CN106188194A - 索菲布韦单晶及制备方法和用途 - Google Patents
索菲布韦单晶及制备方法和用途 Download PDFInfo
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- CN106188194A CN106188194A CN201510407660.6A CN201510407660A CN106188194A CN 106188194 A CN106188194 A CN 106188194A CN 201510407660 A CN201510407660 A CN 201510407660A CN 106188194 A CN106188194 A CN 106188194A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000013078 crystal Substances 0.000 claims abstract description 61
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 21
- 239000000843 powder Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- -1 alkyl cyanide Chemical compound 0.000 claims description 6
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 6
- 208000005176 Hepatitis C Diseases 0.000 claims description 5
- 238000002441 X-ray diffraction Methods 0.000 claims description 5
- 125000005910 alkyl carbonate group Chemical group 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 3
- 208000006154 Chronic hepatitis C Diseases 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000005755 formation reaction Methods 0.000 description 17
- TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 description 8
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229940011051 isopropyl acetate Drugs 0.000 description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
- IJMWOMHMDSDKGK-UHFFFAOYSA-N Isopropyl propionate Chemical compound CCC(=O)OC(C)C IJMWOMHMDSDKGK-UHFFFAOYSA-N 0.000 description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 229960000329 ribavirin Drugs 0.000 description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 0 C*C1=CC=CCC1 Chemical compound C*C1=CC=CCC1 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
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- 208000006454 hepatitis Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229960002063 sofosbuvir Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- JRMAQQQTXDJDNC-UHFFFAOYSA-M 2-ethoxy-2-oxoacetate Chemical compound CCOC(=O)C([O-])=O JRMAQQQTXDJDNC-UHFFFAOYSA-M 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 150000002243 furanoses Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229950000038 interferon alfa Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 229940076563 sovaldi Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (9)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2014105917106 | 2014-10-29 | ||
CN201410591710.6A CN104277088A (zh) | 2014-10-29 | 2014-10-29 | 索菲布韦单晶m及其制备方法和用途 |
Publications (1)
Publication Number | Publication Date |
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CN106188194A true CN106188194A (zh) | 2016-12-07 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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CN201410591710.6A Pending CN104277088A (zh) | 2014-10-29 | 2014-10-29 | 索菲布韦单晶m及其制备方法和用途 |
CN201510407660.6A Pending CN106188194A (zh) | 2014-10-29 | 2015-07-13 | 索菲布韦单晶及制备方法和用途 |
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CN201410591710.6A Pending CN104277088A (zh) | 2014-10-29 | 2014-10-29 | 索菲布韦单晶m及其制备方法和用途 |
Country Status (1)
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CN (2) | CN104277088A (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109053840A (zh) * | 2018-08-07 | 2018-12-21 | 浙江华纳药业有限公司 | 一种索非布韦viii晶型的制备方法 |
CN111004300A (zh) * | 2019-12-25 | 2020-04-14 | 江苏永安制药有限公司 | 一种制备索磷布韦的方法 |
CN109517018B (zh) * | 2018-12-29 | 2021-05-04 | 石药集团中奇制药技术(石家庄)有限公司 | 一种索磷布韦新晶型及其制备方法 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI3524234T1 (sl) | 2014-06-13 | 2021-05-31 | Ratiopharm Gmbh | Trdne oblike sofosbuvira |
CN104829673B (zh) * | 2015-03-12 | 2017-10-27 | 南京旗昌医药科技有限公司 | 一种索氟布韦晶型6的制备方法 |
CN106146589B (zh) * | 2015-04-10 | 2019-03-05 | 正大天晴药业集团股份有限公司 | 氘代核苷衍生物的结晶 |
CN105017359A (zh) * | 2015-07-08 | 2015-11-04 | 苏州晶云药物科技有限公司 | 一种索非布韦晶型的制备方法 |
WO2017029408A1 (en) * | 2015-08-20 | 2017-02-23 | Ratiopharm Gmbh | Solid state forms of sofosbuvir |
CN108084237A (zh) * | 2016-11-23 | 2018-05-29 | 广东东阳光药业有限公司 | 索非布韦的一水合物及其制备方法 |
RU2656228C9 (ru) * | 2017-06-13 | 2019-04-16 | Олег Ростиславович Михайлов | Слабозакристаллизованная β-модификация (S)-изопропил 2-((S)-(((2R,3R,4R,5R)-5-(2,4-диоксо-3,4-дигидропиримидин-(2Н)-ил)-4-фтор-3-гидрокси-4-метилтетрагидрофуран-2-ил)метокси)-(фенокси)фосфориламино)пропаноата, способ её получения и фармацевтическая композиция на её основе |
CN111233956B (zh) * | 2018-11-29 | 2023-04-28 | 北京凯因科技股份有限公司 | 索非布韦的晶型及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102459299A (zh) * | 2009-05-20 | 2012-05-16 | 法莫赛特股份有限公司 | N-[(2′r)-2′-脱氧-2′-氟-2′-甲基-p-苯基-5′-尿苷酰基]-l-丙氨酸1-甲基乙基酯及其制备方法 |
CN103804446A (zh) * | 2014-02-27 | 2014-05-21 | 苏州东南药业股份有限公司 | 一种3,5-二苯甲酰基-2-去氧-2-氟-2甲基-D-核糖-γ-内酯的制备方法 |
CN103848876A (zh) * | 2013-03-25 | 2014-06-11 | 安徽贝克联合制药有限公司 | 一种核苷磷酰胺前药及其制备方法和其应用 |
-
2014
- 2014-10-29 CN CN201410591710.6A patent/CN104277088A/zh active Pending
-
2015
- 2015-07-13 CN CN201510407660.6A patent/CN106188194A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102459299A (zh) * | 2009-05-20 | 2012-05-16 | 法莫赛特股份有限公司 | N-[(2′r)-2′-脱氧-2′-氟-2′-甲基-p-苯基-5′-尿苷酰基]-l-丙氨酸1-甲基乙基酯及其制备方法 |
CN103848876A (zh) * | 2013-03-25 | 2014-06-11 | 安徽贝克联合制药有限公司 | 一种核苷磷酰胺前药及其制备方法和其应用 |
CN103804446A (zh) * | 2014-02-27 | 2014-05-21 | 苏州东南药业股份有限公司 | 一种3,5-二苯甲酰基-2-去氧-2-氟-2甲基-D-核糖-γ-内酯的制备方法 |
Non-Patent Citations (1)
Title |
---|
BRUCE S. ROSS,等: ""Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates"", 《J. ORG. CHEM.》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109053840A (zh) * | 2018-08-07 | 2018-12-21 | 浙江华纳药业有限公司 | 一种索非布韦viii晶型的制备方法 |
CN109517018B (zh) * | 2018-12-29 | 2021-05-04 | 石药集团中奇制药技术(石家庄)有限公司 | 一种索磷布韦新晶型及其制备方法 |
CN111004300A (zh) * | 2019-12-25 | 2020-04-14 | 江苏永安制药有限公司 | 一种制备索磷布韦的方法 |
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CN104277088A (zh) | 2015-01-14 |
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Effective date of registration: 20170103 Address after: 100080 Haidian street, Beijing, 1-4 layer 1-030, Part 27 Applicant after: Zhongke Yunhe (Beijing) bio Pharmaceutical Technology Co., Ltd. Address before: 226000 Nantong workers and peasants Road, Jiangsu, No. 111 Applicant before: Tang Lvjin Applicant before: Zhou Shouming Applicant before: Wang Caiqin Applicant before: Feng Ruhong |
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