FI69467C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara pyrido- och isokinolin(1',2':1,2)imidazo(5,4-c)rifamycin soch sv-derivat - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara pyrido- och isokinolin(1',2':1,2)imidazo(5,4-c)rifamycin soch sv-derivat Download PDFInfo
- Publication number
- FI69467C FI69467C FI811565A FI811565A FI69467C FI 69467 C FI69467 C FI 69467C FI 811565 A FI811565 A FI 811565A FI 811565 A FI811565 A FI 811565A FI 69467 C FI69467 C FI 69467C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- compound
- imidazo
- hydrogen
- acetyl
- Prior art date
Links
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical compound OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 7
- 229960003292 rifamycin Drugs 0.000 title description 2
- 230000001225 therapeutic effect Effects 0.000 title 2
- 229930189077 Rifamycin Natural products 0.000 title 1
- 239000002253 acid Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 9
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 5
- BTVYFIMKUHNOBZ-ODRIEIDWSA-N Rifamycin S Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-ODRIEIDWSA-N 0.000 claims description 5
- BTVYFIMKUHNOBZ-ZDHWWVNNSA-N Rifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C BTVYFIMKUHNOBZ-ZDHWWVNNSA-N 0.000 claims description 5
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 4
- 241000251730 Chondrichthyes Species 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 239000003086 colorant Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- JEHCHYAKAXDFKV-UHFFFAOYSA-J lead tetraacetate Chemical compound CC(=O)O[Pb](OC(C)=O)(OC(C)=O)OC(C)=O JEHCHYAKAXDFKV-UHFFFAOYSA-J 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 235000013379 molasses Nutrition 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000002211 ultraviolet spectrum Methods 0.000 description 15
- 238000002329 infrared spectrum Methods 0.000 description 14
- 238000010521 absorption reaction Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 11
- 230000001580 bacterial effect Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000010828 elution Methods 0.000 description 5
- 210000003608 fece Anatomy 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- -1 sec Chemical group 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- WOAHJDHKFWSLKE-UHFFFAOYSA-N 1,2-benzoquinone Chemical compound O=C1C=CC=CC1=O WOAHJDHKFWSLKE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NMCBWICNRJLKKM-UHFFFAOYSA-N 3-(benzyloxy)pyridin-2-amine Chemical compound NC1=NC=CC=C1OCC1=CC=CC=C1 NMCBWICNRJLKKM-UHFFFAOYSA-N 0.000 description 1
- RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 1
- ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
- CMBSSVKZOPZBKW-UHFFFAOYSA-N 5-methylpyridin-2-amine Chemical compound CC1=CC=C(N)N=C1 CMBSSVKZOPZBKW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 229950011175 aminopicoline Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- XTPGUQSTSWYULT-TXXBDZDDSA-N rifamycin p Chemical class OC1=C(C(O)=C2C)C3=C4N=CSC4=C1NC(=O)\C(C)=C\C=C\C(C)C(O)C(C)C(O)C(C)C(OC(C)=O)C(C)C(OC)\C=C/OC1(C)OC2=C3C1=O XTPGUQSTSWYULT-TXXBDZDDSA-N 0.000 description 1
- 229940109171 rifamycin sv Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 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
