IL102093A - 1-methylcarbapenem derivatives process for the preparation thereof and pharmaceutical compositions containing the same - Google Patents

1-methylcarbapenem derivatives process for the preparation thereof and pharmaceutical compositions containing the same

Info

Publication number: IL102093A
Authority: IL; Israel
Prior art keywords: group; carbon atoms; groups; hydrogen atom; methyl
Prior art date: 1991-06-04

Application number

IL10209392A

Other languages

English (en)

Other versions

IL102093A0 (en

Original Assignee

Sankyo Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-06-04

Filing date

1992-06-03

Publication date

1996-12-05

1992-06-03 Application filed by Sankyo Co filed Critical Sankyo Co

1993-01-14 Publication of IL102093A0 publication Critical patent/IL102093A0/xx

1996-12-05 Publication of IL102093A publication Critical patent/IL102093A/en

Links

238000000034 method Methods 0.000 title claims abstract description 147
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
238000002360 preparation method Methods 0.000 title description 166
YKMONJZIUAOVEM-GDVGLLTNSA-N (5S)-4-methyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class CC1C=CN2[C@H]1CC2=O YKMONJZIUAOVEM-GDVGLLTNSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 435
125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 50
239000003242 anti bacterial agent Substances 0.000 claims abstract description 9
125000004122 cyclic group Chemical group 0.000 claims abstract description 4
125000002015 acyclic group Chemical group 0.000 claims abstract description 3
-1 phenacyl group Chemical group 0.000 claims description 694
125000004432 carbon atom Chemical group C* 0.000 claims description 344
125000000217 alkyl group Chemical group 0.000 claims description 171
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 170
125000001424 substituent group Chemical group 0.000 claims description 133
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 121
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 70
150000003839 salts Chemical class 0.000 claims description 63
125000003545 alkoxy group Chemical group 0.000 claims description 52
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 42
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 40
125000005843 halogen group Chemical group 0.000 claims description 39
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
150000002148 esters Chemical class 0.000 claims description 35
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 35
125000004093 cyano group Chemical group *C#N 0.000 claims description 34
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 32
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 31
125000003342 alkenyl group Chemical group 0.000 claims description 26
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 24
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 24
125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 claims description 22
125000000304 alkynyl group Chemical group 0.000 claims description 22
125000003277 amino group Chemical group 0.000 claims description 18
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 18
230000003115 biocidal effect Effects 0.000 claims description 15
229910003827 NRaRb Inorganic materials 0.000 claims description 14
125000004430 oxygen atom Chemical group O* 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 13
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 12
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 12
125000006239 protecting group Chemical group 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 11
WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
125000004434 sulfur atom Chemical group 0.000 claims description 10
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
125000001931 aliphatic group Chemical group 0.000 claims description 7
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
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 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 6
125000005041 acyloxyalkyl group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
125000005236 alkanoylamino group Chemical group 0.000 claims description 5
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 5
238000011282 treatment Methods 0.000 claims description 5
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 claims description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
208000015181 infectious disease Diseases 0.000 claims description 4
125000002950 monocyclic group Chemical group 0.000 claims description 4
125000005633 phthalidyl group Chemical group 0.000 claims description 4
125000003367 polycyclic group Polymers 0.000 claims description 4
238000011321 prophylaxis Methods 0.000 claims description 4
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 4
125000001443 terpenyl group Chemical group 0.000 claims description 4
239000002671 adjuvant Substances 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
PISHMUNFQHMFRU-RZBMREITSA-N (5S)-3-[5-(1,4-diazepane-1-carbonyl)-1-methylpyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1(CCNCCC1)C(=O)C1N(CC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C)C PISHMUNFQHMFRU-RZBMREITSA-N 0.000 claims description 2
VQPULULJDGLWBN-BSNDHVMCSA-N (5S)-3-[5-(3-aminopyrrolidine-1-carbonyl)-1-methylpyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound NC1CN(CC1)C(=O)C1N(CC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C)C VQPULULJDGLWBN-BSNDHVMCSA-N 0.000 claims description 2
QDHHNFAFZUUAQE-XQPVXRMQSA-N (5S)-3-[5-(3-aminopyrrolidine-1-carbonyl)pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound NC1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C QDHHNFAFZUUAQE-XQPVXRMQSA-N 0.000 claims description 2
ZEIYKRKJKYHIDP-BZPHROGQSA-N (5S)-3-[5-[4-(carboxymethyl)-1,4-diazepane-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C(=O)(O)CN1CCN(CCC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C ZEIYKRKJKYHIDP-BZPHROGQSA-N 0.000 claims description 2
LQHRMTBLKMLGFG-BSNDHVMCSA-N (5S)-6-(1-hydroxyethyl)-3-[5-[3-(hydroxymethyl)piperazine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OCC1CN(CCN1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C LQHRMTBLKMLGFG-BSNDHVMCSA-N 0.000 claims description 2
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 2
125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
230000000813 microbial effect Effects 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 2
125000005353 silylalkyl group Chemical group 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical group 0.000 claims description 2
GKPFLJGWDOEUAZ-QXGXVAPBSA-N (5S)-6-(1-hydroxyethyl)-3-[5-[4-(2-hydroxyethyl)-1,4-diazepane-1-carbonyl]pyrrolidin-3-yl]sulfanyl-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OCCN1CCN(CCC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C GKPFLJGWDOEUAZ-QXGXVAPBSA-N 0.000 claims 1
HALFTGQSOSVAHG-RZBMREITSA-N (5S)-6-(1-hydroxyethyl)-3-[5-[4-(2-hydroxyethyl)piperazine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OCCN1CCN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C HALFTGQSOSVAHG-RZBMREITSA-N 0.000 claims 1
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 1
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
125000005530 alkylenedioxy group Chemical group 0.000 claims 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 51
229910052739 hydrogen Inorganic materials 0.000 abstract description 51
239000001257 hydrogen Substances 0.000 abstract description 51
238000001727 in vivo Methods 0.000 abstract description 12
108090000204 Dipeptidase 1 Proteins 0.000 abstract description 9
102000003850 Dipeptidase 1 Human genes 0.000 abstract description 8
229940088710 antibiotic agent Drugs 0.000 abstract description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 423
239000000203 mixture Substances 0.000 description 347
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
238000000862 absorption spectrum Methods 0.000 description 229
239000000243 solution Substances 0.000 description 200
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 198
239000000843 powder Substances 0.000 description 179
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 142
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 142
230000002829 reductive effect Effects 0.000 description 141
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
238000001816 cooling Methods 0.000 description 108
239000011541 reaction mixture Substances 0.000 description 107
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 92
238000001704 evaporation Methods 0.000 description 83
230000008020 evaporation Effects 0.000 description 83
239000002904 solvent Substances 0.000 description 73
238000004821 distillation Methods 0.000 description 57
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 56
239000007864 aqueous solution Substances 0.000 description 56
238000004440 column chromatography Methods 0.000 description 56
239000003480 eluent Substances 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 51
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 51
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 50
230000005587 bubbling Effects 0.000 description 47
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 45
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 38
239000002253 acid Substances 0.000 description 33
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 32
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 31
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000011780 sodium chloride Substances 0.000 description 28
GUGYCHHWTVUBLV-MSECNUKYSA-N (4-nitrophenyl)methyl (4r,5r,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H](C)[C@@H]1[C@H](C(N11)=O)[C@H](O)C)C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 GUGYCHHWTVUBLV-MSECNUKYSA-N 0.000 description 26
239000000706 filtrate Substances 0.000 description 26
JQWUEVPNOSPHNN-OALUTQOASA-N (2s,4s)-4-[(4-methoxyphenyl)methylsulfanyl]-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CS[C@@H]1CN(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)[C@H](C(O)=O)C1 JQWUEVPNOSPHNN-OALUTQOASA-N 0.000 description 25
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
239000000047 product Substances 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
238000001914 filtration Methods 0.000 description 23
239000000741 silica gel Substances 0.000 description 23
229910002027 silica gel Inorganic materials 0.000 description 23
239000007787 solid Substances 0.000 description 23
239000003054 catalyst Substances 0.000 description 22
239000011734 sodium Substances 0.000 description 22
229910052708 sodium Inorganic materials 0.000 description 22
NFUHGQVNWQOHQB-UHFFFAOYSA-N sodium;trimethylsilyl propanoate Chemical class [Na].CCC(=O)O[Si](C)(C)C NFUHGQVNWQOHQB-UHFFFAOYSA-N 0.000 description 21
239000010410 layer Substances 0.000 description 20
229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
235000017557 sodium bicarbonate Nutrition 0.000 description 20
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 19
239000012071 phase Substances 0.000 description 18
230000002441 reversible effect Effects 0.000 description 18
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 17
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 16
229910052731 fluorine Inorganic materials 0.000 description 14
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 13
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
239000003153 chemical reaction reagent Substances 0.000 description 13
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 13
239000011737 fluorine Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000000725 suspension Substances 0.000 description 12
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 11
239000012141 concentrate Substances 0.000 description 11
235000008504 concentrate Nutrition 0.000 description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 10
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 10
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
125000001309 chloro group Chemical group Cl* 0.000 description 10
PBCKXLVCCOURLL-UHFFFAOYSA-N (4-nitrophenyl)methyl (ne)-n-(aminomethylidene)carbamate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)NC=N)C=C1 PBCKXLVCCOURLL-UHFFFAOYSA-N 0.000 description 9
AKYYURPUIANXHR-UHFFFAOYSA-N (4-nitrophenyl)methyl (nz)-n-(1-aminoethylidene)carbamate Chemical compound CC(=N)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 AKYYURPUIANXHR-UHFFFAOYSA-N 0.000 description 9
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
239000007788 liquid Substances 0.000 description 9
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
150000007513 acids Chemical class 0.000 description 8
150000007942 carboxylates Chemical class 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
150000003573 thiols Chemical class 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 7
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
239000013078 crystal Substances 0.000 description 6
238000010908 decantation Methods 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
125000004185 ester group Chemical group 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
125000005394 methallyl group Chemical group 0.000 description 6
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
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241000589516 Pseudomonas Species 0.000 description 1
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102100027981 Septin-7 Human genes 0.000 description 1
241000607720 Serratia Species 0.000 description 1
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241000191940 Staphylococcus Species 0.000 description 1
241000193998 Streptococcus pneumoniae Species 0.000 description 1
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CVNMBKFJYRAHPO-UHFFFAOYSA-N [chloro(methyl)phosphoryl]methane Chemical compound CP(C)(Cl)=O CVNMBKFJYRAHPO-UHFFFAOYSA-N 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
239000008272 agar Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910052977 alkali metal sulfide Inorganic materials 0.000 description 1
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
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230000001580 bacterial effect Effects 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
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230000015572 biosynthetic process Effects 0.000 description 1
ZOECHGOEOMZVIT-ASYYUYISSA-N bis[(4-nitrophenyl)methyl] 4-[(2s,4s)-1-[(4-nitrophenyl)methoxycarbonyl]-4-sulfanylpyrrolidine-2-carbonyl]piperazine-1,2-dicarboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1N(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)CCN(C(=O)[C@H]2N(C[C@@H](S)C2)C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)C1 ZOECHGOEOMZVIT-ASYYUYISSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
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125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
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125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
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239000002775 capsule Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
229960004106 citric acid Drugs 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229940125961 compound 24 Drugs 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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238000010511 deprotection reaction Methods 0.000 description 1
125000006003 dichloroethyl group Chemical group 0.000 description 1
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239000003814 drug Substances 0.000 description 1
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239000008187 granular material Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
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125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
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238000007911 parenteral administration Methods 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
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UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
125000001189 phytyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])([H])[C@@](C([H])([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])[C@@](C([H])([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
SIRSTRHGFGFVME-UHFFFAOYSA-N piperazin-2-ylmethanol Chemical compound OCC1CNCCN1 SIRSTRHGFGFVME-UHFFFAOYSA-N 0.000 description 1
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125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
DPLVEEXVKBWGHE-UHFFFAOYSA-N potassium sulfide Chemical compound [S-2].[K+].[K+] DPLVEEXVKBWGHE-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
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NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
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PQBKTTIEJLDTOV-UHFFFAOYSA-N pyrrolidin-1-ium;trifluoromethanesulfonate Chemical compound C1CCNC1.OS(=O)(=O)C(F)(F)F PQBKTTIEJLDTOV-UHFFFAOYSA-N 0.000 description 1
NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
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GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
230000008023 solidification Effects 0.000 description 1
238000007711 solidification Methods 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229940031000 streptococcus pneumoniae Drugs 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
FMLPQHJYUZTHQS-MRVPVSSYSA-N tert-butyl (3r)-3-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OC(C)(C)C)CCN1 FMLPQHJYUZTHQS-MRVPVSSYSA-N 0.000 description 1
OKUCEQDKBKYEJY-QMMMGPOBSA-N tert-butyl (3s)-3-(methylamino)pyrrolidine-1-carboxylate Chemical compound CN[C@H]1CCN(C(=O)OC(C)(C)C)C1 OKUCEQDKBKYEJY-QMMMGPOBSA-N 0.000 description 1
FMLPQHJYUZTHQS-UHFFFAOYSA-N tert-butyl 3-methylpiperazine-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CCN1 FMLPQHJYUZTHQS-UHFFFAOYSA-N 0.000 description 1
BZEPVRDRMKGKEI-KFTXQHHCSA-N tert-butyl 4-[(2s,4s)-4-[(4-methoxyphenyl)methylsulfanyl]-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carbonyl]-3-methylpiperazine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CS[C@@H]1CN(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)[C@H](C(=O)N2C(CN(CC2)C(=O)OC(C)(C)C)C)C1 BZEPVRDRMKGKEI-KFTXQHHCSA-N 0.000 description 1
CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
241001148471 unidentified anaerobic bacterium Species 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011701 zinc Substances 0.000 description 1
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Classifications

