IL104588A - Carbafenamim contains phenyl-converted carboxy, a process for their preparation, and pharmaceutical preparations containing them. - Google Patents
Carbafenamim contains phenyl-converted carboxy, a process for their preparation, and pharmaceutical preparations containing them.Info
- Publication number
- IL104588A IL104588A IL10458893A IL10458893A IL104588A IL 104588 A IL104588 A IL 104588A IL 10458893 A IL10458893 A IL 10458893A IL 10458893 A IL10458893 A IL 10458893A IL 104588 A IL104588 A IL 104588A
- Authority
- IL
- Israel
- Prior art keywords
- pyrrolidin
- hydroxyethyl
- carboxy
- ylthio
- methylcarbapenem
- Prior art date
Links
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 title claims abstract description 53
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims description 8
- 238000000034 method Methods 0.000 title abstract description 93
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 229940041011 carbapenems Drugs 0.000 title abstract description 7
- 230000008569 process Effects 0.000 title abstract description 5
- -1 nitro, hydroxy, carboxy Chemical group 0.000 claims abstract description 170
- 150000001875 compounds Chemical class 0.000 claims abstract description 128
- 150000002148 esters Chemical class 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 238000001727 in vivo Methods 0.000 claims abstract description 19
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 8
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 claims abstract description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 77
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 71
- 239000002253 acid Substances 0.000 claims description 52
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 23
- 125000006239 protecting group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 230000000844 anti-bacterial effect Effects 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004986 diarylamino group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- FBEDCFXZESNBQA-UHFFFAOYSA-N methoxy azanylidynemethanesulfonate Chemical compound COOS(=O)(=O)C#N FBEDCFXZESNBQA-UHFFFAOYSA-N 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 275
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 249
- 238000004587 chromatography analysis Methods 0.000 description 98
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
- 235000019439 ethyl acetate Nutrition 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- 239000011734 sodium Substances 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 101150041968 CDC13 gene Proteins 0.000 description 50
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical class OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 37
- 239000002904 solvent Substances 0.000 description 37
- 239000007858 starting material Substances 0.000 description 36
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 29
- 229910019142 PO4 Inorganic materials 0.000 description 27
- 150000001412 amines Chemical class 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 239000010452 phosphate Substances 0.000 description 27
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 27
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 26
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 26
- 230000009467 reduction Effects 0.000 description 25
- 239000000377 silicon dioxide Substances 0.000 description 25
- 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 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- 150000002828 nitro derivatives Chemical class 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- 150000003573 thiols Chemical class 0.000 description 17
- 229910052786 argon Inorganic materials 0.000 description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 238000010828 elution Methods 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- GVXVFYJKQOTMCX-UHFFFAOYSA-N prop-2-enyl 3-aminobenzoate Chemical compound NC1=CC=CC(C(=O)OCC=C)=C1 GVXVFYJKQOTMCX-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 229940064734 aminobenzoate Drugs 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 229960002182 imipenem Drugs 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 4
- 235000011150 stannous chloride Nutrition 0.000 description 4
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
- MYFIPSUFYFSAPD-STQMWFEESA-N (2s,4s)-4-acetylsulfanyl-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](SC(=O)C)C[C@@H](C(O)=O)N1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 MYFIPSUFYFSAPD-STQMWFEESA-N 0.000 description 3
- GHUIBKBNBPSUTC-UHFFFAOYSA-N 3-cyano-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC(C#N)=CC([N+]([O-])=O)=C1 GHUIBKBNBPSUTC-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- JCDVSWJWUDLVTR-UHFFFAOYSA-N SC(=O)CC1CCNC1 Chemical compound SC(=O)CC1CCNC1 JCDVSWJWUDLVTR-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 102000006635 beta-lactamase Human genes 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- QTBSBXVTEAMEQO-DYCDLGHISA-N deuterio acetate Chemical compound [2H]OC(C)=O QTBSBXVTEAMEQO-DYCDLGHISA-N 0.000 description 3
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- MDFSGDMPHMKKGB-UHFFFAOYSA-N 2,4-difluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=C(F)C=C1F MDFSGDMPHMKKGB-UHFFFAOYSA-N 0.000 description 2
- RECRLCHPXXOYHZ-UHFFFAOYSA-N 2,4-dimethoxy-5-nitrobenzoic acid Chemical compound COC1=CC(OC)=C([N+]([O-])=O)C=C1C(O)=O RECRLCHPXXOYHZ-UHFFFAOYSA-N 0.000 description 2
- FZURAQWCFKOCNV-YWZLYKJASA-N 2-acetamido-5-[[(2S,4S)-1-[(4-nitrophenyl)methoxycarbonyl]-4-(2-oxo-2-sulfanylethyl)pyrrolidine-2-carbonyl]amino]benzoic acid Chemical compound C1=C(C(O)=O)C(NC(=O)C)=CC=C1NC(=O)[C@H]1N(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)C[C@H](CC(S)=O)C1 FZURAQWCFKOCNV-YWZLYKJASA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
-
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929202298A GB9202298D0 (en) | 1992-02-04 | 1992-02-04 | Antibiotic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL104588A0 IL104588A0 (en) | 1993-06-10 |
| IL104588A true IL104588A (en) | 1999-03-12 |
Family
ID=10709764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10458893A IL104588A (en) | 1992-02-04 | 1993-02-02 | Carbafenamim contains phenyl-converted carboxy, a process for their preparation, and pharmaceutical preparations containing them. |
Country Status (35)
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| US (7) | US5478820A (de) |
| EP (1) | EP0579826B1 (de) |
| JP (1) | JP2730600B2 (de) |
| KR (1) | KR100200986B1 (de) |
| CN (1) | CN1036006C (de) |
| AP (1) | AP398A (de) |
| AT (1) | ATE173262T1 (de) |
| AU (1) | AU668133B2 (de) |
| CA (1) | CA2106370C (de) |
| CZ (1) | CZ286878B6 (de) |
| DE (2) | DE69322007T2 (de) |
| DK (1) | DK0579826T3 (de) |
| ES (1) | ES2123654T3 (de) |
| FI (1) | FI104074B1 (de) |
| GB (2) | GB9202298D0 (de) |
| GE (1) | GEP20022694B (de) |
| HK (1) | HK1013998A1 (de) |
| HR (1) | HRP930103B1 (de) |
| HU (3) | HU213675B (de) |
| IL (1) | IL104588A (de) |
| LU (1) | LU90970I2 (de) |
| MY (1) | MY111685A (de) |
| NL (1) | NL300104I2 (de) |
| NO (2) | NO304315B1 (de) |
| NZ (2) | NZ246917A (de) |
| PL (3) | PL174649B1 (de) |
| RU (1) | RU2117659C1 (de) |
| SG (1) | SG48817A1 (de) |
| SI (1) | SI9300056B (de) |
| SK (1) | SK280890B6 (de) |
| TW (1) | TW408124B (de) |
| UA (1) | UA44885C2 (de) |
| WO (1) | WO1993015078A1 (de) |
| YU (1) | YU48998B (de) |
| ZA (1) | ZA93453B (de) |
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| US5602118A (en) * | 1993-03-16 | 1997-02-11 | American Cyanamid Company | 2-thiosubstituted carbapenems |
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| AR008255A1 (es) * | 1996-07-12 | 1999-12-29 | Merck & Co Inc | Procedimiento para sintetizar antibioticos de carbapenem |
| US6946468B1 (en) | 1996-08-17 | 2005-09-20 | Zeneca Limited | 3-mercaptopyrrolidines as farnesyl protein transferase inhibitors |
| AU714155B2 (en) * | 1996-10-10 | 1999-12-23 | Merck & Co., Inc. | Process for synthesizing carbapenem side chain intermediates |
| US5877328A (en) * | 1996-10-10 | 1999-03-02 | Merck & Co., Inc. | Process for synthesizing carbapenem side chain intermediates |
| AU725298B2 (en) * | 1996-10-28 | 2000-10-12 | Merck & Co., Inc. | Stabilized carbapenem antibiotic compositions and method of making |
| US6180783B1 (en) | 1997-06-16 | 2001-01-30 | Merck & Co., Inc. | Stabilized carbapenem intermediates and improved process for carbapenem synthesis |
| WO1998057973A1 (en) * | 1997-06-16 | 1998-12-23 | Merck & Co., Inc. | Stabilized carbapenem intermediates and synthetic use |
| CA2294341C (en) * | 1997-07-10 | 2007-09-25 | Merck & Co., Inc. | Crystalline forms of antibiotic side chain intermediates |
| US5965747A (en) * | 1997-07-10 | 1999-10-12 | Merck & Co., Inc. | Crystalline forms of antibiotic side chain intermediates |
| US5872250A (en) * | 1997-07-30 | 1999-02-16 | Merck & Co., Inc. | Process for synthesizing carbapenem antibiotics |
| US6504027B1 (en) | 1998-03-02 | 2003-01-07 | Merck & Co., Inc. | Decarboxylation process for synthesizing carbapenem antibiotics |
| AU749234B2 (en) * | 1998-03-02 | 2002-06-20 | Merck Sharp & Dohme Corp. | Process for synthesizing carbapenem antibiotics |
