TW200404809A - Tricyclic 6-alkylidene-penems as β -lactamase inhibitors - Google Patents
Tricyclic 6-alkylidene-penems as β -lactamase inhibitors Download PDFInfo
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- TW200404809A TW200404809A TW092110031A TW92110031A TW200404809A TW 200404809 A TW200404809 A TW 200404809A TW 092110031 A TW092110031 A TW 092110031A TW 92110031 A TW92110031 A TW 92110031A TW 200404809 A TW200404809 A TW 200404809A
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- substituted
- carbon atom
- attached
- cr4r4
- carboxylic acid
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- 239000003781 beta lactamase inhibitor Substances 0.000 title 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 86
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 8
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 229910052799 carbon Inorganic materials 0.000 claims description 429
- 229920006395 saturated elastomer Polymers 0.000 claims description 184
- 229910052717 sulfur Inorganic materials 0.000 claims description 156
- -1 substituted Chemical class 0.000 claims description 147
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 141
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 125000003118 aryl group Chemical group 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 58
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 claims description 58
- 159000000000 sodium salts Chemical class 0.000 claims description 51
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 49
- 230000015572 biosynthetic process Effects 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000005842 heteroatom Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 32
- 239000011734 sodium Substances 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 25
- 238000006664 bond formation reaction Methods 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 238000006467 substitution reaction Methods 0.000 claims description 19
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 claims description 18
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 150000003254 radicals Chemical class 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 150000003852 triazoles Chemical class 0.000 claims description 14
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 230000003115 biocidal effect Effects 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 7
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000005325 aryloxy aryl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- LGRQUXHYJBFGTM-UHFFFAOYSA-N 4H-imidazole Chemical compound C1C=NC=N1 LGRQUXHYJBFGTM-UHFFFAOYSA-N 0.000 claims description 3
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical group C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000005161 aryl oxy carbonyl group Chemical class 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 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 2
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims 1
- OYJGEOAXBALSMM-UHFFFAOYSA-N 2,3-dihydro-1,3-thiazole Chemical compound C1NC=CS1 OYJGEOAXBALSMM-UHFFFAOYSA-N 0.000 claims 1
- OCVXSFKKWXMYPF-UHFFFAOYSA-N 2-chloroimidazole Chemical compound ClC1=NC=CN1 OCVXSFKKWXMYPF-UHFFFAOYSA-N 0.000 claims 1
- KPRGOTLNGIBVFL-GINZOMEDSA-N 7-ketodehydroepiandrosterone Chemical group C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C(=O)C=C21 KPRGOTLNGIBVFL-GINZOMEDSA-N 0.000 claims 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- 229910000831 Steel Inorganic materials 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- 150000001345 alkine derivatives Chemical class 0.000 claims 1
- 125000005418 aryl aryl group Chemical group 0.000 claims 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000428 dust Substances 0.000 claims 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 1
- CWMPPVPFLSZGCY-UHFFFAOYSA-N oct-2-enoic acid Chemical compound CCCCCC=CC(O)=O CWMPPVPFLSZGCY-UHFFFAOYSA-N 0.000 claims 1
- 125000005429 oxyalkyl group Chemical group 0.000 claims 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 1
- 125000003003 spiro group Chemical group 0.000 claims 1
- 239000010959 steel Substances 0.000 claims 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 474
- 150000001721 carbon Chemical group 0.000 description 377
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 303
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 202
- 239000011541 reaction mixture Substances 0.000 description 179
- 235000019439 ethyl acetate Nutrition 0.000 description 159
- 239000000243 solution Substances 0.000 description 136
- 239000000203 mixture Substances 0.000 description 131
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 130
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 122
- 238000002360 preparation method Methods 0.000 description 116
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- 239000007787 solid Substances 0.000 description 111
- 229910001868 water Inorganic materials 0.000 description 111
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 96
- 239000010410 layer Substances 0.000 description 95
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 94
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 93
- 239000000047 product Substances 0.000 description 93
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- 230000002829 reductive effect Effects 0.000 description 72
- 239000000706 filtrate Substances 0.000 description 68
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 60
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 59
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 53
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 49
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 46
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
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- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 32
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- 239000002244 precipitate Substances 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
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- 238000005481 NMR spectroscopy Methods 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 22
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- 239000003242 anti bacterial agent Substances 0.000 description 15
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
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- 125000000304 alkynyl group Chemical group 0.000 description 9
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- 238000011534 incubation Methods 0.000 description 1
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- 238000002386 leaching Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
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- DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
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- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- CCOXWRVWKFVFDG-UHFFFAOYSA-N pyrimidine-2-carbaldehyde Chemical compound O=CC1=NC=CC=N1 CCOXWRVWKFVFDG-UHFFFAOYSA-N 0.000 description 1
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- 235000019627 satiety Nutrition 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- NMTDPTPUELYEPL-UHFFFAOYSA-M sodium;heptanoate Chemical compound [Na+].CCCCCCC([O-])=O NMTDPTPUELYEPL-UHFFFAOYSA-M 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 1
- 229960003865 tazobactam Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- UUBIWGRMBVAUIK-UHFFFAOYSA-N tetracyclo[5.5.2.04,13.010,14]tetradeca-1(13),4,6,10(14),11-pentaene Chemical group C1CC2=CC=C3CCC4=CC=C1C2=C43 UUBIWGRMBVAUIK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and 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
- C07D499/881—Compounds with a double bond between positions 2 and 3 and 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 a hydrogen atom or an unsubstituted hydrocarbon radical, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37705102P | 2002-05-01 | 2002-05-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200404809A true TW200404809A (en) | 2004-04-01 |
Family
ID=29401436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW092110031A TW200404809A (en) | 2002-05-01 | 2003-04-29 | Tricyclic 6-alkylidene-penems as β -lactamase inhibitors |
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|---|---|
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| EP (1) | EP1499622B1 (enExample) |
| JP (1) | JP4472515B2 (enExample) |
| KR (1) | KR20050007366A (enExample) |
| CN (1) | CN100506825C (enExample) |
| AR (1) | AR039475A1 (enExample) |
| AT (1) | ATE425169T1 (enExample) |
| AU (1) | AU2003239325B8 (enExample) |
| BR (1) | BR0309878A (enExample) |
| CA (1) | CA2483562C (enExample) |
| DE (1) | DE60326562D1 (enExample) |
| DK (1) | DK1499622T3 (enExample) |
| EC (1) | ECSP045405A (enExample) |
| ES (1) | ES2322951T3 (enExample) |
| IL (1) | IL164898A0 (enExample) |
| MX (1) | MXPA04010662A (enExample) |
| NO (1) | NO20044550L (enExample) |
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| RU (1) | RU2004135086A (enExample) |
| TW (1) | TW200404809A (enExample) |
| UA (1) | UA78312C2 (enExample) |
| WO (1) | WO2003093280A1 (enExample) |
