HUP0302466A2 - Eljárások clarithromycin, clarithromycin intermedier, gyakorlatilag oximmentes clarithromycin és ezt tartalmazó gyógyszerkészítmény előállítására - Google Patents
Eljárások clarithromycin, clarithromycin intermedier, gyakorlatilag oximmentes clarithromycin és ezt tartalmazó gyógyszerkészítmény előállítására Download PDFInfo
- Publication number
- HUP0302466A2 HUP0302466A2 HU0302466A HUP0302466A HUP0302466A2 HU P0302466 A2 HUP0302466 A2 HU P0302466A2 HU 0302466 A HU0302466 A HU 0302466A HU P0302466 A HUP0302466 A HU P0302466A HU P0302466 A2 HUP0302466 A2 HU P0302466A2
- Authority
- HU
- Hungary
- Prior art keywords
- clarithromycin
- oxime
- protected
- silylated
- erythromycin
- Prior art date
Links
- 229960002626 clarithromycin Drugs 0.000 title claims abstract description 102
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin 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)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 title claims abstract description 98
- 238000000034 method Methods 0.000 title claims abstract description 86
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 92
- MWBJRTBANFUBOX-UHFFFAOYSA-N 6-[4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-10-hydroxyimino-4-(5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl)oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one Chemical compound CC1C(OC2C(C(CC(C)O2)N(C)C)O)C(C)(OC)CC(C)C(=NO)C(C)C(O)C(O)(C)C(CC)OC(=O)C(C)C1OC1CC(C)(OC)C(O)C(C)O1 MWBJRTBANFUBOX-UHFFFAOYSA-N 0.000 claims abstract description 83
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 55
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- 239000002904 solvent Substances 0.000 claims abstract description 40
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 34
- 239000002253 acid Substances 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 239000012022 methylating agents Substances 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 17
- 239000011541 reaction mixture Substances 0.000 claims abstract description 15
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 15
- 238000010438 heat treatment Methods 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 229960003276 erythromycin Drugs 0.000 claims description 39
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 36
- 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 claims description 33
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 24
- 150000002923 oximes Chemical class 0.000 claims description 24
- 229930006677 Erythromycin A Natural products 0.000 claims description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- 238000007792 addition Methods 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 13
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 12
- 235000019253 formic acid Nutrition 0.000 claims description 12
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims description 8
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 8
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 8
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 6
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 claims description 4
- 229940102396 methyl bromide Drugs 0.000 claims description 4
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- KYTWXIARANQMCA-PGYIPVOXSA-N (3r,4s,5s,6r,7r,9r,10z,11s,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-10-hydroxyimino-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradec Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N\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 KYTWXIARANQMCA-PGYIPVOXSA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims 7
- 239000002585 base Substances 0.000 claims 3
- 239000003513 alkali Substances 0.000 claims 2
- -1 clarithromycin oximes Chemical class 0.000 abstract description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000012535 impurity Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 238000007069 methylation reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000011987 methylation Effects 0.000 description 5
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 230000001035 methylating effect Effects 0.000 description 4
- 125000003544 oxime group Chemical group 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-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 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- FGRVOLIFQGXPCT-UHFFFAOYSA-L dipotassium;dioxido-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound [K+].[K+].[O-]S([O-])(=O)=S FGRVOLIFQGXPCT-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 1
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 description 1
- 229940043349 potassium metabisulfite Drugs 0.000 description 1
- 235000010263 potassium metabisulphite Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000011935 selective methylation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 229940075931 sodium dithionate Drugs 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 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
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 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
- 229940001474 sodium thiosulfate Drugs 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 229910052815 sulfur oxide Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 238000005406 washing Methods 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18588800P | 2000-02-29 | 2000-02-29 | |
| US18912000P | 2000-03-14 | 2000-03-14 | |
| US21323900P | 2000-06-22 | 2000-06-22 | |