| ATE263766T1 (de) | 1998-06-17 | 2004-04-15 | Merck & Co Inc | Verfahren zur synthese von carbapenem- zwischenprodukten |
| US6486150B2 (en) | 1999-10-29 | 2002-11-26 | Merck & Co., Inc. | Process for formulation of antibiotic compounds |
| US6548492B1 (en) | 1999-10-29 | 2003-04-15 | Merck & Co., Inc. | Process for formulation of carbapenem antibiotic compositions |
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| AR035728A1 (es) * | 2001-01-16 | 2004-07-07 | Merck & Co Inc | Proceso perfeccionado para la sintesis de carbapenem |
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| DK1474426T3 (da) * | 2001-09-26 | 2011-11-21 | Merck Sharp & Dohme | Fremgangsmåde til fremstilling af carbapenemforbindelser |
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| ES2323527T3 (es) * | 2002-05-29 | 2009-07-20 | MERCK & CO., INC. | Compuestos utiles en el tratamiento del carbunco y en la inhibicion del factor letal. |
| WO2005111986A2 (en) * | 2004-05-07 | 2005-11-24 | Infinium Labs, Inc. | Multi-position multi-level user interface system |
| EP1747212A4 (de) * | 2004-05-11 | 2009-03-25 | Merck & Co Inc | Verfahren zur herstellung von n-sulfonierten aminosäure-derivaten |
| US20100003276A1 (en) * | 2004-12-07 | 2010-01-07 | Hermes Jeffery D | Methods for treating anthrax and inhibiting lethal factor |
| CN100344613C (zh) * | 2005-10-20 | 2007-10-24 | 上海交通大学 | (2s,4s)－1－(4－硝基苄氧羰基)－2－[(3－烯丙氧羰基)－苯基氨基甲酰基]－吡咯烷－4－基硫醇的制备方法 |
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| CN101357916B (zh) * | 2007-06-22 | 2010-12-15 | 山东轩竹医药科技有限公司 | 含有二氢咪唑甲酰胺基的培南化合物 |
| CN101367807B (zh) * | 2007-06-28 | 2011-01-12 | 山东轩竹医药科技有限公司 | 被巯基吡咯烷甲酰胺基吡啶取代的培南衍生物 |
| CN101367815B (zh) * | 2007-06-28 | 2012-07-04 | 山东轩竹医药科技有限公司 | 六元环甲酰胺取代的巯基吡咯烷碳青霉烯化合物 |
| CN101362760B (zh) * | 2007-08-07 | 2010-12-15 | 山东轩竹医药科技有限公司 | 1β-甲基碳代青霉烯化合物 |
| CN101362761B (zh) * | 2007-08-12 | 2011-05-18 | 山东轩竹医药科技有限公司 | 含有巯基哌啶的碳代青霉烯抗生素 |
| CN101412720B (zh) * | 2007-08-27 | 2011-05-18 | 山东轩竹医药科技有限公司 | 含有巯基氮杂环乙烯基的碳青霉烯化合物 |
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| EP2505191A1 (de) | 2008-06-11 | 2012-10-03 | Ranbaxy Laboratories Limited | Lypholisierte Carbapenem-Antibiotikumzusammensetzung |
| CA2732619A1 (en) * | 2008-07-30 | 2010-02-04 | Ranbaxy Laboratories Limited | Process for the preparation of carbapenem compounds |
| RU2521391C2 (ru) * | 2008-09-18 | 2014-06-27 | Ману ЧАУДХАРИ | Новые однократные единичные составы карбапенема и аминогликозида |
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| CN106565579A (zh) * | 2016-06-26 | 2017-04-19 | 宁夏海诚电化信息科技有限公司 | 一种尔它培南侧链生产工艺 |
| CN110698480B (zh) * | 2018-07-09 | 2023-09-08 | 武汉启瑞药业有限公司 | 一种厄他培南中间体的合成及纯化方法 |
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| CA2099817A1 (en) * | 1992-07-21 | 1994-01-22 | Frederic H. Jung | Antibiotic compounds |
| CA2099818A1 (en) * | 1992-07-21 | 1994-01-22 | Frederic H. Jung | Antibiotic compounds |
| CA2099811A1 (en) * | 1992-07-21 | 1994-01-22 | Frederic H. Jung | Antibiotic compounds |
| CA2106141A1 (en) * | 1992-09-28 | 1994-03-29 | Michael J. Betts | Antibiotic compounds |
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1992
- 1992-02-04 GB GB929202298A patent/GB9202298D0/en active Pending
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1993
- 1993-01-12 GB GB939300456A patent/GB9300456D0/en active Pending
- 1993-01-21 AP APAP/P/1993/000480A patent/AP398A/en active
- 1993-01-21 ZA ZA93453A patent/ZA93453B/xx unknown
- 1993-01-27 MY MYPI93000120A patent/MY111685A/en unknown
- 1993-01-29 YU YU5493A patent/YU48998B/sh unknown
- 1993-02-02 HU HU9302777A patent/HU213675B/hu unknown
- 1993-02-02 AT AT93914514T patent/ATE173262T1/de active
- 1993-02-02 EP EP93914514A patent/EP0579826B1/de not_active Expired - Lifetime
- 1993-02-02 PL PL93300768A patent/PL174649B1/pl unknown
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- 1993-06-18 UA UA93003121A patent/UA44885C2/uk unknown
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1995
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- 1995-06-14 HU HU95P/P00201P patent/HU211840A9/hu active Protection Beyond IP Right Term
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1997
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1998
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2001
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2002
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2005
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Also Published As
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