| 摘要 |
Macrocyclic peptides (I) and their salts and esters are new. Macrocyclic peptides of formula (I) and their salts and esters are new. [Image] W = CH or N; R 21 = H, halo, 1-6C alkyl, 3-6C cycloalkyl, 1-6C haloalkyl, 1-6C alkoxy, 3-6C cycloalkoxy, hydroxy or N(R 23) 2; R 23 = H, 1-6C alkyl or 3-6C cycloalkyl; R 2 2 = H, halo, 1-6C alkyl, 3-6C cycloalkyl, 1-6C haloalkyl, 1-6C thioalkyl, 1-6C alkoxy, 3-6C cycloalkoxy, 2-7C alkoxyalkyl, 3-6C cycloalkyl, 6C or 10C aryl or Het; Het = 5-7-membered optionally saturated heterocycle containing 1-4 N, O or S; cycloalkyl, aryl or Het are substituted by R 24; R 24 = H, halo, 1-6C alkyl, 3-6C cycloalkyl, 1-6C alkoxy, 3-6C cycloalkoxy, NO 2, N(R 25), NHC(O)R 25, NHC(O)NHR 25 or NH-C(O)-OR 26; R 2 5 = H, 1-6C alkyl or 3-6C cycloalkyl; R 26 = 1-6C alkyl or 3-6C cycloalkyl; R 3 = OH, NH 2 or NHR 31; R 31 = 6 or 10C aryl, heteroaryl, C(O)R 32, C(O)NHR or C(O)OR 32; R 32 = 1-6C alkyl or 3-6C cycloalkyl; D = 5-10-atom optionally saturated alkylene chain optionally containing 1-3 O, S or NR 41; R 41 = H, 1-6C alkyl, 3-6C cycloalkyl or C(O)R 42; R 42 = 1-6C alkyl, 3-6C cycloalkyl or 6 or 10C aryl; R 4 = H or 1-3 of 1-6C alkyl, 1-6C haloalkyl, 1-6C alkoxy, hydroxy, halo, amino, oxo, thio or 1-6C thioalkyl; A = C(O)NNHR 5 or a carboxylic acid; R 5 = 1-8C alkyl, 3-6C cycloalkyl, 6 or 10C aryl or 7-16C aralkyl. An independent claim is also included for the use of a composition comprising (I) in admixture with a carrier medium or an auxiliary for the manufacture of a medicament for treating hepatitis C viral infection in a mammal. ACTIVITY : Antiviral. MECHANISM OF ACTION : Selective inhibitors of NS3 protease of HCV. In an NS3 protease cell-based assay using Huh-7 cell, a human cell line derived from a hepatoma cotransfected with 2 DNA constructs, a compound of formula (Ia) exhibited an EC 50 value of less than 1 MicroM. [Image]. |
