Last month we wrote about “sociable”
vs “unsociable” fragments: the former are amenable to straightforward chemistry
for fragment growing, merging, or linking, while the latter are not. This categorization
prompted a poll on how often synthetic challenges have kept you from pursuing a
particular fragment or impeded a fragment-to-lead project. The results are now
in.
(Methods note: the poll was run
on Crowdsignal from 14 June through 16 July. There were 42 responses to the
first question and 44 to the second. Respondents came from a dozen countries with
the most from the US, UK, Germany, Denmark, Netherlands, Australia, France, and
Italy.)
Responses were similar for both
questions: a fifth to a quarter of respondents often found that synthetic
challenges kept them from pursuing a particular fragment or impeded work on a fragment-to-lead
project, nearly half sometimes found this to be the case, while a fifth to a
third rarely experienced this. Only a handful of people never found synthetic
challenges limiting.
It is heartening that around a
third of respondents are rarely if ever impeded by chemistry, perhaps because
they have intentionally constructed their libraries with sociable fragments. Still,
the fact that nearly two thirds of researchers sometimes or often run into
problems suggests a continuing need for
synthetically enabling fragment chemistry.
For academic chemists looking to
make a practical impact, this could be a fertile area. And fragment library
vendors looking to differentiate themselves may want to consider providing robust
synthetic routes and methodologies for their available compounds.
3 comments:
And so what? Why is this the case? My speculation is that the differences must be due to the source of the hits, i.e., the library. Are there differences between those using in-house libraries or libraries from particular vendors? Is there a correlation with screening technique?
Thanks Dan for this poll and for your assessment, which I very much agree with. There is an opportunity for Fragment-to-Lead synthesis to benefit from the impressive (academic) research into selective C-H bond activation, especially if the methodology is compatible with unprotected polar functional groups.
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