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT03429/80A IT1154655B (it) | 1980-05-22 | 1980-05-22 | Derivati imidazo-rifamicinici metodi per la loro preparazione e loro uso come sostanza ad azione antibatterica |
| IT342980 | 1980-05-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI811565L FI811565L (fi) | 1981-11-23 |
| FI69467B FI69467B (fi) | 1985-10-31 |
| FI69467C true FI69467C (fi) | 1986-02-10 |
Family
ID=11107198
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI811565A FI69467C (fi) | 1980-05-22 | 1981-05-21 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara pyrido- och isokinolin(1',2':1,2)imidazo(5,4-c)rifamycin soch sv-derivat |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4341785A (OSRAM) |
| JP (1) | JPS5711987A (OSRAM) |
| AR (1) | AR226212A1 (OSRAM) |
| AT (1) | AT373599B (OSRAM) |
| AU (1) | AU537093B2 (OSRAM) |
| BE (1) | BE888895A (OSRAM) |
| CA (1) | CA1142518A (OSRAM) |
| CH (1) | CH648037A5 (OSRAM) |
| DE (1) | DE3120460A1 (OSRAM) |
| DK (1) | DK157876C (OSRAM) |
| EG (1) | EG14891A (OSRAM) |
| ES (1) | ES8203388A1 (OSRAM) |
| FI (1) | FI69467C (OSRAM) |
| FR (1) | FR2482967A1 (OSRAM) |
| GB (1) | GB2079270B (OSRAM) |
| GR (1) | GR75640B (OSRAM) |
| IE (1) | IE51204B1 (OSRAM) |
| IT (1) | IT1154655B (OSRAM) |
| LU (1) | LU83376A1 (OSRAM) |
| NL (1) | NL187022C (OSRAM) |
| NO (1) | NO155622C (OSRAM) |
| PH (2) | PH17207A (OSRAM) |
| PT (1) | PT73064B (OSRAM) |
| SE (1) | SE453089B (OSRAM) |
| ZA (1) | ZA813430B (OSRAM) |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1199374B (it) | 1984-05-15 | 1988-12-30 | Alfa Farmaceutici Spa | Processo per la preparazione di pirido-imidazo-rifamicine |
| IT1264494B1 (it) * | 1993-03-23 | 1996-09-24 | Alfa Wassermann Spa | Uso di rifaximin e di formulazioni che la contengono nel trattamento delle dispepsie gastriche originate da helicobacter |
| US6861053B1 (en) * | 1999-08-11 | 2005-03-01 | Cedars-Sinai Medical Center | Methods of diagnosing or treating irritable bowel syndrome and other disorders caused by small intestinal bacterial overgrowth |
| US7048906B2 (en) | 1995-05-17 | 2006-05-23 | Cedars-Sinai Medical Center | Methods of diagnosing and treating small intestinal bacterial overgrowth (SIBO) and SIBO-related conditions |
| US5981522A (en) * | 1995-09-01 | 1999-11-09 | Kaneka Corporation | Treatment of disease caused by infection of Helicobacter |
| ES2237809T3 (es) * | 1997-02-28 | 2005-08-01 | Kaneka Corporation | Medicina curativa para la enfermedad causada por infeccion de helicobacter. |
| EP1453837A4 (en) * | 2001-11-21 | 2007-11-07 | Activbiotics Inc | TARGETED THERAPEUTIC AGENTS AND USES THEREOF |
| AU2002364162A1 (en) * | 2001-12-13 | 2003-06-30 | Activbiotics, Inc. | Sulfhydryl rifamycins and uses thereof |
| EP1560566B1 (en) * | 2002-11-05 | 2012-04-11 | Fadim S.r.l. | Controlled and continued delivery of rifaximin |
| US7820652B2 (en) * | 2003-09-24 | 2010-10-26 | Activbiotics Pharma, Llc | Regimen for the administration of rifamycin-class antibiotics |
| ITMI20032144A1 (it) * | 2003-11-07 | 2005-05-08 | Alfa Wassermann Spa | Forme polimorfe di rifaximina, processi per ottenerle e |
| US7906542B2 (en) * | 2004-11-04 | 2011-03-15 | Alfa Wassermann, S.P.A. | Pharmaceutical compositions comprising polymorphic forms α, β, and γ of rifaximin |
| US7902206B2 (en) * | 2003-11-07 | 2011-03-08 | Alfa Wassermann, S.P.A. | Polymorphic forms α, β and γ of rifaximin |
| US20080262024A1 (en) * | 2003-11-07 | 2008-10-23 | Giuseppe Claudio Viscomi | Rifaximin compositions and method of use |
| US7923553B2 (en) * | 2003-11-07 | 2011-04-12 | Alfa Wassermann, S.P.A. | Processes for the production of polymorphic forms of rifaximin |
| US7256187B2 (en) * | 2004-03-10 | 2007-08-14 | Cumbre Pharmaceuticals Inc. | Rifamycin C-11 oxime derivatives effective against drug-resistant microbes |
| US7265107B2 (en) * | 2004-03-10 | 2007-09-04 | Cumbre Pharmaceuticals Inc. | Rifamycin C-11 oxime cyclo derivatives effective against drug-resistant microbes |
| US7202246B2 (en) * | 2004-06-09 | 2007-04-10 | Cumbre Pharmaceuticals Inc. | Spiro-rifamycin derivatives targeting RNA polymerase |
| US20060210483A1 (en) * | 2005-03-02 | 2006-09-21 | Kodsi Robert E | Non-systemic antibiotic formulations and related method of use and treatment of upper respiratory infections |
| US20060210492A1 (en) * | 2005-03-02 | 2006-09-21 | Kodsi Robert E | Use of rifaximin for treatment and prevention of periodontal conditions |
| US8003118B2 (en) * | 2005-03-02 | 2011-08-23 | Kodsi Robert E | Use of rifaximin for the prevention of aspiration pneumonia and/or sepsis |
| DK1698630T3 (da) | 2005-03-03 | 2014-12-08 | Alfa Wassermann Spa | Nye polymorfe former af rifaximin, fremgangsmåde for deres fremstilling og anvendelse deraf i de medicinske præparater |
| ITBO20050123A1 (it) | 2005-03-07 | 2005-06-06 | Alfa Wassermann Spa | Formulazioni farmaceutiche gastroresistenti contenenti rifaximina |
| BRPI0614758A2 (pt) | 2005-08-11 | 2011-04-12 | Targanta Therapeutics Inc | rifamicinas fosfonadas e usos destas para a prevenção e tratamento de infecções na articulação e osso |
| US8987292B2 (en) | 2006-03-09 | 2015-03-24 | Salix Pharmaceuticals, Ltd. | Rifaximin anti-rectal dysfunction preparation |
| PT2054066E (pt) | 2006-08-02 | 2015-07-16 | Salix Pharmaceuticals Inc | Métodos para tratamento de enterite por radiação |
| ITMI20061692A1 (it) | 2006-09-05 | 2008-03-06 | Alfa Wassermann Spa | Uso di polioli per ottenere forme polimorfe stabili di rifaximina |
| US8633234B2 (en) * | 2006-09-22 | 2014-01-21 | Cipla Limited | Rifaximin |
| US20080159987A1 (en) * | 2007-01-03 | 2008-07-03 | Leonard Weinstock | Use of Rifaximin for the Treatment of Restless Legs Syndrome |
| US20080161337A1 (en) * | 2007-01-03 | 2008-07-03 | Leonard Weinstock | Use of Rifaximin for the Treatment of Chronic Prostatitis |
| ITMI20071241A1 (it) * | 2007-06-20 | 2008-12-21 | Solmag S P A | Processo per la preparazione di rifaximina amorfa e rifaximina amorfa cosi' ottenuta |
| ES2389358T5 (es) | 2007-07-06 | 2016-01-19 | Lupin Ltd. | Composiciones farmacéuticas de rifaximina |
| US8383151B2 (en) | 2007-07-06 | 2013-02-26 | Lupin Limited | Pharmaceutical compositions of rifaximin |
| US7709634B2 (en) * | 2007-09-20 | 2010-05-04 | Apotex Pharmachem Inc. | Amorphous form of rifaximin and processes for its preparation |
| SG10201607926VA (en) | 2008-02-25 | 2016-11-29 | Salix Pharmaceuticals Ltd | Forms of rifaximin and uses thereof |
| US8486956B2 (en) * | 2008-02-25 | 2013-07-16 | Salix Pharmaceuticals, Ltd | Forms of rifaximin and uses thereof |
| KR20100122937A (ko) | 2008-02-26 | 2010-11-23 | 샐릭스 파마슈티컬스 리미티드 | 장 질환의 치료 방법 |
| US11779571B2 (en) | 2008-02-26 | 2023-10-10 | Salix Pharmaceuticals, Inc. | Methods for treating irritable bowel syndrome (IBS) |
| AU2009244190B2 (en) | 2008-05-07 | 2016-02-25 | Salix Pharmaceuticals, Ltd. | Methods of treating bowel disease by administering a bowel cleanser and an antibiotic |
| EP2324041A4 (en) | 2008-08-13 | 2012-06-13 | Targanta Therapeutics Corp | PHOSPHONIZED RIFAMYCINS AND ITS APPLICATION FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS |
| AU2009297562B2 (en) | 2008-09-26 | 2015-04-23 | Alfasigma S.P.A. | Agent for preventing and/or treating functional gastrointestinal disorder |
| ES2770308T3 (es) | 2008-10-02 | 2020-07-01 | Salix Pharmaceuticals Ltd | Procedimientos de tratamiento de encefalopatía hepática |
| US12285414B2 (en) | 2008-10-02 | 2025-04-29 | Salix Pharmaceuticals, Inc. | Methods of treating hepatic encephalopathy |
| KR20110107806A (ko) | 2008-12-10 | 2011-10-04 | 시플라 리미티드 | 리팍시민 복합체 |
| IT1397617B1 (it) * | 2009-04-20 | 2013-01-18 | Alfa Wassermann Spa | Nuovi derivati della rifamicina |
| BRPI1010028A2 (pt) | 2009-06-02 | 2019-02-12 | Salix Pharmaceuticals, Ltd. | métodos de tratamento de encefalopatia hepática |
| EP2475392A4 (en) | 2009-09-13 | 2013-01-09 | Salix Pharmaceuticals Ltd | METHOD FOR TREATING IRRITATION SYNDROME |
| KR20190000931A (ko) | 2009-10-27 | 2019-01-03 | 루핀 리미티드 | 리팍시민의 고형 분산물 |
| KR20120117788A (ko) | 2009-11-23 | 2012-10-24 | 시플라 리미티드 | 국소용 폼 조성물 |
| US8952159B2 (en) | 2009-12-28 | 2015-02-10 | Silvio Massimo Lavagna | Method for the production of amorphous rifaximin |
| EP3650022A1 (en) | 2010-02-18 | 2020-05-13 | Salix Pharmaceuticals, Ltd. | Methods for treating rifampin resistant clostridium difficilis infections |
| IT1398550B1 (it) | 2010-03-05 | 2013-03-01 | Alfa Wassermann Spa | Formulazioni comprendenti rifaximina utili per ottenere un effetto prolungato nel tempo |
| EP2544660B1 (en) | 2010-03-10 | 2018-06-13 | Lupin Limited | Rifaximin ready-to-use suspension |
| EP3750526A1 (en) | 2010-07-12 | 2020-12-16 | Salix Pharmaceuticals, Inc. | Formulations of rifaximin and uses thereof |
| US8759513B2 (en) | 2010-09-13 | 2014-06-24 | Sequent Scientific Limited | Polymorphic form of rifaximin and process for its preparation |
| MX350448B (es) | 2011-02-11 | 2017-09-07 | Salix Pharmaceuticals Ltd | Formas de rifaximina y usos de las mismas. |
| AU2012251385A1 (en) | 2011-05-02 | 2013-11-21 | Ranbaxy Laboratories Limited | Rifaximin dimethylformamide solvate |
| ITMI20110890A1 (it) | 2011-05-19 | 2012-11-20 | A M S A Anonima Materie Sint & Affini S P A | Polimorfo di rifaximina e processo per la sua preparazione |
| ITBO20110461A1 (it) | 2011-07-29 | 2013-01-30 | Alfa Wassermann Spa | Composizioni farmaceutiche comprendenti rifaximina, processi per la loro preparazione e loro uso nel trattamento di infezioni vaginali. |
| RU2496475C2 (ru) | 2011-10-26 | 2013-10-27 | Александр Васильевич Иващенко | Фармацевтическая композиция и набор для лечения бактериальных инфекций |
| PL2773205T3 (pl) | 2011-11-02 | 2024-09-02 | Salix Pharmaceuticals, Inc. | Ryfaksymina w leczeniu ustępującej biegunki z przewagą zespołu jelita drażliwego |
| JP2015509105A (ja) | 2012-01-25 | 2015-03-26 | サリックス ファーマスーティカルズ，リミテッド | リファキシミン誘導体及びその使用 |
| ITBO20120368A1 (it) | 2012-07-06 | 2014-01-07 | Alfa Wassermann Spa | Composizioni comprendenti rifaximina e amminoacidi, cristalli di rifaximina derivanti da tali composizioni e loro uso. |
| US9849090B2 (en) | 2012-12-12 | 2017-12-26 | Sun Pharmaceutical Industries Limited | Pharmaceutical compositions of rifaximin |
| EP2971062A2 (en) | 2013-03-15 | 2016-01-20 | ALFA WASSERMANN S.p.A. | Method for diagnosing vaginal infections |
| WO2014140988A1 (en) | 2013-03-15 | 2014-09-18 | Alfa Wassermann S.P.A. | Rifaximin for use in the treating of vaginal infections. |
| ES2829285T3 (es) | 2013-04-12 | 2021-05-31 | Alfasigma Spa | Administración de AINE y composiciones, métodos y sistemas relacionados |
| US9018225B1 (en) | 2013-07-26 | 2015-04-28 | Novel Laboratories | Rifaximin crystalline forms and methods of preparation thereof |
| EP2927235B1 (en) | 2014-03-31 | 2017-02-08 | Euticals S.P.A. | Polymorphic mixture of rifaximin and its use for the preparation of solid formulations |
| EP3134415A4 (en) * | 2014-04-19 | 2017-10-25 | Granules India Limited | An improved process for the preparation of rifamycin derivatives |
| WO2015171493A1 (en) | 2014-05-04 | 2015-11-12 | Salix Pharmaceuticals, Inc. | Ibs microbiota and uses thereof |
| PL3143027T3 (pl) | 2014-05-12 | 2019-11-29 | Alfasigma Spa | Nowe solwatowane krystaliczne postaci rifaksyminy, ich wytwarzanie, kompozycje i zastosowania |
| EP2982764A1 (en) | 2014-08-05 | 2016-02-10 | ALFA WASSERMANN S.p.A. | Identification of vaginal bacteria |
| US9988398B2 (en) | 2016-06-07 | 2018-06-05 | Cadila Healthcare Limited | Crystalline form of rifaximin and process for its preparation |
| EP4137132A1 (en) | 2016-09-30 | 2023-02-22 | Salix Pharmaceuticals, Inc. | Solid dispersion forms of rifaximin |
| IT201700091912A1 (it) * | 2017-08-08 | 2019-02-08 | Biofer Spa | Nuove pirido-imidazo rifamicine |
| RU2020102511A (ru) | 2017-06-26 | 2021-07-27 | Биофер С.П.А. | Соединения пиридо-имидазо рифамицина в качестве антибактериального средства |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE273377C (OSRAM) * | ||||
| AT273377B (de) * | 1967-03-01 | 1969-08-11 | Lepetit Spa | Verfahren zur Herstellung von neuen Rifamycinen |
| AT344898B (de) * | 1975-06-13 | 1978-08-10 | Archifar Ind Chim Trentino | Verfahren zur herstellung neuer rifamycin-verbindungen |
| DK345977A (da) * | 1976-09-30 | 1978-03-31 | Archifar Ind Chim Trentino | G rifamycinforbindelser og fremgangsmaade til deres fremstillin |
| CH629212A5 (it) * | 1976-10-18 | 1982-04-15 | Erba Farmitalia | Procedimento per la preparazione di composti di rifamicina. |
| CH633014A5 (en) * | 1978-06-09 | 1982-11-15 | Erba Farmitalia | Rifamycin compounds |
-
1980
- 1980-05-22 IT IT03429/80A patent/IT1154655B/it active Protection Beyond IP Right Term
-
1981
- 1981-05-11 NL NLAANVRAGE8102290,A patent/NL187022C/xx not_active IP Right Cessation
- 1981-05-11 US US06/262,123 patent/US4341785A/en not_active Expired - Lifetime
- 1981-05-18 AU AU70655/81A patent/AU537093B2/en not_active Expired
- 1981-05-19 AT AT0222781A patent/AT373599B/de not_active IP Right Cessation
- 1981-05-20 PH PH25656A patent/PH17207A/en unknown
- 1981-05-20 FR FR8110058A patent/FR2482967A1/fr active Granted
- 1981-05-20 GR GR65010A patent/GR75640B/el unknown
- 1981-05-20 PT PT73064A patent/PT73064B/pt unknown
- 1981-05-20 LU LU83376A patent/LU83376A1/fr unknown
- 1981-05-20 EG EG280/81A patent/EG14891A/xx active
- 1981-05-21 ES ES502906A patent/ES8203388A1/es not_active Expired
- 1981-05-21 FI FI811565A patent/FI69467C/fi not_active IP Right Cessation
- 1981-05-21 BE BE2/59169A patent/BE888895A/fr not_active IP Right Cessation
- 1981-05-21 IE IE1139/81A patent/IE51204B1/en not_active IP Right Cessation
- 1981-05-21 ZA ZA00813430A patent/ZA813430B/xx unknown
- 1981-05-21 DK DK224781A patent/DK157876C/da active
- 1981-05-21 CA CA000378015A patent/CA1142518A/en not_active Expired
- 1981-05-21 SE SE8103216A patent/SE453089B/sv not_active IP Right Cessation
- 1981-05-21 NO NO811731A patent/NO155622C/no unknown
- 1981-05-22 DE DE19813120460 patent/DE3120460A1/de active Granted
- 1981-05-22 GB GB8115790A patent/GB2079270B/en not_active Expired
- 1981-05-22 JP JP7787781A patent/JPS5711987A/ja active Granted
- 1981-05-22 AR AR285424A patent/AR226212A1/es active
- 1981-05-22 CH CH3381/81A patent/CH648037A5/de not_active IP Right Cessation
-
1982
- 1982-02-09 PH PH26842A patent/PH18704A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI69467C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara pyrido- och isokinolin(1',2':1,2)imidazo(5,4-c)rifamycin soch sv-derivat | |
| Deutsch et al. | Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity | |
| JP2002528548A (ja) | イミダゾナフチリジン | |
| EP0313874B1 (en) | Disulfur analogs of LL-E33288 antitumor agents | |
| CA2162530C (en) | Novel crystalline cephem acid addition salts and processes for their preparation | |
| JPH02240095A (ja) | 環縮合型マクロライド化合物 | |
| EP0222186A2 (en) | Erythromycin derivatives /A | |
| EP0333176A2 (en) | Substituted benzoxazinorifamycin derivative, process for preparing the same and antibacterial agent containing the same | |
| PT81198B (pt) | Novo processo para a sintese de pirido-imidazo-rifamicinas | |
| EP1284984B1 (fr) | Derives de l'uridine comme antibiotiques | |
| WO1989004167A1 (en) | Antibacterial 9-deoxo-9a-allyl and propargyl-9a-aza-9a-homoerythromycin a derivatives | |
| EP0359480B1 (en) | Mitomycin derivatives | |
| CN1462274A (zh) | 三唑并－依泊昔酮 | |
| US3629232A (en) | 2'-o-alkanoyl-4'-alkanoyloxy derivatives of erythromycin | |
| US4880825A (en) | Mitomycin derivatives | |
| EP0114486B1 (en) | Alkylation of oleandomycin | |
| SE436208B (sv) | Sett att framstella 5-fluoro-uracilderivat | |
| HU195667B (en) | Process for production of derivatives of nitroantracyclin | |
| FI81103C (fi) | Foerfarande foer framstaellning av acetoximetyl och -etoxikarbonyloxietyl penemestrar. | |
| CA2346870A1 (en) | Derivatives of erythromycin, clarithromycin, roxithromycin or azithromycin with antibiotic and mucolytic activity | |
| US4271155A (en) | Water soluble hydrazones of 3-formylrifamycin SV, antibacterial compositions thereof and method of use thereof | |
| EP0273357B1 (en) | Fluorine-containing macrolide compounds, pharmaceutical compositions comprising the same and their use for the manufacture of medicaments | |
| IE43252B1 (en) | Quinoxaline-1,4-dioxides | |
| HK1061560B (en) | Triazolo-epothilones | |
| EP0005140A2 (en) | Novel 4-desoxy-thiazolo (5,4-c) rifamycin derivatives and a process for preparing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: ALFA FARMACEUTICI S.P.A. |