الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 187 |  |  |
| | | from | 187 | | |
Abstract
Summary
Protease inhibitors (PIs) are a type of antiviral drugs that are widely used to treat HIV /AIDS and hepatitis disease caused by hepatitis C virus. NS3/4A protease inhibitor is an important antiviral target where The HCV serine protease NS3/NS4A cleaves the polyprotein at the peptide linkages between the structural proteins (Core, E1 and E2) and the nonstructural proteins (P7, NS2, NS3, NS4A, NS4B, NS5A and NS5B), the latter corresponding to the RNA replicase. HCV NS3/4A protease inhibitor has attracted significant efforts in drug discovery and development for the treatment of HCV infection.
We have synthesized and developed small molecules of 2-amino 3-cyanide 4,5,6,7-tetrahydrothiophene that can inhibit HCV infection virus live cycle to be used for the treatment of hepatitis C virus infection. For this purpose we used the 2 amino thiophene nucleuse as starting point to synthesize different thiophene derivatives and study their structure activity relationships (SARs).
2-amino 3-cyanide 4,5,6,7-tetrahydrothiophene (3a) and ethyl 2- amino-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxylate (3b) were synthesized by the condensation of cyclohexanone with malononitrile in case of 3a or ethyle2-cyano-acetate in case of 3b in the presence of ethanol or methanol and added of sulfur in room temperature then added pipredine at 0 ºC as catalyst. 2-amino thiophene derivatives 3a,b were then subjected to different reactions conditions to obtain variety of substituents to study the structure activity relationships and study its activity against HCV.
We have synthesized Schiff base products (5-17) based in react 3a,b with different aldhydes. Moreover, we have coupled 2-amino thiophene derivatives 3a,b using different acid chloride to study the effect of substituents at C2 position of the thiophene ring (18-26). Finally, phenoxyacetamide derivatives (33-35) were synthesized by coupling reacting 2-amino thiophene derivatives 3a with different ether acid chloride. The structure of all the synthesized derivatives has been confirmed by: IR, 1H NMR, 13C NMR, and Mass spectrometry.
Viral activity of some synthesized compounds has been checked where the inhibitory potency of some synthesized compounds was assessed against NS3/4A protease from HCV genotype 4a by cleavage of a fluorescence resonance energy transfer peptide substrate using the SensoLyte 490 HCV protease assay Kit. The effect of two synthesized compounds 33 and 35 on the activity of the purified HCV NS3/4A protease was monitored and showed the most prominent act