EA038393B1 - Соединения и способы для лечения бактериальных инфекций - Google Patents
Соединения и способы для лечения бактериальных инфекций Download PDFInfo
- Publication number
- EA038393B1 EA038393B1 EA201992370A EA201992370A EA038393B1 EA 038393 B1 EA038393 B1 EA 038393B1 EA 201992370 A EA201992370 A EA 201992370A EA 201992370 A EA201992370 A EA 201992370A EA 038393 B1 EA038393 B1 EA 038393B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- mmol
- oxo
- methyl
- tert
- methanopyrazolo
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 143
- 208000035143 Bacterial infection Diseases 0.000 title claims abstract description 24
- 208000022362 bacterial infectious disease Diseases 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 C (O) NR d R e Inorganic materials 0.000 claims description 228
- 239000000203 mixture Substances 0.000 claims description 77
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
- 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 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- 125000000565 sulfonamide group Chemical group 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 329
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 259
- 239000000243 solution Substances 0.000 description 210
- 239000011541 reaction mixture Substances 0.000 description 206
- 239000007787 solid Substances 0.000 description 172
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 144
- 235000019439 ethyl acetate Nutrition 0.000 description 124
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 90
- 239000012043 crude product Substances 0.000 description 88
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 88
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 84
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 78
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 71
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 62
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 57
- 239000012044 organic layer Substances 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 55
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 46
- 229910052757 nitrogen Inorganic materials 0.000 description 45
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 239000000706 filtrate Substances 0.000 description 34
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 31
- 239000000758 substrate Substances 0.000 description 29
- ZSAUCGAVFVWQBK-UHFFFAOYSA-N 5H-1,3-diazepin-6-yl hydrogen sulfate Chemical compound C1C=NC=NC=C1OS(=O)(=O)O ZSAUCGAVFVWQBK-UHFFFAOYSA-N 0.000 description 28
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 239000012298 atmosphere Substances 0.000 description 24
- 125000000623 heterocyclic group Chemical group 0.000 description 23
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
- 125000005336 allyloxy group Chemical group 0.000 description 19
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 18
- 229910052763 palladium Inorganic materials 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- 101710167893 Penicillin-binding protein 3 Proteins 0.000 description 15
- 101710146026 Peptidoglycan D,D-transpeptidase FtsI Proteins 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 15
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 14
- DOLHGQYGWWLDTI-UHFFFAOYSA-N 1,3-diazepin-5-one Chemical compound O=C1C=CN=CN=C1 DOLHGQYGWWLDTI-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 235000019270 ammonium chloride Nutrition 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- 101710205263 Peptidoglycan D,D-transpeptidase MrdA Proteins 0.000 description 12
- 101710116427 Probable peptidoglycan D,D-transpeptidase PenA Proteins 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 10
- 230000001580 bacterial effect Effects 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 208000015181 infectious disease Diseases 0.000 description 10
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 229910004727 OSO3H Inorganic materials 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 description 9
- 150000002923 oximes Chemical class 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N tert-butyl alcohol Substances CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical class NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 8
- 230000010933 acylation Effects 0.000 description 8
- 238000005917 acylation reaction Methods 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 8
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 101710202686 Penicillin-sensitive transpeptidase Proteins 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 7
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229940070891 pyridium Drugs 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 5
- IXLVUUFUDRJUSL-RPBOFIJWSA-N 5-[[4-(3-acetamidophenyl)phenyl]methyl]-n-[(1s,2r)-2-phenylcyclopropyl]-1,3-oxazole-4-carboxamide Chemical compound CC(=O)NC1=CC=CC(C=2C=CC(CC3=C(N=CO3)C(=O)N[C@@H]3[C@H](C3)C=3C=CC=CC=3)=CC=2)=C1 IXLVUUFUDRJUSL-RPBOFIJWSA-N 0.000 description 5
- 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
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 239000003456 ion exchange resin Substances 0.000 description 5
- 229920003303 ion-exchange polymer Polymers 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 208000004235 neutropenia Diseases 0.000 description 5
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DBYUSKYKPWHHJA-ZFWWWQNUSA-N (1R,7S)-N-hydroxy-N',5-dimethyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound C\N=C(/NO)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 DBYUSKYKPWHHJA-ZFWWWQNUSA-N 0.000 description 4
- 241000588626 Acinetobacter baumannii Species 0.000 description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 241000588921 Enterobacteriaceae Species 0.000 description 4
