Druggability of the Arylpyrrole leads (TCMDC-123794 etc)

Project is starting with a couple of leads from the GSK Tres Cantos set. There is a newly-published analysis of the druggability of the compounds in the original data set. The arylpyrrole series is listed as one of the most promising (though the Aryl-F is missing in the published paper - presume that is a clerical error).
Tres Cantos are appealing for collaborators to work with them on these compounds, which is an excellent idea. That's what we're doing, except that the project hosted here is open source, meaning anyone can see what we're doing and guide the direction of the project.
The initial phase is the resynthesis of these leads and their validation. We will soon be moving to analog synthesis. The obvious first question for the community of medicinal chemists is: what should we change?
My gut feeling was to verify the need for the aryl-F and the methyls on the pyrrole. Paul Willis' gut feeling was that ester. Gut feelings and half-formed thoughts enormously welcome as comments below.