LU84864A1 - Produits nouveaux de la classe des carbapenems et leur application en tant qu'antibiotiques - Google Patents
Produits nouveaux de la classe des carbapenems et leur application en tant qu'antibiotiques Download PDFInfo
- Publication number
- LU84864A1 LU84864A1 LU84864A LU84864A LU84864A1 LU 84864 A1 LU84864 A1 LU 84864A1 LU 84864 A LU84864 A LU 84864A LU 84864 A LU84864 A LU 84864A LU 84864 A1 LU84864 A1 LU 84864A1
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- LU
- Luxembourg
- Prior art keywords
- carbon atoms
- alkyl
- group
- chosen
- atoms
- Prior art date
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- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical class C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title claims description 51
- 239000003242 anti bacterial agent Substances 0.000 title claims description 9
- 229940088710 antibiotic agent Drugs 0.000 title description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 270
- 125000000623 heterocyclic group Chemical group 0.000 claims description 203
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 197
- 150000001875 compounds Chemical class 0.000 claims description 173
- 125000001424 substituent group Chemical group 0.000 claims description 140
- 125000000217 alkyl group Chemical group 0.000 claims description 139
- 229910052757 nitrogen Inorganic materials 0.000 claims description 139
- -1 chloro, carboxyl Chemical group 0.000 claims description 135
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 135
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 105
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 90
- 125000004429 atom Chemical group 0.000 claims description 85
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 80
- 125000003118 aryl group Chemical group 0.000 claims description 74
- 125000005842 heteroatom Chemical group 0.000 claims description 72
- 125000006239 protecting group Chemical group 0.000 claims description 70
- 125000001153 fluoro group Chemical group F* 0.000 claims description 66
- 229910052760 oxygen Inorganic materials 0.000 claims description 66
- 239000001301 oxygen Substances 0.000 claims description 66
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 65
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 63
- 125000003342 alkenyl group Chemical group 0.000 claims description 61
- 125000000304 alkynyl group Chemical group 0.000 claims description 59
- 125000001072 heteroaryl group Chemical group 0.000 claims description 58
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 57
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 55
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 53
- 125000001246 bromo group Chemical group Br* 0.000 claims description 53
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 52
- 229910001868 water Inorganic materials 0.000 claims description 52
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
- 125000001931 aliphatic group Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000004434 sulfur atom Chemical group 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 41
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
- 125000000129 anionic group Chemical group 0.000 claims description 34
- 125000002947 alkylene group Chemical group 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 30
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 27
- 125000004979 cyclopentylene group Chemical group 0.000 claims description 27
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- 239000011593 sulfur Substances 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 22
- 125000001118 alkylidene group Chemical group 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims description 18
- 125000003367 polycyclic group Chemical group 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 13
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 8
- 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 claims description 7
- 238000006073 displacement reaction Methods 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 230000003115 biocidal effect Effects 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 150000002500 ions Chemical class 0.000 claims description 5
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 230000001681 protective effect Effects 0.000 claims description 4
