LT3289B - Cephalosporin derivatives with antibacterial activity - Google Patents

Cephalosporin derivatives with antibacterial activity Download PDF

Info

Publication number: LT3289B
Authority: LT; Lithuania
Prior art keywords: amino; oxo; compounds; compound; salts
Prior art date: 1993-04-16

Application number

LTIP1916A

Other languages

English (en)

Lithuanian (lt)

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

1995-06-26

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

1994-11-25 Publication of LTIP1916A publication Critical patent/LTIP1916A/xx

1995-06-26 Publication of LT3289B publication Critical patent/LT3289B/lt

Links

229930186147 Cephalosporin Natural products 0.000 title claims abstract description 7
229940124587 cephalosporin Drugs 0.000 title claims abstract description 7
150000001780 cephalosporins Chemical class 0.000 title claims abstract description 6
230000000844 anti-bacterial effect Effects 0.000 title claims description 6
-1 carboxy, amino Chemical group 0.000 claims abstract description 680
150000001875 compounds Chemical class 0.000 claims abstract description 195
150000003839 salts Chemical class 0.000 claims abstract description 81
125000000217 alkyl group Chemical group 0.000 claims abstract description 64
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
150000002148 esters Chemical class 0.000 claims abstract description 50
239000001257 hydrogen Substances 0.000 claims abstract description 44
150000004677 hydrates Chemical class 0.000 claims abstract description 30
229910052736 halogen Inorganic materials 0.000 claims abstract description 23
150000002431 hydrogen Chemical class 0.000 claims abstract description 23
125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 19
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 19
150000002367 halogens Chemical class 0.000 claims abstract description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
125000003118 aryl group Chemical group 0.000 claims abstract description 17
150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 17
125000002252 acyl group Chemical group 0.000 claims abstract description 16
125000003342 alkenyl group Chemical group 0.000 claims abstract description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
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
125000004104 aryloxy group Chemical group 0.000 claims abstract description 7
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 7
125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
125000006244 carboxylic acid protecting group Chemical group 0.000 claims abstract description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 154
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 137
239000002253 acid Substances 0.000 claims description 28
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 26
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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 16
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 12
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 11
ZBPYTVBKHKUNHG-UHFFFAOYSA-N non-3-enoic acid Chemical compound CCCCCC=CCC(O)=O ZBPYTVBKHKUNHG-UHFFFAOYSA-N 0.000 claims description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
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 5
MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
229910052717 sulfur Chemical group 0.000 claims description 2
239000011593 sulfur Chemical group 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 10
125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
206010039740 Screaming Diseases 0.000 claims 1
208000003443 Unconsciousness Diseases 0.000 claims 1
125000005356 cycloalkylalkenyl group Chemical group 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 206
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 98
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 92
239000000203 mixture Substances 0.000 description 89
238000005481 NMR spectroscopy Methods 0.000 description 85
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
235000002639 sodium chloride Nutrition 0.000 description 73
SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 67
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 60
239000007787 solid Substances 0.000 description 56
239000000243 solution Substances 0.000 description 50
239000002904 solvent Substances 0.000 description 48
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
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238000000034 method Methods 0.000 description 42
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 38
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 38
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 34
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
125000001841 imino group Chemical group [H]N=* 0.000 description 32
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
125000006239 protecting group Chemical group 0.000 description 30
RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000000047 product Substances 0.000 description 27
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
239000011734 sodium Substances 0.000 description 26
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
239000012267 brine Substances 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
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 18
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
238000004452 microanalysis Methods 0.000 description 18
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 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
238000003756 stirring Methods 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
KDBQZXYVWWRTAJ-UHFFFAOYSA-N 2-methyloct-2-enoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCCCC=C(C)C(O)=O KDBQZXYVWWRTAJ-UHFFFAOYSA-N 0.000 description 12
GUBYYDHSFIQMDU-UHFFFAOYSA-N 2-methyloct-3-enoic acid Chemical compound CCCCC=CC(C)C(O)=O GUBYYDHSFIQMDU-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
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125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
125000001246 bromo group Chemical group Br* 0.000 description 10
238000004587 chromatography analysis Methods 0.000 description 10
239000003480 eluent Substances 0.000 description 10
WGGBNFPFDAICPR-UHFFFAOYSA-N 3-methylideneazetidin-2-one Chemical class C=C1CNC1=O WGGBNFPFDAICPR-UHFFFAOYSA-N 0.000 description 9
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 9
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
BUKJBGNGPQXFTH-UHFFFAOYSA-N benzhydryl 2-methyloct-2-enoate Chemical compound C=1C=CC=CC=1C(OC(=O)C(C)=CCCCCC)C1=CC=CC=C1 BUKJBGNGPQXFTH-UHFFFAOYSA-N 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
235000019253 formic acid Nutrition 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
239000003795 chemical substances by application Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
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239000012071 phase Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
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125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
IKWLIQXIPRUIDU-UHFFFAOYSA-N 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCSC2CC(=O)N12 IKWLIQXIPRUIDU-UHFFFAOYSA-N 0.000 description 7
MERIBKCTSSKHJT-UHFFFAOYSA-N benzhydryl 2-methyloct-3-enoate Chemical compound C=1C=CC=CC=1C(OC(=O)C(C)C=CCCCC)C1=CC=CC=C1 MERIBKCTSSKHJT-UHFFFAOYSA-N 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
238000001914 filtration Methods 0.000 description 7
150000007529 inorganic bases Chemical class 0.000 description 7
150000007530 organic bases Chemical class 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
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
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238000007239 Wittig reaction Methods 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
239000000969 carrier Substances 0.000 description 6
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 6
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208000015181 infectious disease Diseases 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
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239000000843 powder Substances 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 5
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 5
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239000000463 material Substances 0.000 description 5
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238000010898 silica gel chromatography Methods 0.000 description 5
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
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229910000104 sodium hydride Inorganic materials 0.000 description 5
150000003512 tertiary amines Chemical class 0.000 description 5
ZCBBAJGSIQDPIF-YLHCSOALSA-N (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(benzotriazol-1-yl)phenyl]-diphenylmethoxy]iminoacetic acid Chemical compound S1C(N)=NC(C(=N\OC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C(=CC=CC=2)N2C3=CC=CC=C3N=N2)\C(O)=O)=C1 ZCBBAJGSIQDPIF-YLHCSOALSA-N 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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239000001828 Gelatine Substances 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
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239000002775 capsule Substances 0.000 description 4
125000001589 carboacyl group Chemical group 0.000 description 4
125000002837 carbocyclic group Chemical group 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 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
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229910052744 lithium Inorganic materials 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
238000004519 manufacturing process Methods 0.000 description 4
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 4
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 4
239000000825 pharmaceutical preparation Substances 0.000 description 4
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230000002441 reversible effect Effects 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
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ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
KLBNVJILLBGDRV-UHFFFAOYSA-N 2,4-dibromo-n-(2,2,2-trifluoroethyl)butanamide Chemical compound FC(F)(F)CNC(=O)C(Br)CCBr KLBNVJILLBGDRV-UHFFFAOYSA-N 0.000 description 2
OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
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QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 2
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ULBYKRDEJLEBER-UHFFFAOYSA-N 3-bromo-1-(2,2,2-trifluoroethyl)pyrrolidin-2-one Chemical compound FC(F)(F)CN1CCC(Br)C1=O ULBYKRDEJLEBER-UHFFFAOYSA-N 0.000 description 2
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NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
VJCLLNXQSYQNOV-UHFFFAOYSA-N 3-methylidene-1-phenylazetidin-2-one Chemical compound O=C1C(=C)CN1C1=CC=CC=C1 VJCLLNXQSYQNOV-UHFFFAOYSA-N 0.000 description 2
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GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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239000004215 Carbon black (E152) Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
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PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 2
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241000589517 Pseudomonas aeruginosa Species 0.000 description 2
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HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
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MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
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SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
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239000000499 gel Substances 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
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125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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 2
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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
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
150000007928 imidazolide derivatives Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical class CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 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
125000001786 isothiazolyl group Chemical group 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960004393 lidocaine hydrochloride Drugs 0.000 description 1
YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
150000002642 lithium compounds Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
LLCOIQRNSJBFSN-UHFFFAOYSA-N methane;sulfurochloridic acid Chemical compound C.OS(Cl)(=O)=O LLCOIQRNSJBFSN-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 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
IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 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
239000012299 nitrogen atmosphere Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
YYZUSRORWSJGET-UHFFFAOYSA-N octanoic acid ethyl ester Natural products CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
150000002916 oxazoles Chemical class 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000003551 oxepanyl group Chemical group 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000005646 oximino group Chemical group 0.000 description 1
150000002924 oxiranes Chemical class 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
238000007911 parenteral administration Methods 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
125000005561 phenanthryl group Chemical group 0.000 description 1
AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 description 1
125000005633 phthalidyl group Chemical group 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
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 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
239000011698 potassium fluoride Substances 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
239000003755 preservative agent Substances 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
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 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
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000000926 separation method Methods 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
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 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
239000005720 sucrose Substances 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 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
150000005621 tetraalkylammonium salts Chemical class 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
125000003507 tetrahydrothiofenyl 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
230000001225 therapeutic effect Effects 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
229960002171 tiocarlide Drugs 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
238000010555 transalkylation reaction Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005208 trialkylammonium group Chemical group 0.000 description 1
125000004306 triazinyl 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
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 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
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)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cephalosporin Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

LTIP1916A 1993-04-16 1994-04-15 Cephalosporin derivatives with antibacterial activity LT3289B (en)

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 (2)

Publication Number	Publication Date
LTIP1916A LTIP1916A (en)	1994-11-25
LT3289B true LT3289B (en)	1995-06-26

Family

ID=26726411

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LTIP1916A LT3289B (en)	1993-04-16	1994-04-15	Cephalosporin derivatives with antibacterial activity

Country Status (32)

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

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
WO1996026943A1 (en) *	1995-02-27	1996-09-06	F.Hoffmann-La Roche Ag	Derivatives of 3-pyrrolidylidene-2-one-cephalosporines
CZ251896A3 (en) *	1995-09-12	1997-04-16	Hoffmann Ka Roche Ag F	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
SG53049A1 (en) *	1996-09-23	1998-09-28	Hoffmann La Roche	1-carba-(dethia)-cephalosporin derivatives
EP0831093A1 (en) *	1996-09-23	1998-03-25	F. Hoffmann-La Roche Ag	1-Carba-(dethia)-Cephalosporin Derivatives
TW446707B (en) *	1996-10-22	2001-07-21	Hoffmann La Roche	Cephalosporin pyridinium 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
ES2281090T3 (es)	1996-11-06	2007-09-16	Basilea Pharmaceutica Ag	Derivados de vinilpirrolidona-cefalosporina.
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
DK1148140T3 (da)	2000-04-19	2007-01-08	Basilea Pharmaceutica Ag	Fremgangsmåde til fremstilling af D-asparaginderivater
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
CN101245081B (zh) *	2007-02-14	2010-10-13	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

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3971778A (en)	1972-05-12	1976-07-27	Glaxo Laboratories Limited	Cephalosporins having (α-etherified oximino)acylamido groups at the 7-position
BE867994A (fr)	1977-06-10	1978-12-11	Yamanouchi Pharma Co Ltd	Procede de preparation de derives de l'acide methoxy-7,alpha-(dithietane-1,3-carboxamido-2)-cephalosporanique

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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 PT PT94104997T patent/PT620225E/pt unknown
- 1994-03-30 ES ES94104997T patent/ES2185634T3/es not_active Expired - Lifetime
- 1994-03-30 AT AT94104997T patent/ATE227728T1/de active
- 1994-03-30 EP EP94104997A patent/EP0620225B1/en not_active Expired - Lifetime
- 1994-03-30 DK DK94104997T patent/DK0620225T3/da active
- 1994-03-30 DE DE69431691T patent/DE69431691T2/de not_active Expired - Lifetime
- 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
- 1994-04-14 SK SK426-94A patent/SK42694A3/sk unknown
- 1994-04-14 NZ NZ260308A patent/NZ260308A/xx unknown
- 1994-04-14 NO NO941342A patent/NO305601B1/no not_active IP Right Cessation
- 1994-04-15 OA OA60495A patent/OA10064A/fr unknown
- 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 BG BG98723A patent/BG61450B1/bg unknown
- 1994-04-15 TW TW083103375A patent/TW412537B/zh not_active IP Right Cessation
- 1994-04-15 HR HR08/048,688A patent/HRP940252A2/hr not_active Application Discontinuation
- 1994-04-15 HU HU9401080A patent/HUT71252A/hu unknown
- 1994-04-15 CZ CZ94913A patent/CZ91394A3/cs unknown
- 1994-04-15 ZW ZW4794A patent/ZW4794A1/xx unknown
- 1994-04-15 LV LVP-94-73A patent/LV10778B/en unknown
- 1994-04-15 IL IL10932194A patent/IL109321A/en not_active IP Right Cessation
- 1994-04-15 FI FI941775A patent/FI115525B/fi not_active IP Right Cessation
- 1994-04-15 JP JP6101558A patent/JP2845752B2/ja not_active Expired - Lifetime
- 1994-04-15 GE GEAP19941859A patent/GEP20002332B/en unknown
- 1994-04-15 BR BR9401503A patent/BR9401503A/pt not_active Application Discontinuation
- 1994-04-15 ZA ZA942612A patent/ZA942612B/xx unknown
- 1994-04-15 IS IS4151A patent/IS4151A/is unknown
- 1994-04-15 AU AU59494/94A patent/AU675695B2/en not_active Expired
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3971778A (en)	1972-05-12	1976-07-27	Glaxo Laboratories Limited	Cephalosporins having (α-etherified oximino)acylamido groups at the 7-position
BE867994A (fr)	1977-06-10	1978-12-11	Yamanouchi Pharma Co Ltd	Procede de preparation de derives de l'acide methoxy-7,alpha-(dithietane-1,3-carboxamido-2)-cephalosporanique

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CZ91394A3 (en)	1994-11-16
ES2185634T3 (es)	2003-05-01
HUT71252A (en)	1995-11-28
EP0620225B1 (en)	2002-11-13
FI941775L (fi)	1994-10-17
BG61450B1 (bg)	1997-08-29
AU675695B2 (en)	1997-02-13
SK42694A3 (en)	1995-02-08
BR9401503A (pt)	1994-10-25
RU2130939C1 (ru)	1999-05-27
FI115525B (fi)	2005-05-31
CN1046524C (zh)	1999-11-17
ZW4794A1 (en)	1995-01-05
NO941342L (no)	1994-10-17
CA2121324A1 (en)	1994-10-17
GEP20002332B (en)	2000-12-25
ATE227728T1 (de)	2002-11-15
CA2121324C (en)	2007-07-10
GB9407400D0 (en)	1994-06-08
CY2189B1 (en)	2002-11-08
DE69431691T2 (de)	2003-08-21
NO941342D0 (no)	1994-04-14
CN1105365A (zh)	1995-07-19
ZA942612B (en)	1994-10-17
DK0620225T3 (da)	2003-03-17
LTIP1916A (en)	1994-11-25
LV10778A (lv)	1995-08-20
LV10778B (en)	1996-06-20
EP0620225A1 (en)	1994-10-19
TW412537B (en)	2000-11-21
JP2845752B2 (ja)	1999-01-13
GB2277737B (en)	1996-09-25
NZ260308A (en)	1996-05-28
NO305601B1 (no)	1999-06-28
HK1000423A1 (en)	1998-03-20
JPH06321954A (ja)	1994-11-22
IS4151A (is)	1994-10-17
SG49814A1 (en)	1998-06-15
GB2277737A (en)	1994-11-09
BG98723A (en)	1995-03-31
HRP940252A2 (en)	1996-08-31
FI941775A0 (fi)	1994-04-15
HU211652A9 (en)	1995-12-28
IL109321A0 (en)	1994-07-31
IL109321A (en)	1998-07-15
PT620225E (pt)	2003-03-31
DE69431691D1 (de)	2002-12-19
HU9401080D0 (en)	1994-07-28
AU5949494A (en)	1994-10-20
OA10064A (fr)	1996-10-14

Legal Events

Date	Code	Title	Description
2002-12-30	MM9A	Lapsed patents	Effective date: 20020415

Publication	Publication Date	Title
LT3289B (en)	1995-06-26	Cephalosporin derivatives with antibacterial activity
KR100309516B1 (ko)	2006-05-25	세팔로스포린유도체
SE450384B (sv)	1987-06-22	Nya cefemforeningar och forfarande for deras framstellning
US6218379B1 (en)	2001-04-17	Tricyclic carbacephems
US5883247A (en)	1999-03-16	Preparation of cephem and isooxacephem derivatives
HU184805B (en)	1984-10-29	Process for preparing new substituted alkyl-oximes derived from 7-/2-amino-4-thazolyl/-acetamido-cephalosporanic acid
US5811419A (en)	1998-09-22	Isooxacephem-derivatives
JP2002518505A (ja)	2002-06-25	プロペニルセファロスポリン誘導体
JPH06500788A (ja)	1994-01-27	セファロスポリン誘導体およびそれらの同族体
EP0831093A1 (en)	1998-03-25	1-Carba-(dethia)-Cephalosporin Derivatives
CH687205A5 (fr)	1996-10-15	Dérivés de thioalkylthiocarbacephalosporine.
KR100256473B1 (ko)	2000-05-15	1-카바-(데티아)-세팔로스포린유도체
AP199A (en)	1992-06-30	Novel B-Lactam and a novel class cephalosporins.
KR100253783B1 (ko)	2000-07-01	세팔로스포린 피리디늄 유도체
NO882652L (no)	1988-12-19	Acylderivater.
FI65780C (fi)	1984-07-10	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara cefalosporiner
CS216936B2 (cs)	1982-12-31	Způsob výroby derivátů 7/3-aminothiazolylacetainido- -3-cefem-4-karboxylové kyseliny
MXPA97007201A (es)	1998-10-30	Derivados de 1-carba-(detia)-cefalosporina
MXPA00012689A (en)	2001-07-31	Propenyl cephalosporin derivatives
JPH08512283A (ja)	1996-12-24	カルバセファロスポリン化合物、その合成および使用