CN1142171C - 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 - Google Patents
9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 Download PDFInfo
- Publication number
- CN1142171C CN1142171C CNB021510326A CN02151032A CN1142171C CN 1142171 C CN1142171 C CN 1142171C CN B021510326 A CNB021510326 A CN B021510326A CN 02151032 A CN02151032 A CN 02151032A CN 1142171 C CN1142171 C CN 1142171C
- Authority
- CN
- China
- Prior art keywords
- ethyl
- methyl
- phosphoroso
- vitamin
- crystal
- 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.)
- Expired - Fee Related
Links
- -1 trimethylacetoxyl Chemical group 0.000 title claims abstract description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title claims abstract description 46
- 239000013078 crystal Substances 0.000 title claims abstract description 37
- 229930024421 Adenine Natural products 0.000 title abstract description 6
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 title abstract description 6
- 229960000643 adenine Drugs 0.000 title abstract description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 title abstract 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims abstract description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 9
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 5
- 239000011782 vitamin Substances 0.000 claims description 52
- 235000013343 vitamin Nutrition 0.000 claims description 52
- 229940088594 vitamin Drugs 0.000 claims description 52
- 229930003231 vitamin Natural products 0.000 claims description 52
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 42
- 239000001301 oxygen Substances 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 21
- 238000002425 crystallisation Methods 0.000 claims description 20
- 230000008025 crystallization Effects 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 18
- 239000012043 crude product Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 7
- 241000701027 Human herpesvirus 6 Species 0.000 claims description 6
- 230000008030 elimination Effects 0.000 claims description 6
- 238000003379 elimination reaction Methods 0.000 claims description 6
- 229960004756 ethanol Drugs 0.000 claims description 6
- 125000006850 spacer group Chemical group 0.000 claims description 4
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 3
- 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims 1
- 229960001997 adefovir Drugs 0.000 abstract description 12
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 6
- 229960003205 adefovir dipivoxil Drugs 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 229960003328 benzoyl peroxide Drugs 0.000 abstract 2
- 210000002858 crystal cell Anatomy 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 13
- 239000011259 mixed solution Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 8
- 238000001291 vacuum drying Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 6
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 6
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical group [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 241000272525 Anas platyrhynchos Species 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N NMP Substances CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 230000000452 restraining effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010025 steaming Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- 241000725618 Duck hepatitis B virus Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical group [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000009834 vaporization Methods 0.000 description 2
- 230000008016 vaporization Effects 0.000 description 2
- UXTFKIJKRJJXNV-UHFFFAOYSA-N 1-$l^{1}-oxidanylethanone Chemical compound CC([O])=O UXTFKIJKRJJXNV-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- 101000807541 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 24 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229910003691 SiBr Inorganic materials 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 102100037176 Ubiquitin carboxyl-terminal hydrolase 24 Human genes 0.000 description 1
- AZVBFIXINWVFEA-UHFFFAOYSA-N [O].C(C)OS(=O)(=O)CC Chemical compound [O].C(C)OS(=O)(=O)CC AZVBFIXINWVFEA-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 238000011951 anti-virus test Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229960004839 potassium iodide Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940083599 sodium iodide Drugs 0.000 description 1
- 150000003527 tetrahydropyrans Chemical class 0.000 description 1
Images
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB021510326A CN1142171C (zh) | 2002-12-04 | 2002-12-04 | 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB021510326A CN1142171C (zh) | 2002-12-04 | 2002-12-04 | 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1421451A CN1421451A (zh) | 2003-06-04 |
CN1142171C true CN1142171C (zh) | 2004-03-17 |
Family
ID=4751892
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB021510326A Expired - Fee Related CN1142171C (zh) | 2002-12-04 | 2002-12-04 | 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1142171C (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7417036B2 (en) * | 2002-11-12 | 2008-08-26 | Tianjin Kinsly Pharmaceutical Co. Ltd. | Crystal form of adefovir dipivoxil and its preparation |
CN102716136A (zh) * | 2012-06-25 | 2012-10-10 | 上海益生源药业有限公司 | 高剂量三斜晶阿德福韦酯制剂、其制备方法及其应用 |
-
2002
- 2002-12-04 CN CNB021510326A patent/CN1142171C/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN1421451A (zh) | 2003-06-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1052227C (zh) | 作为粘结受体拮抗剂的噁唑烷酮,其制备方法和含它们的药物组合物 | |
CN1035829A (zh) | (环烷基胺基)亚甲基双(膦酸)以及以此化合物作为活性成份的药物 | |
CN1489463A (zh) | 阿托伐他汀半钙的新晶型及其制备方法,以及其它晶型的新制备方法 | |
CN1045089C (zh) | 2-(2-氨基-1,6-二氢-6-氧代-嘌呤-9-基)甲氧基-1,3-丙二醇衍生物 | |
CN1292785A (zh) | 降低血脂的苯并硫氮䓬化合物 | |
CN101031548A (zh) | N-(4-氟苄基)-n-(1-甲基哌啶-4-基)-n'-(4-(2-甲基丙氧基)-苯基甲基)脲的盐及其制备 | |
CN1898233A (zh) | 罗苏伐他汀( e )-7-[4-(4-氟苯基)-6-异丙基-2-[甲基(甲磺酰基)氨基 ]嘧啶-5-基] (3r , 5s)-3, 5-二羟庚-6-烯酸钙盐及其结晶中间体的制备方法 | |
CN1259951A (zh) | 新化合物 | |
CN1886383A (zh) | 无定形罗苏伐他汀钙的制备方法 | |
CN1040985C (zh) | 苯并氮杂䓬类化合物的制备方法 | |
CN1942437A (zh) | 作为环氧化酶-1-环氧化酶-2抑制剂的取代氮杂环丁烷化合物及其制备方法和作为药物的用途 | |
CN1029968C (zh) | N-杂芳基-嘌呤-6-胺的制备方法 | |
CN1551880A (zh) | 阿昔洛韦缬氨酸酯盐酸盐的晶型 | |
CN1039910C (zh) | 雪花胺衍生物、其制备方法及其作为药物的用途 | |
CN1874998A (zh) | 1-苄基-4-[(5,6-二甲氧基-1-二氢茚酮)-2-基]甲基哌啶草酸盐(多奈哌齐草酸盐)及其多晶型物 | |
CN1675193A (zh) | 1-甲基-2-(4-脒基苯基氨甲基)-苯并咪唑-5-基-羧酸-(n-2-吡啶基-n-2-羟基羰基乙基-酰胺的新颖前药,其制法及其作为药物制剂的用途 | |
CN1049664A (zh) | 旋光活性4-羟基-8-(3-低烷氧基-4-苯基亚磺酰基苯基)吡唑并[1,5-α]-1,3,5-三嗪盐及其制法 | |
CN1043042C (zh) | 7-[2-(2-氨基噻唑-4-基)-2-(Z)-羟亚胺基-乙酰胺基]-3-(甲氧甲基)-3-头孢烯-4-羧酸-α-(2,2-二甲基丙酰氧)乙酯拆分的方法 | |
CN1142170C (zh) | 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 | |
CN1142171C (zh) | 9-[2-[[[双(三甲基乙酰氧)甲基]氧磷基]甲氧基]-乙基]腺嘌呤晶体,制备方法和晶体的应用 | |
CN1092074A (zh) | 二氮杂䓬衍生物 | |
CN1849320A (zh) | 制备伦扎必利及其中间体的方法 | |
CN1101259A (zh) | 新型七叶亭衍生物及医药组合物 | |
CN1886371A (zh) | 氟伐他汀钠多晶型物的制备方法 | |
CN1868996A (zh) | 纯化普伐他汀的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: SHANGHAI YISHENGYUAN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHANGHAI RUIGUANG BIOCHEMICAL TECHNOLOGY DEVELOPMENT CO., LTD.; LI QISHENG Effective date: 20060609 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20060609 Address after: 201318 Shanghai city Nanhui District Zhoupu town inntech Road No. 98 Patentee after: Shanghai Yishengyuan Pharmaceutical Co., Ltd. Address before: 902 room 1, 200002 Ningbo Road, Shanghai Co-patentee before: Li Qisheng Patentee before: Shanghai Ruiguang Biochemical Sci-Tech Development Co., Ltd. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Effective date of registration: 20091015 Pledge (preservation): Pledge |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20100429 Granted publication date: 20040317 Pledgee: Agricultural Bank of China, Limited by Share Ltd, Shanghai, Nanhui branch Pledgor: Shanghai Yishengyuan Pharmaceutical Co., Ltd. Registration number: 2009310000627 |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20040317 Termination date: 20201204 |