Ring-equivalent bioisosteres

It was with Erlenmeyer that the concept of bioisosterism was introduced to differentiate from classical isosteres, ensuring its relevance to medicinal chemistry. The introduction of ring equivalences is significant. This was the formalization of what we consider to be a bioisosteric comparison and is the first definition of most relevance to medicinal chemistry. 

Finally, in 1970, Alfred Burger classified bioisosteres into classical and nonclas-sical [6]. The former include atoms or groups of the same valence as well as ring equivalents, while the latter are basically those that do not fit the first definition. Several reviews on bioisosteres have been reported in the literature over the years [7-11], and in the next sections a selection of examples for each of the two categories will be provided. 

Glaxo scientists have reported on a new series of H3 antagonists that contain a 1,2,4-oxadiazole ring as a bioisostere equivalent of the isothiourea functionality of... 

Brotilzolam represents a twofold modification the fused benzo ring is replaced by the bioisosteric thiazole (the Br substituent apparently in the No. 7 equivalent position), and a triazolo fusion also is carried out. The drug, which is marketed in Germany and Portugal, is about equipotent to triazolam. 

Can it be replaced by homopiperazine (b), by piperidine (c and d), by ring-opened diamines (e)7 Can it be substituted (g and h) or bridged (i)7 Can it be replaced by some vague bioisosteric equivalent such as a guanidino group (Af-methyl piperazine was used as a guanidine substitute in the design of thrombine inhibitors) ... 

---