CN107663217B - 替诺福韦艾拉酚胺结晶化合物及其制备方法 - Google Patents
替诺福韦艾拉酚胺结晶化合物及其制备方法 Download PDFInfo
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- CN107663217B CN107663217B CN201610625799.2A CN201610625799A CN107663217B CN 107663217 B CN107663217 B CN 107663217B CN 201610625799 A CN201610625799 A CN 201610625799A CN 107663217 B CN107663217 B CN 107663217B
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- Prior art keywords
- tenofovir alafenamide
- crystal form
- monofumarate
- crystalline compound
- preparation
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- 239000013078 crystal Substances 0.000 title claims abstract description 35
- LDEKQSIMHVQZJK-CAQYMETFSA-N tenofovir alafenamide Chemical compound O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 LDEKQSIMHVQZJK-CAQYMETFSA-N 0.000 title claims abstract description 15
- 229960004946 tenofovir alafenamide Drugs 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 10
- MEJAFWXKUKMUIR-FHPNUNMMSA-N (e)-but-2-enedioic acid;propan-2-yl (2s)-2-[[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phenoxyphosphoryl]amino]propanoate Chemical compound OC(=O)\C=C\C(O)=O.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 MEJAFWXKUKMUIR-FHPNUNMMSA-N 0.000 claims abstract description 27
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 9
- 229940079593 drug Drugs 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- 239000002994 raw material Substances 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 6
- 230000009385 viral infection Effects 0.000 claims description 6
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- SVUJNSGGPUCLQZ-FQQAACOVSA-N tenofovir alafenamide fumarate Chemical compound OC(=O)\C=C\C(O)=O.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 SVUJNSGGPUCLQZ-FQQAACOVSA-N 0.000 abstract description 9
- 229960003560 tenofovir alafenamide fumarate Drugs 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 6
- 238000002411 thermogravimetry Methods 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 229960001355 tenofovir disoproxil Drugs 0.000 description 4
- JFVZFKDSXNQEJW-CQSZACIVSA-N tenofovir disoproxil Chemical compound N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N JFVZFKDSXNQEJW-CQSZACIVSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 229960004556 tenofovir Drugs 0.000 description 3
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 3
- 101001093997 Homo sapiens Solute carrier family 22 member 8 Proteins 0.000 description 2
- 108091006739 SLC22A6 Proteins 0.000 description 2
- 102100036930 Solute carrier family 22 member 6 Human genes 0.000 description 2
- 102100035227 Solute carrier family 22 member 8 Human genes 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 102000007990 Organic Anion Transporters Human genes 0.000 description 1
- 108010089503 Organic Anion Transporters Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- LDEKQSIMHVQZJK-GNGHXOLXSA-N propan-2-yl (2s)-2-[[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phenoxyphosphoryl]amino]propanoate Chemical compound O([P@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 LDEKQSIMHVQZJK-GNGHXOLXSA-N 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- -1 tenofovir alafenamide compound Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
Images
Classifications
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims (4)
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CN201610625799.2A CN107663217B (zh) | 2016-07-28 | 2016-07-28 | 替诺福韦艾拉酚胺结晶化合物及其制备方法 |
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CN201610625799.2A CN107663217B (zh) | 2016-07-28 | 2016-07-28 | 替诺福韦艾拉酚胺结晶化合物及其制备方法 |
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CN107663217A CN107663217A (zh) | 2018-02-06 |
CN107663217B true CN107663217B (zh) | 2021-03-02 |
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CN201610625799.2A Active CN107663217B (zh) | 2016-07-28 | 2016-07-28 | 替诺福韦艾拉酚胺结晶化合物及其制备方法 |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102365283A (zh) * | 2009-03-26 | 2012-02-29 | 株式会社大熊制药 | 阿德福韦酯的新晶型及其制备方法 |
CN105646584A (zh) * | 2014-11-12 | 2016-06-08 | 四川海思科制药有限公司 | 替诺福韦艾拉酚胺富马酸盐新晶型及其制备方法和用途 |
WO2016108205A1 (en) * | 2015-01-03 | 2016-07-07 | Mylan Laboratories Limited | Processes for the preparation of amorphous tenofovir alafenamide hemifumarate and a premix thereof |
-
2016
- 2016-07-28 CN CN201610625799.2A patent/CN107663217B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102365283A (zh) * | 2009-03-26 | 2012-02-29 | 株式会社大熊制药 | 阿德福韦酯的新晶型及其制备方法 |
CN105646584A (zh) * | 2014-11-12 | 2016-06-08 | 四川海思科制药有限公司 | 替诺福韦艾拉酚胺富马酸盐新晶型及其制备方法和用途 |
WO2016108205A1 (en) * | 2015-01-03 | 2016-07-07 | Mylan Laboratories Limited | Processes for the preparation of amorphous tenofovir alafenamide hemifumarate and a premix thereof |
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Address after: 215123 Suzhou Industrial Park, Suzhou, Jiangsu, No. 388, Nanshui, 7 D, National Science and Technology Park, Nanshui University. Applicant after: SUZHOU LANXITE BIOTECHNOLOGY Co.,Ltd. Address before: 215000 Jiangsu Suzhou Industrial Park 388, Nanshui, Nanshui, 7 D, National Science and technology park. Applicant before: SUZHOU LANXITE BIOTECHNOLOGY Co.,Ltd. |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Crystalline compound of tenofovir alachlor and its preparation method Effective date of registration: 20221008 Granted publication date: 20210302 Pledgee: Agricultural Bank of China Limited Suzhou Industrial Park sub branch Pledgor: SUZHOU LANXITE BIOTECHNOLOGY Co.,Ltd. Registration number: Y2022320010565 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |