ES2542431T3 - Monobactamas - Google Patents
Monobactamas Download PDFInfo
- Publication number
- ES2542431T3 ES2542431T3 ES11794237.5T ES11794237T ES2542431T3 ES 2542431 T3 ES2542431 T3 ES 2542431T3 ES 11794237 T ES11794237 T ES 11794237T ES 2542431 T3 ES2542431 T3 ES 2542431T3
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- 229940041009 monobactams Drugs 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 228
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 96
- 239000001257 hydrogen Substances 0.000 claims abstract description 96
- -1 2-aminothiazol-4-yl Chemical group 0.000 claims abstract description 95
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 86
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 14
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 150000003852 triazoles Chemical class 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 69
- 239000003814 drug Substances 0.000 claims description 23
- 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
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 208000035143 Bacterial infection Diseases 0.000 claims description 12
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 12
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 39
- 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 326
- 239000007787 solid Substances 0.000 description 237
- 239000000243 solution Substances 0.000 description 220
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 218
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 202
- 238000002360 preparation method Methods 0.000 description 197
- 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 162
- 239000000203 mixture Substances 0.000 description 159
- 238000005160 1H NMR spectroscopy Methods 0.000 description 155
- 235000019439 ethyl acetate Nutrition 0.000 description 153
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 146
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 141
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 134
- 239000011541 reaction mixture Substances 0.000 description 131
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 98
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 92
- 238000000034 method Methods 0.000 description 86
- 238000006243 chemical reaction Methods 0.000 description 85
- 239000002904 solvent Substances 0.000 description 83
- 239000000725 suspension Substances 0.000 description 83
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- 239000012074 organic phase Substances 0.000 description 76
- 238000004587 chromatography analysis Methods 0.000 description 70
- 208000015181 infectious disease Diseases 0.000 description 68
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 68
- 239000000741 silica gel Substances 0.000 description 66
- 229910002027 silica gel Inorganic materials 0.000 description 66
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 61
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 60
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- 239000013058 crude material Substances 0.000 description 51
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 48
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- 239000008346 aqueous phase Substances 0.000 description 42
- 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
- 239000012071 phase Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- 239000012267 brine Substances 0.000 description 37
- 150000001721 carbon Chemical group 0.000 description 36
- 239000012043 crude product Substances 0.000 description 36
- 239000000706 filtrate Substances 0.000 description 36
- 238000001914 filtration Methods 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 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 34
- 235000019441 ethanol Nutrition 0.000 description 34
- 235000019253 formic acid Nutrition 0.000 description 34
- 238000003756 stirring Methods 0.000 description 32
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- 235000017557 sodium bicarbonate Nutrition 0.000 description 30
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- 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
- 229910052757 nitrogen Inorganic materials 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- 239000012065 filter cake Substances 0.000 description 24
- 239000003607 modifier Substances 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- 229960004592 isopropanol Drugs 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
- 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 18
- 229940086542 triethylamine Drugs 0.000 description 18
- 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
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 16
- 230000002496 gastric effect Effects 0.000 description 14
- 208000027096 gram-negative bacterial infections Diseases 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 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
- 239000007864 aqueous solution Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000003242 anti bacterial agent Substances 0.000 description 11
- 239000000010 aprotic solvent Substances 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 239000012467 final product 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
- 229940079593 drug Drugs 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 125000001424 substituent group Chemical group 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
- 241000588626 Acinetobacter baumannii Species 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 9
- 241000588724 Escherichia coli Species 0.000 description 9
- 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
- 239000003153 chemical reaction reagent 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
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 238000000825 ultraviolet detection Methods 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 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
- 201000003883 Cystic fibrosis Diseases 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 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
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 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
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 8
- 206010040047 Sepsis Diseases 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 206010052428 Wound Diseases 0.000 description 8
- 239000006196 drop Substances 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
- 239000002244 precipitate Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 206010040872 skin infection Diseases 0.000 description 8
- 229910052717 sulfur Chemical group 0.000 description 8
- 125000001425 triazolyl group Chemical group 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
- 208000005623 Carcinogenesis Diseases 0.000 description 7
- 208000001860 Eye Infections Diseases 0.000 description 7
- 208000032376 Lung infection Diseases 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 206010062255 Soft tissue infection Diseases 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000036952 cancer formation Effects 0.000 description 7
- 231100000504 carcinogenesis Toxicity 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 208000011323 eye infectious disease Diseases 0.000 description 7
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000003828 vacuum filtration Methods 0.000 description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- 238000005481 NMR spectroscopy Methods 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
- 102000006635 beta-lactamase Human genes 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 238000009472 formulation 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
- 125000000325 methylidene group Chemical group [H]C([H])=* 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
- 239000011780 sodium chloride Substances 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 6
- 208000019206 urinary tract infection Diseases 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-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
- 229930186147 Cephalosporin Natural products 0.000 description 5
- 206010060803 Diabetic foot infection Diseases 0.000 description 5
- 208000005141 Otitis 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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N alpha-isobutyric acid Natural products CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 5
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 5
- 229940124587 cephalosporin Drugs 0.000 description 5
- 150000001780 cephalosporins Chemical class 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 208000019258 ear infection Diseases 0.000 description 5
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000007788 liquid Substances 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
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 5
- 230000006103 sulfonylation Effects 0.000 description 5
- 238000005694 sulfonylation reaction Methods 0.000 description 5
- 150000003952 β-lactams Chemical class 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
- 108090000204 Dipeptidase 1 Proteins 0.000 description 4
- 241000282412 Homo Species 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
- 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
- 125000004429 atom Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
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- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 1
- 229960003865 tazobactam Drugs 0.000 description 1
- 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 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- KHVCOYGKHDJPBZ-WDCZJNDASA-N tetrahydrooxazine Chemical compound OC[C@H]1ONC[C@@H](O)[C@@H]1O KHVCOYGKHDJPBZ-WDCZJNDASA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229960004089 tigecycline Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005881 triazolinyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41757510P | 2010-11-29 | 2010-11-29 | |
| US417575P | 2010-11-29 | ||
| PCT/IB2011/055104 WO2012073138A1 (en) | 2010-11-29 | 2011-11-15 | Monobactams |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2542431T3 true ES2542431T3 (es) | 2015-08-05 |
Family
ID=45315854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11794237.5T Active ES2542431T3 (es) | 2010-11-29 | 2011-11-15 | Monobactamas |
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 (22)
| 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 |
| MA39777B1 (fr) | 2014-03-24 | 2019-03-29 | Novartis Ag | Composes organiques de la famille des monobactams pour le traitement d'infections bactériennes |
| RU2754180C2 (ru) * | 2015-09-23 | 2021-08-30 | Новартис Аг | Соли и твердые формы монобактамного антибиотика |
| 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 |
| EP3390357B1 (en) * | 2015-12-15 | 2021-11-10 | Merck Sharp & Dohme Corp. | Biaryl monobactam compounds for the treatment of bacterial infections |
| KR102408800B1 (ko) | 2016-03-07 | 2022-06-13 | 머크 샤프 앤드 돔 코포레이션 | 비시클릭 아릴 모노박탐 화합물 및 박테리아 감염의 치료를 위한 그의 사용 방법 |
| 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 |
| JP7235718B2 (ja) | 2017-08-02 | 2023-03-08 | ノバルティス アーゲー | モノバクタム系抗生物質およびその中間体を製造するための化学的方法 |
| KR102425959B1 (ko) | 2017-10-02 | 2022-07-27 | 머크 샤프 앤드 돔 코포레이션 | 박테리아 감염의 치료를 위한 크로만 모노박탐 화합물 |
| US10513504B2 (en) | 2018-03-08 | 2019-12-24 | Apotex Inc. | Processes for the preparation of apalutamide and intermediates thereof |
| US12516049B2 (en) | 2019-11-22 | 2026-01-06 | Suzhou Erye Pharmaceutical Co., Ltd | Sulfonylurea ring substituted monocyclic β-lactam antibiotics |
| FI4069691T3 (fi) | 2019-12-06 | 2024-11-13 | Vertex Pharma | Substituoituja tetrahydrofuraaneja natriumkanavien modulaattoreina |
| 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 |
| AU2022250095B2 (en) | 2021-03-31 | 2023-11-23 | Fedora Pharmaceuticals Inc. | Lactivicin compounds, their preparation and use as antibacterial agents |
| US12528804B2 (en) | 2021-03-31 | 2026-01-20 | Fedora Pharmaceuticals Inc. | Lactivicin compounds, their preparation and use as antibacterial agents |
| WO2022235077A1 (ko) * | 2021-05-07 | 2022-11-10 | 한국생명공학연구원 | 신규 사이드로포어 화합물 및 이를 이용한 금속 나노입자 복합체 |
| CR20230586A (es) | 2021-06-04 | 2024-05-07 | Vertex Pharma | N-(hydroxyalquil (hetero)aril) tetrahidrofurano carboxamidas como moduladores de canales de sodio |
| AU2022391635B2 (en) | 2021-11-18 | 2025-10-02 | Merck Sharp & Dohme Llc | Chromane amidine monobactam antibiotics |
| 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 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR880701238A (ko) * | 1986-05-23 | 1988-07-26 | 로버트 에이 아르미티즈 | N-1 치환 설포닐아미노카르보닐,c-4 치환 모노박탐 |
| SI1965798T1 (sl) | 2005-12-07 | 2012-01-31 | Basilea Pharmaceutica Ag | Uporabni monobaktamski antibiotiki |
| AU2008232262B2 (en) | 2007-03-28 | 2013-02-14 | Apotex Inc. | Fluorinated derivatives of deferiprone |
| MX2011006541A (es) * | 2008-12-19 | 2011-07-20 | Pfizer | Monocarbamas. |
-
2011
- 2011-11-15 ES ES11794237.5T patent/ES2542431T3/es active Active
- 2011-11-15 SG SG2013031752A patent/SG190007A1/en unknown
- 2011-11-15 KR KR1020137016718A patent/KR101514587B1/ko not_active Expired - Fee Related
- 2011-11-15 CA CA2815821A patent/CA2815821C/en not_active Expired - Fee Related
- 2011-11-15 MX MX2013005994A patent/MX2013005994A/es active IP Right Grant
- 2011-11-15 AU AU2011336209A patent/AU2011336209B2/en not_active Ceased
- 2011-11-15 DK DK11794237.5T patent/DK2646436T3/en active
- 2011-11-15 CN CN201180057264.5A patent/CN103228652B/zh not_active Expired - Fee Related
- 2011-11-15 WO PCT/IB2011/055104 patent/WO2012073138A1/en not_active Ceased
- 2011-11-15 JP JP2013541445A patent/JP5777725B2/ja not_active Expired - Fee Related
- 2011-11-15 EP EP11794237.5A patent/EP2646436B1/en not_active Not-in-force
- 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 |
|---|---|
| CA2815821C (en) | 2015-07-07 |
| HK1184462A1 (en) | 2014-01-24 |
| IL226052A0 (en) | 2013-06-27 |
| MX2013005994A (es) | 2013-07-15 |
| KR20130112054A (ko) | 2013-10-11 |
| EP2646436A1 (en) | 2013-10-09 |
| AU2011336209B2 (en) | 2015-03-19 |
| AR084001A1 (es) | 2013-04-17 |
| JP2013544276A (ja) | 2013-12-12 |
| DK2646436T3 (en) | 2015-06-29 |
| WO2012073138A1 (en) | 2012-06-07 |
| JP5777725B2 (ja) | 2015-09-09 |
| CN103228652A (zh) | 2013-07-31 |
| SG190007A1 (en) | 2013-06-28 |
| TW201247661A (en) | 2012-12-01 |
| UY33754A (es) | 2012-06-29 |
| AU2011336209A1 (en) | 2013-05-30 |
| EP2646436B1 (en) | 2015-05-27 |
| US20150148326A1 (en) | 2015-05-28 |
| KR101514587B1 (ko) | 2015-04-22 |
| US20120302542A1 (en) | 2012-11-29 |
| ZA201304479B (en) | 2014-03-26 |
| CN103228652B (zh) | 2015-02-18 |
| CA2815821A1 (en) | 2012-06-07 |
| US20130252935A1 (en) | 2013-09-26 |
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