- 239000003643 water by type Substances 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 3
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims 1
- 150000001805 chlorine compounds Chemical class 0.000 claims 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims 1
- 229940006461 iodide ion Drugs 0.000 claims 1
- 125000006502 nitrobenzyl group Chemical group 0.000 claims 1
- 230000001012 protector Effects 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 39
- 239000000543 intermediate Substances 0.000 description 34
- 239000000203 mixture Substances 0.000 description 31
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 150000003254 radicals Chemical class 0.000 description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 23
- 238000001228 spectrum Methods 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 150000001450 anions Chemical class 0.000 description 18
- 230000000704 physical effect Effects 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- 150000002367 halogens Chemical class 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 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 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
- 239000008363 phosphate buffer Substances 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-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
- 150000007942 carboxylates Chemical class 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 229940041011 carbapenems Drugs 0.000 description 10
- 238000007918 intramuscular administration Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 9
- 238000004108 freeze drying Methods 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 241000588697 Enterobacter cloacae Species 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 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 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 150000003952 β-lactams Chemical class 0.000 description 7
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 5
- 244000038458 Nepenthes mirabilis Species 0.000 description 5
- 230000036765 blood level Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 150000003573 thiols Chemical class 0.000 description 5
- 230000002485 urinary effect Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 4
- 241000194032 Enterococcus faecalis Species 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 241000588772 Morganella morganii Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 244000110797 Polygonum persicaria Species 0.000 description 4
- 241000588777 Providencia rettgeri Species 0.000 description 4
- 241000607715 Serratia marcescens Species 0.000 description 4
- 241000193996 Streptococcus pyogenes Species 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 125000004185 ester group Chemical group 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
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- 125000002950 monocyclic group Chemical group 0.000 description 4
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- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000421809 Brisaster fragilis Species 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
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- 238000001704 evaporation Methods 0.000 description 3
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- 238000002955 isolation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KDTVWEHAAISPNW-UHFFFAOYSA-N 4-methylthiomorpholine Chemical compound CN1CCSCC1 KDTVWEHAAISPNW-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
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- 125000002541 furyl group Chemical group 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 125000002636 imidazolinyl group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
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- 125000002757 morpholinyl group Chemical group 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
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- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38965282A | 1982-06-18 | 1982-06-18 | |
| US38965282 | 1982-06-18 | ||
| US49969083 | 1983-06-07 | ||
| US06/499,690 US4536335A (en) | 1982-06-18 | 1983-06-07 | Carbapenem antibiotics |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU84864A1 true LU84864A1 (fr) | 1984-03-07 |
Family
