OA10064A - Derives de la cephalosporine compositions pharmaceutiques les contenant et procede de fabrication - Google Patents

Derives de la cephalosporine compositions pharmaceutiques les contenant et procede de fabrication Download PDF

Info

Publication number: OA10064A
Authority: OA; OAPI
Prior art keywords: oxo; amino; carboxylic acid; azabicyclo; thia
Prior art date: 1993-04-16

Application number

OA60495A

Other languages

English (en)

French (fr)

Inventor

Peter Angehrn

Chung-Chen Wei

Original Assignee

Hoffmann La Roche

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

1993-04-16

Filing date

1994-04-15

Publication date

1996-10-14

1994-03-21 Priority claimed from US08/213,562 external-priority patent/US5523400A/en

1994-04-15 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1996-10-14 Publication of OA10064A publication Critical patent/OA10064A/fr

Links

229940124587 cephalosporin Drugs 0.000 title claims abstract description 7
229930186147 Cephalosporin Natural products 0.000 title claims abstract description 6
150000001780 cephalosporins Chemical class 0.000 title claims abstract description 6
238000000034 method Methods 0.000 title claims description 55
230000008569 process Effects 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title description 3
-1 carboxy, amino Chemical group 0.000 claims abstract description 721
150000001875 compounds Chemical class 0.000 claims abstract description 206
150000002148 esters Chemical class 0.000 claims abstract description 115
150000003839 salts Chemical class 0.000 claims abstract description 90
125000000217 alkyl group Chemical group 0.000 claims abstract description 63
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
239000001257 hydrogen Substances 0.000 claims abstract description 46
150000004677 hydrates Chemical class 0.000 claims abstract description 32
150000002431 hydrogen Chemical class 0.000 claims abstract description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 24
125000003545 alkoxy group Chemical group 0.000 claims abstract description 23
229910052736 halogen Inorganic materials 0.000 claims abstract description 22
150000002367 halogens Chemical class 0.000 claims abstract description 21
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 21
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
125000002252 acyl group Chemical group 0.000 claims abstract description 17
125000003118 aryl group Chemical group 0.000 claims abstract description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 14
125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 8
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 8
125000004104 aryloxy group Chemical group 0.000 claims abstract description 7
125000006244 carboxylic acid protecting group Chemical group 0.000 claims abstract description 7
125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 193
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 169
239000002253 acid Substances 0.000 claims description 156
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 31
125000006239 protecting group Chemical group 0.000 claims description 24
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 17
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 13
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 11
239000003795 chemical substances by application Substances 0.000 claims description 10
230000002829 reductive effect Effects 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
GBEPMLYZCPHOBB-UHFFFAOYSA-N 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCSC2CCN12 GBEPMLYZCPHOBB-UHFFFAOYSA-N 0.000 claims description 7
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 6
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
230000032050 esterification Effects 0.000 claims description 6
238000005886 esterification reaction Methods 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
239000000825 pharmaceutical preparation Substances 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
208000035473 Communicable disease Diseases 0.000 claims description 5
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
239000013543 active substance Substances 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 9
238000011321 prophylaxis Methods 0.000 claims 6
150000001735 carboxylic acids Chemical class 0.000 claims 3
101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 claims 1
125000005842 heteroatom Chemical group 0.000 claims 1
125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
101150035983 str1 gene Proteins 0.000 claims 1
150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 194
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 121
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 102
239000000203 mixture Substances 0.000 description 102
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
238000005481 NMR spectroscopy Methods 0.000 description 75
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 68
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 64
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 63
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
239000000243 solution Substances 0.000 description 61
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
125000001841 imino group Chemical group [H]N=* 0.000 description 48
238000006243 chemical reaction Methods 0.000 description 47
239000002904 solvent Substances 0.000 description 45
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 37
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
239000000047 product Substances 0.000 description 35
SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 29
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 28
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
239000012265 solid product Substances 0.000 description 26
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
239000007787 solid Substances 0.000 description 24
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 22
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 21
238000002360 preparation method Methods 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
239000011734 sodium Substances 0.000 description 19
238000001914 filtration Methods 0.000 description 18
235000017557 sodium bicarbonate Nutrition 0.000 description 18
229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
239000012267 brine Substances 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
