Abstract A series of tryptamine derivatives were synthesized and evaluated for their anti- hepatitis B virus (HBV) activity and cytotoxicity in the HepG2. 2.15 cell line. The preliminary SAR was discussed. Compounds 2e and 4a showed potent antiviral activity (IC 50= 0.4 and< 1 μM, respectively) and low cytotoxicity (CC 50= 40.6 and> 25 μM, respectively).