ES2322951T3 - Heterotriciclil 6-alquiliden-penems como inhibidores de l-lactamasa. - Google Patents
Heterotriciclil 6-alquiliden-penems como inhibidores de l-lactamasa. Download PDFInfo
- Publication number
- ES2322951T3 ES2322951T3 ES03733911T ES03733911T ES2322951T3 ES 2322951 T3 ES2322951 T3 ES 2322951T3 ES 03733911 T ES03733911 T ES 03733911T ES 03733911 T ES03733911 T ES 03733911T ES 2322951 T3 ES2322951 T3 ES 2322951T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- optionally substituted
- independently
- aryl
- quad
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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- 239000003112 inhibitor Substances 0.000 title description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 492
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 464
- -1 alkanyl Chemical group 0.000 claims abstract description 108
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 94
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 80
- 125000001424 substituent group Chemical group 0.000 claims abstract description 78
- 125000003118 aryl group Chemical group 0.000 claims abstract description 71
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 61
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 26
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 25
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 23
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 22
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 12
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000006574 non-aromatic ring group Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 456
- 150000001721 carbon Chemical group 0.000 claims description 330
- 229920006395 saturated elastomer Polymers 0.000 claims description 195
- 239000002253 acid Substances 0.000 claims description 174
- 238000002360 preparation method Methods 0.000 claims description 116
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 106
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 78
- 230000002829 reductive effect Effects 0.000 claims description 69
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 125000004429 atom Chemical group 0.000 claims description 62
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 40
- 239000011734 sodium Substances 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 36
- 159000000000 sodium salts Chemical class 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 229910052708 sodium Inorganic materials 0.000 claims description 21
- 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 20
- 208000015181 infectious disease Diseases 0.000 claims description 16
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 15
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 14
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 14
- 239000002132 β-lactam antibiotic Substances 0.000 claims description 14
- 229940124586 β-lactam antibiotics Drugs 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 claims description 12
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000003003 spiro group Chemical group 0.000 claims description 11
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 9
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 230000003115 biocidal effect Effects 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 6
- 125000005325 aryloxy aryl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 5
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 5
- 150000001336 alkenes Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- ZQZVENIYZGCSFN-VYLZPFMQSA-N (5r,6z)-6-(imidazo[2,1-b][1,3]benzothiazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2SC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O ZQZVENIYZGCSFN-VYLZPFMQSA-N 0.000 claims description 3
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 3
