CH656130A5 - Carbapenemantibiotika. - Google Patents
Carbapenemantibiotika. Download PDFInfo
- Publication number
- CH656130A5 CH656130A5 CH5263/83A CH526383A CH656130A5 CH 656130 A5 CH656130 A5 CH 656130A5 CH 5263/83 A CH5263/83 A CH 5263/83A CH 526383 A CH526383 A CH 526383A CH 656130 A5 CH656130 A5 CH 656130A5
- Authority
- CH
- Switzerland
- Prior art keywords
- alkyl
- formula
- substituents
- phenyl
- alkylamino
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 260
- -1 alkyl radical Chemical class 0.000 claims description 258
- 125000000217 alkyl group Chemical group 0.000 claims description 184
- 125000001424 substituent group Chemical group 0.000 claims description 171
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 141
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 103
- 150000002367 halogens Chemical group 0.000 claims description 102
- 229910052736 halogen Inorganic materials 0.000 claims description 96
- 150000003839 salts Chemical class 0.000 claims description 96
- 125000004432 carbon atom Chemical group C* 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 72
- 125000003282 alkyl amino group Chemical group 0.000 claims description 71
- 229910052757 nitrogen Inorganic materials 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 70
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 69
- 125000005842 heteroatom Chemical group 0.000 claims description 69
- 239000000460 chlorine Substances 0.000 claims description 62
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
- 229910052801 chlorine Inorganic materials 0.000 claims description 56
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 55
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 55
- 229910052794 bromium Inorganic materials 0.000 claims description 55
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 54
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 52
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 50
- 239000011737 fluorine Substances 0.000 claims description 50
- 229910052731 fluorine Inorganic materials 0.000 claims description 50
- 229910052760 oxygen Inorganic materials 0.000 claims description 49
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical group C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 44
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 39
- 150000003254 radicals Chemical class 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 125000004434 sulfur atom Chemical group 0.000 claims description 34
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 229910052740 iodine Inorganic materials 0.000 claims description 25
- 230000008569 process Effects 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 20
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 13
- 125000002837 carbocyclic group Chemical group 0.000 claims description 12
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 12
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000000129 anionic group Chemical group 0.000 claims description 9
- 150000002500 ions Chemical class 0.000 claims description 9
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 8
- 238000005956 quaternization reaction Methods 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 7
- 238000001228 spectrum Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000003367 polycyclic group Chemical group 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- 230000003115 biocidal effect Effects 0.000 claims description 4
- 229930014626 natural product Natural products 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 3
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 2
- MDQRDWAGHRLBPA-UHFFFAOYSA-N fluoroamine Chemical compound FN MDQRDWAGHRLBPA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002132 β-lactam antibiotic Substances 0.000 claims description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- 241000589516 Pseudomonas Species 0.000 claims 1
- GWDQURJBGWHTKL-UHFFFAOYSA-N [(diaminomethylideneamino)-nitro-lambda3-chloranyl]methanimidamide Chemical compound C(N)(=N)Cl([N+](=O)[O-])NC(=N)N GWDQURJBGWHTKL-UHFFFAOYSA-N 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- FQQFFZPBGYGDSX-NJFHWYBASA-N epithienamycin E Chemical compound C1C(S\C=C\NC(C)=O)=C(C(O)=O)N2C(=O)[C@@H]([C@@H](OS(O)(=O)=O)C)[C@H]21 FQQFFZPBGYGDSX-NJFHWYBASA-N 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 125000004954 trialkylamino group Chemical group 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 332
- 239000000243 solution Substances 0.000 description 256
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 231
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 189
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 147
- 239000000203 mixture Substances 0.000 description 145
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 98
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 86
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 85
- 239000007787 solid Substances 0.000 description 79
- 239000011541 reaction mixture Substances 0.000 description 77
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 67
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 63
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 54
- 239000000543 intermediate Substances 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 239000000843 powder Substances 0.000 description 38
- 239000000047 product Substances 0.000 description 38
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 36
- 238000004458 analytical method Methods 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 238000001914 filtration Methods 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- 239000002244 precipitate Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 239000012299 nitrogen atmosphere Substances 0.000 description 28
- 239000000706 filtrate Substances 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 239000012071 phase Substances 0.000 description 26
- 239000008363 phosphate buffer Substances 0.000 description 24
- 150000003573 thiols Chemical class 0.000 description 24
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 23
- 101150041968 CDC13 gene Proteins 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 23
- 239000012267 brine Substances 0.000 description 23
- 238000001704 evaporation Methods 0.000 description 23
- 230000008020 evaporation Effects 0.000 description 23
- 239000011630 iodine Substances 0.000 description 23
- 230000002441 reversible effect Effects 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 22
- 239000003054 catalyst Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 18
- 238000004108 freeze drying Methods 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 241000588724 Escherichia coli Species 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 16
- 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 16
- 229930194542 Keto Natural products 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 15
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 238000010521 absorption reaction Methods 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 14
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 14
- 239000003643 water by type Substances 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 13
- 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 13
- 125000000468 ketone group Chemical group 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 12
- 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 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 150000001450 anions Chemical class 0.000 description 12
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- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
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- 238000005984 hydrogenation reaction Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
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- XDNBGBASBLCTIN-UHFFFAOYSA-L 2-(dimethylamino)ethyl 4-(butylamino)benzoate;n,n-dimethylformamide;n-[2-ethyl-2-(3-methoxyphenyl)butyl]-4-hydroxybutanamide;trimethyl-[4-[[4-(trimethylazaniumyl)cyclohexyl]methyl]cyclohexyl]azanium;diiodide;hydrochloride Chemical compound Cl.[I-].[I-].CN(C)C=O.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1.OCCCC(=O)NCC(CC)(CC)C1=CC=CC(OC)=C1.C1CC([N+](C)(C)C)CCC1CC1CCC([N+](C)(C)C)CC1 XDNBGBASBLCTIN-UHFFFAOYSA-L 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- 239000003242 anti bacterial agent Substances 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- 238000004821 distillation Methods 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
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- BIRVVRGTJRWSKV-UHFFFAOYSA-N phosphoric acid;propan-2-ol Chemical compound CC(C)O.OP(O)(O)=O BIRVVRGTJRWSKV-UHFFFAOYSA-N 0.000 description 1
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- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 1
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- JOTSFBGEBKBZHG-UHFFFAOYSA-N s-[(3-methylpyridin-4-yl)methyl] ethanethioate Chemical compound CC(=O)SCC1=CC=NC=C1C JOTSFBGEBKBZHG-UHFFFAOYSA-N 0.000 description 1
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- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
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- RBBWNXJFTBCLKT-UHFFFAOYSA-M sodium;ethanethioate Chemical compound [Na+].CC([S-])=O RBBWNXJFTBCLKT-UHFFFAOYSA-M 0.000 description 1
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- CHHDHVBATKGUSP-UHFFFAOYSA-N thiadiazol-4-ylmethanol Chemical compound OCC1=CSN=N1 CHHDHVBATKGUSP-UHFFFAOYSA-N 0.000 description 1
- FBCYVVWNGZKMJJ-UHFFFAOYSA-N thiadiazol-4-ylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CSN=N1 FBCYVVWNGZKMJJ-UHFFFAOYSA-N 0.000 description 1
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- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
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- 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
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- 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
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65611—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system (X = CH2, O, S, NH) optionally with an additional double bond and/or substituents, e.g. penicillins and analogs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US42575582A | 1982-09-28 | 1982-09-28 | |
US53001183A | 1983-09-09 | 1983-09-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
CH656130A5 true CH656130A5 (de) | 1986-06-13 |
Family
ID=27026797
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH5263/83A CH656130A5 (de) | 1982-09-28 | 1983-09-28 | Carbapenemantibiotika. |
Country Status (29)
Country | Link |
---|---|
KR (1) | KR890002228B1 (cs) |
AR (1) | AR241785A1 (cs) |
AT (1) | AT382621B (cs) |
AU (1) | AU575541B2 (cs) |
CA (1) | CA1269978A (cs) |
CH (1) | CH656130A5 (cs) |
CS (1) | CS247168B2 (cs) |
DD (1) | DD212255A5 (cs) |
DE (1) | DE3334937A1 (cs) |
DK (1) | DK442383A (cs) |
ES (1) | ES8503354A1 (cs) |
FI (1) | FI78094C (cs) |
FR (1) | FR2533568B1 (cs) |
GB (1) | GB2128187B (cs) |
GR (1) | GR78696B (cs) |
HU (1) | HU191066B (cs) |
IE (1) | IE55947B1 (cs) |
IL (1) | IL69824A (cs) |
IT (1) | IT1163944B (cs) |
LU (1) | LU85021A1 (cs) |
NL (1) | NL8303310A (cs) |
NO (1) | NO163284C (cs) |
NZ (1) | NZ205626A (cs) |
OA (1) | OA07548A (cs) |
PT (1) | PT77404B (cs) |
SE (1) | SE461734B (cs) |
SU (1) | SU1493108A3 (cs) |
YU (1) | YU43196B (cs) |
ZW (1) | ZW20783A1 (cs) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4683296A (en) * | 1983-03-07 | 1987-07-28 | Bristol-Myers Company | Carbapenem intermediates |
CA1273012A (en) * | 1984-07-02 | 1990-08-21 | Burton G. Christensen | 1-methylcarbapenems having an externally alkylated mono- of bicyclic 2-quarternary heteroarylalkylthio substituent |
CA1273011A (en) * | 1984-07-02 | 1990-08-21 | Susan M. Schmitt | Carbapenems having an externally alkylated mono- or bicyclic 2-quaternary heteroarylalkylthio substituent |
US4729993A (en) * | 1984-12-13 | 1988-03-08 | Merck & Co., Inc. | Carbapenems and 1-methylcarbapenems having an externally alkylated mono- or bicyclic 2-quaternary heteroarylalkyl substituent |
US4725594A (en) * | 1984-12-13 | 1988-02-16 | Merck & Co., Inc. | Carbapenems having an internally or externally alkylated mono- or bicyclic 2-quaternary heteroarylalxyl heteromethyl substituent |
US4680292A (en) * | 1984-12-13 | 1987-07-14 | Merck & Co., Inc. | Carbapenems and 1-methylcarbapenems having a 2-heteroaryliumaliphatic substituent |
US4665169A (en) * | 1985-09-11 | 1987-05-12 | Bristol-Myers Company | Carbapenem antibiotics |
US4880922A (en) * | 1985-11-22 | 1989-11-14 | Bristol-Myers Company | Carbapenems with quaternized heterothioalkylthio substitution at position 2 |
NZ219892A (en) * | 1986-04-15 | 1991-02-26 | Merck & Co Inc | N-amino quaternised heteroarylium carbapenem derivatives and pharmaceutical compositions thereof |
DK168047B1 (da) * | 1987-12-07 | 1994-01-24 | Lederle Japan Ltd | (1r,5s,6s)-2-substitueret thio-6-oe(r)-1-hydroxyethylaa-1-methyl-carbapenem-3-carboxylsyrederivater, fremgangsmaade til remstilling deraf, midler og praeparater indeholdende den krystallinske forbindelse samt dens anvendelse. |
EP0876370A1 (en) | 1996-01-12 | 1998-11-11 | Takeda Chemical Industries, Ltd. | Carbapenem compounds, their production and use |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0017992A1 (en) * | 1979-04-19 | 1980-10-29 | Merck & Co. Inc. | 2-Substituted-6-substituted-1-carbadethiapen-2-em-3-carboxylic acids, processes for preparing them, antibiotic pharmaceutical compositions containing same and process for preparing intermediates |
IE52147B1 (en) * | 1980-03-27 | 1987-07-08 | Merck & Co Inc | 4-(3-carboxy-2-oxopropyl)-azetidin-2-ones and process for their preparation |
EP0038869A1 (en) * | 1980-04-30 | 1981-11-04 | Merck & Co. Inc. | Process for the preparation of 1-carbapenems, and intermediates for their preparation |
PT73791B (en) * | 1980-10-17 | 1983-10-14 | Merck & Co Inc | Process for preparing 2-carbamimidoyl-6-substituted-1- -carbadethiapen-2-em-3-carboxylic acids |
EP0050927B1 (en) * | 1980-10-25 | 1985-03-27 | Beecham Group Plc | The preparation of beta-lactam antibiotics |
US4552873A (en) * | 1981-08-19 | 1985-11-12 | Sankyo Company Limited | Carbapenem compounds, and compositions containing them |
EP0074599A1 (en) * | 1981-09-09 | 1983-03-23 | Takeda Chemical Industries, Ltd. | 5,6-cis-Carbapenem derivatives, their production and use |
-
1983
- 1983-09-16 CA CA000436924A patent/CA1269978A/en not_active Expired - Lifetime
- 1983-09-16 NZ NZ205626A patent/NZ205626A/en unknown
- 1983-09-21 AU AU19342/83A patent/AU575541B2/en not_active Ceased
- 1983-09-22 GR GR72509A patent/GR78696B/el unknown
- 1983-09-22 YU YU1906/83A patent/YU43196B/xx unknown
- 1983-09-22 FR FR838315069A patent/FR2533568B1/fr not_active Expired - Fee Related
- 1983-09-23 FI FI833417A patent/FI78094C/fi not_active IP Right Cessation
- 1983-09-27 NL NL8303310A patent/NL8303310A/nl not_active Application Discontinuation
- 1983-09-27 NO NO833479A patent/NO163284C/no unknown
- 1983-09-27 SU SU833648007A patent/SU1493108A3/ru active
- 1983-09-27 AR AR83294329A patent/AR241785A1/es active
- 1983-09-27 DE DE19833334937 patent/DE3334937A1/de active Granted
- 1983-09-27 GB GB08325744A patent/GB2128187B/en not_active Expired
- 1983-09-27 ES ES525983A patent/ES8503354A1/es not_active Expired
- 1983-09-27 DK DK442383A patent/DK442383A/da not_active Application Discontinuation
- 1983-09-27 CS CS837049A patent/CS247168B2/cs unknown
- 1983-09-27 IE IE2266/83A patent/IE55947B1/en not_active IP Right Cessation
- 1983-09-27 SE SE8305217A patent/SE461734B/sv not_active IP Right Cessation
- 1983-09-27 OA OA58118A patent/OA07548A/xx unknown
- 1983-09-27 IT IT23022/83A patent/IT1163944B/it active
- 1983-09-27 HU HU833351A patent/HU191066B/hu not_active IP Right Cessation
- 1983-09-27 IL IL69824A patent/IL69824A/xx unknown
- 1983-09-27 PT PT77404A patent/PT77404B/pt not_active IP Right Cessation
- 1983-09-28 ZW ZW207/83A patent/ZW20783A1/xx unknown
- 1983-09-28 KR KR1019830004574A patent/KR890002228B1/ko not_active IP Right Cessation
- 1983-09-28 CH CH5263/83A patent/CH656130A5/de not_active IP Right Cessation
- 1983-09-28 AT AT0344983A patent/AT382621B/de not_active IP Right Cessation
- 1983-09-28 DD DD83255191A patent/DD212255A5/de not_active IP Right Cessation
- 1983-09-28 LU LU85021A patent/LU85021A1/fr unknown
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