical compound C1=CC=CC2=CCCN=C21 ALDYFKCYVAOMJY-UHFFFAOYSA-N 0.000 claims 4
- HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 claims 2
- UWHWNFVVODLFIQ-UHFFFAOYSA-N methyl pyrrolidine-1-carboxylate Chemical compound COC(=O)N1CCCC1 UWHWNFVVODLFIQ-UHFFFAOYSA-N 0.000 claims 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 claims 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims 1
- VBNNAMMESJXTMX-CLRJQRCDSA-N COC1=CN=C2C=CC3=C(C(CCO3)N[C@@H]3C[C@H](CNCC4=CN=C5SCC(=O)NC5=N4)[C@H](O)[C@@H]3O)C2=N1 Chemical compound COC1=CN=C2C=CC3=C(C(CCO3)N[C@@H]3C[C@H](CNCC4=CN=C5SCC(=O)NC5=N4)[C@H](O)[C@@H]3O)C2=N1 VBNNAMMESJXTMX-CLRJQRCDSA-N 0.000 claims 1
- HEIZPACCIHXHKV-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyrazine Chemical compound C1=CN=C2SC=NC2=N1 HEIZPACCIHXHKV-UHFFFAOYSA-N 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 316
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 316
- 239000000243 solution Substances 0.000 description 181
- 239000007787 solid Substances 0.000 description 177
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 107
- 238000006243 chemical reaction Methods 0.000 description 106
- 239000000047 product Substances 0.000 description 91
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 84
- 206010057190 Respiratory tract infections Diseases 0.000 description 80
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 238000005481 NMR spectroscopy Methods 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 57
- 239000007858 starting material Substances 0.000 description 54
- 238000001914 filtration Methods 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 39
- 239000012044 organic layer Substances 0.000 description 37
- 239000012453 solvate Substances 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 150000001204 N-oxides Chemical class 0.000 description 32
- 235000019441 ethanol Nutrition 0.000 description 32
- 239000000706 filtrate Substances 0.000 description 31
- 238000002360 preparation method Methods 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 28
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 28
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 28
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 239000011734 sodium Substances 0.000 description 25
- 239000004698 Polyethylene Substances 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- 229920006395 saturated elastomer Polymers 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000012535 impurity Substances 0.000 description 21
- 239000000463 material Substances 0.000 description 21
- 238000004809 thin layer chromatography Methods 0.000 description 21
- 239000002502 liposome Substances 0.000 description 20
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- 239000012267 brine Substances 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 239000004094 surface-active agent Substances 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 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
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- 229940079593 drug Drugs 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 150000002632 lipids Chemical class 0.000 description 12
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
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- 238000004458 analytical method Methods 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
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- 239000000843 powder Substances 0.000 description 9
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 8
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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 8
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- FHDYLAMSIRNDDL-UHFFFAOYSA-N 3-amino-5-chloro-1h-pyrazin-2-one Chemical compound NC1=NC(Cl)=CN=C1O FHDYLAMSIRNDDL-UHFFFAOYSA-N 0.000 description 5
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- 241000894006 Bacteria Species 0.000 description 5
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- 241000872931 Myoporum sandwicense Species 0.000 description 5
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- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 5
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- 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
Landscapes
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| PCT/IB2016/054890 WO2017029602A2 (en) | 2015-08-16 | 2016-08-15 | Compounds for use in antibacterial applications |
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| 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 |
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