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 claims description 3
- 150000001345 alkine derivatives Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 150000003952 β-lactams Chemical class 0.000 claims description 3
- FNBVVWRNKCSCSF-JKLGPDONSA-N (5r,6e)-6-[(5-benzyl-6-oxobenzo[b][1,4]benzoxazepin-3-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C/C(C=C12)=CC=C1OC1=CC=CC=C1C(=O)N2CC1=CC=CC=C1 FNBVVWRNKCSCSF-JKLGPDONSA-N 0.000 claims description 2
- GOFJCPGJAAJPHI-XGICHPGQSA-N (6z)-6-(5h-imidazo[2,1-a]isoindol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=CC=C2C3=NC(/C=C4/C(=O)N5C4SC=C5C(=O)O)=CN3CC2=C1 GOFJCPGJAAJPHI-XGICHPGQSA-N 0.000 claims description 2
- SBFSPMJWFBHKNG-GHXNOFRVSA-N (6z)-6-(imidazo[1,2-a]quinolin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2C=CC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2C1SC=C2C(=O)O SBFSPMJWFBHKNG-GHXNOFRVSA-N 0.000 claims description 2
- KURIZNLSKVWYAT-UITAMQMPSA-N (6z)-7-oxo-6-(5,6,7,8-tetrahydroimidazo[1,2][1,2,4]triazolo[2,4-a]pyridin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1CCCC2=NC3=NC(/C=C4/C(=O)N5C4SC=C5C(=O)O)=CN3N21 KURIZNLSKVWYAT-UITAMQMPSA-N 0.000 claims description 2
- NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 2
- OWKFKAWHZKUXBM-WSVPDTOYSA-N (5R,6Z)-6-[(7-methoxy-1,8,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-11-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound COC1=NC2=NC(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)=CN2C2=C1CCC2 OWKFKAWHZKUXBM-WSVPDTOYSA-N 0.000 claims 1
- RITQDZWBRPLXHO-NUZRTGFDSA-N (5R,6Z)-7-oxo-6-[[7-(2-phenylmethoxyethoxy)-1,8,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-11-yl]methylidene]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(N=C1N=2)=CN1C=1CCCC=1C=2OCCOCC1=CC=CC=C1 RITQDZWBRPLXHO-NUZRTGFDSA-N 0.000 claims 1
- ZMVPSTWCZFOKMA-VYLZPFMQSA-N (5r,6z)-6-(1,2-dihydro-[1,3]thiazolo[3,2-a]benzimidazol-7-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(C=C12)=CC=C1N=C1N2CCS1 ZMVPSTWCZFOKMA-VYLZPFMQSA-N 0.000 claims 1
- UIEWFJZVZVDQLA-IZIDJEDMSA-N (5r,6z)-6-(3,4-dihydro-2h-[1,3]thiazino[3,2-a]benzimidazol-7-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1CCCN2C3=CC(/C=C4/C(=O)N5[C@@H]4SC=C5C(=O)O)=CC=C3N=C21 UIEWFJZVZVDQLA-IZIDJEDMSA-N 0.000 claims 1
- GVIJNDBUPIEBNV-VYLZPFMQSA-N (5r,6z)-6-[(5-methyl-7,8-dihydro-6h-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC1=NC2=NC(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)=NN2C2=C1CCC2 GVIJNDBUPIEBNV-VYLZPFMQSA-N 0.000 claims 1
- HXVDRENWBJTNFL-RXTQTKKPSA-N (5r,6z)-6-[(6-chloroimidazo[2,1-b][1,3]benzothiazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2SC3=CC(Cl)=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O HXVDRENWBJTNFL-RXTQTKKPSA-N 0.000 claims 1
- RLOBCNKTHMNWDX-RXTQTKKPSA-N (5r,6z)-6-[(6-fluoroimidazo[2,1-b][1,3]benzothiazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2SC3=CC(F)=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O RLOBCNKTHMNWDX-RXTQTKKPSA-N 0.000 claims 1
- FINRLGAWOGFDKT-OZVSCIAHSA-N (5r,6z)-6-[(6-methoxyimidazo[2,1-b][1,3]benzothiazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound COC1=CC=C2N3C=C(\C=C/4C(N5C(=CS[C@@H]5\4)C(O)=O)=O)N=C3SC2=C1 FINRLGAWOGFDKT-OZVSCIAHSA-N 0.000 claims 1
- QIAAAFQSVXOMRB-WSVPDTOYSA-N (5r,6z)-6-[(6-methylimidazo[2,1-b][1,3]benzothiazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC1=CC=C2N3C=C(\C=C/4C(N5C(=CS[C@@H]5\4)C(O)=O)=O)N=C3SC2=C1 QIAAAFQSVXOMRB-WSVPDTOYSA-N 0.000 claims 1
- OXWWPWZFBQZZPH-WSVPDTOYSA-N (5r,6z)-6-[(8-methylimidazo[2,1-b][1,3]benzothiazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC1=CC=CC2=C1N1C=C(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)N=C1S2 OXWWPWZFBQZZPH-WSVPDTOYSA-N 0.000 claims 1