159000000000 sodium salts Chemical class 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 14
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
239000002585 base Substances 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
ABRDZPQSYYGSIP-SSDOTTSWSA-N (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-4-carbaldehyde Chemical compound S1C(=CCN2[C@H]1CC2=O)C=O ABRDZPQSYYGSIP-SSDOTTSWSA-N 0.000 description 12
239000004305 biphenyl Substances 0.000 description 12
238000004452 microanalysis Methods 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 11
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 11
125000001246 bromo group Chemical group Br* 0.000 description 11
239000012071 phase Substances 0.000 description 11
YDYAZTJQRUOGAH-NQPNHJOESA-N (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-4-carbaldehyde Chemical compound S1C(C=CN2[C@H]1CC2=O)C=O YDYAZTJQRUOGAH-NQPNHJOESA-N 0.000 description 10
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
235000019253 formic acid Nutrition 0.000 description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 10
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
WGGBNFPFDAICPR-UHFFFAOYSA-N 3-methylideneazetidin-2-one Chemical class C=C1CNC1=O WGGBNFPFDAICPR-UHFFFAOYSA-N 0.000 description 9
HMTPCCAUKGNCQI-UHFFFAOYSA-N FC(C(=O)O)(F)F.N12C(=CCCC2CC1)C(=O)O Chemical compound FC(C(=O)O)(F)F.N12C(=CCCC2CC1)C(=O)O HMTPCCAUKGNCQI-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
150000007513 acids Chemical class 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
239000003480 eluent Substances 0.000 description 9
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
150000007530 organic bases Chemical class 0.000 description 8
239000003960 organic solvent Substances 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 7
150000007529 inorganic bases Chemical class 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
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 7
RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 description 6
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
125000004185 ester group Chemical group 0.000 description 6
150000004820 halides Chemical class 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
239000000843 powder Substances 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000007239 Wittig reaction Methods 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
235000010290 biphenyl Nutrition 0.000 description 5
125000001589 carboacyl group Chemical group 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
239000013078 crystal Substances 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
150000004702 methyl esters Chemical class 0.000 description 5
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 5
229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
230000007017 scission Effects 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 4
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 4
238000005903 acid hydrolysis reaction Methods 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 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
230000000694 effects Effects 0.000 description 4
239000000499 gel Substances 0.000 description 4
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
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OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000003925 fat Substances 0.000 description 1
239000011790 ferrous sulphate Substances 0.000 description 1
235000003891 ferrous sulphate Nutrition 0.000 description 1
201000007794 fetal alcohol syndrome Diseases 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
150000002222 fluorine compounds Chemical class 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000010931 gold Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000001072 heteroaryl 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
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
239000000852 hydrogen donor Substances 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
ZTUJDPKOHPKRMO-UHFFFAOYSA-N hydron;2,2,2-trifluoroethanamine;chloride Chemical compound Cl.NCC(F)(F)F ZTUJDPKOHPKRMO-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
150000007928 imidazolide derivatives Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
239000011147 inorganic material Substances 0.000 description 1
229910017053 inorganic salt Inorganic materials 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
229960004194 lidocaine Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
VMVNZNXAVJHNDJ-UHFFFAOYSA-N methyl 2,2,2-trifluoroacetate Chemical compound COC(=O)C(F)(F)F VMVNZNXAVJHNDJ-UHFFFAOYSA-N 0.000 description 1
UFEJKYYYVXYMMS-UHFFFAOYSA-N methylcarbamic acid Chemical class CNC(O)=O UFEJKYYYVXYMMS-UHFFFAOYSA-N 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
239000012285 osmium tetroxide Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000003551 oxepanyl group Chemical group 0.000 description 1
238000005949 ozonolysis reaction Methods 0.000 description 1
125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
BJDYCCHRZIFCGN-UHFFFAOYSA-N pyridin-1-ium;iodide Chemical compound I.C1=CC=NC=C1 BJDYCCHRZIFCGN-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000000926 separation method Methods 0.000 description 1
208000013223 septicemia Diseases 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
CUXKZYSCZCNPNX-UHFFFAOYSA-N tetradecan-1-amine;hydrobromide Chemical compound [Br-].CCCCCCCCCCCCCC[NH3+] CUXKZYSCZCNPNX-UHFFFAOYSA-N 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
239000003451 thiazide diuretic agent Substances 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
238000010555 transalkylation reaction Methods 0.000 description 1
125000005208 trialkylammonium group Chemical group 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
JJPVWQWOOQYHCB-UHFFFAOYSA-N triethyl(phenyl)azanium Chemical compound CC[N+](CC)(CC)C1=CC=CC=C1 JJPVWQWOOQYHCB-UHFFFAOYSA-N 0.000 description 1
CPRPKIMXLHBUGA-UHFFFAOYSA-N triethyltin Chemical group CC[Sn](CC)CC CPRPKIMXLHBUGA-UHFFFAOYSA-N 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
125000005023 xylyl group Chemical group 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000002132 β-lactam antibiotic Substances 0.000 description 1
229940124586 β-lactam antibiotics Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cephalosporin Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

OA60495A 1993-04-16 1994-04-15 Derives de la cephalosporine compositions pharmaceutiques les contenant et procede de fabrication OA10064A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US4868893A	1993-04-16	1993-04-16
US08/213,562 US5523400A (en)	1993-04-16	1994-03-21	Cephalosporin antibiotics

Publications (1)

Publication Number	Publication Date
OA10064A true OA10064A (fr)	1996-10-14

Family

ID=26726411

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60495A OA10064A (fr)	1993-04-16	1994-04-15	Derives de la cephalosporine compositions pharmaceutiques les contenant et procede de fabrication

Country Status (32)

Country	Link
EP (1)	EP0620225B1 (is)
JP (1)	JP2845752B2 (is)
CN (1)	CN1046524C (is)
AT (1)	ATE227728T1 (is)
AU (1)	AU675695B2 (is)
BG (1)	BG61450B1 (is)
BR (1)	BR9401503A (is)
CA (1)	CA2121324C (is)
CY (1)	CY2189B1 (is)
CZ (1)	CZ91394A3 (is)
DE (1)	DE69431691T2 (is)
DK (1)	DK0620225T3 (is)
ES (1)	ES2185634T3 (is)
FI (1)	FI115525B (is)
GB (1)	GB2277737B (is)
GE (1)	GEP20002332B (is)
HR (1)	HRP940252A2 (is)
HU (2)	HUT71252A (is)
IL (1)	IL109321A (is)
IS (1)	IS4151A (is)
LT (1)	LT3289B (is)
LV (1)	LV10778B (is)
NO (1)	NO305601B1 (is)
NZ (1)	NZ260308A (is)
OA (1)	OA10064A (is)
PT (1)	PT620225E (is)
RU (1)	RU2130939C1 (is)
SG (1)	SG49814A1 (is)
SK (1)	SK42694A3 (is)
TW (1)	TW412537B (is)
ZA (1)	ZA942612B (is)
ZW (1)	ZW4794A1 (is)