- 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
- 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

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Cephalosporin Compounds (AREA)

IL10209392A 1991-06-04 1992-06-03 1-methylcarbapenem derivatives process for the preparation thereof and pharmaceutical compositions containing the same IL102093A (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
JP13154591		1991-06-04
JP34573791		1991-12-27
JP3052192		1992-02-18
JP9128392		1992-04-10

Publications (2)

Publication Number	Publication Date
IL102093A0 IL102093A0 (en)	1993-01-14
IL102093A true IL102093A (en)	1996-12-05

Family

ID=27459269

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10209392A IL102093A (en)	1991-06-04	1992-06-03	1-methylcarbapenem derivatives process for the preparation thereof and pharmaceutical compositions containing the same

Country Status (20)

Country	Link
EP (1)	EP0518558B1 (de)
JP (1)	JP2559949B2 (de)
KR (1)	KR100247855B1 (de)
CN (1)	CN1030767C (de)
AT (1)	ATE170521T1 (de)
AU (1)	AU651887B2 (de)
CA (1)	CA2070305A1 (de)
CZ (1)	CZ167792A3 (de)
DE (1)	DE69226815T2 (de)
DK (1)	DK0518558T3 (de)
ES (1)	ES2120992T3 (de)
FI (1)	FI101226B1 (de)
HU (2)	HU218289B (de)
IE (1)	IE921796A1 (de)
IL (1)	IL102093A (de)
MX (1)	MX9202670A (de)
NO (1)	NO302475B1 (de)
NZ (1)	NZ243022A (de)
RU (1)	RU2093514C1 (de)
TW (1)	TW203612B (de)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5712267A (en) *	1991-06-04	1998-01-27	Sankyo Company,. Limited	Carbapenem derivatives, their preparation and their use as antibiotics
GB9202298D0 (en) *	1992-02-04	1992-03-18	Ici Plc	Antibiotic compounds
CZ290002B6 (cs) *	1992-03-11	2002-05-15	Sankyo Company Limited	Antimikrobiální karbapenemové deriváty, způsob výroby a farmaceutický prostředek
GB9304156D0 (en) *	1992-03-26	1993-04-21	Zeneca Ltd	Antibiotic compounds
CA2099818A1 (en) *	1992-07-21	1994-01-22	Frederic H. Jung	Antibiotic compounds
EP0581502B1 (de) *	1992-07-21	1998-10-21	Zeneca Limited	Antibiotische carbapenemverbindungen
AU4912393A (en) *	1993-06-15	1994-12-22	Dong Kook Pharmaceutical Co., Ltd.	1-beta-methyl-2-thiolic carbapenem derivatives
JP3848693B2 (ja) *	1994-07-06	2006-11-22	エーザイ・アール・アンド・ディー・マネジメント株式会社	新規カルバペネム誘導体
GB9515975D0 (en)	1995-08-04	1995-10-04	Zeneca Ltd	Chemical compounds
EP0882728B1 (de) *	1995-12-21	2002-09-04	Sankyo Company Limited	1-methylcarbapenem-derivate
WO1997041123A1 (en) *	1996-04-26	1997-11-06	Sankyo Company, Limited	1-methylcarbapenem derivatives
AU4020897A (en)	1996-08-17	1998-03-06	Zeneca Limited	3-mercaptopyrrolidines as farnesyl protein transferase inhibitors
WO2000034282A1 (en) *	1998-12-07	2000-06-15	Sankyo Company, Limited	1-methylcarbapenem derivatives
GB9930318D0 (en)	1999-12-22	2000-02-09	Zeneca Ltd	Novel compounds
GB9930317D0 (en)	1999-12-22	2000-02-09	Zeneca Ltd	Novel compounds
JP4619655B2 (ja)	2001-09-14	2011-01-26	ハイ・ポイント・ファーマスーティカルズ、エルエルシー	新規アミノアゼチジン、−ピロリジンおよび−ピペリジン誘導体
US6673829B2 (en)	2001-09-14	2004-01-06	Novo Nordisk A/S	Aminoazetidine,-pyrrolidine and -piperidine derivatives
CN101367814B (zh) *	2007-06-28	2010-12-15	山东轩竹医药科技有限公司	被巯基吡咯烷甲酰哌啶取代的培南衍生物
US8236792B2 (en) *	2008-05-23	2012-08-07	Janssen Pharmaceutica Nv	Substituted pyrrolidine amides as modulators of the histamine H3 receptor
WO2017158616A1 (en)	2016-03-16	2017-09-21	Orchid Pharma Ltd.	Carbapenem compounds

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1283906C (en) *	1983-05-09	1991-05-07	Makoto Sunagawa	.beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF
JPS60233076A (ja) *	1984-05-03	1985-11-19	Sumitomo Chem Co Ltd	新規なβ−ラクタム化合物およびその製造法
DE3780344T2 (de) *	1986-03-27	1993-01-28	Sumitomo Pharma	Beta-lactam-verbindungen und deren herstellung.
CA2036163C (en) *	1990-02-14	2001-06-19	Makoto Sunagawa	Novel beta-lactam compounds and their production
CA2036941A1 (en) *	1990-02-23	1991-08-24	Isao Kawamoto	Carbapenem derivatives having antibiotic activity, their preparation and their use
TW198034B (de) *	1990-03-27	1993-01-11	Manyu Seiyaku Kk
AU644008B2 (en) *	1990-08-10	1993-12-02	Sumitomo Pharmaceuticals Company, Limited	Beta-lactam compounds, and their production and use
CZ290002B6 (cs) *	1992-03-11	2002-05-15	Sankyo Company Limited	Antimikrobiální karbapenemové deriváty, způsob výroby a farmaceutický prostředek

1992
- 1992-06-03 FI FI922561A patent/FI101226B1/fi active
- 1992-06-03 JP JP4142286A patent/JP2559949B2/ja not_active Expired - Fee Related
- 1992-06-03 AU AU17390/92A patent/AU651887B2/en not_active Ceased
- 1992-06-03 IL IL10209392A patent/IL102093A/en not_active IP Right Cessation
- 1992-06-03 NO NO922185A patent/NO302475B1/no unknown
- 1992-06-03 RU SU5052110/04A patent/RU2093514C1/ru not_active IP Right Cessation
- 1992-06-03 CA CA002070305A patent/CA2070305A1/en not_active Abandoned
- 1992-06-03 CZ CS921677A patent/CZ167792A3/cs unknown
- 1992-06-04 MX MX9202670A patent/MX9202670A/es unknown
- 1992-06-04 ES ES92305130T patent/ES2120992T3/es not_active Expired - Lifetime
- 1992-06-04 TW TW081104407A patent/TW203612B/zh active
- 1992-06-04 DK DK92305130T patent/DK0518558T3/da active
- 1992-06-04 NZ NZ243022A patent/NZ243022A/xx unknown
- 1992-06-04 KR KR1019920009702A patent/KR100247855B1/ko not_active Expired - Fee Related
- 1992-06-04 HU HU9201871A patent/HU218289B/hu not_active IP Right Cessation
- 1992-06-04 CN CN92108826A patent/CN1030767C/zh not_active Expired - Fee Related
- 1992-06-04 DE DE69226815T patent/DE69226815T2/de not_active Expired - Fee Related
- 1992-06-04 EP EP92305130A patent/EP0518558B1/de not_active Expired - Lifetime
- 1992-06-04 AT AT92305130T patent/ATE170521T1/de not_active IP Right Cessation
- 1992-07-01 IE IE179692A patent/IE921796A1/en not_active IP Right Cessation
1995
- 1995-06-29 HU HU95P/P00604P patent/HU211822A9/hu unknown

Also Published As

Publication number	Publication date
JP2559949B2 (ja)	1996-12-04
ATE170521T1 (de)	1998-09-15
CZ167792A3 (en)	1995-12-13
KR100247855B1 (ko)	2000-05-01
CA2070305A1 (en)	1992-12-05
NO922185D0 (no)	1992-06-03
CN1069494A (zh)	1993-03-03
JPH05339269A (ja)	1993-12-21
FI922561L (fi)	1992-12-05
IL102093A0 (en)	1993-01-14
FI922561A0 (fi)	1992-06-03
HU9201871D0 (en)	1992-08-28
HK1011980A1 (en)	1999-07-23
CN1030767C (zh)	1996-01-24
ES2120992T3 (es)	1998-11-16
DE69226815D1 (de)	1998-10-08
AU651887B2 (en)	1994-08-04
NZ243022A (en)	1993-07-27
KR930000515A (ko)	1993-01-15
EP0518558A1 (de)	1992-12-16
EP0518558B1 (de)	1998-09-02
DK0518558T3 (da)	1999-05-31
AU1739092A (en)	1993-03-11
NO302475B1 (no)	1998-03-09
HU211822A9 (en)	1995-12-28
TW203612B (de)	1993-04-11
FI101226B (fi)	1998-05-15
FI101226B1 (fi)	1998-05-15
IE921796A1 (en)	1992-12-16
DE69226815T2 (de)	1999-05-20
NO922185L (no)	1992-12-07
HU218289B (en)	2000-07-28
HUT61551A (en)	1993-01-28
RU2093514C1 (ru)	1997-10-20
MX9202670A (es)	1993-01-01

Legal Events

Date	Code	Title
1997-06-10	FF	Patent granted
1997-11-20	KB	Patent renewed
1998-12-06	KB	Patent renewed
2002-07-25	KB	Patent renewed
2007-02-12	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0518558B1 (de)	1998-09-02	1-Methyl-carbapenemderivate, deren Herstellung und Verwendung als Antibiotika
US5104867A (en)	1992-04-14	2-(heterocyclylthio)carbapenem derivatives, their preparation and their use as antibiotics
US5310735A (en)	1994-05-10	Carbapenem derivatives having antibiotic activity, their preparation and their use
AU711135B2 (en)	1999-10-07	1-methylcarbapenem derivatives
US5242914A (en)	1993-09-07	2-(heterocyclylthio) carbapenem derivatives, their preparation and their use as antibiotics
RU2097383C1 (ru)	1997-11-27	Производные карбапенема и способ их получения
DE60130916T2 (de)	2008-07-10	Neue beta-lactamverbindungen und verfahren zu deren herstellung
JP3199300B2 (ja)	2001-08-13	１−メチルカルバペネム誘導体
RU2160737C2 (ru)	2000-12-20	Производные 1-метилкарбапенема, способ их получения, фармацевтическая композиция на их основе и способ антибактериального воздействия
JP2003183281A (ja)	2003-07-03	カルバペネム化合物
HK1011980B (en)	2000-03-24	1-methylcarbapenem derivatives, their preparation and their use as antibiotics
JP2003183280A (ja)	2003-07-03	カルバペネム化合物
HK1015766B (en)	2003-05-02	1-methylcarbapenem derivatives
HK1011015A (en)	1999-07-02	2-(heterocyclylthio) carbapenem derivatives their preparation and their use as antibiotics