JP5777725B2 - モノバクタム - Google Patents

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Publication number

JP5777725B2

JP5777725B2 JP2013541445A JP2013541445A JP5777725B2 JP 5777725 B2 JP5777725 B2 JP 5777725B2 JP 2013541445 A JP2013541445 A JP 2013541445A JP 2013541445 A JP2013541445 A JP 2013541445A JP 5777725 B2 JP5777725 B2 JP 5777725B2

Authority

JP

Japan

Prior art keywords

mmol

formula

give

solid

preparation

Prior art date

2010-11-29

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• 229960003644 aztreonam Drugs 0.000 title description 6
• 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 title 1
• 150000001875 compounds Chemical class 0.000 claims description 234
• 239000001257 hydrogen Substances 0.000 claims description 96
• 229910052739 hydrogen Inorganic materials 0.000 claims description 96
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 86
• -1 (1- (2-aminothiazol-4-yl) -2-(((2S, 3R) -2-((3-((1,5-dihydroxy- 4-oxo-1,4-dihydropyridin-2-yl) methyl) ureido) methyl) -4-oxo-1-sulfoazetidin-3-yl) amino) -2-oxoethylidene) amino Chemical group 0.000 claims description 76
• 150000003839 salts Chemical class 0.000 claims description 69
• 229910052799 carbon Inorganic materials 0.000 claims description 39
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 29
• 239000003814 drug Substances 0.000 claims description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 14
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 13
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 13
• 208000035143 Bacterial infection Diseases 0.000 claims description 12
• 239000002253 acid Substances 0.000 claims description 12
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 12
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 11
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 10
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
• 150000003852 triazoles Chemical class 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 457
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 359
• 239000007787 solid Substances 0.000 description 240
• 239000000243 solution Substances 0.000 description 226
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 212
• 238000002360 preparation method Methods 0.000 description 210
• 239000000203 mixture Substances 0.000 description 196
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 183
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
• 238000005481 NMR spectroscopy Methods 0.000 description 164
• 235000019439 ethyl acetate Nutrition 0.000 description 153
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 143
• 239000011541 reaction mixture Substances 0.000 description 136
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 134
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 131
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 107
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 93
• 238000000034 method Methods 0.000 description 90
• 239000002904 solvent Substances 0.000 description 82
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
• 239000012044 organic layer Substances 0.000 description 75
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 72
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 70
• 238000004587 chromatography analysis Methods 0.000 description 69
• 239000010410 layer Substances 0.000 description 69
• 239000000741 silica gel Substances 0.000 description 66
• 229910002027 silica gel Inorganic materials 0.000 description 66
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 65
• 208000015181 infectious disease Diseases 0.000 description 65
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 56
• 239000000725 suspension Substances 0.000 description 56
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
• 239000013058 crude material Substances 0.000 description 52
• 239000007795 chemical reaction product Substances 0.000 description 51
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 48
• 229910052757 nitrogen Inorganic materials 0.000 description 45
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
• 229910052938 sodium sulfate Inorganic materials 0.000 description 41
• 235000011152 sodium sulphate Nutrition 0.000 description 41
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
• 238000006243 chemical reaction Methods 0.000 description 40
• 239000000706 filtrate Substances 0.000 description 40
• 239000012267 brine Substances 0.000 description 38
• 238000001914 filtration Methods 0.000 description 38
• 235000019441 ethanol Nutrition 0.000 description 37
• 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 36
• 150000001721 carbon Chemical group 0.000 description 36
• 235000019253 formic acid Nutrition 0.000 description 36
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
• 239000012043 crude product Substances 0.000 description 34
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
• 235000019341 magnesium sulphate Nutrition 0.000 description 32
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 32
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 30
• 239000012065 filter cake Substances 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• 239000000047 product Substances 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 235000017557 sodium bicarbonate Nutrition 0.000 description 27
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 27
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 25
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 25
• 239000002002 slurry Substances 0.000 description 25
• 239000003607 modifier Substances 0.000 description 24
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 24
• 238000007792 addition Methods 0.000 description 23
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 17
• 229920006395 saturated elastomer Polymers 0.000 description 17
• 238000004128 high performance liquid chromatography Methods 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• 125000004093 cyano group Chemical group *C#N 0.000 description 14
