Notes of Malaria Libre 3project meeting - Discussion points: :

Aryl piperazine scaffold: It was emphasized that in order to achieve the early lead criteria, in addition to overcoming the current challenges, potency of compounds has to be improved by 1 log unit (Pf IC50<100nM). [...] Clint suggested a few molecules to fill in the SAR gaps and also to understand the effect on potency of flipping substitutions at 2nd and 5th position of the scaffold. [...] Venkat also shared his proposal (slide 19 of the presentation) – In relation to fused molecules on the RHS, it was clarified that one example was synthesized and was inactive but will be worth synthesizing a few more compounds to confirm the effect of rigidification on potency. [...] Understanding the role of linker length on RHS of the molecule is important; Kishore highlighted that synthesis of a few compounds is complete and characterization is ongoing. [...] Post meeting note: Niti has shared references for minor groove binders TCGLS has shared list of amines available in house Action Items Action Item Responsible group/ scientist Synthesis of compounds TCGLS: ongoing CDRI: 6 compounds will be registered in the week of 14th September Clint: to initiate synthesis of proposed molecules Ram: to take up synthesis of MMV023227 analogs 42-46 once the studen.