Studies On The Synthesis Of β-anilinoacrylamides And Their Anti-trypanosomiasis Activities

Cliagas?disease is a serious endemic illness that affects millions of people in Central and South America. Trypanosoma cruzi, a protozoan parasite, is the etiologic agent of this disease. Unfortunately, there is no effective treatment for it. Biological studies of T cruzi showed that cruzain was a new target for potential drug design to develop biological selective inhibitors. Based on the 3D structure of cruzain and lead compound identified through computer DOCK program, twenty substituted ~3-anilinoacrylamides were designed by using bioisosteric replacement. The target compounds were identified by IR, æ…”-NMR and MS. The pharmacological test against cruzain in vitro indicated that the compouds AA-02, AA-03, AA-04, AA-06, AA- 10 and AA- 15 had definite activities. The best one among them was compound AA-15 with an IC50 value of 2.3 j~mol/L. At the same time, the SAR of substituted f3-anilinoacrylamides was studied for direction of further modification.