- 241000589602 Francisella tularensis Species 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 239000012448 Lithium borohydride Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- SSUCKKNRCOFUPT-UHFFFAOYSA-N o-[tert-butyl(dimethyl)silyl]hydroxylamine Chemical compound CC(C)(C)[Si](C)(C)ON SSUCKKNRCOFUPT-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 4
- YZOQHJMBUVLKTN-JUIRDXJGSA-N (1R,7Z,7S)-N-hydroxy-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidoyl chloride Chemical compound Cn1ncc2[C@@H]3CN([C@H](\C(Cl)=N\O)c12)C(=O)N3OCc1ccccc1 YZOQHJMBUVLKTN-JUIRDXJGSA-N 0.000 description 3
- MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 description 3
- JPPREFOETTUXDK-UHFFFAOYSA-N 1h-1,3-diazepine Chemical compound N1C=CC=CN=C1 JPPREFOETTUXDK-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000193738 Bacillus anthracis Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 241000607479 Yersinia pestis Species 0.000 description 3
- UJNPCEIDOFLILK-WPRPVWTQSA-N [[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-sulfooxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino] N-(2-aminoethyl)carbamate Chemical compound C\N=C(/NOC(=O)NCCN)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 UJNPCEIDOFLILK-WPRPVWTQSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 239000012455 biphasic mixture Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- YSEIIPXDAAJQSY-HOCLYGCPSA-N methyl (1R,7S)-5-(2-hydroxyethyl)-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCO)N=C2 YSEIIPXDAAJQSY-HOCLYGCPSA-N 0.000 description 3
- RXJQKHLSDKCWNQ-ZFWWWQNUSA-N methyl (1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 RXJQKHLSDKCWNQ-ZFWWWQNUSA-N 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- KKNKTNXIPXJGFZ-UHFFFAOYSA-N tert-butyl 4-(dimethylaminomethylidene)-3,5-dioxopiperidine-1-carboxylate Chemical compound CN(C)C=C1C(=O)CN(C(=O)OC(C)(C)C)CC1=O KKNKTNXIPXJGFZ-UHFFFAOYSA-N 0.000 description 3
- KAJZZLBZXOBEMD-UHFFFAOYSA-N tert-butyl n-chlorosulfonylcarbamate Chemical compound CC(C)(C)OC(=O)NS(Cl)(=O)=O KAJZZLBZXOBEMD-UHFFFAOYSA-N 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 3
- UVTDRXAIXPQKFC-BYCMXARLSA-N (1R,7S)-7-[(1R)-1-hydroxyethyl]-5-methyl-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound C[C@@H](O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 UVTDRXAIXPQKFC-BYCMXARLSA-N 0.000 description 2
- AAGYTTGCSLANIN-FQMMZHFNSA-N (1R,7S)-7-[(E)-N-[tert-butyl(dimethyl)silyl]oxy-C-methylcarbonimidoyl]-10-hydroxy-5-methyl-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound [Si](C)(C)(C(C)(C)C)O\N=C(/C)\[C@H]1N2C(N([C@H](C3=C1N(N=C3)C)C2)O)=O AAGYTTGCSLANIN-FQMMZHFNSA-N 0.000 description 2
- CYHBHDPBLIQMGV-ICSRJNTNSA-N (1R,7S)-N-[tert-butyl(dimethyl)silyl]oxy-N',5-dimethyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound C\N=C(/NO[Si](C)(C)C(C)(C)C)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 CYHBHDPBLIQMGV-ICSRJNTNSA-N 0.000 description 2
- GCFBFGAGEIYDHB-QHZVRINDSA-N (1R,7Z,7S)-N-[tert-butyl(dimethyl)silyl]oxy-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidoyl cyanide Chemical compound C(C1=CC=CC=C1)ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3C)/C(=N/O[Si](C)(C)C(C)(C)C)/C#N)=O GCFBFGAGEIYDHB-QHZVRINDSA-N 0.000 description 2
- PSQOGJFWKZPHLO-REMNUJDTSA-N (2Z)-2-hydroxyimino-2-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]acetonitrile Chemical compound Cn1ncc2[C@@H]3CN([C@H](\C(=N\O)C#N)c12)C(=O)N3OCc1ccccc1 PSQOGJFWKZPHLO-REMNUJDTSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- ZZZSOTOZBJNEMF-BBRMVZONSA-N 2-[(1R,7S)-7-(N-hydroxy-N'-methylcarbamimidoyl)-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-5-yl]acetic acid Chemical compound CN\C(=N/O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CC(O)=O)N=C2 ZZZSOTOZBJNEMF-BBRMVZONSA-N 0.000 description 2
- RCQJLZGMPPKUAB-YOEHRIQHSA-N 2-[[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino]oxyacetic acid Chemical compound CN\C(=N/OCC(O)=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 RCQJLZGMPPKUAB-YOEHRIQHSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- LYPFMWLZWKNRRA-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl methanesulfonate Chemical compound CC(C)(C)OC(=O)NCCCCOS(C)(=O)=O LYPFMWLZWKNRRA-UHFFFAOYSA-N 0.000 description 2
- RCFIFJXLMARPSD-UHFFFAOYSA-N 4-hydroxy-6-[(2-methylpropan-2-yl)oxycarbonyl]-2-trityl-5,7-dihydro-4H-pyrazolo[3,4-c]pyridine-7-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1C(C=2C(C(C1)O)=CN(N=2)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C(=O)O RCFIFJXLMARPSD-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- RIIKHAJMPRLNCC-UHFFFAOYSA-N 6-O-tert-butyl 7-O-methyl 1-methyl-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-6,7-dicarboxylate Chemical compound COC(=O)C1N(CC(=O)C2=C1N(C)N=C2)C(=O)OC(C)(C)C RIIKHAJMPRLNCC-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 241000589291 Acinetobacter Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 241001453380 Burkholderia Species 0.000 description 2
- 241000722910 Burkholderia mallei Species 0.000 description 2
- 241001136175 Burkholderia pseudomallei Species 0.000 description 2
- PQOLUGYXTBPKNF-UHFFFAOYSA-N CCCCOC(=O)C1C2=C(C=NN2)C3CN1C(=O)N3 Chemical compound CCCCOC(=O)C1C2=C(C=NN2)C3CN1C(=O)N3 PQOLUGYXTBPKNF-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 2
- ODBYIMUTLRGAOU-HOCLYGCPSA-N N-[2-[(1R,7S)-7-[N-[tert-butyl(dimethyl)silyl]oxy-N'-methylcarbamimidoyl]-10-hydroxy-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-5-yl]ethyl]acetamide Chemical compound CN\C(=N/O[Si](C)(C)C(C)(C)C)[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(CCNC(C)=O)N=C2 ODBYIMUTLRGAOU-HOCLYGCPSA-N 0.000 description 2
