DE69730138T2 - Herstellung von kristallinen form ii von clarithromycin - Google Patents
Herstellung von kristallinen form ii von clarithromycin Download PDFInfo
- Publication number
- DE69730138T2 DE69730138T2 DE69730138T DE69730138T DE69730138T2 DE 69730138 T2 DE69730138 T2 DE 69730138T2 DE 69730138 T DE69730138 T DE 69730138T DE 69730138 T DE69730138 T DE 69730138T DE 69730138 T2 DE69730138 T2 DE 69730138T2
- Authority
- DE
- Germany
- Prior art keywords
- carbon atoms
- solvent
- methylerythromycin
- water
- alkanol
- 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.)
- Revoked
Links
- 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 118
- 229960002626 clarithromycin Drugs 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 81
- 239000002904 solvent Substances 0.000 claims abstract description 64
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 63
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000013078 crystal Substances 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 19
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 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 abstract description 14
- 229930006677 Erythromycin A Natural products 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 14
- 229960003276 erythromycin Drugs 0.000 claims abstract description 14
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 229940011051 isopropyl acetate Drugs 0.000 claims abstract description 10
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 239000003880 polar aprotic solvent Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 150000002430 hydrocarbons Chemical class 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 13
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- FFOPEPMHKILNIT-UHFFFAOYSA-N Isopropyl butyrate Chemical compound CCCC(=O)OC(C)C FFOPEPMHKILNIT-UHFFFAOYSA-N 0.000 claims description 8
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 8
- 150000001555 benzenes Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 5
- 239000008096 xylene Substances 0.000 claims description 5
- 229940072049 amyl acetate Drugs 0.000 claims description 4
- PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 claims description 4
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 claims description 3
- BCUMPULZWNQMKD-UHFFFAOYSA-N methanol;propan-2-yl acetate Chemical compound OC.CC(C)OC(C)=O BCUMPULZWNQMKD-UHFFFAOYSA-N 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 claims description 2
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- KYTWXIARANQMCA-RWJQBGPGSA-N (3r,4s,5s,6r,7r,9r,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-oxacyclotetradecan-2 Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=NO)[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-RWJQBGPGSA-N 0.000 claims 2
- 230000003115 biocidal effect Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 239000012022 methylating agents Substances 0.000 claims 1
- 210000002345 respiratory system Anatomy 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 6
- 125000001475 halogen functional group Chemical group 0.000 abstract 3
- 239000007787 solid Substances 0.000 description 31
- 238000010992 reflux Methods 0.000 description 28
- 239000000706 filtrate Substances 0.000 description 23
- 239000000725 suspension Substances 0.000 description 23
- 238000001953 recrystallisation Methods 0.000 description 19
- 238000001914 filtration Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 7
