I just came across a new website that might be interesting, BoBER gives access to a database of bioisosteres.
BoBER (Base of Bioisosterically Exchangeable Replacements) is a freely available method which implements an interface to a database of bioisosteric and scaffold hopping replacements. The web-server enables fast and user-friendly searches for bioisosteric replacements which were obtained by mining the whole Protein Data Bank. BoBER enables medicinal chemists to quickly search and get new and unique ideas about possible bioisosteric or scaffold hoping replacements that could be used to improve specific hit or lead drug-like compounds.
You can submit whole molecule structures which are divided into fragments and then bioisosteric replacements for each fragment can then be identified.
There is a section on bioisosters in the Drug Discovery Resources.