- WXMWNILRMRYBNF-GMAHTHKFSA-N N-[2-[(1R,7S)-7-[N-[tert-butyl(dimethyl)silyl]oxy-N'-methylcarbamimidoyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-5-yl]ethyl]acetamide Chemical compound CN\C(=N/O[Si](C)(C)C(C)(C)C)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCNC(C)=O)N=C2 WXMWNILRMRYBNF-GMAHTHKFSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 229910020346 SiS 2 Inorganic materials 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- MQRWVCIXLQAMCS-ZSOXZCCMSA-N [(1R)-5-(2-amino-2-oxoethyl)-7-[N-[tert-butyl(dimethyl)silyl]oxy-N'-methylcarbamimidoyl]-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound S(=O)(=O)(ON1C(N2C(C3=C([C@@H]1C2)C=NN3CC(=O)N)/C(/NC)=N/O[Si](C)(C)C(C)(C)C)=O)O MQRWVCIXLQAMCS-ZSOXZCCMSA-N 0.000 description 2
- QWKTUZBEVPRNSM-HOCLYGCPSA-N [(1R,7S)-5-(2-acetamidoethyl)-7-[N-[tert-butyl(dimethyl)silyl]oxy-N'-methylcarbamimidoyl]-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound S(=O)(=O)(ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3CCNC(C)=O)/C(/NC)=N/O[Si](C)(C)C(C)(C)C)=O)O QWKTUZBEVPRNSM-HOCLYGCPSA-N 0.000 description 2
- XUIJKVPHDMDGHP-FQMMZHFNSA-N [(1R,7S)-7-[(E)-N-[tert-butyl(dimethyl)silyl]oxy-C-methylcarbonimidoyl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound S(=O)(=O)(ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3C)/C(/C)=N/O[Si](C)(C)C(C)(C)C)=O)O XUIJKVPHDMDGHP-FQMMZHFNSA-N 0.000 description 2
- PKJYAFSTYYYUGG-AAEUAGOBSA-N [(1R,7S)-7-[N-[tert-butyl(dimethyl)silyl]oxy-N'-methylcarbamimidoyl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound S(=O)(=O)(ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3C)/C(/NC)=N/O[Si](C)(C)C(C)(C)C)=O)O PKJYAFSTYYYUGG-AAEUAGOBSA-N 0.000 description 2
- SFOIVKGXSGEMLJ-XPUUQOCRSA-N [[C-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-N-methylcarbonimidoyl]amino] carbamate Chemical compound C\N=C(/NOC(N)=O)[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(C)N=C2 SFOIVKGXSGEMLJ-XPUUQOCRSA-N 0.000 description 2
- BCRWAFNDVLGDDP-RDJZCZTQSA-N [[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino] acetate Chemical compound C\N=C(/NOC(C)=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 BCRWAFNDVLGDDP-RDJZCZTQSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229960003376 levofloxacin Drugs 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- NWMKVZIUEYHNDW-RDJZCZTQSA-N methyl (1R,7S)-5-(2-methylsulfonyloxyethyl)-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCOS(C)(=O)=O)N=C2 NWMKVZIUEYHNDW-RDJZCZTQSA-N 0.000 description 2
- DESVTLBFXBWPQT-HBYGCAHESA-N methyl (1R,7S)-5-[(2E)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxyimino]ethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C\C=N\OCCNC(=O)OC(C)(C)C)N=C2 DESVTLBFXBWPQT-HBYGCAHESA-N 0.000 description 2
- ZBGNCOJCOITFIE-UHFFFAOYSA-N methyl 1-methyl-4-(phenylmethoxyamino)-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridine-7-carboxylate Chemical compound C(C1=CC=CC=C1)ONC1C2=C(C(NC1)C(=O)OC)N(N=C2)C ZBGNCOJCOITFIE-UHFFFAOYSA-N 0.000 description 2
- VHIGSGMUCCPWFE-UHFFFAOYSA-N methyl 4-(phenylmethoxyamino)-4,5,6,7-tetrahydro-1h-pyrazolo[3,4-c]pyridine-7-carboxylate Chemical compound C12=CNN=C2C(C(=O)OC)NCC1NOCC1=CC=CC=C1 VHIGSGMUCCPWFE-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000008261 resistance mechanism Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- GVFXQWVQNDXEEL-UHFFFAOYSA-N tert-butyl 1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-4-hydroxy-5,7-dihydro-4H-pyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound [Si](C)(C)(C(C)(C)C)OCCN1N=CC2=C1CN(CC2O)C(=O)OC(C)(C)C GVFXQWVQNDXEEL-UHFFFAOYSA-N 0.000 description 2
- SDDNHCVVOSYLCT-UHFFFAOYSA-N tert-butyl 1-methyl-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC(=O)C2=C1N(C)N=C2 SDDNHCVVOSYLCT-UHFFFAOYSA-N 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- PIBBIUFDMJQHDY-ICSRJNTNSA-N tert-butyl 2-methyl-2-[[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino]oxypropanoate Chemical compound C1(=O)N2C[C@H](N1OCC1=CC=CC=C1)C1=C([C@H]2/C(=N/OC(C(=O)OC(C)(C)C)(C)C)/NC)N(N=C1)C PIBBIUFDMJQHDY-ICSRJNTNSA-N 0.000 description 2
- HQNFYLYOZNJLOC-NKUTVCTDSA-N tert-butyl 3-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-4,5-dihydro-1,2-oxazole-5-carboxylate Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C1=NOC(C1)C(=O)OC(C)(C)C HQNFYLYOZNJLOC-NKUTVCTDSA-N 0.000 description 2
- FOACYMWDXLSAPQ-UHFFFAOYSA-N tert-butyl 4-oxo-2-trityl-5,7-dihydropyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound O=C1C=2C(CN(C1)C(=O)OC(C)(C)C)=NN(C=2)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 FOACYMWDXLSAPQ-UHFFFAOYSA-N 0.000 description 2
- HWZVJVTXFFMPDF-NBNFEVQESA-N tert-butyl N-[[(Z)-N-hydroxy-C-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]-methylamino]carbamate Chemical compound CN(NC(=O)OC(C)(C)C)C(=N/O)\[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 HWZVJVTXFFMPDF-NBNFEVQESA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- UEITVNRAAYCYFD-CBAPKCEASA-N (1R,7S)-10-hydroxy-N-methoxy-N',5-dimethyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound CON\C(=N/C)[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(C)N=C2 UEITVNRAAYCYFD-CBAPKCEASA-N 0.000 description 1
- AKRBEKKJUNLZRX-FPOVZHCZSA-N (1R,7S)-5-(2-aminoethyl)-N-[tert-butyl(dimethyl)silyl]oxy-N'-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound C\N=C(/NO[Si](C)(C)C(C)(C)C)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCN)N=C2 AKRBEKKJUNLZRX-FPOVZHCZSA-N 0.000 description 1
- JJLPQXCUDIINNK-LSDHHAIUSA-N (1R,7S)-5-(2-azidoethyl)-7-(hydroxymethyl)-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound OC[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCN=[N+]=[N-])N=C2 JJLPQXCUDIINNK-LSDHHAIUSA-N 0.000 description 1
- YETXYCRREJHKNJ-LSDHHAIUSA-N (1R,7S)-5-(2-azidoethyl)-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carbaldehyde Chemical compound [N-]=[N+]=NCCN1N=CC2=C1[C@@H](C=O)N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O YETXYCRREJHKNJ-LSDHHAIUSA-N 0.000 description 1
- NMPMLCYSXKUGPS-OLMJXDNASA-N (1R,7S)-5-[(2E)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxyimino]ethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylic acid Chemical compound CC(C)(C)OC(=O)NCCO\N=C\CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C(O)=O NMPMLCYSXKUGPS-OLMJXDNASA-N 0.000 description 1
- BSEPUVDAEAXOKP-YJBOKZPZSA-N (1R,7S)-5-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylic acid Chemical compound CC(C)(C)OC(=O)CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C(O)=O BSEPUVDAEAXOKP-YJBOKZPZSA-N 0.000 description 1
- JLBOQNLXWQEOFZ-UONOGXRCSA-N (1R,7S)-7-(hydroxymethyl)-5-methyl-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound CN1N=CC2=C1[C@@H](CO)N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O JLBOQNLXWQEOFZ-UONOGXRCSA-N 0.000 description 1
- ANQTXOXZKFQKOH-TWZNPMNKSA-N (1R,7S)-7-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydro-1,2-oxazol-3-yl]-10-hydroxy-5-methyl-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(O)C1=O)C1=NOC(CO[Si](C)(C)C(C)(C)C)C1 ANQTXOXZKFQKOH-TWZNPMNKSA-N 0.000 description 1
- UMPFOWNYZQZXMW-LSDHHAIUSA-N (1R,7S)-7-acetyl-5-methyl-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C(C)=O UMPFOWNYZQZXMW-LSDHHAIUSA-N 0.000 description 1
- DYCSGFUAKRDCES-AAEUAGOBSA-N (1R,7S)-N-[tert-butyl(dimethyl)silyl]oxy-10-hydroxy-N',5-dimethyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound C\N=C(/NO[Si](C)(C)C(C)(C)C)[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(C)N=C2 DYCSGFUAKRDCES-AAEUAGOBSA-N 0.000 description 1
- OXNRWSBHFGMKOY-HOCLYGCPSA-N (1R,7S)-N-methoxy-N',5-dimethyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboximidamide Chemical compound CON\C(=N/C)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 OXNRWSBHFGMKOY-HOCLYGCPSA-N 0.000 description 1
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- FZENGILVLUJGJX-IHWYPQMZSA-N (Z)-acetaldehyde oxime Chemical compound C\C=N/O FZENGILVLUJGJX-IHWYPQMZSA-N 0.000 description 1
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 1
- SEPMCVDJMHIMOQ-UHFFFAOYSA-N 1,4,5,7-tetrahydropyrazolo[3,4-c]pyridine-6-carboxylic acid Chemical compound C1N(C(=O)O)CCC2=C1NN=C2 SEPMCVDJMHIMOQ-UHFFFAOYSA-N 0.000 description 1
- RYZCOJFLAFWWBQ-UHFFFAOYSA-N 1-(2-hydroxyethyl)-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-6-carboxylic acid Chemical compound OCCn1ncc2c1CN(CC2=O)C(O)=O RYZCOJFLAFWWBQ-UHFFFAOYSA-N 0.000 description 1
- FIGWHZAZVQJDNF-UHFFFAOYSA-N 1-methyl-6-[(2-methylpropan-2-yl)oxycarbonyl]-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-7-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1C(C2=C(C(C1)=O)C=NN2C)C(=O)O FIGWHZAZVQJDNF-UHFFFAOYSA-N 0.000 description 1
- ZMIIQXLXWATXIB-UHFFFAOYSA-N 1-n',6-n'-bis(4-methoxybenzoyl)hexanedihydrazide Chemical compound C1=CC(OC)=CC=C1C(=O)NNC(=O)CCCCC(=O)NNC(=O)C1=CC=C(OC)C=C1 ZMIIQXLXWATXIB-UHFFFAOYSA-N 0.000 description 1
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- QQDCXQURAAVVHQ-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl methanesulfonate Chemical compound CC(C)(C)OC(=O)NCCOS(C)(=O)=O QQDCXQURAAVVHQ-UHFFFAOYSA-N 0.000 description 1
- MLZAFEOJTFYGSN-IDTAVKCVSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(4-methylpiperidin-1-yl)-3h-purin-6-one Chemical compound C1CC(C)CCN1C(N1[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=NC2=C1NC(N)=NC2=O MLZAFEOJTFYGSN-IDTAVKCVSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- GBHCABUWWQUMAJ-UHFFFAOYSA-N 2-hydrazinoethanol Chemical compound NNCCO GBHCABUWWQUMAJ-UHFFFAOYSA-N 0.000 description 1
- HMDOHALMCRHCFZ-UHFFFAOYSA-N 2-nitro-n-phenylmethoxybenzenesulfonamide Chemical compound [O-][N+](=O)C1=CC=CC=C1S(=O)(=O)NOCC1=CC=CC=C1 HMDOHALMCRHCFZ-UHFFFAOYSA-N 0.000 description 1
- DFNLGXASDHNZNF-XVKPBYJWSA-N 3-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-4-methyl-1,2,4-oxadiazin-5-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(O)C1=O)C1=NOCC(=O)N1C DFNLGXASDHNZNF-XVKPBYJWSA-N 0.000 description 1
- JMWUKXJODXWHCS-XPUUQOCRSA-N 3-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-4-methyl-1,2,4-oxadiazol-5-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(O)C1=O)C1=NOC(=O)N1C JMWUKXJODXWHCS-XPUUQOCRSA-N 0.000 description 1
- JPSGFNBHAYOLEK-UHFFFAOYSA-N 4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-1,3,6-trien-10-yl hydrogen sulfate Chemical compound S(=O)(=O)(O)ON1CN2C=C3C(=C1C2)C=NN3 JPSGFNBHAYOLEK-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- MELUQKLYNOBGHT-RDJZCZTQSA-N 4,6,6-trimethyl-3-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-1,2,4-oxadiazin-5-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C1=NOC(C)(C)C(=O)N1C MELUQKLYNOBGHT-RDJZCZTQSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- SXVBQOZRZIUHKU-UHFFFAOYSA-N 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride Chemical compound CCN1CCN(C(Cl)=O)C(=O)C1=O SXVBQOZRZIUHKU-UHFFFAOYSA-N 0.000 description 1
- BXAPQGLJWSPVFE-ZFWWWQNUSA-N 4-methyl-3-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-1,2,4-oxadiazol-5-one Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(OCC2=CC=CC=C2)C1=O)C1=NOC(=O)N1C BXAPQGLJWSPVFE-ZFWWWQNUSA-N 0.000 description 1
- ZVUDPIBVNIMXAV-ZVBGSRNCSA-N 5-(2-azidoethyl)-7-[(E)-hydroxyiminomethyl]-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-9-one Chemical compound N(=[N+]=[N-])CCN1N=CC2=C1C(N1C(N(C2C1)OCC1=CC=CC=C1)=O)/C=N/O ZVUDPIBVNIMXAV-ZVBGSRNCSA-N 0.000 description 1
- LXNIACDLPLCQCW-UHFFFAOYSA-N 6-O-tert-butyl 7-O-methyl 4-(phenylmethoxyamino)-2-trityl-5,7-dihydro-4H-pyrazolo[3,4-c]pyridine-6,7-dicarboxylate Chemical compound C(C1=CC=CC=C1)ONC1C=2C(C(N(C1)C(=O)OC(C)(C)C)C(=O)OC)=NN(C=2)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 LXNIACDLPLCQCW-UHFFFAOYSA-N 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CYHBHDPBLIQMGV-UHFFFAOYSA-N C\N=C(/NO[Si](C)(C)C(C)(C)C)C1N2CC(N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 Chemical compound C\N=C(/NO[Si](C)(C)C(C)(C)C)C1N2CC(N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 CYHBHDPBLIQMGV-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000014912 Central Nervous System Infections Diseases 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108010054814 DNA Gyrase Proteins 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 229910021617 Indium monochloride Inorganic materials 0.000 description 1
- 208000036209 Intraabdominal Infections Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 241000589242 Legionella pneumophila Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102220470425 Melanoregulin_H35N_mutation Human genes 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 102220507945 Meteorin-like protein_H15N_mutation Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- SCEGRDBWXYBBDU-UHFFFAOYSA-N N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-4,5-dihydropyrazolo[3,4-c]pyridin-4-yl]-4-nitro-N-phenylmethoxybenzenesulfonamide Chemical compound C(C1=CC=CC=C1)ON(S(=O)(=O)C1=CC=C(C=C1)[N+](=O)[O-])C1C2=C(C=NC1)N(N=C2)CCO[Si](C)(C)C(C)(C)C SCEGRDBWXYBBDU-UHFFFAOYSA-N 0.000 description 1
- SNBQPIOSOYDSRA-YOEHRIQHSA-N N-hydroxy-2-[[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino]oxyacetamide Chemical compound CN\C(=N/OCC(=O)NO)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(C)N=C2 SNBQPIOSOYDSRA-YOEHRIQHSA-N 0.000 description 1
- 229910017864 NH2NH2-H2O Inorganic materials 0.000 description 1
- 229910017830 NH2NH2—H2O Inorganic materials 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 101150026476 PAO1 gene Proteins 0.000 description 1
- 102220526729 PHD finger protein 24_H37N_mutation Human genes 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108700020474 Penicillin-Binding Proteins Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 108010013381 Porins Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000122973 Stenotrophomonas maltophilia Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 102220634196 Transmembrane protein 126A_H45N_mutation Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- PDOHHLHGQXCHAE-XPUUQOCRSA-N [(1R,7S)-5-methyl-7-(N'-methyl-N-sulfamoyloxycarbamimidoyl)-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound C\N=C(/NOS(N)(=O)=O)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 PDOHHLHGQXCHAE-XPUUQOCRSA-N 0.000 description 1
- LKSYGBGWDFURIG-CPCISQLKSA-N [(1R,7S)-7-[4-[(4-amino-1,3-thiazol-2-yl)methyl]-5-oxo-1,2,4-oxadiazol-3-yl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound Cn1ncc2[C@@H]3CN([C@H](c4noc(=O)n4Cc4nc(N)cs4)c12)C(=O)N3OS(O)(=O)=O LKSYGBGWDFURIG-CPCISQLKSA-N 0.000 description 1
- OSEFHLHDYGEOTM-QKXFTURESA-N [(1R,7S)-7-[5-(hydroxymethyl)-4,5-dihydro-1,2-oxazol-3-yl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound Cn1ncc2[C@@H]3CN([C@H](C4=NOC(CO)C4)c12)C(=O)N3OS(O)(=O)=O OSEFHLHDYGEOTM-QKXFTURESA-N 0.000 description 1
- PWTBRXYGZXNAAI-FVKKKHHLSA-N [(1R,7S)-7-[5-(hydroxymethyl)-4-methyl-4,5-dihydro-1,2-oxazol-3-yl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound CC1C(CO)ON=C1[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 PWTBRXYGZXNAAI-FVKKKHHLSA-N 0.000 description 1
- CAELKSPICAATMQ-TWZNPMNKSA-N [(1R,7S)-7-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydro-1,2-oxazol-3-yl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound S(=O)(=O)(ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3C)C1=NOC(C1)CO[Si](C)(C)C(C)(C)C)=O)O CAELKSPICAATMQ-TWZNPMNKSA-N 0.000 description 1
- HKJOSUYXWNKZRN-CABZTGNLSA-N [(1R,7S)-7-[N-[2-(2-aminoethylamino)-2-oxoethoxy]-N'-methylcarbamimidoyl]-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] hydrogen sulfate Chemical compound C\N=C(/NOCC(=O)NCCN)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 HKJOSUYXWNKZRN-CABZTGNLSA-N 0.000 description 1
- ZSJSUGQFCVLMIX-WPRPVWTQSA-N [[C-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-N-methylcarbonimidoyl]amino] acetate Chemical compound C\N=C(/NOC(C)=O)[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(C)N=C2 ZSJSUGQFCVLMIX-WPRPVWTQSA-N 0.000 description 1
- SCPVENBELKQFHD-JQWIXIFHSA-N [[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-sulfooxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino] N-(2-acetamidoethyl)carbamate Chemical compound C\N=C(/NOC(=O)NCCNC(C)=O)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 SCPVENBELKQFHD-JQWIXIFHSA-N 0.000 description 1
- VQMHUXZUAMCGTF-JQWIXIFHSA-N [[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-sulfooxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino] N-(4-aminobutyl)carbamate Chemical compound S(=O)(=O)(ON1C(N2[C@@H](C3=C([C@@H]1C2)C=NN3C)/C(/NC)=N/OC(NCCCCN)=O)=O)O VQMHUXZUAMCGTF-JQWIXIFHSA-N 0.000 description 1
- MYWKFJGQRUOOSW-XPUUQOCRSA-N [[N-methyl-C-[(1R,7S)-5-methyl-9-oxo-10-sulfooxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]amino] carbamate Chemical compound C\N=C(/NOC(N)=O)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(C)c12 MYWKFJGQRUOOSW-XPUUQOCRSA-N 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 229960001171 acetohydroxamic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 208000037815 bloodstream infection Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 108010068385 carbapenemase Proteins 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 208000010227 enterocolitis Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 208000011323 eye infectious disease Diseases 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229940118764 francisella tularensis Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 244000000058 gram-negative pathogen Species 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- APHGZSBLRQFRCA-UHFFFAOYSA-M indium(1+);chloride Chemical compound [In]Cl APHGZSBLRQFRCA-UHFFFAOYSA-M 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 229940115932 legionella pneumophila Drugs 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- PCAYUZJIIVJQNV-LPHOPBHVSA-N methyl (1R,7S)-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2,5-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=CN(CC(=O)OC(C)(C)C)N=C12 PCAYUZJIIVJQNV-LPHOPBHVSA-N 0.000 description 1
- LPTPPVKZCJZNRD-BBRMVZONSA-N methyl (1R,7S)-5-(2,2-dihydroxyethyl)-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CC(O)O)N=C2 LPTPPVKZCJZNRD-BBRMVZONSA-N 0.000 description 1
- JAHMYTCFGYQNOI-LPHOPBHVSA-N methyl (1R,7S)-5-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CC(=O)OC(C)(C)C)N=C2 JAHMYTCFGYQNOI-LPHOPBHVSA-N 0.000 description 1
- KGYPNQVFVXVPTK-FPOVZHCZSA-N methyl (1R,7S)-5-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-9-oxo-10-phenylmethoxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-diene-7-carboxylate Chemical compound COC(=O)[C@H]1N2C[C@H](N(OCC3=CC=CC=C3)C2=O)C2=C1N(CCO[Si](C)(C)C(C)(C)C)N=C2 KGYPNQVFVXVPTK-FPOVZHCZSA-N 0.000 description 1
- GZLITLMKZBSRLD-XOMXBQTJSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C.COC(=O)\C=C\C GZLITLMKZBSRLD-XOMXBQTJSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 206010033072 otitis externa Diseases 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- UKODFQOELJFMII-UHFFFAOYSA-N pentamethyldiethylenetriamine Chemical compound CN(C)CCN(C)CCN(C)C UKODFQOELJFMII-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- 102000007739 porin activity proteins Human genes 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000004929 pyrrolidonyl group Chemical group N1(C(CCC1)=O)* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 102220342166 rs138070585 Human genes 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- DENRJGZATCJYJD-QMGYSKNISA-M sodium [(1R,7S)-7-(N-hydroxy-N'-methylcarbamimidoyl)-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-10-yl] sulfate Chemical compound [Na+].CN\C(=N/O)[C@H]1N2C[C@H](N(OS([O-])(=O)=O)C2=O)C2=C1N(C)N=C2 DENRJGZATCJYJD-QMGYSKNISA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- CQJIUOSNROVOKO-ZSOIEALJSA-N tert-butyl (4E)-4-hydrazinylidene-5,7-dihydro-1H-pyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound N(/N)=C\1/C2=C(CN(C/1)C(=O)OC(C)(C)C)NN=C2 CQJIUOSNROVOKO-ZSOIEALJSA-N 0.000 description 1
- GWXBFNDBHVWCCY-UHFFFAOYSA-N tert-butyl 1-(2-hydroxyethyl)-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound CC(C)(C)OC(=O)N1Cc2c(cnn2CCO)C(=O)C1 GWXBFNDBHVWCCY-UHFFFAOYSA-N 0.000 description 1
- LTYDJYVNADLXOC-UHFFFAOYSA-N tert-butyl 1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxo-5,7-dihydropyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound [Si](C)(C)(C(C)(C)C)OCCN1N=CC2=C1CN(CC2=O)C(=O)OC(C)(C)C LTYDJYVNADLXOC-UHFFFAOYSA-N 0.000 description 1
- IGVNJALYNQVQIT-UHFFFAOYSA-N tert-butyl 2-bromo-2-methylpropanoate Chemical compound CC(C)(C)OC(=O)C(C)(C)Br IGVNJALYNQVQIT-UHFFFAOYSA-N 0.000 description 1
- KWNDKZADLGFSKE-UHFFFAOYSA-N tert-butyl 3,5-dioxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(=O)CC(=O)C1 KWNDKZADLGFSKE-UHFFFAOYSA-N 0.000 description 1
- ASDTVVPUAINJAC-CCQDYZPNSA-N tert-butyl 3-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]-4,5-dihydro-1,2-oxazole-5-carboxylate Chemical compound CN1N=CC2=C1[C@H](N1C[C@@H]2N(O)C1=O)C1=NOC(C1)C(=O)OC(C)(C)C ASDTVVPUAINJAC-CCQDYZPNSA-N 0.000 description 1
- CQJIUOSNROVOKO-UHFFFAOYSA-N tert-butyl 4-hydrazinylidene-5,7-dihydro-1H-pyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound N(N)=C1C=2C(CN(C1)C(=O)OC(C)(C)C)=NNC=2 CQJIUOSNROVOKO-UHFFFAOYSA-N 0.000 description 1
- PPMNMHLOYSFMNR-UHFFFAOYSA-N tert-butyl 4-hydroxy-2-trityl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound N1=C2CN(C(=O)OC(C)(C)C)CC(O)C2=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 PPMNMHLOYSFMNR-UHFFFAOYSA-N 0.000 description 1
- CVZHZXNTNPPKKB-UHFFFAOYSA-N tert-butyl 4-oxo-5,7-dihydro-1H-pyrazolo[3,4-c]pyridine-6-carboxylate Chemical compound O=C1C2=C(CN(C1)C(=O)OC(C)(C)C)NN=C2 CVZHZXNTNPPKKB-UHFFFAOYSA-N 0.000 description 1
- TXPLJSKVSPTWOM-JQWIXIFHSA-N tert-butyl N-[2-[(1R,7S)-7-(N-hydroxy-N'-methylcarbamimidoyl)-9-oxo-10-sulfooxy-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-5-yl]ethyl]carbamate Chemical compound C\N=C(/NO)[C@H]1N2C[C@H](N(OS(O)(=O)=O)C2=O)c2cnn(CCNC(=O)OC(C)(C)C)c12 TXPLJSKVSPTWOM-JQWIXIFHSA-N 0.000 description 1
- QPTSIQMAUGGRRZ-KXVQEXJKSA-N tert-butyl N-[[(Z)-N-hydroxy-C-[(1R,7S)-10-hydroxy-5-methyl-9-oxo-4,5,8,10-tetrazatricyclo[6.2.1.02,6]undeca-2(6),3-dien-7-yl]carbonimidoyl]-methylamino]carbamate Chemical compound CN(NC(=O)OC(C)(C)C)C(=N/O)\[C@H]1N2C[C@H](N(O)C2=O)C2=C1N(C)N=C2 QPTSIQMAUGGRRZ-KXVQEXJKSA-N 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- JRLJOAREDJOYLW-UHFFFAOYSA-N tert-butyl n-(2-aminooxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCON JRLJOAREDJOYLW-UHFFFAOYSA-N 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- LIYMTLVBAVHPBU-UHFFFAOYSA-N tert-butyl n-(4-hydroxybutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCO LIYMTLVBAVHPBU-UHFFFAOYSA-N 0.000 description 1
- UZRUVUYVHGPEAP-UHFFFAOYSA-N tert-butyl n-(methylamino)carbamate Chemical compound CNNC(=O)OC(C)(C)C UZRUVUYVHGPEAP-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Classifications
-
- 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
- C07D471/18—Bridged 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
- C07D471/08—Bridged 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
- A61K31/435—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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762502867P | 2017-05-08 | 2017-05-08 | |
| PCT/US2018/031593 WO2018208769A1 (en) | 2017-05-08 | 2018-05-08 | Compounds and methods for treating bacterial infections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201992370A1 EA201992370A1 (ru) | 2020-03-10 |
| EA038393B1 true EA038393B1 (ru) | 2021-08-20 |
Family
ID=62223332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201992370A EA038393B1 (ru) | 2017-05-08 | 2018-05-08 | Соединения и способы для лечения бактериальных инфекций |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US11046694B2 (https=) |
| EP (1) | EP3630111B1 (https=) |
| JP (1) | JP7058322B2 (https=) |
| KR (1) | KR102611447B1 (https=) |
| CN (1) | CN110709081B (https=) |
| AU (1) | AU2018266640B2 (https=) |
| CY (1) | CY1125340T1 (https=) |
| DK (1) | DK3630111T3 (https=) |
| EA (1) | EA038393B1 (https=) |
| ES (1) | ES2907858T3 (https=) |
| HR (1) | HRP20220231T1 (https=) |
| HU (1) | HUE057592T2 (https=) |
| IL (1) | IL270380B (https=) |
| LT (1) | LT3630111T (https=) |
| MA (1) | MA48743A (https=) |
| MX (1) | MX385203B (https=) |
| MY (1) | MY201377A (https=) |
| NZ (1) | NZ758200A (https=) |
| PE (1) | PE20200333A1 (https=) |
| PH (1) | PH12019502509A1 (https=) |
| PL (1) | PL3630111T3 (https=) |
| PT (1) | PT3630111T (https=) |
| SG (1) | SG11201909443YA (https=) |
| SI (1) | SI3630111T1 (https=) |
| SM (1) | SMT202200110T1 (https=) |
| TW (1) | TWI791018B (https=) |
| WO (1) | WO2018208769A1 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11905286B2 (en) | 2018-08-09 | 2024-02-20 | Antabio Sas | Diazabicyclooctanones as inhibitors of serine beta-lactamases |
| SG11202101255UA (en) | 2018-08-09 | 2021-03-30 | Antabio Sas | Diazabicyclooctanones as inhibitors of serine beta-lactamases |
| CN111675641B (zh) * | 2020-06-04 | 2023-09-08 | 宁夏农林科学院农业资源与环境研究所（宁夏土壤与植物营养重点实验室） | 单环β-内酰胺类化合物、单环内酰胺类化合物盐及其制备方法 |
| US12410166B2 (en) | 2021-05-07 | 2025-09-09 | Ningxia Academy Of Agriculture And Forestry Sciences | Sulfonylamidine substituted compounds and their use as beta-lactamase inhibitors |
| US11814385B2 (en) | 2021-06-25 | 2023-11-14 | University Of South Florida | Small molecule inhibitors targeting Clostridioides difficile sporulation |
| WO2025064681A1 (en) * | 2023-09-19 | 2025-03-27 | Entasis Therapeutics Inc. | Compounds and methods for treating bacterial infections |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090018329A1 (en) * | 2002-12-06 | 2009-01-15 | Novexel | Novel heterocyclic compounds, their preparation and their use as medicaments, in particular as antibacterials and beta-lactamase inhibitors |
| US20100093784A1 (en) * | 2008-10-10 | 2010-04-15 | Novexel | Novel heterocyclic nitrogenous compounds, their preparation and their use as antibacterial medicaments |
| WO2013030735A1 (en) * | 2011-08-30 | 2013-03-07 | Wockhardt Limited | 1,6- diazabicyclo [3,2,1] octan- 7 - one derivatives and their use in the treatment of bacterial infections |
| US20130289012A1 (en) * | 2012-03-30 | 2013-10-31 | Cubist Pharmaceuticals, Inc. | 1,2,4-oxadiazole and 1,2,4-thiadiazole beta-lactamase inhibitors |
| WO2014141132A1 (en) * | 2013-03-14 | 2014-09-18 | Naeja Pharmaceutical Inc. | NEW HETEROCYCLIC COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS AND β-LACTAMASE INHIBITORS |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUT74682A (en) | 1993-12-29 | 1997-01-28 | Pfizer | Diazabicyclic neurokinin antagonists and pharmaceutical compositions containing them |
| FR2812635B1 (fr) | 2000-08-01 | 2002-10-11 | Aventis Pharma Sa | Nouveaux composes heterocycliques, preparation et utilisation comme medicaments notamment comme anti- bacteriens |
| FR2825705B1 (fr) | 2001-06-08 | 2005-05-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens |
| FR2835186B1 (fr) | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
| FR2848210B1 (fr) * | 2002-12-06 | 2007-10-19 | Aventis Pharma Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens et inhibiteurs de beta-lactamases |
| US7507727B2 (en) * | 2003-04-07 | 2009-03-24 | Cylene Pharmaceuticals, Inc. | Substituted quinobenzoxazine analogs and methods of using thereof |
| FR2914923B1 (fr) | 2007-04-12 | 2013-06-14 | Novexel | Nouveaux composes heterocycliques azotes,leur preparation et leur utilisation comme medicaments antibacteriens. |
| ES2533826T3 (es) | 2008-01-18 | 2015-04-15 | Merck Sharp & Dohme Corp. | Inhibidores de beta-lactamasa |
| FR2930553B1 (fr) | 2008-04-29 | 2010-05-21 | Novexel | Composes azabicycliques, leur preparation et leur utilisation comme medicaments, notamment inhibiteurs de beta-lactamases |
| EP2921559A1 (en) | 2008-06-19 | 2015-09-23 | Astra Zeneca Holding France | Use of (1r,2s,5r) 1,6-diazabicyclo [3.2.1]octane-2-carboxamide, 7-oxo-6-(sulfooxy)-, monosodium salt as a diagnostic reagent for detecting serine beta-lactamases |
| FR2936798B1 (fr) | 2008-10-03 | 2012-09-28 | Novexel | Nouveaux composes heterocycliques azotes, leur preparation et leur utilisation comme medicaments antibacteriens. |
| FR2936951B1 (fr) | 2008-10-10 | 2010-12-03 | Novexel | Nouvelles combinaisons de composes heterocycliques azotes antibacteriens avec d'autres composes antibacteriens et leur utilisation comme medicaments |
| FR2951171A1 (fr) | 2009-10-09 | 2011-04-15 | Novexel | Nouveau sel de sodium d'un compose azabicyclique sous forme enantiomere cristallisee et nouvelles formes polymorphes et pseudopolymorphes ainsi que leur preparation |
| US9744160B2 (en) | 2011-07-26 | 2017-08-29 | Wockhardt Limited | Pharmaceutical compositions comprising sulbactam and beta-lactamase inhibitor |
| EP2768503A1 (en) | 2011-07-26 | 2014-08-27 | Wockhardt Limited | Pharmaceutical compositions comprising beta-lactam antibiotic, sulbactam and beta-lactamase inhibitor |
| RU2578370C2 (ru) | 2011-08-27 | 2016-03-27 | Вокхардт Лимитед | Производные 1,6- диазабицикло [3,2,1] октан-7-она и их применение при лечении бактериальных инфекционных болезней |
| EP3052497B1 (en) | 2011-09-13 | 2017-06-28 | Wockhardt Limited | Nitrogen containing compounds and their use |
