RU2733402C2 - Бициклические арильные монобактамовые соединения и способы их применения для лечения бактериальных инфекций - Google Patents

Info

Publication number

RU2733402C2

RU2733402C2 RU2018134948A RU2018134948A RU2733402C2 RU 2733402 C2 RU2733402 C2 RU 2733402C2 RU 2018134948 A RU2018134948 A RU 2018134948A RU 2018134948 A RU2018134948 A RU 2018134948A RU 2733402 C2 RU2733402 C2 RU 2733402C2

Authority

RU

Russia

Prior art keywords

tert

amino

mmol

oxy

butyl

Prior art date

2016-03-07

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 330
• -1 Bicyclic aryl monobactam compounds Chemical class 0.000 title abstract description 545
• 238000000034 method Methods 0.000 title abstract description 70
• 208000035143 Bacterial infection Diseases 0.000 title abstract description 18
• 208000022362 bacterial infectious disease Diseases 0.000 title abstract description 18
• 150000003839 salts Chemical class 0.000 claims abstract description 179
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 112
• 239000003814 drug Substances 0.000 abstract description 16
• 239000000126 substance Substances 0.000 abstract description 8
• 230000000694 effects Effects 0.000 abstract description 6
• 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
• 239000000243 solution Substances 0.000 description 252
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 212
• 239000000203 mixture Substances 0.000 description 186
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 168
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 156
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 130
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
• 235000019439 ethyl acetate Nutrition 0.000 description 102
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
• 239000011541 reaction mixture Substances 0.000 description 96
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 89
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 88
• KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 description 76
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
• 239000002904 solvent Substances 0.000 description 71
• 239000000741 silica gel Substances 0.000 description 66
• 229910002027 silica gel Inorganic materials 0.000 description 66
• 229910052757 nitrogen Inorganic materials 0.000 description 64
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 56
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
• 238000005481 NMR spectroscopy Methods 0.000 description 54
• 125000005842 heteroatom Chemical group 0.000 description 54
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 53
• 125000001841 imino group Chemical group [H]N=* 0.000 description 52
• 125000006413 ring segment Chemical group 0.000 description 52
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 50
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 49
• 229910052739 hydrogen Inorganic materials 0.000 description 44
• 239000001257 hydrogen Substances 0.000 description 44
• 239000012071 phase Substances 0.000 description 42
• 239000011734 sodium Substances 0.000 description 42
• 239000000047 product Substances 0.000 description 40
• 229910052717 sulfur Inorganic materials 0.000 description 40
• 239000007787 solid Substances 0.000 description 38
• 239000000460 chlorine Substances 0.000 description 37
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 36
• 229910052760 oxygen Inorganic materials 0.000 description 36
• 125000003118 aryl group Chemical group 0.000 description 34
• 125000000753 cycloalkyl group Chemical group 0.000 description 34
• 239000000543 intermediate Substances 0.000 description 33
• 238000004007 reversed phase HPLC Methods 0.000 description 33
• 229920006395 saturated elastomer Polymers 0.000 description 32
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 31
• 239000000706 filtrate Substances 0.000 description 30
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 30
• 229910052736 halogen Inorganic materials 0.000 description 28
• 150000002367 halogens Chemical class 0.000 description 28
• 125000002950 monocyclic group Chemical group 0.000 description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 27
• 238000004440 column chromatography Methods 0.000 description 26
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 23
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 23
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 23
• 239000012074 organic phase Substances 0.000 description 23
• 235000019260 propionic acid Nutrition 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 21
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 20
• 102000006635 beta-lactamase Human genes 0.000 description 20
• 125000002619 bicyclic group Chemical group 0.000 description 20
• 125000001424 substituent group Chemical group 0.000 description 20
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
• 239000003153 chemical reaction reagent Substances 0.000 description 19
• 241000894006 Bacteria Species 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 230000001580 bacterial effect Effects 0.000 description 18
• 239000003781 beta lactamase inhibitor Substances 0.000 description 18
• 229940126813 beta-lactamase inhibitor Drugs 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 18
• 230000002441 reversible effect Effects 0.000 description 18
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
• 235000017557 sodium bicarbonate Nutrition 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• 238000011282 treatment Methods 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
• 239000003242 anti bacterial agent Substances 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 125000004093 cyano group Chemical group *C#N 0.000 description 15
• 125000001072 heteroaryl group Chemical group 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• 150000002431 hydrogen Chemical class 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
• 239000003480 eluent Substances 0.000 description 13
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 13
• 238000001914 filtration Methods 0.000 description 13
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 12
• 229940088710 antibiotic agent Drugs 0.000 description 12
• 125000001153 fluoro group Chemical group F* 0.000 description 12
• 235000019253 formic acid Nutrition 0.000 description 12
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
• 208000015181 infectious disease Diseases 0.000 description 12
• 150000003952 β-lactams Chemical class 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 11
• LDTMNHIZDFDFFY-UHFFFAOYSA-N 2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoacetic acid Chemical compound CC(C)(C)OC(=O)NC1=NC(C(=O)C(O)=O)=CS1 LDTMNHIZDFDFFY-UHFFFAOYSA-N 0.000 description 11
• 108090000204 Dipeptidase 1 Proteins 0.000 description 11
• CDGJTKZKKHLQQN-GSVOUGTGSA-N [(3s)-3-amino-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound CC1(C)[C@H](N)C(=O)N1OS(O)(=O)=O CDGJTKZKKHLQQN-GSVOUGTGSA-N 0.000 description 11
• 125000000217 alkyl group Chemical group 0.000 description 11
• 239000008194 pharmaceutical composition Substances 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• 125000003831 tetrazolyl group Chemical group 0.000 description 11
• 239000003039 volatile agent Substances 0.000 description 11
• 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 11
• WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 10
• 230000003115 biocidal effect Effects 0.000 description 10
• 229910052799 carbon Inorganic materials 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 125000004122 cyclic group Chemical group 0.000 description 10
• 230000002401 inhibitory effect Effects 0.000 description 10
• 108060004734 metallo-beta-lactamase Proteins 0.000 description 10
• 102000020235 metallo-beta-lactamase Human genes 0.000 description 10
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 10
• CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 9
• XZLRJCSXDLXBSC-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 2-cyanoacetate Chemical group CC(C)(C)OC(=O)NCCCOC(=O)CC#N XZLRJCSXDLXBSC-UHFFFAOYSA-N 0.000 description 9
• 108020004256 Beta-lactamase Proteins 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 description 9
• DPZMUWXOAMOYDT-UHFFFAOYSA-N tert-butyl oxirane-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1CO1 DPZMUWXOAMOYDT-UHFFFAOYSA-N 0.000 description 9
• 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 8
• 125000002947 alkylene group Chemical group 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• QGXFDKHOSNJQKE-UHFFFAOYSA-N sulfuric acid;2,2,2-trifluoroacetic acid Chemical compound OS(O)(=O)=O.OC(=O)C(F)(F)F QGXFDKHOSNJQKE-UHFFFAOYSA-N 0.000 description 8
• 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 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 7
• 229960003644 aztreonam Drugs 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 229960004592 isopropanol Drugs 0.000 description 7
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• KYEHIZRUAHBSDK-GFCCVEGCSA-N tert-butyl (2R)-3-(3-formyl-4-nitrophenoxy)-2-hydroxypropanoate Chemical compound C(=O)C=1C=C(OC[C@H](C(=O)OC(C)(C)C)O)C=CC=1[N+](=O)[O-] KYEHIZRUAHBSDK-GFCCVEGCSA-N 0.000 description 7
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 239000013543 active substance Substances 0.000 description 6
• 239000003782 beta lactam antibiotic agent Substances 0.000 description 6
• 229910052681 coesite Inorganic materials 0.000 description 6
• 229910052906 cristobalite Inorganic materials 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• QSQHZXBTJCXIAV-UHFFFAOYSA-N propan-1-amine;2,2,2-trifluoroacetic acid Chemical compound CCCN.OC(=O)C(F)(F)F QSQHZXBTJCXIAV-UHFFFAOYSA-N 0.000 description 6
• NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• 239000012453 solvate Substances 0.000 description 6
• 229910052682 stishovite Inorganic materials 0.000 description 6
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 6
• 229910052905 tridymite Inorganic materials 0.000 description 6
• 239000002132 β-lactam antibiotic Substances 0.000 description 6
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• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 5
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
• 150000001412 amines Chemical group 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• FINPLSBBDVRBPA-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane;2-methoxy-2-methylpropane;2-phenylethanamine Chemical compound [Pd+]Cl.COC(C)(C)C.NCCC1=CC=CC=[C-]1.CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 FINPLSBBDVRBPA-UHFFFAOYSA-M 0.000 description 5
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 5
• 239000003937 drug carrier Substances 0.000 description 5
• 125000000623 heterocyclic group Chemical group 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 229940041009 monobactams Drugs 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• JPQCZOUBLNGLCZ-UHFFFAOYSA-N 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-oxoacetic acid Chemical compound CC(C)(C)OC(=O)NC1=NC(C(=O)C(O)=O)=NS1 JPQCZOUBLNGLCZ-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• 150000001204 N-oxides Chemical class 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
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• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 4
• 239000004599 antimicrobial Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• NDCUAPJVLWFHHB-UHNVWZDZSA-N avibactam Chemical compound C1N2[C@H](C(N)=O)CC[C@@]1([H])N(OS(O)(=O)=O)C2=O NDCUAPJVLWFHHB-UHNVWZDZSA-N 0.000 description 4
• 229960002379 avibactam Drugs 0.000 description 4
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
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• 229910017052 cobalt Inorganic materials 0.000 description 4
• 239000010941 cobalt Substances 0.000 description 4
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