CN1891710A - L-nucleoside prodrug - Google Patents
L-nucleoside prodrug Download PDFInfo
- Publication number
- CN1891710A CN1891710A CN 200510040848 CN200510040848A CN1891710A CN 1891710 A CN1891710 A CN 1891710A CN 200510040848 CN200510040848 CN 200510040848 CN 200510040848 A CN200510040848 A CN 200510040848A CN 1891710 A CN1891710 A CN 1891710A
- Authority
- CN
- China
- Prior art keywords
- methyl
- fluoro
- arabinose
- uridine
- deoxidation
- 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.)
- Granted
Links
- 229940002612 prodrug Drugs 0.000 title description 60
- 239000000651 prodrug Substances 0.000 title description 60
- 239000002777 nucleoside Substances 0.000 title description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 15
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims abstract description 13
- 208000037262 Hepatitis delta Diseases 0.000 claims abstract description 11
- 241000700605 Viruses Species 0.000 claims abstract description 3
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 146
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 73
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 73
- 229940045145 uridine Drugs 0.000 claims description 73
- 239000002253 acid Substances 0.000 claims description 50
- -1 butyl dimethylsilyl Chemical group 0.000 claims description 44
- 239000003814 drug Substances 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
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- 125000006239 protecting group Chemical group 0.000 claims description 16
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- 239000004305 biphenyl Substances 0.000 claims description 14
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- 125000002252 acyl group Chemical group 0.000 claims description 13
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- 230000000903 blocking effect Effects 0.000 claims description 6
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
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- 238000000034 method Methods 0.000 description 25
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
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- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 14
- 238000001819 mass spectrum Methods 0.000 description 14
- 125000003835 nucleoside group Chemical group 0.000 description 14
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- 239000011734 sodium Substances 0.000 description 10
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- SRBFZHDQGSBBOR-QMKXCQHVSA-N alpha-L-arabinopyranose Chemical compound O[C@H]1CO[C@@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-QMKXCQHVSA-N 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
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- 239000002775 capsule Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 150000003833 nucleoside derivatives Chemical class 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
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- 239000013078 crystal Substances 0.000 description 5
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- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 5
- 229960002963 ganciclovir Drugs 0.000 description 5
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 5
- 150000002460 imidazoles Chemical class 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 4
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200510040848A CN100577679C (en) | 2005-07-01 | 2005-07-01 | L-nucleoside prodrug |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200510040848A CN100577679C (en) | 2005-07-01 | 2005-07-01 | L-nucleoside prodrug |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200910258767 Division CN101735294B (en) | 2005-07-01 | 2005-07-01 | Prodrug of L-nucleoside |
Publications (2)
Publication Number | Publication Date |
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CN1891710A true CN1891710A (en) | 2007-01-10 |
CN100577679C CN100577679C (en) | 2010-01-06 |
Family
ID=37596933
Family Applications (1)
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CN200510040848A Expired - Fee Related CN100577679C (en) | 2005-07-01 | 2005-07-01 | L-nucleoside prodrug |
Country Status (1)
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CN (1) | CN100577679C (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105254695A (en) * | 2014-11-10 | 2016-01-20 | 南京曼杰生物科技有限公司 | Nucleoside phosphoramidate ramification and application thereof |
CN114404391A (en) * | 2022-02-16 | 2022-04-29 | 深圳厚存纳米药业有限公司 | Nano particle, preparation method and application thereof |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105254695A (en) * | 2014-11-10 | 2016-01-20 | 南京曼杰生物科技有限公司 | Nucleoside phosphoramidate ramification and application thereof |
WO2016074596A1 (en) * | 2014-11-10 | 2016-05-19 | 南京曼杰生物科技有限公司 | Nucleoside phosphoramidate derivative and application thereof |
CN105254695B (en) * | 2014-11-10 | 2019-01-18 | 南京曼杰生物科技有限公司 | Nucleoside phosphoramidate derivative and its application |
CN114404391A (en) * | 2022-02-16 | 2022-04-29 | 深圳厚存纳米药业有限公司 | Nano particle, preparation method and application thereof |
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