| US8796257B2 (en) | 2011-12-02 | 2014-08-05 | Naeja Pharmaceutical Inc. | Bicyclic compounds and their use as antibacterial agents and β-lactamase inhibitors |
| EP2814483A2 (en) | 2012-02-15 | 2014-12-24 | Rempex Pharmaceuticals, Inc. | Methods of treating bacterial infections |
| US8969570B2 (en) | 2012-03-30 | 2015-03-03 | Cubist Pharmaceuticals, Inc. | Beta-lactamase inhibitors |
| TW201343645A (zh) | 2012-03-30 | 2013-11-01 | Cubist Pharm Inc | １，３，４－□二唑及１，３，４－噻二唑β－內醯胺酶抑制劑 |
| KR20150003777A (ko) | 2012-03-30 | 2015-01-09 | 큐비스트 파마슈티컬즈 인코포레이티드 | 이속사졸 β-락타마제 억제제 |
| AR090539A1 (es) * | 2012-04-02 | 2014-11-19 | Astrazeneca Ab | COMPUESTOS INHIBIDORES DE b LACTAMASA |
| RU2693898C2 (ru) | 2012-05-30 | 2019-07-05 | Мейдзи Сейка Фарма Ко., Лтд. | НОВЫЙ ИНГИБИТОР бета-ЛАКТАМАЗЫ И СПОСОБ ЕГО ПОЛУЧЕНИЯ |
| BR112015003592B1 (pt) | 2012-08-25 | 2020-04-14 | Wockhardt Ltd | derivados de 1,6-diazabiciclo[3,2,1]octan-7-ona e seu uso no tratamento de infecções bacterianas |
| WO2014033561A1 (en) | 2012-09-03 | 2014-03-06 | Wockhardt Limited | Antibacterial compositions |
| WO2014122468A1 (en) | 2013-02-06 | 2014-08-14 | Astrazeneca Ab | Combination therapy for the treatment of nosocomial pneumonia |
| KR102542392B1 (ko) | 2014-11-17 | 2023-06-09 | 엔타시스 테라퓨틱스 리미티드 | 내성 박테리아 감염의 치료를 위한 배합물 치료제 |
| CN114591223B (zh) | 2016-09-16 | 2025-01-24 | 恩塔西斯治疗有限公司 | β-内酰胺酶抑制剂化合物 |
-
2018
- 2018-05-08 NZ NZ758200A patent/NZ758200A/en unknown
- 2018-05-08 EP EP18726702.6A patent/EP3630111B1/en active Active
- 2018-05-08 DK DK18726702.6T patent/DK3630111T3/da active
- 2018-05-08 MY MYPI2019006163A patent/MY201377A/en unknown
- 2018-05-08 PL PL18726702T patent/PL3630111T3/pl unknown
- 2018-05-08 AU AU2018266640A patent/AU2018266640B2/en active Active
- 2018-05-08 LT LTEPPCT/US2018/031593T patent/LT3630111T/lt unknown
- 2018-05-08 MX MX2019013291A patent/MX385203B/es unknown
- 2018-05-08 US US16/611,065 patent/US11046694B2/en active Active
- 2018-05-08 SG SG11201909443Y patent/SG11201909443YA/en unknown
- 2018-05-08 HU HUE18726702A patent/HUE057592T2/hu unknown
- 2018-05-08 ES ES18726702T patent/ES2907858T3/es active Active
- 2018-05-08 CN CN201880030289.8A patent/CN110709081B/zh active Active
- 2018-05-08 MA MA048743A patent/MA48743A/fr unknown
- 2018-05-08 SI SI201830571T patent/SI3630111T1/sl unknown
- 2018-05-08 KR KR1020197035865A patent/KR102611447B1/ko active Active
- 2018-05-08 JP JP2020512769A patent/JP7058322B2/ja active Active
- 2018-05-08 HR HRP20220231TT patent/HRP20220231T1/hr unknown
- 2018-05-08 TW TW107115559A patent/TWI791018B/zh active
- 2018-05-08 EA EA201992370A patent/EA038393B1/ru unknown
- 2018-05-08 SM SM20220110T patent/SMT202200110T1/it unknown
- 2018-05-08 IL IL270380A patent/IL270380B/en unknown
- 2018-05-08 PT PT187267026T patent/PT3630111T/pt unknown
- 2018-05-08 PE PE2019002309A patent/PE20200333A1/es unknown
- 2018-05-08 WO PCT/US2018/031593 patent/WO2018208769A1/en not_active Ceased
-
2019
- 2019-11-08 PH PH12019502509A patent/PH12019502509A1/en unknown
-
2022
- 2022-02-23 CY CY20221100157T patent/CY1125340T1/el unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090018329A1 (en) * | 2002-12-06 | 2009-01-15 | Novexel | Novel heterocyclic compounds, their preparation and their use as medicaments, in particular as antibacterials and beta-lactamase inhibitors |
| US20100093784A1 (en) * | 2008-10-10 | 2010-04-15 | Novexel | Novel heterocyclic nitrogenous compounds, their preparation and their use as antibacterial medicaments |
| WO2013030735A1 (en) * | 2011-08-30 | 2013-03-07 | Wockhardt Limited | 1,6- diazabicyclo [3,2,1] octan- 7 - one derivatives and their use in the treatment of bacterial infections |
| US20130289012A1 (en) * | 2012-03-30 | 2013-10-31 | Cubist Pharmaceuticals, Inc. | 1,2,4-oxadiazole and 1,2,4-thiadiazole beta-lactamase inhibitors |
| WO2014141132A1 (en) * | 2013-03-14 | 2014-09-18 | Naeja Pharmaceutical Inc. | NEW HETEROCYCLIC COMPOUNDS AND THEIR USE AS ANTIBACTERIAL AGENTS AND β-LACTAMASE INHIBITORS |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA038393B1 (ru) | Соединения и способы для лечения бактериальных инфекций | |
| JP7299837B2 (ja) | 化合物、組成物、および使用方法 | |
| US10227331B2 (en) | Metallo-β-lactamase inhibitors | |
| KR102932904B1 (ko) | 새로운 화합물 및 그 용도 | |
| RS51927B (sr) | Jedinjenja pirido (2,3-d)pirimidinona i njihova upotreba kao inhibitora p13 | |
| JP2013533868A (ja) | タンパク質チロシンキナーゼ阻害剤としての新規ホモピペラジン誘導体およびそれらの医薬使用 | |
| KR20180066264A (ko) | 세펨 화합물, 그의 제조 및 용도 | |
| TW200914457A (en) | Pyrimidodiazepinone derivative | |
| WO2018045971A1 (zh) | 吡啶并五元芳香环类化合物、其制备方法及用途 | |
| WO2014072930A2 (en) | Fused pyridine derivatives as antibacterial agents | |
| HK1197238A1 (en) | 5 - benzylaminomethyl - 6 - aminopyrazolo [3, 4 -b] pyridine derivatives as cholesteryl ester -transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis | |
| CA3059773C (en) | Compounds and methods for treating bacterial infections | |
| HK40026676B (en) | Compounds and methods for treating bacterial infections | |
| WO2018129008A1 (en) | Compounds and methods for treating bacterial infections | |
| BR112019023130B1 (pt) | Compostos antibacterianos, composição farmacêutica que os compreende, e usos dos mesmos | |
| EP4482583B1 (en) | Zwitterionic antibacterial compounds | |
| JPWO2014051055A1 (ja) | キヌクリジンウレア誘導体及びその医薬用途 | |
| WO2025248051A1 (en) | Acrylamide derivatives for the treatment of diseases associated with pathogenic bacteria in the gastrointestinal system | |
| US20250282785A1 (en) | Pyrrolidinone derivatives as inhibitors of nf kappa b inducing kinase | |
| CN120569379A (zh) | 芳香乙炔类衍生物及其制备方法和用途 | |
| CN120518607A (zh) | 并环类衍生物抑制剂、其制备方法和应用 | |
| WO2015114317A1 (en) | 5h-isothiazolo[4,5-c]pyridine-3,4-dione or 5h-pyrazolo[4,3-c]pyridin-3,4-dione as antibacterial compounds | |
| HK1117503A (en) | Novel oxadiazole derivatives and their medical use |