- 238000000634 powder X-ray diffraction Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000003386 deoximation reaction Methods 0.000 description 6
- 230000011987 methylation Effects 0.000 description 6
- 238000007069 methylation reaction Methods 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 238000001757 thermogravimetry curve Methods 0.000 description 5
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- -1 6-O-methylerythromycin A-9 oxime Chemical class 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N methyl n-propyl ketone Natural products CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 238000006485 reductive methylation reaction Methods 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- MWBJRTBANFUBOX-SQYJNGITSA-N (3r,4s,5s,6r,7r,9r,10e,11s,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-10-hydroxyimino-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclot Chemical compound 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)([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 MWBJRTBANFUBOX-SQYJNGITSA-N 0.000 description 1
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 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 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229940087430 biaxin Drugs 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 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
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 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
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 238000006146 oximation reaction Methods 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US681695 | 1996-07-29 | ||
| US08/681,695 US5844105A (en) | 1996-07-29 | 1996-07-29 | Preparation of crystal form II of clarithromycin |
| US90027197A | 1997-07-25 | 1997-07-25 | |
| US900271 | 1997-07-25 | ||
| PCT/US1997/013166 WO1998004574A1 (en) | 1996-07-29 | 1997-07-28 | Preparation of crystal form ii of clarithromycin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69730138D1 DE69730138D1 (de) | 2004-09-30 |
| DE69730138T2 true DE69730138T2 (de) | 2005-03-03 |
Family
ID=27102712
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69730138T Revoked DE69730138T2 (de) | 1996-07-29 | 1997-07-28 | Herstellung von kristallinen form ii von clarithromycin |
| DE29724846U Expired - Lifetime DE29724846U1 (de) | 1996-07-29 | 1997-07-28 | Herstellung von kristalliner Form II von Clarithromycin |
| DE0000915899T Pending DE97934319T1 (de) | 1996-07-29 | 1997-07-28 | Herstellung von kristallinen form ii von clarithromycin |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE29724846U Expired - Lifetime DE29724846U1 (de) | 1996-07-29 | 1997-07-28 | Herstellung von kristalliner Form II von Clarithromycin |
| DE0000915899T Pending DE97934319T1 (de) | 1996-07-29 | 1997-07-28 | Herstellung von kristallinen form ii von clarithromycin |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0915899B1 (cg-RX-API-DMAC7.html) |
| JP (4) | JP4104660B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR100524214B1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE272646T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU733646B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2261732C (cg-RX-API-DMAC7.html) |
| DE (3) | DE69730138T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0915899T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2173057T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL127833A (cg-RX-API-DMAC7.html) |
| PT (1) | PT915899E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1998004574A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5945405A (en) * | 1997-01-17 | 1999-08-31 | Abbott Laboratories | Crystal form O of clarithromycin |
| US6245903B1 (en) | 1998-08-21 | 2001-06-12 | Apotex, Inc. | Azithromycin monohydrate isopropanol clathrate and methods for the manufacture thereof |
| KR100377159B1 (ko) * | 1998-09-09 | 2003-08-19 | 한미약품공업 주식회사 | 잔류 용매가 없는 클라리스로마이신의 결정형 2의 제조 방법 |
| GB9827355D0 (en) | 1998-12-11 | 1999-02-03 | Biochemie Sa | Organic compounds |
| KR20010008496A (ko) * | 1999-07-01 | 2001-02-05 | 유충식 | 6-오-메틸 에리트로마이신의 제조방법 |
| KR100322313B1 (ko) * | 1999-10-21 | 2002-02-06 | 민경윤 | 클라리스로마이신 결정형 2의 제조방법 및 이에 사용되는 클라리스로마이신 포르메이트 |
| US6627743B1 (en) | 1999-12-03 | 2003-09-30 | Abbott Laboratories | 6-O-methylerythromycin A crystal form III |
| CZ20021999A3 (cs) * | 1999-12-16 | 2003-02-12 | Teva Pharmaceutical Industries Ltd. | Způsob přípravy klaritromycinových polymorfních forem a nového polymorfu IV |
| CA2397092A1 (en) * | 2000-01-11 | 2001-07-19 | Teva Pharmaceutical Industries Ltd. | Processes for preparing clarithromycin polymorphs |
| WO2001064224A1 (en) | 2000-02-29 | 2001-09-07 | Teva Pharmaceutical Industries Ltd. | Processes for preparing clarithromycin and clarithromycin intermediate, essentially oxime-free clarithromycin, and pharmaceutical composition comprising the same |
| KR100361397B1 (ko) * | 2000-03-15 | 2002-11-23 | 한미약품공업 주식회사 | 에리스로마이신 에이 9-오-트로필옥심 유도체를 이용한클라리스로마이신의 제조방법 |
| KR100367981B1 (ko) * | 2000-11-23 | 2003-01-14 | 한미약품공업 주식회사 | 클라리스로마이신 결정형 2의 제조 방법 및 이 방법에사용되는 결정성 클라리스로마이신 메실레이트 삼수화물 |
| DE60122791T2 (de) * | 2000-03-15 | 2007-10-04 | Hanmi Pharm. Co., Ltd. | Verfahren zur Herstellung von Clarythromycin mit nicht pharmazeutischer Qualität |
| KR100408848B1 (ko) * | 2001-03-12 | 2003-12-06 | 주식회사 씨트리 | 클래리스로마이신의 정제방법 |
| DE60209704T2 (de) | 2001-05-22 | 2006-11-16 | Pfizer Products Inc., Groton | Neue kristallforme von azithromycin |
| US6861413B2 (en) | 2001-05-22 | 2005-03-01 | Pfizer Inc. | Stable non-dihydrate azithromycin oral suspensions |
| EP1652851A1 (en) * | 2001-05-22 | 2006-05-03 | Pfizer Products Inc. | New crystal form of Azithromycin |
| KR100372254B1 (en) * | 2002-07-15 | 2003-02-19 | Korea United Pharm Inc | Erythromycin a 9-o-pseudosaccharinyl oxime derivative and process for preparing clarithromycin using the same |
| EP1435359A1 (en) * | 2002-12-31 | 2004-07-07 | Alembic Limited | A process for the purification of roxithromycin |
| US7384921B2 (en) * | 2004-02-20 | 2008-06-10 | Enanta Pharmaceuticals, Inc. | Polymorphic forms of 6-11 bicyclic ketolide derivatives |
| MX2009005977A (es) * | 2006-12-05 | 2009-06-17 | Pfizer | Polimorfos de motilida. |
| DE102007016367A1 (de) * | 2007-04-03 | 2008-10-09 | Grünenthal GmbH | Polymorph von Clarithromycin (Form V) |
| CN103087130B (zh) * | 2013-02-06 | 2015-12-23 | 浙江国邦药业有限公司 | 一种克拉霉素晶型转换方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS572298A (en) * | 1980-06-04 | 1982-01-07 | Taisho Pharmaceut Co Ltd | Erythromycin derivative |
| JPS5782400A (en) | 1980-11-12 | 1982-05-22 | Taisho Pharmaceut Co Ltd | Erythromycin derivative |
| US4331803A (en) | 1980-06-04 | 1982-05-25 | Taisho Pharmaceutical Co., Ltd. | Novel erythromycin compounds |
| JPS60214796A (ja) | 1984-04-06 | 1985-10-28 | Taisho Pharmaceut Co Ltd | ６−０−メチルエリスロマイシン類の製法 |
| JPS61103890A (ja) | 1984-10-26 | 1986-05-22 | Taisho Pharmaceut Co Ltd | ６−０−メチルエリスロマイシンａ誘導体 |
