CA2587413A1 - Macrolones - amino substituted quinolones - Google Patents
Macrolones - amino substituted quinolones Download PDFInfo
- Publication number
- CA2587413A1 CA2587413A1 CA002587413A CA2587413A CA2587413A1 CA 2587413 A1 CA2587413 A1 CA 2587413A1 CA 002587413 A CA002587413 A CA 002587413A CA 2587413 A CA2587413 A CA 2587413A CA 2587413 A1 CA2587413 A1 CA 2587413A1
- Authority
- CA
- Canada
- Prior art keywords
- oxo
- dihydro
- dimethylamino
- carboxy
- erythromycin
- 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.)
- Abandoned
Links
- 229920004011 Macrolon® Polymers 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 398
- 238000000034 method Methods 0.000 claims abstract description 63
- 238000002360 preparation method Methods 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 19
- 230000008569 process Effects 0.000 claims abstract description 16
- 229960003276 erythromycin Drugs 0.000 claims description 146
- 229960002626 clarithromycin Drugs 0.000 claims description 107
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- -1 2-{[3-Carboxy-1-(dimethylamino)-4-oxo-1,4-dihydro-1,7-naphthyridin-6-yl]thio}ethyl Chemical group 0.000 claims description 80
- 238000006243 chemical reaction Methods 0.000 claims description 77
- 239000001257 hydrogen Substances 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 46
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 41
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 125000006308 propyl amino group Chemical group 0.000 claims description 29
- 125000004122 cyclic group Chemical group 0.000 claims description 27
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 23
- 150000002431 hydrogen Chemical group 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 241000282414 Homo sapiens Species 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 229960004099 azithromycin Drugs 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 229930006677 Erythromycin A Natural products 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 150000002923 oximes Chemical class 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 230000000813 microbial effect Effects 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- 101100294104 Caenorhabditis elegans nhr-34 gene Proteins 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Chemical group 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 230000009885 systemic effect Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- TYQXKHPOXXXCTP-CSLYCKPJSA-N erythromycin A 2'-propanoate 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)OC(=O)CC)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 TYQXKHPOXXXCTP-CSLYCKPJSA-N 0.000 claims description 2
- 229950001028 erythromycin propionate Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 182
- 230000000845 anti-microbial effect Effects 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 609
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 405
- 239000000543 intermediate Substances 0.000 description 231
- 239000000243 solution Substances 0.000 description 197
- 230000002829 reductive effect Effects 0.000 description 179
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 164
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 155
- 239000007787 solid Substances 0.000 description 154
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 141
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 135
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
- 229910001868 water Inorganic materials 0.000 description 132
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 126
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 120
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 115
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 114
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 99
- 239000000741 silica gel Substances 0.000 description 87
- 229910002027 silica gel Inorganic materials 0.000 description 87
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- 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 71
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 62
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 62
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 50
- 238000004587 chromatography analysis Methods 0.000 description 48
- 229910021529 ammonia Inorganic materials 0.000 description 44
- 238000003756 stirring Methods 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- 239000006260 foam Substances 0.000 description 40
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- 150000003839 salts Chemical class 0.000 description 35
- 229910052786 argon Inorganic materials 0.000 description 34
- 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 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- 235000019253 formic acid Nutrition 0.000 description 31
- 229910052938 sodium sulfate Inorganic materials 0.000 description 31
