JP2005502687A - β−ラクタマーゼ阻害剤としての７−アルキリデン−３−置換型−３−セフェム−４−カルボキシラート - Google Patents
β−ラクタマーゼ阻害剤としての７−アルキリデン−３−置換型−３−セフェム−４−カルボキシラート Download PDFInfo
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- JP2005502687A JP2005502687A JP2003525002A JP2003525002A JP2005502687A JP 2005502687 A JP2005502687 A JP 2005502687A JP 2003525002 A JP2003525002 A JP 2003525002A JP 2003525002 A JP2003525002 A JP 2003525002A JP 2005502687 A JP2005502687 A JP 2005502687A
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- compound
- alkyl
- aryl
- hydrogen
- alkanoyloxy
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- 239000003781 beta lactamase inhibitor Substances 0.000 title description 12
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 149
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims abstract description 18
- 102000006635 beta-lactamase Human genes 0.000 claims abstract description 18
- 239000002132 β-lactam antibiotic Substances 0.000 claims abstract description 18
- 229940124586 β-lactam antibiotics Drugs 0.000 claims abstract description 18
- 108090000204 Dipeptidase 1 Proteins 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 11
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 4
- 150000003952 β-lactams Chemical class 0.000 claims abstract description 4
- -1 hydroxy, cyano, cyanato, nitro, mercapto Chemical class 0.000 claims description 123
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 52
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 35
- 125000004423 acyloxy group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 16
- 125000001589 carboacyl group Chemical group 0.000 claims description 16
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 238000013160 medical therapy Methods 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 44
- 239000000543 intermediate Substances 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 30
- 239000011734 sodium Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 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 description 16
- 238000010511 deprotection reaction Methods 0.000 description 15
- 239000007788 liquid Substances 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- 239000010410 layer Substances 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 230000003115 biocidal effect Effects 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 5
- 229960003022 amoxicillin Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- 108020004256 Beta-lactamase Proteins 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
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- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
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- 125000004076 pyridyl group Chemical group 0.000 description 3
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- 150000003457 sulfones Chemical class 0.000 description 3
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- LHNIIDJCEODSHA-OQRUQETBSA-N (6r,7r)-3-[(e)-2-(2,4-dinitrophenyl)ethenyl]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)O)\C=C\C=1C(=CC(=CC=1)[N+]([O-])=O)[N+]([O-])=O)C(=O)CC1=CC=CS1 LHNIIDJCEODSHA-OQRUQETBSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
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- 229930186147 Cephalosporin Natural products 0.000 description 2
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
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- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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- 229940088710 antibiotic agent Drugs 0.000 description 2
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- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 2
- 229960005361 cefaclor Drugs 0.000 description 2
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 2
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- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 2
- ORFOPKXBNMVMKC-DWVKKRMSSA-N ceftazidime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-N 0.000 description 2