| PCT/US2000/033843 WO2001064224A1 (en) | 2000-02-29 | 2000-12-15 | Processes for preparing clarithromycin and clarithromycin intermediate, essentially oxime-free clarithromycin, and pharmaceutical composition comprising the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUP0302466A2 true HUP0302466A2 (hu) | 2003-11-28 |
Family
ID=27392028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU0302466A HUP0302466A2 (hu) | 2000-02-29 | 2000-12-15 | Eljárások clarithromycin, clarithromycin intermedier, gyakorlatilag oximmentes clarithromycin és ezt tartalmazó gyógyszerkészítmény előállítására |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US6617436B2 (show.php) |
| EP (1) | EP1313486A1 (show.php) |
| JP (1) | JP2004509062A (show.php) |
| KR (1) | KR20030047873A (show.php) |
| AU (2) | AU2001225787C1 (show.php) |
| CA (1) | CA2401571A1 (show.php) |
| CZ (1) | CZ20023167A3 (show.php) |
| HR (1) | HRP20020709A2 (show.php) |
| HU (1) | HUP0302466A2 (show.php) |
| IL (1) | IL151496A0 (show.php) |
| IS (1) | IS6531A (show.php) |
| PL (1) | PL366021A1 (show.php) |
| SK (1) | SK13722002A3 (show.php) |
| WO (1) | WO2001064224A1 (show.php) |
| YU (1) | YU64202A (show.php) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020070991A (ko) * | 1999-12-16 | 2002-09-11 | 테바 파마슈티컬 인더스트리즈 리미티드 | 클라리트로마이신 다형체 및 신규의 다형체 ⅳ의 제조 방법 |
| SI1280535T1 (show.php) * | 2000-01-11 | 2005-08-31 | Teva Pharma | |
| US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
| US6565882B2 (en) | 2000-02-24 | 2003-05-20 | Advancis Pharmaceutical Corp | Antibiotic composition with inhibitor |
| SK13722002A3 (sk) * | 2000-02-29 | 2003-08-05 | Teva Pharmaceutical Industries Ltd. | Spôsob prípravy klaritromycínu a klaritromycínového medziproduktu, v podstate prostého oxímu a farmaceutický prostriedok, ktorý ho obsahuje |
| BR0109544A (pt) * | 2000-03-28 | 2003-06-10 | Biochemie Gmbh | Partìculas granuladas com sabor ocultado |
| US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
| US6541014B2 (en) | 2000-10-13 | 2003-04-01 | Advancis Pharmaceutical Corp. | Antiviral product, use and formulation thereof |
| CA2533292C (en) | 2003-07-21 | 2013-12-31 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| AU2004258949B2 (en) | 2003-07-21 | 2011-02-10 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
| WO2005009364A2 (en) | 2003-07-21 | 2005-02-03 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| JP2007502296A (ja) | 2003-08-11 | 2007-02-08 | アドバンシス ファーマスーティカル コーポレイション | ロバストペレット |
| EP1653924A4 (en) | 2003-08-12 | 2009-09-09 | Middlebrook Pharmaceuticals In | ANTIBIOTICS, USE AND FORMULATION ASSOCIATED |
| AU2004270170B2 (en) * | 2003-08-29 | 2011-01-27 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
| WO2005027877A1 (en) | 2003-09-15 | 2005-03-31 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| AU2005269981A1 (en) | 2004-07-02 | 2006-02-09 | Bonck, John A | Tablet for pulsed delivery |
| US20070015719A1 (en) * | 2005-07-07 | 2007-01-18 | Elan Pharma International Limited | Nanoparticulate clarithromycin formulations |
| US8778924B2 (en) | 2006-12-04 | 2014-07-15 | Shionogi Inc. | Modified release amoxicillin products |
| US8357394B2 (en) | 2005-12-08 | 2013-01-22 | Shionogi Inc. | Compositions and methods for improved efficacy of penicillin-type antibiotics |
| US8299052B2 (en) | 2006-05-05 | 2012-10-30 | Shionogi Inc. | Pharmaceutical compositions and methods for improved bacterial eradication |
| WO2009023191A2 (en) * | 2007-08-09 | 2009-02-19 | Teva Pharmaceutical Industries Ltd. | An improved process for the preparation of clarithromycin |
| CN102417532A (zh) * | 2011-12-20 | 2012-04-18 | 浙江国邦药业有限公司 | 一种泰利霉素关键中间体5-德胺糖基-6-o-甲基红霉素的合成方法 |
| CN102718821B (zh) * | 2012-06-27 | 2014-12-03 | 浙江国邦药业有限公司 | 一种克拉霉素合成过程中甲基化反应以及甲基化试剂的回收套用方法 |
| CN103880901A (zh) * | 2012-12-23 | 2014-06-25 | 菏泽市方明制药有限公司 | 一种克拉霉素中间甲化物的制备方法 |
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2000
- 2000-12-15 SK SK1372-2002A patent/SK13722002A3/sk not_active Application Discontinuation
- 2000-12-15 AU AU2001225787A patent/AU2001225787C1/en not_active Ceased
- 2000-12-15 JP JP2001563121A patent/JP2004509062A/ja not_active Withdrawn
- 2000-12-15 US US09/736,447 patent/US6617436B2/en not_active Expired - Fee Related
- 2000-12-15 CZ CZ20023167A patent/CZ20023167A3/cs unknown
- 2000-12-15 AU AU2578701A patent/AU2578701A/xx active Pending
- 2000-12-15 HU HU0302466A patent/HUP0302466A2/hu unknown
- 2000-12-15 YU YU64202A patent/YU64202A/sh unknown
- 2000-12-15 CA CA002401571A patent/CA2401571A1/en not_active Abandoned
- 2000-12-15 IL IL15149600A patent/IL151496A0/xx unknown
- 2000-12-15 WO PCT/US2000/033843 patent/WO2001064224A1/en not_active Ceased
- 2000-12-15 KR KR1020027011330A patent/KR20030047873A/ko not_active Ceased
- 2000-12-15 EP EP00989252A patent/EP1313486A1/en not_active Withdrawn
- 2000-12-15 PL PL00366021A patent/PL366021A1/xx not_active Application Discontinuation
- 2000-12-15 HR HRP20020709 patent/HRP20020709A2/hr not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
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| JP2004509062A (ja) | 2004-03-25 |
| AU2001225787B2 (en) | 2005-12-08 |
| US7101858B2 (en) | 2006-09-05 |
| US20030216556A1 (en) | 2003-11-20 |
| HRP20020709A2 (en) | 2004-12-31 |
| AU2001225787C1 (en) | 2006-09-21 |
| AU2578701A (en) | 2001-09-12 |
| YU64202A (sh) | 2005-03-15 |
| EP1313486A1 (en) | 2003-05-28 |
| US20010037015A1 (en) | 2001-11-01 |
| WO2001064224A1 (en) | 2001-09-07 |
| US6617436B2 (en) | 2003-09-09 |
| CA2401571A1 (en) | 2001-09-07 |
| CZ20023167A3 (cs) | 2003-10-15 |
| IL151496A0 (en) | 2003-04-10 |
| KR20030047873A (ko) | 2003-06-18 |
| IS6531A (is) | 2002-08-28 |
| PL366021A1 (en) | 2005-01-24 |
| US20060205683A1 (en) | 2006-09-14 |
| SK13722002A3 (sk) | 2003-08-05 |
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