| US4670549A (en) * | 1985-03-18 | 1987-06-02 | Taisho Pharmaceutical Co., Ltd. | Method for selective methylation of erythromycin a derivatives |
| DE3782994T2 (de) | 1986-09-18 | 1993-04-08 | Taisho Pharma Co Ltd | Erythromycin-a-derivate und verfahren zu ihrer herstellung. |
| JPH0755958B2 (ja) * | 1986-10-03 | 1995-06-14 | 大正製薬株式会社 | エリスロマイシンａ誘導体の製造方法 |
| KR960000434B1 (ko) * | 1986-12-17 | 1996-01-06 | 다이쇼 세이야꾸 가부시끼가이샤 | 에리스로마이신 a유도체 및 그의 제조 방법 |
| JP2526951B2 (ja) * | 1986-12-17 | 1996-08-21 | 大正製薬株式会社 | エリスロマイシンａ誘導体およびその製造方法 |
| JP2782793B2 (ja) * | 1988-06-15 | 1998-08-06 | 大正製薬株式会社 | エリスロマイシンａ誘導体およびその製造方法 |
| ZA922776B (en) * | 1991-04-29 | 1993-10-15 | Lilly Co Eli | Pharmaceutical compounds |
| US5872229A (en) | 1995-11-21 | 1999-02-16 | Abbott Laboratories | Process for 6-O-alkylation of erythromycin derivatives |
| US5719272A (en) | 1996-04-02 | 1998-02-17 | Abbott Laboratories | 2'-protected 3'-dimethylamine, 9-etheroxime erythromycin A derivatives |
| US5837829A (en) | 1996-04-02 | 1998-11-17 | Abbott Laboratories | 9-oximesilyl erythromycin a derivatives |
-
1997
- 1997-07-28 PT PT97934319T patent/PT915899E/pt unknown
- 1997-07-28 ES ES97934319T patent/ES2173057T3/es not_active Expired - Lifetime
- 1997-07-28 JP JP50903898A patent/JP4104660B2/ja not_active Expired - Lifetime
- 1997-07-28 AU AU37405/97A patent/AU733646B2/en not_active Expired
- 1997-07-28 AT AT97934319T patent/ATE272646T1/de active
- 1997-07-28 DE DE69730138T patent/DE69730138T2/de not_active Revoked
- 1997-07-28 EP EP97934319A patent/EP0915899B1/en not_active Revoked
- 1997-07-28 IL IL12783397A patent/IL127833A/en not_active IP Right Cessation
- 1997-07-28 CA CA002261732A patent/CA2261732C/en not_active Expired - Lifetime
- 1997-07-28 WO PCT/US1997/013166 patent/WO1998004574A1/en not_active Ceased
- 1997-07-28 DE DE29724846U patent/DE29724846U1/de not_active Expired - Lifetime
- 1997-07-28 DK DK97934319T patent/DK0915899T3/da active
- 1997-07-28 KR KR10-1999-7000654A patent/KR100524214B1/ko not_active Expired - Lifetime
- 1997-07-28 DE DE0000915899T patent/DE97934319T1/de active Pending
-
2005
- 2005-12-12 JP JP2005357782A patent/JP2006137765A/ja active Pending
-
2009
- 2009-06-15 JP JP2009141790A patent/JP2009242411A/ja not_active Withdrawn
-
2013
- 2013-04-03 JP JP2013077418A patent/JP2013151542A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE29724846U1 (de) | 2004-12-16 |
| CA2261732A1 (en) | 1998-02-05 |
| DE69730138D1 (de) | 2004-09-30 |
| JP2006137765A (ja) | 2006-06-01 |
| KR100524214B1 (ko) | 2005-11-01 |
| KR20000029591A (ko) | 2000-05-25 |
| JP2013151542A (ja) | 2013-08-08 |
| ES2173057T1 (es) | 2002-10-16 |
| DE97934319T1 (de) | 2004-08-26 |
| IL127833A0 (en) | 1999-10-28 |
| JP2009242411A (ja) | 2009-10-22 |
| ATE272646T1 (de) | 2004-08-15 |
| AU733646B2 (en) | 2001-05-17 |
| EP0915899A1 (en) | 1999-05-19 |
| CA2261732C (en) | 2001-07-24 |
| WO1998004574A1 (en) | 1998-02-05 |
| DK0915899T3 (da) | 2004-11-29 |
| IL127833A (en) | 2004-06-20 |
| JP2002514171A (ja) | 2002-05-14 |
| PT915899E (pt) | 2004-11-30 |
| AU3740597A (en) | 1998-02-20 |
| ES2173057T3 (es) | 2004-11-16 |
| EP0915899B1 (en) | 2004-08-04 |
| JP4104660B2 (ja) | 2008-06-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8363 | Opposition against the patent | ||
| 8339 | Ceased/non-payment of the annual fee | ||
| 8331 | Complete revocation | ||
| 8380 | Miscellaneous part iii |
Free format text: DIE ZURUECKNAHME VOM 15.05.2008 WURDE GELOESCHT. |