Preparation of pyrimidines as HCV entry inhibitors and antiviral agents.

Abstract

Disclosed are novel compds. with formula I, comprising substituted pyrimidines, pyrazolopyrimtdines, and imidazolopyrimidines, the syntheses, and compns., including pharmaceutical compns., comprising them and related compds. Compds. of I [L2, L4 and L6 independently = none, H, O, S, etc.; R2, R4, and R6 independently = none, H, amino, alkoxy, etc.], and their pharmaceutically acceptable salts, polymorphs, hydrates, stereoisomers, metabolites, or prodrugs, are prepd. and disclosed. Thus, e.g., II was prepd. in a multi-step synthesis starting from 2-chloro-4,6-dimethoxypyrimidine and aniline. Such compds. function to inhibit entry of viruses of the Flaviviridae family, including Hepatitis C virus (HCV), into cells that are susceptible to virus infection. The tested compds. showed inhibition of HCV entry with IC50 value of ranging from 6 nM to 1 μM against HCV HCV of genotype 1a. These compds. are useful for the treatment, therapy and/or prophylaxis of viral diseases and infection, including HCV infection. [on SciFinder(R)]