• 230000002496 gastric effect Effects 0.000 description 14
• 208000027096 gram-negative bacterial infections Diseases 0.000 description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 14
• 125000006239 protecting group Chemical group 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 239000012071 phase Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 239000006260 foam Substances 0.000 description 12
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 239000000010 aprotic solvent Substances 0.000 description 11
• 239000012467 final product Substances 0.000 description 11
• 230000014759 maintenance of location Effects 0.000 description 11
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000011521 glass Substances 0.000 description 10
• 239000000543 intermediate Substances 0.000 description 10
• 125000004433 nitrogen atom Chemical group N* 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• 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 10
• 241000588747 Klebsiella pneumoniae Species 0.000 description 9
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 238000001514 detection method Methods 0.000 description 9
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
• LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 9
• 229910052717 sulfur Chemical group 0.000 description 9
• 230000009885 systemic effect Effects 0.000 description 9
• 241000589291 Acinetobacter Species 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• 208000031729 Bacteremia Diseases 0.000 description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
• 208000014912 Central Nervous System Infections Diseases 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
• 241000588724 Escherichia coli Species 0.000 description 8
• 208000008745 Healthcare-Associated Pneumonia Diseases 0.000 description 8
• 241000590002 Helicobacter pylori Species 0.000 description 8
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
• 206010031252 Osteomyelitis Diseases 0.000 description 8
• URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 8
• 208000008469 Peptic Ulcer Diseases 0.000 description 8
• 206010035664 Pneumonia Diseases 0.000 description 8
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 8
• 206010040047 Sepsis Diseases 0.000 description 8
• 206010062255 Soft tissue infection Diseases 0.000 description 8
• 125000000217 alkyl group Chemical group 0.000 description 8
• 208000025222 central nervous system infectious disease Diseases 0.000 description 8
• 239000000460 chlorine Substances 0.000 description 8
• 238000010828 elution Methods 0.000 description 8
• 206010014665 endocarditis Diseases 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 150000002367 halogens Chemical class 0.000 description 8
• 229940037467 helicobacter pylori Drugs 0.000 description 8
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 8
• 238000007912 intraperitoneal administration Methods 0.000 description 8
• 208000011906 peptic ulcer disease Diseases 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
• 208000019206 urinary tract infection Diseases 0.000 description 8
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 7
• 241000894006 Bacteria Species 0.000 description 7
• 208000005623 Carcinogenesis Diseases 0.000 description 7
• 208000001860 Eye Infections Diseases 0.000 description 7
• 208000005141 Otitis Diseases 0.000 description 7
• 239000003242 anti bacterial agent Substances 0.000 description 7
• 230000036952 cancer formation Effects 0.000 description 7
• 231100000504 carcinogenesis Toxicity 0.000 description 7
• 208000019258 ear infection Diseases 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 208000011323 eye infectious disease Diseases 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 125000004430 oxygen atom Chemical group O* 0.000 description 7
• 230000002685 pulmonary effect Effects 0.000 description 7
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 206010040872 skin infection Diseases 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000003828 vacuum filtration Methods 0.000 description 7
• 150000003952 β-lactams Chemical class 0.000 description 7
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 239000005909 Kieselgur Substances 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
• 239000010452 phosphate Substances 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 125000001425 triazolyl group Chemical group 0.000 description 6
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 6
• WZPBZJONDBGPKJ-VEHQQRBSSA-L 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2s,3s)-2-methyl-4-oxo-1-sulfonatoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoate Chemical class O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C([O-])=O)\C1=CSC(N)=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-L 0.000 description 5
• 201000003883 Cystic fibrosis Diseases 0.000 description 5
• 206010060803 Diabetic foot infection Diseases 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 5
• 239000003781 beta lactamase inhibitor Substances 0.000 description 5
• 102000006635 beta-lactamase Human genes 0.000 description 5
• 229940126813 beta-lactamase inhibitor Drugs 0.000 description 5
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• AFDQGRURHDVABZ-UHFFFAOYSA-N n,n-dimethylformamide;sulfur trioxide Chemical compound O=S(=O)=O.CN(C)C=O AFDQGRURHDVABZ-UHFFFAOYSA-N 0.000 description 5
• 239000011698 potassium fluoride Substances 0.000 description 5
• 239000000376 reactant Substances 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 230000006103 sulfonylation Effects 0.000 description 5
• 238000005694 sulfonylation reaction Methods 0.000 description 5
• 125000004434 sulfur atom Chemical group 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 239000005695 Ammonium acetate Substances 0.000 description 4
• 108090000204 Dipeptidase 1 Proteins 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• 229930182555 Penicillin Natural products 0.000 description 4
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