Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery

By M. Hann, Andrew R. Leach, G. Harper. Journal of chemical information and computer sciences, 2001

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A guide to drug discovery: Hit and lead generation: beyond high-throughput screening (2003, background): “The first generation of such combinatorial libraries were unattractive for most screening groups due to overloaded molecular complexit”
Twenty years on: the impact of fragments on drug discovery (2016, neutral): “2001 (REFS 9,10) .”
The use of a graph database is a complementary approach to a classical similarity search for identifying commercially available fragment merges (2022, background): “While fragments tend to bind with weak afnity (typically in the high micromolar to low millimolar range) [1], their small size and lower likelihood of steric impediments result in increased likelihood of binding and higher hit rates compared with more traditional high-throughput screens (HTS) [3, 4”
A decade of fragment-based drug design: strategic advances and lessons learned (2007, background): “An additional factor working in favour of fragment-based screening is that less complex molecules should show higher hit rates against protein targets, as theoretically formulated by Hann and co-worker”
The impact of aromatic ring count on compound developability--are too many aromatic rings a liability in drug design? (2009, background): “In this context, it is interesting to note that the average number of aromatic rings in oral drugs is 1.6 [ 6 ], although it is not known whether this number is increasing over time.b It has also been shown that”