CN1257912C - 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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- CN1257912C CN1257912C CNB998095532A CN99809553A CN1257912C CN 1257912 C CN1257912 C CN 1257912C CN B998095532 A CNB998095532 A CN B998095532A CN 99809553 A CN99809553 A CN 99809553A CN 1257912 C CN1257912 C CN 1257912C
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
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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
- C07H19/06—Pyrimidine radicals
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- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
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- 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
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- 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
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- 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
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- 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
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- 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 | DNAαKi 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 | 43636914010274 | 423451461 | 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 (31)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
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)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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 |
---|---|
CN1320128A CN1320128A (zh) | 2001-10-31 |
CN1257912C true CN1257912C (zh) | 2006-05-31 |
Family
ID=26791121
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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 |
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 |
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 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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 |
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 |
Country Status (22)
Country | Link |
---|---|
US (5) | US6395716B1 (zh) |
EP (2) | EP1104436B1 (zh) |
JP (2) | JP4294870B2 (zh) |
KR (4) | KR100568035B1 (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) | DE122007000062I1 (zh) |
DK (3) | DK1104436T3 (zh) |
ES (3) | ES2255295T3 (zh) |
FR (1) | FR07C0046I2 (zh) |
HK (3) | HK1034083A1 (zh) |
LU (1) | LU91348I2 (zh) |
MX (1) | MXPA01001507A (zh) |
NL (1) | NL300286I2 (zh) |
PT (2) | PT2415776T (zh) |
RU (1) | RU2424016C2 (zh) |
SG (1) | SG132498A1 (zh) |
WO (1) | WO2000009531A2 (zh) |
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