- YJHLAPIOTYDKSI-VYLZPFMQSA-N (5r,6z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-7-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(C=C12)=CC=C1N=C1N2C=CS1 YJHLAPIOTYDKSI-VYLZPFMQSA-N 0.000 claims 1
- AHICGCNKVSGCLQ-WSVPDTOYSA-N (5r,6z)-7-oxo-6-(spiro[1,3-dioxolane-2,7'-8,9-dihydro-6h-[1,2,4]triazolo[1,5-a]quinazoline]-2'-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(=NN1C=2CC3)N=C1N=CC=2CC13OCCO1 AHICGCNKVSGCLQ-WSVPDTOYSA-N 0.000 claims 1
- OPXDMOAEUDFAOG-UITAMQMPSA-N (6z)-6-(imidazo[2,1-b][1,3]benzothiazol-6-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=C2N3C=CN=C3SC2=CC(/C=C2/C(=O)N3C2SC=C3C(=O)O)=C1 OPXDMOAEUDFAOG-UITAMQMPSA-N 0.000 claims 1
- LVDAGEHCAGXUMS-UITAMQMPSA-N (6z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C2=NC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2C1SC=C2C(=O)O LVDAGEHCAGXUMS-UITAMQMPSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000005017 substituted alkenyl group Chemical group 0.000 claims 1
- 125000004426 substituted alkynyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 379
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 285
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 208
- 239000011541 reaction mixture Substances 0.000 description 153
- 239000000203 mixture Substances 0.000 description 137
- 235000019439 ethyl acetate Nutrition 0.000 description 128
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 122
- 239000000243 solution Substances 0.000 description 122
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
- 229910001868 water Inorganic materials 0.000 description 101
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 100
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 99
- 239000007787 solid Substances 0.000 description 99
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 87
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 87
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 84
- 239000000047 product Substances 0.000 description 84
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 67
- 239000010410 layer Substances 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- 239000000706 filtrate Substances 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 52
- 239000012044 organic layer Substances 0.000 description 48
- 238000004440 column chromatography Methods 0.000 description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- 239000011888 foil Substances 0.000 description 40
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 39
- 235000019341 magnesium sulphate Nutrition 0.000 description 39
- 239000012267 brine Substances 0.000 description 38
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
- 229910052782 aluminium Inorganic materials 0.000 description 37
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 36
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 33
- 229910001623 magnesium bromide Inorganic materials 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
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- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 1
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- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
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- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
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- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- MBWXLICVQZUJOW-UHFFFAOYSA-N diethyl 1h-pyrazole-3,5-dicarboxylate Chemical compound CCOC(=O)C=1C=C(C(=O)OCC)NN=1 MBWXLICVQZUJOW-UHFFFAOYSA-N 0.000 description 1
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- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005058 dihydrotriazolyl group Chemical group N1(NNC=C1)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
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- 229920001971 elastomer Polymers 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- XQKOXWIOMWAGIY-UHFFFAOYSA-N ethyl 1h-indene-2-carboxylate Chemical compound C1=CC=C2CC(C(=O)OCC)=CC2=C1 XQKOXWIOMWAGIY-UHFFFAOYSA-N 0.000 description 1
- LYLCINUJPMPFMR-UHFFFAOYSA-N ethyl 3-(2-oxocyclohexyl)oxy-1h-pyrazole-5-carboxylate Chemical compound N1N=C(C(=O)OCC)C=C1OC1C(=O)CCCC1 LYLCINUJPMPFMR-UHFFFAOYSA-N 0.000 description 1
- UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 1
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- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
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- 244000000058 gram-negative pathogen Species 0.000 description 1
- 244000000059 gram-positive pathogen Species 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000005367 heteroarylalkylthio group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- INSWZAQOISIYDT-UHFFFAOYSA-N imidazo[1,2-a]pyrimidine Chemical compound C1=CC=NC2=NC=CN21 INSWZAQOISIYDT-UHFFFAOYSA-N 0.000 description 1
- HJMONQQZFQKQPS-UHFFFAOYSA-N imidazo[1,2-a]quinoline Chemical compound C1=CC=C2N3C=CN=C3C=CC2=C1 HJMONQQZFQKQPS-UHFFFAOYSA-N 0.000 description 1
- VTNBGTYLJIUATL-UHFFFAOYSA-N imidazo[1,2-a]quinoxaline Chemical compound C1=CC=C2N3C=CN=C3C=NC2=C1 VTNBGTYLJIUATL-UHFFFAOYSA-N 0.000 description 1
- DZQKDZOLBZUBGK-UHFFFAOYSA-N imidazo[2,1-b][1,3]benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2N3C=CN=C3SC2=C1 DZQKDZOLBZUBGK-UHFFFAOYSA-N 0.000 description 1
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- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- JGZKUKYUQJUUNE-UHFFFAOYSA-L magnesium;ethoxyethane;dibromide Chemical compound [Mg+2].[Br-].[Br-].CCOCC JGZKUKYUQJUUNE-UHFFFAOYSA-L 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LTQVYKXOLVPCIN-UHFFFAOYSA-N molport-006-370-283 Chemical compound C1=NC2=NC=NN2C2=C1CCC2 LTQVYKXOLVPCIN-UHFFFAOYSA-N 0.000 description 1
- 230000021332 multicellular organism growth Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
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- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
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- 235000015277 pork Nutrition 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
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
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- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- BKRKYGDGROPRDS-UHFFFAOYSA-N pyrazolo[5,1-b][1,3]oxazole Chemical compound O1C=CN2N=CC=C21 BKRKYGDGROPRDS-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- YIYRXCXJFKZQBC-UHFFFAOYSA-N quinazoline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=NC=C21 YIYRXCXJFKZQBC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 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
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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 (2)
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|---|---|---|---|
| US37705102P | 2002-05-01 | 2002-05-01 | |
| US377051P | 2002-05-01 |
Publications (1)
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|---|---|
| ES2322951T3 true ES2322951T3 (es) | 2009-07-02 |
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| ES03733911T Expired - Lifetime ES2322951T3 (es) | 2002-05-01 | 2003-04-30 | Heterotriciclil 6-alquiliden-penems como inhibidores de l-lactamasa. |
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| AU (1) | AU2003239325B8 (enExample) |
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| 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) |
| NZ (1) | NZ536181A (enExample) |
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
| AR039774A1 (es) * | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
| 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 |
| US20110288063A1 (en) * | 2010-05-19 | 2011-11-24 | Naeja Pharmaceutical Inc. | Novel fused bridged bicyclic heteroaryl substituted 6-alkylidene penems as potent beta-lactamase inhibitors |
| KR20240036571A (ko) | 2021-07-15 | 2024-03-20 | 제넨테크, 인크. | 치료 화합물 및 방법 |
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| US3644825A (en) * | 1969-12-31 | 1972-02-22 | Texas Instruments Inc | Magnetic detection system for detecting movement of an object utilizing signals derived from two orthogonal pickup coils |
| US3821469A (en) * | 1972-05-15 | 1974-06-28 | Amperex Electronic Corp | Graphical data device |
| US3868565A (en) * | 1973-07-30 | 1975-02-25 | Jack Kuipers | Object tracking and orientation determination means, system and process |
| US4017858A (en) * | 1973-07-30 | 1977-04-12 | Polhemus Navigation Sciences, Inc. | Apparatus for generating a nutating electromagnetic field |
| US3983474A (en) * | 1975-02-21 | 1976-09-28 | Polhemus Navigation Sciences, Inc. | Tracking and determining orientation of object using coordinate transformation means, system and process |
| US4054881A (en) * | 1976-04-26 | 1977-10-18 | The Austin Company | Remote object position locater |
| DE2718804C3 (de) * | 1977-04-27 | 1979-10-31 | Karlheinz Prof. Dr. 3000 Hannover Renner | Vorrichtung zur PositionierungskontroUe von Patienten und/oder Bestrahlungsquellen |
| US4182312A (en) * | 1977-05-20 | 1980-01-08 | Mushabac David R | Dental probe |
| US4206067A (en) * | 1978-10-02 | 1980-06-03 | Chevron Research Company | Thermally stabilized erosion-inhibited functional fluids containing perhalometal compounds and an organic base |
| US4256112A (en) * | 1979-02-12 | 1981-03-17 | David Kopf Instruments | Head positioner |
| US4341220A (en) * | 1979-04-13 | 1982-07-27 | Pfizer Inc. | Stereotactic surgery apparatus and method |
| US4314251A (en) * | 1979-07-30 | 1982-02-02 | The Austin Company | Remote object position and orientation locater |
| US4608977A (en) * | 1979-08-29 | 1986-09-02 | Brown Russell A | System using computed tomography as for selective body treatment |
| US4319136A (en) * | 1979-11-09 | 1982-03-09 | Jinkins J Randolph | Computerized tomography radiograph data transfer cap |
| US4328548A (en) * | 1980-04-04 | 1982-05-04 | The Austin Company | Locator for source of electromagnetic radiation having unknown structure or orientation |
| US4346384A (en) * | 1980-06-30 | 1982-08-24 | The Austin Company | Remote object position and orientation locator |
| DE3176517D1 (en) | 1980-04-24 | 1987-12-17 | Beecham Group Plc | Beta-lactam compounds, their preparation and use |
| US4688037A (en) * | 1980-08-18 | 1987-08-18 | Mcdonnell Douglas Corporation | Electromagnetic communications and switching system |
| US4638798A (en) * | 1980-09-10 | 1987-01-27 | Shelden C Hunter | Stereotactic method and apparatus for locating and treating or removing lesions |
| US4506676A (en) * | 1982-09-10 | 1985-03-26 | Duska Alois A | Radiographic localization technique |
| EP0120613A1 (en) | 1983-03-02 | 1984-10-03 | Beecham Group Plc | Penem derivatives and precursors |
| US4651732A (en) * | 1983-03-17 | 1987-03-24 | Frederick Philip R | Three-dimensional light guidance system for invasive procedures |
| US4613866A (en) * | 1983-05-13 | 1986-09-23 | Mcdonnell Douglas Corporation | Three dimensional digitizer with electromagnetic coupling |
| NL8302228A (nl) * | 1983-06-22 | 1985-01-16 | Optische Ind De Oude Delft Nv | Meetstelsel voor het onder gebruikmaking van een op driehoeksmeting berustend principe, contactloos meten van een door een oppervlakcontour van een objectvlak gegeven afstand tot een referentieniveau. |
| DE3342675A1 (de) * | 1983-11-25 | 1985-06-05 | Fa. Carl Zeiss, 7920 Heidenheim | Verfahren und vorrichtung zur beruehrungslosen vermessung von objekten |
| US4753528A (en) * | 1983-12-13 | 1988-06-28 | Quantime, Inc. | Laser archery distance device |
| GB8402086D0 (en) | 1984-01-26 | 1984-02-29 | Beecham Group Plc | Compounds |
| FI82471C (fi) | 1984-01-26 | 1991-03-11 | Beecham Group Plc | Foerfarande foer framstaellning av farmakologiskt aktiva 6-metylenpenemderivater. |
| EP0150984B1 (en) | 1984-01-30 | 1991-09-11 | Pfizer Inc. | 6-(substituted) methylenepenicillanic and 6-(substituted) hydroxymethylpenicillanic acids and derivatives thereof |
| US4841967A (en) * | 1984-01-30 | 1989-06-27 | Chang Ming Z | Positioning device for percutaneous needle insertion |
| US4583538A (en) * | 1984-05-04 | 1986-04-22 | Onik Gary M | Method and apparatus for stereotaxic placement of probes in the body utilizing CT scanner localization |
| EP0167050A1 (en) | 1984-06-21 | 1986-01-08 | Beecham Group Plc | Clavulanate compounds, their preparation and use and intermediates thereof |
| US4617925A (en) * | 1984-10-01 | 1986-10-21 | Laitinen Lauri V | Adapter for definition of the position of brain structures |
| US4618975A (en) * | 1984-12-21 | 1986-10-21 | At&T Technologies, Inc. | Method and apparatus for analyzing a porous nonhomogeneous cylindrical object |
| US4838265A (en) * | 1985-05-24 | 1989-06-13 | Cosman Eric R | Localization device for probe placement under CT scanner imaging |
| SE447848B (sv) * | 1985-06-14 | 1986-12-15 | Anders Bengtsson | Instrument for metning av ytors topografi |
| US4805615A (en) * | 1985-07-02 | 1989-02-21 | Carol Mark P | Method and apparatus for performing stereotactic surgery |
| GB8518422D0 (en) | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
| GB8518416D0 (en) * | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
| GB8518421D0 (en) * | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
| US4737032A (en) * | 1985-08-26 | 1988-04-12 | Cyberware Laboratory, Inc. | Surface mensuration sensor |
| US4737794A (en) * | 1985-12-09 | 1988-04-12 | Mcdonnell Douglas Corporation | Method and apparatus for determining remote object orientation and position |
| US4742356A (en) * | 1985-12-09 | 1988-05-03 | Mcdonnell Douglas Corporation | Method and apparatus for determining remote object orientation and position |
| ATE159021T1 (de) | 1986-01-17 | 1997-10-15 | Beecham Group Plc | Verfahren zur herstellung von penem derivaten und zwischenprodukte zu dieser herstellung |
| SE469321B (sv) * | 1986-04-14 | 1993-06-21 | Joenkoepings Laens Landsting | Saett och anordning foer att framstaella en modifierad tredimensionell avbildning av ett elastiskt deformerbart foeremaal |
| US4821731A (en) * | 1986-04-25 | 1989-04-18 | Intra-Sonix, Inc. | Acoustic image system and method |
| US4822163A (en) * | 1986-06-26 | 1989-04-18 | Robotic Vision Systems, Inc. | Tracking vision sensor |
| US4723544A (en) * | 1986-07-09 | 1988-02-09 | Moore Robert R | Hemispherical vectoring needle guide for discolysis |
| US4733969A (en) * | 1986-09-08 | 1988-03-29 | Cyberoptics Corporation | Laser probe for determining distance |
| US4761072A (en) * | 1986-09-30 | 1988-08-02 | Diffracto Ltd. | Electro-optical sensors for manual control |
| US4750487A (en) * | 1986-11-24 | 1988-06-14 | Zanetti Paul H | Stereotactic frame |
| US4891369A (en) * | 1986-12-03 | 1990-01-02 | Taiho Pharmaceutical Company, Limited | 2β-Substituted-methylpenicillanic acid derivatives, and salts and esters thereof |
| DE3703422A1 (de) * | 1987-02-05 | 1988-08-18 | Zeiss Carl Fa | Optoelektronischer abstandssensor |
| US4745290A (en) * | 1987-03-19 | 1988-05-17 | David Frankel | Method and apparatus for use in making custom shoes |
| US4804261A (en) * | 1987-03-27 | 1989-02-14 | Kirschen David G | Anti-claustrophobic glasses |
| US4809694A (en) * | 1987-05-19 | 1989-03-07 | Ferrara Vincent L | Biopsy guide |
| DE3717871C3 (de) * | 1987-05-27 | 1995-05-04 | Georg Prof Dr Schloendorff | Verfahren und Vorrichtung zum reproduzierbaren optischen Darstellen eines chirururgischen Eingriffes |
