CN1320128A - 用于治疗乙型肝炎的β-L-2′-脱氧-核苷 - Google Patents
用于治疗乙型肝炎的β-L-2′-脱氧-核苷 Download PDFInfo
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- CN1320128A CN1320128A CN99809553A CN99809553A CN1320128A CN 1320128 A CN1320128 A CN 1320128A CN 99809553 A CN99809553 A CN 99809553A CN 99809553 A CN99809553 A CN 99809553A CN 1320128 A CN1320128 A CN 1320128A
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- Prior art keywords
- prodrug
- alkyl
- deoxidation
- acceptable salt
- stable
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Images
Classifications
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- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
- A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- 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
- C07H19/16—Purine radicals
Abstract
Description
抑制剂 | WHV DNAIC50 | DNA αKi b(μM) | DNA βKi b(μM) | DNA γKi b(μM) |
β-L-dT-TP | 0.34 | >100 | >100 | >100 |
β-L-dA-TP | 2.3 | >100 | >100 | >100 |
β-L-dC-TP | 2.0 | >100 | >100 | >100 |
β-L-dU-TP | 8 | >100 | >100 | >100 |
化合物 | HBV病毒颗粒aEC50(μM) | HBV RibEC50(μM) | 细胞毒性1C50(μM) | 选择性指数1C50/EC50 |
β-L-dT | 0.05 | 0.05 | >200 | >4000 |
β-L-dC | 0.05 | 0.05 | >200 | >4000 |
β-L-dA | 0.05 | 0.05 | >200 | >2000 |
β-L-dI | 1.0 | 1.0 | >200 | >200 |
β-L-dU | 5.0 | 5.0 | >200 | >40 |
组合物 | 比例 | EC50 |
L-dC+L-dT | 1∶3 | 0.023 |
L-dC+L-dT | 1∶1 | 0.053 |
L-dC+L-dT | 3∶1 | 0.039 |
L-dC+L-dA | 1∶30 | 0.022 |
L-dC+L-dA | 1∶10 | 0.041 |
L-dC+L-dA | 1∶3 | 0.075 |
L-dT+L-dA | 1∶30 | 0.054 |
L-dT+L-dA | 1∶10 | 0.077 |
L-dT+L-dA | 1∶3 | 0.035 |
aβ-L-2'-脱氧腺苷(μM) | bβ-L-2'-脱氧胞苷(μM) | 抑制率% | cC.I. |
0.5 | 90 | ||
0.05 | 24 | ||
0.005 | 1 | ||
0.5 | 95 | ||
0.05 | 40 | ||
0.005 | 10 | ||
0.05 | 0.05 | 80 | 0.34 |
0.05 | 0.005 | 56 | 0.20 |
0.05 | 0.0005 | 50 | 0.56 |
0.005 | 0.05 | 72 | 0.35 |
0.005 | 0.005 | 54 | 0.35 |
0.005 | 0.0005 | 30 | 0.16 |
0.0005 | 0.05 | 50 | 0.83 |
0.0005 | 0.005 | 15 | 0.28 |
0.0005 | 0.0005 | 0 | N.A. |
天 | 对照 | LdA LdT | LdC |
ng/ml WHV-DNA/ml血清1,2 | |||
013714 | 381398412446392 | 436 423369 45140 14102 674 1 | 426123624620 |
化合物 | CFU-GM(μM) | BFU-E(μM) |
β-L-dA | >10 | >10 |
β-L-dC | >10 | >10 |
β-L-dT | >10 | >10 |
β-L-dU | >10 | >10 |
拉米夫定 | >10 | >10 |
Claims (26)
Applications Claiming Priority (4)
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US9611098P | 1998-08-10 | 1998-08-10 | |
US60/096,110 | 1998-08-10 | ||
US13135299P | 1999-04-28 | 1999-04-28 | |
US60/131,352 | 1999-04-28 |
Related Child Applications (4)
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CNB021265739A Division CN100482236C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2’-脱氧-核苷 |
CN2006101007520A Division CN101120947B (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2′-脱氧-核苷 |
CN2006100997025A Division CN1911237B (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
CNB2004100028639A Division CN100387237C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
Publications (2)
Publication Number | Publication Date |
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CN1320128A true CN1320128A (zh) | 2001-10-31 |
CN1257912C CN1257912C (zh) | 2006-05-31 |
Family
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CNB2004100028639A Expired - Lifetime CN100387237C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
CNB998095532A Expired - Lifetime CN1257912C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2′-脱氧-核苷 |
CNB021265739A Expired - Lifetime CN100482236C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2’-脱氧-核苷 |
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CNB2004100028639A Expired - Lifetime CN100387237C (zh) | 1998-08-10 | 1999-08-10 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
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US (5) | US6395716B1 (zh) |
EP (2) | EP2415776B1 (zh) |
JP (2) | JP4294870B2 (zh) |
KR (4) | KR100702230B1 (zh) |
CN (3) | CN100387237C (zh) |
AT (1) | ATE313550T1 (zh) |
AU (1) | AU5475799A (zh) |
BR (1) | BRPI9912896B8 (zh) |
CA (1) | CA2340156C (zh) |
CY (2) | CY2007017I2 (zh) |
DE (2) | DE69929060T2 (zh) |
DK (3) | DK1104436T3 (zh) |
ES (3) | ES2579903T3 (zh) |
FR (1) | FR07C0046I2 (zh) |
HK (3) | HK1034083A1 (zh) |
LU (1) | LU91348I2 (zh) |
MX (1) | MXPA01001507A (zh) |
NL (1) | NL300286I2 (zh) |
PT (2) | PT1431304E (zh) |
RU (1) | RU2424016C2 (zh) |
SG (1) | SG132498A1 (zh) |
WO (1) | WO2000009531A2 (zh) |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100376593C (zh) * | 2002-08-06 | 2008-03-26 | 埃迪尼克斯(开曼)有限公司 | β-L-2'-脱氧胸苷的结晶形及非晶形 |
CN1315863C (zh) * | 2003-12-12 | 2007-05-16 | 河南省科学院质量检验与分析测试研究中心 | β-L-2'-脱氧-核苷衍生物、其合成方法及其药物用途 |
CN102649788A (zh) * | 2011-02-28 | 2012-08-29 | 四川大学 | β-L-2’-脱氧-胸腺嘧啶核苷衍生物及其制备方法和用途 |
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