ID=27012789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU84864A LU84864A1 (fr) | 1982-06-18 | 1983-06-17 | Produits nouveaux de la classe des carbapenems et leur application en tant qu'antibiotiques |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4536335A (en]) |
| KR (1) | KR890000192B1 (en]) |
| AT (1) | AT381941B (en]) |
| AU (1) | AU567294B2 (en]) |
| CA (1) | CA1273009A (en]) |
| CH (1) | CH658657A5 (en]) |
| DE (1) | DE3321864A1 (en]) |
| DK (1) | DK276683A (en]) |
| ES (1) | ES523315A0 (en]) |
| FI (1) | FI77036C (en]) |
| FR (1) | FR2528847B1 (en]) |
| GB (1) | GB2122196B (en]) |
| GR (1) | GR78375B (en]) |
| HU (1) | HU191052B (en]) |
| IE (1) | IE55432B1 (en]) |
| IL (1) | IL69002A (en]) |
| IT (1) | IT1206324B (en]) |
| LU (1) | LU84864A1 (en]) |
| MY (1) | MY8800124A (en]) |
| NL (1) | NL8302183A (en]) |
| OA (1) | OA07468A (en]) |
| PT (1) | PT76887B (en]) |
| SE (1) | SE460791B (en]) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683301A (en) * | 1982-04-08 | 1987-07-28 | Bristol-Myers Company | Carbapenem antibiotics |
| CA1198440A (en) * | 1982-04-08 | 1985-12-24 | Choung U. Kim | Carbapenem antibiotics |
| US4552696A (en) * | 1982-04-09 | 1985-11-12 | Bristol-Myers Company | Carbapenem antibiotics |
| US4640799A (en) * | 1982-06-18 | 1987-02-03 | Bristol-Myers Company | Carbapenem antibiotics |
| US4746736A (en) * | 1982-09-28 | 1988-05-24 | Bristol-Myers Company | Carbapenem antibiotics |
| DK140584A (da) * | 1983-03-08 | 1984-09-09 | Bristol Myers Co | Fremgangsmaade til fremstilling af carbapenemderivater |
| GB8416651D0 (en) * | 1984-06-29 | 1984-08-01 | Erba Farmitalia | Penem derivatives |
| IE851586L (en) * | 1984-07-02 | 1986-01-02 | Interchem Internat S A | I methylcarbapenems having a 2-quaternary¹heteroarylalkylthio substituent |
| US4757066A (en) * | 1984-10-15 | 1988-07-12 | Sankyo Company Limited | Composition containing a penem or carbapenem antibiotic and the use of the same |
| US4680292A (en) * | 1984-12-13 | 1987-07-14 | Merck & Co., Inc. | Carbapenems and 1-methylcarbapenems having a 2-heteroaryliumaliphatic 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 |
| 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 |
| GB8509181D0 (en) * | 1985-04-10 | 1985-05-15 | Erba Farmitalia | Penem derivatives |
| US4788282A (en) * | 1985-06-07 | 1988-11-29 | Bristol-Myers Company | Deprotection of allylic esters and ethers |
| 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 |
| CA1272719A (en) * | 1986-03-06 | 1990-08-14 | Pierre Dextraze | Carbapenem antibiotics |
| US4894450A (en) * | 1987-05-11 | 1990-01-16 | Merck & Co., Inc. | Process for 2-(aminoalkylthio) carbapenems |
| US5362723A (en) * | 1991-07-29 | 1994-11-08 | Merck & Co., Inc. | 2-(heterocyclylheteroaryliumalkyl) phenyl carbapenem antibacterial agents |
| EP1612211A4 (en) * | 2003-04-08 | 2008-07-02 | Dainippon Sumitomo Pharma Co | NEW CARBAPENEM COMPOUNDS |
| EP2623821A1 (de) | 2012-02-06 | 2013-08-07 | Siemens Aktiengesellschaft | Getriebegehäuse, Getriebeeinheit mit einem solchen Getriebegehäuse und Getriebemotor mit einer solchen Getriebeeinheit |
| WO2018175670A1 (en) | 2017-03-22 | 2018-09-27 | The Research Foundation For The State University Of New York | Matrix metalloproteinase-9 hemopexin domain inhibitors and methods of treatment using same |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235920A (en) * | 1975-11-21 | 1980-11-25 | Merck & Co., Inc. | N-Alkylated derivatives of thienamycin |
| FR2332014A1 (fr) * | 1975-11-21 | 1977-06-17 | Merck & Co Inc | Derives n-alcoyles de thienamycine utiles en tant qu'antibiotiques |
| US4226870A (en) * | 1975-11-21 | 1980-10-07 | Merck & Co., Inc. | O-, N- and carboxyl derivatives of thienamycin |
| GB1591439A (en) * | 1976-10-01 | 1981-06-24 | Glaxo Operations Ltd | 7-syn (oxyimino -acylamido) cephalosporins |
| US4234596A (en) * | 1976-11-19 | 1980-11-18 | Merck & Co., Inc. | 3-(2-Aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| US4235917A (en) * | 1977-05-05 | 1980-11-25 | Merck & Co., Inc. | N-Alkyl-N-acyl derivatives of thienamycin |
| AU531084B2 (en) * | 1977-10-19 | 1983-08-11 | Merck & Co., Inc. | Azetidine derivatives |
| AU4061378A (en) * | 1977-10-19 | 1980-04-17 | Merck & Co., Inc. | 1-azabicyclo (3.2.0) hept-2-enes |
| US4218463A (en) * | 1977-12-28 | 1980-08-19 | Merck & Co., Inc. | 3-Substituted thio-6-amido-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| US4189493A (en) * | 1977-12-28 | 1980-02-19 | Merck & Co., Inc. | N-heterocyclic derivatives of thienamycin |
| US4174316A (en) * | 1978-08-14 | 1979-11-13 | Merck & Co., Inc. | 4-Iodomethylazetidin-2-one |
| DE2966497D1 (en) * | 1978-10-24 | 1984-01-26 | Merck & Co Inc | 6-, 1- and 2-substituted-1-carbapen-2-em-3-carboxylic acids, processes for the preparation of such compounds and pharmaceutical composition comprising such compounds |
| US4318912A (en) * | 1979-01-02 | 1982-03-09 | Merck & Co., Inc. | 6-(1-Hydroxyethyl)-3-substituted-1-azabicyclo(3.2.0)-hept-2-en-7-one-2-carboxylic acid |
| 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 |
| US4290947A (en) * | 1979-04-27 | 1981-09-22 | Merck & Co., Inc. | Process for the preparation of thienamycin and intermediates |
| US4376774A (en) * | 1979-05-29 | 1983-03-15 | Merck & Co., Inc. | Antibiotic N-heterocyclyl thienamycin |
| US4273709A (en) * | 1979-07-23 | 1981-06-16 | Merck & Co., Inc. | Process for the preparation of thienamycin and intermediates |
| EP0055990B1 (en) * | 1979-08-10 | 1986-06-11 | Beecham Group Plc | Beta-lactam antibiotics, their preparation and use |
| US4287123A (en) * | 1980-01-14 | 1981-09-01 | Merck & Co., Inc. | Synthesis of thienamycin via (3SR, 4RS)-3-((RS)-1-acyloxyethyl)-2-oxo-4-azetidineacetate |
| US4269772A (en) * | 1980-01-14 | 1981-05-26 | Merck & Co., Inc. | Synthesis of thienamycin via trans-3-carboxymethylene-4-carboxy-5-methyl-Δ2 -isoxazoline |
| US4282148A (en) * | 1980-01-14 | 1981-08-04 | Merck & Co., Inc. | Synthesis of thienamycin via esters of (3SR, 4RS)-3-[(SR)-1-hydroxyethyl]-β,2-dioxo-4-azetidinebutanoic acid |
| DE3169321D1 (en) * | 1980-03-27 | 1985-04-25 | Merck & Co Inc | Process for the preparation of 1-carbapenems and intermediates via silyl-substituted dithioacetals |
| US4309346A (en) * | 1980-03-27 | 1982-01-05 | Merck & Co., Inc. | Process for the preparation of 1-carbapenems and intermediates via trithioorthoacetates |
| 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 |
| JPS56161393A (en) * | 1980-05-16 | 1981-12-11 | Sanraku Inc | Beta-lactam compound |
| EP0044170A1 (en) * | 1980-07-11 | 1982-01-20 | Beecham Group Plc | Beta-lactam antibiotics, their preparation and use |
| 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 |
| 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 |
| CA1198440A (en) * | 1982-04-08 | 1985-12-24 | Choung U. Kim | Carbapenem antibiotics |
| US4552696A (en) * | 1982-04-09 | 1985-11-12 | Bristol-Myers Company | Carbapenem antibiotics |
-
1983
- 1983-06-07 US US06/499,690 patent/US4536335A/en not_active Expired - Fee Related
- 1983-06-14 FR FR8309814A patent/FR2528847B1/fr not_active Expired
- 1983-06-15 CA CA000430410A patent/CA1273009A/en not_active Expired - Lifetime
- 1983-06-15 DK DK276683A patent/DK276683A/da not_active Application Discontinuation
- 1983-06-15 FI FI832175A patent/FI77036C/fi not_active IP Right Cessation
- 1983-06-15 IL IL69002A patent/IL69002A/xx unknown
- 1983-06-15 GR GR71689A patent/GR78375B/el unknown
- 1983-06-16 DE DE3321864A patent/DE3321864A1/de active Granted
- 1983-06-16 ES ES523315A patent/ES523315A0/es active Granted
- 1983-06-17 OA OA58035A patent/OA07468A/xx unknown
- 1983-06-17 GB GB08316617A patent/GB2122196B/en not_active Expired
- 1983-06-17 SE SE8303502A patent/SE460791B/sv not_active IP Right Cessation
- 1983-06-17 PT PT76887A patent/PT76887B/pt not_active IP Right Cessation
- 1983-06-17 KR KR8302711A patent/KR890000192B1/ko not_active Expired
- 1983-06-17 LU LU84864A patent/LU84864A1/fr unknown
- 1983-06-17 AU AU15891/83A patent/AU567294B2/en not_active Ceased
- 1983-06-17 IE IE1431/83A patent/IE55432B1/en not_active IP Right Cessation
- 1983-06-17 HU HU832173A patent/HU191052B/hu not_active IP Right Cessation
- 1983-06-17 NL NL8302183A patent/NL8302183A/xx not_active Application Discontinuation
- 1983-06-17 IT IT8321682A patent/IT1206324B/it active
- 1983-06-20 CH CH3372/83A patent/CH658657A5/de not_active IP Right Cessation
- 1983-06-20 AT AT0226583A patent/AT381941B/de not_active IP Right Cessation
-
1988
- 1988-12-30 MY MY8316617A patent/MY8800124A/xx unknown
Also Published As
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| DT | Application date | ||
| TA | Annual fee |