| US4836778A (en) * | 1987-05-26 | 1989-06-06 | Vexcel Corporation | Mandibular motion monitoring system |
| DE3725375A1 (de) * | 1987-07-31 | 1989-02-09 | Bayer Ag | Stabile oxapenem-3-carbonsaeuren |
| US4829373A (en) * | 1987-08-03 | 1989-05-09 | Vexcel Corporation | Stereo mensuration apparatus |
| US4931056A (en) * | 1987-09-04 | 1990-06-05 | Neurodynamics, Inc. | Catheter guide apparatus for perpendicular insertion into a cranium orifice |
| JPS6472736A (en) * | 1987-09-14 | 1989-03-17 | Toshiba Corp | Mri apparatus |
| GB8724566D0 (en) | 1987-10-20 | 1987-11-25 | Roussel Lab Ltd | Chemical compounds |
| US4991579A (en) * | 1987-11-10 | 1991-02-12 | Allen George S | Method and apparatus for providing related images over time of a portion of the anatomy using fiducial implants |
| US5027818A (en) * | 1987-12-03 | 1991-07-02 | University Of Florida | Dosimetric technique for stereotactic radiosurgery same |
| GB8729614D0 (en) | 1987-12-18 | 1988-02-03 | Beecham Group Plc | Novel compounds |
| GB8729613D0 (en) | 1987-12-18 | 1988-02-03 | Beecham Group Plc | Novel compounds |
| US4869247A (en) * | 1988-03-11 | 1989-09-26 | The University Of Virginia Alumni Patents Foundation | Video tumor fighting system |
| US5099846A (en) * | 1988-12-23 | 1992-03-31 | Hardy Tyrone L | Method and apparatus for video presentation from a variety of scanner imaging sources |
| US5098426A (en) * | 1989-02-06 | 1992-03-24 | Phoenix Laser Systems, Inc. | Method and apparatus for precision laser surgery |
| US5197476A (en) * | 1989-03-16 | 1993-03-30 | Christopher Nowacki | Locating target in human body |
| US5285787A (en) * | 1989-09-12 | 1994-02-15 | Kabushiki Kaisha Toshiba | Apparatus for calculating coordinate data of desired point in subject to be examined |
| EP0427358B1 (en) * | 1989-11-08 | 1996-03-27 | George S. Allen | Mechanical arm for and interactive image-guided surgical system |
| NZ237202A (en) | 1990-02-23 | 1994-01-26 | Bristol Myers Squibb Co | Composition containing beta-lactam antibiotic and cationic oligopeptide |
| US5224049A (en) * | 1990-04-10 | 1993-06-29 | Mushabac David R | Method, system and mold assembly for use in preparing a dental prosthesis |
| US5107839A (en) * | 1990-05-04 | 1992-04-28 | Pavel V. Houdek | Computer controlled stereotaxic radiotherapy system and method |
| US5017139A (en) * | 1990-07-05 | 1991-05-21 | Mushabac David R | Mechanical support for hand-held dental/medical instrument |
| US5193106A (en) * | 1990-08-28 | 1993-03-09 | Desena Danforth | X-ray identification marker |
| EP0931516B1 (en) * | 1990-10-19 | 2008-08-20 | St. Louis University | Surgical probe locating system for head use |
| US5480439A (en) * | 1991-02-13 | 1996-01-02 | Lunar Corporation | Method for periprosthetic bone mineral density measurement |
| US5279309A (en) * | 1991-06-13 | 1994-01-18 | International Business Machines Corporation | Signaling device and method for monitoring positions in a surgical operation |
| GB9116236D0 (en) | 1991-07-27 | 1991-09-11 | Smithkline Beecham Plc | Novel compounds |
| US5207688A (en) * | 1991-10-31 | 1993-05-04 | Medco, Inc. | Noninvasive head fixation method and apparatus |
| US5330485A (en) * | 1991-11-01 | 1994-07-19 | Clayman David A | Cerebral instrument guide frame and procedures utilizing it |
| US5230623A (en) * | 1991-12-10 | 1993-07-27 | Radionics, Inc. | Operating pointer with interactive computergraphics |
| US5306271A (en) * | 1992-03-09 | 1994-04-26 | Izi Corporation | Radiation therapy skin markers |
| US5299253A (en) * | 1992-04-10 | 1994-03-29 | Akzo N.V. | Alignment system to overlay abdominal computer aided tomography and magnetic resonance anatomy with single photon emission tomography |
| US5389101A (en) * | 1992-04-21 | 1995-02-14 | University Of Utah | Apparatus and method for photogrammetric surgical localization |
| GB9222700D0 (en) * | 1992-10-29 | 1992-12-09 | Smithkline Beecham Plc | Chemical compounds |
| US5517990A (en) * | 1992-11-30 | 1996-05-21 | The Cleveland Clinic Foundation | Stereotaxy wand and tool guide |
| US5309913A (en) * | 1992-11-30 | 1994-05-10 | The Cleveland Clinic Foundation | Frameless stereotaxy system |
| US5799099A (en) * | 1993-02-12 | 1998-08-25 | George S. Allen | Automatic technique for localizing externally attached fiducial markers in volume images of the head |
| US5730130A (en) * | 1993-02-12 | 1998-03-24 | Johnson & Johnson Professional, Inc. | Localization cap for fiducial markers |
| US5483961A (en) * | 1993-03-19 | 1996-01-16 | Kelly; Patrick J. | Magnetic field digitizer for stereotactic surgery |
| DE69431875T2 (de) * | 1993-04-22 | 2003-05-28 | Image Guided Technologies, Inc. | Anordnung zur bestimmung der gegenseitigen lage von körpern |
| US5738096A (en) * | 1993-07-20 | 1998-04-14 | Biosense, Inc. | Cardiac electromechanics |
| US5391199A (en) * | 1993-07-20 | 1995-02-21 | Biosense, Inc. | Apparatus and method for treating cardiac arrhythmias |
| FR2709656B1 (fr) * | 1993-09-07 | 1995-12-01 | Deemed Int Sa | Installation pour opération de microchirurgie assistée par ordinateur et procédés mis en Óoeuvre par ladite installation. |
| DE9314075U1 (de) * | 1993-09-17 | 1994-01-20 | DWL Elektronische Systeme GmbH, 78354 Sipplingen | Vorrichtung zur Aufnahme wenigstens einer sonographischen Sonde |
| US5558091A (en) * | 1993-10-06 | 1996-09-24 | Biosense, Inc. | Magnetic determination of position and orientation |
| US5446548A (en) * | 1993-10-08 | 1995-08-29 | Siemens Medical Systems, Inc. | Patient positioning and monitoring system |
| US5394875A (en) * | 1993-10-21 | 1995-03-07 | Lewis; Judith T. | Automatic ultrasonic localization of targets implanted in a portion of the anatomy |
| GB9326248D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Plc | Pharmaceutical formulations |
| ES2206502T3 (es) | 1994-04-25 | 2004-05-16 | Smithkline Beecham Plc | Formulaciones farmaceuticas que contienen un penem inhibidor de beta-lactamasa en combinacion con un antibiotico de beta-lactama y su uso en el tratamiento de infecciones bacterianas. |
| US5600330A (en) * | 1994-07-12 | 1997-02-04 | Ascension Technology Corporation | Device for measuring position and orientation using non-dipole magnet IC fields |
| US5769861A (en) * | 1995-09-28 | 1998-06-23 | Brainlab Med. Computersysteme Gmbh | Method and devices for localizing an instrument |
| OA11666A (en) * | 1998-10-15 | 2004-12-08 | Sarawak Medichem Pharmaceuticals Inc | Method and composition for treating and preventingtuberculosis. |
| GB9928290D0 (en) * | 1999-12-01 | 2000-01-26 | Univ Belfast | Process for preparing ambient temperature ionic liquids |
| EP1199077A1 (en) * | 2000-10-19 | 2002-04-24 | Amura Limited | Stable compositions of oxapenem-3-carboxylic acids by Co-lyophilisation with pharmaceutical carriers |
| GB0106428D0 (en) * | 2001-03-15 | 2001-05-02 | Amura Ltd | Antibacterial composition |
| AR039774A1 (es) * | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
| US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
| 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 |
| AR046041A1 (es) * | 2003-10-03 | 2005-11-23 | Aventis Pharma Inc | Procedimiento para la preparacion de compuestos heterociclicos n-amino sustituidos |
| TW200716102A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| TW200716104A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Tricyclic 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 |
-
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 |
| TW200404809A (en) | 2004-04-01 |
| 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 |
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