IL125107A - Derivatives of antibiotics GE2270 factors D2, C2a and E, process for their preparation and pharmaceutical compounds containing them - Google Patents
Derivatives of antibiotics GE2270 factors D2, C2a and E, process for their preparation and pharmaceutical compounds containing themInfo
- Publication number
- IL125107A IL125107A IL12510797A IL12510797A IL125107A IL 125107 A IL125107 A IL 125107A IL 12510797 A IL12510797 A IL 12510797A IL 12510797 A IL12510797 A IL 12510797A IL 125107 A IL125107 A IL 125107A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- alkyl
- group
- compound
- alkylamino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 104
- 230000008569 process Effects 0.000 title claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 42
- 101000655610 Planobispora rosea Thiocillin GE2270 Proteins 0.000 title description 13
- -1 2-(aminocarbonyl)- pyrrolidinyl moiety Chemical group 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 20
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 230000003115 biocidal effect Effects 0.000 claims abstract description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 13
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 13
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 239000001301 oxygen Substances 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
- 238000006243 chemical reaction Methods 0.000 claims description 72
- 239000002904 solvent Substances 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 239000011541 reaction mixture Substances 0.000 claims description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 36
- 239000002585 base Substances 0.000 claims description 33
- 239000003960 organic solvent Substances 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 28
- MGOGKPMIZGEGOZ-REOHCLBHSA-N (2s)-2-amino-3-hydroxypropanamide Chemical compound OC[C@H](N)C(N)=O MGOGKPMIZGEGOZ-REOHCLBHSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 125000006239 protecting group Chemical group 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 16
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 230000007935 neutral effect Effects 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical group C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
- 230000000845 anti-microbial effect Effects 0.000 claims description 6
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 5
- 229960004592 isopropanol Drugs 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000004599 antimicrobial Substances 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- 150000008039 phosphoramides Chemical class 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- UCOJJXSOXHUJJY-UHFFFAOYSA-N 1-[azido(ethoxy)phosphoryl]oxyethane Chemical compound CCOP(=O)(OCC)N=[N+]=[N-] UCOJJXSOXHUJJY-UHFFFAOYSA-N 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 claims description 3
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 claims description 3
- 150000002334 glycols Chemical class 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 229920005862 polyol Polymers 0.000 claims description 3
- 150000003077 polyols Chemical class 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 150000003462 sulfoxides Chemical class 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 claims description 2
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 claims description 2
- POIOOCHMXHKUHV-UHFFFAOYSA-N [nitro-[nitro(phenyl)methoxy]methyl]benzene Chemical compound C=1C=CC=CC=1C([N+](=O)[O-])OC([N+]([O-])=O)C1=CC=CC=C1 POIOOCHMXHKUHV-UHFFFAOYSA-N 0.000 claims description 2
- 150000001356 alkyl thiols Chemical class 0.000 claims description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 claims description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 3
- ABOJYSQGDXEDKJ-UHFFFAOYSA-N N-diazo-(2-nitrophenoxy)phosphonamidic acid Chemical compound [N-]=[N+]=NP(=O)(O)OC1=CC=CC=C1[N+]([O-])=O ABOJYSQGDXEDKJ-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 description 62
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- 239000007787 solid Substances 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 15
- 238000001556 precipitation Methods 0.000 description 15
- 239000000843 powder Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000003480 eluent Substances 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 7
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000004359 castor oil Substances 0.000 description 6
- 229940125898 compound 5 Drugs 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229960001153 serine Drugs 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000013375 chromatographic separation Methods 0.000 description 5
- 238000011097 chromatography purification Methods 0.000 description 5
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 241001495389 Planobispora rosea Species 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000003637 basic solution Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 235000019438 castor oil Nutrition 0.000 description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- 239000003883 ointment base Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
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- 230000003381 solubilizing effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
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- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102100025597 Caspase-4 Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 241000606768 Haemophilus influenzae Species 0.000 description 3
- 101100273284 Homo sapiens CASP4 gene Proteins 0.000 description 3
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- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 3
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- JXGVXCZADZNAMJ-NSHDSACASA-N (2s)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 JXGVXCZADZNAMJ-NSHDSACASA-N 0.000 description 2
- PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 208000003383 pontocerebellar hypoplasia type 3 Diseases 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical group C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96102145 | 1996-02-14 | ||
| PCT/EP1997/000628 WO1997030078A1 (en) | 1996-02-14 | 1997-02-12 | DERIVATIVES OF ANTIBIOTIC GE2270 FACTORS C2a, D2 AND E |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL125107A0 IL125107A0 (en) | 1999-01-26 |
| IL125107A true IL125107A (en) | 2002-12-01 |
Family
ID=8222478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12510797A IL125107A (en) | 1996-02-14 | 1997-02-12 | Derivatives of antibiotics GE2270 factors D2, C2a and E, process for their preparation and pharmaceutical compounds containing them |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6008225A (hu) |
| EP (1) | EP0880541B1 (hu) |
| JP (1) | JP2000505438A (hu) |
| KR (1) | KR19990082541A (hu) |
| AT (1) | ATE231163T1 (hu) |
| AU (1) | AU714958B2 (hu) |
| CA (1) | CA2242067A1 (hu) |
| DE (1) | DE69718442T2 (hu) |
| DK (1) | DK0880541T3 (hu) |
| ES (1) | ES2186866T3 (hu) |
| HU (1) | HUP9901007A3 (hu) |
| IL (1) | IL125107A (hu) |
| WO (1) | WO1997030078A1 (hu) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0451486T3 (da) * | 1990-03-08 | 1995-05-08 | Lepetit Spa | Antibiotikum GE 2270 faktorer B1, B2, C1, C2, D1, D2, E og T |
| US5882900A (en) * | 1992-09-10 | 1999-03-16 | Gruppo Lepetit S.P.A. | Process for the selective increase of production of antibiotic GE 2270 factor a by adding vitamin B12 to nutrient medium |
| CA2212437A1 (en) * | 1995-02-07 | 1996-08-15 | Biosearch Italia S.P.A. | Basic oxazoline-amide derivatives of ge 2270 and ge 2270-like antibiotics |
| JP2825667B2 (ja) * | 1995-02-07 | 1998-11-18 | バイオサーチ・イタリア・ソチエタ・ペル・アチオニ | Ｇｅ２２７０及びｇｅ２２７０−様抗生物質の塩基性プロリン−アミド誘導体 |
| JP4723857B2 (ja) * | 2002-06-17 | 2011-07-13 | ヴィキュロン ファーマシューティカルズ インコーポレイテッド | アクネの治療のためのｇｅ２２７０因子ａ３のアミド誘導体の使用 |
| US7119061B2 (en) * | 2002-11-18 | 2006-10-10 | Vicuron Pharmaceuticals, Inc. | Dalbavancin compositions for treatment of bacterial infections |
| WO2004045637A1 (en) * | 2002-11-18 | 2004-06-03 | Vicuron Pharmaceuticals Inc. | Dalbavancin compositions for treatment of bacterial infections |
| US20060074014A1 (en) * | 2002-11-18 | 2006-04-06 | Vicuron Pharmaceuticals Inc. | Dalbavancin compositions for treatment of bacterial infections |
| PE20121011A1 (es) * | 2006-05-31 | 2012-08-25 | Novartis Ag | AMINOTIAZOLES COMO MODULADORES DEL FACTOR DE ELONGACION EF-Tu |
| ATE500259T1 (de) * | 2006-12-20 | 2011-03-15 | Novartis Ag | Aminothiazolmakrocyclen, ihre verwendung als antibakterielle verbindungen und verfahren zu ihrer herstellung |
| BRPI0812340A2 (pt) | 2007-06-04 | 2015-01-27 | Novartis Ag | Macrociclos e seus usos |
| CA2708793C (en) | 2007-12-12 | 2016-06-21 | Novartis Ag | Aminothiazoles and their uses |
| WO2024136758A1 (en) * | 2022-12-21 | 2024-06-27 | Agency For Science, Technology And Research | Thiopeptide compounds |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5202241A (en) * | 1988-09-09 | 1993-04-13 | Gruppo Lepetit S.P.A. | Antibiotic GE 2270 |
| US5139778A (en) * | 1989-07-04 | 1992-08-18 | Gruppo Lepetit Spa | Antibiotic ge 2270 factors a1, a2, a3 and h |
| DK0451486T3 (da) * | 1990-03-08 | 1995-05-08 | Lepetit Spa | Antibiotikum GE 2270 faktorer B1, B2, C1, C2, D1, D2, E og T |
| IL100572A (en) * | 1991-01-03 | 1997-01-10 | Lepetit Spa | Amides of antibiotic ge 2270 factors their preparation and pharmaceutical compositions containing them |
| ATE163428T1 (de) * | 1991-08-30 | 1998-03-15 | Biosearch Italia Spa | Faktor c2a des antibiotikums ce 2270 |
| WO1994005798A1 (en) * | 1992-09-10 | 1994-03-17 | Gruppo Lepetit S.P.A. | Process for the selective increase of production of antibiotic ge 2270 factor a |
| JPH10508476A (ja) * | 1994-11-08 | 1998-08-25 | グルポ・レペチツト・エス・ピー・エイ | 抗生物質ｇｅ２２７０因子ｄ▲下２▼を得るための微生物変換法 |
| CA2212437A1 (en) * | 1995-02-07 | 1996-08-15 | Biosearch Italia S.P.A. | Basic oxazoline-amide derivatives of ge 2270 and ge 2270-like antibiotics |
| JP2825667B2 (ja) * | 1995-02-07 | 1998-11-18 | バイオサーチ・イタリア・ソチエタ・ペル・アチオニ | Ｇｅ２２７０及びｇｅ２２７０−様抗生物質の塩基性プロリン−アミド誘導体 |
-
1997
- 1997-02-12 AU AU17687/97A patent/AU714958B2/en not_active Ceased
- 1997-02-12 HU HU9901007A patent/HUP9901007A3/hu unknown
- 1997-02-12 US US09/101,077 patent/US6008225A/en not_active Expired - Fee Related
- 1997-02-12 IL IL12510797A patent/IL125107A/en not_active IP Right Cessation
- 1997-02-12 WO PCT/EP1997/000628 patent/WO1997030078A1/en not_active Application Discontinuation
- 1997-02-12 DK DK97903258T patent/DK0880541T3/da active
- 1997-02-12 JP JP9528975A patent/JP2000505438A/ja not_active Ceased
- 1997-02-12 DE DE69718442T patent/DE69718442T2/de not_active Expired - Fee Related
- 1997-02-12 AT AT97903258T patent/ATE231163T1/de not_active IP Right Cessation
- 1997-02-12 ES ES97903258T patent/ES2186866T3/es not_active Expired - Lifetime
- 1997-02-12 CA CA002242067A patent/CA2242067A1/en not_active Abandoned
- 1997-02-12 EP EP97903258A patent/EP0880541B1/en not_active Expired - Lifetime
- 1997-02-12 KR KR1019980706278A patent/KR19990082541A/ko not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2000505438A (ja) | 2000-05-09 |
| EP0880541B1 (en) | 2003-01-15 |
| EP0880541A1 (en) | 1998-12-02 |
| HUP9901007A3 (en) | 1999-11-29 |
| DE69718442T2 (de) | 2003-04-30 |
| ATE231163T1 (de) | 2003-02-15 |
| ES2186866T3 (es) | 2003-05-16 |
| KR19990082541A (ko) | 1999-11-25 |
| DK0880541T3 (da) | 2003-05-05 |
| HUP9901007A2 (hu) | 1999-07-28 |
| US6008225A (en) | 1999-12-28 |
| WO1997030078A1 (en) | 1997-08-21 |
| AU714958B2 (en) | 2000-01-13 |
| IL125107A0 (en) | 1999-01-26 |
| CA2242067A1 (en) | 1997-08-21 |
| DE69718442D1 (de) | 2003-02-20 |
| AU1768797A (en) | 1997-09-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| FF | Patent granted | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |