AU773678B2 - Macrolide antiinfective agents - Google Patents
Macrolide antiinfective agents Download PDFInfo
- Publication number
- AU773678B2 AU773678B2 AU42379/00A AU4237900A AU773678B2 AU 773678 B2 AU773678 B2 AU 773678B2 AU 42379/00 A AU42379/00 A AU 42379/00A AU 4237900 A AU4237900 A AU 4237900A AU 773678 B2 AU773678 B2 AU 773678B2
- Authority
- AU
- Australia
- Prior art keywords
- substituted
- compound
- unsubstituted
- added
- nil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 239000004599 antimicrobial Substances 0.000 title abstract description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 title description 13
- 229960005475 antiinfective agent Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 302
- 239000000203 mixture Substances 0.000 claims abstract description 122
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000005018 aryl alkenyl group Chemical group 0.000 claims abstract description 13
- 125000005015 aryl alkynyl group Chemical group 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 102
- -1 3-quinolyl Chemical group 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 150000002923 oximes Chemical class 0.000 abstract description 32
- 125000000304 alkynyl group Chemical group 0.000 abstract description 11
- 125000006239 protecting group Chemical group 0.000 abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 abstract description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 125000004663 dialkyl amino group Chemical group 0.000 abstract description 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 273
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 168
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
- 239000000243 solution Substances 0.000 description 152
- 238000006243 chemical reaction Methods 0.000 description 142
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 101
- 239000012267 brine Substances 0.000 description 97
- 235000019439 ethyl acetate Nutrition 0.000 description 97
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 97
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 96
- 239000000047 product Substances 0.000 description 90
- 238000002360 preparation method Methods 0.000 description 83
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- 229920006395 saturated elastomer Polymers 0.000 description 71
- 239000000741 silica gel Substances 0.000 description 67
- 229910002027 silica gel Inorganic materials 0.000 description 67
- 238000007792 addition Methods 0.000 description 60
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 238000004587 chromatography analysis Methods 0.000 description 49
- 239000012074 organic phase Substances 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 47
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 41
- 239000012043 crude product Substances 0.000 description 41
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 239000000543 intermediate Substances 0.000 description 38
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
- 230000015572 biosynthetic process Effects 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 35
- 239000000463 material Substances 0.000 description 35
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 125000001424 substituent group Chemical group 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
- 239000007787 solid Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 28
- 239000000284 extract Substances 0.000 description 27
- 238000003818 flash chromatography Methods 0.000 description 26
- 239000002904 solvent Substances 0.000 description 23
- ZGIKWINFUGEQEO-UHFFFAOYSA-N 3-bromoquinoline Chemical compound C1=CC=CC2=CC(Br)=CN=C21 ZGIKWINFUGEQEO-UHFFFAOYSA-N 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229960003276 erythromycin Drugs 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
- 235000010633 broth Nutrition 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 16
- HQZOLNNEQAKEHT-UHFFFAOYSA-N (3R,4S,5R,6S,7S,9R,11R,12S,13R,14R)-14-ethyl-4,6,12-trihydroxy-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione Natural products CCC1OC(=O)C(C)C(O)C(C)C(O)C(C)CC(C)C(=O)C(C)C(O)C1C HQZOLNNEQAKEHT-UHFFFAOYSA-N 0.000 description 15
- 239000003835 ketolide antibiotic agent Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 239000003039 volatile agent Substances 0.000 description 15
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- 239000012298 atmosphere Substances 0.000 description 14
- 238000000855 fermentation Methods 0.000 description 14
- 230000004151 fermentation Effects 0.000 description 14
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 14
- 230000008569 process Effects 0.000 description 14
- 239000006260 foam Substances 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- 229920002554 vinyl polymer Polymers 0.000 description 13
- 239000002002 slurry Substances 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 229930006677 Erythromycin A Natural products 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 108010030975 Polyketide Synthases Proteins 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 241000187432 Streptomyces coelicolor Species 0.000 description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 229930001119 polyketide Natural products 0.000 description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 150000007970 thio esters Chemical class 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 150000003881 polyketide derivatives Chemical class 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 241000187559 Saccharopolyspora erythraea Species 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 238000004949 mass spectrometry Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 6
- 239000002168 alkylating agent Substances 0.000 description 6
- 229940100198 alkylating agent Drugs 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- AJSDVNKVGFVAQU-BIIVOSGPSA-N cladinose Chemical group O=CC[C@@](C)(OC)[C@@H](O)[C@H](C)O AJSDVNKVGFVAQU-BIIVOSGPSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 239000002054 inoculum Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000013587 production medium Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 6
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- AXFZADXWLMXITO-UHFFFAOYSA-N N-acetylcysteamine Chemical compound CC(=O)NCCS AXFZADXWLMXITO-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 229910004298 SiO 2 Inorganic materials 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 235000011089 carbon dioxide Nutrition 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000000468 ketone group Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 4
- HQZOLNNEQAKEHT-IBBGRPSASA-N 6-deoxyerythronolide B Chemical class CC[C@H]1OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@@H](C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H]1C HQZOLNNEQAKEHT-IBBGRPSASA-N 0.000 description 4
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000000287 crude extract Substances 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 4
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
- HRNGDAQBEIFYGL-UHFFFAOYSA-N 3,4-dihydroxy-4-tetradeca-3,6-dienoyloxybutanoic acid Chemical compound CCCCCCCC=CCC=CCC(=O)OC(O)C(O)CC(O)=O HRNGDAQBEIFYGL-UHFFFAOYSA-N 0.000 description 3
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
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- PPKKOTLGXBHLAB-XVHSACDVSA-N nocii Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=C(O)C=C1 PPKKOTLGXBHLAB-XVHSACDVSA-N 0.000 description 1
- PFDLUBNRHMFBGI-HRVFELILSA-N oleandolide Chemical compound O=C1[C@H](C)[C@@H](O)[C@@H](C)[C@@H](C)OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@@H](C)C[C@]11OC1 PFDLUBNRHMFBGI-HRVFELILSA-N 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- WXHIJDCHNDBCNY-UHFFFAOYSA-N palladium dihydride Chemical compound [PdH2] WXHIJDCHNDBCNY-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- VKKZSJQQRIGUIE-UHFFFAOYSA-N quinolin-3-ylmethanamine Chemical compound C1=CC=CC2=CC(CN)=CN=C21 VKKZSJQQRIGUIE-UHFFFAOYSA-N 0.000 description 1
- ALQUTEKNDPODSS-UHFFFAOYSA-N quinoline-4-carbaldehyde-oxime Natural products C1=CC=C2C(C=NO)=CC=NC2=C1 ALQUTEKNDPODSS-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 102200057226 rs2241714 Human genes 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical compound C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23B—PRESERVATION OF FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES; CHEMICAL RIPENING OF FRUIT OR VEGETABLES
- A23B2/00—Preservation of foods or foodstuffs, in general
- A23B2/70—Preservation of foods or foodstuffs, in general by treatment with chemicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Food Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12972999P | 1999-04-16 | 1999-04-16 | |
| US60/129729 | 1999-04-16 | ||
| US14017599P | 1999-06-18 | 1999-06-18 | |
| US60/140175 | 1999-06-18 | ||
| US17215499P | 1999-12-17 | 1999-12-17 | |
| US17215999P | 1999-12-17 | 1999-12-17 | |
| US60/172154 | 1999-12-17 | ||
| US60/172159 | 1999-12-17 | ||
| US17380499P | 1999-12-30 | 1999-12-30 | |
| US17380599P | 1999-12-30 | 1999-12-30 | |
| US60/173804 | 1999-12-30 | ||
| US60/173805 | 1999-12-30 | ||
| PCT/US2000/009914 WO2000063224A2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| US09/550,045 US6395710B1 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| US09/550045 | 2000-04-14 |
Publications (2)
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|---|---|
| AU4237900A AU4237900A (en) | 2000-11-02 |
| AU773678B2 true AU773678B2 (en) | 2004-06-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU42379/00A Ceased AU773678B2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
| AU44578/00A Ceased AU775637B2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU44578/00A Ceased AU775637B2 (en) | 1999-04-16 | 2000-04-14 | Macrolide antiinfective agents |
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|---|---|
| US (3) | US6395710B1 (enExample) |
| EP (1) | EP1171446B1 (enExample) |
| JP (1) | JP2003523938A (enExample) |
| KR (2) | KR20020007374A (enExample) |
| CN (1) | CN1241931C (enExample) |
| AT (1) | ATE340183T1 (enExample) |
| AU (2) | AU773678B2 (enExample) |
| BR (1) | BR0010680A (enExample) |
| CA (1) | CA2369816A1 (enExample) |
| DE (1) | DE60030847T2 (enExample) |
| ES (1) | ES2272273T3 (enExample) |
| ID (1) | ID30547A (enExample) |
| IL (2) | IL145777A0 (enExample) |
| MX (1) | MXPA01010524A (enExample) |
| NZ (1) | NZ515027A (enExample) |
| WO (2) | WO2000063225A2 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AP1060A (en) * | 1998-01-02 | 2002-04-23 | Pfizer Prod Inc | Novel erythromycin derivatives. |
| HRP20010559A2 (en) | 1999-01-27 | 2002-08-31 | Pfizer Prod Inc | Ketolide antibiotics |
| US6451768B1 (en) | 1999-04-16 | 2002-09-17 | Kosan Biosciences, Inc. | Macrolide antiinfective agents |
| US6590083B1 (en) * | 1999-04-16 | 2003-07-08 | Ortho-Mcneil Pharmaceutical, Inc. | Ketolide antibacterials |
| EP1167376B1 (en) | 2000-06-30 | 2004-07-14 | Pfizer Products Inc. | Macrolide antibiotics |
| US6472372B1 (en) | 2000-12-06 | 2002-10-29 | Ortho-Mcneil Pharmaceuticals, Inc. | 6-O-Carbamoyl ketolide antibacterials |
| JP4554158B2 (ja) * | 2001-03-21 | 2010-09-29 | ダウ・アグロサイエンス・エル・エル・シー | 有害生物防除性スピノシン誘導体 |
| JP2005503416A (ja) | 2001-09-17 | 2005-02-03 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | ６−ｏ−カルバメート−１１，１２−ラクト−ケトライド抗菌剤 |
| HUP0500018A3 (en) | 2001-12-05 | 2009-09-28 | Ortho Mcneil Pharm Inc | 6-o-acyl ketolide derivatives of erythromycine processes for preparing them and using them as antibacterials |
| US8063021B2 (en) * | 2002-01-17 | 2011-11-22 | Kosan Biosciences Incorporated | Ketolide anti-infective compounds |
| AU2003218110A1 (en) | 2002-03-12 | 2003-09-29 | Bristol-Myers Squibb Company | C3-cyano epothilone derivatives |
| US20040014691A1 (en) * | 2002-04-25 | 2004-01-22 | Searle Xenia Beebe | 9-Oxime macrolide antibacterials |
| US20040009932A1 (en) * | 2002-04-26 | 2004-01-15 | Kathleen Phelan | Antibacterial compounds with activity against penicillin-resistant streptococcus pneumoniae |
| AU2003234650A1 (en) | 2002-05-31 | 2003-12-19 | Janssen Pharmaceutica N.V. | 3-descladinosyl-6-o-carbamoyl and 6-o-carbonoyl macrolide antibacterial agents |
| WO2004003169A2 (en) | 2002-06-28 | 2004-01-08 | Kosan Biosciences, Inc. | Recombinant genes for polyketide modifying enzymes |
| ATE417856T1 (de) * | 2002-08-29 | 2009-01-15 | Pfizer | Motilidverbindungen |
| CA2529817C (en) * | 2003-03-10 | 2013-02-12 | Optimer Pharmaceuticals, Inc. | Novel antibacterial agents |
| US7407941B2 (en) * | 2003-08-26 | 2008-08-05 | Pfizer, Inc. | N-desmethyl-N-substituted-11-deoxyerythromycin compounds |
| US20050113319A1 (en) * | 2003-08-26 | 2005-05-26 | Christopher Carreras | 11-Deoxy-6,9-ether erythromycin compounds |
| US6953782B2 (en) * | 2003-12-24 | 2005-10-11 | Enanta Pharmaceuticals, Inc. | 11-C-substituted erythromycin derivatives |
| CA2591746A1 (en) * | 2004-12-21 | 2006-06-29 | Pfizer Products Inc. | Macrolides |
| US7595300B2 (en) | 2005-12-13 | 2009-09-29 | Kosan Biosciences Incorporated | 7-quinolyl ketolide antibacterial agents |
| EP2214484A4 (en) * | 2007-10-25 | 2013-01-02 | Cempra Pharmaceuticals Inc | PROCESS FOR PREPARING ANTIBACTERIAL MAKROLIDE AGENTS |
| KR101589960B1 (ko) * | 2008-02-08 | 2016-01-29 | 바실리어 파마슈티카 아게 | Ｐｄｅ 억제를 통해 중재되는 질환의 치료를 위한 마크로라이드 |
| WO2010048601A1 (en) | 2008-10-24 | 2010-04-29 | Cempra Pharmaceuticals, Inc. | Biodefenses using triazole-containing macrolides |
| US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
| CN102724874B (zh) | 2009-09-10 | 2018-06-01 | 森普拉制药公司 | 治疗疟疾、结核病和mac疾病的方法 |
| US8975386B2 (en) | 2010-03-22 | 2015-03-10 | Cempra Pharmaceuticals, Inc. | Crystalline forms of a macrolide, and uses therefor |
| EP2571506B1 (en) | 2010-05-20 | 2017-05-10 | Cempra Pharmaceuticals, Inc. | Processes for preparing macrolides and ketolides and intermediates therefor |
| US8796474B1 (en) | 2010-08-23 | 2014-08-05 | Rutgers, The State University Of New Jersey | Macrolide compounds and methods and intermediates useful for their preparation |
| KR20180110181A (ko) | 2010-09-10 | 2018-10-08 | 셈프라 파마슈티컬스, 인크. | 질환을 치료하기 위한 수소결합 형성 플루오로 케토라이드 |
| EP2681222B1 (en) * | 2011-03-01 | 2018-02-28 | Wockhardt Limited | Process for preparation of ketolide intermediates |
| CN104470527B (zh) | 2012-03-27 | 2019-05-28 | 森普拉制药公司 | 用于施用大环内酯抗生素的肠胃外制剂 |
| CN102718816B (zh) * | 2012-07-11 | 2014-11-05 | 山东大学 | 4''-O-(反式-β-芳基烯丙酰胺)氨基甲酰基阿奇霉素衍生物 |
| CN105163785A (zh) | 2013-03-14 | 2015-12-16 | 森普拉制药公司 | 用于治疗呼吸道疾病的方法及其制剂 |
| WO2014145210A1 (en) | 2013-03-15 | 2014-09-18 | Cempra Pharmaceuticals, Inc. | Convergent processes for preparing macrolide antibacterial agents |
| US20230174567A1 (en) * | 2020-05-22 | 2023-06-08 | Merck Sharp & Dohme Llc | Synthesis of fluorinated nucleotides |
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| FR2754821A1 (fr) * | 1996-10-23 | 1998-04-24 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
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2000
- 2000-04-14 CN CNB008090718A patent/CN1241931C/zh not_active Expired - Fee Related
- 2000-04-14 ES ES00922149T patent/ES2272273T3/es not_active Expired - Lifetime
- 2000-04-14 ID IDW00200102465A patent/ID30547A/id unknown
- 2000-04-14 AT AT00922149T patent/ATE340183T1/de not_active IP Right Cessation
- 2000-04-14 JP JP2000612314A patent/JP2003523938A/ja active Pending
- 2000-04-14 IL IL14577700A patent/IL145777A0/xx active IP Right Grant
- 2000-04-14 DE DE60030847T patent/DE60030847T2/de not_active Expired - Fee Related
- 2000-04-14 BR BR0010680-1A patent/BR0010680A/pt not_active IP Right Cessation
- 2000-04-14 KR KR1020017013225A patent/KR20020007374A/ko not_active Withdrawn
- 2000-04-14 WO PCT/US2000/009915 patent/WO2000063225A2/en not_active Ceased
- 2000-04-14 KR KR1020017013150A patent/KR100710605B1/ko not_active Expired - Fee Related
- 2000-04-14 MX MXPA01010524A patent/MXPA01010524A/es active IP Right Grant
- 2000-04-14 EP EP00922149A patent/EP1171446B1/en not_active Expired - Lifetime
- 2000-04-14 NZ NZ515027A patent/NZ515027A/xx unknown
- 2000-04-14 CA CA002369816A patent/CA2369816A1/en not_active Abandoned
- 2000-04-14 US US09/550,045 patent/US6395710B1/en not_active Expired - Lifetime
- 2000-04-14 AU AU42379/00A patent/AU773678B2/en not_active Ceased
- 2000-04-14 WO PCT/US2000/009914 patent/WO2000063224A2/en not_active Ceased
- 2000-04-14 AU AU44578/00A patent/AU775637B2/en not_active Ceased
-
2001
- 2001-10-04 IL IL145777A patent/IL145777A/en unknown
-
2002
- 2002-02-13 US US10/075,466 patent/US6593302B2/en not_active Ceased
-
2005
- 2005-07-13 US US11/182,038 patent/USRE39836E1/en not_active Expired - Lifetime
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| WO1997042206A1 (en) * | 1996-05-07 | 1997-11-13 | Abbott Laboratories | 6-o-substituted erythromycin compounds and method for making same |
| FR2754821A1 (fr) * | 1996-10-23 | 1998-04-24 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
Also Published As
| Publication number | Publication date |
|---|---|
| KR100710605B1 (ko) | 2007-04-24 |
| WO2000063224A3 (en) | 2001-01-18 |
| ES2272273T3 (es) | 2007-05-01 |
| US6395710B1 (en) | 2002-05-28 |
| EP1171446A2 (en) | 2002-01-16 |
| WO2000063225A3 (en) | 2001-01-18 |
| BR0010680A (pt) | 2002-02-19 |
| IL145777A0 (en) | 2002-07-25 |
| JP2003523938A (ja) | 2003-08-12 |
| AU4457800A (en) | 2000-11-02 |
| ID30547A (id) | 2001-12-20 |
| US20020119938A1 (en) | 2002-08-29 |
| MXPA01010524A (es) | 2002-03-14 |
| IL145777A (en) | 2007-02-11 |
| AU4237900A (en) | 2000-11-02 |
| ATE340183T1 (de) | 2006-10-15 |
| CN1384838A (zh) | 2002-12-11 |
| US6593302B2 (en) | 2003-07-15 |
| DE60030847T2 (de) | 2007-04-19 |
| KR20020007374A (ko) | 2002-01-26 |
| NZ515027A (en) | 2004-01-30 |
| AU775637B2 (en) | 2004-08-12 |
| WO2000063225A2 (en) | 2000-10-26 |
| KR20020007372A (ko) | 2002-01-26 |
| WO2000063224A2 (en) | 2000-10-26 |
| CN1241931C (zh) | 2006-02-15 |
| DE60030847D1 (de) | 2006-11-02 |
| USRE39836E1 (en) | 2007-09-11 |
| EP1171446B1 (en) | 2006-09-20 |
| CA2369816A1 (en) | 2000-10-26 |
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| FGA | Letters patent sealed or granted (standard patent) |