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The last twenty years have seen noteworthy success in efforts to control HAT (Human African Trypanosomiasis) in Africa. HAT is a neglected tropical disease with major public health and economic effects in sub-Saharan Africa, and its effects on livestock productivity and development are considered major constraints to alleviating poverty in this region. The identification of important chemical features using the existing molecules will be helpful to discover the potent candidate to treat HAT. The development of novel HAT inhibitors is done using pharmacophore based virtual screening and docking study. The 3DQSAR was also performed to determine the predicted biological activity. The best hypothesis from PHASE, gave the five point pharmacophore hypothesis, AAPRR.687 with two hydrogen bond acceptors (A), two aromatic rings (R) and one charged group (P). Amongst them the pharmacophore hypothesis yielded a statistically significant 3D-QSAR model with 0.9521 as coefficient of determination (r2), a Pearson coefficient of 0.8796 and good F value and was considered to be the best pharmacophore hypothesis. The developed pharmacophore based 3D-QSAR model was validated by predicting the activity of test set molecules. The squared predictive correlation coefficient (q2) of 0.7359 was observed between experimental and predicted activity values of test set molecules. The developed pharmacophore was used to screen the chemical database. Subsequently the screened compounds were filtered by molecular docking. Finally five compounds were obtained as novel lead against human African trypanosomiasis. [ABSTRACT FROM AUTHOR]