发明公开
- 专利标题: NUCLEOSIDE DERIVATIVES FOR THE TREATMENT OF HEPATITIS C
- 专利标题(中): 核苷丙型肝炎用于治疗
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申请号: EP01976128.7申请日: 2001-08-21
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公开(公告)号: EP1315736A2公开(公告)日: 2003-06-04
- 发明人: DEVOS, Rene , DYMOCK, Brian William , HOBBS, Christopher John , JIANG, Wen-Rong , MARTIN, Joseph Armstrong , MERRETT, John Herbert , NAJERA, Isabel , SHIMMA, Nobuo , TSUKUDA, Takuo
- 申请人: F. HOFFMANN-LA ROCHE AG
- 申请人地址: 124 Grenzacherstrasse 4070 Basel CH
- 专利权人: F. HOFFMANN-LA ROCHE AG
- 当前专利权人: F. HOFFMANN-LA ROCHE AG
- 当前专利权人地址: 124 Grenzacherstrasse 4070 Basel CH
- 代理机构: Schager, Frank, Dr.
- 优先权: GB0021285 20000830; GB0026611 20001031
- 国际公布: WO02018404 20020307
- 主分类号: C07H19/06
- IPC分类号: C07H19/06 ; C07H19/16 ; A61K31/7064 ; A61K31/7076 ; A61P31/14
摘要:
Use of compounds of formula (I), wherein R1 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxy, halogen, cyano, isocyano or azido; R2 is hydrogen, hydroxy, alkoxy, chlorine, bromine or iodine; R3 is hydrogen; or R?2 and R3¿ together represent =CH¿2?; or R?2 and R3¿ represent fluorine; X is O, s or CH¿2?; a, b, c, d denoting asymmetric carbon atoms each of which is substituted with 4 different substituents; and B signifies a purine base B1 which is connected through the 9-nitrogen of formula (B1), wherein R?4¿ is hydrogen, hydroxyl, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen or SH; R5 is hydrogen, hydroxy, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8¿ or SH; R6 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen, SH or cyano; R?7 and R8¿ are independently of each other hydrogen, alkyl, aryl, hydroxyalkyl, alkenylalkyl, alkynylalkyl, cycloalkyl or acyl; R9 is hydrogen, alkyl or aryl; or B signifies an oxidised purine base B2 which is connected through the 9-nitrogen of formula (B2), wherein R?4, R5 and R6¿ are as defined above; or B signifies a purine base B3 which is connected through the 9-nitrogen of formula (B3), wherein R?4 and R6¿ are as defined above; R10 is hydrogen, alkyl or aryl; Y is O, S or NR11; R11 is hydrogen, hydroxy, alkyl, OR9, heterocyclyl or NR?7R8; R7, R8 and R9¿ are as defined above; or B signifies a pyrimidine base B4 which is connected through the 1-nitrogen of formula (B4), wherein Z is O or S; R12 is hydrogen, hydroxy, alkyl, alkoxy, haloalkyl, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8¿ or SH; R13 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl or halogen; R?7, R8 and R9¿ are as defined above; or B signifies a pyrimidine base B5 which is connected through the 1-nitrogen of formula (B5), wherein Y, Z, R10 are as defined above for the treatment of diseases mediated by the Hepatitis C Virus (HIV) or for the preparation of a medicament for such treatment. The invention is concerned with novel and known purine and pyrimidine nucleoside derivatives, their use as inhibitors of subgenomic Hepatitis C Virus (HCV) RNA replication and pharmaceutical compositions of such compounds.
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