Chagas Disease Drug Discovery: Multiparametric Lead Optimization against in Acylaminobenzothiazole Series.

Acylaminobenzothiazole hits were identified as potential inhibitors of replication, a parasite responsible for Chagas disease. We selected compound for lead optimization, aiming to improve in parallel its anti- activity (IC = 0.63 μM) and its human metabolic stability (human clearance = 9.

Optimisation of a key cross-coupling reaction towards the synthesis of a promising antileishmanial compound.

During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of -(-4-((4-methoxy-3-(()-3-methylmorpholino)-1-pyrazolo[3,4-]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide (( )) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of ( ), as well as further compounds in the series.

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments.