CN100482236C - 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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- CN100482236C CN100482236C CNB021265739A CN02126573A CN100482236C CN 100482236 C CN100482236 C CN 100482236C CN B021265739 A CNB021265739 A CN B021265739A CN 02126573 A CN02126573 A CN 02126573A CN 100482236 C CN100482236 C CN 100482236C
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- C07—ORGANIC CHEMISTRY
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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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- 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
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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
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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
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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
- A61K31/7068—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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- 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
- A61K31/7068—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
- 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
- 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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- 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
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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 DNAIC<sub>50</sub> | DNA αK<sub>i</sub>b(μM) | DNA βK<sub>i</sub>b(μM) | DNA γK<sub>i</sub>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aEC<sub>50</sub>(μM) | HBV RibEC<sub>50</sub>(μM) | 细胞毒性1C<sub>50</sub>(μM) | 选择性指数1C<sub>50</sub>/EC<sub>50</sub> |
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 | EC<sub>50</sub> |
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. |
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 (36)
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 Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998095532A Division CN1257912C (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 |
---|---|
CN1478483A CN1478483A (zh) | 2004-03-03 |
CN100482236C true CN100482236C (zh) | 2009-04-29 |
Family
ID=26791121
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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 |
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 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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 |
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 |
Country Status (22)
Country | Link |
---|---|
US (5) | US6395716B1 (zh) |
EP (2) | EP1104436B1 (zh) |
JP (2) | JP4294870B2 (zh) |
KR (4) | KR100568035B1 (zh) |
CN (3) | CN1257912C (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) | DK1431304T3 (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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