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US5523400A (en) *	1993-04-16	1996-06-04	Hoffmann-La Roche Inc.	Cephalosporin antibiotics
US5856474A (en)	1994-04-25	1999-01-05	Biochemie Gesellschaft, M.B.H.	Cephalosporin synthesis
TR199700859T1 (xx) *	1995-02-27	1998-02-21	F. Hoffmann-La Roche Ag	3-Pirolidiliden-2-on-sefalosporin t�revleri.
US5804577A (en) *	1995-09-12	1998-09-08	Hoffmann-La Roche Inc.	Cephalosporin derivatives
EP0761673A1 (en) *	1995-09-12	1997-03-12	F. Hoffmann-La Roche Ag	Cephalosporin derivatives
US5811419A (en) *	1996-01-16	1998-09-22	Hoffmann-La Roche Inc.	Isooxacephem-derivatives
US5883247A (en) *	1996-06-10	1999-03-16	Hoffmann-La Roche Inc.	Preparation of cephem and isooxacephem derivatives
EP0831093A1 (en) *	1996-09-23	1998-03-25	F. Hoffmann-La Roche Ag	1-Carba-(dethia)-Cephalosporin Derivatives
SG53049A1 (en) *	1996-09-23	1998-09-28	Hoffmann La Roche	1-carba-(dethia)-cephalosporin derivatives
EP0838465A1 (en) *	1996-10-22	1998-04-29	F. Hoffmann-La Roche Ag	Pyridinium-substituted (lactamylvinyl)cephalosporin derivatives, their preparation and their use as antibiotics
TW446707B (en) *	1996-10-22	2001-07-21	Hoffmann La Roche	Cephalosporin pyridinium derivatives
DE69737382T2 (de) *	1996-11-06	2007-10-31	Basilea Pharmaceutica Ag	Vinylpyrrolidinon-Cephalosporin-Derivate
TW415949B (en) *	1996-12-19	2000-12-21	Hoffmann La Roche	Vinyl pyrrolidine cephalosporin derivatives with basic substituents
US6114541A (en) *	1997-03-10	2000-09-05	Hoffmann-La Roche Inc.	Method for the preparation of α-Bromo-Lactam derivatives
US6150350A (en) *	1997-09-15	2000-11-21	Hoffman-La Roche Inc.	Antimicrobial compositions
ATE370146T1 (de) *	1999-07-05	2007-09-15	Basilea Pharmaceutica Ag	Verfahren zur herstellung von cephalosporin- derivaten
KR100342944B1 (ko) *	1999-11-08	2002-07-02	민경윤	고순도 세프포독심 프록세틸의 제조방법
ATE341642T1 (de)	2000-04-19	2006-10-15	Basilea Pharmaceutica Ag	Verfahren zur herstellung von d- asparaginderivaten
US6504025B2 (en) *	2000-05-24	2003-01-07	Basilea Pharmaceutica Ag	Process for the preparation of vinyl-pyrrolidinone cephalosporin derivatives
US20090176206A1 (en) *	2004-03-04	2009-07-09	James Russell	Toll-like receptor 2 (tlr-2) haplotypes predict outcome of patients
CN101309916A (zh) *	2005-11-18	2008-11-19	卫材R&D管理有限公司	制备肉桂酰胺衍生物的方法
CN101245077B (zh) *	2007-02-14	2010-06-02	山东轩竹医药科技有限公司	头孢菌素衍生物
JP5403205B2 (ja) *	2007-10-29	2014-01-29	日産化学工業株式会社	２−アミノ−ｎ−（２，２，２−トリフルオロエチル）アセトアミド化合物又はその塩の製造方法
UY35103A (es)	2012-10-29	2014-05-30	Glaxo Group Ltd	Compuestos de cefem 2-sustituidos

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US3971778A (en) *	1972-05-12	1976-07-27	Glaxo Laboratories Limited	Cephalosporins having (α-etherified oximino)acylamido groups at the 7-position
JPS5854157B2 (ja)	1977-06-10	1983-12-02	山之内製薬株式会社	セフアロスポリン化合物の新規誘導体ならびにその製造方法
US4255423A (en) *	1977-07-27	1981-03-10	Merck & Co., Inc.	Cephalosporin compounds
JPH0686463B2 (ja) *	1988-07-01	1994-11-02	明治製菓株式会社	新規セフェム化合物、その製造法及び抗菌剤
GB8821797D0 (en) *	1988-09-16	1988-10-19	Beecham Group Plc	Novel compounds

1994
- 1994-03-30 ES ES94104997T patent/ES2185634T3/es not_active Expired - Lifetime
- 1994-03-30 DK DK94104997T patent/DK0620225T3/da active
- 1994-03-30 EP EP94104997A patent/EP0620225B1/en not_active Expired - Lifetime
- 1994-03-30 PT PT94104997T patent/PT620225E/pt unknown
- 1994-03-30 DE DE69431691T patent/DE69431691T2/de not_active Expired - Lifetime
- 1994-03-30 AT AT94104997T patent/ATE227728T1/de active
- 1994-04-14 NO NO941342A patent/NO305601B1/no not_active IP Right Cessation
- 1994-04-14 NZ NZ260308A patent/NZ260308A/xx unknown
- 1994-04-14 SK SK426-94A patent/SK42694A3/sk unknown
- 1994-04-14 RU RU94012924A patent/RU2130939C1/ru active
- 1994-04-14 CA CA002121324A patent/CA2121324C/en not_active Expired - Lifetime
- 1994-04-14 GB GB9407400A patent/GB2277737B/en not_active Expired - Lifetime
- 1994-04-15 JP JP6101558A patent/JP2845752B2/ja not_active Expired - Lifetime
- 1994-04-15 LT LTIP1916A patent/LT3289B/lt not_active IP Right Cessation
- 1994-04-15 CN CN94104429A patent/CN1046524C/zh not_active Expired - Lifetime
- 1994-04-15 GE GEAP19941859A patent/GEP20002332B/en unknown
- 1994-04-15 HR HR08/048,688A patent/HRP940252A2/hr not_active Application Discontinuation
- 1994-04-15 FI FI941775A patent/FI115525B/fi not_active IP Right Cessation
- 1994-04-15 LV LVP-94-73A patent/LV10778B/en unknown
- 1994-04-15 BG BG98723A patent/BG61450B1/bg unknown
- 1994-04-15 AU AU59494/94A patent/AU675695B2/en not_active Expired
- 1994-04-15 HU HU9401080A patent/HUT71252A/hu unknown
- 1994-04-15 ZW ZW4794A patent/ZW4794A1/xx unknown
- 1994-04-15 OA OA60495A patent/OA10064A/fr unknown
- 1994-04-15 ZA ZA942612A patent/ZA942612B/xx unknown
- 1994-04-15 BR BR9401503A patent/BR9401503A/pt not_active Application Discontinuation
- 1994-04-15 CZ CZ94913A patent/CZ91394A3/cs unknown
- 1994-04-15 IS IS4151A patent/IS4151A/is unknown
- 1994-04-15 IL IL10932194A patent/IL109321A/en not_active IP Right Cessation
- 1994-04-15 TW TW083103375A patent/TW412537B/zh not_active IP Right Cessation
1995
- 1995-06-20 HU HU95P/P00262P patent/HU211652A9/hu unknown
1996
- 1996-03-28 SG SG1996006705A patent/SG49814A1/en unknown
1999
- 1999-07-26 CY CY9900020A patent/CY2189B1/xx unknown

Also Published As

Publication number	Publication date
HU9401080D0 (en)	1994-07-28
FI115525B (fi)	2005-05-31
ATE227728T1 (de)	2002-11-15
LV10778A (lv)	1995-08-20
DE69431691T2 (de)	2003-08-21
GB9407400D0 (en)	1994-06-08
LTIP1916A (en)	1994-11-25
LT3289B (en)	1995-06-26
AU5949494A (en)	1994-10-20
CA2121324C (en)	2007-07-10
HRP940252A2 (en)	1996-08-31
GEP20002332B (en)	2000-12-25
HK1000423A1 (en)	1998-03-20
AU675695B2 (en)	1997-02-13
EP0620225B1 (en)	2002-11-13
HUT71252A (en)	1995-11-28
FI941775L (fi)	1994-10-17
HU211652A9 (en)	1995-12-28
BR9401503A (pt)	1994-10-25
NZ260308A (en)	1996-05-28
NO941342D0 (no)	1994-04-14
NO941342L (no)	1994-10-17
JP2845752B2 (ja)	1999-01-13
IL109321A (en)	1998-07-15
RU2130939C1 (ru)	1999-05-27
PT620225E (pt)	2003-03-31
CN1105365A (zh)	1995-07-19
FI941775A0 (fi)	1994-04-15
TW412537B (en)	2000-11-21
CA2121324A1 (en)	1994-10-17
ZW4794A1 (en)	1995-01-05
IS4151A (is)	1994-10-17
BG61450B1 (bg)	1997-08-29
CZ91394A3 (en)	1994-11-16
EP0620225A1 (en)	1994-10-19
IL109321A0 (en)	1994-07-31
DE69431691D1 (de)	2002-12-19
JPH06321954A (ja)	1994-11-22
BG98723A (en)	1995-03-31
CN1046524C (zh)	1999-11-17
ZA942612B (en)	1994-10-17
NO305601B1 (no)	1999-06-28
GB2277737A (en)	1994-11-09
CY2189B1 (en)	2002-11-08
SG49814A1 (en)	1998-06-15
ES2185634T3 (es)	2003-05-01
DK0620225T3 (da)	2003-03-17
SK42694A3 (en)	1995-02-08
GB2277737B (en)	1996-09-25
LV10778B (en)	1996-06-20

Publication	Publication Date	Title
OA10064A (fr)	1996-10-14	Derives de la cephalosporine compositions pharmaceutiques les contenant et procede de fabrication
KR100309516B1 (ko)	2006-05-25	세팔로스포린유도체
FI75163C (fi)	1988-05-09	Foerfarande foer framstaellning av nya penemkarboxylsyror eller -estrar.
US4482565A (en)	1984-11-13	β-Lactam-containing antibacterial agents and β-lactamase inhibitors
HU194876B (en)	1988-03-28	Process for production of new derivatives of 1-sulpha-2-azetidinon and medical preparatives containing these compounds
FR2531427A1 (fr)	1984-02-10	Composes d'azetidine a action therapeutique
MC2021A1 (fr)	1990-02-23	Preparation de derives acyliques utilisables notamment pour la fabrication de medicaments
US6218379B1 (en)	2001-04-17	Tricyclic carbacephems
EP0153229B1 (fr)	1993-04-07	Nouveaux dérivés de l'acide 1-déthia 2-thia céphalosporanique, leur procédé et leurs intermédiaires de préparation, leur application comme médicaments et les compositions les renfermant
IE63026B1 (en)	1995-03-22	Stable oxapenem-3-carboxylic acids
HU198943B (en)	1989-12-28	Process for producing 2-/methoxymethyl/-penem derivatives and pharmaceutical compositions comprising same
CN1083814A (zh)	1994-03-16	杂环化合物
HU186556B (en)	1985-08-28	Process for producing 2-oxo-1-square bracket-bracket-acyl-amine-bracket closed-sulfonyl-square bracket closed-azetidine derivatives
EP0548186B1 (en)	1997-03-05	Cephalosporin derivatives and their homologues
US4558042A (en)	1985-12-10	β-Lactam-containing antibacterial agents and β-lactamase inhibitors
US4831130A (en)	1989-05-16	β-lactam antibacterial agents
HUT53650A (en)	1990-11-28	Process for producing pharmaceutical compositions with beta-lactamase inhibiting effect and comprising stable oxapenem-3-carboxylic acids
US5811419A (en)	1998-09-22	Isooxacephem-derivatives
FR2534253A1 (fr)	1984-04-13	Acide azetidinyl sulfonique et analogues, a action therapeutique
EP0100041B1 (en)	1986-10-22	1-sulfo-2-azetidinone derivatives, their production and use
GB2124614A (en)	1984-02-22	Easily cleavable carboxylic esters and their use in the synthesis of penems and other b-lactam antibiotics
JPH04364183A (ja)	1992-12-16	フルオロアルキル化カルバペネム中間体
MC2069A1 (fr)	1990-10-03	Nouveaux composes antibacteriens
AP199A (en)	1992-06-30	Novel B-Lactam and a novel class cephalosporins.
HU209817B (en)	1994-11-28	Process for the production of antibacterial 2-carbapenem derivatives