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- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 description 2
- 229960001991 ceftizoxime Drugs 0.000 description 2
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 2
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- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 229940106164 cephalexin Drugs 0.000 description 2
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
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| US30740301P | 2001-07-24 | 2001-07-24 | |
| PCT/US2002/023613 WO2003020732A2 (en) | 2001-07-24 | 2002-07-24 | 7-alkylidene-3-substituted-3-cephem-4-carboxylates as beta-lactamase inhibitors. |
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| JP2005502687A true JP2005502687A (ja) | 2005-01-27 |
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| DE (1) | DE60214740T2 (https=) |
| ES (1) | ES2272795T3 (https=) |
| WO (1) | WO2003020732A2 (https=) |
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| JP2012509351A (ja) * | 2008-11-20 | 2012-04-19 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 有機化合物のフッ素化 |
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| WO1999033838A1 (en) | 1997-12-29 | 1999-07-08 | Research Corporation Technologies, Inc. | 2-β-SUBSTITUTED-6-ALKYLIDENE PENICILLANIC ACID DERIVATIVES AS β-LACTAMASE INHIBITORS |
| US6407091B1 (en) | 1999-04-15 | 2002-06-18 | Research Corporation Technologies, Inc. | β-lactamase inhibiting compounds |
| US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
| US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
| WO2003020732A2 (en) | 2001-07-24 | 2003-03-13 | Alamx, L.L.C. | 7-alkylidene-3-substituted-3-cephem-4-carboxylates as beta-lactamase inhibitors. |
| AU2003224874A1 (en) | 2002-04-04 | 2003-10-27 | Alamx, L.L.C. | INHIBITORS OF SERINE AND METALLO-ss-LACTAMASES |
| JP2007503447A (ja) * | 2003-08-25 | 2007-02-22 | リヴァアックス ファーマスーティカルズ，エルエルシー | 神経治療セファゾリン経口投与組成物 |
| US8299051B2 (en) * | 2008-05-13 | 2012-10-30 | Southern Methodist University | Beta-lactamase inhibitory compounds |
| WO2012142162A2 (en) | 2011-04-12 | 2012-10-18 | President And Fellows Of Harvard College | Fluorination of organic compounds |
| US9273083B2 (en) | 2012-09-26 | 2016-03-01 | President And Fellows Of Harvard College | Nickel fluorinating complexes and uses thereof |
| CN103387584B (zh) * | 2013-07-17 | 2015-02-25 | 盐城开元医药化工有限公司 | 一种7-氨基-3-氯-3-头孢环-4-羧酸的合成方法 |
| WO2015058047A2 (en) | 2013-10-18 | 2015-04-23 | President And Fellows Of Harvard College | Fluorination of organic compounds |
| CN105254648B (zh) * | 2015-11-13 | 2018-04-03 | 广东温氏大华农生物科技有限公司 | 一种头孢维星及其钠盐的合成方法 |
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| US4053468A (en) | 1976-02-25 | 1977-10-11 | Smithkline Corporation | Process for preparing 7-oxo cephalosporins and 6-oxo penicillins |
| AT368506B (de) | 1979-02-24 | 1982-10-25 | Erba Farmitalia | Verfahren zur herstellung von neuen penemcarbonsaeuren und deren salzen |
| ZA80993B (en) | 1979-02-24 | 1981-02-25 | Erba Farmitalia | -lactam-containing antibacterial agents and -lactamase inhibitors and preparation thereof |
| GB2076812A (en) | 1980-05-22 | 1981-12-09 | Ciba Geigy Ag | Penam-dioxide compounds, processes for their manufacture, and their use |
| US4369312A (en) | 1980-07-04 | 1983-01-18 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing oxo-containing azetidinone compounds |
| CA1180005A (en) | 1980-10-24 | 1984-12-27 | Solange Adam-Molina | .beta.-LACTAMS |
| ZA826687B (en) | 1981-09-14 | 1983-07-27 | Pfizer | Beta-lactamase inhibiting 2-beta-substituted-2-alpha-methyl 5(r)penam-3-alpha-carboxylic acid 1,1-dioxides and intermediates therefor |
| US4559157A (en) | 1983-04-21 | 1985-12-17 | Creative Products Resource Associates, Ltd. | Cosmetic applicator useful for skin moisturizing |
| LU84979A1 (fr) | 1983-08-30 | 1985-04-24 | Oreal | Composition cosmetique ou pharmaceutique sous forme aqueuse ou anhydre dont la phase grasse contient un polyether oligomere et polyethers oligomeres nouveaux |
| EP0150984B1 (en) | 1984-01-30 | 1991-09-11 | Pfizer Inc. | 6-(substituted) methylenepenicillanic and 6-(substituted) hydroxymethylpenicillanic acids and derivatives thereof |
| US4826833A (en) | 1984-01-30 | 1989-05-02 | Pfizer Inc. | 6-(Substituted)methylene-penicillanic and 6-(substituted)hydroxymethylpenicillanic acids and derivatives thereof |
| DD234015A5 (de) | 1984-01-30 | 1986-03-19 | Pfizer | Verfahren zur herstellung von 6-(subst.)-methylen-penicillan-und 6-(subst.)-hydroxymethyl-penicillansaeure und deren derivaten |
| DE3586021D1 (de) | 1984-07-30 | 1992-06-17 | Merck & Co Inc | Penicillin-derivate als entzuendungshemmende und degenerierungskaempfende arzneimittel. |
| US4861768A (en) | 1986-02-27 | 1989-08-29 | Taiho Pharmaceutical Company, Limited | 2 β-substituted thiomethylpenicillin derivatives and their preparation and use |
| JPS62198687A (ja) | 1986-02-27 | 1987-09-02 | Taiho Yakuhin Kogyo Kk | ２β−置換チオメチルペニシリン誘導体 |
| US4820508A (en) | 1987-06-23 | 1989-04-11 | Neutrogena Corporation | Skin protective composition |
| JP2603082B2 (ja) | 1987-09-07 | 1997-04-23 | 大塚化学株式会社 | ペニシラン酸誘導体の製造法 |
| US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| IT1227462B (it) | 1988-11-04 | 1991-04-11 | Glaxo Spa | Procedimento di preparazione di 6-ossopenicillanati |
| TW383308B (en) | 1993-08-24 | 2000-03-01 | Hoffmann La Roche | 2-beta-alkenyl penam sulfones as beta-lactamase inhibitors |
| US5629306A (en) | 1994-12-09 | 1997-05-13 | Research Corporation Technologies, Inc. | 7-alkylidene cephalosporanic acid derivatives and methods of using the same |
| US5597817A (en) | 1994-12-09 | 1997-01-28 | Southern Methodist University | 7-vinylidene cephalosporins and methods of using the same |
| US5760027A (en) | 1996-12-06 | 1998-06-02 | Research Corporation Technologies, Inc. | Use of 7-alkylidene cephalosporins to inhibit elastase activity |
| WO1999033838A1 (en) | 1997-12-29 | 1999-07-08 | Research Corporation Technologies, Inc. | 2-β-SUBSTITUTED-6-ALKYLIDENE PENICILLANIC ACID DERIVATIVES AS β-LACTAMASE INHIBITORS |
| DE60029023T2 (de) | 1999-04-15 | 2007-01-18 | Southern Methodist University Foundation for Research, Dallas | Beta-Lactamase hemmende Verbindungen |
| US6391855B1 (en) * | 1999-06-02 | 2002-05-21 | Adherex Technologies, Inc. | Compounds and methods for modulating junctional adhesion molecule-mediated functions |
| WO2003020732A2 (en) | 2001-07-24 | 2003-03-13 | Alamx, L.L.C. | 7-alkylidene-3-substituted-3-cephem-4-carboxylates as beta-lactamase inhibitors. |
-
2002
- 2002-07-24 WO PCT/US2002/023613 patent/WO2003020732A2/en not_active Ceased
- 2002-07-24 CA CA002454413A patent/CA2454413A1/en not_active Abandoned
- 2002-07-24 US US10/202,405 patent/US6916801B2/en not_active Expired - Fee Related
- 2002-07-24 JP JP2003525002A patent/JP2005502687A/ja active Pending
- 2002-07-24 DE DE60214740T patent/DE60214740T2/de not_active Expired - Fee Related
- 2002-07-24 AU AU2002353768A patent/AU2002353768A1/en not_active Abandoned
- 2002-07-24 ES ES02789149T patent/ES2272795T3/es not_active Expired - Lifetime
- 2002-07-24 EP EP02789149A patent/EP1430060B1/en not_active Expired - Lifetime
- 2002-07-24 AT AT02789149T patent/ATE339424T1/de not_active IP Right Cessation
-
2005
- 2005-05-10 US US11/126,061 patent/US7488724B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012509351A (ja) * | 2008-11-20 | 2012-04-19 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 有機化合物のフッ素化 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1430060B1 (en) | 2006-09-13 |
| US20030092696A1 (en) | 2003-05-15 |
| DE60214740D1 (en) | 2006-10-26 |
| WO2003020732A3 (en) | 2003-05-22 |
| WO2003020732A2 (en) | 2003-03-13 |
| US20060074065A1 (en) | 2006-04-06 |
| ATE339424T1 (de) | 2006-10-15 |
| CA2454413A1 (en) | 2003-03-13 |
| EP1430060A2 (en) | 2004-06-23 |
| US6916801B2 (en) | 2005-07-12 |
| US7488724B2 (en) | 2009-02-10 |
| AU2002353768A1 (en) | 2003-03-18 |
| ES2272795T3 (es) | 2007-05-01 |
| DE60214740T2 (de) | 2007-10-04 |
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