- 235000011152 sodium sulphate Nutrition 0.000 description 31
- 239000003480 eluent Substances 0.000 description 30
- 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 29
- 239000007832 Na2SO4 Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 239000000725 suspension Substances 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 25
- 235000017557 sodium bicarbonate Nutrition 0.000 description 25
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
- 239000012267 brine Substances 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 22
- 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 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 235000011181 potassium carbonates Nutrition 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 239000012071 phase Substances 0.000 description 15
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- 239000003120 macrolide antibiotic agent Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 12
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 12
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- 238000002953 preparative HPLC Methods 0.000 description 12
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 239000002808 molecular sieve Substances 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 11
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 239000012453 solvate Substances 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 8
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- 150000003254 radicals Chemical class 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
- 239000008259 solid foam Substances 0.000 description 8
- 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 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
- 150000001735 carboxylic acids Chemical class 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- MVUMJYQUKKUOHO-AATRIKPKSA-N ethyl (e)-3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)\C=C\N(C)C MVUMJYQUKKUOHO-AATRIKPKSA-N 0.000 description 7
- 239000001632 sodium acetate Substances 0.000 description 7
- 235000017281 sodium acetate Nutrition 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 6
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- CBJHDUMQMKOPEQ-UHFFFAOYSA-N ethyl 6-[3-(cyclopropylamino)propyl]-1-(dimethylamino)-4-oxoquinoline-3-carboxylate Chemical compound C1=C2C(=O)C(C(=O)OCC)=CN(N(C)C)C2=CC=C1CCCNC1CC1 CBJHDUMQMKOPEQ-UHFFFAOYSA-N 0.000 description 1
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- WRZXRRWKVPDKLN-UHFFFAOYSA-N ethyl 8-fluoro-6-iodo-1-(methylamino)-4-oxoquinoline-3-carboxylate Chemical compound C1=C(I)C=C2C(=O)C(C(=O)OCC)=CN(NC)C2=C1F WRZXRRWKVPDKLN-UHFFFAOYSA-N 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 150000003141 primary amines Chemical class 0.000 description 1
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- 125000006413 ring segment Chemical group 0.000 description 1
- XSCSSBJLKZEACJ-UHFFFAOYSA-N s-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethyl] ethanethioate Chemical compound CC(=O)SCCOCCNC(=O)OC(C)(C)C XSCSSBJLKZEACJ-UHFFFAOYSA-N 0.000 description 1
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- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- POPGBGYTSRQYLK-UHFFFAOYSA-N tert-butyl n-(2-prop-2-ynoxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCOCC#C POPGBGYTSRQYLK-UHFFFAOYSA-N 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- KSFVNEXYCULLEJ-UHFFFAOYSA-N tert-butyl n-[2-(2-hydroxyethoxy)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCO KSFVNEXYCULLEJ-UHFFFAOYSA-N 0.000 description 1
- QVMLIHFGUIRVKU-UHFFFAOYSA-N tert-butyl n-methyl-n-prop-2-ynylcarbamate Chemical compound C#CCN(C)C(=O)OC(C)(C)C QVMLIHFGUIRVKU-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0424959A GB0424959D0 (en) | 2004-11-11 | 2004-11-11 | Novel compounds |
| GB0424959.5 | 2004-11-11 | ||
| PCT/EP2005/012038 WO2006050942A1 (en) | 2004-11-11 | 2005-11-09 | Macrolones - amino substituted quinolones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2587413A1 true CA2587413A1 (en) | 2006-05-18 |
Family
ID=33523587
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002587413A Abandoned CA2587413A1 (en) | 2004-11-11 | 2005-11-09 | Macrolones - amino substituted quinolones |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US7718621B2 (enExample) |
| EP (1) | EP1824870A1 (enExample) |
| JP (1) | JP2008519788A (enExample) |
| KR (1) | KR20070085919A (enExample) |
| CN (1) | CN101098881A (enExample) |
| AR (1) | AR053311A1 (enExample) |
| AU (1) | AU2005303961A1 (enExample) |
| BR (1) | BRPI0517792A (enExample) |
| CA (1) | CA2587413A1 (enExample) |
| GB (1) | GB0424959D0 (enExample) |
| IL (1) | IL182978A0 (enExample) |
| MA (1) | MA29213B1 (enExample) |
| MX (1) | MX2007005776A (enExample) |
| NO (1) | NO20072939L (enExample) |
| PE (1) | PE20061137A1 (enExample) |
| RU (1) | RU2007121581A (enExample) |
| TW (1) | TW200630378A (enExample) |
| WO (1) | WO2006050942A1 (enExample) |
| ZA (1) | ZA200703603B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7601695B2 (en) | 2003-03-10 | 2009-10-13 | Optimer Pharmaceuticals, Inc. | Antibacterial agents |
| WO2007054295A1 (en) * | 2005-11-09 | 2007-05-18 | Glaxo Group Limited | New 4*-substituted erythromycin derivative |
| EP1879904A1 (en) * | 2005-05-10 | 2008-01-23 | GlaxoSmithKline istrazivacki centar Zagreb d.o.o. | 4" amino linked macrolides useful for the treatment of microbial infections |
| WO2007054296A1 (en) * | 2005-11-09 | 2007-05-18 | Glaxo Group Limited | Macrolones |
| NZ583878A (en) | 2007-09-14 | 2012-10-26 | Vertex Pharma | Modulators of ABC transporter and cystic fibrosis transmembrane conductance regulator (CFTR) |
| AU2008316830B2 (en) | 2007-10-25 | 2016-03-17 | Cempra Pharmaceuticals, Inc. | Process for the preparation of macrolide antibacterial agents |
| TW200946109A (en) * | 2008-05-09 | 2009-11-16 | Enanta Pharm Inc | Anti-bacterial activity of 9-hydroxy derivatives 6, 11-bicyclolides |
| CN107854477A (zh) | 2008-10-24 | 2018-03-30 | 森普拉制药公司 | 使用含三唑的大环内酯治疗抗性疾病的方法 |
| US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
| US9480679B2 (en) | 2009-09-10 | 2016-11-01 | Cempra Pharmaceuticals, Inc. | Methods for treating malaria, tuberculosis and MAC diseases |
| BR112012029586A2 (pt) * | 2010-05-20 | 2016-08-02 | Cempra Pharmaceuticals Inc | processos para preparar macrolídeos e cetolídeos e intermediários dos mesmos |
| KR20130120458A (ko) | 2010-09-10 | 2013-11-04 | 셈프라 파마슈티컬스, 인크. | 질환을 치료하기 위한 수소결합 형성 플루오로 케토라이드 |
| WO2013148891A1 (en) | 2012-03-27 | 2013-10-03 | Cempra Pharmaceuticals, Inc. | Parenteral formulations for administering macrolide antibiotics |
| WO2014152326A1 (en) | 2013-03-14 | 2014-09-25 | Cempra Pharmaceuticals, Inc. | Methods for treating respiratory diseases and formulations therefor |
| AU2014233240B2 (en) | 2013-03-15 | 2018-08-09 | Cempra Pharmaceuticals, Inc. | Convergent processes for preparing macrolide antibacterial agents |
| CN106589023A (zh) * | 2016-11-22 | 2017-04-26 | 宜昌东阳光药业股份有限公司 | 一种罗红霉素杂质及其合成方法 |
| CN110475777B (zh) | 2017-03-30 | 2022-04-15 | 豪夫迈·罗氏有限公司 | 用于治疗和预防细菌感染的新吡啶并[2,3-b]吲哚化合物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2808070A1 (de) * | 1978-02-24 | 1979-08-30 | Bayer Ag | Verfahren zur herstellung von 4-pyridon-3-carbonsaeuren und/oder deren derivaten |
| GB0127349D0 (en) | 2001-11-14 | 2002-01-02 | Glaxo Group Ltd | Macrolides |
| GB0225384D0 (en) | 2002-10-31 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
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2004
- 2004-11-11 GB GB0424959A patent/GB0424959D0/en not_active Ceased
-
2005
- 2005-11-09 AU AU2005303961A patent/AU2005303961A1/en not_active Abandoned
- 2005-11-09 CA CA002587413A patent/CA2587413A1/en not_active Abandoned
- 2005-11-09 JP JP2007540573A patent/JP2008519788A/ja not_active Withdrawn
- 2005-11-09 RU RU2007121581/04A patent/RU2007121581A/ru not_active Application Discontinuation
- 2005-11-09 BR BRPI0517792-8A patent/BRPI0517792A/pt not_active IP Right Cessation
- 2005-11-09 MX MX2007005776A patent/MX2007005776A/es unknown
- 2005-11-09 WO PCT/EP2005/012038 patent/WO2006050942A1/en not_active Ceased
- 2005-11-09 CN CNA2005800463765A patent/CN101098881A/zh active Pending
- 2005-11-09 US US11/719,004 patent/US7718621B2/en not_active Expired - Fee Related
- 2005-11-09 KR KR1020077012942A patent/KR20070085919A/ko not_active Withdrawn
- 2005-11-09 EP EP05801894A patent/EP1824870A1/en not_active Withdrawn
- 2005-11-09 TW TW094139277A patent/TW200630378A/zh unknown
- 2005-11-09 AR ARP050104704A patent/AR053311A1/es not_active Application Discontinuation
- 2005-11-09 PE PE2005001311A patent/PE20061137A1/es not_active Application Discontinuation
-
2006
- 2006-11-07 US US12/093,145 patent/US20080269146A1/en not_active Abandoned
-
2007
- 2007-05-03 IL IL182978A patent/IL182978A0/en unknown
- 2007-05-04 ZA ZA200703603A patent/ZA200703603B/en unknown
- 2007-05-22 MA MA29930A patent/MA29213B1/fr unknown
- 2007-06-08 NO NO20072939A patent/NO20072939L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| US20080090773A1 (en) | 2008-04-17 |
| MX2007005776A (es) | 2007-07-16 |
| PE20061137A1 (es) | 2006-12-13 |
| AR053311A1 (es) | 2007-05-02 |
| TW200630378A (en) | 2006-09-01 |
| EP1824870A1 (en) | 2007-08-29 |
| US20080269146A1 (en) | 2008-10-30 |
| NO20072939L (no) | 2007-08-08 |
| MA29213B1 (fr) | 2008-02-01 |
| KR20070085919A (ko) | 2007-08-27 |
| RU2007121581A (ru) | 2008-12-20 |
| US7718621B2 (en) | 2010-05-18 |
| CN101098881A (zh) | 2008-01-02 |
| GB0424959D0 (en) | 2004-12-15 |
| AU2005303961A1 (en) | 2006-05-18 |
| JP2008519788A (ja) | 2008-06-12 |
| IL182978A0 (en) | 2007-08-19 |
| WO2006050942A1 (en) | 2006-05-18 |
| ZA200703603B (en) | 2008-07-30 |
| BRPI0517792A (pt) | 2008-10-21 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |