DK2646436T3 - monobactams - Google Patents
monobactams Download PDFInfo
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- DK2646436T3 DK2646436T3 DK11794237.5T DK11794237T DK2646436T3 DK 2646436 T3 DK2646436 T3 DK 2646436T3 DK 11794237 T DK11794237 T DK 11794237T DK 2646436 T3 DK2646436 T3 DK 2646436T3
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- DK
- Denmark
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- 229940041009 monobactams Drugs 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 227
- 239000001257 hydrogen Substances 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 96
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 82
- -1 2-aminothiazol-4-yl Chemical group 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 229910052799 carbon Inorganic materials 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000000842 isoxazolyl 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
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 9
- 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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 463
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 367
- 239000007787 solid Substances 0.000 description 242
- 239000000243 solution Substances 0.000 description 229
- 239000000203 mixture Substances 0.000 description 223
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 218
- 238000002360 preparation method Methods 0.000 description 209
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 200
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 186
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 186
- 235000019439 ethyl acetate Nutrition 0.000 description 155
- 238000005160 1H NMR spectroscopy Methods 0.000 description 154
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 141
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 140
- 239000011541 reaction mixture Substances 0.000 description 137
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
- 238000006243 chemical reaction Methods 0.000 description 93
- 238000000034 method Methods 0.000 description 90
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- 239000002904 solvent Substances 0.000 description 83
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 77
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- 239000012044 organic layer Substances 0.000 description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 74
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 72
- 239000010410 layer Substances 0.000 description 70
- 238000004587 chromatography analysis Methods 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
- 208000015181 infectious disease Diseases 0.000 description 61
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
- 239000000725 suspension Substances 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
- 239000013058 crude material Substances 0.000 description 51
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
- 238000001914 filtration Methods 0.000 description 41
- 229910052757 nitrogen Inorganic materials 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
- 239000000706 filtrate Substances 0.000 description 40
- 239000012267 brine Substances 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 36
- 239000012043 crude product Substances 0.000 description 34
- 235000019441 ethanol Nutrition 0.000 description 34
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 33
- 239000012065 filter cake Substances 0.000 description 33
- 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
- 238000003756 stirring Methods 0.000 description 32
- 235000017557 sodium bicarbonate Nutrition 0.000 description 29
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
- 239000002002 slurry Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 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
- 239000003607 modifier Substances 0.000 description 24
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 24
- 229960004592 isopropanol Drugs 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- 229940086542 triethylamine Drugs 0.000 description 20
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 16
- 230000002496 gastric effect Effects 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 208000027096 gram-negative bacterial infections Diseases 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- 230000002829 reductive effect Effects 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
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 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 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
- 229940079593 drug Drugs 0.000 description 11
- 239000012467 final product Substances 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 10
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 10
- 241000588626 Acinetobacter baumannii Species 0.000 description 9
- 241000588747 Klebsiella pneumoniae Species 0.000 description 9
- 208000032376 Lung infection Diseases 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 9
- 239000002585 base Substances 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
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 208000031729 Bacteremia Diseases 0.000 description 8
- 241000894006 Bacteria Species 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
- 201000003883 Cystic fibrosis Diseases 0.000 description 8
- 206010060803 Diabetic foot infection Diseases 0.000 description 8
- 208000008745 Healthcare-Associated Pneumonia Diseases 0.000 description 8
- 241000590002 Helicobacter pylori Species 0.000 description 8
- 208000036209 Intraabdominal Infections Diseases 0.000 description 8
- 206010031252 Osteomyelitis Diseases 0.000 description 8
- 208000008469 Peptic Ulcer Diseases 0.000 description 8
- 206010035664 Pneumonia Diseases 0.000 description 8
- 206010040047 Sepsis Diseases 0.000 description 8
- 206010062255 Soft tissue infection Diseases 0.000 description 8
- 206010052428 Wound Diseases 0.000 description 8
- 208000025222 central nervous system infectious disease Diseases 0.000 description 8
- 206010014665 endocarditis Diseases 0.000 description 8
- 239000000284 extract Substances 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 208000011906 peptic ulcer disease Diseases 0.000 description 8
- 206010040872 skin infection Diseases 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 208000005623 Carcinogenesis Diseases 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 208000001860 Eye Infections Diseases 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 239000003781 beta lactamase inhibitor Substances 0.000 description 7
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 7
- 230000036952 cancer formation Effects 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 231100000504 carcinogenesis Toxicity 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000003981 vehicle Substances 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
- 239000005909 Kieselgur Substances 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000003545 alkoxy group Chemical group 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 125000004430 oxygen atom Chemical group O* 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
- 239000011698 potassium fluoride Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 229910052717 sulfur Chemical group 0.000 description 6
- 125000004434 sulfur atom Chemical group 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
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- 238000003828 vacuum filtration Methods 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 5
- 229930186147 Cephalosporin Natural products 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 5
- 102000006635 beta-lactamase Human genes 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 229940124587 cephalosporin Drugs 0.000 description 5
- 150000001780 cephalosporins Chemical class 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 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
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 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
- 241000282412 Homo Species 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 125000002393 azetidinyl group Chemical group 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 229940041011 carbapenems Drugs 0.000 description 4
- 229960004106 citric acid Drugs 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41757510P | 2010-11-29 | 2010-11-29 | |
| PCT/IB2011/055104 WO2012073138A1 (en) | 2010-11-29 | 2011-11-15 | Monobactams |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2646436T3 true DK2646436T3 (en) | 2015-06-29 |
Family
ID=45315854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11794237.5T DK2646436T3 (en) | 2010-11-29 | 2011-11-15 | monobactams |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US20120302542A1 (enExample) |
| EP (1) | EP2646436B1 (enExample) |
| JP (1) | JP5777725B2 (enExample) |
| KR (1) | KR101514587B1 (enExample) |
| CN (1) | CN103228652B (enExample) |
| AR (1) | AR084001A1 (enExample) |
| AU (1) | AU2011336209B2 (enExample) |
| CA (1) | CA2815821C (enExample) |
| DK (1) | DK2646436T3 (enExample) |
| ES (1) | ES2542431T3 (enExample) |
| IL (1) | IL226052A0 (enExample) |
| MX (1) | MX2013005994A (enExample) |
| SG (1) | SG190007A1 (enExample) |
| TW (1) | TW201247661A (enExample) |
| UY (1) | UY33754A (enExample) |
| WO (1) | WO2012073138A1 (enExample) |
| ZA (1) | ZA201304479B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9988373B2 (en) | 2013-12-26 | 2018-06-05 | Shionogi & Co., Ltd. | Nitrogen-containing six-membered cyclic derivatives and pharmaceutical composition comprising the same |
| HUE042134T2 (hu) * | 2014-03-24 | 2019-06-28 | Novartis Ag | Monobaktám szerves vegyületek bakteriális fertõzések kezelésére |
| AU2016327264B2 (en) | 2015-09-23 | 2019-06-27 | Novartis Ag | Salts and solid forms of monobactam antibiotic |
| CN105481812B (zh) * | 2015-11-30 | 2020-04-21 | 重庆天奕恒化科技有限公司 | 一种5-苄氧基-4-氧代-4h-吡喃-2-羧酸的制备方法 |
| AU2016371600B2 (en) | 2015-12-15 | 2021-02-18 | Merck Sharp & Dohme Llc | Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections |
| US10407421B2 (en) | 2016-03-07 | 2019-09-10 | Merck Sharp & Dohme Corp | Bicyclic aryl monobactam compounds and methods of use thereof for the treatment of bacterial infections |
| US10047077B2 (en) | 2016-04-13 | 2018-08-14 | Skyline Antiinfectives, Inc. | Deuterated O-sulfated beta-lactam hydroxamic acids and deuterated N-sulfated beta-lactams |
| CN107641119B (zh) | 2016-07-21 | 2019-11-08 | 中国科学院上海药物研究所 | 单环β-内酰胺-铁载体轭合物及其制备方法和用途 |
| ES2912656T3 (es) | 2017-08-02 | 2022-05-26 | Novartis Ag | Proceso para preparar ácido 1-(((Z)-(1-(2-aminotiazol-4-il)-2-oxo-2-(((3S,4R)-2-oxo-4-((2-oxooxazolidin-3-il)metil)-1-sulfoacetidin-3-il)amino)etiliden)amino)oxi)ciclopropano carboxílico |
| GEAP202215303A (en) | 2017-10-02 | 2022-04-11 | Merck Sharp & Dohme | Chromane monobactam compounds for the treatment of bacterial infections |
| US10513504B2 (en) | 2018-03-08 | 2019-12-24 | Apotex Inc. | Processes for the preparation of apalutamide and intermediates thereof |
| KR102786898B1 (ko) * | 2019-11-22 | 2025-03-25 | 쑤저우 얼예 파마슈티칼 컴퍼니 리미티드 | 설포닐우레아 고리 치환 모노시클릭 β-락탐계 항생제 |
| PH12022551379A1 (en) | 2019-12-06 | 2023-05-03 | Vertex Pharma | Substituted tetrahydrofurans as modulators of sodium channels |
| CN111303144B (zh) * | 2019-12-13 | 2020-11-27 | 苏州信诺维医药科技有限公司 | 一种治疗细菌感染的化合物 |
| US12528804B2 (en) | 2021-03-31 | 2026-01-20 | Fedora Pharmaceuticals Inc. | Lactivicin compounds, their preparation and use as antibacterial agents |
| US11780832B2 (en) | 2021-03-31 | 2023-10-10 | Fedora Pharmaceuticals Inc. | Lactivicin compounds, their preparation and use as antibacterial agents |
| KR102781293B1 (ko) * | 2021-05-07 | 2025-03-17 | 한국생명공학연구원 | 신규 사이드로포어 화합물 및 이를 이용한 금속 나노입자 복합체 |
| SI4347031T1 (sl) | 2021-06-04 | 2026-01-30 | Vertex Pharmaceuticals Incorporated | N-(hidroksialkil (hetero)aril) tetrahidrofuran karboksamidi kot modulatorji natrijevih kanalčkov |
| CR20240212A (es) | 2021-11-18 | 2024-07-01 | Merck Sharp & Dohme Llc | Compuestos monobactámicos de cromano amidina para tratar las infecciones bacterianas |
| JP7671398B2 (ja) * | 2021-11-18 | 2025-05-01 | メルク・シャープ・アンド・ドーム・エルエルシー | クロマンアミジンモノバクタム抗生物質 |
| JP2025513455A (ja) | 2022-04-22 | 2025-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | 疼痛の治療のためのヘテロアリール化合物 |
| CN115304594B (zh) * | 2022-10-12 | 2023-02-14 | 苏州二叶制药有限公司 | 磺酰脲环取代的化合物的盐型及其晶型 |
| WO2026043829A1 (en) * | 2024-08-21 | 2026-02-26 | Merck Sharp & Dohme Llc | Chromane cyclic amidine monobactam compounds for the treatment of bacterial infections |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01502660A (ja) * | 1986-05-23 | 1989-09-14 | ジ・アップジョン・カンパニー | Ｎ―１置換スルホニルアミノカルボニル、ｃ―４置換モノバクタム類 |
| KR101403164B1 (ko) | 2005-12-07 | 2014-06-03 | 바실리어 파마슈티카 아게 | 베타-락타마아제 저해제 및 모노박탐 항생물질의 유용한조합 |
| WO2008116301A1 (en) | 2007-03-28 | 2008-10-02 | Apotex Technologies Inc. | Fluorinated derivatives of deferiprone |
| CA2744756C (en) * | 2008-12-19 | 2013-05-28 | Pfizer Inc. | Monocarbams and their use as antibacterial agent |
-
2011
- 2011-11-15 JP JP2013541445A patent/JP5777725B2/ja not_active Expired - Fee Related
- 2011-11-15 WO PCT/IB2011/055104 patent/WO2012073138A1/en not_active Ceased
- 2011-11-15 AU AU2011336209A patent/AU2011336209B2/en not_active Ceased
- 2011-11-15 CN CN201180057264.5A patent/CN103228652B/zh not_active Expired - Fee Related
- 2011-11-15 DK DK11794237.5T patent/DK2646436T3/en active
- 2011-11-15 KR KR1020137016718A patent/KR101514587B1/ko not_active Expired - Fee Related
- 2011-11-15 EP EP11794237.5A patent/EP2646436B1/en not_active Not-in-force
- 2011-11-15 MX MX2013005994A patent/MX2013005994A/es active IP Right Grant
- 2011-11-15 CA CA2815821A patent/CA2815821C/en not_active Expired - Fee Related
- 2011-11-15 ES ES11794237.5T patent/ES2542431T3/es active Active
- 2011-11-15 SG SG2013031752A patent/SG190007A1/en unknown
- 2011-11-24 TW TW100143172A patent/TW201247661A/zh unknown
- 2011-11-25 AR ARP110104404A patent/AR084001A1/es not_active Application Discontinuation
- 2011-11-28 UY UY0001033754A patent/UY33754A/es not_active Application Discontinuation
- 2011-11-29 US US13/306,581 patent/US20120302542A1/en not_active Abandoned
-
2013
- 2013-02-27 US US13/778,670 patent/US20130252935A1/en not_active Abandoned
- 2013-04-29 IL IL226052A patent/IL226052A0/en unknown
- 2013-06-18 ZA ZA2013/04479A patent/ZA201304479B/en unknown
-
2015
- 2015-01-29 US US14/608,826 patent/US20150148326A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR084001A1 (es) | 2013-04-17 |
| US20150148326A1 (en) | 2015-05-28 |
| ZA201304479B (en) | 2014-03-26 |
| EP2646436A1 (en) | 2013-10-09 |
| AU2011336209A1 (en) | 2013-05-30 |
| UY33754A (es) | 2012-06-29 |
| JP5777725B2 (ja) | 2015-09-09 |
| CA2815821A1 (en) | 2012-06-07 |
| JP2013544276A (ja) | 2013-12-12 |
| KR101514587B1 (ko) | 2015-04-22 |
| KR20130112054A (ko) | 2013-10-11 |
| IL226052A0 (en) | 2013-06-27 |
| CN103228652B (zh) | 2015-02-18 |
| CA2815821C (en) | 2015-07-07 |
| HK1184462A1 (en) | 2014-01-24 |
| TW201247661A (en) | 2012-12-01 |
| US20130252935A1 (en) | 2013-09-26 |
| AU2011336209B2 (en) | 2015-03-19 |
| MX2013005994A (es) | 2013-07-15 |
| WO2012073138A1 (en) | 2012-06-07 |
| EP2646436B1 (en) | 2015-05-27 |
| CN103228652A (zh) | 2013-07-31 |
| ES2542431T3 (es) | 2015-08-05 |
| US20120302542A1 (en) | 2012-11-29 |
| SG190007A1 (en) | 2013-06-28 |
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