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In the previous post, I noted that two Astex kinase inhibitors were derived from fragments that lacked acyclic substituents. Dan points out that this is actually uncommon and wonders if this reflects a reluctance of medicinal chemists to work on fragments that were seen to be too simple.
The presence of certain molecular recognition elements, for example hydroxyl or carboxylate, implies that at least one acyclic substituent be present. I think this it probably the main reason that fragments are normally encountered with acyclic substituents. However, I do agree with Dan that some fragments can be seen as too simple and re-iterate my point that in the Brave New World of FBDD we really need to start seeing phenyl rings as synthetic handles.
A lack of acyclic substituents typically implies the presence of one or more polar atoms in a ring or spacer. When assembling screening libraries, I do try to select compounds that present heterocyclic molecular recognition elements without acyclic substituents (e.g. 4-phenypyrazole, 2-anilinopyrimidine). Interestingly compounds like these are not as easy to source as you might think.