| ZA (1) | ZA200409691B (enExample) |
Families Citing this family (12)
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|---|---|---|---|---|
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| AR039476A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | Proceso para preparar derivados de 6-alquiliden penem |
| AR039475A1 (es) | 2002-05-01 | 2005-02-23 | Wyeth Corp | 6-alquiliden-penems triciclicos como inhibidores de beta-lactamasa |
| TW200716104A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Tricyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| TW200716102A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| AU2006285308A1 (en) * | 2005-07-27 | 2007-03-08 | Wyeth | Tricyclic 6-alkylidene-penem beta-lactamase inhibitors and beta-lactam antibiotic combination: a broad spectrum antibiotic |
| RU2008102912A (ru) * | 2005-07-27 | 2009-09-10 | Вайет (Us) | Сочетание ингибиторов бетта-лактазмы бициклического 6-алкилиденпенема с бетта-лактанным антибиотиком: антибиотик широкого спектра |
| GT200600380A (es) * | 2005-08-24 | 2007-03-29 | Proceso para la preparacion de inhibidores de beta-lactamasa | |
| US20100063023A1 (en) * | 2008-09-10 | 2010-03-11 | Wyeth | Bicyclic and Tricyclic Substituted 6-Methylidene Carbapenems as Broad Spectrum Beta-Lactamase Inhibitors |
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| KR20240036571A (ko) | 2021-07-15 | 2024-03-20 | 제넨테크, 인크. | 치료 화합물 및 방법 |
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-
2003
- 2003-04-28 AR ARP030101469A patent/AR039475A1/es not_active Application Discontinuation
- 2003-04-29 TW TW092110031A patent/TW200404809A/zh unknown
- 2003-04-30 CN CNB038097192A patent/CN100506825C/zh not_active Expired - Fee Related
- 2003-04-30 RU RU2004135086/04A patent/RU2004135086A/ru not_active Application Discontinuation
- 2003-04-30 UA UA20041109780A patent/UA78312C2/uk unknown
- 2003-04-30 EP EP03733911A patent/EP1499622B1/en not_active Expired - Lifetime
- 2003-04-30 NZ NZ536181A patent/NZ536181A/en unknown
- 2003-04-30 DK DK03733911T patent/DK1499622T3/da active
- 2003-04-30 BR BR0309878-8A patent/BR0309878A/pt not_active IP Right Cessation
- 2003-04-30 CA CA2483562A patent/CA2483562C/en not_active Expired - Fee Related
- 2003-04-30 AU AU2003239325A patent/AU2003239325B8/en not_active Ceased
- 2003-04-30 KR KR10-2004-7017588A patent/KR20050007366A/ko not_active Withdrawn
- 2003-04-30 WO PCT/US2003/013451 patent/WO2003093280A1/en not_active Ceased
- 2003-04-30 MX MXPA04010662A patent/MXPA04010662A/es active IP Right Grant
- 2003-04-30 DE DE60326562T patent/DE60326562D1/de not_active Expired - Lifetime
- 2003-04-30 ES ES03733911T patent/ES2322951T3/es not_active Expired - Lifetime
- 2003-04-30 JP JP2004501419A patent/JP4472515B2/ja not_active Expired - Lifetime
- 2003-04-30 AT AT03733911T patent/ATE425169T1/de not_active IP Right Cessation
- 2003-05-01 US US10/427,427 patent/US7018997B2/en not_active Expired - Fee Related
-
2004
- 2004-10-22 NO NO20044550A patent/NO20044550L/no not_active Application Discontinuation
- 2004-10-28 IL IL16489804A patent/IL164898A0/xx unknown
- 2004-10-29 EC EC2004005405A patent/ECSP045405A/es unknown
- 2004-11-30 ZA ZA200409691A patent/ZA200409691B/xx unknown
-
2005
- 2005-11-18 US US11/283,288 patent/US20060074064A1/en not_active Abandoned
-
2008
- 2008-08-07 US US12/187,707 patent/US7691842B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AR039475A1 (es) | 2005-02-23 |
| CA2483562C (en) | 2011-06-21 |
| CN100506825C (zh) | 2009-07-01 |
| AU2003239325B2 (en) | 2009-04-23 |
| ECSP045405A (es) | 2005-01-03 |
| ZA200409691B (en) | 2009-09-30 |
| KR20050007366A (ko) | 2005-01-17 |
| DE60326562D1 (de) | 2009-04-23 |
| JP2005533018A (ja) | 2005-11-04 |
| US7018997B2 (en) | 2006-03-28 |
| WO2003093280A1 (en) | 2003-11-13 |
| BR0309878A (pt) | 2005-04-19 |
| DK1499622T3 (da) | 2009-06-08 |
| JP4472515B2 (ja) | 2010-06-02 |
| NO20044550L (no) | 2005-01-28 |
| US20080318921A1 (en) | 2008-12-25 |
| NZ536181A (en) | 2007-06-29 |
| US20040043978A1 (en) | 2004-03-04 |
| AU2003239325A1 (en) | 2003-11-17 |
| RU2004135086A (ru) | 2005-05-10 |
| AU2003239325B8 (en) | 2009-06-18 |
| US20060074064A1 (en) | 2006-04-06 |
| CA2483562A1 (en) | 2003-11-13 |
| ATE425169T1 (de) | 2009-03-15 |
| EP1499622A1 (en) | 2005-01-26 |
| CN1649882A (zh) | 2005-08-03 |
| MXPA04010662A (es) | 2005-01-25 |
| EP1499622B1 (en) | 2009-03-11 |
| US7691842B2 (en) | 2010-04-06 |
| IL164898A0 (en) | 2005-12-18 |
| UA78312C2 (en) | 2007-03-15 |
| ES2322951T3 (es) | 2009-07-02 |
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